Structural Analysis for Antiviral Compounds

Structural Analysis for Antiviral Compounds

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The coronavirus main protease (M(pro)) is critical in viral gene expression (Xue et al., 2008).
  • The viral replication through the proteolytic processing of replicase polyproteins may be a potential antiviral target.
  • The crystal structures of infectious bronchitis virus (IBV) M(pro) and SARS-CoV M(pro) mutant (H41A) are important.
  • The structures of the N-terminal autocleavage substrate are also critical.
  • These structures can be used to describe the structural flexibility and substrate binding of M(pro).
  • A monomeric form of IBV M(pro) was identified in CoV M(pro) structures.
  • A comparison of these M(pro) structures may be helpful for the design of substrate-based inhibitors targeting CoV M(pro)s.
  • A Michael acceptor inhibitor (N3) was co-crystallized with IBV M(pro) and led to inactivation of IBV M(pro).
  • The structure-based optimization of N3 has led to compounds N27 and H16 that may inhibit SARS-CoV M(pro) (Xue et al., 2008).

A Potential Antiviral Molecule for SARS-CoV and Ebola

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • SARS-CoV and Ebola, Hendra, and Nipah viruses belong to different viral families.
  • These viruses need cathepsin L for entering their target cells (Elshabrawy et al., 2014).
  • The viral glycoproteins are primed by protease cleavage before fusing with the host cell membrane (Elshabrawy et al., 2014).
  • A high-throughput assay has been used to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins.
  • A broad-spectrum small molecule was able to inhibit the cathepsin L-mediated cleavage and the entry of glycoprotein pseudotypes.
  • The small molecule may be a candidate as a broad-spectrum antiviral drug against these viruses (Elshabrawy et al., 2014).

References:

Elshabrawy, H. A., Fan, J., Haddad, C. S., Ratia, K., Broder, C. C., Caffrey, M., & Prabhakar, B. S. (2014). Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay. Journal of Virology, 88(8), 4353–4365. https://doi.org/10.1128/JVI.03050-13

Xue, X., Yu, H., Yang, H., Xue, F., Wu, Z., Shen, W., Li, J., Zhou, Z., Ding, Y., Zhao, Q., Zhang, X. C., Liao, M., Bartlam, M., & Rao, Z. (2008). Structures of two coronavirus main proteases: Implications for substrate binding and antiviral drug design. Journal of Virology, 82(5), 2515–2527. https://doi.org/10.1128/JVI.02114-07

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Potential Antiviral Compounds for Coronaviruses: Tests and Screenings

Potential Antiviral Compounds for Coronaviruses: Tests and Screenings

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Some agents inhibiting coronaviral replication have been investigated (Golda and Pyrc, 2008).
  • The potential antiviral agents include (Golda and Pyrc, 2008):
    • Carbohydrate-binding agents;
    • Neutralizing antibodies;
    • Drugs targeting the coronaviral envelope protein.
  • Real-time PCR has been used for testing antivirals against Lassa virus, SARS coronavirus, and Ebola virus (Günther et al., 2004).
  • A small-scale screening found a class of imidazole nucleoside/nucleotide analogues with antiviral activities against Lassa virus.
  • The analogues had dinitrile or diester groups at the imidazole 4,5-positions (Günther et al., 2004).
  • Many of these had an acyclic sugar or sugar phosphonate moiety at the imidazole 1-position.
  • The compounds also suppressed the replications of SARS and Ebola viruses (Günther et al., 2004).
  • These compounds may be useful for the development of broad-spectrum drugs against viruses.

References:

Golda, A., & Pyrc, K. (2008). Recent antiviral strategies against human coronavirus-related respiratory illnesses. Current Opinion in Pulmonary Medicine, 14(3), 248–253. https://doi.org/10.1097/MCP.0b013e3282f7646f

Günther, S., Asper, M., Röser, C., Luna, L. K. S., Drosten, C., Becker-Ziaja, B., Borowski, P., Chen, H.-M., & Hosmane, R. S. (2004). Application of real-time PCR for testing antiviral compounds against Lassa virus, SARS coronavirus and Ebola virus in vitro. Antiviral Research, 63(3), 209–215. https://doi.org/10.1016/j.antiviral.2004.05.001

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Antiviral Antibodies, Immunity, and Coronaviruses

Antiviral Antibodies and Coronaviruses

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Mutations in virus-derived CD8 T-cell epitopes may abolish cytotoxic T-lymphocyte (CTL) recognition (Butler et al., 2007).
  • The mutations may block virus clearance in coronavirus-infected hosts.
  • These “CTL escape variant viruses” may lead to disease progression and elevated disease severity.
  • Antiviral antibody-mediated inhibition of virus replication and subsequent virus clearance may help prevent the CTL escape.
  • B-cell-deficient mice may shelter the CTL escape and would not eliminate infectious viruses effectively (Butler et al., 2007).
  • Antiviral antibodies are crucial for the protection from the CTL escape variant viruses.

Antiviral Immunity and Coronavirus Vaccine Vectors

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Effective vaccination against infectious viruses relies on specific antigens targeting dendritic cells (DCs).
  • Vaccine vectors may help with the delivery of antigens to antigen-presenting cells (APCs) (Cervantes-Barragan et al., 2010).
  • Vaccine vectors derived from attenuated murine coronavirus genomes were produced to express epitopes.
  • These epitopes can be from the lymphocytic choriomeningitis virus glycoprotein or human Melan-A.
  • They can be combined with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF).
  • These vectors may selectively target DCs and lead to vector-mediated antigen expression and the maturation of DCs.
  • Single application of low vector doses may cause strong and long-term cytotoxic T-cell responses.
  • Such responses may enable protective antiviral and antitumor immune functions.
  • The DCs transduced with Melan-A-recombinant virus may activate tumor-specific CD8(+) T cells (Cervantes-Barragan et al., 2010).
  • Such a vaccine platform can be used to transport antigens and immunostimulatory cytokines to DCs to enable protective immunity.

References:

Butler, N. S., Dandekar, A. A., & Perlman, S. (2007). Antiviral antibodies are necessary to prevent cytotoxic T-lymphocyte escape in mice infected with a coronavirus. Journal of Virology, 81(24), 13291–13298. https://doi.org/10.1128/JVI.01580-07

Cervantes-Barragan, L., Züst, R., Maier, R., Sierro, S., Janda, J., Levy, F., Speiser, D., Romero, P., Rohrlich, P.-S., Ludewig, B., & Thiel, V. (2010). Dendritic cell-specific antigen delivery by coronavirus vaccine vectors induces long-lasting protective antiviral and antitumor immunity. MBio, 1(4). https://doi.org/10.1128/mBio.00171-10

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Potential Antiviral Agents for SARS and Various Coronaviruses

Indomethacin for Various Coronaviruses

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • Cyclopentenone cyclooxygenase (COX) metabolites have been found to be useful targets against RNA viruses (Amici et al., 2006).
  • The COX inhibitor indomethacin (INDO) may have antiviral effects against SARS-CoV and canine coronavirus (CCoV).
  • INDO may inhibit the viral RNA synthesis and replication.
  • The antiviral effects of INDO have been tested in CCoV-infected dogs (Amici et al., 2006).
  • INDO has both anti-inflammatory and antiviral effects with potentials for the treatment of SARS and other coronaviruses.

P-PMOs for Murine Hepatitis Virus (MHV)

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The antiviral effects of peptide-conjugated antisense phosphorodiamidate morpholino oligomers (P-PMOs) were examined.
  • P-PMOs were tested for several strains of murine hepatitis virus (MHV) (Burrer et al., 2007).
  • One of the P-PMOs (5TERM) complementary to the 5’ terminus of the genomic RNA was found effective against six strains of MHV.
  • The 5TERM P-PMO therapy decreased viral titers in target organs and protected from virus-induced tissue damages in mouse models.
  • The prophylactic 5TERM P-PMO therapy alleviated weight loss caused by infections and prolonged survival.
  • However, 5TERM P-PMO was not protective in the cases of high-dose viral infections followed by delayed treatment.
  • P-PMO may have toxic effects in late-stage diseased mice (Burrer et al., 2007).  
  • With its antiviral effects, further development of P-PMO may provide treatments for a broad spectrum of coronavirus infections.

Potential Antiviral Agents for Hepatitis C Virus and SARS

(From Potential Antiviral Agents for Coronaviruses: Compounds, Herbal Products, and Drug Targets)

  • The 5-hydroxychromone (5b-5g) may be a potential antiviral agent with anti-hepatitis C virus (HCV) effects (Kim et al., 2011).
  • Some of the derivatives 5b-5f were found effective against SARS-associated coronavirus (SCV).
  • The 5b-5f were effective against both NTPase and helicase activities of the target enzymes of SCV.
  • The 3-iodobenzyloxy-substituted derivative 5e had the most potent activity against HCV and SCV.
  • Such platform structures may be useful for the design of multi-targets or broad-spectrum antiviral drugs (Kim et al., 2011).

References:

Amici, C., Di Caro, A., Ciucci, A., Chiappa, L., Castilletti, C., Martella, V., Decaro, N., Buonavoglia, C., Capobianchi, M. R., & Santoro, M. G. (2006). Indomethacin has a potent antiviral activity against SARS coronavirus. Antiviral Therapy, 11(8), 1021–1030.

Burrer, R., Neuman, B. W., Ting, J. P. C., Stein, D. A., Moulton, H. M., Iversen, P. L., Kuhn, P., & Buchmeier, M. J. (2007). Antiviral effects of antisense morpholino oligomers in murine coronavirus infection models. Journal of Virology, 81(11), 5637–5648. https://doi.org/10.1128/JVI.02360-06

Kim, M. K., Yu, M.-S., Park, H. R., Kim, K. B., Lee, C., Cho, S. Y., Kang, J., Yoon, H., Kim, D.-E., Choo, H., Jeong, Y.-J., & Chong, Y. (2011). 2,6-Bis-arylmethyloxy-5-hydroxychromones with antiviral activity against both hepatitis C virus (HCV) and SARS-associated coronavirus (SCV). European Journal of Medicinal Chemistry, 46(11), 5698–5704. https://doi.org/10.1016/j.ejmech.2011.09.005

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Remdesivir and Chloroquine as Potential Broad-Spectrum Antiviral Drugs

Remdesivir As A Potential Broad-Spectrum Antiviral Drug

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • The nucleoside analogue GS-5734 (remdesivir) has been found to inhibit human and zoonotic CoVs (Agostini et al., 2018).
  • GS-5734 may inhibit murine hepatitis virus (MHV), SARS-CoV and MERS-CoV.
  • GS-5734 could be a broad-spectrum drug to protect against current and novel CoVs.
  • The effects of nucleoside-based therapeutics may be blocked by a proofreading exoribonuclease (ExoN), e.g., the CoV nsp14 ExoN.
  • To solve the problem, a group β-2a CoV was added to the nucleotide prodrug remdesivir (GS-5734).
  • Higher and nontoxic concentrations of GS-5734 may help overcome the viral resistance.
  • Further development of GS-5734 has the potential to make it as an effective pan-CoV antiviral agent (Agostini et al., 2018).        

The Broad-Spectrum Antiviral Effects of Chloroquine

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • HCoVs including HCoV-OC43 may cause 15 to 30% of mild upper respiratory tract infections (Keyaerts et al., 2009).
  • Chloroquine has been used for its antimalarial functions, and may inhibit HCoV-OC43 replication.
  • Chloroquine may also prevent HCoV-OC43-induced death in newborn mice given through maternal milk.
  • The high survival rate occurred when the mother mice were given the drug with 15 mg/kg of body weight/day.
  • Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg and 13% survival with 1 mg/kg.
  • Chloroquine has been found effective against HCoV-OC43 infection in mice as a potential drug (Keyaerts et al., 2009).

References:

Agostini, M. L., Andres, E. L., Sims, A. C., Graham, R. L., Sheahan, T. P., Lu, X., Smith, E. C., Case, J. B., Feng, J. Y., Jordan, R., Ray, A. S., Cihlar, T., Siegel, D., Mackman, R. L., Clarke, M. O., Baric, R. S., & Denison, M. R. (2018). Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. MBio, 9(2). https://doi.org/10.1128/mBio.00221-18

Keyaerts, E., Li, S., Vijgen, L., Rysman, E., Verbeeck, J., Van Ranst, M., & Maes, P. (2009). Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrobial Agents and Chemotherapy, 53(8), 3416–3421. https://doi.org/10.1128/AAC.01509-08

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Broad-Spectrum Antiviral Drugs for Coronaviruses

Broad-Spectrum Antiviral Drugs for Coronaviruses

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • Broad-spectrum antiviral drugs may lower the vulnerability of public health systems to the coronavirus pandemic.
  • Broad-spectrum antiviral drugs are needed to
    • Combat the emergence of novel coronaviruses, e.g., COVID-19;
    • Prevent the re-emergence of SARS-CoV, its mutants, and other related viruses;
    • Combat the continuance of MERS-CoV infections (Totura and Bavari, 2019).
  • Experiences from SARS and MERS outbreaks have revealed the demands for drugs with pan-coronavirus antiviral activities.

Antiviral Strategies for Coronaviruses

(From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • Nucleoside analogues may have antiviral effects against SARS-CoV (Chu et al., 2006).
  • Methods can be developed to antagonize viral nonstructural proteins (Totura and Bavari, 2019).
  • Agents can be designed to neutralize structural proteins of the coronaviruses.
  • Approaches can be developed to modulate essential host elements of viral infections.

References:

Chu, C. K., Gadthula, S., Chen, X., Choo, H., Olgen, S., Barnard, D. L., & Sidwell, R. W. (2006). Antiviral activity of nucleoside analogues against SARS-coronavirus (SARS-coV). Antiviral Chemistry & Chemotherapy, 17(5), 285–289. https://doi.org/10.1177/095632020601700506

Totura, A. L., & Bavari, S. (2019). Broad-spectrum coronavirus antiviral drug discovery. Expert Opinion on Drug Discovery, 14(4), 397–412. https://doi.org/10.1080/17460441.2019.1581171

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About Coronaviruses (CoVs)

About Coronaviruses (CoVs) (From Potential Antiviral Agents for Coronavirus-es: Compounds, Herbal Products, and Drug Targets)

  • Coronaviruses (CoVs) may lead to lethal infections, but currently no effective antiviral therapeutics or vaccines are available.
  • The pandemic of the deadly coronavirus disease 2019 (COVID-19) is a reminder that such coronaviruses can emerge at any time.
  • COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • Novel human coronaviruses (HCoVs) may lead to severe respiratory tract infections such as bronchiolitis and pneumonia.
  • More than 15 years have passed since the severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from China.
  • SARS is an acute respiratory disease with high morbidity and mortality.
  • The Middle East respiratory syndrome coronavirus (MERS-CoV) is another fatal zoonotic virus (Totura and Bavari, 2019).
  • These coronaviruses can cause Acute Respiratory Distress Syndrome (ARDS) and renal failure.
  • They are highly transmissible and can spread from person-to-person through close contact (Totura and Bavari, 2019).

References:

Totura, A. L., & Bavari, S. (2019). Broad-spectrum coronavirus antiviral drug discovery. Expert Opinion on Drug Discovery, 14(4), 397–412. https://doi.org/10.1080/17460441.2019.1581171

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Studies about Antiviral Drugs for Coronaviruses


The Antiviral Remdesivir and the Coronavirus SARS-CoV

Agostini, M. L., Andres, E. L., Sims, A. C., Graham, R. L., Sheahan, T. P., Lu, X., Smith, E. C., Case, J. B., Feng, J. Y., Jordan, R., Ray, A. S., Cihlar, T., Siegel, D., Mackman, R. L., Clarke, M. O., Baric, R. S., & Denison, M. R. (2018). Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. MBio, 9(2). https://doi.org/10.1128/mBio.00221-18

The Antiviral Compound β-d-N4-Hydroxycytidine and the Coronavirus MERS-CoV

Agostini, M. L., Pruijssers, A. J., Chappell, J. D., Gribble, J., Lu, X., Andres, E. L., Bluemling, G. R., Lockwood, M. A., Sheahan, T. P., Sims, A. C., Natchus, M. G., Saindane, M., Kolykhalov, A. A., Painter, G. R., Baric, R. S., & Denison, M. R. (2019). Small-Molecule Antiviral β-d-N4-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance. Journal of Virology, 93(24). https://doi.org/10.1128/JVI.01348-19

The Antiviral Indomethacin and the Coronavirus SARS-CoV

Amici, C., Di Caro, A., Ciucci, A., Chiappa, L., Castilletti, C., Martella, V., Decaro, N., Buonavoglia, C., Capobianchi, M. R., & Santoro, M. G. (2006). Indomethacin has a potent antiviral activity against SARS coronavirus. Antiviral Therapy, 11(8), 1021–1030.

The Antiviral Effects of P-PMOs

Burrer, R., Neuman, B. W., Ting, J. P. C., Stein, D. A., Moulton, H. M., Iversen, P. L., Kuhn, P., & Buchmeier, M. J. (2007). Antiviral effects of antisense morpholino oligomers in murine coronavirus infection models. Journal of Virology, 81(11), 5637–5648. https://doi.org/10.1128/JVI.02360-06

Antiviral Flavonoids and DENV

Chiow, K. H., Phoon, M. C., Putti, T., Tan, B. K. H., & Chow, V. T. (2016). Evaluation of antiviral activities of Houttuynia cordata Thunb. Extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. Asian Pacific Journal of Tropical Medicine, 9(1), 1–7. https://doi.org/10.1016/j.apjtm.2015.12.002

Nucleoside Analogues and SARS-CoV

Chu, C. K., Gadthula, S., Chen, X., Choo, H., Olgen, S., Barnard, D. L., & Sidwell, R. W. (2006). Antiviral activity of nucleoside analogues against SARS-coronavirus (SARS-coV). Antiviral Chemistry & Chemotherapy, 17(5), 285–289. https://doi.org/10.1177/095632020601700506

The Antiviral Effects of Common Household Disinfectants for SARS-CoV

Dellanno, C., Vega, Q., & Boesenberg, D. (2009). The antiviral action of common household disinfectants and antiseptics against murine hepatitis virus, a potential surrogate for SARS coronavirus. American Journal of Infection Control, 37(8), 649–652. https://doi.org/10.1016/j.ajic.2009.03.012

A Potential Antiviral Molecule for SARS-CoV and Ebola

Elshabrawy, H. A., Fan, J., Haddad, C. S., Ratia, K., Broder, C. C., Caffrey, M., & Prabhakar, B. S. (2014). Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay. Journal of Virology, 88(8), 4353–4365. https://doi.org/10.1128/JVI.03050-13

The Antiviral Effects of Glycyrrhizin and SARS-CoV

Hoever, G., Baltina, L., Michaelis, M., Kondratenko, R., Baltina, L., Tolstikov, G. A., Doerr, H. W., & Cinatl, J. (2005). Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. Journal of Medicinal Chemistry, 48(4), 1256–1259. https://doi.org/10.1021/jm0493008

Antiviral Effects of Chloroquine for the Coronavirus OC43

Keyaerts, E., Li, S., Vijgen, L., Rysman, E., Verbeeck, J., Van Ranst, M., & Maes, P. (2009). Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrobial Agents and Chemotherapy, 53(8), 3416–3421. https://doi.org/10.1128/AAC.01509-08

Antiviral Herbal Compounds for SARS

Schwarz, S., Sauter, D., Wang, K., Zhang, R., Sun, B., Karioti, A., Bilia, A. R., Efferth, T., & Schwarz, W. (2014). Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus. Planta Medica, 80(2–3), 177–182. https://doi.org/10.1055/s-0033-1360277

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Resources for Studying the 2019-nCoV Coronavirus (COVID-19): Databases and Tools

Resources for Studying the 2019-nCoV Coronavirus (COVID-19): Databases and Tools

  • “human coronaviruses such as …endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days…”

From Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents (https://www.journalofhospitalinfection.com/article/S0195-6701(20)30046-3/fulltext)

Including the sequence data and the BLAST tool.

  • Coronavirus COVID-19 Global Cases by Johns Hopkins CSSE:

https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6

Bioinformatics Analysis: Genes Identified in the 2019-nCoV Coronavirus (COVID-19)

  • E (envelope protein [Wuhan seafood market pneumonia virus])
  • M (membrane glycoprotein [Wuhan seafood market pneumonia virus])
  • N (nucleocapsid phosphoprotein [Wuhan seafood market pneumonia virus])
  • orf1ab (orf1a polyprotein;orf1ab polyprotein [Wuhan seafood market pneumonia virus])
  • ORF3a (ORF3a protein [Wuhan seafood market pneumonia virus])
  • ORF6 (ORF6 protein [Wuhan seafood market pneumonia virus])
  • ORF7a (ORF7a protein [Wuhan seafood market pneumonia virus])
  • ORF7b (ORF7b [Wuhan seafood market pneumonia virus])
  • ORF8 (ORF8 protein [Wuhan seafood market pneumonia virus])
  • ORF10 (ORF10 protein [Wuhan seafood market pneumonia virus])
  • S (surface glycoprotein [Wuhan seafood market pneumonia virus])

Publications about the 2019-nCoV Coronavirus (COVID-19)

Transmission and Epidemiology of 2019-nCoV (COVID-19)

  • Backer, J. A., Klinkenberg, D., & Wallinga, J. (2020). Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020. Euro Surveillance: Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, 25(5). https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000062
  • Giovanetti, M., Benvenuto, D., Angeletti, S., & Ciccozzi, M. (2020). The first two cases of 2019-nCoV in Italy: Where they come from? Journal of Medical Virology. https://doi.org/10.1002/jmv.25699
  • Habibzadeh, P., & Stoneman, E. K. (2020). The Novel Coronavirus: A Bird’s Eye View. The International Journal of Occupational and Environmental Medicine, 11(2), 65–71. https://doi.org/10.15171/ijoem.2020.1921
  • Holshue, M. L., DeBolt, C., Lindquist, S., Lofy, K. H., Wiesman, J., Bruce, H., Spitters, C., Ericson, K., Wilkerson, S., Tural, A., Diaz, G., Cohn, A., Fox, L., Patel, A., Gerber, S. I., Kim, L., Tong, S., Lu, X., Lindstrom, S., … Washington State 2019-nCoV Case Investigation Team. (2020). First Case of 2019 Novel Coronavirus in the United States. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2001191
  • Nishiura, H., Jung, S.-M., Linton, N. M., Kinoshita, R., Yang, Y., Hayashi, K., Kobayashi, T., Yuan, B., & Akhmetzhanov, A. R. (2020). The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020. Journal of Clinical Medicine, 9(2). https://doi.org/10.3390/jcm9020330
  • Nishiura, H., Kobayashi, T., Yang, Y., Hayashi, K., Miyama, T., Kinoshita, R., Linton, N. M., Jung, S.-M., Yuan, B., Suzuki, A., & Akhmetzhanov, A. R. (2020). The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights. Journal of Clinical Medicine, 9(2). https://doi.org/10.3390/jcm9020419
  • Patel, A., Jernigan, D. B., & 2019-nCoV CDC Response Team. (2020). Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak—United States, December 31, 2019-February 4, 2020. MMWR. Morbidity and Mortality Weekly Report, 69(5), 140–146. https://doi.org/10.15585/mmwr.mm6905e1
  • Riou, J., & Althaus, C. L. (2020). Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020. Euro Surveillance: Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, 25(4). https://doi.org/10.2807/1560-7917.ES.2020.25.4.2000058
  • Ryu, S., Chun, B. C., & Korean Society of Epidemiology 2019-nCoV Task Force Team. (2020). An interim review of the epidemiological characteristics of 2019 novel coronavirus. Epidemiology and Health, 42, e2020006. https://doi.org/10.4178/epih.e2020006
  • Wu, J. T., Leung, K., & Leung, G. M. (2020). Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: A modelling study. Lancet (London, England). https://doi.org/10.1016/S0140-6736(20)30260-9
  • Wu, P., Hao, X., Lau, E. H. Y., Wong, J. Y., Leung, K. S. M., Wu, J. T., Cowling, B. J., & Leung, G. M. (2020). Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020. Euro Surveillance: Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, 25(3). https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000044

Virus Evolution and Molecular Studies of 2019-nCoV (COVID-19)

  • Benvenuto, D., Giovanetti, M., Ciccozzi, A., Spoto, S., Angeletti, S., & Ciccozzi, M. (2020). The 2019-new coronavirus epidemic: Evidence for virus evolution. Journal of Medical Virology. https://doi.org/10.1002/jmv.25688
  • Benvenuto, D., Giovanetti, M., Salemi, M., Prosperi, M., De Flora, C., Junior Alcantara, L. C., Angeletti, S., & Ciccozzi, M. (2020). The global spread of 2019-nCoV: A molecular evolutionary analysis. Pathogens and Global Health, 1–4. https://doi.org/10.1080/20477724.2020.1725339
  • Ceraolo, C., & Giorgi, F. M. (2020). Genomic variance of the 2019-nCoV coronavirus. Journal of Medical Virology. https://doi.org/10.1002/jmv.25700

Detection and Diagnosis of 2019-nCoV (COVID-19)

  • Corman, V. M., Landt, O., Kaiser, M., Molenkamp, R., Meijer, A., Chu, D. K., Bleicker, T., Brünink, S., Schneider, J., Schmidt, M. L., Mulders, D. G., Haagmans, B. L., van der Veer, B., van den Brink, S., Wijsman, L., Goderski, G., Romette, J.-L., Ellis, J., Zambon, M., … Drosten, C. (2020). Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveillance: Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, 25(3). https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045
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Metabolomics of Obesity: Gut Microbiota

Recent Development in Metabolomics of Obesity: Gut Microbiota and Metabolic Syndrome

Abu Bakar, M. H., Sarmidi, M. R., Cheng, K.-K., Ali Khan, A., Suan, C. L., Zaman Huri, H., & Yaakob, H. (2015). Metabolomics – the complementary field in systems biology: A review on obesity and type 2 diabetes. Molecular BioSystems, 11(7), 1742–1774. https://doi.org/10.1039/c5mb00158g

Aguilar-Salinas, C. A., & Viveros-Ruiz, T. (2019). Recent advances in managing/understanding the metabolic syndrome. F1000Research, 8. https://doi.org/10.12688/f1000research.17122.1

Aw, W., & Fukuda, S. (2015). Toward the comprehensive understanding of the gut ecosystem via metabolomics-based integrated omics approach. Seminars in Immunopathology, 37(1), 5–16. https://doi.org/10.1007/s00281-014-0456-2

Heinken, A., & Thiele, I. (2015). Systems biology of host-microbe metabolomics. Wiley Interdisciplinary Reviews. Systems Biology and Medicine, 7(4), 195–219. https://doi.org/10.1002/wsbm.1301

Hoek, M. J. A. van, & Merks, R. M. H. (2017). Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism. BMC Systems Biology, 11(1), 56. https://doi.org/10.1186/s12918-017-0430-4

Jaitin, D. A., Adlung, L., Thaiss, C. A., Weiner, A., Li, B., Descamps, H., … Amit, I. (2019). Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner. Cell, 178(3), 686-698.e14. https://doi.org/10.1016/j.cell.2019.05.054

Kieffer, D. A., Piccolo, B. D., Marco, M. L., Kim, E. B., Goodson, M. L., Keenan, M. J., … Adams, S. H. (2016). Mice Fed a High-Fat Diet Supplemented with Resistant Starch Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria. The Journal of Nutrition, 146(12), 2476–2490. https://doi.org/10.3945/jn.116.238931

Mathur, S. K., Tiwari, P., Gupta, S., Gupta, N., Nimesh, S., Medicherla, K. M., & Suravajhala, P. (2018). Genetics of Lipodystrophy: Can It Help in Understanding the Pathophysiology of Metabolic Syndrome? Biomolecules, 8(3). https://doi.org/10.3390/biom8030047

Meijnikman, A. S., Gerdes, V. E., Nieuwdorp, M., & Herrema, H. (2018). Evaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans. Endocrine Reviews, 39(2), 133–153. https://doi.org/10.1210/er.2017-00192

Wang, J., Ma, M. C. J., Mennie, A. K., Pettus, J. M., Xu, Y., Lin, L., … Kwitek, A. E. (2015). Systems biology with high-throughput sequencing reveals genetic mechanisms underlying the metabolic syndrome in the Lyon hypertensive rat. Circulation. Cardiovascular Genetics, 8(2), 316–326. https://doi.org/10.1161/CIRCGENETICS.114.000520

Wu, H., Tremaroli, V., & Bäckhed, F. (2015). Linking Microbiota to Human Diseases: A Systems Biology Perspective. Trends in Endocrinology and Metabolism: TEM, 26(12), 758–770. https://doi.org/10.1016/j.tem.2015.09.011

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Biomarkers Database: Obesity in Different Populations

Park, B.-Y., Hong, J., & Park, H. (2017). Neuroimaging biomarkers to associate obesity and negative emotions. Scientific Reports, 7(1), 7664. https://doi.org/10.1038/s41598-017-08272-8

Pecht, T., Gutman-Tirosh, A., Bashan, N., & Rudich, A. (2014). Peripheral blood leucocyte subclasses as potential biomarkers of adipose tissue inflammation and obesity subphenotypes in humans. Obesity Reviews: An Official Journal of the International Association for the Study of Obesity, 15(4), 322–337. https://doi.org/10.1111/obr.12133

Pescador, N., Pérez-Barba, M., Ibarra, J. M., Corbatón, A., Martínez-Larrad, M. T., & Serrano-Ríos, M. (2013). Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers. PloS One, 8(10), e77251. https://doi.org/10.1371/journal.pone.0077251

Petrásová, D., Bertková, I., Petrásová, M., Hijová, E., Mareková, M., Babinská, I., … HepaMeta Team. (2014). Biomarkers associated with obesity and overweight in the Roma population residing in eastern Slovakia. Central European Journal of Public Health, 22 Suppl, S18-21. https://doi.org/10.21101/cejph.a3896

Pinheiro Volp, A. C., Santos Silva, F. C., & Bressan, J. (2015). Hepatic inflammatory biomarkers and its link with obesity and chronic diseases. Nutricion Hospitalaria, 31(5), 1947–1956. https://doi.org/10.3305/nh.2015.31.5.8525

Porter Starr, K. N., Orenduff, M., McDonald, S. R., Mulder, H., Sloane, R., Pieper, C. F., & Bales, C. W. (2019). Influence of Weight Reduction and Enhanced Protein Intake on Biomarkers of Inflammation in Older Adults with Obesity. Journal of Nutrition in Gerontology and Geriatrics, 38(1), 33–49. https://doi.org/10.1080/21551197.2018.1564200

Randell, E. W., Twells, L. K., Gregory, D. M., Lester, K. K., Daneshtalab, N., Dillon, C., … Boone, D. (2018). Pre-operative and post-operative changes in CRP and other biomarkers sensitive to inflammatory status in patients with severe obesity undergoing laparoscopic sleeve gastrectomy. Clinical Biochemistry, 52, 13–19. https://doi.org/10.1016/j.clinbiochem.2017.10.010

Rashad, N. M., El-Shabrawy, R. M., Sabry, H. M., Fathy, H. A., Said, D., & Yousef, M. S. (2018). Interleukin-6 and hs-CRP as Early Diagnostic Biomarkers for Obesity-Related Peripheral Polyneuropathy in Non-Diabetic Patients. The Egyptian Journal of Immunology, 25(2), 153–165.

Rauschert, S., Uhl, O., Koletzko, B., & Hellmuth, C. (2014). Metabolomic biomarkers for obesity in humans: a short review. Annals of Nutrition & Metabolism, 64(3–4), 314–324. https://doi.org/10.1159/000365040

Recker, E. N., Brogden, K. A., Avila-Ortiz, G., Fischer, C. L., Pagan-Rivera, K., Dawson, D. V., … Elangovan, S. (2015). Novel biomarkers of periodontitis and/or obesity in saliva-An exploratory analysis. Archives of Oral Biology, 60(10), 1503–1509. https://doi.org/10.1016/j.archoralbio.2015.07.006

Ribeiro, C., Dourado, G., & Cesar, T. (2017). Orange juice allied to a reduced-calorie diet results in weight loss and ameliorates obesity-related biomarkers: A randomized controlled trial. Nutrition (Burbank, Los Angeles County, Calif.), 38, 13–19. https://doi.org/10.1016/j.nut.2016.12.020

Rivera, P., Martos-Moreno, G. Á., Barrios, V., Suárez, J., Pavón, F. J., Chowen, J. A., … Argente, J. (2019). A novel approach to childhood obesity: circulating chemokines and growth factors as biomarkers of insulin resistance. Pediatric Obesity, 14(3), e12473. https://doi.org/10.1111/ijpo.12473

Rodríguez-Rivera, C., Pérez-García, C., Muñoz-Rodríguez, J. R., Vicente-Rodríguez, M., Polo, F., Ford, R.-M., … Alguacil, L. F. (2019). Proteomic Identification of Biomarkers Associated with Eating Control and Bariatric Surgery Outcomes in Patients with Morbid Obesity. World Journal of Surgery, 43(3), 744–750. https://doi.org/10.1007/s00268-018-4851-z

Sandhu, R. K., Ezekowitz, J. A., Hijazi, Z., Westerbergh, J., Aulin, J., Alexander, J. H., … Wallentin, L. (2018). Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers: insights from the ARISTOTLE trial. Open Heart, 5(2), e000908. https://doi.org/10.1136/openhrt-2018-000908

Santilli, F., Guagnano, M. T., Vazzana, N., La Barba, S., & Davi, G. (2015). Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach. Current Medicinal Chemistry, 22(5), 582–595.

Schlesinger, S., Herder, C., Kannenberg, J. M., Huth, C., Carstensen-Kirberg, M., Rathmann, W., … Ziegler, D. (2019). General and Abdominal Obesity and Incident Distal Sensorimotor Polyneuropathy: Insights Into Inflammatory Biomarkers as Potential Mediators in the KORA F4/FF4 Cohort. Diabetes Care, 42(2), 240–247. https://doi.org/10.2337/dc18-1842

Scrivo, R., Vasile, M., Müller-Ladner, U., Neumann, E., & Valesini, G. (2013). Rheumatic diseases and obesity: adipocytokines as potential comorbidity biomarkers for cardiovascular diseases. Mediators of Inflammation, 2013, 808125. https://doi.org/10.1155/2013/808125

Selma, M. V., González-Sarrías, A., Salas-Salvadó, J., Andrés-Lacueva, C., Alasalvar, C., Örem, A., … Espín, J. C. (2018). The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome. Clinical Nutrition (Edinburgh, Scotland), 37(3), 897–905. https://doi.org/10.1016/j.clnu.2017.03.012

Serra, M. C., Beavers, D. P., Henderson, R. M., Kelleher, J. L., Kiel, J. R., & Beavers, K. M. (2019). Effects of a Hypocaloric, Nutritionally Complete, Higher Protein Meal Plan on Regional Body Fat and Cardiometabolic Biomarkers in Older Adults with Obesity. Annals of Nutrition & Metabolism, 74(2), 149–155. https://doi.org/10.1159/000497066

Shaver, L. N., Beavers, D. P., Kiel, J., Kritchevsky, S. B., & Beavers, K. M. (2018). Effect of Intentional Weight Loss on Mortality Biomarkers in Older Adults With Obesity. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. https://doi.org/10.1093/gerona/gly192

Shen, S.-H., Shen, S.-Y., Liou, T.-H., Hsu, M.-I., Chang, Y. I., Cheng, C.-Y., … Tzeng, C.-R. (2015). Obesity and inflammatory biomarkers in women with polycystic ovary syndrome. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 192, 66–71. https://doi.org/10.1016/j.ejogrb.2015.06.022

Shin, Y. H., Kim, K. E., Lee, Y.-J., Nam, J.-H., Hong, Y. M., & Shin, H.-J. (2014). Associations of matrix metalloproteinase (MMP)-8, MMP-9, and their inhibitor, tissue inhibitor of metalloproteinase-1, with obesity-related biomarkers in apparently healthy adolescent boys. Korean Journal of Pediatrics, 57(12), 526–532. https://doi.org/10.3345/kjp.2014.57.12.526

Socha, P., Hellmuth, C., Gruszfeld, D., Demmelmair, H., Rzehak, P., Grote, V., … European Childhood Obesity Trial Study Group. (2016). Endocrine and Metabolic Biomarkers Predicting Early Childhood Obesity Risk. Nestle Nutrition Institute Workshop Series, 85, 81–88. https://doi.org/10.1159/000439489

Tenório, T. R. S., Balagopal, P. B., Andersen, L. B., Ritti-Dias, R. M., Hill, J. O., Lofrano-Prado, M. C., & Prado, W. L. (2018). Effect of Low- Versus High-Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study. Pediatric Exercise Science, 30(1), 96–105. https://doi.org/10.1123/pes.2017-0067

Tolusso, B., Gigante, M. R., Alivernini, S., Petricca, L., Fedele, A. L., Di Mario, C., … Gremese, E. (2018). Chemerin and PEDF Are Metaflammation-Related Biomarkers of Disease Activity and Obesity in Rheumatoid Arthritis. Frontiers in Medicine, 5, 207. https://doi.org/10.3389/fmed.2018.00207

Torres-Perez, E., Valero, M., Garcia-Rodriguez, B., Gonzalez-Irazabal, Y., Calmarza, P., Calvo-Ruata, L., … Arbones-Mainar, J. M. (2015). The FAT expandability (FATe) Project: Biomarkers to determine the limit of expansion and the complications of obesity. Cardiovascular Diabetology, 14, 40. https://doi.org/10.1186/s12933-015-0203-6

Tsai, C.-L., Huang, T.-H., & Tsai, M.-C. (2017). Neurocognitive performances of visuospatial attention and the correlations with metabolic and inflammatory biomarkers in adults with obesity. Experimental Physiology, 102(12), 1683–1699. https://doi.org/10.1113/EP086624

Tulipani, S., Palau-Rodriguez, M., Miñarro Alonso, A., Cardona, F., Marco-Ramell, A., Zonja, B., … Andres-Lacueva, C. (2016). Biomarkers of Morbid Obesity and Prediabetes by Metabolomic Profiling of Human Discordant Phenotypes. Clinica Chimica Acta; International Journal of Clinical Chemistry, 463, 53–61. https://doi.org/10.1016/j.cca.2016.10.005

Vasquez, M. M., Hu, C., Roe, D. J., Chen, Z., Halonen, M., & Guerra, S. (2016). Least absolute shrinkage and selection operator type methods for the identification of serum biomarkers of overweight and obesity: simulation and application. BMC Medical Research Methodology, 16(1), 154. https://doi.org/10.1186/s12874-016-0254-8

Vernarelli, J. A., Mitchell, D. C., Rolls, B. J., & Hartman, T. J. (2015). Dietary energy density is associated with obesity and other biomarkers of chronic disease in US adults. European Journal of Nutrition, 54(1), 59–65. https://doi.org/10.1007/s00394-014-0685-0

Vernini, J. M., Moreli, J. B., Costa, R. A. A., Negrato, C. A., Rudge, M. V. C., & Calderon, I. M. P. (2016). Maternal adipokines and insulin as biomarkers of pregnancies complicated by overweight and obesity. Diabetology & Metabolic Syndrome, 8(1), 68. https://doi.org/10.1186/s13098-016-0184-y

Vigna, L., Vassalle, C., Tirelli, A. S., Gori, F., Tomaino, L., Sabatino, L., & Bamonti, F. (2017). Gender-related association between uric acid, homocysteine, γ-glutamyltransferase, inflammatory biomarkers and metabolic syndrome in subjects affected by obesity. Biomarkers in Medicine. https://doi.org/10.2217/bmm-2017-0072

Vurbic, D., Harder, V. S., Redner, R. R., Lopez, A. A., Phillips, J. K., & Higgins, S. T. (2015). Co-occurring obesity and smoking among U.S. women of reproductive age: Associations with educational attainment and health biomarkers and outcomes. Preventive Medicine, 80, 60–66. https://doi.org/10.1016/j.ypmed.2015.05.020

Wiseman, A. J., Lynch, B. M., Cameron, A. J., & Dunstan, D. W. (2014). Associations of change in television viewing time with biomarkers of postmenopausal breast cancer risk: the Australian Diabetes, Obesity and Lifestyle Study. Cancer Causes & Control: CCC, 25(10), 1309–1319. https://doi.org/10.1007/s10552-014-0433-z

Yassour, M., Lim, M. Y., Yun, H. S., Tickle, T. L., Sung, J., Song, Y.-M., … Huttenhower, C. (2016). Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Medicine, 8(1), 17. https://doi.org/10.1186/s13073-016-0271-6

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Biomarkers Database: Obesity, Cognition, and Inflammation

Garcia-Mazcorro, J. F., Mills, D. A., Murphy, K., & Noratto, G. (2018). Effect of barley supplementation on the fecal microbiota, caecal biochemistry, and key biomarkers of obesity and inflammation in obese db/db mice. European Journal of Nutrition, 57(7), 2513–2528. https://doi.org/10.1007/s00394-017-1523-y

Ghosh, S., Murinova, L., Trnovec, T., Loffredo, C. A., Washington, K., Mitra, P. S., & Dutta, S. K. (2014). Biomarkers linking PCB exposure and obesity. Current Pharmaceutical Biotechnology, 15(11), 1058–1068.

Goguet-Rubio, P., Klug, R. L., Sharma, D. L., Srikanthan, K., Puri, N., Lakhani, V. H., … Sodhi, K. (2017). Existence of a Strong Correlation of Biomarkers and miRNA in Females with Metabolic Syndrome and Obesity in a Population of West Virginia. International Journal of Medical Sciences, 14(6), 543–553. https://doi.org/10.7150/ijms.18988

Hawkins, M. a. W., Colaizzi, J., Gunstad, J., Hughes, J. W., Mullins, L. L., Betts, N., … Lovallo, W. R. (2018). Cognitive and Self-regulatory Mechanisms of Obesity Study (COSMOS): Study protocol for a randomized controlled weight loss trial examining change in biomarkers, cognition, and self-regulation across two behavioral treatments. Contemporary Clinical Trials, 66, 20–27. https://doi.org/10.1016/j.cct.2017.12.010

Hilger-Kolb, J., Bosle, C., Motoc, I., & Hoffmann, K. (2017). Associations between dietary factors and obesity-related biomarkers in healthy children and adolescents – a systematic review. Nutrition Journal, 16(1), 85. https://doi.org/10.1186/s12937-017-0300-3

Hulsmans, M., & Holvoet, P. (2013). MicroRNAs as early biomarkers in obesity and related metabolic and cardiovascular diseases. Current Pharmaceutical Design, 19(32), 5704–5717.

Indumathy, J., Pal, G. K., Pal, P., Ananthanarayanan, P. H., Parija, S. C., Balachander, J., & Dutta, T. K. (2015). Association of sympathovagal imbalance with obesity indices, and abnormal metabolic biomarkers and cardiovascular parameters. Obesity Research & Clinical Practice, 9(1), 55–66. https://doi.org/10.1016/j.orcp.2014.01.007

Iwasaki, M., Le Marchand, L., Franke, A. A., Hamada, G. S., Miyajima, N. T., Sharma, S., … Tsugane, S. (2016). Comparison of plasma levels of obesity-related biomarkers among Japanese populations in Tokyo, Japan, São Paulo, Brazil, and Hawaii, USA. European Journal of Cancer Prevention: The Official Journal of the European Cancer Prevention Organisation (ECP), 25(1), 41–49. https://doi.org/10.1097/CEJ.0000000000000123

Jacobs, C. A., Vranceanu, A.-M., Thompson, K. L., & Lattermann, C. (2018). Rapid Progression of Knee Pain and Osteoarthritis Biomarkers Greatest for Patients with Combined Obesity and Depression: Data from the Osteoarthritis Initiative. Cartilage, 1947603518777577. https://doi.org/10.1177/1947603518777577

Ji, Y., Park, S., Chung, Y., Kim, B., Park, H., Huang, E., … Holzapfel, W. H. (2019). Amelioration of obesity-related biomarkers by Lactobacillus sakei CJLS03 in a high-fat diet-induced obese murine model. Scientific Reports, 9(1), 6821. https://doi.org/10.1038/s41598-019-43092-y

Kannan, S., Acosta, L. M., Acevedo-Garcia, D., Divjan, A., Bracero, L. A., Perzanowski, M. S., & Chew, G. L. (2013). Sociocultural characteristics, obesity and inflammatory biomarkers in Puerto Rican toddlers born in New York City. Pediatric Allergy and Immunology: Official Publication of the European Society of Pediatric Allergy and Immunology, 24(5), 487–492. https://doi.org/10.1111/pai.12084

Katsareli, E. A., & Dedoussis, G. V. (2014). Biomarkers in the field of obesity and its related comorbidities. Expert Opinion on Therapeutic Targets, 18(4), 385–401. https://doi.org/10.1517/14728222.2014.882321

Kim, D.-H., Kim, H., Jeong, D., Kang, I.-B., Chon, J.-W., Kim, H.-S., … Seo, K.-H. (2017). Kefir alleviates obesity and hepatic steatosis in high-fat diet-fed mice by modulation of gut microbiota and mycobiota: targeted and untargeted community analysis with correlation of biomarkers. The Journal of Nutritional Biochemistry, 44, 35–43. https://doi.org/10.1016/j.jnutbio.2017.02.014

Lafortuna, C. L., Tovar, A. R., Rastelli, F., Tabozzi, S. A., Caramenti, M., Orozco-Ruiz, X., … Bertoli, G. (2017). Clinical, functional, behavioural and epigenomic biomarkers of obesity. Frontiers in Bioscience (Landmark Edition), 22, 1655–1681.

Levy, E., Saenger, A. K., Steffes, M. W., & Delvin, E. (2017). Pediatric Obesity and Cardiometabolic Disorders: Risk Factors and Biomarkers. EJIFCC, 28(1), 6–24.

Lloret-Linares, C., Miyauchi, E., Luo, H., Labat, L., Bouillot, J.-L., Poitou, C., … Declèves, X. (2016). Oral Morphine Pharmacokinetic in Obesity: The Role of P-Glycoprotein, MRP2, MRP3, UGT2B7, and CYP3A4 Jejunal Contents and Obesity-Associated Biomarkers. Molecular Pharmaceutics, 13(3), 766–773. https://doi.org/10.1021/acs.molpharmaceut.5b00656

Lorente-Cebrián, S., González-Muniesa, P., Milagro, F. I., & Martínez, J. A. (2019). MicroRNAs and other non-coding RNAs in adipose tissue and obesity: emerging roles as biomarkers and therapeutic targets. Clinical Science (London, England: 1979), 133(1), 23–40. https://doi.org/10.1042/CS20180890

Lubrano, C., Valacchi, G., Specchia, P., Gnessi, L., Rubanenko, E. P., Shuginina, E. A., … De Luca, C. (2015). Integrated Haematological Profiles of Redox Status, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome. Oxidative Medicine and Cellular Longevity, 2015, 490613. https://doi.org/10.1155/2015/490613

Luciano, R., Barraco, G. M., Muraca, M., Ottino, S., Spreghini, M. R., Sforza, R. W., … Manco, M. (2015). Biomarkers of Alzheimer disease, insulin resistance, and obesity in childhood. Pediatrics, 135(6), 1074–1081. https://doi.org/10.1542/peds.2014-2391

MacKintosh, M. L., Derbyshire, A. E., McVey, R. J., Bolton, J., Nickkho-Amiry, M., Higgins, C. L., … Crosbie, E. J. (2019). The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk. International Journal of Cancer, 144(3), 641–650. https://doi.org/10.1002/ijc.31913

Marcondes, J. P. de C., Andrade, P. F. B., Sávio, A. L. V., Silveira, M. A. D., Rudge, M. V. C., & Salvadori, D. M. F. (2018). BCL2 and miR-181a transcriptional alterations in umbilical-cord blood cells can be putative biomarkers for obesity. Mutation Research. Genetic Toxicology and Environmental Mutagenesis, 836(Pt B), 90–96. https://doi.org/10.1016/j.mrgentox.2018.06.009

Miller, A. L., Lee, H. J., & Lumeng, J. C. (2015). Obesity-associated biomarkers and executive function in children. Pediatric Research, 77(1–2), 143–147. https://doi.org/10.1038/pr.2014.158

Montilla, M., Santi, M. J., Carrozas, M. A., & Ruiz, F. A. (2014). Biomarkers of the prothrombotic state in abdominal obesity. Nutricion Hospitalaria, 31(3), 1059–1066. https://doi.org/10.3305/nh.2015.31.3.8168

Mozafarizadeh, M., Mohammadi, M., Sadeghi, S., Hadizadeh, M., Talebzade, T., & Houshmand, M. (2019). Evaluation of FTO rs9939609 and MC4R rs17782313 Polymorphisms as Prognostic Biomarkers of Obesity: A Population-based Cross-sectional Study. Oman Medical Journal, 34(1), 56–62. https://doi.org/10.5001/omj.2019.09

Nasr, H. B., Dimassi, S., M’hadhbi, R., Debbabi, H., Kortas, M., Tabka, Z., & Chahed, K. (2016). Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians. Obesity Research & Clinical Practice, 10(4), 465–475. https://doi.org/10.1016/j.orcp.2015.04.008

Netto, B. D. M., Bettini, S. C., Clemente, A. P. G., Ferreira, J. P. de C., Boritza, K., Souza, S. de F., … Dâmaso, A. R. (2015). Roux-en-Y gastric bypass decreases pro-inflammatory and thrombotic biomarkers in individuals with extreme obesity. Obesity Surgery, 25(6), 1010–1018. https://doi.org/10.1007/s11695-014-1484-7

Nimptsch, K., Konigorski, S., & Pischon, T. (2019). Diagnosis of obesity and use of obesity biomarkers in science and clinical medicine. Metabolism: Clinical and Experimental, 92, 61–70. https://doi.org/10.1016/j.metabol.2018.12.006

Nimptsch, K., & Pischon, T. (2016). Obesity Biomarkers, Metabolism and Risk of Cancer: An Epidemiological Perspective. Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progres Dans Les Recherches Sur Le Cancer, 208, 199–217. https://doi.org/10.1007/978-3-319-42542-9_11

Olza, J., Ruperez, A. I., Gil-Campos, M., Leis, R., Fernandez-Orth, D., Tojo, R., … Aguilera, C. M. (2013). Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case-control multicentre study. BMC Medical Genetics, 14, 123. https://doi.org/10.1186/1471-2350-14-123

O’Neil, C. E., Nicklas, T. A., Rampersaud, G. C., & Fulgoni, V. L. (2012). 100% orange juice consumption is associated with better diet quality, improved nutrient adequacy, decreased risk for obesity, and improved biomarkers of health in adults: National Health and Nutrition Examination Survey, 2003-2006. Nutrition Journal, 11, 107. https://doi.org/10.1186/1475-2891-11-107

Osadnik, T., Bujak, K., Osadnik, K., Czarnecka, H., Pawlas, N., Reguła, R., … Gąsior, M. (2019). Novel inflammatory biomarkers may reflect subclinical inflammation in young healthy adults with obesity. Endokrynologia Polska, 70(2), 135–142. https://doi.org/10.5603/EP.a2019.0002

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Biomarkers Database: Obesity, Metabolic Disorders, and Cardiovascular Risks

Aleksandrova, K., Mozaffarian, D., & Pischon, T. (2018). Addressing the Perfect Storm: Biomarkers in Obesity and Pathophysiology of Cardiometabolic Risk. Clinical Chemistry, 64(1), 142–153. https://doi.org/10.1373/clinchem.2017.275172

Bagheri, M., Djazayery, A., Qi, L., Yekaninejad, M. S., Chamari, M., Naderi, M., … Farzadfar, F. (2018). Effectiveness of vitamin D therapy in improving metabolomic biomarkers in obesity phenotypes: Two randomized clinical trials. International Journal of Obesity (2005), 42(10), 1782–1796. https://doi.org/10.1038/s41366-018-0107-0

Bollineni, R. C., Fedorova, M., Blüher, M., & Hoffmann, R. (2014). Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus. Journal of Proteome Research, 13(11), 5081–5093. https://doi.org/10.1021/pr500324y

Borato, D. C. K., Parabocz, G. C., Ribas, J. T., Netto, H. P., Erdmann, F. C., Wiecheteck, L. D., … Vellosa, J. C. R. (2016). Biomarkers in Obesity: Serum Myeloperoxidase and Traditional Cardiac Risk Parameters. Experimental and Clinical Endocrinology & Diabetes: Official Journal, German Society of Endocrinology [and] German Diabetes Association, 124(1), 49–54. https://doi.org/10.1055/s-0035-1565093

Caira, S., Iannelli, A., Sciarrillo, R., Picariello, G., Renzone, G., Scaloni, A., & Addeo, P. (2017). Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity. Journal of Enzyme Inhibition and Medicinal Chemistry, 32(1), 672–682. https://doi.org/10.1080/14756366.2017.1292262

Camargos, A. C. R., Mendonça, V. A., Oliveira, K. S. C., de Andrade, C. A., Leite, H. R., da Fonseca, S. F., … Lacerda, A. C. R. (2017). Association between obesity-related biomarkers and cognitive and motor development in infants. Behavioural Brain Research, 325(Pt A), 12–16. https://doi.org/10.1016/j.bbr.2017.02.030

Campbell, R., Tasevska, N., Jackson, K. G., Sagi-Kiss, V., di Paolo, N., Mindell, J. S., … Kuhnle, G. G. C. (2017). Association between urinary biomarkers of total sugars intake and measures of obesity in a cross-sectional study. PloS One, 12(7), e0179508. https://doi.org/10.1371/journal.pone.0179508

Cioates Negut, C., Stefan-van Staden, R.-I., Ungureanu, E.-M., & Udeanu, D. I. (2016). Stochastic sensors designed for assessment of biomarkers specific to obesity. Journal of Pharmaceutical and Biomedical Analysis, 128, 280–285. https://doi.org/10.1016/j.jpba.2016.05.040

Corrêa, T. A., & Rogero, M. M. (2019). Polyphenols regulating microRNAs and inflammation biomarkers in obesity. Nutrition (Burbank, Los Angeles County, Calif.), 59, 150–157. https://doi.org/10.1016/j.nut.2018.08.010

Dalamaga, M. (2013). Obesity, insulin resistance, adipocytokines and breast cancer: New biomarkers and attractive therapeutic targets. World Journal of Experimental Medicine, 3(3), 34–42. https://doi.org/10.5493/wjem.v3.i3.34

Day, S. E., Coletta, R. L., Kim, J. Y., Garcia, L. A., Campbell, L. E., Benjamin, T. R., … Coletta, D. K. (2017). Potential epigenetic biomarkers of obesity-related insulin resistance in human whole-blood. Epigenetics, 12(4), 254–263. https://doi.org/10.1080/15592294.2017.1281501

de Siqueira, L. T., Wanderley, M. S. O., da Silva, R. A., da Silva Andrade Pereira, A., de Lima Filho, J. L., & Ferraz, Á. A. B. (2018). A Screening Study of Potential Carcinogen Biomarkers After Surgical Treatment of Obesity. Obesity Surgery, 28(8), 2487–2493. https://doi.org/10.1007/s11695-018-3191-2

Dias, K. A., Ingul, C. B., Tjønna, A. E., Keating, S. E., Gomersall, S. R., Follestad, T., … Coombes, J. S. (2018). Effect of High-Intensity Interval Training on Fitness, Fat Mass and Cardiometabolic Biomarkers in Children with Obesity: A Randomised Controlled Trial. Sports Medicine (Auckland, N.Z.), 48(3), 733–746. https://doi.org/10.1007/s40279-017-0777-0

Dibaba, D. T., Judd, S. E., Gilchrist, S. C., Cushman, M., Pisu, M., Safford, M., & Akinyemiju, T. (2019). Association between obesity and biomarkers of inflammation and metabolism with cancer mortality in a prospective cohort study. Metabolism: Clinical and Experimental, 94, 69–76. https://doi.org/10.1016/j.metabol.2019.01.007

Dieli-Conwright, C. M., Courneya, K. S., Demark-Wahnefried, W., Sami, N., Lee, K., Buchanan, T. A., … Mortimer, J. E. (2018). Effects of Aerobic and Resistance Exercise on Metabolic Syndrome, Sarcopenic Obesity, and Circulating Biomarkers in Overweight or Obese Survivors of Breast Cancer: A Randomized Controlled Trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 36(9), 875–883. https://doi.org/10.1200/JCO.2017.75.7526

Dimassi, S., Karkeni, E., Laurant, P., Tabka, Z., Landrier, J.-F., & Riva, C. (2018). Microparticle miRNAs as Biomarkers of Vascular Function and Inflammation Response to Aerobic Exercise in Obesity? Obesity (Silver Spring, Md.), 26(10), 1584–1593. https://doi.org/10.1002/oby.22298

Doumatey, A. P., Zhou, J., Zhou, M., Prieto, D., Rotimi, C. N., & Adeyemo, A. (2016). Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study. Obesity (Silver Spring, Md.), 24(6), 1257–1265. https://doi.org/10.1002/oby.21482

Elangovan, S., Brogden, K. A., Dawson, D. V., Blanchette, D., Pagan-Rivera, K., Stanford, C. M., … Avila-Ortiz, G. (2014). Body fat indices and biomarkers of inflammation: a cross-sectional study with implications for obesity and peri-implant oral health. The International Journal of Oral & Maxillofacial Implants, 29(6), 1429–1434. https://doi.org/10.11607/jomi.3758

Elfassy, T., Yi, S. S., Llabre, M. M., Schneiderman, N., Gellman, M., Florez, H., … Zeki Al Hazzouri, A. (2017). Neighbourhood socioeconomic status and cross-sectional associations with obesity and urinary biomarkers of diet among New York City adults: the heart follow-up study. BMJ Open, 7(12), e018566. https://doi.org/10.1136/bmjopen-2017-018566

Ergören, M. C., Söyler, G., Sah, H., & Becer, E. (2019). Investigation of potential genomic biomarkers for obesity and personalized medicine. International Journal of Biological Macromolecules, 122, 493–498. https://doi.org/10.1016/j.ijbiomac.2018.10.059

Eschalier, R., Rossignol, P., Kearney-Schwartz, A., Adamopoulos, C., Karatzidou, K., Fay, R., … Zannad, F. (2014). Features of cardiac remodeling, associated with blood pressure and fibrosis biomarkers, are frequent in subjects with abdominal obesity. Hypertension (Dallas, Tex.: 1979), 63(4), 740–746. https://doi.org/10.1161/HYPERTENSIONAHA.113.02419

Fang, C., Kim, H., Barnes, R. C., Talcott, S. T., & Mertens-Talcott, S. U. (2018). Obesity-Associated Diseases Biomarkers Are Differently Modulated in Lean and Obese Individuals and Inversely Correlated to Plasma Polyphenolic Metabolites After 6 Weeks of Mango (Mangifera indica L.) Consumption. Molecular Nutrition & Food Research, e1800129. https://doi.org/10.1002/mnfr.201800129

Farook, V. S., Reddivari, L., Chittoor, G., Puppala, S., Arya, R., Fowler, S. P., … Vanamala, J. (2015). Metabolites as novel biomarkers for childhood obesity-related traits in Mexican-American children. Pediatric Obesity, 10(4), 320–327. https://doi.org/10.1111/ijpo.270

Fernández-Bergés, D., Consuegra-Sánchez, L., Peñafiel, J., Cabrera de León, A., Vila, J., Félix-Redondo, F. J., … Marrugat, J. (2014). Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study. Revista Espanola De Cardiologia (English Ed.), 67(8), 624–631. https://doi.org/10.1016/j.rec.2013.10.019

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Potential Biomarkers of Obesity

For obesity with cardiovascular diseases:

Peterson, S. J., Shapiro, J. I., Thompson, E., Singh, S., Liu, L., Weingarten, J. A., … Abraham, N. G. (2019). Oxidized HDL, Adipokines, and Endothelial Dysfunction: A Potential Biomarker Profile for Cardiovascular Risk in Women with Obesity. Obesity (Silver Spring, Md.), 27(1), 87–93. https://doi.org/10.1002/oby.22354

Ahmad, A., Memon, A. A., Sundquist, J., Svensson, P. J., Zöller, B., & Sundquist, K. (2018). Fat mass and obesity-associated gene rs9939609 polymorphism is a potential biomarker of recurrent venous thromboembolism in male but not in female patients. Gene, 647, 136–142. https://doi.org/10.1016/j.gene.2018.01.013

Popovic, D. S., Mitrovic, M., Tomic-Naglic, D., Icin, T., Bajkin, I., Vukovic, B., … Stokic, E. (2017). The Wnt/β-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity. Current Neurovascular Research, 14(3), 200–206. https://doi.org/10.2174/1567202614666170619080526

Baumann, S., Koepp, J., Becher, T., Huseynov, A., Bosch, K., Behnes, M., … Akin, I. (2016). Biomarker evaluation as a potential cause of gender differences in obesity paradox among patients with STEMI. Cardiovascular Revascularization Medicine: Including Molecular Interventions, 17(2), 88–94. https://doi.org/10.1016/j.carrev.2015.12.012

For obesity with liver diseases:

Mesarwi, O. A., Shin, M.-K., Drager, L. F., Bevans-Fonti, S., Jun, J. C., Putcha, N., … Polotsky, V. Y. (2015). Lysyl Oxidase as a Serum Biomarker of Liver Fibrosis in Patients with Severe Obesity and Obstructive Sleep Apnea. Sleep, 38(10), 1583–1591. https://doi.org/10.5665/sleep.5052

For obesity with autoimmune diseases and cancer:

Dalamaga, M., & Christodoulatos, G. S. (2015). Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies. Hormone Molecular Biology and Clinical Investigation, 23(1), 5–20. https://doi.org/10.1515/hmbci-2015-0016

Perl, A. (2015). mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging. Annals of the New York Academy of Sciences, 1346(1), 33–44. https://doi.org/10.1111/nyas.12756

For obesity with metabolic disorders:

Maltais-Payette, I., Boulet, M.-M., Prehn, C., Adamski, J., & Tchernof, A. (2018). Circulating glutamate concentration as a biomarker of visceral obesity and associated metabolic alterations. Nutrition & Metabolism, 15, 78. https://doi.org/10.1186/s12986-018-0316-5

Larsen, M. A., Isaksen, V. T., Moen, O. S., Wilsgaard, L., Remijn, M., Paulssen, E. J., … Goll, R. (2018). Leptin to adiponectin ratio – A surrogate biomarker for early detection of metabolic disturbances in obesity. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD, 28(11), 1114–1121. https://doi.org/10.1016/j.numecd.2018.06.020

Balampanis, K., Chasapi, A., Kourea, E., Tanoglidi, A., Hatziagelaki, E., Lambadiari, V., … Sotiropoulou-Bonikou, G. (2018). Inter-tissue expression patterns of the key metabolic biomarker PGC-1α in severely obese individuals: Implication in obesity-induced disease. Hellenic Journal of Cardiology: HJC = Hellenike Kardiologike Epitheorese. https://doi.org/10.1016/j.hjc.2018.08.002

Fanelli, F., Mezzullo, M., Repaci, A., Belluomo, I., Ibarra Gasparini, D., Di Dalmazi, G., … Pagotto, U. (2018). Profiling plasma N-Acylethanolamine levels and their ratios as a biomarker of obesity and dysmetabolism. Molecular Metabolism, 14, 82–94. https://doi.org/10.1016/j.molmet.2018.06.002

O’Neill, S., Larsen, M. B., Gregersen, S., Hermansen, K., & O’Driscoll, L. (2018). miR-758-3p: a blood-based biomarker that’s influence on the expression of CERP/ABCA1 may contribute to the progression of obesity to metabolic syndrome. Oncotarget, 9(10), 9379–9390. https://doi.org/10.18632/oncotarget.24314

Tacke, C., Aleksandrova, K., Rehfeldt, M., Murahovschi, V., Markova, M., Kemper, M., … Rudovich, N. (2018). Assessment of circulating Wnt1 inducible signalling pathway protein 1 (WISP-1)/CCN4 as a novel biomarker of obesity. Journal of Cell Communication and Signaling, 12(3), 539–548. https://doi.org/10.1007/s12079-017-0427-1

Mojbafan, M., Afsartala, Z., Amoli, M. M., Mahmoudi, M., Yaghmaei, P., Larijani, B., & Ebrahim-Habibi, A. (2017). Liver alpha-amylase gene expression as an early obesity biomarker. Pharmacological Reports: PR, 69(2), 229–234. https://doi.org/10.1016/j.pharep.2016.11.001

Al Haj Ahmad, R. M., & Al-Domi, H. A. (2017). Complement 3 serum levels as a pro-inflammatory biomarker for insulin resistance in obesity. Diabetes & Metabolic Syndrome, 11 Suppl 1, S229–S232. https://doi.org/10.1016/j.dsx.2016.12.036

Horakova, O., Hansikova, J., Bardova, K., Gardlo, A., Rombaldova, M., Kuda, O., … Kopecky, J. (2016). Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice. PloS One, 11(5), e0155776. https://doi.org/10.1371/journal.pone.0155776

Lau, E., Marques, C., Pestana, D., Santoalha, M., Carvalho, D., Freitas, P., & Calhau, C. (2016). The role of I-FABP as a biomarker of intestinal barrier dysfunction driven by gut microbiota changes in obesity. Nutrition & Metabolism, 13, 31. https://doi.org/10.1186/s12986-016-0089-7

Voigt, A., Ribot, J., Sabater, A. G., Palou, A., Bonet, M. L., & Klaus, S. (2015). Identification of Mest/Peg1 gene expression as a predictive biomarker of adipose tissue expansion sensitive to dietary anti-obesity interventions. Genes & Nutrition, 10(5), 27. https://doi.org/10.1007/s12263-015-0477-z

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Whole Grain Cereal, Obesity, and the PI3K/Akt Pathway

Whole grain cereal contains fibers, minerals, vitamins, and phytochemicals. Whole grain cereal has been found to inhibit body weight gain and non-alcoholic fatty liver (Lee et al., 2017).

Whole grain cereal could decrease the atrophy-associated factors, fat pad mass, and adipocyte size (Lee et al., 2017). The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway may be involved in muscle hypertrophy and myogenesis. Whole grain cereal could enhance the PI3K/Akt pathway activities and the regulators of muscle hypertrophy and myogenesis.

Therefore, whole grain cereal has been suggested as beneficial for relieving obesity-induced muscle atrophy and the overall obesity (Lee et al., 2017).

[References]
Lee S, Kim MB, Kim C, Hwang JK. Whole grain cereal attenuates obesity-induced muscle atrophy by activating the PI3K/Akt pathway in obese C57BL/6N mice. Food Sci Biotechnol. 2017 Dec 12;27(1):159-168. doi: 10.1007/s10068-017-0277-x.

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Psychoneuroimmunology and Anxiety: A Collection of Current Studies

Psychoneuroimmunology, Anxiety, Stress, and Inflammation

Duivis HE, Vogelzangs N, Kupper N, de Jonge P, Penninx BW. Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA). Psychoneuroendocrinology. 2013 Sep;38(9):1573-85. doi: 10.1016/j.psyneuen.2013.01.002.

Furtado M, Katzman MA. Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive compulsive disorders. Psychiatry Res. 2015 Sep 30;229(1-2):37-48. doi: 10.1016/j.psychres.2015.05.036.

Gariup M, Gonzalez A, Lázaro L, Torres F, Serra-Pagès C, Morer A. IL-8 and the innate immunity as biomarkers in acute child and adolescent psychopathology. Psychoneuroendocrinology. 2015 Dec;62:233-42. doi: 10.1016/j.psyneuen.2015.08.017.

Hou R, Baldwin DS. A neuroimmunological perspective on anxiety disorders. Hum Psychopharmacol. 2012 Jan;27(1):6-14. doi: 10.1002/hup.1259.

Hou R, Garner M, Holmes C, Osmond C, Teeling J, Lau L, Baldwin DS. Peripheral inflammatory cytokines and immune balance in Generalised Anxiety Disorder: Case-controlled study. Brain Behav Immun. 2017 May;62:212-218. doi: 10.1016/j.bbi.2017.01.021.

Hou R, Tang Z, Baldwin DS. Potential neuroimmunological targets in the treatment of anxiety disorders. Mod Trends Pharmacopsychiatry. 2013;29:67-84. doi: 10.1159/000351965.

Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology. 2017 Jan;42(1):254-270. doi: 10.1038/npp.2016.146.

Miller AH. Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun. 2009 Feb;23(2):149-58. doi: 10.1016/j.bbi.2008.08.006.

Myint AM, Schwarz MJ, Steinbusch HW, Leonard BE. Neuropsychiatric disorders related to interferon and interleukins treatment. Metab Brain Dis. 2009 Mar;24(1):55-68. doi: 10.1007/s11011-008-9114-5.

Moons WG, Shields GS. Anxiety, not anger, induces inflammatory activity: An avoidance/approach model of immune system activation. Emotion. 2015 Aug;15(4):463 76. doi: 10.1037/emo0000055.

Nemeth CL, Miller AH, Tansey MG, Neigh GN. Inflammatory mechanisms contribute to microembolism-induced anxiety-like and depressive-like behaviors. Behav Brain Res. 2016 Apr 15;303:160-7. doi: 10.1016/j.bbr.2016.01.057.

Ogłodek EA, Szota AM, Just MJ, Moś DM, Araszkiewicz A. The MCP-1, CCL-5 and SDF-1 chemokines as pro-inflammatory markers in generalized anxiety disorder and personality disorders. Pharmacol Rep. 2015 Feb;67(1):85-9. doi: 10.1016/j.pharep.2014.08.006.

Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull. 2014 May;140(3):774-815. doi: 10.1037/a0035302.

Vogelzangs N, Beekman AT, de Jonge P, Penninx BW. Anxiety disorders and inflammation in a large adult cohort. Transl Psychiatry. 2013 Apr 23;3:e249. doi: 10.1038/tp.2013.27.

Psychoneuroimmunology, Anxiety and Chronic Diseases

Capuron L, Poitou C, Machaux-Tholliez D, Frochot V, Bouillot JL, Basdevant A, Layé S, Clément K. Relationship between adiposity, emotional status and eating behaviour in obese women: role of inflammation. Psychol Med. 2011 Jul;41(7):1517-28. doi: 10.1017/S0033291710001984.

Dutheil S, Ota KT, Wohleb ES, Rasmussen K, Duman RS. High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation. Neuropsychopharmacology. 2016 Jun;41(7):1874-87. doi: 10.1038/npp.2015.357.

Jafferany M, Franca K. Psychodermatology: Basics Concepts. Acta Derm Venereol. 2016 Aug 23;96(217):35-7. doi: 10.2340/00015555-2378.

Malcarne VL, Fox RS, Mills SD, Gholizadeh S. Psychosocial aspects of systemic sclerosis. Curr Opin Rheumatol. 2013 Nov;25(6):707-13. doi: 10.1097/01.bor.0000434666.47397.c2.

Peruga I, Hartwig S, Thöne J, Hovemann B, Gold R, Juckel G, Linker RA. Inflammation modulates anxiety in an animal model of multiple sclerosis. Behav Brain Res. 2011 Jun 20;220(1):20-9. doi: 10.1016/j.bbr.2011.01.018.

Pierce GL, Kalil GZ, Ajibewa T, Holwerda SW, Persons J, Moser DJ, Fiedorowicz JG. Anxiety independently contributes to elevated inflammation in humans with obesity. Obesity (Silver Spring). 2017 Feb;25(2):286-289. doi: 10.1002/oby.21698.

Pyter LM, Suarez-Kelly LP, Carson WE 3rd, Kaur J, Bellasario J, Bever SR. Novel rodent model of breast cancer survival with persistent anxiety-like behavior and inflammation. Behav Brain Res. 2017 May 4. pii: S0166-4328(17)30090-6. doi: 10.1016/j.bbr.2017.05.011.

Rodrigues AR, Trufelli DC, Fonseca F, de Paula LC, Giglio AD. Fatigue in Patients With Advanced Terminal Cancer Correlates With Inflammation, Poor Quality of Life and Sleep, and Anxiety/Depression. Am J Hosp Palliat Care. 2016 Dec;33(10):942-947.

Steptoe A, Wikman A, Molloy GJ, Messerli-Bürgy N, Kaski JC. Inflammation and symptoms of depression and anxiety in patients with acute coronary heart disease. Brain Behav Immun. 2013 Jul;31:183-8. doi: 10.1016/j.bbi.2012.09.002.

Trikojat K, Luksch H, Rösen-Wolff A, Plessow F, Schmitt J, Buske-Kirschbaum A. “Allergic mood” – Depressive and anxiety symptoms in patients with seasonal allergic rhinitis (SAR) and their association to inflammatory, endocrine, and allergic markers. Brain Behav Immun. 2017 May 8. pii: S0889-1591(17)30151-4. doi: 10.1016/j.bbi.2017.05.005.

Zamora-Racaza G, Azizoddin DR, Ishimori ML, Ormseth SR, Wallace DJ, Penserga EG, Sumner L, Ayeroff J, Draper T, Nicassio PM, Weisman MH. Role of psychosocial reserve capacity in anxiety and depression in patients with systemic lupus erythematosus. Int J Rheum Dis. 2017 Mar 6. doi: 10.1111/1756-185X.13033.

Psychoneuroimmunology, Anxiety and Aging

Baune BT, Smith E, Reppermund S, Air T, Samaras K, Lux O, Brodaty H, Sachdev P, Trollor JN. Inflammatory biomarkers predict depressive, but not anxiety symptoms during aging: the prospective Sydney Memory and Aging Study. Psychoneuroendocrinology. 2012 Sep;37(9):1521-30. doi: 10.1016/j.psyneuen.2012.02.006.

Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, Malinowski P, Jackson W, Blennerhassett P, Neufeld KA, Lu J, Khan WI, Corthesy-Theulaz I, Cherbut C, Bergonzelli GE, Collins SM. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology. 2010 Dec;139(6):2102-2112.e1. doi: 10.1053/j.gastro.2010.06.063.

Martin S, Vincent A, Taylor AW, Atlantis E, Jenkins A, Januszewski A, O’Loughlin P, Wittert G. Lower Urinary Tract Symptoms, Depression, Anxiety and Systemic Inflammatory Factors in Men: A Population-Based Cohort Study. PLoS One. 2015 Oct 7;10(10):e0137903. doi: 10.1371/journal.pone.0137903.

Patki G, Solanki N, Atrooz F, Allam F, Salim S. Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res. 2013 Nov 20;1539:73-86. doi: 10.1016/j.brainres.2013.09.033.

Salim S, Asghar M, Taneja M, Hovatta I, Chugh G, Vollert C, Vu A. Potential contribution of oxidative stress and inflammation to anxiety and hypertension. Brain Res. 2011 Aug 2;1404:63-71. doi: 10.1016/j.brainres.2011.06.024.

Ventura LM. Psychoneuroimmunology: application to ocular diseases. J Ocul Biol Dis Infor. 2009 Jun;2(2):84-93.

Vida C, González EM, De la Fuente M. Increase of oxidation and inflammation in nervous and immune systems with aging and anxiety. Curr Pharm Des. 2014;20(29):4656-78.

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Mindfulness, Behaviors, and Weight Loss

Can mindfulness trainings have effects on behaviors and weight control among those with overweight and obesity? A meta-analysis examined such possible effects from 12 randomized controlled trials (Ruffault et al., 2016). The studies were about the influences of mindfulness trainings on weight control and eating behaviors such as impulsive eating and binge eating, as well as physical activities in people with overweight and obesity.

The meta-analysis found that although mindfulness trainings may not have direct or obvious effects on weight control, such exercises may help manage the behaviors of impulsive eating and binge eating (Ruffault et al., 2016). Such strategies may also help promote the involvement of physical activities.

In addition, the meta-analysis indicated that longer follow-up periods were related to higher levels of weight loss (Ruffault et al., 2016). Such findings suggest that mindfulness trainings may lead to health-associated behaviors not just in short term. They may also have benefits for weight management in the long term. More studies are still needed to detect the long-term effects of mindfulness trainings on weight loss to ease the problems of overweight and obesity.

References:

Ruffault, A., Czernichow, S., Hagger, M. S., Ferrand, M., Erichot, N., Carette, C., … Flahault, C. (2016). The effects of mindfulness training on weight-loss and health related behaviours in adults with overweight and obesity: A systematic review and meta-analysis. Obesity Research & Clinical Practice.

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Mindfulness and Obesity-Related Eating

Obesity is closely related to eating behaviors including binge eating, emotional eating and external eating (O’Reilly et al., 2014). Mindfulness-based interventions (MBIs) have been found to be helpful for easing the obesity problem by improving eating behaviors.

A meta-analysis examined 21 published studies about the effects of mindfulness-based interventions on obesity-associated eating behaviors (O’Reilly et al., 2014). The MBIs included mindfulness-based stress reduction, the combination of mindfulness and cognitive behavioral methods, acceptance-based methods, as well as mindful eating trainings. The programs aimed at improving eating behaviors such as binge eating and dietary intake.

The analysis found that most of the studies observed obvious progress in the targeted obesity-associated eating behaviors including emotional eating and external eating (O’Reilly et al., 2014). Such findings support the potential applications of integrative interventions such as mindfulness-based strategies for weight management.

References:

O’Reilly, G. A., Cook, L., Spruijt-Metz, D., & Black, D. S. (2014). Mindfulness-based interventions for obesity-related eating behaviours: a literature review. Obesity Reviews : An Official Journal of the International Association for the Study of Obesity, 15(6), 453–61.

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Mindfulness and Stress-Eating

Overweight and obesity problems have been associated with emotional eating behaviors, especially stress-related eating (Corsica et al., 2014). Although such problems are critical for weight management, it is not easy to provide effective interventions for improving eating behaviors.

Potential interventions may need to focus on the management of stress and the improvement of thoughts and behaviors associated with emotional eating. Such interventions may include mindfulness-based stress management programs and cognitive-behavioral therapies (Corsica et al., 2014).

A study of 53 overweight subjects (mostly women) with high levels of stress and stress-eating behaviors examined the effects of different interventions that lasted for six weeks (Corsica et al., 2014). One intervention was a modified mindfulness-based stress reduction (MBSR) program. Another intervention was a cognitive behavioral stress-eating intervention (SEI). The third program combined the elements from both stress reduction (MBSR) and cognitive behavioral interventions (SEI).

The study found that perceived stress and stress-eating behaviors were relieved remarkably in all three programs (Corsica et al., 2014). In addition, the combination program covering both stress reduction and cognitive behavioral elements had the most significant effects and led to immediate weight loss. Such effects continued even 6 weeks after the completion of the programs.

These observations support the potential weight loss strategies that aim at both stress-management and the control of stress-eating behaviors. Further studies would be needed to understand the mechanisms of the mindfulness and cognitive behavioral therapies for obesity and weight control.

References:

Corsica, J., Hood, M. M., Katterman, S., Kleinman, B., & Ivan, I. (2014). Development of a novel mindfulness and cognitive behavioral intervention for stress-eating: a comparative pilot study. Eating Behaviors, 15(4), 694–9.

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Mindful Decision-Making Training and Obesity

Excessive caloric intake such as the overeating of “junk” foods including salty snacks may contribute to the problem of obesity. Such eating decisions may be related to neurobiological preferences. The training of mindful decision-making processes may provide a helpful intervention to improve the eating behavior.

A recent study investigated the effects of a computerized inhibitory control training (ICT) and a mindful decision-making training (MDT) on eating habits (Forman et al., 2016). A total of 119 individuals with the habit of eating salty snack foods participated in the study. They were divided into 4 groups, one group had MDT, one group had ICT, one group had both MDT and ICT, and one group only had psychoeducation.

The participants reported their salty snack food consumption two times each day during the one week before and after the trainings. The study found that MDT, the mindfulness training, had consistent effects for all levels of trait emotional eating (Forman et al., 2016). In comparison, ICT showed influences on the lower levels of emotional eating.

The study indicated that both ICT and MDT may have beneficial effects by reducing hedonically-motivated eating (Forman et al., 2016). In addition, the combination of ICT and MDT may be beneficial for those with lower levels in emotional eating. More studies are still needed to find out the mechanisms and the possible differences between the training programs.

References:

Forman, E. M., Shaw, J. A., Goldstein, S. P., Butryn, M. L., Martin, L. M., Meiran, N., … Manasse, S. M. (2016). Mindful decision making and inhibitory control training as complementary means to decrease snack consumption. Appetite, 103, 176–83.

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Mindfulness, Emotional Eating, and Overweight

Mindfulness training may influence the eating habits and weight management. A recent study investigated the effects of a mindfulness and compassion-based method among 53 overweight or obese women (Palmeira et al., 2017). The study examined the possible influences of the intervention on the quality of life, weight self-stigma, body mass index, as well as the behaviors of emotional eating.

After the intervention, including the 3-month follow-up, higher quality of life was reported with higher levels of mindfulness and self-compassion among the participants (Palmeira et al., 2017). In addition, lower levels of emotional eating or weight-related experiential avoidance were observed. Other changes included lower levels of self-criticism and body mass index.

Among the changes, the lower levels of shame and self-criticism were found to be more associated with the improvements in health-related outcomes (Palmeira et al., 2017). In addition, the elevated levels of mindfulness and self-compassion were related to the weight loss and improved eating behaviors. These changes demonstrate the potential effects of mindfulness training. However, trials based on larger populations are still needed.

References:

Palmeira L, Cunha M, Pinto-Gouveia J. Processes of change in quality of life, weight self-stigma, body mass index and emotional eating after an acceptance-, mindfulness- and compassion-based group intervention (Kg-Free) for women with overweight and obesity. J Health Psychol. 2017 Jan 1:1359105316686668. doi: 10.1177/1359105316686668.

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Weight Loss Programs and Mindfulness Meditation for Obesity

Obesity is becoming a health crisis affecting more and more people. Clinical standard behavioral weight loss programs (SBWP) have been proposed to ease the problem (Spadaro et al., 2017). Such programs are often combined with trainings on mindfulness meditation (MM) to promote self-regulation behaviors and to improve the psychological wellbeing and physical health.

To investigate the effects of such trainings, 46 adults in a northeastern US city participated in a 6-month program with SBWP only or with SBWP plus MM (Spadaro et al., 2017). The participating adults were taught to reduce caloric intake, with more physical activities of 300 minutes per week, in addition to SBWP or SBWP plus MM trainings each week.

The researchers analyzed the changes in weight, eating behaviors, physical activities, and the levels of mindfulness (Spadaro et al., 2017). They observed that the SBWP plus MM group had more significant weight loss than the SBWP-only group. In addition, the SBWP plus MM group showed more improvements in eating behaviors and dietary restraint, which may contribute to the more significant weight loss.

The results suggest better effects of the mindfulness meditation methods for weight management among overweight and obese people (Spadaro et al., 2017). Such studies may encourage more investigations about the relevant scientific mechanisms. They may also be useful for developing standard protocols for weight management programs.

References:

Spadaro KC, Davis KK, Sereika SM, Gibbs BB, Jakicic JM, Cohen SM. Effect of mindfulness meditation on short-term weight loss and eating behaviors in overweight and obese adults: A randomized controlled trial. J Complement Integr Med. 2017 Dec 5. pii: /j/jcim.ahead-of-print/jcim-2016-0048/jcim-2016-0048.xml. doi: 10.1515/jcim-2016-0048.

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Rhizoma Anemarrhenae for Infectious Diseases, Fever, and Diabetes

[Name]
Rhizoma Anemarrhenae

[Chinese Name]
Zhi Mu

[Parts Used and Preparation]
Rhizome

[Flavors in Chinese Medicine]
Bitter, sweet; cold

[Chinese Medicine Meridians/Channels]
Lung, Stomach and Kidney

[Actions in Chinese Medicine]
The herb can clear the pathogenic Heat and Fire factors, and nourish Yin.

[Uses in Chinese Medicine]
• Infectious diseases with the symptoms of high fever, irritability, and thirst.
• Cough caused by the pathogenic Heat factor in the Lung, or the factor of Yin-deficiency.
• Low-grade fever and night sweats caused by Yin-deficiency in the Kidney and/or Lung.
• Diabetes with the symptoms of thirst and polyuria.

[Recommended Dosages]
6–12 grams. Add water to make decoctions.

[Warnings, Interactions, Side Effects]
Because the herb has cold and moistening effects, it should not be used by those having diarrhea or with Spleen-deficiency.

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Gypsum for Infectious Diseases, Fever, and Skin Disorders

[Name]

Gypsum Fibrosum, CaSO4, Gypsum

[Chinese Name]
Shi Gao

[Parts Used and Preparation]
Gypsum (a mineral)

[Flavors in Chinese Medicine]
Pungent, sweet; very cold

[Chinese Medicine Meridians/Channels]
Lung and Stomach

[Actions in Chinese Medicine]
The material may clear the pathogenic Heat and Fire factors, and ease irritability and thirst.

[Uses in Chinese Medicine]
• Infectious diseases caused by the pathogenic Heat factor at the Qi-Level with the symptoms including high fever, irritability, and thirst.
• Infectious diseases with the symptoms including cough, difficulties in breathing, yellow sputum, and fever.
• Headaches and gingivitis caused by the pathogenic Stomach-Fire factors.
• Calcined gypsum powder can be applied for skin disorders including skin ulcers, eczema, and burns.

[Recommended Dosages]
15–60 grams. The calcined powder can be applied for external usages.

[Warnings, Interactions, Side Effects]
The material should not be used by those with the Cold factor in the Spleen and
Stomach.

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Fructus Arctii for Sore Throat and Skin Rashes

[Name]
Fructus Arctii, Arctium lappa

[Chinese Name]
Niu Bang Zi

[Parts Used and Preparation]
Fruits

[Flavors in Chinese Medicine]
Pungent, bitter; cold

[Chinese Medicine Meridians/Channels]
Lung and Stomach

[Actions in Chinese Medicine]
The herb may detoxify and relieve rashes and swelling. It may also soothe the sore throat.

[Uses in Chinese Medicine]
• Infectious diseases including the symptoms of cough, and swollen and sore throat.
• The early stages of measles before the skin rashes appear, caused by the Wind–Heat factors.
• Skin inflammation including boils and abscesses caused by the pathogenic Heat factor.

[Recommended Dosages]
3–10 grams. Add water to make decoctions.

[Warnings, Interactions, Side Effects]
The herb should not be used by those with diarrhea.

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