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Biology subjects

Chamberlin, S.

Publications and source records attributed to Chamberlin, S..

3 recordsLinked to original sources

Data mining and experimental approaches to identify combination of natural herbs against bacterial infections

Various studies have identified that natural herbs can be repurposed to treat infectious and bacterial diseases. The purpose of this study is first to test the medicinal value of five herbs including asafoetida, cumin, fenugreek, neem, and turmeric as single agent and in pairs using the bacterial zone of inhibition assay. Second, we used target and network analyses to predict the best combinations. We found that all the herbs as single agent were effective against bacterial infection in the following descending order of efficacy: cumin > turmeric > neem > fenugreek > asafoetida as compared to vehicle (ethanol) treated control. Among all the tested combinations the turmeric and fenugreek combination had the best efficacy in inhibiting the bacterial growth. Next to understand the mechanism of action and to predict the effective combinations among available herbs, we used a data mining and computational analysis approach. Using NPASS, BindingDB, and pathway analysis tools, we identified the bioactive compounds for each herb, then identified the targets for each bioactive compound, and then identified associated pathways for these targets. Then we measured the target/pathway overlap for each herb and identified that the most effective combinations were those which have non-overlapping targets/pathways. For example, we showed as a proof-of-concept that turmeric and fenugreek have the least overlapping targets/pathways and thus is most effective in inhibiting bacteria growth. Our approach is applicable to treat bacterial infections and other human diseases such as cancer. Overall, the computational prediction along with experimental validation can help identify novel combinations that have significant antibacterial activity and may help prevent drug-resistant microbial diseases in human and plants.

microbiology↗

Common Mechanism of SARS-CoV and SARS-CoV-2 Pathogenesis across Species

Sarbecovirus (CoV) infections, including Severe Acute Respiratory CoV (SARS-CoV) and SARS-CoV-2, are considerable human threats. Human GWAS studies have recently identified loci associated with variation in SARS-CoV-2 susceptibility. However, genetically tractable models that reproduce human CoV disease outcomes are needed to mechanistically evaluate genetic determinants of CoV susceptibility. We used the Collaborative Cross (CC) and human GWAS datasets to elucidate host susceptibility loci that regulate CoV infections and to identify host quantitative trait loci that modulate severe CoV and pan-CoV disease outcomes including a major disease regulating loci including CCR9. CCR9 ablation resulted in enhanced titer, weight loss, respiratory dysfunction, mortality, and inflammation, providing mechanistic support in mitigating protection from severe SARS-CoV-2 pathogenesis across species. This study represents a comprehensive analysis of susceptibility loci for an entire genus of human pathogens conducted, identifies a large collection of susceptibility loci and candidate genes that regulate multiple aspects type-specific and cross-CoV pathogenesis, and also validates the paradigm of using the CC platform to identify common cross-species susceptibility loci and genes for newly emerging and pre-epidemic viruses.

microbiology↗

Short-term effectiveness of HIV care coordination among persons with recent HIV diagnosis or history of poor HIV outcomes

The New York City HIV Care Coordination Program (CCP) combines multiple evidence-based strategies to support persons living with HIV (PLWH) at risk for, or with a recent history of, poor HIV outcomes. We assessed the comparative effectiveness of the CCP by merging programmatic data on CCP clients with population-based surveillance data on all New York City PLWH. A non-CCP comparison group of similar PLWH who met CCP eligibility criteria was identified using surveillance data. The CCP and non-CCP groups were matched on propensity for CCP enrollment within four baseline treatment status groups (newly diagnosed or previously diagnosed and either consistently unsuppressed, inconsistently suppressed or consistently suppressed). We compared CCP to non-CCP proportions with viral load suppression at 12-month follow-up. Among the 13,624 persons included, 15{middle dot}3% were newly diagnosed; among the 84{middle dot}7% previously diagnosed, 14{middle dot}2% were consistently suppressed, 28{middle dot}9% were inconsistently suppressed, and 41 {middle dot}6% were consistently unsuppressed in the year prior to baseline. At 12-month follow-up, 59{middle dot}9% of CCP and 53{middle dot}9% of non-CCP participants had viral load suppression (Relative Risk=1.11, 95%CI:1.08-1.14). Among those newly diagnosed and those consistently unsuppressed at baseline, the relative risk of viral load suppression in the CCP versus non-CCP participants was 1.15 (95%CI:1.09-1.23) and 1.32 (95%CI:1.23-1.42), respectively. CCP exposure shows benefits over no CCP exposure for persons newly diagnosed or consistently unsuppressed, but not for persons suppressed in the year prior to baseline. We recommend more targeted case finding for CCP enrollment and increased attention to viral load suppression maintenance.

epidemiology↗