Histopathological examination of vaginal tissues after intravaginal application of SFT gel and other microbicide candidates.

<p>Slides were prepared from vaginal tissues treated with placebo (1.5% HEC gel) (<b>a</b>), 0.03 mM SFT gel (<b>b</b>), 0.3 mM SFT gel (<b>c</b>), 3 mM SFT gel (<b>d</b>), 1% TFV gel (<b>e</b>), 3% carrageenan gel (<b>f</b>), 6% CS gel-treated group (<b>g</b>), or 1% N-9 gel-treated group (<b>h</b>). Hematoxylin-eosin staining was used for all slides. Magnification, ×100.</p

The content of SFT in HEC gel or PBS monitored by HPLC.

<p>(a) Representative chromatograms of SFT in 1.5% HEC and PBS. The retention time was 14 min for SFT. (b) Percent of SFT recovery from the 1.5% HEC and PBS after 8 weeks of storage at 40°C (n = 5, means ± SD).</p

Inflammatory cytokines in CVLs after treatment of SFT gel and other microbicide candidates.

<p>Inflammatory cytokines, including IL-6 (<b>a</b>), TNF-α (<b>b</b>), IFN-γ (<b>c</b>), IL-10 (<b>d</b>) and IL-17A (<b>e</b>), were quantified in CVLs collected at 12 h post final dosage in the context of 3 consecutive days of intravaginal application of placebo (1.5% HEC), 0.03 mM SFT gel, 0.3 mM SFT gel, 3 mM SFT gel, 3% carrageenan gel, 1% TFV gel, 6% CS gel and 1% N-9 gel, respectively. The X-axis indicated the administration of different microbicide candidates; the Y-axis indicated the production of corresponding inflammatory cytokines. Data represent means ± SD from 5 mice per group. Student's <i>t</i>-test was performed to determine the significance of difference between the placebo gel control group and the treatment group for each microbicide candidate, *<i>p</i><0.05.</p

An accelerated stability study of SFT in the gel formulation.

a<p>Data represent mean ± SD (n = 3).</p>b<p>RT: room temperature.</p

Efficacy of SFT gel against infections by HIV-1 pseudoviruses.

<p>(<b>a</b>) SFT is more effective <i>in vitro</i> against HIV-1 subtype C pseudovirus than TFV. The IC₅₀ value of TFV in PBS against subtype C was 5.2 µM, whereas that of SFT in PBS was only 25.6 nM. (<b>b</b>) Efficacy of SFT in PBS or in 0.015% HEC gel to inhibit infection by HIV-1 pseudoviruses bearing the Env of CRF07_BC (upper left), CRF01_AE (upper right), B (lower left) and C (lower right), respectively. Data represent means ± SD from triplicate experiments. Student's <i>t</i>-test was performed to determine the significance of difference between various groups as shown in the graph, *<i>p</i><0.05.</p

In vitro evaluation on the safety of SFT gel.

<p>(<b>a</b>) MTT assay was used to determine the cell viability of epithelial line Caco-2 (left) or macrophage cell line RAW264.7 (right) after the treatment of different concentrations (3 nM, 30 nM and 300 nM) of SFT in PBS solution or corresponding gel versions (formulated with 0.015% HEC). (<b>b</b>) Production of IL-6 (left) and TNF-α (right) in macrophage cell line RAW264.7 was analyzed by CBA assay after incubation for 12 h with the above-mentioned three concentrations of SFT in PBS solutions or 0.015% HEC gel. Data represent means ±SD from triplicate experiments. Student's <i>t</i>-test was performed to determine the significance of difference between the PBS-treated group and each microbicide candidate or LPS-treated groups, *<i>p</i><0.05.</p

Viscosity and pH profiles of SFT HEC gel stored at 40°C for 8 weeks.

a<p>1.5% HEC;</p>b<p>0.3 mM SFT in 1.5% HEC;</p>c<p>Unit: mPa.s; Samples were tested in triplicate and the data were represented in mean ± SD.</p

Network pharmacology and molecular docking elucidate the underlying pharmacological mechanisms of the herb Houttuynia cordata in treating pneumonia caused by SARS-CoV-2

Used in Asian countries, including China, Japan, and Thailand, Houttuynia cordata Thumb (H. cordata; Saururaceae, HC) is a traditional herbal medicine that possesses favorable antiviral properties. As a potent folk therapy used to treat pulmonary infections, further research is required to fully elucidate the mechanisms of its pharmacological activities and explore its therapeutic potential for treating pneumonia caused by SARS-CoV-2. This study explores the pharmacological mechanism of HC on pneumonia using a network pharmacological approach combined with reprocessing expression profiling by high-throughput sequencing to demonstrate the therapeutic mechanisms of HC for treating pneumonia at a systemic level. The integration of these analyses suggested that target factors are involved in four signaling pathways, including PI3K-Akt, Jak-STAT, MAPK, and NF-kB. Molecular docking and molecular dynamics simulation were applied to verify these results, indicating a stable combination between four metabolites (Afzelin, Apigenin, Kaempferol, Quercetin) and six targets (DPP4, ELANE, HSP90AA1, IL6, MAPK1, SERPINE1). These natural metabolites have also been reported to bind with ACE2 and 3CLpro of SARS-CoV-2, respectively. The data suggest that HC exerts collective therapeutic effects against pneumonia caused by SARS-CoV-2 and provides a theoretical basis for further study of the active drug-like ingredients and mechanism of HC in treating pneumonia. </p

Mutation trend analysis of signature and non-signature amino acid residues in the functional domains of the proteins of 2009 H1N1pdm during the influenza pandemic in 2009.

<p>Note: the number in brackets indicates the percent (%) of sequences with the mutated amino acid in total number of the sequences collected in the period; ‘-’ means unavailable in non-H1N1 virus.</p

Exploring binding sites of anti-MPER.

<p>(A) Schematic representation of peptides used for scanning the binding sites of anti-MPER. (B) Results of anti-MPER binding to peptides in ELISA. MAbs 2F5 and 4E10 were used as control. The concentration of each antibody was 0.2 µg/ml.</p