Screening of anti-melanoma compounds from Morus alba L.: Sanggenon C promotes melanoma cell apoptosis by disrupting intracellular Ca2+ homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. is a widespread plant that has long been considered to have remarkable medical values, including anti-inflammation in Traditional Chinese Medicine (TCM). The components of Morus Alba L. constituents have been extensively studied and have been shown to have high prospects for cancer therapy. However, limited investigations have been done on the bioactive compounds in Morus alba L. AIM OF THE STUDY: This study aimed to systematically examine the anticancer properties of 28 commercially available compounds from Morus alba L. against melanoma cells in vitro. Additionally, the anticancer mechanisms of the bioactive compound exhibiting the most significant potential were further studied. MATERIALS AND METHODS: The anti-proliferative effects of Morus alba L.-derived compounds on melanoma cells were determined by colony formation assays. Their effects on cell viability and apoptosis were determined using the CCK8 assay and flow cytometry, respectively. The binding affinity of identified Morus alba L. compounds with anticancer activities towards melanoma targets was analyzed via molecular docking. The molecular mechanism of Sanggenon C was explored using soft agar assays, EdU incorporation assays, flow cytometry, western blotting, transcriptome analysis, and xenograft assays. RESULTS: Based on colony formation assays, 11 compounds at 20 µM significantly inhibited colony growth on a panel of melanoma cells. These compounds displayed IC50 values (half maximal inhibitory concentrations) ranging from 5 µM to 30 µM. Importantly, six compounds were identified as novel anti-melanoma agents, including Sanggenon C, 3'-Geranyl-3-prenyl-2',4',5,7-tetrahydroxyflavone, Moracin P, Moracin O, Kuwanon A, and Kuwanon E. Among them, Sanggenon C showed the most potent effects, with an IC50 of about 5 µM, significantly reducing proliferation and inducing apoptosis in melanoma cells. Based on the xenograft model assay, Sanggenon C significantly inhibited melanoma cell proliferation in vivo. Sanggenon C triggered ER stress in a dose-dependent manner, which further disrupted cellular calcium ion (Ca2+) homeostasis. The Ca2+ chelator BAPTA partially restored cell apoptosis induced by Sanggenon C, confirming that Ca2+ signaling contributed to the anticancer activity of Sanggenon C against melanoma. CONCLUSIONS: In our study, 11 compounds demonstrated anti-melanoma properties. Notably, Sanggenon C was found to promote apoptosis by disrupting the intracellular calcium homeostasis in melanoma cells. This study provides valuable information for the future development of novel cancer therapeutic agents from Morus alba L.

An integrated approach for studying the metabolic profiling of herbal medicine in mice using high-resolution mass spectrometry and metabolomics data processing tools.

Analysis of exposure to traditional Chinese medicine (TCM) in vivo based on mass spectrometry is helpful for the screening of effective ingredients of TCM and the development of new drugs. The method of screening biomarkers through metabolomics technology is a nontargeted research method to explore the differential components between two sets of biological samples. By taking this advantage, this study aims to takes Forsythia suspensa, which is a TCM also known as Lian Qiao (LQ), as the research object and to study its in vivo exposure by using metabolomics technology. By comparing the significant differences between biological samples before and after administration, it could be focused on the components that were significantly upregulated, where a complete set of analysis strategies for nontargeted TCM in vivo exposure mass spectrometry was established. Furthermore, the threshold parameters for peak extraction, parameter selection during statistical data analysis, and sample concentration multiples in this method have also been optimized. More interestingly, by using the established analysis strategy, we found 393 LQ-related chemical components in mice after administration, including 102 prototypes and 291 LQ-related metabolites, and plotted their metabolic profiles in vivo. In short, this study has obtained a complete mass spectrum of LQ exposure in mice in vivo for the first time, which provides a reference for research on the active ingredients of LQ in vivo. More importantly, compared with other methods, the analysis strategy of nontargeted exposure of TCM in vivo-based mass spectrometry, constructed by using this research method, has good universality and does not require self-developed postprocessing software. It is worth mentioning that, for the identification and characterization of trace amounts of metabolites in vivo, this analysis strategy has no discrimination and has a detection capability similar to that of highly exposed components.

Characterization of the Endophytic Bacillus subtilis KRS015 Strain for Its Biocontrol Efficacy Against Verticillium dahliae.

Endophytes play important roles in promoting plant growth and controlling plant diseases. Verticillium wilt is a vascular wilt disease caused by Verticillium dahliae, a widely distributed soilborne pathogen that causes significant economic losses on cotton each year. In this study, an endophyte KRS015, isolated from the seed of the Verticillium wilt-resistant Gossypium hirsutum 'Zhongzhimian No. 2', was identified as Bacillus subtilis by morphological, phylogenetic, physiological, and biochemical analyses. The volatile organic compounds (VOCs) produced by KRS015 or its cell-free fermentation extract had significant antagonistic effects on various pathogenic fungi, including V. dahliae. KRS015 reduced Verticillium wilt index and colonization of V. dahliae in treated cotton seedlings significantly; the disease reduction rate was ∼62%. KRS015 also promoted plant growth, potentially mediated by the growth-related cotton genes GhACL5 and GhCPD-3. The cell-free fermentation extract of KRS015 triggered a hypersensitivity response, including reactive oxygen species (ROS) and expression of resistance-related plant genes. VOCs from KRS015 also inhibited germination of conidia and the mycelial growth of V. dahliae, and were mediated by growth and development-related genes such as VdHapX, VdMcm1, Vdpf, and Vel1. These results suggest that KRS015 is a potential agent for controlling Verticillium wilt and promoting growth of cotton.

Online-merge-offline (OMO)-based music therapy for asthmatic children during the COVID-19 pandemic in China.

The purpose of this study is to evaluate online-merge-offline (OMO)-based music therapy (MT) as a complementary option for asthma management in pediatric patients. A total of 86 children diagnosed with mild asthma were enrolled and treated with the same drug therapy. They were assigned into three groups: Music I group (standard medical care plus a single individualized MT session along with singing training and breathing exercise), Music II group (similar as Music I as well as further wind instrument playing), and Control group (standard medical care). Primary endpoints included pulmonary function tests FEV1, FVC, FEV1/FVC, MMEF 75/25, and PEF, c-ACT, PAQLQ, and PACQLQ. After 6 months of continuous intervention of MT, significant differences in FEV1, FVC, MMEF75/25, PEF, c-ACT score, PAQLQ, PACQLQ (p < 0.001), and FEV1/FVC (p < 0.05) were observed among Music I, Music II, and Control groups. Besides, FEV1, FVC, FEV1/FVC, MMEF75/25, and PEF showed positive trends in Music I and Music II groups compared to those in Control group (p < 0.05). The c-ACT score of children was significantly increased in Music I (p < 0.001) and II (p < 0.001) groups in contrast with Control group. Children in Music I and II groups had better quality of life than those in Control group (PAQLQ, p < 0.001), and the parents in Music I and II groups also showed better quality of life than those in Control group (PACQLQ, p < 0.001).     Conclusion: As a child-friendly, low-risk, and convenient intervention, the OMO-based MT has a positive impact on pediatric asthma management during the COVID-19 pandemic. What is Known: • A few findings proved the positive effect of MT on pediatric asthma. What is New: • Our study further proving the validation and effectiveness of MT with OMO-based model on pediatric asthma, wind instrument playing has a greater impact on pediatric asthma control via small airways and might be recommended to mix to singing and breathing to improve effectiveness of MT for asthmatic children.

Structure, Health Benefits, Mechanisms, and Gut Microbiota of Dendrobium officinale Polysaccharides: A Review.

Dendrobium officinale polysaccharides (DOPs) are important active polysaccharides found in Dendrobium officinale, which is commonly used as a conventional food or herbal medicine and is well known in China. DOPs can influence the composition of the gut microbiota and the degradation capacity of these symbiotic bacteria, which in turn may determine the efficacy of dietary interventions. However, the necessary analysis of the relationship between DOPs and the gut microbiota is lacking. In this review, we summarize the extraction, structure, health benefits, and related mechanisms of DOPs, construct the DOPs-host axis, and propose that DOPs are potential prebiotics, mainly composed of 1,4-ß-D-mannose, 1,4-ß-D-glucose, and O-acetate groups, which induce an increase in the abundance of gut microbiota such as Lactobacillus, Bifidobacterium, Akkermansia, Bacteroides, and Prevotella. In addition, we found that when exposed to DOPs with different structural properties, the gut microbiota may exhibit different diversity and composition and provide health benefits, such as metabolism regulations, inflammation modulation, immunity moderation, and cancer intervention. This may contribute to facilitating the development of functional foods and health products to improve human health.

Danlou Recipe promotes cholesterol efflux in macrophages RAW264.7 and reverses cholesterol transport in mice with hyperlipidemia induced by P407.

INTRODUCTION: Liver X Receptor (LXR) agonists could attenuate the development of atherosclerosis but bring excess lipid accumulation in the liver. Danlou Recipe was believed to be a benefit for improving the lipid profile. Thus, it is unclear whether Danlou Recipe could attenuate hyperlipidemia without excess lipid accumulated in the liver of mice. This study aimed to clarify if Danlou Recipe could alleviate the progression of hyperlipidemia in mice without extra lipids accumulated in the liver. METHODS: Male murine macrophage RAW264.7 cells and murine peritoneal macrophages were used for the in vitro experiments. Cellular cholesterol efflux was determined using the fluorescent cholesterol labeling method. Those genes involved in lipid metabolism were evaluated by qRT-PCR and western blotting respectively. In vivo, a mouse model of hyperlipidemia induced by P407 was used to figure out the effect of Danlou Recipe on reverse cholesterol transport (RCT) and hyperlipidemia. Ethanol extract of Danlou tablet (EEDL) was prepared by extracting the whole powder of Danlou Prescription from ethanol, and the chemical composition was analyzed by ultra-performance liquid chromatography (UPLC). RESULTS: EEDL inhibits the formation of RAW264.7 macrophage-derived foam cells, and promotes ABCA1/apoA1 conducted cholesterol efflux in RAW264.7 macrophages and mouse peritoneal macrophages. In the P407-induced hyperlipidemia mouse model, oral administration of EEDL can promote RCT in vivo and improve fatty liver induced by a high-fat diet. Consistent with the findings in vitro, EEDL promotes RCT by upregulating the LXR activities. CONCLUSION: Our results demonstrate that EEDL has the potential for targeting RCT/LXR in the treatment of lipid metabolism disorders to be developed as a safe and effective therapy.

Wheat Alkylresorcinols Modulate Glucose Homeostasis through Improving GLP-1 Secretion in High-Fat-Diet-Induced Obese Mice.

Wheat alkylresorcinols (ARs) consumption has been evidenced to improve obesity and its associated insulin resistance. However, the effect of ARs on glucagon-like peptide 1 (GLP-1) secretion and the underlying mechanism of action are still unclear. In this study, C57BL/6J mice were fed low-fat diet (LFD), high-fat diet (HFD), and HFD supplemented with 0.4% (w/w) ARs separately for 9 weeks. The results showed that ARs intervention significantly improved glucose homeostasis and restored the serum level of GLP-1 compared with the HFD control group. Moreover, ARs treatment alleviated HFD-induced ileal epithelium damage according to TUNEL staining, immunofluorescence, and transmission electron microscopy observation. The alleviative effect was further verified by apoptosis analysis and mitochondrial function evaluation. Furthermore, palmitic acid (PA) was administered to the intestinal secretin tumor cell line (STC-1) to clarify the protective effect of ARs on GLP-1 secretion in vitro. In consistence with the results of animal studies, ARs treatment could significantly improve GLP-1 secretion in STC-1 cells compared with PA treatment alone in a dose-dependent manner, accompanied by a reduction in apoptosis and mitochondrial dysfunction. In addition, ARs treatment notably enhanced the abundance of SCFA (short-chain fatty acid)-producing bacteria, such as Bacteroides, Bifidobacterium, and Akkermansia. The increased levels of intestinal SCFAs, such as acetic acid, propionic acid, and butyric acid, improved the expression of short-chain fatty acid receptors (FFAR3) and glucagon-like peptide-1 receptor (GLP-1R), enhancing the secretion of the intestinal hormones GLP-1. Thus, this study provides potential clinical implications of whole wheat as a dietary strategy to improve glucose homeostasis for obese populations.

Music Therapy in Pediatric Asthma: A Short Review.

Music therapy (MT) is a common modality that performs a complementary and integrative role along with standard treatments for many pediatric diseases. This article briefly reviewed the effects of MT on children aged 5-11 years old and adolescents with asthma from previous studies, specified its functional target towards asthma symptoms, and sorted out the design and investigation of selected research. Medline/PubMed, Embase, SportDis-cus, Cochrane Library, Teacher Reference Centre, Web of Science, Academic Search Complete, PsycARTICLES, and Scopus were queried for experimental and observational studies published between 1990 and 2021. Then, researchers showed that MT lessened patients' asthma symptoms, improved medication compliance, pulmonary function, and quality of life, and helped children and their parents manage anxiety and depression. This article may serve as a reference for clinical research for pediatric asthma therapies and lay the foundation for future research on MT and its clinical practice.

Alpha-lipoic acid supplementation reverses the declining quality of oocytes exposed to cyclophosphamide.

Cyclophosphamide (CY) is a chemotherapeutic drug that is commonly used to treat malignancies of the ovary, breast, and hematology, as well as autoimmune disorders. As a cofactor of mitochondrial multienzyme complexes, alpha lipoic acid (ALA) is well known for its antioxidant characteristics, which operate directly on the scavenging of reactive oxygen species (ROS) and indirectly on the intracellular recycling of other antioxidants. However, the underlying mechanisms through which CY exerts its toxic effects on meiosis and oocyte quality, as well as a viable approach for protecting oocyte quality and preserving fertility, remain unknown. In present study, immunostaining and fluorescence intensity quantification were applied to assess the effects of CY and ALA supplementation on the key processes during the oocyte meiotic maturation. Our results show that supplementing oocytes with ALA, a well-known antioxidant and free radical scavenger, can reverse CY-induced oocyte meiotic maturation failure. Specifically, we found that CY exposure caused oocyte meiotic failure by disrupting meiotic organelle dynamics and arrangement, as well as a prominently impaired cytoskeleton assembly. In addition, CY caused an abnormal distribution of mitochondrion and cortical granules, two indicators of oocyte cytoplasmic maturation. More importantly, we show that ALA supplementation effectively reverses CY-induced meiotic failure and oocyte quality decline by suppressing oxidative stress-induced DNA damage and apoptosis in oocytes. Collectively, our data reveal that ALA supplementation is a feasible approach to protect oocytes from CY-exposed deterioration, providing a better understanding of the mechanisms involved in chemotherapy-induced meiotic failure.

Two zinc finger proteins, VdZFP1 and VdZFP2, interact with VdCmr1 to promote melanized microsclerotia development and stress tolerance in Verticillium dahliae.

BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

Real-Time Monitoring of Translocation, Dissipation, and Cumulative Risk of Maleic Hydrazide in Potato Plants and Tubers by Ion Exclusion Chromatography.

In this paper, a high-performance ion exclusion chromatographic (ICE) method was developed and applied for monitoring maleic hydrazide (MH) translocation in complex potato plant tissue and tuber matrices. After middle leaf uptake, most MH was trapped and dissipated in the middle leaf, and the rest was transported to other parts mainly through the phloem. Soil absorption significantly reduced the uptake efficiency of the root system, in which MH was partitioned to dissipate in root protoplasts or transfer through the xylem and persisted in the plant. Tuber uptake enabled MH to remain in the flesh and maintain stable levels under storage conditions, but during germination, MH was translocated from the flesh to the growing buds, where it dissipated through the short-day photoperiodic regime. The results demonstrated successful application of the ICE method and provided necessary insights for real-time monitoring of MH translocation behavior to effectively improve potato edible safety.

Identification of the key mechanisms of action of Si-Ni-San in uveitis using bioinformatics and network pharmacology.

BACKGROUND: Uveitis is an eye disease with a high rate of blindness, whose pathogenesis is not completely understood. Si-Ni-San (SNS) has been used as a traditional medicine to treat uveitis in China. However, its mechanism of action remains unclear. This study explored the potential mechanisms of SNS in the treatment of uveitis through network pharmacology and bioinformatics. METHODS: Using R language and Perl software, the active components and predicted targets of SNS, as well as the related gene targets of uveitis, were mined through the Traditional Chinese Medicine Systems Pharmacology, Therapeutic Target, Gene Expression Omnibus, GeneCards, and DrugBank databases. The network diagram of active components and intersection targets was constructed using Cytoscape software and the String database. The CytoNCA plug-in was used to conduct topological analysis on the network diagram and screen out the core compounds and key targets. The genes were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Chemoffice, Pymol, AutoDock, and Vina were used to analyze the molecular docking of key targets and core compounds of diseases through the PubChem database. RESULTS: JUN, RELA, and MAPK may play important roles in the treatment of uveitis by SNS. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that core genes were mainly concentrated in MAPK, toll-like receptor, tumor necrosis factor, and nucleotide oligomerization domain-like receptor signaling pathways. In addition, molecular docking results showed that the bioactive compounds (kaempferol, luteolin, naringin, and quercetin) exhibited good binding ability to JUN, RELA, and MAPK. CONCLUSION: Based on these findings, SNS exhibits multi-component and multi-target synergistic action in the treatment of uveitis, and its mechanism may be related to anti-inflammatory and immune regulation.

Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review.

BACKGROUND: Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time. In recent years, interaction with gut microbiota is hypothesized to be a reasonable explanation of the potential mechanisms for natural compounds especially polyphenols. OBJECTIVES: This review aims to present a persuasive explanation for the contradiction between the limited bioavailability and the remarkable bioactivities of polyphenols by examining their interactions with gut microbiota. METHODS: We assessed literatures published before April 10, 2023, from several databases, including Scopus, PubMed, Google Scholar, and Web of Science. The keywords used include "polyphenols", "gut microbiota", "short-chain fatty acids", "bile acids", "trimethylamine N-oxide", "lipopolysaccharides" "tryptophan", "dopamine", "intestinal barrier", "central nervous system", "lung", "anthocyanin", "proanthocyanidin", "baicalein", "caffeic acid", "curcumin", "epigallocatechin-3-gallate", "ferulic acid", "genistein", "kaempferol", "luteolin", "myricetin", "naringenin", "procyanidins", "protocatechuic acid", "pterostilbene", "quercetin", "resveratrol", etc. RESULTS: The review first demonstrates that polyphenols significantly alter gut microbiota diversity (α- and ß-diversity) and the abundance of specific microorganisms. Polyphenols either promote or inhibit microorganisms, with various factors influencing their effects, such as dosage, treatment duration, and chemical structure of polyphenols. Furthermore, the review reveals that polyphenols regulate several gut microbiota metabolites, including short-chain fatty acids, dopamine, trimethylamine N-oxide, bile acids, and lipopolysaccharides. Polyphenols affect these metabolites by altering gut microbiota composition, modifying microbial enzyme activity, and other potential mechanisms. The changed microbial metabolites induced by polyphenols subsequently trigger host responses in various ways, such as acting as intestinal acid-base homeostasis regulators and activating on specific target receptors. Additionally, polyphenols are transformed into microbial derivatives by gut microbiota and these polyphenols' microbial derivatives have many potential advantages (e.g., increased bioactivity, improved absorption). Lastly, the review shows polyphenols maintain intestinal barrier, central nervous system, and lung function homeostasis by regulating gut microbiota. CONCLUSION: The interaction between polyphenols and gut microbiota provides a credible explanation for the exceptional bioactivities of polyphenols. This review aids our understanding of the underlying mechanisms behind the bioactivity of polyphenols.

Ameliorative effect of Aconite aqueous extract on diarrhea is associated with modulation of the gut microbiota and bile acid metabolism.

Introduction: Aconite is a form of traditional Chinese medicine (TCM) that has been widely used to treat diarrhea for thousands of years. However, it is not clear whether the anti-diarrhea role of aconite aqueous extract (AA) is associated with regulation of the gut microbiota or with bile acid (BA) metabolism. This study aimed to confirm whether AA exerts its anti-diarrhea effects by regulating the gut microbiota and BA metabolism. Methods: The therapeutic effect of AA in a mouse model of diarrhea was measured based on analysis of body weight, fecal water content, diarrhea scores, intestinal propulsion rate, colonic pathology, and colonic immunohistochemistry. In addition, 16S rRNA high-throughput sequencing was conducted to analyze the effect of AA on the gut microbiota, and targeted metabolomics was employed to analyze the effect of AA on metabolism of BAs. Results: The results showed that treatment with AA reduced fecal water content and diarrhea scores, inhibited intestinal propulsion rate and pathological changes in the colon, and increased AQP3 and AQP4 content in the colon. In addition, AA was found to be capable of regulating the gut microbiota. Effects included increasing its richness (according to the ACE and Chao1 indices); altering the gut microbiota community structure (PCA, PCoA, and NMDS); increasing the relative abundance of norank_f_Muribaculaceae, Ruminococcus, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, and norank_f_norank_o_Clostridia_UCG-014; and decreasing the relative abundance of Escherichia-Shigella, unclassified_f_Ruminococcaceae, Ruminococcus_torques_group, and Parasutterella. More importantly, AA significantly increased fecal TCA (a primary BA) and DCA, LCA, GDCA, dehydro-LCA, and 12-keto-LCA (secondary BAs), thus restoring BA homeostasis. Moreover, AA increased the ratios of DCA/CA, DCA/TCA, and LCA/CDCA and decreased the ratios of TLCA/LCA, GLCA/LCA, and TUDCA/UDCA. Conclusion: The anti-diarrhea effect of AA was associated with restoration of the gut microbiota and BA metabolism-related homeostasis. The results of this study provide insights into the application of AA and the treatment of diarrhea.

Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China.

OBJECTIVE: Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19). METHODS: This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis. RESULTS: Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals. CONCLUSION: Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.

Functional Axis of PDE5/cGMP Mediates Timosaponin-AIII-Elicited Growth Suppression of Glioblastoma U87MG Cells.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.

Mechanism of Danggui Sini underlying the treatment of peripheral nerve injury based on network pharmacology and molecular docking: A review.

Danggui Sini is a traditional Chinese medicine prescription for treating peripheral nerve injury (PNI). We studied the mechanisms of this decoction through network pharmacology analysis and molecular docking. Using R language and Perl software, the active components and predicted targets of Danggui Sini, as well as the related gene targets of PNI, were mined through TCMSP, GeneCards, OMIM, TTD, and DrugBank. The network diagram of active components and intersection targets was constructed using Cytoscape software and the STRING database. The CytoNCA plug-in was used to screen out the core compounds and key targets. The genes were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. AutoDock was used to analyze the molecular docking of key targets and core compounds of diseases. The drug component disease target regulatory network showed that the key components included quercetin, kaempferol, naringenin, and licochalcone A, which play key roles in the whole network and may be the primary compounds associated with the action of Danggui Sini against PNI. PPI network topology analysis showed high degree values for RELA, JUN, MAPK1, RB1, and FOS. Enrichment analysis showed that the core targets of Danggui Sini participated in pathways associated with neurogenesis-multiple diseases. Molecular docking showed that the active ingredients in Danggui Sini had a good binding ability with key targets. We conclude that many active components of Danggui Sini play therapeutic roles in PNI treatment by regulating RELA, JUN, MAPK1, RB1, and FOS, and multiple other targets in inflammation, immunity, and lipid metabolism.

RNAseq analysis of the drug jian-yan-ling (JYL) using both in vivo and in vitro models.

Ethnopharmacological relevance: Jian-yan-ling (JYL) is a drug used in traditional Chinese medicine (TCM) prescriptions for the treatment of tumors after radiotherapy and chemotherapy, to effectively alleviate leukocytopenia. However, the genetic mechanisms underlying the function of JYL remain unclear. Aim of the study: This study aimed to explore the RNA changes and potential biological processes related to the anti-aging or life-extending effects of JYL treatments. Materials and methods: In vivo treatments were performed using Canton-S Drosophila corresponding to three groups: control, low-concentration (low-conc.), and high-concentration (high-conc.) groups. The low-conc. And the high-conc. Groups were treated with 4 mg/mL JYL and 8 mg/mL JYL, respectively. Thirty Drosophila eggs were placed in each vial, and the third instar larvae and adults 7 and 21 days post-eclosion were collected for RNA sequencing, irrespective of the gender.In vitro treatments were conducted using humanized immune cell lines HL60 and Jurkat, which were divided into 3 groups: control (0 µg/mL JYL), low-concentration (40 µg/mL JYL), and high-concentration (80 µg/mL JYL). The cells were collected after 48 h of each JYL drug treatment. Both the Drosophila and cell samples were analyzed using RNA sequencing. Results: The in vivo experiments revealed 74 upregulated genes in the low-concentration group, and CG13078 was a commonly downregulated differential gene, which is involved in ascorbate iron reductase activity. Further analysis of the co-expression map identified the key genes: regulatory particle non-ATPase (RPN), regulatory particle triple-A ATPase (RPT), and tripeptidyl-peptidase II (TPP II). For the in vitro experiments, 19 co-differential genes were compared between different concentrations of the HL 60 cell line, of which three genes were upregulated: LOC107987457 (phostensin-like gene), HSPA1A (heat shock protein family A member 1 A), and H2AC19 (H2A clustered histone 19). In the HL 60 cell line, JYL activated proteasome-related functions. In the Jurkat cell line, there were no common differential genes despite the presence of a dosage-dependent trend. Conclusions: The RNA-seq results showed that the traditional Chinese medicine JYL has longevity and anti-aging effects, indicating that further investigation is required.

Screening the effective components in treating dampness stagnancy due to spleen deficiency syndrome and elucidating the potential mechanism of Poria water extract.

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/ß/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.