Theabrownin from Fu Brick tea ameliorates high-fat induced insulin resistance, hepatic steatosis, and inflammation in mice by altering the composition and metabolites of gut microbiota.

Fu Brick tea belongs to fermented dark tea, which is one of the six categories of tea. Fu Brick tea has been reported to reduce adiposity and has beneficial effects in the treatment of hypercholesterolemia and cardiovascular disease. Theabrownin (TB) is one of the pigments with the most abundant content in Fu Brick tea. TB has also been reported to have lipid-lowering effects, but its mechanism remains unclear. We found that TB could effectively reduce the insulin resistance and fat deposition induced by a high fat diet (HFD), decrease inflammation in the liver, improve intestinal integrity, and reduce endotoxins in circulation. Further studies showed that TB increased the abundance of Verrucomicrobiota and reduced the abundance of Firmicutes and Desulfobacterota in the intestinal tract of obese mice. The alteration of gut microbiota is closely linked to the metabolic phenotype after TB treatment through correlation analysis. Moreover, TB changed the gut microbial metabolites including L-ornithine, α-ketoglutarate, and glutamine, which have also been found to be upregulated in the liver after TB intervention. In vitro, L-ornithine, α-ketoglutarate, or glutamine significantly reduced lipopolysaccharide (LPS)-induced inflammation in macrophages. Therefore, our results suggest that TB can reduce adiposity, systemic insulin resistance, and liver inflammation induced by a HFD through altering gut microbiota and improving the intestinal tight junction integrity. The metabolites of gut microbiota might also play a role in ameliorating the HFD-induced phenotype by TB.

A novel bioprospecting strategy via 13C-based high-throughput probing of active methylotrophs inhabiting oil reservoir surface soil.

Methane-oxidizing bacteria (MOB) have long been considered as a microbial indicator for oil and gas prospecting. However, due to the phylogenetically narrow breath of ecophysiologically distinct MOB, classic culture-dependent approaches could not discriminate MOB population at fine resolution, and accurately reflect the abundance of active MOB in the soil above oil and gas reservoirs. Here, we presented a novel microbial anomaly detection (MAD) strategy to quantitatively identify specific indicator methylotrophs in the surface soils for bioprospecting oil and gas reservoirs by using a combination of 13C-DNA stable isotope probing (SIP), high-throughput sequencing (HTS), quantitative PCR (qPCR) and geostatistical analysis. The Chunguang oilfield of the Junggar Basin was selected as a model system in western China, and type I methanotrophic Methylobacter was most active in the topsoil above the productive oil wells, while type II methanotrophic Methylosinus predominated in the dry well soils, exhibiting clear differences between non- and oil reservoir soils. Similar results were observed by quantification of Methylobacter pmoA genes as a specific bioindicator for the prediction of unknown reservoirs by grid sampling. A microbial anomaly distribution map based on geostatistical analysis further showed that the anomalous zones were highly consistent with petroleum, geological and seismic data, and validated by subsequent drilling. Over seven years, a total of 24 wells have been designed and drilled into the targeted anomaly, and the success rate via the MAD prospecting strategy was 83 %. Our results suggested that molecular techniques are powerful tools for oil and gas prospecting. This study indicates that the exploration efficiency could be significantly improved by integrating multi-disciplinary information in geophysics and geomicrobiology while reducing the drilling risk to a greater extent.

Exploring the Effect of Xiao-Chai-Hu Decoction on Treating Psoriasis Based on Network Pharmacology and Experiment Validation.

BACKGROUND: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. OBJECTIVE: To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, in vivo experiments were carried out further to validate the therapeutic effects of XCHD on psoriasis. RESULTS: 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. CONCLUSION: XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

An Umbrella Insight into the Phytochemistry Features and Biological Activities of Corn Silk: A Narrative Review.

Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.

Research Status in the Use of Surface-Enhanced Raman Scattering (SERS) to Detect Pesticide Residues in Foods and Plant-Derived Chinese Herbal Medicines.

Surface-enhanced Raman scattering (SERS) technology has unique advantages in the rapid detection of pesticides in plant-derived foods, leading to reduced detection limits and increased accuracy. Plant-derived Chinese herbal medicines have similar sources to plant-derived foods; however, due to the rough surfaces and complex compositions of herbal medicines, the detection of pesticide residues in this context continues to rely heavily on traditional methods, which are time consuming and laborious and are unable to meet market demands for portability. The application of flexible nanomaterials and SERS technology in this realm would allow rapid and accurate detection in a portable format. Therefore, in this review, we summarize the underlying principles and characteristics of SERS technology, with particular focus on applications of SERS for the analysis of pesticide residues in agricultural products. This paper summarizes recent research progress in the field from three main directions: sample pretreatment, SERS substrates, and data processing. The prospects and limitations of SERS technology are also discussed, in order to provide theoretical support for rapid detection of pesticide residues in Chinese herbal medicines.

Two Omics Methods Expose Anti-Depression Mechanism of Raw and Vinegar-Baked Bupleurum Scorzonerifolium Willd.

Bupleurum scorzonerifolium willd. (BS) and its vinegar-baked product (VBS) has been frequently utilized for depression management in clinical Chinese medicine. This paper aims to elucidate the antidepressant mechanism of BS and VBS from the perspectives of metabonomics and gut microbiota. A rat model of depression was established by CUMS combined with feeding alone to evaluate the antidepressant effects of BS and VBS. UPLC-Q-TOF-MS/MS-based metabolomics and 16S rRNA sequencing of rat feces were applied and the correlation of differential metabolic markers and intestinal floras was analyzed. The result revealed that BS and VBS significantly improved depression-like behaviors and the levels of monoamine neurotransmitters in CUMS rats. There were 27 differential endogenous metabolites between CUMS and normal rats, which were involved in 8 metabolic pathways. Whereas, BS and VBS could regulate 18 and 20 metabolites respectively, wherein fifteen of them were shared metabolites. On the genus level, BS and VBS could regulate twenty-five kinds of intestinal floras in CUMS rats, that is, they increased the abundance of beneficial bacteria and decreased the abundance of harmful bacteria. In conclusion, both BS and VBS exert excellent antidepressant effects by regulating various metabolic pathways and ameliorating intestinal microflora dysfunction.

Oral administration of punicalagin attenuates imiquimod-induced psoriasis by reducing ROS generation and inflammation via MAPK/ERK and NF-κB signaling pathways.

Psoriasis, an immune-mediated chronic inflammatory skin disease, imposes a huge mental and physical burden on patients and severely affects their quality of life. Punicalagin (PU), the most abundant ellagitannin in pomegranates, has become a research hotspot owing to its diverse biological activities. However, its effects on psoriasis remain unclear. We explored the impact and molecular mechanism of PU on M5-stimulated keratinocyte cell lines and imiquimod (IMQ)-induced psoriasis-like skin inflammation in BABL/c mice using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), hematoxylin and eosin (H&E) stain, immunohistochemistry, and immunofluorescent. Administration of PU-enriched pomegranate extract at dosages of 150 and 250 mg/kg/day markedly attenuated psoriatic severity, abrogated splenomegaly, and reduced IMQ-induced abnormal epidermal proliferation, CD4+ T-cell infiltration, and inflammatory factor expression. Moreover, PU could decrease expression levels of pro-inflammatory cytokines, such as IL-1ß, IL-1α, IL-6, IL-8, TNF-α, IL-17A, IL-22, IL-23A, and reactive oxygen species (ROS), followed by keratinocyte proliferation inhibition in the M5-stimulated cell line model of inflammation through inhibition of mitogen-activated protein kinases/extracellular regulated protein kinases (MAPK/ERK) and nuclear factor kappaB (NF-κB) signaling pathways. Our results indicate that PU may serve as a promising nutritional intervention for psoriasis by ameliorating cellular oxidative stress and inflammation.

[Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation].

This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1ß, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1ß, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

VAMP726 from maize and Arabidopsis confers pollen resistance to heat and UV radiation by influencing lignin content of sporopollenin.

Sporopollenin in the pollen cell wall protects male gametophytes from stresses. Phenylpropanoid derivatives, including guaiacyl (G) lignin units, are known to be structural components of sporopollenin, but the exact composition of sporopollenin remains to be fully resolved. We analyzed the phenylpropanoid derivatives in sporopollenin from maize and Arabidopsis by thioacidolysis coupled with nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS). The NMR and GC-MS results confirmed the presence of p-hydroxyphenyl (H), G, and syringyl (S) lignin units in sporopollenin from maize and Arabidopsis. Strikingly, H units account for the majority of lignin monomers in sporopollenin from these species. We next performed a genome-wide association study to explore the genetic basis of maize sporopollenin composition and identified a vesicle-associated membrane protein (ZmVAMP726) that is strongly associated with lignin monomer composition of maize sporopollenin. Genetic manipulation of VAMP726 affected not only lignin monomer composition in sporopollenin but also pollen resistance to heat and UV radiation in maize and Arabidopsis, indicating that VAMP726 is functionally conserved in monocot and dicot plants. Our work provides new insight into the lignin monomers that serve as structural components of sporopollenin and characterizes VAMP726, which affects sporopollenin composition and stress resistance in pollen.

Label-free quantitative proteomic analysis of milk fat globule membrane proteins in porcine colostrum and mature milk.

Milk fat globule membrane (MFGM) proteins are nutritional components with various biological functions. This study aimed to analyze and compare MFGM proteins in porcine colostrum (PC) and porcine mature milk (PM), via label-free quantitative proteomics. In total, 3917 and 3966 MFGM proteins were identified in PC and PM milk, respectively. A total of 3807 common MFGM proteins were found in both groups, including 303 significant differentially expressed MFGM proteins. Gene Ontology (GO) analysis revealed that the differentially expressed MFGM proteins were mainly related to the cellular process, cell, and binding. The dominant pathway of the differentially expressed MFGM proteins was related to the phagosome according to Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. These results reveal crucial insights into the functional diversity of MFGM proteins in porcine milk during lactation and provide theoretical guidance for the development of MFGM proteins in the future.

Electroacupuncture improves cardiac function after myocardial infarction by regulating the mobilization and migration of endogenous stem cells.

OBJECTIVE: The aim of this study was to explore the role and mechanisms of electroacupuncture (EA) in the regulation of chemokines in endogenous stem cell mobilization and myocardial regeneration after myocardial infarction (MI). METHODS: An MI model was constructed in adult male Sprague-Dawley rats by ligating the left anterior descending coronary artery. After 4 weeks of treatment, echocardiography was used to detect changes in cardiac function, and Masson's trichrome staining was used to detect collagen deposition. In addition, immunofluorescence staining was applied to examine von Willebrand factor (vWF)-positive vessels, the expression of cardiac troponin T (cTnT) and proliferation marker Ki67, and the number of c-kit-positive, C-X-C chemokine receptor type 4 (CXCR4)-positive, and Sca-1-positive endogenous stem cells in the infarcted area. In addition, the expression of stromal cell-derived factor (SDF)-1 and stem cell factor (SCF) was detected. RESULTS: EA increased the ejection fraction after MI, reduced collagen deposition and cellular apoptosis, and increased the number of blood vessels compared with an untreated model group. EA significantly promoted cellular proliferation, except for myocardial cells, and significantly increased the number of c-kit-, CXCR4- and Sca-1-positive stem cells. Moreover, the expression of SDF-1 and SCF in myocardial tissue in the EA group was significantly higher than that in the (untreated) MI group. CONCLUSIONS: EA appears to promote angiogenesis and reduce collagen deposition, thus improving the cardiac function of rats with MI. The underlying mechanism of action may involve endogenous stem cell mobilization mediated by SDF-1/CXCR4 and SCF/c-kit.

[Systematic review and Meta-analysis of Gusongbao preparation in treatment of primary osteoporosis].

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.

Change in habitual intakes of flavonoid-rich foods and mortality in US males and females.

BACKGROUND: Higher baseline intakes of flavonoid-rich foods and beverages are associated with a lower risk of chronic disease and mortality in observational studies. However, associations between changes in intakes and mortality remain unclear. We aimed to evaluate associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a composite measure (termed the 'flavodiet') of foods and beverages that are known to be main contributors to flavonoid intake and subsequent total and cause-specific mortality. METHODS: We evaluated associations between 8-year changes in intakes of (1) individual flavonoid-rich foods and (2) a novel 'flavodiet' score and total and cause-specific mortality. We included 55,786 females from the Nurses' Health Study (NHS) and 29,800 males from the Health Professionals Follow-up Study (HPFS), without chronic disease at baseline in our analyses. Using multivariable-adjusted Cox proportional hazard models, we examined associations of 8-year changes in intakes of (1) flavonoid-rich foods and (2) the flavodiet score with subsequent 2-year lagged 6-year risk of mortality adjusting for baseline intakes. Data were pooled using fixed-effects meta-analyses. RESULTS: We documented 15,293 deaths in the NHS and 8988 deaths in HPFS between 1986 and 2018. For blueberries, red wine and peppers, a 5%, 4% and 9% lower risk of mortality, respectively, was seen for each 3.5 servings/week increase in intakes while for tea, a 3% lower risk was seen for each 7 servings/week increase [Pooled HR (95% CI) for blueberries; 0.95 (0.91, 0.99); red wine: 0.96 (0.93, 0.99); peppers: 0.91 (0.88, 0.95); and tea: 0.97 (0.95, 0.98)]. Conversely, a 3.5 servings/week increase in intakes of onions and grapefruit plus grapefruit juice was associated with a 5% and 6% higher risk of total mortality, respectively. An increase of 3 servings per day in the flavodiet score was associated with an 8% lower risk of total mortality [Pooled HR: 0.92 (0.89, 0.96)], and a 13% lower risk of neurological mortality [Pooled HR: 0.87 (0.79, 0.97)], after multivariable adjustments. CONCLUSIONS: Encouraging an increased intake of specific flavonoid-rich foods and beverages, namely tea, blueberries, red wine, and peppers, even in middle age, may lower early mortality risk.

Comparative transcriptomics provides insights into the pathogenic immune response of brown leaf spots in weeping forsythia.

Weeping forsythia is an important ornamental, ecological and medicinal plant. Brown leaf spots limit the large-scale production of weeping forsythia as a medicinal crop. Alternaria alternata is a pathogen causing brown leaf spots in weeping forsythia; however, its pathogenesis and the immune response mechanisms of weeping forsythia remain unclear. In this study, we identified two mechanisms based on morphological anatomy, physiological indexes and gene expression analyses. Our results showed that A. alternata induced leaf stomata to open, invaded the mesophyll, dissolved the cell wall, destroyed the cell membrane and decreased the number of chloroplasts by up-regulating the expression of auxin-activated signaling pathway genes. Alternaria alternata also down-regulated iron-ion homeostasis and binding-related genes, which caused an increase in the levels of iron ions and reactive oxygen species in leaves. These processes eventually led to programmed cell death, destroying palisade and spongy tissues and causing the formation of iron rust spots. Alternaria alternata also caused defense and hypersensitive responses in weeping forsythia through signaling pathways mediated by flg22-like and elf18-like polypeptides, ethylene, H2O2 and bacterial secretion systems. Our study provides a theoretical basis for the control of brown leaf spots in weeping forsythia.

Ginseng polysaccharide reduces autoimmune hepatitis inflammatory response by inhibiting PI3K/AKT and TLRs/NF-κB signaling pathways.

BACKGROUND: Ginseng polysaccharides (GP) have been found to exhibit significant immune regulatory effects, making them a promising candidate for treating immune-related diseases. However, their mechanism of action in immune liver injury is not yet clear. The innovation of this study lies in exploring the mechanism of action of ginseng polysaccharides (GP) in immune liver injury. While GP has been previously identified for its immune regulatory effects, this study aims to provide a clearer understanding of its therapeutic potential for immune-related liver diseases. PURPOSE: The purpose of this study is to characterize low molecular weight gingeng polysaccharides (LGP), investigate their effect on ConA-induced autoimmune hepatitis (AIH), and identify their potential molecular mechanisms. METHODS: LGP was extracted and purified using water-alcohol precipitation, DEAE-52 cellulose column, and Sephadex G200. And its structure was analyzed. It was then evaluated for anti-inflammatory and hepatoprotective effects in ConA-induced cells and mice, assessing cellular viability and inflammation with Cell Counting Kit-8 (CCK-8), Reverse Transcription-polymerase Chain Reaction (RT-PCR), and Western Blot, and hepatic injury, inflammation, and apoptosis with various biochemical and staining methods. RESULTS: LGP is a polysaccharide composed of glucose (Glu), galactose (Gal), and arabinose (Ara), with a molar ratio of 12.9:1.6:1.0. LGP has a low crystallinity amorphous powder structure and is free from impurities. LGP enhances cell viability and reduces inflammatory factors in ConA-induced RAW264.7 cells and inhibits inflammation and hepatocyte apoptosis in ConA-induced mice. LGP inhibits Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and Toll-like receptors/Nuclear factor kappa B (TLRs/NF-κB) signaling pathways in vitro and in vivo to treat AIH. CONCLUSIONS: LGP was successfully extracted and purified, exhibiting potential as a treatment for ConA-induced autoimmune hepatitis due to its ability to inhibit the PI3K/AKT and TLRs/NF-κB signaling pathways and protect liver cells from damage.

Qianjin Wenwu decoction suppresses renal interstitial fibrosis by enhancing the degradation of extracellular matrix in mice with unilateral ureteral obstruction.

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF-ß1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- ß1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.

[Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism].

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.