Therapeutic Potential of Danyankang Capsule in High-Fat Diet-Induced Cholelithiasis and Its Impact on Liver FXR Signaling and Gut Microbiota.

Cholelithiasis, commonly known as gallstones, represents a prevalent hepatobiliary disorder. This study aimed to elucidate the therapeutic role and mechanism of Danyankang capsulein treating cholelithiasis induced by a high-fat diet in C57BL/6 mice. The therapeutical potential of Danyankang was assessed through biochemical analyses, histopathological examinations, protein detection, and 16S rDNA sequencing. A high-fat diet resulted in cholelithiasis manifestation in mice, with discernable abnormal serum biochemical indices and disrupted biliary cholesterol homeostasis. Danyankang treatment notably ameliorated liver inflammation symptoms and rectified serum and liver biochemical abnormalities. Concurrently, it addressed biliary imbalances. Elevated expressions of toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB)/pNF-κB, HMGCR, CYP7A1, and CYP8B1 observed at the inception of cholelithiasis, were notably reduced upon Danyankang administration. Furthermore, 16S rDNA analysis revealed a decline in species number and diversity of the intestinal flora in cholelithiasis-treated mice, while the decline was reversed with Danyankang treatment. Danyankang capsules reduced the abundance of Verrucomicrobiota and increased the abundance of Actinobacteriota and Proteobacteria. In conclusion, the present study demonstrates that Danyankang exerts potent therapeutic efficacy against high-fat diet-induced cholelithiasis. This beneficial outcome is potentially linked to the inhibition of the TLR4/pNF-κB and SHP/CYP7A1/CYP8B1 signaling pathways, as well as the enhancement of intestinal flora species abundance.

Active components from Lagotis brachystachya maintain uric acid homeostasis by inhibiting renal TLR4-NLRP3 signaling in hyperuricemic mice.

Lagotis brachystachya Maxim is a herb widely used in traditional Tibetan medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and in vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which was consistent with the finding in the kidneys of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind Toll-like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3). Congruently, western blot analysis showed that the components inhibited TLR4/myeloid differentiation primary response 88 (MyD88)/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by inhibiting inflammatory signaling pathways.

Panaxatriol saponins promotes angiogenesis and enhances cerebral perfusion after ischemic stroke in rats.

BACKGROUND: Panaxatriol saponins (PTS), an extract from the traditional Chinese herb Panax notoginseng, which has been used to treat ischemic stroke for many years in China. However, the mechanism underlying the effects of PTS remains unclear. This study aimed to determine whether PTS can protect against ischemic brain injury by promoting angiogenesis and to explore the possible mechanism by which it promotes angiogenesis. METHODS: Middle cerebral artery occlusion (MCAO) was induced in rats, and neurological deficit scores and brain infarct volumes were assessed. Micro-Positron emission tomography (PET) was adopted to assess cerebral perfusion, and real-time PCR and western blotting were used to evaluate vascular growth factor and Sonic hedgehog (Shh) pathway component levels. Immunofluorescence staining was used to determine capillary densities in ischemic penumbrae. RESULTS: We showed that PTS improved neurological function and reduced infarct volumes in MCAO rats. Micro-PET indicated that PTS can significantly increase 18F-fluorodeoxyglucose (18F-PDG) uptake by ischemic brain tissue and enhance cerebral perfusion after MCAO surgery. Moreover, PTS was able to increase capillary densities and enhance angiogenesis in ischemic boundary zones and up-regulate vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1) expression by activating the Shh signaling pathway. CONCLUSION: These findings indicate that PTS exerts protective effects against cerebral ischemic injury by enhancing angiogenesis and improving microperfusion.

Light and classical music therapies attenuate chronic unpredictable mild stress-induced depression via BDNF signaling pathway in mice.

Depression, a pervasive mental health issue, often necessitates innovative therapeutic interventions. This study explores the efficacy of music therapy, a non-pharmacological approach, in ameliorating depression symptoms in a murine model. Employing a chronic unpredictable mild stress (CUMS) model to induce depressionlike behaviors in mice, we investigated the therapeutic potential of four distinct music genres: light, classical, atonal composition, and rock music. Behavioral assessments, including sucrose preference and immobility time, were conducted to evaluate the impact of music therapy. Additionally, we measured the levels of brain-derived neurotrophic factor (BDNF), synaptic proteins and neurogenesis to elucidate the underlying biological mechanisms. Our findings indicated that light and classical music significantly alleviated depression-like behaviors in mice, evidenced by increased sucrose preference and reduced immobility time. Conversely, atonal composition and rock music did not yield similar therapeutic benefits. Biochemically, light and classical music were associated with decreased levels of corticosterone and increased levels of glucocorticoid receptor, alongside enhanced BDNF signaling, synaptic proteins and neurogenesis. In conclusion, the study demonstrates that specific genres of music, notably light and classical music, may contribute to alleviating depression-like symptoms, potentially through mechanisms associated with BDNF signaling and neurogenesis. These results highlight the potential of targeted music therapy as a complementary approach in treating depression, with implications for its incorporation into broader therapeutic regimes. Further re-search is warranted to translate these findings into clinical practice.

Lagotis brachystachya maxim attenuates chronic alcoholic liver injury combined with gouty arthritis in rats via its anti-inflammatory activity.

Lagotis brachystachya Maxim, a common herb in Tibetan medicine, is mainly used to treat pneumonia, hepatitis, yellow water disease (gouty arthritis). Since long-term heavy drinking is also a risk factor for gouty arthritis, the present study aimed to evaluate the underlying protective role and mechanism of extracts of Lagotis brachystachya (ELB) in chronic alcoholic liver injury combined with gouty arthritis. The rat chronic alcoholic liver injury combined with gouty arthritis model was established by long-term alcohol consumption and monosodium urate (MSU) injection. The therapeutical action of ELB was then evaluated by biochemical measurement, histopathological examination, ankle swelling assessment, and protein detection. According to biochemical measurements and histopathological evaluation, ELB could alleviate the symptoms of alcoholic liver injury combined with gouty arthritis. In addition, chronic alcohol consumption and MSU activated inflammatory-related signaling such as TLR4/MyD88/NF-κB, NLRP3, and JAK2/STAT3 pathways in the liver and synovial tissues, while ELB significantly inhibited the activation of the inflammatory signaling pathway. In conclusion, ELB is protective in rats with chronic alcoholic liver injury and gouty arthritis, possibly mediated by the inhibition of TLR4/MyD88/NF-κB, NLRP3, and JAK2-STAT3 signaling pathways in both the hepatic and synovial tissues.

Correlation of the SNPs of FGFR1, FGF10, FGF18 with nonsyndromic cleft lip with or without palate in Chinese population.

OBJECTIVE: To explore the relationship between the polymorphisms in gene FGFR1, FGF10, FGF18 and the nonsyndromic cleft lip with or without cleft palate (NS CLP) in Chinese population. METHODS: Genomic DNA was isolated from peripheral lymphocytes of 75 patients with NS CLP and their parents and 75 unimpaired healthy children. The polymorphisms in FGFR1 gene rs13317, p.E467K, p.M369I and p.S393S, FGF10 gene rs1448037 and FGF18 gene rs4043716 were detected by applying three-dimensional (3-D) polyacrylamide gel microarray technology. The data were performed using statistical analysis: the genotype frequency and allele frequency between patients with NSCL/P and control subjects were performed. Haplotype relative risk (HRR), family based association test (FBAT), and transmission disequilibrium test (TDT) in nuclear family were performed. RESULTS: There were no polymorphism in FGFR1 gene p. E467K, p. M369I and p.S393S site, the corresponding base was all G. The polymorphisms of rs13317 and rs1448037 were detected and their genotype frequency and allele frequency showed no significant difference between 75 patients with NSCL/P and 75 normal children. TDT, HRR and FBAT were also no significant differences. The genotype frequency of gene FGF18 rs4043716 showed significant difference, but allele frequency were no significant difference. TDT, HRR and FBAT were also no significant difference. CONCLUSION: Our studies suggest an association between gene FGF18 rs4043716 and the NS CLP in Chinese population, and no association among gene FGFR1 rs13317, p. E467K, p. M369I, p. S393S and gene FGF10 rs1448037.

Interactions Between the Gut Microbiota and the Host Innate Immune Response Against Pathogens.

The mammalian intestine is colonized by over a trillion microbes that comprise the "gut microbiota," a microbial community which has co-evolved with the host to form a mutually beneficial relationship. Accumulating evidence indicates that the gut microbiota participates in immune system maturation and also plays a central role in host defense against pathogens. Here we review some of the mechanisms employed by the gut microbiota to boost the innate immune response against pathogens present on epithelial mucosal surfaces. Antimicrobial peptide secretion, inflammasome activation and induction of host IL-22, IL-17, and IL-10 production are the most commonly observed strategies employed by the gut microbiota for host anti-pathogen defense. Taken together, the body of evidence suggests that the host gut microbiota can elicit innate immunity against pathogens.

Characterization of Volatile Profiles of Six Popular Edible Mushrooms Using Headspace-Solid-Phase Microextraction Coupled with Gas Chromatography Combined with Chemometric Analysis.

The classification of six mushroom species (white beech, brown beech, button, oyster, king oyster, and enoki mushrooms) was successfully achieved using canonical discriminant analysis (CDA) on volatile metabolite data sets obtained by headspace-solid-phase microextraction gas chromatography (HS-SPME-GC). Twenty-seven major volatile compounds in six edible mushrooms were positively identified by HS-SPME-GC mass spectroscopy. The total volatile content was highest in brown beech mushroom (P < 0.05). Significant difference in volatile profile was observed between brown beach and white beech mushrooms. Button mushroom contained significantly higher contents of benzaldehyde and benzyl alcohol than the other mushrooms (P < 0.05). Oyster mushroom contained 1-octen-3-ol as the most prevalent volatile, representing 67% out of total volatiles. Hexanal (35.0%) and 1-octen-3-ol (22.5%) were the most abundant volatiles found in king oyster. Hexanal (29.1%) was the most prevalent volatile in enoki mushroom only. Several volatile pairs with very high positive correlation in their levels were identified, representing the highest correlation coefficient (r = 0.970) for the pair of t-2-octenal and 2,4-octandienal. CDA was much more efficient than principal component analysis for the differentiation of mushroom species. PRACTICAL APPLICATION: The present study provided the important information on the volatile metabolite profiles of popular six commercial mushroom species. The present data will be useful for the quality control of mushrooms cultivated in farms and mushroom products processed in food industry. The strategy of canonical discriminant analysis in combination with HS-SPME-GC could be expanded for the determining the authentication of mushroom species.

Pathogenicity of blood orf virus isolates in the development of dairy goat contagious pustular dermatitis.

Contagious pustular dermatitis is an exanthematous zoonotic disease caused by the orf virus. Pandemic outbreaks of this disease cause great economic losses, while the pathogenesis of this disease still remains obscure. In this study, blood samples were collected from 628 asymptomatic goats across China for PCR-based virus detection. We detected the orf virus in the blood of asymptomatic goats. Moreover, the orf virus obtained from the blood of infected goats was infectious and induced typical symptoms of contagious pustular dermatitis after inoculation of uninfected dairy goats. In summary, our data provide evidence that asymptomatic animals may be carriers of orf virus. Our findings should contribute to elucidating the details underlying the pathogenesis of contagious pustular dermatitis.

Habitual coffee consumption and risk of cognitive decline/dementia: A systematic review and meta-analysis of prospective cohort studies.

OBJECTIVE: Findings from epidemiologic studies of coffee consumption and risk for cognitive decline or dementia are inconclusive. The aim of this study was to conduct a meta-analysis of prospective studies to assess the association between coffee consumption and the risk for cognitive decline and dementia. METHODS: Relevant studies were identified by searching PubMed and Embase databases between 1966 and December 2014. Prospective cohorts that reported relative risk (RRs) and 95% confidence intervals (CIs) for the association of coffee consumption with dementia incidence or cognitive changing were eligible. Study-specific RRs were combined by using a random-effects model. RESULTS: Eleven prospective studies, including 29,155 participants, were included in the meta-analysis. The combined RR indicated that high coffee consumption was not associated with the different measures of cognitive decline or dementia (summary RR, 0.97; 95% CI, 0.84-1.11). Subgroup analyses suggested a significant inverse association between highest coffee consumption and the risk for Alzheimer disease (summary RR, 0.73; 95% CI, 0.55-0.97). The dose-response analysis, including eight studies, did not show an association between the increment of coffee intake and cognitive decline or dementia risk (an increment of 1 cup/d of coffee consumed; summary RR, 1.00; 95% CI, 0.98-1.02). CONCLUSIONS: The present study suggests that higher coffee consumption is associated with reduced risk for Alzheimer disease. Further randomized controlled trials or well-designed cohort studies are needed to determine the association between coffee consumption and cognitive decline or dementia.