Background: Zhijing Powder (ZJP) is a traditional Chinese medicine prescription containing two kinds of Chinese medicine. The purpose of this study is to analyze the molecular mechanism of ZJP in treating hypertension through network pharmacology, combined with in animal experiments. Methods: Firstly, the effective ingredients and potential targets of the drug were obtained through the drug target databases, while the targets of disease obtained through disease target databases. Then, the potential targets, cellular bioanalysis and signaling pathways were obtained through some platforms by analyzing the collected targets. Finally, further experiment was conducted to verify the effect and mechanism of drugs on cold and high salt induced hypertension rat model. Results: 17 effective components of centipede and 10 effective components of scorpion were obtained, and 464 drug targets were obtained after screening. A total of 1263 hypertension targets were obtained after screening and integration. Protein-protein interaction network (PPI) with 145 points and 1310 edges was constructed. GO analysis shows that blood circulation regulation and activation of G protein-coupled receptors are mainly biological processes. KEGG pathway analysis shows that Neuroactive Ligand-receptor Interaction, Calcium signaling Pathway, PI3K-Akt Signaling pathway are the most abundant gene-enriched pathway. Animal experiments indicated that ZJP can reduce blood pressure, affect the expression of PI3K-Akt signaling pathway, and improve oxidative stress in the body. Conclusion: ZJP ameliorates oxidative stress and reduces blood pressure on hypertensive rats caused by cold stimuli and high salt, revealing the effect of ZJP on the expression of PI3K/Akt signaling pathway in rat aorta.Funding Information: Funding support provided by the school of basic medicine, Hebei University of traditional Chinese Medicine.Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: All animals were approved by The Ethics Committee for Animal Experiments of Hebei University of Chinese Medicine(DWLL2020084).
Abstract Well-orchestrated maternal-fetal crosstalk occurs via secreted ligands, interacting receptors, and coupled intracellular pathways between the conceptus and endometrium, and is essential for successful embryo implantation. However, previous studies mostly focus on either the conceptus or the endometrium in isolation. The lack of integrated analysis impedes our understanding of early maternal-fetal crosstalk. Herein, focusing on ligand–receptor complexes and coupled pathways at the maternal-fetal interface in sheep, we provide the first comprehensive proteomic map of ligand-receptor pathway cascades essential for embryo implantation. We demonstrate that these cascades are associated with cell adhesion and invasion, redox homeostasis, and the immune response. Candidate interactions and their physiological roles were further validated by functional experiments. We reveal the physical interaction of albumin and claudin 4 and their roles in facilitating embryo attachment to endometrium. We also demonstrate a novel function of enhanced conceptus glycolysis in remodeling uterine receptivity by inducing endometrial histone lactylation, a newly identified histone modification. Results from in vitro and in vivo models supported the essential role of lactate in inducing endometrial H3K18 lactylation and in regulating redox homeostasis and apoptotic balance to ensure successful implantation. By reconstructing a map of potential ligand-receptor pathway cascades at the maternal-fetal interface, our study presents new concepts for understanding molecular and cellular mechanisms that fine-tune conceptus-endometrium crosstalk during implantation. This provides more direct and accurate insights for developing potential clinical intervention strategies to improve pregnancy outcomes following both natural and assisted conception.
In this study, simulated drinking water distribution systems (DWDSs) with chlorine/chloramine disinfectants were followed using household water purifiers (HWPs) with five steps of filtration involving nanofiltration membrane (NM). After 150 d, the fouled filters, influents, and effluents of HWPs were profiled for bacterial communities, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and viral factor genes (VFGs) using metagenomics. Among the fouled filters, the diversity of dominant species in Poly Propylene 1μm (PP1) and NM was significantly higher than that in other filters. Post-activated carbon (AC) was detected for low species richness or diversity, and the highest proportion of dominant species, which contributes to the greater microbial risk of HWPs effluents in drinking water. The number of dominant bacterial genera in the filters disinfected with chloramine was higher than that in the same group disinfected with chlorine. The bacterial species richness or diversity in water was reduced by the purification of HWPs due to the filter elements especially NM, which effectively trapped a variety of microorganisms. The relative abundance of Antibiotic efflux in the effluents of chlorinated and chloraminated HWPs was 5.58×10 -3 and 4.60×10 -3 , respectively, which was the main resistance mechanism . High abundance of VFGs was found in HWPs effluents and the relative abundance of aggressive VFGs was significantly higher than those of defensive VFGs. Based on the co-occurrence results, 243 subtypes of ARGs co-occurred with VFGs, and a variety of bacteria were thought to be possible ARGs hosts, which indicated that the host bacteria of VFGs in HWP effluents had a stronger attack ability. Using comparative analysis, the effluent of HWPs with only filtration processes is exposed to the risk of ARGs and VFGs. Especially Post-AC, set as the last filters in the HWPs contributed to more health hazards in HWPs effluents in drinking water.
Lactobacillus casei strain Shirota (LcS) is a widely used probiotic strain with health benefits. In this study, the survival of LcS in the intestines of healthy Chinese adults was assessed and the effects of LcS on stool consistency, stool SCFAs and intestinal microbiota evaluated. Subjects consumed 100 mL per day of a probiotic beverage containing 1.0 × 10(8) CFU/mL of LcS for 14 days. LcS were enumerated using a culture method and the colony identity confirmed by ELISA. Fourteen days after ingestion, the amount of LcS recovered from fecal samples was between 6.86 ± 0.80 and 7.17 ± 0.57 Log10 CFU/g of feces (mean ± SD). The intestinal microbiotas were analyzed by denaturing gradient gel electrophoresis. Principal component analysis showed that consuming LcS significantly changed fecal microbiota profiles. According to redundancy analysis, the amounts of 25 bacterial strains were significantly correlated with LcS intake (P < 0.05), 11 of them positively and fourteen negatively. Concentrations of acetic acid and propionic acid in feces were significantly lower during the ingestion period than during the baseline period (P < 0.05). These results confirm that LcS can survive passage through the gastrointestinal tract of Chinese people; however, they were found to have little ability to persist once their consumption had ceased. Furthermore, consumption of probiotic beverages containing LcS can modulate the composition of the intestinal microbiota on a long-term basis, resulting in decreased concentrations of SCFAs in the gut.
Abstract Background Buserelin is a luteinizing hormone releasing hormone (LHRH) agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not fully understood. This study was designed to develop a sensitive method to determine the concentration of buserelin in blood plasma and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studied in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC 0-t ) was 25.02 ± 6.93 h × ng/mL for pigs and 5.63 ± 1.86 h × ng/mL for cows. The maximum plasma concentration (C max ) and time to reach the maximum concentration (t max ) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ± 0.27 h for cows, respectively. The apparent volume of distribution (V z ) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t 1/2 ), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.
Abstract Well-orchestrated maternal-fetal crosstalk involves secreted ligands, interacting receptors, and coupled pathways between the conceptus and endometrium. However, previous researches mainly focused on either the conceptus or endometrium in isolation. The lack of integrated analysis, especially on protein levels, has made it challenging to advance our understanding of the crosstalk. Herein, focusing on ligand–receptor complexes and coupled pathways at maternal-fetal interface in sheep, a well-established embryo implantation model, we provide the first comprehensive proteomic atlas of ligand-receptor-pathway cascades that may be essential for implantation. Based on these candidate interactions, we further revealed the physical interaction of albumin-claudin 4 and their role in facilitating embryo attachment to endometrium. More interestingly, we demonstrated a novel non-metabolic function of enhanced conceptus glycolysis in remodeling uterine receptivity, by inducing endometrial histone lactylation, a newly identified histone modification. Our results from in vitro and in vivo models supported the essential role of lactate, as a key embryonic signal, in regulating redox homeostasis and apoptotic balance to ensure successful implantation. Our study identified many putative molecular and cellular mechanisms that fine-tuned conceptus-endometrium crosstalk during implantation, thus providing important clues for developing potential clinical intervention strategies to improve pregnancy outcomes following both natural conception and assisted reproduction.
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