Dissection of the mechanism of traditional Chinese medical prescription-Yiqihuoxue formula as an effective anti-fibrotic treatment for systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue fibrotic disease for which there is no effective treatment. Traditional Chinese Medicine (TCM), such as the Yiqihuoxue formula used in Shanghai TCM-integrated Hospital, has shown the efficacy of anti-fibrosis in clinical applications. This study was aiming to dissect the anti-fibrotic mechanism of Yiqihuoxue treatment for SSc. METHODS: Bleomycin-induced mice and SSc dermal fibroblasts were treated with Yiqihuoxue decoction; NIH-3T3 fibroblasts were exposed to exogenous TGF-β1, and then cultured with or without Yiqihuoxue decoction. Luciferase reporter gene assay was used to determine the activity of Smad binding element (SBE). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA levels of extracellular matrix (ECM) genes. The protein levels of type I collagen, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected by western blotting. Student’s t-tests were used to determine the significance of the results. RESULTS: Bleomycin-induced mice, SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts showed higher levels of ECM gene transcriptions and collagen production. In addition, the phosphorylation level of Smad3 and activity of SBE were significantly increased after exogenous TGF-β1 induction. Whereas, Yiqihuoxue treatment could obviously attenuate fibrosis in bleomycin-induced mice, down regulate ECM gene expressions and collagen production in SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts. Furthermore, the aberrantly high phosphorylation level of Smad3 and activity of SBE in the TGF-β1-induced NIH/3T3 fibroblasts were also dramatically decreased by Yiqihuoxue treatment. CONCLUSIONS: Yiqihuoxue treatment could effectively reduce collagen production via down-regulating the phosphorylation of Smad3 and then the activity of SBE, which are involved in the TGF-β pathway and constitutively activated in the progression of SSc

Epidemiology and immunoprotection of nephropathogenic avian infectious bronchitis virus in southern China

<p>Abstract</p> <p>Background</p> <p>In last three years, 96 suspected poultry farms from different provinces in China were diagnosed for avian infectious bronchitis (IB) survey. Finally, 221 IBV strains were confirmed by dwarf embryo test and RT-PCR assay. By virus recovery trials, 187 of the isolates caused the birds died or distressed from nephritis, which was accordant with the clinical record.</p> <p>Results</p> <p>Based on epidemiology analysis of recent field isolates of nephropathogenic IB in vaccinated farms in China, YL6 strain were used for vaccination and evaluated by antibody titer and challenge tests. The immunoprotection test indicated that the practical application of vaccine based on the recent field strains could finely facilitate controlling the nephropathogenic IB.</p> <p>Conclusions</p> <p>Our study was aim at setting a guide for safeguard against nephropathogenic IBV-caused disease in China.</p

Isolation and complete genomic characterization of H1N1 subtype swine influenza viruses in southern China through the 2009 pandemic

<p>Abstract</p> <p>Background</p> <p>The swine influenza (SI) is an infectious disease of swine and human. The novel swine-origin influenza A (H1N1) that emerged from April 2009 in Mexico spread rapidly and caused a human pandemic globally. To determine whether the tremendous virus had existed in or transmitted to pigs in southern China, eight H1N1 influenza strains were identified from pigs of Guangdong province during 2008-2009.</p> <p>Results</p> <p>Based on the homology and phylogenetic analyses of the nucleotide sequences of each gene segments, the isolates were confirmed to belong to the classical SI group, with HA, NP and NS most similar to 2009 human-like H1N1 influenza virus lineages. All of the eight strains were low pathogenic influenza viruses, had the same host range, and not sensitive to class of antiviral drugs.</p> <p>Conclusions</p> <p>This study provides the evidence that there is no 2009 H1N1-like virus emerged in southern China, but the importance of swine influenza virus surveillance in China should be given a high priority.</p

Phylogenetic distribution and predominant genotype of the avian infectious bronchitis virus in China during 2008-2009

<p>Abstract</p> <p>Background</p> <p>The nephropathogenic avian infectious bronchitis (IB) caused unprecedented economic losses to the commercial chicken industry of China in 2008-2009. To investigate the prevalence of nephropathogenic IB in China, eighty IBV isolates from different provinces during 2008-2009 were identified by dwarf embryo test and RT-PCR.</p> <p>Results</p> <p>The strains were mostly isolated in winter and spring with a wide age range of IB outbreaks, from 4 to 69 days. By the virus recovery trials, 70/80 of the strains resulted in the deaths or distresses of birds from nephritis. To learn more about the molecular evolutionary characteristics of the circulating field strains, the coding region of major spike 1 (S1) protein gene of these strains was RT-PCR amplified and sequenced. Compared to the published representative strains, nucleotides and amino acids sequence analysis indicated that the S1 genes of these strains and the reference strains displayed homologies ranging from 75.1% to 99.8% and from 73.1% to 99.8% respectively. S1 protein of the major pandemic strains contained 540 or 542 amino acids with the cleavage site of HRRRR or RRFRR. Phylogenetic analysis revealed that recent field isolates of IBV in China were mostly belonged to A2-branch (QXIBV-branch) and HN08-branch, only one isolate was belonged to Gray-branch and M41-branch respectively. Most of the 80 strains showed evolutionarily distant from vaccine strains.</p> <p>Conclusions</p> <p>The results of this study suggested that nephropathogenic IBVs were mainly A2-like strains in China during 2008-2009.</p

Alterations of microbiota and metabolites in the feces of calves with diarrhea associated with rotavirus and coronavirus infections

The changes in the composition of intestinal microbiota and metabolites have been linked to digestive disorders in calves, especially neonatal calf diarrhea. Bovine rotavirus (BRV) and bovine coronavirus (BCoV) are known to be the primary culprits behind neonatal calf diarrhea. In this study, we analyzed changes in the fecal microbiota and metabolites of calves with neonatal diarrhea associated with BRV and BCoV infection using high-throughput 16S rRNA sequencing and metabolomics technology. The microbial diversity in the feces of calves infected with BRV and BCoV with diarrhea decreased significantly, and the composition changed significantly. The significant increase of Fusobacterium and the reductions of some bacteria genera, including Faecalibacterium, Bifidobacterium, Ruminococcus, Subdoligranulum, Parabacteroides, Collinsella, and Olsenella, etc., were closely related to diarrhea associated with BRV and BCoV infection. Metabolites in the feces of BRV and BCoV-infected calves with diarrhea were significantly changed. Phosphatidylcholine [PC; 16:1(9 Z)/16:1(9 Z)], lysophosphatidylethanolamine (LysoPE; 0:0/22:0), lysophosphatidylcholine (LysoPC; P-16:0) and LysoPE (0:0/18:0) were significantly higher in the feces of BRV-infected calves with diarrhea. In contrast, some others, such as desthiobiotin, were significantly lower. BRV infection affects glycerophospholipid metabolism and biotin metabolism in calves. Two differential metabolites were significantly increased, and 67 differential metabolites were significantly reduced in the feces of BCoV-infected calves with diarrhea. Seven significantly reduced metabolites, including deoxythymidylic acid (DTMP), dihydrobiopterin, dihydroneopterin triphosphate, cortexolone, cortisol, pantetheine, and pregnenolone sulfate, were enriched in the folate biosynthesis, pantothenate and CoA biosynthesis, pyrimidine metabolism, and steroid hormone biosynthesis pathway. The decrease in these metabolites was closely associated with increased harmful bacteria and reduced commensal bacteria. The content of short-chain fatty acids (SCFAs) such as acetic acid and propionic acid in the feces of BRV and BCoV-infected calves with diarrhea was lower than that of healthy calves, which was associated with the depletion of SCFAs-producing bacteria such as Parabacteroides, Fournierella, and Collinsella. The present study showed that BRV and BCoV infections changed the composition of the calf fecal microbiota and were associated with changes in fecal metabolites. This study lays the foundation for further revealing the roles of intestinal microbiota in neonatal calf diarrhea associated with BRV and BCoV infection

Human papillomavirus and cervical cancer in the microbial world: exploring the vaginal microecology

The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing. However, its relationship with human papillomavirus (HPV) infection and cervical cancer is not yet clear. Therefore, this article provides a review of the association between the vaginal microbiota, HPV infection, and cervical cancer. We discuss the composition of the vaginal microbiota, its dysbiosis, and its relationship with HPV infection, as well as potential mechanisms in the development of cervical cancer. In addition, we assess the feasibility of treatment strategies such as probiotics and vaginal microbiota transplantation to modulate the vaginal microbiota for the prevention and treatment of diseases related to HPV infection and cervical cancer. In the future, extensive replication studies are still needed to gain a deeper understanding of the complex relationship between the vaginal microbiota, HPV infection, and cervical cancer, and to clarify the role of the vaginal microbiota as a potential biomarker for predicting disease outcomes, thus providing a theoretical basis for personalized testing

The combination of deoxynivalenol and zearalenone at permitted feed concentrations causes serious physiological effects in young pigs

This study was to investigate the effects of the combination of deoxynivalenol (DON) and zearalenone (ZON) on pigs. Twenty-four weaning piglets were divided into a control group fed a diet free of mycotoxins and a toxin group fed a diet containing 1 mg/kg DON and 250 µg/kg ZON. The results showed that supplementation of DON and ZON in diets had extensive effects on pigs. More specifically, DON and ZON caused levels of total protein, albumin, and globulin in sera to decrease (p < 0.05) by 14.5%, 6.5% and 11.3%, respectively, and at the same time increased (p < 0.05) the serum enzyme activities of γ-glutamyltransferase, aspartate aminotransferase and alanine aminotransferase by 72.0%, 32.6% and 36.6%, respectively. In addition, DON and ZON decreased (p < 0.05) the level of anti-classical swine fever antibody titers by 14.8%. Real-time PCR showed that DON and ZON caused the mRNA expression levels of IFN-γ, TNF-α, IL-2, to decrease (p < 0.05) by 36.0%, 29.0% and 35.4%, respectively. Histopathological studies demonstrated that DON and ZON caused abnormalities in the liver, spleen, lymph nodes, uterus, and kidney. The concentrations of DON and ZON used in this study are in line with the published critical values permitted by BML. Our study clearly put the standard and adequacy of safety measures for these toxins into question. The authors suggest that with the increasing availability of cellular and molecular technologies, it is time to revisit the safety standards for toxins in feeds so as to make feeds safer, providing consumers with safer products

Integrated proteomic and metabolomic analysis elucidates the effects and mechanisms of Qiziyusi decoction on IVF outcomes in advanced maternal age infertility

BackgroundAdvanced maternal age (AMA) is associated with increased infertility and poor outcomes of in vitro fertilization (IVF), with limited effective treatments available. The traditional Chinese medicine (TCM) formula Qiziyusi decoction (QZYSD) is promising for addressing infertility in older women; however, its effects and mechanisms on IVF outcomes remain poorly understood. This study integrated a prospective cohort study, proteomics, and metabolomics to elucidate the effects and mechanisms by which QZYSD improves IVF outcomes in AMA infertility.MethodsThis prospective cohort study included 87 patients with tubal factor infertility who underwent IVF at the Reproductive and Genetic Center of Shandong University of TCM from April 2019 to October 2020, and stratified according to maternal age into the AMA (≥ 35 and ≤ 41), AMA-QZYSD (≥ 35 and ≤ 41), and young maternal age (YMA; ≥ 21 and ≤ 27) groups. The three groups of patients underwent controlled ovarian hyperstimulation using a short luteal phase protocol. In the AMA-QZYSD group, patients started oral administration of QZYSD from the day of pituitary downregulation until the day of oocyte retrieval, and follicular fluid (FF) was collected from all groups. The effects of QZYSD on improving IVF outcomes in AMA infertility were evaluated primarily by assessing cumulative clinical pregnancy (CCP) and miscarriage (CCM) rates, with secondary endpoints including the duration and dosage of gonadotropin (Gn) use, serum levels of follicle stimulating hormone (FSH), luteinizing Hormone (LH) and estrogen (E2) after pituitary downregulation, serum levels of E2 and progesterone (P) on the day of human chorionic gonadotropin (hCG) administration, endometrial thickness (EMt), number of oocytes retrieved, fertilization and cleavage rates, number of high-quality embryos on day 3, and embryo freezing status. Differential metabolites and proteins in FF were detected using ultra-performance liquid chromatography-tandem mass spectrometry and label-free quantitative proteomics. Correlation analysis was conducted to identify metabolites and proteins with significant correlations, and potential pathways were enriched and constructed using the common pathway analysis function in MetaboAnalyst (version 5.0). Finally, a “core target protein-metabolite-signaling pathway” network diagram was constructed using Cytoscape to further elucidate the mechanisms by which QZYSD improves IVF outcomes in patients with AMA infertility.ResultsThe study included 87 patients in the AMA-QZYSD experimental (n = 28), AMA control (n = 28), and YMA (n = 31) groups. The baseline demographic and clinical characteristics, such as maternal and paternal age, antral follicle count, basal serum levels of FSH, and E2 levels, were comparable across the groups. Regarding the primary endpoint, there was a trend toward a higher CCP rate in the AMA-QZYSD group compared to the AMA group. However, this difference was statistically non-significant (53.57% vs. 39.29%, P = 0.28), while the CCP rate in the AMA group was significantly lower than in the YMA group (P &lt; 0.05). The CCM rates indicated non-significant differences among the three groups (P &gt; 0.05). For the secondary endpoint, serum levels of E2 on the day of HCG (2391.57 ± 985.09 versus 1833.39 ± 763.49, P = 0.04), the number of retrieved oocytes (9.18 ± 3.90 versus 7.07 ± 2.92, P = 0.04) and high-quality embryos on day 3 (1.86 ± 1.58 versus 1.04 ± 1.20, P = 0.05) were slightly higher in the AMA-QZYSD group compared to the AMA control group, but both were lower than the YMA group (P &lt; 0.05). There were non-significant differences between the AMA-QZYSD and AMA groups regarding Gn usage days, Gn dosage, serum levels of FSH, LH and E2 after pituitary downregulation, serum levels of P on the day of hCG administration, EMt, IVF 2PN fertilizations, and embryo freezing status (P &gt; 0.05). A total of 35 differentially abundant metabolites were identified through metabolomics, and 492 differential proteins were detected using proteomics. The integrated metabolomics and proteomics results suggested that QZYSD may improve IVF outcomes in AMA infertility primarily by regulating the expression of component C8 alpha chain (C8A), carboxypeptidase B2 (CPB2), serum paraoxonase/arylesterase 1 (PON1), immunoglobulin heavy variable 3-9 (IGHV3-9) and pantetheinase (VNN1), as well as influencing the protein digestion and absorption and pantothenate and coenzyme A biosynthesis pathways.ConclusionQZYSD in IVF for women with AMA infertility is promising for improving clinical pregnancy rates and overall IVF outcomes, potentially through its effect on the FF microenvironment. However, further research is needed to conduct larger randomized controlled double-blind clinical trials and experimental studies to elucidate the efficacy and mechanisms of QZYSD on IVF success in this population

Evaluating the sustainable cultivation of 'Fuji' apples: suitable crop load and the impact of chemical thinning agents on fruit quality and transcription

The optimal load capacity provides sustainable production and high quality in 'Fuji' apple production. Determining optimal crop loads with simple and affordable thinning methods is critical for apple. We set different load capacities on different apple tree rootstocks and evaluated their effects on tree development, fruit yield and quality. The optimal load capacity for vigorous stock, dwarfing rootstock, and dwarfing interstock were 240, 90, and 100 for apples above 80 mm in diameter, respectively. To explore the optimal strategies of diverse fruit thinning agents (carbaryl, 6-BA, NAA, and Metamitron) used in the 'Fuji' apple tree, we assess from thinning agents' types, varying spraying concentrations, and application time in the most widely used dwarfing interstock. The results showed that the best use of fruit thinning agents is 2,000 mg/L carbaryl at 10 d after flowering could significantly reduce fruit set rate and improve the fruit quality in the dwarfing interstock. During the research, only the fruit thinner NAA treatment suppresses fruit development. Thus, we performed the transcriptome analysis on the NAA-treated and control fruits at 60 (FS1), 90 (FS2), 120 (FS3), and 150 (FS4) days after flowering stages to investigate the potential transcriptional regulations of NAA on fruit development and ripening. Transcriptome results showed that genes related to fruit expansion (expansin A15, expansin B3), phytohormone-related genes (HVA22C, PRE1, AHP1, etc.), fruit coloring-related genes (PAL), and many ripening-related transcription factors (EIN3, ERF, ARF, etc.) might be regulated by exogenous NAA. Our results provide an important reference for the sustainable production and optimal use of fruit thinning agents

Effect of blood flow-restrictive resistance training on metabolic disorder and body composition in older adults with type 2 diabetes: a randomized controlled study

IntroductionTo explore whether blood flow-restrictive resistance exercise (BFRE) can be used as an alternative strategy to moderate-intensity resistance training (RT) to improve metabolic disorder and body composition in older adults with type 2 diabetes (T2DM).MethodsThis is a single-blind, randomized, controlled trial. Ninety-eight older adults with T2DM were randomly divided into three groups: BFRE group (n = 34), RT group (n = 31) and control group (n = 33). Two exercise groups received supervised collective training for a period of six months, each lasting 50 min, three times a week. The primary outcomes included fasting plasma glucose (FPG), Glycosylated hemoglobin (HbA1c), blood lipids, blood pressure, and body composition. The secondary outcome was muscle performance.ResultsAfter six months of intervention, the FPG, HbA1c, blood lipids, diastolic blood pressure, body composition, and muscle performance of the two exercise groups were significantly improved relative to the control group and baseline measurements (P &lt; 0.05). There was no significant increase in lean mass between the two exercise groups compared to the control group and baseline (p &gt; 0.05). There was no significant decrease in systolic blood pressure between the two exercise groups compared to the control group (p &gt; 0.05), but it was significantly lower than their baseline (P &lt; 0.05). There was no significant difference in all indicators between the two exercise groups at the baseline, third and sixth months of intervention (p &gt; 0.05).DiscussionBFRE can safely and effectively improve the metabolic disorder and body composition of older adults with T2DM. For elderly exercise beginners, BFRE can be used as an alternative strategy to moderate-intensity resistance training.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357