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Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.
Subject(s)
Humans , Gastrointestinal Microbiome , Medicine, Chinese Traditional , Renal Insufficiency, Chronic/drug therapyABSTRACT
BACKGROUND: Isolation of nuclei or nuclear proteins is a prerequisite for western blot, nuclear proteome profiling, and other evaluations of nuclear proteins. Here, we developed a simple method for in situ isolation of nuclei or nuclear proteins by in situ removing the extranuclear part of adherent cells via a classical nonionic detergent triton X-100. RESULTS: First, the feasibility of our method was confirmed by confocal microscopy, atomic force microscopy, scanning electron microscopy, dynamic light scattering, immunofluorescence imaging, and time-lapse dynamic observation. Next, the optimal concentration range (approximately 0.1-1% for ~ 10 min) of triton X-100 and the optimal treatment time (< 30 min) of 0.1-1% Triton X-100 for our method were determined via western blotting of eight extra-/ intra-nuclear proteins. Subsequently, the effectiveness, sensitivity, and cytoplasmic contamination of our method were tested by investigating the levels of phosphorylated p65 (a NF-κB subunit) in the nuclei of endothelial or tumor cells treated with/without lipopolysaccharide (LPS) via western blotting and by comparing with a commercial nuclear protein extraction kit (a classical detergent-based method). The data show that compared with the commercial kit our method obtained a higher yield of total nuclear proteins, a higher pP65 level in both control and LPS groups, and much lower content of GAPDH (as a reference for cytoplasmic contamination) in nuclei. CONCLUSIONS: The in situ isolation of nuclei or nuclear proteins from adherent cells in this study is a simple, effective method with less cytoplasmic contamination. This method/strategy has the potential of improving the quality of downstream evaluations including western blotting and proteomic profiling.
Subject(s)
Nuclear Proteins , Lipopolysaccharides , NF-kappa B/metabolism , Octoxynol/pharmacology , Proteomics , Detergents/pharmacologyABSTRACT
@#Abstract: Objective To analyze the impact of the flood disaster on the distribution of Oncomelania snails in 2020 in Wuhu City, to provide scientific basis for formulating the "14th Five-Year Plan" for schistosomiasis control and precise prevention and control measures in Wuhu City. Methods Systematic sampling combined with environmental spot check was used to investigate the distribution of snails in the historical snail's environment, existing snail's environment and suspected snail's environment in Wuhu City. The collected snails were crushed and examined by microscope to understand the death and life of snails and the infection of Schistosoma japonicum, and the density of live snails and other indicators were counted. Results The historical area of snails was 14 475.24 hm2 in Wuhu City, and the existing area of snails was 4 588.72 hm2, including 4 210.32 hm2 for lake type and 378.40 hm2 for hill type snails. The average occurrence rate of live snails was 14.59%, and the average density of live snails was 0.50 snails/0.1 m2 in Wuhu City. There were 2 745 snail breeding environments, of which 491 were lake type and 2 254 are hill type, accounting for 17.89% and 82.11% respectively. The existing snail area was mainly distributed in the beaches and ditches, accounting for 92.51% and 6.29% of the existing snail area respectively. Some snails were distributed in ponds, paddy fields and other environments. Among all the historical snail habitats, the majority were class Ⅱ and class Ⅲ environments (which still have the basic conditions for snail breeding at present), with a total of 1 739 sites (blocks), accounting for 63.35% of the total environment. No schistosomiasis infected snails have been found, and the newly discovered and recovered snails cover an area of 268.21 hm2 in Wuhu City. Conclusions The distribution of snails is extensive in Wuhu City, and snails are mostly distributed in beaches, which are vulnerable to the impact of flood disasters. The spread of Oncomelania snails is found in 30 marshlands in 3 counties in this survey. It is necessary to continue to strengthen snail monitoring after disasters, and take class Ⅱ and class Ⅲ environments as key areas for snail monitoring, so as to find, identify and evaluate the risk of schistosomiasis transmission as soon as possible, to avoid or reduce the impact of flood disasters on the process of schistosomiasis control, and promote the process of schistosomiasis elimination.
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Abstract Objective This study aimed to assess the correlation between Sjögren′s Syndrome (SS) and adverse pregnancy outcomes, with the aim of providing a basis for preconception and pregnancy interventions in women with SS. Methods A search of electronic databases in English and Chinese databases from January 2005 to December 2021, was conducted to collect the literature of case-control studies or cohort studies on the association between SS and pregnancy outcome studies. Literature inclusion and data extraction were performed according to established criteria, and the Newcastle-Ottawa scale was used to evaluate the quality of the literature. Stata 15 software was used for meta-analysis. Results A total of nine papers were included in this study. Meta-analysis results showed that SS was associated with spontaneous abortion (RR = 8.85, 95% CI 3.10‒25.26), preterm birth (RR = 2.27, 95% CI 1.46‒3.52), low birth mass (RR = 1.99, 95% CI 1.34‒2.97), and birth defects (RR = 4.28, 95% CI 3.08‒5.96). Conclusion SS can increase the incidence of adverse pregnancy outcomes.
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Purpose@#There is no consensus regarding adjuvant therapies following Kasai portoenterostomy (KP) for biliary atresia (BA). This study aimed to analyze the effect of extended perioperative intravenous antibiotics (PI-Abx) and adjuvant corticosteroid on cholangitis and jaundice clearance rates in the 3 years post-KP in children with BA. @*Methods@#Data of patients who underwent KP between 1999-2018 at a single center were retrospectively analyzed. Group A (1999–2010) received PI-Abx for 5 days, Group B (2010–2012) received PI-Abx for 5 days plus low-dose prednisolone (2 mg/kg), and Group C (2012–2017) received PI-Abx for 14 days plus high-dose prednisolone (5 mg/kg). @*Results@#Fifty-four patients were included with groups A, B, and C comprising 25, 9, and 20 patients, respectively. The number of episodes of cholangitis was 1.0, 1.6, and 1.3 per patient (p=NS) within the first year and 1.8, 2.3, and 1.7 (p=NS) over 3 years in Groups A, B, and C, respectively. The jaundice clearance rate at 6 months was 52%, 78%, and 50% (p=NS), and the 3-year native liver survival (NLS) rate was 76%, 100%, and 80% (p=NS) in Groups A, B, and C, respectively. A near-significant association was observed between the incidence of cholangitis within the first year and decompensated liver cirrhosis/death at 3 years post KP (p=0.09). Persistence of jaundice at 6 months was significantly associated with decompensated cirrhosis/death at 3 years (p<0.001). @*Conclusion@#The extended duration of PI-Abx and adjuvant corticosteroids was not associated with improved rates of cholangitis, jaundice clearance, or NLS in patients with BA.
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Purpose@#There is no consensus regarding adjuvant therapies following Kasai portoenterostomy (KP) for biliary atresia (BA). This study aimed to analyze the effect of extended perioperative intravenous antibiotics (PI-Abx) and adjuvant corticosteroid on cholangitis and jaundice clearance rates in the 3 years post-KP in children with BA. @*Methods@#Data of patients who underwent KP between 1999-2018 at a single center were retrospectively analyzed. Group A (1999–2010) received PI-Abx for 5 days, Group B (2010–2012) received PI-Abx for 5 days plus low-dose prednisolone (2 mg/kg), and Group C (2012–2017) received PI-Abx for 14 days plus high-dose prednisolone (5 mg/kg). @*Results@#Fifty-four patients were included with groups A, B, and C comprising 25, 9, and 20 patients, respectively. The number of episodes of cholangitis was 1.0, 1.6, and 1.3 per patient (p=NS) within the first year and 1.8, 2.3, and 1.7 (p=NS) over 3 years in Groups A, B, and C, respectively. The jaundice clearance rate at 6 months was 52%, 78%, and 50% (p=NS), and the 3-year native liver survival (NLS) rate was 76%, 100%, and 80% (p=NS) in Groups A, B, and C, respectively. A near-significant association was observed between the incidence of cholangitis within the first year and decompensated liver cirrhosis/death at 3 years post KP (p=0.09). Persistence of jaundice at 6 months was significantly associated with decompensated cirrhosis/death at 3 years (p<0.001). @*Conclusion@#The extended duration of PI-Abx and adjuvant corticosteroids was not associated with improved rates of cholangitis, jaundice clearance, or NLS in patients with BA.
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Objective@#To analyze the mortality trend of bladder cancer among residents in Qidong, Jiangsu Province from 1972 to 2016, so as to provide the basis for the prevention and treatment strategy of bladder cancer in Qidong.@*Methods@#The data of bladder cancer was collected from Qidong Cancer Registry.The crude mortality rate ( CR ), age-standardized rate by Chinese population in 2000 (CASR) and world population in 1960 ( WASR ), truncated rate (35-64 years) and cumulative rate ( 0-74 years ) were calculated. The annual percent change ( APC ) was used to analyze the trend of mortality in bladder cancer.@*Results@#During from 1972 to 2016, There were 1 497 deaths due to bladder cancer in Qidong from 1972 to 2016. The CR, CASR and WASR were 2.96/105, 1.83/105 and 1.80/105, respectively. The APCs in CR, CASR, WASR of bladder cancer were 5.29%, 1.86% and 1.81%, respectively ( P<0.05 ), showing upward trends. The truncated rate, cumulative rate and cumulative risk were 1.47/105, 0.17% and 0.17%, respectively. The CR, CASR and WASR in males were 4.71/105, 2.97/105 and 3.31/105, respectively, which was higher than that of 1.26/105, 0.75/105, and 0.66/105 in females ( P<0.05 ). The APC of CR, CASR and WASR in males were 5.71%, 1.96% and 2.17%, respectively ( P<0.05 ), all showed upward trends. For females, the APC of CR was 4.47% ( P<0.05 ), showing an upward trend, but there was no significant change in CASR and WASR ( P>0.05 ). The CR of bladder cancer was high among people aged more than 55 years. The CR in 55-64-year-old group, 65-74-year-old group and more than 75-year-old group showed upward trends, with APC of 4.50%, 2.22% and 4.51%, respectively ( P<0.05 ). @*Conclusions@#From 1972 to 2016, the mortality of bladder cancer in Qidong showed an upward trend, which was relatively high in men and people aged over 55 years.
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Aims@#Acinetobacter baumannii has been identified as one of the six most pathogenic bacteria that is the cause of most hospital bacterial infections according to Infectious Disease Society of America (IDSA). These nosocomial pathogens are notorious worldwide due to its ability in causing lethal infections among immunocompromised patients and its resistance to many strong antibiotics. This study aims to compare the expressed proteins of two A. baumannii strain, ATCC 19606 and a pathogenic clinically isolated strain known as AB-13. @*Methodology and results@#AB-13 clinically strain was isolated from the lower respiratory tract of a patient with pneumonia. In this study, the proteomic profile of both ATCC 19606 and AB-13 are produced using 2-dimensional gel electrophoresis. The total protein contents were extracted, quantified and separated using 2-DE with a pH range of 4-7 to acquire the proteomic profile for comparison. The final analytical gel was analysed using Delta2D software and among the 324 protein spots successfully resolved, 10 spots exhibited signs of differential expression with 7 spots found to be downregulated and 3 spots upregulated (p< 0.01). These differences could signify the evolution AB-13 has undergone as it acquires traits ultimately aiding in its survivability, antimicrobial resistance and pathogenicity within varied environments especially during infections.@*Conclusion, significance and impact of study@#These findings support the presence of variation in AB-13 from a proteomic perspective, highlighting the pathogen’s evolution improving survivability and pathogenicity, warranting in-depth exploration towards understanding A. baumannii virulence and pathogenicity.
Subject(s)
Two-Dimensional Difference Gel Electrophoresis , ProteomicsABSTRACT
BACKGROUND: Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson's disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. Methods: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. RESULTS: Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. CONCLUSION: SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.