1.Role and mechanism of intestinal flora metabolites in obesity regulation
Qihang YANG ; Rui PU ; Ziyang CHEN ; Siyi LENG ; Yongjing SONG ; Hui LIU ; Guangyou DU
Chinese Journal of Tissue Engineering Research 2024;28(2):308-314
BACKGROUND:Gut microbiota is closely related to host energy balance and metabolism.The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity. OBJECTIVE:To summarize the interaction between the intestinal flora and obesity,as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora,thereby providing a new reference and basis for the prevention and treatment of obesity. METHODS:"Intestinal microbiota,intestinal bacteria,intestinal microbiota metabolites,short-chain fatty acids,bile acids,ipopolysaccharide,trimethylamine N-oxide,medium-chain fatty acids,tryptophan derivatives,obesity"were used as search terms in Chinese and English.Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases.According to inclusion and exclusion criteria,88 articles were finally selected. RESULTS AND CONCLUSION:Intestinal flora is closely related to the occurrence and development of obesity.For example,changes in the Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity,and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve,Lactobacillus and Akkermansia.Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity.For example,short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41,43 and peroxisome proliferator-activated receptor γ,thus delaying the occurrence and development of obesity.Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor.In addition,lipopolysaccharide,trimethylamine oxide,medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways.Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways.For example,under the influence of high-fat diet,acetic acids can activate the parasympathetic nervous system,leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity.
2.Intestinal flora and osteoporosis and exercise intervention
Qihang YANG ; Rui PU ; Ziyang CHEN ; Siyi LENG ; Yongjing SONG ; Hui LIU ; Guangyou DU
Chinese Journal of Tissue Engineering Research 2024;28(26):4250-4256
BACKGROUND:Intestinal flora and its metabolites can participate in the pathological process of osteoporosis and play an important role in the diagnosis and treatment of osteoporosis.In addition,exercise can regulate the intestinal flora and thus affect the occurrence and development of osteoporosis. OBJECTIVE:To summarize the effects and mechanism of intestinal flora on osteoblasts,osteoclasts,and bone marrow mesenchymal stem cells,and the potential role of exercise-mediated intestinal flora in regulating osteoporosis. METHODS:"Intestinal flora,intestinal bacteria,metabolites of intestinal flora,bone metabolism,osteoporosis,exercise"were selected as keywords.Literatures from 1990 to 2023 were retrieved from PubMed and CNKI databases. RESULTS AND CONCLUSION:Changes in the abundance and diversity of intestinal flora and changes in the levels of intestinal flora metabolites such as trimethylamine oxide and bile acid can be used as biomarkers for the diagnosis of osteoporosis.The imbalance of intestinal flora can lead to intestinal barrier dysfunction and excessive production of lipopolysaccharides and trimethylamine oxide,induce the secretion of tumor necrosis factor-α and other inflammatory cytokines,activate the nuclear factor κB signaling pathway and aggravate oxidative stress,thus promoting osteoclast differentiation,inducing osteoblast apoptosis and affecting bone marrow mesenchymal cell migration.Remodeling intestinal flora homeostasis can inhibit inflammatory response,downregulate oxidative stress,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate the osteogenic migration of bone marrow mesenchymal cells to prevent and treat osteoporosis.Exercise can regulate intestinal flora homeostasis,improve intestinal barrier function,promote the secretion of short-chain fatty acids and bile acids,down-regulate serum lipopolysaccharide level,reduce oxidative stress,and then inhibit osteocyte apoptosis,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate osteocyte nutrient metabolism to exert the potential of preventing and treating osteoporosis.
3.Astragalus Mongholicus Bunge-Curcuma Aromatica-Paridis Rhizoma Inhibits Metastasis of Colon Cancer via the PERK/eIF2α/ATF4 Signaling Pathway
Huilan ZHANG ; Wenhui GUO ; Tingting SU ; Si CHEN ; Qianhui YU ; Qihang YIN ; Linlu WAN ; Xu WANG ; Decai TANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(3):240-248
OBJECTIVE To investigate the mechanism of anti-colorectal cancer growth and metastasis-related effects of Astraga-lus mongholicus Bunge-Curcuma aromatica-Paridis Rhizoma(Qi-Zhu-Zao)pairing through PERK/eIF2α/ATF4 signaling pathway mediating endoplasmic reticulum stress.METHODS Twenty-four BALB/c male mice were randomly divided into sham-operated group,model group,5-FU(5-fluorouracil)group(25 mg·kg-1),and Qi-Zhu-Zao high dose group(5.85 g·kg-1),Qi-Zhu-Zao low dose group(2.925 g·kg-1)(n=6)to construct a mouse model of colorectal cancer in situ transplantation tumor,and the inter-vention effect of Qi-Zhu-Zao combination on tumor growth was assessed by the change of tumor volume size after 15 days of administra-tion;the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by H&E.Pathological staining was used to eval-uate the effect of Qi-Zhu-Zao combination on the liver and tumor tissues of mice.The changes of MDA,SOD and GSH-Px levels were detected by enzyme-linked immunosorbent assay(ELISA);the expression of PERK/eIF2α/ATF4 signaling pathway and EMT-related proteins were detected by protein immunoblotting(Western blot).RESULTS Compared with the model group,the tumor volume was significantly reduced(P<0.000 1),liver and spleen metastases were less pronounced in the Qi-Zhu-Zao high-dose group,and his-topathological staining results of liver tissue and tumor produced changes in oxidative stress indicators SOD,MDA,and GSH-Px,up-regulation of ER stress-related proteins p-PERK,p-IF2α,and ATF4,etc.,upregulated the protein expression levels of E-Cadherin,downregulated N-Cadherin,Vimentin,and Snail,and inhibited the EMT process(P<0.01 or P<0.05).CONCLUSION In this paper,we investigated the regulatory mechanism related to the inhibition of colorectal cancer growth and metastasis by the combination of Qi-Zhu-Zao trigonal medicine,and demonstrated that it may inhibit the growth and metastasis of colorectal cancer by activating the PERK/eIF2α/ATF4 pathway to induce sustained ER stress and affect the EMT process of colorectal cancer.
4.Timing and safety of lung cancer surgery after SARS-CoV-2 infection: A multicenter retrospective study
Zhe HE ; Qihang ZHU ; Xianglin LI ; Dezhao TANG ; Junhan WU ; Yizhang CHEN ; Qibin CHEN ; Qipeng ZHANG ; Enwu XU ; Haiping XIAO ; Yong TANG ; Guibin QIAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):945-949
Objective To explore the timing and safety of limited-period lung cancer surgery in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Clinical data of of patients infected with COVID-19 undergoing lung cancer surgery (an observation group) in the Department of Thoracic Surgery of Guangdong Provincial People's Hospital, the Department of Thoracic Surgery of General Hospital of Southern Theater Command of PLA, and the Department of Cardiothoracic Surgery of the First Affiliated Hospital of Guangdong Pharmaceutical University from December 2022 to January 2023 were retrospectively analyzed and compared with patients who underwent surgery during the same period but were not infected with COVID-19 (a control group), to explore the impact of COVID-19 infection on lung cancer surgery. Results We finally included 110 patients with 73 patients in the observation group (28 males and 45 females at age of 52.62±12.80 years) and 37 patients in the control group (22 males and 15 females at age of 56.84±11.14 years). The average operation time of the observation group was longer than that of the control group, and the incidence of anhelation was higher than that of the control group (P<0.05). There were no statistcal differences in blood loss, length of hospital stay, moderate or above fever rate, degree of cough and chest pain, or blood routine between the two groups. Conclusion It is safe and feasible to perform lung cancer surgery early after recovery for COVID-19 patients with lung cancer.
5.Discovery of a new nosiheptide-producing strain and its fermentation optimization for nosiheptide production
Qihang SUN ; Yuncong XU ; Lingrui WU ; Jiale RONG ; Yanwen WANG ; Yudan CAO ; Chen LUO ; Xuri WU
Journal of China Pharmaceutical University 2022;53(6):725-733
Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.
7.An overview of animal models of diabetic nephropathy
Qihang LI ; Wenbin CHEN ; Longyu SUN ; Ling GAO ; Xia ZHONG
Chinese Journal of Endocrinology and Metabolism 2020;36(3):257-262
Diabetic nephropathy is a microvascular complication in the advanced stage of diabetes. About 20%-40% of patients with diabetes will progress to diabetic nephropathy. And worldwide, diabetic nephropathy has become the leading cause of end-stage renal disease. Animal model is a useful tool to study the pathogenesis and treatment of diabetic nephropathy. Currently, the commonly used diabetic nephropathy models all simulate partial characteristics of human diabetic nephropathy in different degrees of pathophysiology. However, the research on diabetic nephropathy has not achieved considerable progress. The main obstacle is that there is no effective animal model that can fully simulate all the characteristics of human diabetic nephropathy. In this paper, the animal models of diabetic nephropathy were reviewed from the aspects of modeling mechanism, pathophysiology, their advantages and disadvantages.
8.Application of β-Folding Peptide Self-assembly in Biomedicine
Qihang CHEN ; Liying SUN ; Weibing DONG
Chinese Journal of Biochemical Pharmaceutics 2017;37(8):443-445
The β-sheet peptides can be self-assembled to form different supramolecular solids. The supramolecular solid can be linked to a wide range of functional domains, for example, with cell adhesion sequences, signal domains, and vaccine epitopes to form complex nanostructures, which can be widely used in biomedical fields. In this paper, we mainly reviewed the self-assembly of peptides using β-folding secondary structure to form nanostructures, and discussed the application of nanostructures in drug delivery and tissue engineering.
9.Application of heuristic teaching in film-reading session of radiology education for medical students
Jie ZHU ; Mingzhu ZOU ; Qihang CHEN ; Cheng ZHOU
Chinese Journal of Medical Education Research 2015;14(6):611-614
Objective to probe the potential application and advantages of heuristic method in the film-reading session of Imaging Radiology.Methods 66 eight-year program clinical medical juniors in the grade of 2008 to 2010 in Beijing University were selected as the subject and were evenly divided into two groups.Experimental group(n=33) was taught with heuristic method,in which the teacher ask questions and lead the students to find the way to solve problems in the way of clinical thinking mode.Control group(n=33) was taught with didactic method.The analysis of final examination of radiology course and an anonymous questionnaire survey were carried out at the end of semester,and the questionnaire survey to the students in grade 2008 and 2009 was conducted again after 1 years of their clinical practice.Results The score of students in experimental group were higher than those of control group (P=0.015,0.001,0.026 for the students in the grade of 2008,2009 and 2010 seperately).The two survey shows that the experimental group is better than the control group in the aspects of learning interest,clinical thinking ability,clinical application ability,solving difficult problem ability and language expression ability.Conclusion In the medical imaging practice teaching for clinical medical specialty undergraduate,the reasonable application of heuristic teaching,helps to improve students' learning enthusiasm and initiative,helps to cultivate medical students' ability of clinical application,and at the same time,can also improve teachers' teaching level.
10.Induced sputum culture for the identification of Mycobacterium avium complex lung disease with severe renal insufficiency: a case report and review
Yong DING ; Xuefeng ZHONG ; Baomin FANG ; Huixing KE ; Tieying SUN ; Qihang CHEN
Chinese Journal of Geriatrics 2013;32(10):1069-1072
Objective To study the diagnosis and treatment of Mycobacterium avium complex lung disease with severe renal insufficiency,and to provide a basis for improving the clinical diagnosis and treatment of MAC lung disease with severe renal insufficiency.Methods Clinical data of an elderly patient with MAC lung disease confirmed by induced sputum culture and complicated with chronic kidney disease (CKD 4) was reported.The related literatures at home and abroad were reviewed.Results A male patient aged 80 years with poor nutrition was suffering from progressive weight loss,exhaustion and night sweats.His weight was only 43-44 Kg.Chest CT showed that multiple small nodules,small spot pieces of shadow and ground glass shadows in bilateral lung tissues.PET/CT indicated that spot pieces and nodules with metabolic activity in high performance.Bronchoalveolar lavage fluid (BALF) inspection was negative.MAC was identified by induced sputum culture through high permeability brine induced sputum.It was difficult to choose drugs for the treatment of MAC lung disease due to his poor kidney function [GFR of left kidney:9.0 ml /min,GFR of right kidney:18.8 ml/min].Conventional anti-mycobacterium drugs showed a low to high resistance to MAC.Moxifloxacin was discontinued for renal insufficiency.His condition was stable after choosing trimodality therapy including azithromycin 0.25 g/d tiw,rifapentine 0.3 g/d biw,ethambutol 0.375 g /d tiw and the joining immunotherapy.Conclusions PET/ CT is not useful in identifying tuberculosis and MAC lung disease.The treatment of MAC lung disease is difficult in elderly patients with severe renal insufficiency and low weight.Individual therapy combined with immunotherapy and improving the nutrition state is a good choice for the treatment of MAC lung disease in elderly patients with severe renal insufficiency.The anti-MAC drugs should be carefully selected and the adverse reactions should be closely observed in order to obtain the satisfactory clinical results.

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