1.Extracellular vesicles: Roles in oocytes and emerging therapeutic opportunities.
Zhongyu ZHAO ; Yinrui SUN ; Renhao GUO ; Junzhi LIANG ; Wanlin DAI ; Yutao JIANG ; Yafan YU ; Yuexin YU ; Lixia HE ; Da LI
Chinese Medical Journal 2025;138(9):1050-1060
The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans
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Extracellular Vesicles/physiology*
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Oocytes/cytology*
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Female
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Animals
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Cell Communication/physiology*
2.High serum cystatin C is an independent risk factor for poor renal prognosis in IgA nephropathy.
Tianwei TANG ; Luan LI ; Yuanhan CHEN ; Li ZHANG ; Lixia XU ; Zhilian LI ; Zhonglin FENG ; Huilin ZHANG ; Ruifang HUA ; Zhiming YE ; Xinling LIANG ; Ruizhao LI
Journal of Southern Medical University 2025;45(2):379-386
OBJECTIVES:
To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients.
METHODS:
We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC).
RESULTS:
A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ2=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945).
CONCLUSIONS
Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.
Humans
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Glomerulonephritis, IGA/diagnosis*
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Cystatin C/blood*
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Prognosis
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Risk Factors
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Retrospective Studies
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Glomerular Filtration Rate
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Kidney Failure, Chronic
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Male
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Female
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Adult
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Nomograms
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Middle Aged
3.Influence and its mechanism of allogeneic dermal papilla cells on the wound healing of full-thickness skin defects in mice
Yage SHANG ; Lixia ZHANG ; Chao HAN ; Mengyang LI ; Liang LUO ; Xujie WANG ; Dahai HU
Chinese Journal of Burns 2024;40(8):772-780
Objective:To explore the influence and its mechanism of allogeneic dermal papilla cells (DPCs) on the wound healing of full-thickness skin defects in mice.Methods:This study was an experimental study. DPCs were isolated from the whisker follicles of five 6-week-old male C57BL/6J mice by combining microdissection with collagenase digestion and were successfully identified. Eighteen 8-week-old male C57BL/6J mice were divided into phosphate buffer solution (PBS) group and DPC group according to the random number table, with 9 mice in each group, and the full-thickness skin defect wound model was created on the back of all mice. On day 2, 4, and 6 after injury, the mice in DPC group were administered 100 μL of cell suspension containing 1×10 6 DPCs of the 4 th passage by subcutaneous injection around the wound, and the mice in PBS group was administered an equal volume of PBS. On day 3, 7, 10, and 14 after injury, the wound healing and hair growth of mice in two groups were observed, and the residual wound area was measured, and the hair coverage area on the wound of mice in two groups was measured on day 14 after injury. On day 14 after injury, the wound tissue samples of mice in two groups were collected. Hematoxylin-eosin staining was performed to observe the condition of newborn hair follicles and the number was counted, Masson staining was performed to observe the collagen deposition in the dermis and the collagen deposition area was measured, the immunofluorescence method was used to detect the protein expressions of Wnt/β-catenin signaling pathway related molecules β-catenin and lymphoid enhancer binding factor 1 (Lef1), and Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction were used to detect the protein and mRNA expressions of β-catenin and Lef1, respectively. The number of samples in each experiment was 3. Results:Compared with those in PBS group, the mice in DPC group had accelerated wound re-epithelialization at each time point after injury, and more hair growth on day 10 and 14 after injury. On day 7, 10, and 14 after injury, the residual wound areas of mice in DPC group were (13.92±2.90), (3.69±1.78), and (1.09±0.14) mm 2, respectively, which were significantly smaller than (26.19±2.06), (10.84±3.59), and (6.75±2.11) mm 2 in PBS group, respectively (with t values of 5.85, 3.09, and 4.63, respectively, P values all <0.05). On day 14 after injury, the hair coverage area on the wound of mice in DPC group was (62±7) mm 2, which was significantly larger than (35±6) mm 2 in PBS group ( t=2.89, P<0.05). On day 14 after injury, compared with those in PBS group, the number of newborn hair follicles in the wound tissue of mice in DPC group was significantly increased ( t=5.43, P<0.05), and the dermal collagen deposition area was significantly reduced ( t=3.56, P<0.05). On day 14 after injury, both the immunofluorescence method and the Western blotting detection showed that the protein expressions of β-catenin (with t values of 5.49 and 4.25, respectively, P values all <0.05) and Lef1 (with t values of 7.50 and 11.54, respectively, P values all <0.05) in the wound tissue of mice in DPC group were significantly higher than those in PBS group; the mRNA expressions of β-catenin and Lef1 in the wound tissue of mice in DPC group were significantly higher than those in PBS group (with t values of 7.68 and 9.67, respectively, P<0.05). Conclusions:DPCs can accelerate the re-epithelialization of full-thickness skin defect wounds in mice by activating Wnt/β-catenin signaling pathway and promote hair follicle regeneration during the process of wound healing.
4.The effect of Rhubarb ultrasonic electroconductive targeted dialysis therapy on the recovery of gastrointestinal dysfunction in sepsis patients:an observational study
Minggui CHEN ; Xuefei LIANG ; Fangfang WANG ; Lixia HUANG ; Ruixiang ZENG ; Yafeng HE ; Minzhou ZHANG ; Jiaping ZENG ; Xiaoxuan ZHANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(3):262-266
Objective To explore the effect of Rhubarb ultrasonic electrical conduction target penetration therapy on the gastrointestinal function of sepsis patients.Methods A total of 88 cases of inpatient sepsis patients diagnosed and treated at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from October 2021 to June 2023 were selected as the participants and the patients were divided into the treatment group and the control group by a simple random method.Both groups were given routine treatments such as anti-infection,fluid resuscitation,nutritional support,blood sugar management,and prevention of stress ulcers,while the treatment group was treated with ultrasonic conductance target penetration Rhubarb therapy at Shenque point and Zhongwan point on the basis of the control group.The main observational indexes were the number of bowel sounds in the two groups before treatment and after 3 days,and 7 days of treatment.The secondary observational indexes were gastric retention,serum C-reactive protein(CRP),procalcitonin(PCT),acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ),the first defecation time,time to mechanical ventilation,length of stay in the intensive care unit(ICU),hospitalization cost,and 28 days readmission rate of the two groups.The gastric retention was evaluated and recorded every 4 hours before treatment and 3 days and 7 days after treatment,CRP and APACHE Ⅱ score were evaluated before treatment and 7 days after treatment,the 28-day readmission was followed up by telephone.Results A total of 44 cases in the treatment group and 43 cases in the control group completed the intervention.The difference between the bowel sounds and the amount of gastric retention of the two groups was not statistically significant before treatment,with the prolongation of time,the bowel sounds of the two groups gradually increased and the amount of gastric retention gradually decreased,and the number of bowel sounds in the treatment group increased significantly compared to the control group 3 days and 7 days after treatment[beats/minute:4.49(4.23,4.74)vs.3.07(2.80,3.33)3rd day of and 4.79(4.49,5.10)vs.3.36(3.06,3.66)on the 7th day of treatment,both P<0.01],and the amount of gastric retention was significantly reduced compared with the control group[mL:20.93(9.22,32.64)vs.53.52(41.16,65.88)for 3rd day of and 3.72(0.17,7.28)vs.31.59(24.87,38.31)on the 7th day of treatment,both P<0.01].The first defecation time was significantly shorter in the treatment group than in the control group(hours:25.67±9.99 vs.33.64±11.30,P<0.01).After 7 days treatment,the CRP,PCT,and APACHE Ⅱ score were significantly reduced in the treatment group compared to those in the control group[CRP(mg/L):45.97(35.68,56.26)vs.77.30(57.20,97.38),PCT(μg/L):0.94(0.56,1.31)vs.2.73(1.36,4.09),APACHE Ⅱ score:24.11±7.01 vs.28.06±9.25,all P<0.05],the mechanical ventilation time and ICU length of stay were significantly shortened[mechanical ventilation time(hours):107.05±70.76 vs.168.83±136.62,ICU stay time(days):7.58±3.72 vs.9.70±5.15,both P<0.05],the hospitalization cost and 28-day readmission rate were significantly reduced[hospitalization cost(yuan):80337.89±36483.72 vs.109100.24±87080.84,28-day readmission rate:9.1%(4/44)vs.27.9%(12/43),both P<0.05].Conclusion Rhubarb ultrasonic conductive target penetration therapy is a safe,simple,and effective characteristic therapy of external Chinese medicine that can provide a new basis for the protection of gastrointestinal function in patients with sepsis.
5.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
6.Clinical application progression of ultrasound-guided quadratus lumborum block
Yi AN ; Lixia LI ; Zhongjia LI ; Chuanyu LIANG ; Pei WANG ; Tianlong WANG ; Lei ZHAO
The Journal of Clinical Anesthesiology 2024;40(11):1209-1213
Quadratus lumborum block(QLB)is a regional anesthesia technique that provides sen-sory and sympathetic nerves block of the unilateral trunk and lower limb by an injection of local anesthetic into the fascia space around the quadratus lumborum.At present,ultrasound-guided QLB is widely used in postoperative analgesia in abdominal and lower limb surgery with satisfied analgesia efficacy.This article will review the anatomical basis,mechanisms,puncture approaches,local anesthetic selection,clinical applica-tion and complications of QLB.
7.Effect of extra corporeal reducing pre-load on pulmonary mechanical power in patients with acute respiratory distress syndrome.
Wenwen ZHANG ; Xin'gang HU ; Lixia YUE ; Jie ZHANG ; Zhida LIU ; Shuai GAO ; Zhigang ZHAO ; Xinliang LIANG
Chinese Critical Care Medicine 2024;36(12):1244-1248
OBJECTIVE:
To explore the effects of veno-venous extra corporeal carbon dioxide removal (V-V ECCO2R) on local mechanical power and gas distribution in the lungs of patients with mild to moderate acute respiratory distress syndrome (ARDS) receiving non-invasive ventilation.
METHODS:
Retrospective research methods were conducted. Sixty patients with mild to moderate ARDS complicated with renal insufficiency who were transferred to the respiratory intensive care unit (RICU) through the 96195 platform critical care transport green channel from January 2018 to January 2020 at the collaborative hospitals of Henan Provincial People's Hospital were enrolled. According to different treatment methods, they were divided into a conventional treatment group and an ECCO2R group, with 30 patients in each group. Both groups received standard treatments including primary disease treatment, airway management, and non-invasive ventilation. The conventional treatment group received bedside continuous renal replacement therapy (CRRT), and the ECCO2R group received V-V ECCO2R treatment. General information of patient such as gender, age, cause of disease, and acute physiology and chronic health evaluation II (APACHE II) were recorded; arterial blood gas analysis was performed before treatment and at 12 hours and 24 hours during treatment, recording arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and oxygenation index (PaO2/FiO2). Respiratory mechanics parameters [tidal volume, respiratory rate, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP)] were recorded, and the rapid shallow breathing index (RSBI) was calculated; electrical impedance tomography (EIT) was used to measure regional of interest (ROI) values in different lung areas at 12 hours and 24 hours of treatment, and the pulmonary mechanical energy was calculated.
RESULTS:
The arterial blood gas analysis indicators, respiratory mechanics parameters, and pulmonary mechanical energy of patients in the conventional treatment group and ECCO2R group improved significantly after 24 hours of treatment compared to 12 hours of treatment (all P < 0.05). The levels of PaCO2, RSBI, total mechanical power, and non-dependent zone mechanical power in the ECCO2R group were significantly lower than those in the conventional treatment group at both 12 hours and 24 hours during the treatment [PaCO2 (mmHg, 1 mmHg ≈ 0.133 kPa): 44.03±2.96 vs. 49.96±2.50 at 12 hours, 41.65±3.21 vs. 48.53±2.33 at 24 hours; RSBI (times×min-1×L-1): 88.67±4.05 vs. 92.35±4.03 at 12 hours, 77.66±4.64 vs. 90.98±4.21 at 24 hours; total mechanical power (mJ): 10.40±1.15 vs. 12.93±1.68 at 12 hours, 11.13±1.18 vs. 14.05±1.69 at 24 hours; non-dependent zone mechanical power (mJ): 7.15±0.84 vs. 7.98±0.75 at 12 hours, 7.77±0.93 vs. 9.13±1.10 at 24 hours], and MEP and MIP in the ECCO2R group were significantly higher than those in the conventional treatment group at both 12 hours and 24 hours during the treatment [MEP (cmH2O, 1 cmH2O ≈ 0.098 kPa): 89.88±5.04 vs. 86.09±5.57 at 12 hours, 96.57±2.59 vs. 88.66±2.98 at 24 hours; MIP (cmH2O): 47.64±2.82 vs. 41.93±2.44 at 12 hours, 60.11±6.53 vs. 43.63±2.80 at 24 hours], the differences were statistically significant (all P < 0.05).
CONCLUSIONS
V-V ECCO2R combined with non-invasive ventilation can effectively reduce the regional tidal volume, mechanical power, and respiratory rate in the non-gravitational dependent zones of patients with mild to moderate ARDS, and improve respiratory distress and oxygenation status.
Humans
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Respiratory Distress Syndrome/physiopathology*
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Retrospective Studies
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Carbon Dioxide
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Blood Gas Analysis
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Lung/physiopathology*
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Intensive Care Units
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Male
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Female
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Noninvasive Ventilation/methods*
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Continuous Renal Replacement Therapy/methods*
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APACHE
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Middle Aged
8.Effect of Modified Dahuang Huanglian Xiexintang on Oxidative Stress Injury of Liver in Type 2 Diabetes Mellitus Rats Based on Nrf2/HO-1 Axis
Chengjun MA ; Fengzhe YAN ; Lixia YANG ; Yonglin LIANG ; Xiangdong ZHU ; Dong AN ; Yankui GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):121-130
ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus (T2DM) rats based on the nuclear factor erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis. MethodSix ZDF (fa/+) rats were as assigned to the blank group, and 30 ZDF (fa/fa) rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling, the rats were randomly divided into the model group, metformin group (0.18 g·kg-1), and low, medium, and high dose groups of modified Dahuang Huanglian Xiexintang (0.54, 1.08, 2.16 g·kg-1), with six rats in each group. After 12 weeks of drug intervention, the body mass, liver mass, fasting blood glucose (FBG), and oral glucose tolerance test (OGTT) levels were measured. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group, the model group showed a significant increase in body mass, liver mass, and liver index (P<0.01). Compared with the model group, the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight, liver mass, and liver index (P<0.01). Compared with the normal group, the model group showed significantly increased TC, TG, and LDL levels (P<0.01), and significantly decreased HDL levels (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels (P<0.01), and significantly reduced TG levels (P<0.05). The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels (P<0.05). The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels (P<0.05). Compared with the normal group, the model group showed significantly increased ALT and AST activities (P<0.01). Compared with the model group, all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities (P<0.05) and significantly reduced AST activities (P<0.01). Compared with normal group, the model group showed significantly increased FBG at all time points (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8, 10, 12 weeks. The OGTT results showed that compared with the normal group, the model group had significantly increased blood glucose at all time points (P<0.01). Compared with the model group, the metformin group showed significantly reduced blood glucose at all time points (P<0.01), and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90, 120 min (P<0.01). HE pathology showed clear and regular liver cell structure in the normal group, while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang, with fewer necrotic cells. Compared with the normal group, the model group showed significantly reduced SOD and GSH-Px levels (P<0.01), and significantly increased ROS and MDA levels (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels (P<0.01), and significantly reduced MDA levels (P<0.01). The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels (P<0.05). Compared with the normal group, the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels (P<0.01). Compared with the model group, the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels (P<0.05). Immunohistochemistry showed that compared with the normal group, the model group had significantly reduced positive expression of Nrf2 and HO-1 (P<0.05). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1, with a significant increase in brown-yellow granules around the cell nucleus (P<0.05). Western blot results showed that compared with the normal group, the model group had significantly reduced protein expression of Nrf2 and HO-1 (P<0.01). Compared with the model group, the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 (P<0.01). ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.
9. Mechanism of Dahuangtang pellets in regulating podocyte autophagy of diabetic nephropathy mice through AMPK/mTOR/ULK1 signaling pathway
Beibei SU ; Yonglin LIANG ; Chunxia XUE ; Pu ZHANG ; Xiaoli PEI ; Lixia YANG ; Xiangdong ZHU ; Xia YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):260-269
AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.
10.Effects of Shenyan 1 Prescription on renal fibrosis improvement in rats with unilateral ureteral obstruction based on TGF-β1/Smad3 signaling pathway
Guoqiang LIANG ; Jin XU ; Lixia ZHOU ; Daolei NI ; Yan REN ; Chunbo JIANG
International Journal of Traditional Chinese Medicine 2024;46(1):42-48
Objective:To investigate the protective effects and mechanism of Shenyan 1 Prescription on renal fibrosis of unilateral ureteral obstruction (UUO) rats through TGF- β 1/Smad homologous 3 (Smad3) pathway regulating ferroptosis.Methods:Totally 48 male SD rats were divided into four groups: sham-operation group, UUO model group, and Shenyan 1 Prescription low-(10 drug/kg) , and high-dosage (20 crude drug/kg) groups according to random number table method, with 12 rats in each group. The UUO model was induced by the method of unilateral ureteral obstruction except for those sham-operation group. After modeling, rats received corresponding drugs or normal saline by gavage for 4 weeks, once per day. After 4 weeks, the body mass and the left kidney weight were measured. The 24 h urine protein and the levels of serum albumin (ALB), alanine aminotransferase (ALT), serum creatinine (SCr) and blood urea nitrogen (BUN) were detected by biochemical analysis method; the ROS level in renal tissue was measured using a chemical fluorescence assay kit, and the SOD and MDA levels in left renal tissue of rats were measured using ELISA method; the morphology of renal tissue and the specific blue staining of hemosiderin were observed using HE and Prussian blue staining methods, respectively; the expressions of transforming growth factor-β1 (TGF-β1), Smad3, glutathione peroxidase 4 (GPX4), and solute carrier family 1 member 5 (SLC1A5) were detected by Western blot.Results:Compared with the model group, the 24 h urinary protein excretion in Shenyan 1 Prescription high-dosage group decreased ( P<0.05), the serum ALB level increased ( P<0.05), the ALT level decreased ( P<0.05), and the expression of SLC1A5 in renal tissue decreased ( P<0.05); the left kidney weight/body decreased in Shenyan 1 Prescription low- and high-dosage groups ( P<0.05); the levels of serum ROS and MDA decreased ( P<0.05), and the activity of SOD significantly increased ( P<0.05); the expressions of TGF-β1 and Smad3 in renal tissue decreased ( P<0.05), and the expression of GPX4 increased ( P<0.05), and the renal pathological injury and ion deposition were improved. Conclusion:Shenyan 1 Prescription has a protective effect on the structure and function of renal tissues in UUO rats through regulating ferroptosis via inhibition of the TGF-β1/ Smad3 pathway to inhibit renal fibrosis of UUO rats.

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