1.miR-27a rs895819 and lnc-LRFN2-2 rs61516247 polymorphism could increase risk of kidney transplantation rejection
Bengang WANG ; Zhi LYU ; Qian XU ; Liping SUN ; Lei YANG ; Hao LIU ; Yongfeng LIU
Chinese Journal of Organ Transplantation 2016;37(12):726-730
Objective To explore whether polymorphisms in non-coding RNA has potential as biomarkers for predicting the risk of kidney transplantation rejection.Methods A total of 79 patients who had received kidney transplants were recruited from the First Affiliated Hospital of China Medical University and divided into the rejection group (n =26) and non-rejection group (n =53).Four polymorphisms in miRNA and 8 polymorphisms in lncRNA were detected by MALDI-TOF-MS.Results When compared with the wild genotype,the mutation genotype in miR-27a rs895819 and lnc-LRFN2-2 rs61516247 had 11.72 and 4.87 folds increased risk of kidney transplantation rejection (P =0.046,OR=1.04-131.74 and P =0.047,95% CI =1.02-23.21,respectively).The other three polymorphisms in miRNA and 7 polymorphisms in lncRNA showed no significant associations with transplantation rejection risk (P > 0.05).Conclusion The miR-27a rs895819 and lnc-LRFN2-2 rs61516247 polymorphisms were associated with the risk of kidney transplantation rejection.
2.Role of SIRT1/Nrf2 signaling pathway in berberine-induced reduction of renal ischemia-reperfusion injury in mice
Linlin SUN ; Mingyue HAO ; Mingwei SHENG ; Jingshu LYU ; Yuhua YANG ; Jiahao ZHI ; Yiqi WENG ; Wenli YU ; Hongyin DU
Chinese Journal of Anesthesiology 2021;41(5):598-602
Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.
3.Effect of autophagy regulation on hypoxia/reoxygenation injury of mouse spermatogonia
Zhi HU ; Qiao FU ; Wei ZHANG ; Wei SUN ; Lyu XU ; Yiyan CHEN ; Hao CHU
Chongqing Medicine 2023;52(23):3527-3532
Objective To study the effect of autophagy regulation on hypoxia/reoxygenation injury(H/RI)in mouse spermatogonia,and to explore the effect of autophagy on ischemia-reperfusion injury(IRI)in mouse testicular tissue.Methods The mouse spermatogonial cell line GC1 spg was used as the research object to construct the H/RI model.Rapamycin(RAPA)and 3-methyladenine(3-MA)were used as autophagy ago-nists and inhibitors.The control group,the model group,the autophagy agonist intervention group(H/RI+autophagy agonist intervention),and the autophagy inhibitor intervention group(H/RI+autophagy inhibitor intervention)were set up.The cells proliferation ability of each group was detected by methyl thiazol tetrazoli-um(MTT)method.The release level of reactive oxygen species(ROS)and apoptosis level of each group were detected by flow cytometry.The expression levels of autophagy-related gene Beclin1 and apoptosis-relat-ed genes Bcl-2 and Bax mRNA in each group were detected by real-time fluorescence quantitative PCR(qPCR).The expression levels of autophagy-related proteins LC3-Ⅰ,LC3-Ⅱ,Beclin1,p62 and apoptosis-relat-ed proteins Bcl-2,Bax,caspase-3 in each group were detected by Western blot.Results Compared with the control group,the proliferation abiliy,the expression levels of Beclin1 and Bcl-2 mRNA in the model group were significantly decreased(P<0.01),the relative expression levels of p62 and Bcl-2 proteins were significantly decreased(P<0.01).The ROS level,apoptosis rate and the mRNA expression level of Bax were significantly increased(P<0.01),and the protein expresion levels of Beclin1,Bax,caspase-3 and the protein ratio of LC3-Ⅱ/LC3-Ⅰ were significantly increased(P<0.01).Compared with the model group,the cell proliferation a-bility,the expression levels of Beclin1 and Bcl-2 mRNA in the autophagy agonist intervention group were the protein ratio of significantly increased(P<0.01),the protein expression levels of Beclin1 and Bcl-2 and the protein ration of LC3-Ⅱ/LC3-Ⅰ were significantly increased(P<0.01).The ROS level,apoptosis rate and the expression level of Bax mRNA were significantly decreased(P<0.01),and the protein expression levels of p62,Bax,caspase-3 and the protein ratio of LC3-Ⅱ/LC3-Ⅰ were significantly decreased(P<0.01).Com-pared with the model group,the cell proliferation ability,the mRNA expression levels of Beclin1 and Bcl-2 in the autophagy inhibitor intervention group were significantly decreased(P<0.01),the protein expression lev-els of Beclin1 and Bcl-2 protein were significantly decreased(P<0.01).The ROS level,apoptosis rate and the mRNA expression level of Bax were significantly increased(P<0.01),and the protein expression levels of p62,Bax,caspase-3 and the protein ratio of LC3-Ⅱ/LC3-Ⅰwere significantly iecreased(P<0.01).Conclusion Enhanced au-tophagy can inhibit apoptosis of spermatogonia and repair H/RI in mice,which provides a theoretical basis for the treatment of testicular tissue IRI.
4.Acumed intramedullary nailing for AO type A3 forearm diaphyseal fracture in adults
Hao WANG ; Hongying HE ; Huayong ZHENG ; Dongdong LYU ; Jianzheng ZHANG ; Zhi LIU
Chinese Journal of Orthopaedic Trauma 2021;23(10):896-899
Objective:To evaluate the clinical outcomes of Acumed intramedullary nailing for AO type A3 forearm diaphyseal fracture in adults.Methods:A retrospective study was conducted of the 20 adult patients with AO type A3 forearm diaphyseal fracture who had been treated by Acumed intramedullary nailing from January 2016 to November 2018 at PLA General Hospital. They were 18 males and 2 females, aged from 18 to 56 years (average, 36.5 years). There were 6 radius diaphyseal fractures, 9 ulna diaphyseal fractures and 5 diaphyseal fractures of both forearm bones. The clinical outcomes of Acumed intramedullary nailing for AO type A3 forearm diaphyseal fractures were evaluated by recording the perioperative complications, fracture union time, forearm rotation range at 12-month follow-up, and Disability of the Arm, Shoulder and Hand Questionnaire (DASH) scores for the upper limb function.Results:The 20 patients were followed up for 12 to 18 months (mean, 15.8 months). Bony union was achieved in all the patients after 3 to 4 months (average, 3.3 months). Partial rupture of the extensor pollicis longus tendon happened during operation in one patient and at 3 months post-operation in another due to fixation irritation, and linear ossification of interosseous membranes was observed in one patient with diaphyseal fractures of both forearm bones. 12-month follow-ups showed that, in the 20 patients, forearm pronation ranged from 80° to 90° (average, 89°), supination from 60° to 90° (average, 86.3°) and DASH scores from 0 to 37 (average, 6.5).Conclusions:In the treatment of AO type A3 forearm diaphyseal fracture in adults, Acumed intramedullary nailing can lead to successful fracture union and excellent rotational activity at one year after operation. Therefore, adult AO type A3 forearm diaphyseal fracture can be listed as an indication for Acumed intramedullary nailing.
5.Fragility fractures of the pelvis in the elderly: characteristics and therapy
Hongying HE ; Hao WANG ; Wenxing HAN ; Xiaowei WANG ; Xiuhong WANG ; Dongdong LYU ; Yueru LIANG ; Jianzheng ZHANG ; Zhi LIU ; Tiansheng SUN
Chinese Journal of Orthopaedic Trauma 2021;23(12):1044-1050
Objective:To investigate the characteristics of fragility fractures of pelvis(FFP) in the elderly and compare the clinical efficacy between conservative treatment and minimally invasive surgery.Methods:A retrospective study was conducted in the 56 elderly FFP patients who had been treated at Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army from January 2017 to January 2019. They were 16 males and 40 females, with an age of 73.4 years (from 65 to 93 years). By the American Society of Anesthesiologists (ASA) classification, there were 12 cases of grade Ⅰ, 16 cases of grade Ⅱ, 20 cases of grade Ⅲ, and 8 cases of grade Ⅳ; by the FFP classification, there were 6 cases of type Ⅰ, 10 cases of type Ⅱ, 36 cases of type Ⅲ, and 4 cases of type Ⅳ. The morphological characteristics and injury mechanisms of FFP were analyzed. According to the treatment methods, the patients were divided into a conservative treatment group of 32 cases and a minimally invasive surgery group of 24 cases. The 2 groups were compared in terms of complication incidence, mortality and the Koval attenuation rate of walking ability after one-year follow-up.Results:There were mostly the fractures of pubic branches on both sides of the pubic symphysis and compression fractures of the sacral wing caused by lateral crush injury. The 2 groups were comparable due to no significant differences in the preoperative general data between them other than FFP classification ( P>0.05). By one year after treatment, the conservative treatment group had a complication incidence of 34.4% (11/32), a mortality of 9.4% (3/32) and a Koval attenuation rate of walking ability of 13.8% (4/29) while the minimally invasive surgery group had a complication incidence of 20.8% (5/24), a mortality of 4.2% (1/24) and a Koval attenuation rate of walking ability of 8.7%(2/23), showing no significant difference between the 2 groups ( P>0.05). Conclusions:The injury mechanism of geriatric FFP is mostly lateral compression injury. The fracture sites are mostly located on both sides of the pubic symphysis, pubic branches and the sacral wing of anterior and posterior rings simultaneously. Although there may be no significant difference in complication incidence, mortality or Koval attenuation rate of walking ability between conservative treatment and minimally invasive surgery after one year, the minimally invasive surgery deals with more unstable fracture types.
6.Effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice: Relationship with AMPK/STAT6 pathway
Mingyue HAO ; Linlin SUN ; Mingwei SHENG ; Jingshu LYU ; Yuanbang LIN ; Yuhua YANG ; Jiahao ZHI ; Wenli YU ; Hongyin DU
Chinese Journal of Endocrinology and Metabolism 2022;38(3):225-230
Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.
7.Clinical characteristics, pathology, and prognosis of children with diffuse endocapillary proliferative Henoch-Schönlein purpura nephritis.
Ting-Ting YIN ; Xiao-Jie PENG ; Rui FU ; Ying WANG ; Yan LYU ; Yan-Qing DENG ; Jia-Qi FU ; Zhi-Hao ZHANG
Chinese Journal of Contemporary Pediatrics 2023;25(8):837-842
OBJECTIVES:
To investigate the clinical characteristics, pathology, and prognosis of children with diffuse endocapillary proliferative Henoch-Schönlein purpura nephritis (DEP-HSPN).
METHODS:
A retrospective analysis was performed on the clinical, pathological, and prognosis data of 44 children with DEP-HSPN and 765 children without DEP-HSPN. The children with DEP-HSPN were diagnosed by renal biopsy in Jiangxi Provincial Children's Hospital from January 2006 to December 2021.
RESULTS:
Among the 809 children with purpura nephritis, 44 (5.4%) had DEP-HSPN, with a mean age of (8±3) years, and there were 29 boys (65.9%) and 15 girls (34.1%). Compared with the non-DEP-HSPN group, the DEP-HSPN group had a significantly shorter time from onset to renal biopsy and a significantly higher proportion of children with respiratory infection or gross hematuria, and most children had nephrotic syndrome. The DEP-HSPN group had significantly higher levels of 24-hour urinary protein, urinary protein grading, microscopic hematuria grading, serum creatinine, and blood urea nitrogen and significantly lower levels of serum albumin and complement C3 (P<0.05). The DEP-HSPN group had a higher pathological grading, with predominant deposition of IgA in the mesangial area and capillary loops, and higher activity scores in the modified semi-quantitative scoring system (P<0.05). The Kaplan-Meier survival analysis showed that there was no significant difference in the renal complete remission rate between the two groups (P>0.05).
CONCLUSIONS
Children with DEP-HSPN have a rapid onset, severe clinical manifestations and pathological grading, and high activity scores in the modified semi-quantitative scoring system. However, most of the children with DEP-HSPN have a good prognosis, with a comparable renal complete remission rate to the children without DEP-HSPN.
Male
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Female
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Humans
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Child
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Child, Preschool
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Hematuria
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IgA Vasculitis
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Retrospective Studies
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Prognosis
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Nephritis
8.Colorectal Cancer Modeling and Difference Analysis in Cold and Heat Conditions
Hui-xuan LI ; Jing-chun QIN ; Zhi-hao LYU ; Yu-qi LIANG ; Bin WEN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(21):109-117
Objective:To explore the correlation between the occurrence of colorectal cancer and different internal environment (cold and heat). Method:The 70 Wistar rats (male and female) were randomly divided into blank group (10 cases), cold model group (30 cases) and heat model group (30 cases). The cold syndrome model was made by intragastric infusion of cold water (0 ℃) and soaking in cold water (10 ℃). The heat model was made by ethanol (30%) and capsaicin solution (0.9 g·L-1). The blank group was given normal saline by gavage, 10 mL·kg-1·d-1, for 5 consecutive weeks. The colorectal cancer model was made by subcutaneous injection of DMH solution in the back of neck in the cold model group and heat model group at the 6th week, 25 mg·kg-1,once a week,for 12 consecutive times. During the carcinogenesis, only 30% ethanol solution was given to the heat model group, and the modeling was maintained in cold model group, 10 mL·kg-1·d-1, for 38 weeks. The general state of the rats in each group was observed, and the changes of food intake and body weight were measured. At the 27th, 29th, 32th, 35th and 38th weeks, samples were collected in batches. Intestinal tissues were subjected to hematoxylin-eosin staining (HE) and detection of sodium, potassium-adenosine triphosphate (Na+ K+-ATP), calcium, magnesium-adenosine triphosphate (Ca2+ Mg2+-ATP) activity, lactate dehydrogenase (LDH) activity and succinate dehydrogenase (SDH) activity. Result:The symptoms of hematochezia and ascites in cold model group were earlier than those in heat model group. As compared with the blank group, the food intake and body weight were decreased in cold model group and heat model group. As compared with the blank group, the length of the large intestine was shorter in cold model group at the 32nd and 35th week (
9.Research progress on molecular mechanism of Dendrobium officinale and its active components to metabolic syndrome.
Yu-Yang LI ; Cheng-Hao LYU ; Guang WU ; Zhi-Bing ZHENG ; Yi-Bo LUO ; Si QIN
China Journal of Chinese Materia Medica 2019;44(23):5102-5108
Metabolic syndrome,a kind of clinical syndrome marked by the presence of symptoms such as hyperglycemia,dyslipidemia and hypertension,has an increasing incidence and comes to be present in younger people. More importantly,prolonged maintenance of this condition can significantly increase the incidence of chronic diseases such as diabetes,cardiovascular disease and cancer.However,the formation mechanism of metabolic syndrome is very complex and has not been fully studied and revealed. Dendrobium officinale is a traditional medicine and food substance with multiple physiological functions. In recent years,D. officinale has attracted much attention from the scholars both at home and abroad due to its functions such as improving blood lipid,lowering blood pressure and regulating blood sugar. However,there is no systematic review on the current studies about D. officinale in intervening metabolic syndrome and its underlying molecular mechanism. In this paper,the biological activity of the main active components,and the research or application status of D. officinale extract in the recent years were reviewed. Then,we analyzed the digestion,absorption and the safety and toxicity of D. officinale and its active components in the body. Finally,we summarized the effects of D. officinale and its active components on metabolic syndrome in animals and human bodies,and discussed its possible molecular mechanisms at the cellular level. This paper provides solid theoretical guidance and reliable molecular basis for further research and advanced development of D. officinale and its active components,especially for its oncoming clinical application.
Animals
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Blood Pressure
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Dendrobium/chemistry*
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Humans
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Metabolic Syndrome/drug therapy*
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Plant Preparations/pharmacology*
10.Berberine alleviates programmed necrosis of metabolic-associated fatty liver disease via activating Nrf2 pathway in mice.
Ming Yue HAO ; Lin Lin SUN ; Ming Wei SHENG ; Jing Shu LYU ; Yuan Bang LIN ; Yu Hua YANG ; Jia Hao ZHI ; Wen Li YU ; Hong Yin DU
Chinese Journal of Hepatology 2022;30(2):224-229
Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.
Animals
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Berberine/therapeutic use*
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Fatty Liver
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Male
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Mice
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Mice, Inbred C57BL
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NF-E2-Related Factor 2/metabolism*
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Necrosis