[Objectives]This study was conducted to observe the mechanism of Dendrobium officinale Kimura et Migo on gastrocnemius muscle in rats with exercise-induced muscle damage(EIMD).[Methods]The micro-injury model of skelet...[Objectives]This study was conducted to observe the mechanism of Dendrobium officinale Kimura et Migo on gastrocnemius muscle in rats with exercise-induced muscle damage(EIMD).[Methods]The micro-injury model of skeletal muscle was established by treadmill training.Forty two SD rats were randomly divided into a control group,1,12 and 24 h exercise groups,D.officinale 2 ml+1 h exercise group,D.officinale 2 ml+12 h exercise group,and D.officinale 2 ml+24 h exercise group,with 6 rats in each group.Various D.officinale groups were given the drug once in the morning and once in the evening at a dose of 2 ml/time,a week in advance.Except for the quiet group,the samples were collected from the 1,12 and 24 h exercise groups after anesthesia following 1,12 and 24 h of exercise for the last time,respectively,and the D.officinale 2 ml+1 h exercise group,D.officinale 2 ml+12 h exercise group and D.officinale 2 ml+24 h exercise group were also sampled after anesthesia following 1,12 and 24 h of exercise for the last time,respectively.The contents of ATP,CK-MM and CK in rat serum were determined by enzyme-linked immunosorbent assay(ELISA).The histopathological changes of gastrocnemius muscle were observed by HE staining.PCR and Western-blot detection were carried out to analyze the effects of D.officinale on IGF-1 mRNA and protein expression in gastrocnemius muscle.[Results]Compared with the quiet group,the ATP contents in the serum of rats in the 1,12 and 24 h exercise groups significantly decreased(P<0.01),while the CK and CK-MM contents significantly increased(P<0.01).The expression of IGF-1 mRNA and protein in the gastrocnemius muscle tissue significantly increased(P<0.01).Compared with the 1 h exercise group,the ATP content and IGF-1 protein expression in the gastrocnemius muscle tissue of the D.officinale liquid+1 h exercise group significantly increased(P<0.05),while the CK and CK-MM contents significantly decreased(P<0.01).Compared with the 12 h exercise group,the D.officinale liquid+12 h exercise group showed a significant increase in ATP content(P<0.01),significant increases in IGF-1 mRNA and protein expression in the gastrocnemius muscle tissue(P<0.01),and significant decreases in CK and CK-MM contents(P<0.01).Compared with the 24 h exercise group,the ATP content and IGF-1 mRNA and protein expression in the gastrocnemius muscle tissue of the D.officinale liquid+24 h exercise group significantly increased(P<0.01),while the CK and CK-MM contents significantly decreased(P<0.01).From the pathological tissue morphology of the gastrocnemius muscle in rats with EIMD treated with D.officinale,it could be concluded that the gastrocnemius muscle of each exercise group was significantly damaged,and the damage was significantly alleviated after administration of D.officinale liquid.[Conclusions]The effects and mechanism of D.officinale on prevention and treatment of EIMD in rats might be related to the promotion of IGF-1 mRNA and protein expression in injured tissues by reducing ATP energy consumption,CK-MM and CK activity.展开更多
Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor dete...Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
Kidney damage has been associated with administration diclofenac, a phenylacetic acid derivative belonging to the nonsteroidal anti-inflammatory drugs (NSAIDs), which is commonly used for the treatment of various dise...Kidney damage has been associated with administration diclofenac, a phenylacetic acid derivative belonging to the nonsteroidal anti-inflammatory drugs (NSAIDs), which is commonly used for the treatment of various diseases such as rheumatoid arthritis, ankylosing spondylitis, acute muscle pain conditions and osteoarthritis. This study investigated the exact mechanism of diclofenac in renal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were divided into two groups of eight rats in each group and orogastrically treated for three days. Group 1 served as the normal control and received normal saline (0.9% w/v) and group 2 received 40 mg/kg body weight of diclofenac for three days. Administration of diclofenac caused degeneration of the kidney of rats as evidenced by significant elevation in the serum levels of creatinine, urea, albumin, uric acid, protein and electrolytes and the activities of renal-5’-nucleotidase and glucose-6-phosphate-dehydrogenase (G6PDH) compared with control. Furthermore, administration of diclofenac decreased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) and the level of glutathione with concomitant increase in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in the kidney of the diclofenac treated groups compared with control. These findings reveal that administration of diclofenac may impair kidney functions through induction of oxidative stress.展开更多
Objective To study the protective function of Salvia Miltiorrhizae on high-energy shockwaves (HESW) induced renal damage. Methods Thirty healthy New Zealand adult male white rabbits were randomly divided into Salvia...Objective To study the protective function of Salvia Miltiorrhizae on high-energy shockwaves (HESW) induced renal damage. Methods Thirty healthy New Zealand adult male white rabbits were randomly divided into Salvia Miltiorrhizae group and control group with 15 in each. Three days before extracorpeal shock wave lithotripsy (ESWL) the two groups were injected Salvia Miltiorrhizae and physiological saline respectively. Plasma endothelin-1 (ET-1), Superoxide dismutase (SOD) and malondialdehyde (MDA) were determined and renal morphology was observed. Results After ESWL, levels of ET-1 and MDA increased significantly, the activity of SOD decreased significantly compared with those before ESWL in control group (P< 0.05, respectively); the Salvia Miltiorrhizae treated group showed a much increase in ET-1 and MDA (P< 0.05, respectively), which kept no more than a week. And MDA in Salvia Miltiorrhizae group was not statistically significant as compared with the pre-shocking's (P> 0.05). After shocking, SOD, related to renal protection, in Salvia Miltiorrhizae group was significantly higher than that of controls (P< 0.05). Renal morphological injury was slight in Salvia Miltiorrhizae group. Conclusion Salvia Miltiorrhizae injection has protective function on renal toxicity induced by high-energy shock waves.展开更多
Coronavirus particles contain four main structural proteins. These are the spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins, all of which are encoded within the 3’ end of the viral genome. The S p...Coronavirus particles contain four main structural proteins. These are the spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins, all of which are encoded within the 3’ end of the viral genome. The S protein (~150 kDa) utilizes an N-terminal signal sequence to gain access to the ER, and is heavily N-linked glycosylated. In view of the increase in death due to COVID-19 (coronavirus disease), it is important to investigate the potential effects the coronavirus on different organs. A literature search was performed from Elsevier, Pubmed, Springer, and Hindawi, and literature is reviewed using customized search strategies. The search strategy included the following terms Cardiovascular effect, Neurological effect, and kidney. Myocardial damage is a common occurrence in patients with COVID-19 disease hospitalisation. This is characterized by a rise in troponin. Vascular endothelial damage in both small and mid-sized pulmonary vessels was noted together with Disseminated intravascular coagulation (DIC), Deep vein thrombosis (DVT), and Pulmonary embolism (PE), resulting in pulmonary infarction. Liver damage in patients with coronavirus infections might be directly caused by the viral infection of liver cells. Neuronal pathway is an important vehicle for neurotropic viruses to enter the CNS (Central Nervous system). Recent research studies show that apoptosis is implicated in a variety of ocular disorders, including glaucoma, retinitis pigmentosa, cataract development, retinoblastoma, retinal ischemia, diabetic retinopathy, and ocular murine glaucoma. The more the understanding about this new virus and its occurrence, the better the ability of people to cope with it. It’s far hoped that we will conquer COVID-19 soon with the invention of powerful vaccines, pills, and remedies.展开更多
Introduction: Chronic kidney disease [CKD], as defined by the National Kidney Foundation/Kidney Disease and Outcome Quality Initiative (KDOQI) Group, refers to bilateral kidney injury and/or impaired kidney function o...Introduction: Chronic kidney disease [CKD], as defined by the National Kidney Foundation/Kidney Disease and Outcome Quality Initiative (KDOQI) Group, refers to bilateral kidney injury and/or impaired kidney function of at least 3 months duration. Persistent proteinuria has been recognized as one of the early markers of chronic kidney disease and has been associated with persistent and progressive damage in both children and adult. This study was conducted with the aim of determining the prevalence and severity of persistent proteinuria over three months in primary school children in Ile-Ife. It was a cross-sectional study done over a period of six months. The subjects were 1335 primary school pupils, aged 6 to 14 years selected by multi stage random sampling method from twelve primary schools from a total of 96,301 pupils in the two Local Government Areas (LGA) of Ile-Ife, after meeting the recruitment criteria. The biodata, physical examination, blood pressure measurements and urine testing by dipstick were carried out on all the recruited pupils according to standard protocols while serial monitoring of proteinuria and estimated glomerular filtration rate was done for those with persistent proteinuria over 6 months. Results: Initially 34 (2.6%) of the subjects recruited had significant proteinuria with a M:F ratio of 1:1.6 following first screening and it was persistent in six (0.4%) of them subsequently over three months with a M:F ratio of 1:1.5. The severity of the persistent proteinuria was in the range of 30 mg/dL to 100 mg/dL. Three of them (50%) had worsened level of proteinuria from 30 mg/dL to 100 mg/dl on follow up. Conclusion: Children with undetected persistent proteinuria stand the risk of further glomerular damage over time.展开更多
Chronic kidney disease(CKD)and heart failure(HF)are highly prevalent,aggravate each other,and account for substantial mortality.However,the mechanisms underlying cardiorenal interaction and the role of kidney afferent...Chronic kidney disease(CKD)and heart failure(HF)are highly prevalent,aggravate each other,and account for substantial mortality.However,the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and their precise central pathway remain limited.Here,we combined virus tracing techniques with optogenetic techniques to map a polysynaptic central pathway linking kidney afferent nerves to subfornical organ(SFO)and thereby to paraventricular nucleus(PVN)and rostral ventrolateral medulla that modulates sympathetic outflow.This kidney-brain neural circuit was overactivated in mouse models of CKD or HF and subsequently enhanced the sympathetic discharge to both the kidney and the heart in each model.Interruption of the pathway by kidney deafferentation,selective deletion of angiotensin II type 1a receptor(AT1a)in SFO,or optogenetic silence of the kidney-SFO or SFO-PVN projection decreased the sympathetic discharge and lessened structural damage and dysfunction of both kidney and heart in models of CKD and HF.Thus,kidney afferent nerves activate a kidney-brain neural circuit in CKD and HF that drives the sympathetic nervous system to accelerate disease progression in both organs.These results demonstrate the crucial role of kidney afferent nerves and their central connections in engaging cardiorenal interactions under both physiological and disease conditions.This suggests novel therapies for CKD or HF targeting this kidney-brain neural circuit.展开更多
Objective To evaluate histopathological alterations of the liver and kidney of female rats exposed to low doses of DM and its potential genotoxic activity. Methods Female Wistar rats were randomly assigned to control ...Objective To evaluate histopathological alterations of the liver and kidney of female rats exposed to low doses of DM and its potential genotoxic activity. Methods Female Wistar rats were randomly assigned to control (3 groups, 6 rats in each) and treatment groups (3 groups, 6 rats in each). They were subjected to subcutaneous injections of DM (at doses of 0.003, 0.03, and 0.3 mg/kg bw/d) after 30, 45, and 60 d, respectively. Results Significant alterations were recorded in liver parenchyma induced by hepatic vacuolization, fragmented chromatin in nuclei, dilatation of sinusoids and congestions. Lesions within proximal and distal tubules were observed in the kidneys. Tissue congestions and severe alterations within glomeruli were visible. DM as a pyrethroid insecticide induced significant increase (P〈_O.05) of plasma MDA concentrations after 45 d. A significant increase (P_〈0.05) in plasma ALT (after 45 and 60 d) and AST (after 60 d) concentrations was recorded as compared to controls. During the whole experimental period the toxic agent provoked significant DNA damages (P〈0.05), especially in the dominance of classes 3 and 4 of obtained comet. Conclusion DM even at a very low dose displays harmful effects by disrupting hepatic and renal function and causing DNA damages in puberscent female rats. Low doses of DM are hepatotoxic and nephrotoxic.展开更多
The present study was performed in order to discern the effects of combined exposure to cadmium and mercury on liver function and histopathological alterations in male adult Wistar rats. In the present investigation, ...The present study was performed in order to discern the effects of combined exposure to cadmium and mercury on liver function and histopathological alterations in male adult Wistar rats. In the present investigation, cadmium (100 mg/l) and mercury (25 mg/l) were administered orally for 10 weeks separately or in combination. The rational for studying cadmium and mercury is that both of these metals are encountered frequently in the same contaminated areas. In liver, the activities of serum alanine aminotransferase (ALT) and aspartate amino tranferase (AST) increased significantly in the cadmium (Cd) and mercury (Hg) alone or in combination (Cd + Hg) compared to the control suggesting that both cadmium and mercury cause hepatotoxicity spatially when co-administrated. We noted an increase in serum lactate dehydrogenase (LDH) activity in Cd and combined Cd + Hg treated groups while it decreased in Hg treated group. There was no statistically significant change in the level of total bilirubilin. Serum urea concentration showed a significant increase in the Cd and Hg groups compared to the control group. However an increase in serum creatinine concentration was noted only in the combined treated rats showing that renal insufficiency is more serious in the co-exposed group. Light microscopic examination indicated severe histological changes in the two organs under Cd and mercury influence. Results of the present investigation clearly showed that mercury has profound effects of hepatic handling of cadmium (synergistic effect) as shown by histological and biochemical results. Moreover, we observed a antagonist effect between these two toxic metals on kidney markers such as urea.展开更多
Background: There are many programs which focus on late-stage chronic kidney disease (CKD), and it is considered that further evidence needs to be generated regarding the effectiveness of the programs used before rena...Background: There are many programs which focus on late-stage chronic kidney disease (CKD), and it is considered that further evidence needs to be generated regarding the effectiveness of the programs used before renal replacement therapy. Study Design: A cohort study. Settings & Participants: Patients over 15 years of age who had been diagnosed with CKD according to the KDOQI (Kidney Disease Outcomes Quality Initiative) guidelines and who had undergone conventional treatment (CT) or a renal protection program (RPP). These were patients of two Colombian health insurance companies. Predictors: Age, sex, marital status, comorbidities, CKD stage, and clinical indicators. Outcomes: First CKD progression, and need for renal replacement therapy (RRT). Measures: Clinical marker. Results: The RPP is structurally and functionally different from the CT. It offers the interdisciplinary management of patients, a greater number of medical appointments, and patients start to receive treatment at younger ages and at earlier stages of their condition. The clinical markers of the patients following the RPP are within adequate ranges, and their renal function is less impaired, despite the differences in basal conditions. Upon finishing the study, we found that patients who received CT had a higher risk of receiving nephrotoxic drugs and not receiving nephroprotective drugs. The explanatory variables for the first progression were age, stage, history of dyslipidemia, and hemoglobin, potassium, and albumin levels. These variables, together with glycemia levels were also valid for RRT, except for history of dyslipidemia, as it was not significant. Upon adjusting for the explanatory variables, it was found that belonging to the RPP and attending more appointments had a protective effect in the process of controlling renal damage. Limitations: A possible selection bias. Conclusions: Belonging to a structured renal protection program is an effective way to keeping the clinical markers associated with renal impairment within normal ranges.展开更多
Acetaminophen is a drug used to treat many conditions as headache, muscle aches, arthritis, backache, toothache, and fever between others, but collateral effects of this drug are not well known yet. Here is tested its...Acetaminophen is a drug used to treat many conditions as headache, muscle aches, arthritis, backache, toothache, and fever between others, but collateral effects of this drug are not well known yet. Here is tested its effect on proximal tubule epithelium. Acetaminophen (APAP) at doses of 200, 500, 1000 and 1500 mg/Kg i.p. caused cell damage and changes in F-actin distribution in the proximal tubule of male Wistar rats. After 48 hours of treatment, the proximal tubule epithelium showed tumefaction and necrosis. Dose of 200 mg/kg decreased the F-actin and was observed a structure in patches in the basal cytoplasm of epithelial cells of the proximal tubule. This effect was increased depending on the administered dose. Dose of 1000 mg/kg produced the highest histological damage and changes in the actin cytoskeleton. Results of this study suggested that nephrotoxic damage produced by high doses of APAP included breakdown of cytoskeleton in proximal tubule epithelium.展开更多
BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediat...BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediated apoptosis in high glucose(HG)-induced primary rat kidney cells(PRKs),with emphasis on the role of miR-503 and sirtuin 4(SIRT4)in this process.METHODS Single intraperitoneal injection of streptozotocin(65 mg/kg)in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model.Glucose-treated PRKs were used as an in vitro HG model.An immunofluorescence assay identified isolated PRKs.Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis,respectively.Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stressrelated proteins.Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed.RESULTS ICA treatment alleviated the upregulated miR-503 expression in vivo(DN)and in vitro(HG).Mechanistically,ICA reduced HG-induced miR-503 overexpression,thereby counteracting its function in downregulating SIRT4 levels.ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury.CONCLUSION ICA reduced HG-mediated inhibition of cell viability,promotion of apoptosis,and ER stress in PRKs.These effects involved regulation of the miR-503/SIRT4 axis.These findings indicate the potential of ICA to treat DN,and implicate miR-503 as a viable target for therapeutic interventions in DN.展开更多
Background:Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage.However,the relationship between the patterns of blood pressure...Background:Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage.However,the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear.This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort.Methods:This study included 4556 diabetic participants among 101,510 participants.BP,estimated glomerular filtration rate (eGFR),and urinary protein were measured every 2 years from 2006 to 2014.SBP trajectory was identified by the censored normal modeling.Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time.Kidney damage was evaluated through eGFR and urinary protein value.A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage.Results:We identified five discrete SBP trajectories:low-stable group (n =864),moderate-stable group (n =1980),moderate increasing group (n =609),elevated decreasing group,(n =679),and elevated stable group (n =424).The detection rate of kidney damage in the low-stable group (SBP:118-124 mmHg) was the lowest among the five groups.The detection rate of each kidney damage index was higher in the elevated stable group (SBP:159-172 mmHg) compared with the low-stable group.For details,the gap was 4.14 (11.6% vs.2.8%) in eGFR 〈60 ml.min-1.1.73 m 2 and 3.66 (17.2% vs.4.7%),3.38 (25.0% vs.7.4%),and 1.8 (10.6% vs.5.9%) times in positive urinary protein,eGFR 〈60 ml.min-1.1.73 m 2 and/or positive urinary protein,and eGFR decline ≥30%,respectively (P 〈 0.01).Conclusion:An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.展开更多
To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has alre...To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has already progressed to the third disease stage,and finding biomarkers that are more sensitive than microalbuminuria is therefore necessary to indicate kidney damage at an earlier stage of DKD.[2]Both glomerular and tubulointerstitial damages have been repeatedly demonstrated to be important factors in the pathophysiology of DKD.[3] Therefore,we investigated the expression levels of six markers closely related to the glomerulus and renal tubule.展开更多
Objective: To find some objective criteria for Syndrome Differentiation of Kidney Deficiency by analysing the relationship between Kidney and hearing as well as serum trace elements. Methods: The hearing and serum tra...Objective: To find some objective criteria for Syndrome Differentiation of Kidney Deficiency by analysing the relationship between Kidney and hearing as well as serum trace elements. Methods: The hearing and serum trace element of 73 cases of chronic nephropathy were measured. Results: The incidence of hearing damage in high frequency was 68. 5% with a mean hypoacusis of 35. 1 ±6. 1 dB, while in the 55 patients of Kidney deficiency type, the incidence of hearing damage in high frequency was 83. 6%, which was significantly higher than that in patients without Kidney Deficiency. The serum levels of trace elements (iron and zinc) in patients with Kidney Deficiency were lower than the normal level and that in patients without Kidney Deficiency, and the decrease of serum iron was directly proPOrtional to the degree of hearing damage. Conclusion: There was close relationship between Kidney Deficiency and hearing damage as well as the serum levels of iron and zinc.展开更多
OBJECTIVE:To investigate the inhibitory effect of Yiguanjian decoction(YD) on DNA damage in Concanavalin A(Con A)-induced liver injury mice model and to explain the possible mechanism.METHODS:Totally 120 male BALB/c m...OBJECTIVE:To investigate the inhibitory effect of Yiguanjian decoction(YD) on DNA damage in Concanavalin A(Con A)-induced liver injury mice model and to explain the possible mechanism.METHODS:Totally 120 male BALB/c mice were randomly divided into 6 groups,20 mice each:normal group,model group,Bifendate group,YD low dose group,YD middle dose group and YD high dose group.Except normal group,liver injury model induced by Con A was established.While modeling,each mouse in YD group was given YD(0.4 m L/20 g per day) by intragastric administration(0.13 g YD for YD low dose group;0.26 g for YD middle dose group;0.52 g for YD high dose group).Bifendate group was given Bifendate(0.2 gnd model·kg-1 grou·d-1) by gavage.Normal group ap were fed with same volume of physiological saline daily.After 8 weeks,the serum alanine transaminase(ALT)and aspartate transaminase(AST) were tested.The hematoxylin-eosin staining was used to evaluate the grade of liver inflammation and liver fibrosis stage.Hepatocellular DNA damage was detected by single cell gel electrophoresis technology.The protein expression of tumor necrosis factor-α(TNF-α),Bax and Mut T Homolog 1(MTH1) was detected by western blotting and enzyme linked immunosorbent assay.Bax m RNA and MTH1 m RNA were detected by Real-time Polymerase Chain Reaction(PCR).RESULTS:YD can improve the degree of liver inflammation and fibrosis in the liver of chronic hepatitis mice,the dose effect relationship is remarkable(P < 0.05).YD can reduce liver cell DNA damage.The difference between YD middle dose group and model group was statistically significant(P < 0.05).YD middle dose group had decreased the protein expression of TNF-α in the mice liver of immunological liver injury(P < 0.05).YD can increase the protein expression of Bax(P < 0.05).Compared with normal group,the protein expression of MTH1 was decreased(P < 0.05),but there was no statistical significance between YD group and model group(P >0.05).YD can increase the m RNA expression of Bax and MTH1(both P < 0.05).CONCLUSION:YD can effectively inhibit the DNA damage in immunological liver injury mice,the mechanism may be that it can decrease the TNF-αand increase the Bax and MTH1 expression.展开更多
Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver,type 2 diabetes,metabolic syndrome,and cardiovascular disease.From a pathogenic point of view,insulin resis...Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver,type 2 diabetes,metabolic syndrome,and cardiovascular disease.From a pathogenic point of view,insulin resistance(IR)represents the key factor underlying the spectrum of these obesity consequences.As observed in adults,recent data supported the occurrence of microalbuminuria(MA)as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity.In fact,a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics.Based on the clinical and prognostic relevance of this relationship in daily practice(including an increased risk of chronic kidney disease development overtime),more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity.In this paper,we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity:(1)What is the prevalence of pediatric MA?(2)What is the state of art of MA in children with obesity?and(3)Is there a link between IR and MA in children with obesity?展开更多
Impotence refers to complete or partialinability of penial erection,so that normalsexual life is compromised.Clinically,only aminority of cases are of organic etiology,while the majority are only functional in or-igin...Impotence refers to complete or partialinability of penial erection,so that normalsexual life is compromised.Clinically,only aminority of cases are of organic etiology,while the majority are only functional in or-igin that respond well to treatment.The common causes of impotence isdue to excessive sexual activity,indulgencein masturbation that damages the virile es-展开更多
A simulate daily oriental dietary pattern(a blend of lard and soybean oil)was performed in this research to investigate influence on liver and kidney function.Sixty mice were randomly divided into 6 groups with diets ...A simulate daily oriental dietary pattern(a blend of lard and soybean oil)was performed in this research to investigate influence on liver and kidney function.Sixty mice were randomly divided into 6 groups with diets of different fat added oils respectively for 12 weeks.Malondialdehyde and uric acid contents in mice fed with blended oil were significantly lower than in those fed only with soybean oil and lard due to the improved activities of antioxidant enzymes.Daily use of a blend of lard with soybean oil significantly increased antioxidant capacity,reduced lipid peroxidation of liver and serum uric acid production,thus protected liver and renal function.It also suggests that the oriental dietary pattern might reduce the risk of gout.展开更多
基金Supported by Undergraduate Innovation and Entrepreneurship Training Program of Guizhou University of Traditional Chinese Medicine(GZYDCHZ[2019]42)National Key R&D Plan(2019YFC1712500)Guizhou Provincial Science and Technology Planning Project(QKHHBZ[2020]3003),QSKH[2019006].
文摘[Objectives]This study was conducted to observe the mechanism of Dendrobium officinale Kimura et Migo on gastrocnemius muscle in rats with exercise-induced muscle damage(EIMD).[Methods]The micro-injury model of skeletal muscle was established by treadmill training.Forty two SD rats were randomly divided into a control group,1,12 and 24 h exercise groups,D.officinale 2 ml+1 h exercise group,D.officinale 2 ml+12 h exercise group,and D.officinale 2 ml+24 h exercise group,with 6 rats in each group.Various D.officinale groups were given the drug once in the morning and once in the evening at a dose of 2 ml/time,a week in advance.Except for the quiet group,the samples were collected from the 1,12 and 24 h exercise groups after anesthesia following 1,12 and 24 h of exercise for the last time,respectively,and the D.officinale 2 ml+1 h exercise group,D.officinale 2 ml+12 h exercise group and D.officinale 2 ml+24 h exercise group were also sampled after anesthesia following 1,12 and 24 h of exercise for the last time,respectively.The contents of ATP,CK-MM and CK in rat serum were determined by enzyme-linked immunosorbent assay(ELISA).The histopathological changes of gastrocnemius muscle were observed by HE staining.PCR and Western-blot detection were carried out to analyze the effects of D.officinale on IGF-1 mRNA and protein expression in gastrocnemius muscle.[Results]Compared with the quiet group,the ATP contents in the serum of rats in the 1,12 and 24 h exercise groups significantly decreased(P<0.01),while the CK and CK-MM contents significantly increased(P<0.01).The expression of IGF-1 mRNA and protein in the gastrocnemius muscle tissue significantly increased(P<0.01).Compared with the 1 h exercise group,the ATP content and IGF-1 protein expression in the gastrocnemius muscle tissue of the D.officinale liquid+1 h exercise group significantly increased(P<0.05),while the CK and CK-MM contents significantly decreased(P<0.01).Compared with the 12 h exercise group,the D.officinale liquid+12 h exercise group showed a significant increase in ATP content(P<0.01),significant increases in IGF-1 mRNA and protein expression in the gastrocnemius muscle tissue(P<0.01),and significant decreases in CK and CK-MM contents(P<0.01).Compared with the 24 h exercise group,the ATP content and IGF-1 mRNA and protein expression in the gastrocnemius muscle tissue of the D.officinale liquid+24 h exercise group significantly increased(P<0.01),while the CK and CK-MM contents significantly decreased(P<0.01).From the pathological tissue morphology of the gastrocnemius muscle in rats with EIMD treated with D.officinale,it could be concluded that the gastrocnemius muscle of each exercise group was significantly damaged,and the damage was significantly alleviated after administration of D.officinale liquid.[Conclusions]The effects and mechanism of D.officinale on prevention and treatment of EIMD in rats might be related to the promotion of IGF-1 mRNA and protein expression in injured tissues by reducing ATP energy consumption,CK-MM and CK activity.
基金Supported by the National Natural Science Foundation of China,No.82100883the Research Project of Educational Commission of Jilin Province of China,No.JJKH20231214KJ.
文摘Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
文摘Kidney damage has been associated with administration diclofenac, a phenylacetic acid derivative belonging to the nonsteroidal anti-inflammatory drugs (NSAIDs), which is commonly used for the treatment of various diseases such as rheumatoid arthritis, ankylosing spondylitis, acute muscle pain conditions and osteoarthritis. This study investigated the exact mechanism of diclofenac in renal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were divided into two groups of eight rats in each group and orogastrically treated for three days. Group 1 served as the normal control and received normal saline (0.9% w/v) and group 2 received 40 mg/kg body weight of diclofenac for three days. Administration of diclofenac caused degeneration of the kidney of rats as evidenced by significant elevation in the serum levels of creatinine, urea, albumin, uric acid, protein and electrolytes and the activities of renal-5’-nucleotidase and glucose-6-phosphate-dehydrogenase (G6PDH) compared with control. Furthermore, administration of diclofenac decreased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) and the level of glutathione with concomitant increase in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in the kidney of the diclofenac treated groups compared with control. These findings reveal that administration of diclofenac may impair kidney functions through induction of oxidative stress.
文摘Objective To study the protective function of Salvia Miltiorrhizae on high-energy shockwaves (HESW) induced renal damage. Methods Thirty healthy New Zealand adult male white rabbits were randomly divided into Salvia Miltiorrhizae group and control group with 15 in each. Three days before extracorpeal shock wave lithotripsy (ESWL) the two groups were injected Salvia Miltiorrhizae and physiological saline respectively. Plasma endothelin-1 (ET-1), Superoxide dismutase (SOD) and malondialdehyde (MDA) were determined and renal morphology was observed. Results After ESWL, levels of ET-1 and MDA increased significantly, the activity of SOD decreased significantly compared with those before ESWL in control group (P< 0.05, respectively); the Salvia Miltiorrhizae treated group showed a much increase in ET-1 and MDA (P< 0.05, respectively), which kept no more than a week. And MDA in Salvia Miltiorrhizae group was not statistically significant as compared with the pre-shocking's (P> 0.05). After shocking, SOD, related to renal protection, in Salvia Miltiorrhizae group was significantly higher than that of controls (P< 0.05). Renal morphological injury was slight in Salvia Miltiorrhizae group. Conclusion Salvia Miltiorrhizae injection has protective function on renal toxicity induced by high-energy shock waves.
文摘Coronavirus particles contain four main structural proteins. These are the spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins, all of which are encoded within the 3’ end of the viral genome. The S protein (~150 kDa) utilizes an N-terminal signal sequence to gain access to the ER, and is heavily N-linked glycosylated. In view of the increase in death due to COVID-19 (coronavirus disease), it is important to investigate the potential effects the coronavirus on different organs. A literature search was performed from Elsevier, Pubmed, Springer, and Hindawi, and literature is reviewed using customized search strategies. The search strategy included the following terms Cardiovascular effect, Neurological effect, and kidney. Myocardial damage is a common occurrence in patients with COVID-19 disease hospitalisation. This is characterized by a rise in troponin. Vascular endothelial damage in both small and mid-sized pulmonary vessels was noted together with Disseminated intravascular coagulation (DIC), Deep vein thrombosis (DVT), and Pulmonary embolism (PE), resulting in pulmonary infarction. Liver damage in patients with coronavirus infections might be directly caused by the viral infection of liver cells. Neuronal pathway is an important vehicle for neurotropic viruses to enter the CNS (Central Nervous system). Recent research studies show that apoptosis is implicated in a variety of ocular disorders, including glaucoma, retinitis pigmentosa, cataract development, retinoblastoma, retinal ischemia, diabetic retinopathy, and ocular murine glaucoma. The more the understanding about this new virus and its occurrence, the better the ability of people to cope with it. It’s far hoped that we will conquer COVID-19 soon with the invention of powerful vaccines, pills, and remedies.
文摘Introduction: Chronic kidney disease [CKD], as defined by the National Kidney Foundation/Kidney Disease and Outcome Quality Initiative (KDOQI) Group, refers to bilateral kidney injury and/or impaired kidney function of at least 3 months duration. Persistent proteinuria has been recognized as one of the early markers of chronic kidney disease and has been associated with persistent and progressive damage in both children and adult. This study was conducted with the aim of determining the prevalence and severity of persistent proteinuria over three months in primary school children in Ile-Ife. It was a cross-sectional study done over a period of six months. The subjects were 1335 primary school pupils, aged 6 to 14 years selected by multi stage random sampling method from twelve primary schools from a total of 96,301 pupils in the two Local Government Areas (LGA) of Ile-Ife, after meeting the recruitment criteria. The biodata, physical examination, blood pressure measurements and urine testing by dipstick were carried out on all the recruited pupils according to standard protocols while serial monitoring of proteinuria and estimated glomerular filtration rate was done for those with persistent proteinuria over 6 months. Results: Initially 34 (2.6%) of the subjects recruited had significant proteinuria with a M:F ratio of 1:1.6 following first screening and it was persistent in six (0.4%) of them subsequently over three months with a M:F ratio of 1:1.5. The severity of the persistent proteinuria was in the range of 30 mg/dL to 100 mg/dL. Three of them (50%) had worsened level of proteinuria from 30 mg/dL to 100 mg/dl on follow up. Conclusion: Children with undetected persistent proteinuria stand the risk of further glomerular damage over time.
基金supported by the Major International(Regional)Joint Research Project of the National Natural Science Foundation of China(81620108003 to F.F.H.)Program of Introducing Talents of Discipline to Universities,111 Plan(D18005 to F.F.H.)+2 种基金The National Natural Science Foundation of China(Key Program)(82030022 to F.F.H.)Guangdong key program of precision medicine(2022 to F.F.H.)the National Natural Science Foundation of China(82270776,81922014,81870473 to W.C.).
文摘Chronic kidney disease(CKD)and heart failure(HF)are highly prevalent,aggravate each other,and account for substantial mortality.However,the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and their precise central pathway remain limited.Here,we combined virus tracing techniques with optogenetic techniques to map a polysynaptic central pathway linking kidney afferent nerves to subfornical organ(SFO)and thereby to paraventricular nucleus(PVN)and rostral ventrolateral medulla that modulates sympathetic outflow.This kidney-brain neural circuit was overactivated in mouse models of CKD or HF and subsequently enhanced the sympathetic discharge to both the kidney and the heart in each model.Interruption of the pathway by kidney deafferentation,selective deletion of angiotensin II type 1a receptor(AT1a)in SFO,or optogenetic silence of the kidney-SFO or SFO-PVN projection decreased the sympathetic discharge and lessened structural damage and dysfunction of both kidney and heart in models of CKD and HF.Thus,kidney afferent nerves activate a kidney-brain neural circuit in CKD and HF that drives the sympathetic nervous system to accelerate disease progression in both organs.These results demonstrate the crucial role of kidney afferent nerves and their central connections in engaging cardiorenal interactions under both physiological and disease conditions.This suggests novel therapies for CKD or HF targeting this kidney-brain neural circuit.
基金supported by the funds allocated to the Research Unit of Histology & Genetic 02/UR/08-03the Tunisian Ministry of the Higher Education
文摘Objective To evaluate histopathological alterations of the liver and kidney of female rats exposed to low doses of DM and its potential genotoxic activity. Methods Female Wistar rats were randomly assigned to control (3 groups, 6 rats in each) and treatment groups (3 groups, 6 rats in each). They were subjected to subcutaneous injections of DM (at doses of 0.003, 0.03, and 0.3 mg/kg bw/d) after 30, 45, and 60 d, respectively. Results Significant alterations were recorded in liver parenchyma induced by hepatic vacuolization, fragmented chromatin in nuclei, dilatation of sinusoids and congestions. Lesions within proximal and distal tubules were observed in the kidneys. Tissue congestions and severe alterations within glomeruli were visible. DM as a pyrethroid insecticide induced significant increase (P〈_O.05) of plasma MDA concentrations after 45 d. A significant increase (P_〈0.05) in plasma ALT (after 45 and 60 d) and AST (after 60 d) concentrations was recorded as compared to controls. During the whole experimental period the toxic agent provoked significant DNA damages (P〈0.05), especially in the dominance of classes 3 and 4 of obtained comet. Conclusion DM even at a very low dose displays harmful effects by disrupting hepatic and renal function and causing DNA damages in puberscent female rats. Low doses of DM are hepatotoxic and nephrotoxic.
文摘The present study was performed in order to discern the effects of combined exposure to cadmium and mercury on liver function and histopathological alterations in male adult Wistar rats. In the present investigation, cadmium (100 mg/l) and mercury (25 mg/l) were administered orally for 10 weeks separately or in combination. The rational for studying cadmium and mercury is that both of these metals are encountered frequently in the same contaminated areas. In liver, the activities of serum alanine aminotransferase (ALT) and aspartate amino tranferase (AST) increased significantly in the cadmium (Cd) and mercury (Hg) alone or in combination (Cd + Hg) compared to the control suggesting that both cadmium and mercury cause hepatotoxicity spatially when co-administrated. We noted an increase in serum lactate dehydrogenase (LDH) activity in Cd and combined Cd + Hg treated groups while it decreased in Hg treated group. There was no statistically significant change in the level of total bilirubilin. Serum urea concentration showed a significant increase in the Cd and Hg groups compared to the control group. However an increase in serum creatinine concentration was noted only in the combined treated rats showing that renal insufficiency is more serious in the co-exposed group. Light microscopic examination indicated severe histological changes in the two organs under Cd and mercury influence. Results of the present investigation clearly showed that mercury has profound effects of hepatic handling of cadmium (synergistic effect) as shown by histological and biochemical results. Moreover, we observed a antagonist effect between these two toxic metals on kidney markers such as urea.
文摘Background: There are many programs which focus on late-stage chronic kidney disease (CKD), and it is considered that further evidence needs to be generated regarding the effectiveness of the programs used before renal replacement therapy. Study Design: A cohort study. Settings & Participants: Patients over 15 years of age who had been diagnosed with CKD according to the KDOQI (Kidney Disease Outcomes Quality Initiative) guidelines and who had undergone conventional treatment (CT) or a renal protection program (RPP). These were patients of two Colombian health insurance companies. Predictors: Age, sex, marital status, comorbidities, CKD stage, and clinical indicators. Outcomes: First CKD progression, and need for renal replacement therapy (RRT). Measures: Clinical marker. Results: The RPP is structurally and functionally different from the CT. It offers the interdisciplinary management of patients, a greater number of medical appointments, and patients start to receive treatment at younger ages and at earlier stages of their condition. The clinical markers of the patients following the RPP are within adequate ranges, and their renal function is less impaired, despite the differences in basal conditions. Upon finishing the study, we found that patients who received CT had a higher risk of receiving nephrotoxic drugs and not receiving nephroprotective drugs. The explanatory variables for the first progression were age, stage, history of dyslipidemia, and hemoglobin, potassium, and albumin levels. These variables, together with glycemia levels were also valid for RRT, except for history of dyslipidemia, as it was not significant. Upon adjusting for the explanatory variables, it was found that belonging to the RPP and attending more appointments had a protective effect in the process of controlling renal damage. Limitations: A possible selection bias. Conclusions: Belonging to a structured renal protection program is an effective way to keeping the clinical markers associated with renal impairment within normal ranges.
文摘Acetaminophen is a drug used to treat many conditions as headache, muscle aches, arthritis, backache, toothache, and fever between others, but collateral effects of this drug are not well known yet. Here is tested its effect on proximal tubule epithelium. Acetaminophen (APAP) at doses of 200, 500, 1000 and 1500 mg/Kg i.p. caused cell damage and changes in F-actin distribution in the proximal tubule of male Wistar rats. After 48 hours of treatment, the proximal tubule epithelium showed tumefaction and necrosis. Dose of 200 mg/kg decreased the F-actin and was observed a structure in patches in the basal cytoplasm of epithelial cells of the proximal tubule. This effect was increased depending on the administered dose. Dose of 1000 mg/kg produced the highest histological damage and changes in the actin cytoskeleton. Results of this study suggested that nephrotoxic damage produced by high doses of APAP included breakdown of cytoskeleton in proximal tubule epithelium.
基金The First Affiliated Hospital of Guangzhou University of Chinese Medicine Innovation and Strengthening Fund,No.2019QN14.
文摘BACKGROUND Dysregulated microRNA(miRNA)is crucial in the progression of diabetic nephropathy(DN).AIM To investigate the potential molecular mechanism of Icariin(ICA)in regulating endoplasmic reticulum(ER)stress-mediated apoptosis in high glucose(HG)-induced primary rat kidney cells(PRKs),with emphasis on the role of miR-503 and sirtuin 4(SIRT4)in this process.METHODS Single intraperitoneal injection of streptozotocin(65 mg/kg)in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model.Glucose-treated PRKs were used as an in vitro HG model.An immunofluorescence assay identified isolated PRKs.Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis,respectively.Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stressrelated proteins.Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed.RESULTS ICA treatment alleviated the upregulated miR-503 expression in vivo(DN)and in vitro(HG).Mechanistically,ICA reduced HG-induced miR-503 overexpression,thereby counteracting its function in downregulating SIRT4 levels.ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury.CONCLUSION ICA reduced HG-mediated inhibition of cell viability,promotion of apoptosis,and ER stress in PRKs.These effects involved regulation of the miR-503/SIRT4 axis.These findings indicate the potential of ICA to treat DN,and implicate miR-503 as a viable target for therapeutic interventions in DN.
文摘Background:Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage.However,the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear.This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort.Methods:This study included 4556 diabetic participants among 101,510 participants.BP,estimated glomerular filtration rate (eGFR),and urinary protein were measured every 2 years from 2006 to 2014.SBP trajectory was identified by the censored normal modeling.Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time.Kidney damage was evaluated through eGFR and urinary protein value.A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage.Results:We identified five discrete SBP trajectories:low-stable group (n =864),moderate-stable group (n =1980),moderate increasing group (n =609),elevated decreasing group,(n =679),and elevated stable group (n =424).The detection rate of kidney damage in the low-stable group (SBP:118-124 mmHg) was the lowest among the five groups.The detection rate of each kidney damage index was higher in the elevated stable group (SBP:159-172 mmHg) compared with the low-stable group.For details,the gap was 4.14 (11.6% vs.2.8%) in eGFR 〈60 ml.min-1.1.73 m 2 and 3.66 (17.2% vs.4.7%),3.38 (25.0% vs.7.4%),and 1.8 (10.6% vs.5.9%) times in positive urinary protein,eGFR 〈60 ml.min-1.1.73 m 2 and/or positive urinary protein,and eGFR decline ≥30%,respectively (P 〈 0.01).Conclusion:An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.
基金the grants from the National Key R&D Program of China (No.2016YFC1305500and No.2016YFC 1305404)the National Natural Science Foundation of China (No.61471399,No.61671479,and No.81670663)+1 种基金the Joint Funds of National Natural Science Foundation of China and Henan Province (No.U1604284) the Special Research Project on Health Care of the Chinese People's Liberation Army (No.15BJZ35).
文摘To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has already progressed to the third disease stage,and finding biomarkers that are more sensitive than microalbuminuria is therefore necessary to indicate kidney damage at an earlier stage of DKD.[2]Both glomerular and tubulointerstitial damages have been repeatedly demonstrated to be important factors in the pathophysiology of DKD.[3] Therefore,we investigated the expression levels of six markers closely related to the glomerulus and renal tubule.
文摘Objective: To find some objective criteria for Syndrome Differentiation of Kidney Deficiency by analysing the relationship between Kidney and hearing as well as serum trace elements. Methods: The hearing and serum trace element of 73 cases of chronic nephropathy were measured. Results: The incidence of hearing damage in high frequency was 68. 5% with a mean hypoacusis of 35. 1 ±6. 1 dB, while in the 55 patients of Kidney deficiency type, the incidence of hearing damage in high frequency was 83. 6%, which was significantly higher than that in patients without Kidney Deficiency. The serum levels of trace elements (iron and zinc) in patients with Kidney Deficiency were lower than the normal level and that in patients without Kidney Deficiency, and the decrease of serum iron was directly proPOrtional to the degree of hearing damage. Conclusion: There was close relationship between Kidney Deficiency and hearing damage as well as the serum levels of iron and zinc.
基金Supported by Beijing Natural Science Foundation-funded Project(Yiguanjian on the Regulation of Microenvironment and Signal Pathway of Reactive Oxygen Species in Mouse with Immunological Liver Injury,No.7122024)
文摘OBJECTIVE:To investigate the inhibitory effect of Yiguanjian decoction(YD) on DNA damage in Concanavalin A(Con A)-induced liver injury mice model and to explain the possible mechanism.METHODS:Totally 120 male BALB/c mice were randomly divided into 6 groups,20 mice each:normal group,model group,Bifendate group,YD low dose group,YD middle dose group and YD high dose group.Except normal group,liver injury model induced by Con A was established.While modeling,each mouse in YD group was given YD(0.4 m L/20 g per day) by intragastric administration(0.13 g YD for YD low dose group;0.26 g for YD middle dose group;0.52 g for YD high dose group).Bifendate group was given Bifendate(0.2 gnd model·kg-1 grou·d-1) by gavage.Normal group ap were fed with same volume of physiological saline daily.After 8 weeks,the serum alanine transaminase(ALT)and aspartate transaminase(AST) were tested.The hematoxylin-eosin staining was used to evaluate the grade of liver inflammation and liver fibrosis stage.Hepatocellular DNA damage was detected by single cell gel electrophoresis technology.The protein expression of tumor necrosis factor-α(TNF-α),Bax and Mut T Homolog 1(MTH1) was detected by western blotting and enzyme linked immunosorbent assay.Bax m RNA and MTH1 m RNA were detected by Real-time Polymerase Chain Reaction(PCR).RESULTS:YD can improve the degree of liver inflammation and fibrosis in the liver of chronic hepatitis mice,the dose effect relationship is remarkable(P < 0.05).YD can reduce liver cell DNA damage.The difference between YD middle dose group and model group was statistically significant(P < 0.05).YD middle dose group had decreased the protein expression of TNF-α in the mice liver of immunological liver injury(P < 0.05).YD can increase the protein expression of Bax(P < 0.05).Compared with normal group,the protein expression of MTH1 was decreased(P < 0.05),but there was no statistical significance between YD group and model group(P >0.05).YD can increase the m RNA expression of Bax and MTH1(both P < 0.05).CONCLUSION:YD can effectively inhibit the DNA damage in immunological liver injury mice,the mechanism may be that it can decrease the TNF-αand increase the Bax and MTH1 expression.
文摘Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver,type 2 diabetes,metabolic syndrome,and cardiovascular disease.From a pathogenic point of view,insulin resistance(IR)represents the key factor underlying the spectrum of these obesity consequences.As observed in adults,recent data supported the occurrence of microalbuminuria(MA)as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity.In fact,a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics.Based on the clinical and prognostic relevance of this relationship in daily practice(including an increased risk of chronic kidney disease development overtime),more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity.In this paper,we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity:(1)What is the prevalence of pediatric MA?(2)What is the state of art of MA in children with obesity?and(3)Is there a link between IR and MA in children with obesity?
文摘Impotence refers to complete or partialinability of penial erection,so that normalsexual life is compromised.Clinically,only aminority of cases are of organic etiology,while the majority are only functional in or-igin that respond well to treatment.The common causes of impotence isdue to excessive sexual activity,indulgencein masturbation that damages the virile es-
基金supported by the grants of Innovation and Entrepreneurship Investment Project in Hunan(2017GK5009)Postgraduate Scientific Research and Innovation Project of Hunan(CX20190500)+1 种基金the Hunan Collaborative Innovation Center of Animal Production Safety,Laboratory of Animal Clinical Toxicology at The Department of Veterinary,Hunan Agriculture UniversityAnimal Health Care Engineering Technology Research Center of Hunan Agricultural University。
文摘A simulate daily oriental dietary pattern(a blend of lard and soybean oil)was performed in this research to investigate influence on liver and kidney function.Sixty mice were randomly divided into 6 groups with diets of different fat added oils respectively for 12 weeks.Malondialdehyde and uric acid contents in mice fed with blended oil were significantly lower than in those fed only with soybean oil and lard due to the improved activities of antioxidant enzymes.Daily use of a blend of lard with soybean oil significantly increased antioxidant capacity,reduced lipid peroxidation of liver and serum uric acid production,thus protected liver and renal function.It also suggests that the oriental dietary pattern might reduce the risk of gout.