Shenkang injection for the treatment of acute kidney injury: a systematic review and meta-analysis.

OBJECTIVE: Shenkang injection (SKI) has been widely used in China for many years for the treatment of kidney disease. The objective of this systematic review was to assess the efficacy of Shenkang injection for the treatment of acute kidney injury (AKI). METHODS: A search was conducted across seven databases, encompassing data from the inception of each database through October 8th, 2023. Randomized controlled trials comparing SKI-treated AKI patients with control subjects were extracted. The main outcome measure was serum creatinine (SCr) levels. Secondary outcomes included blood urea nitrogen (BUN), serum cystatin C (CysC), 24-h urine protein (24 h-Upro) levels, APACHE II score and adverse reactions. RESULTS: This meta-analysis included eleven studies, and the analysis indicated that, compared with the control group, SKI significantly decreased SCr [WMD = -23.31, 95% CI (-28.06, -18.57); p < 0.001]; BUN [WMD = -2.07, 95% CI (-2.56, -1.57); p < 0.001]; CysC [WMD = -0.55, 95% CI (-0.78, -0.32), p < 0.001]; 24-h urine protein [WMD = -0.43, 95% CI (-0.53, -0.34), p < 0.001]; and the APACHE II score [WMD = -3.07, 95% CI (-3.67, -2.48), p < 0.001]. There was no difference in adverse reactions between the SKI group and the control group [RR = 1.32, 95% CI (0.66, 2.63), p = 0.431]. CONCLUSION: The use of SKI in AKI patients may reduce SCr, BUN, CysC, 24-h Upro levels, and APACHE II scores in AKI patients. The incidence of adverse reactions did not differ from that in the control group. Additional rigorous clinical trials will be necessary in the future to thoroughly evaluate and establish the effectiveness of SKI in the treatment of AKI.

Attenuating Renal Interstitial Fibrosis by Shenqi Pill via Reducing Inflammation Response Regulated by NF-κB Pathway In Vitro and In Vivo.

INTRODUCTION: One of the most significant clinical features of chronic  kidney disease is renal interstitial fibrosis (RIF). This study aimed  to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. METHODS: RIF model was established by conducting unilateral  ureteral obstruction (UUO) surgery on rat or stimulating human  kidney-2 (HK-2) cell with transforming growth factor ß1 (TGFß1).  After modeling, the rats in the SQP low dose group (SQP-L), SQP  middle dose group (SQP-M) and SQP high dose group (SQP-H)  were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the  TGFß1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing  serum. In in vivo assays, serum creatinine (SCr) and blood urea  nitrogen (BUN) content were measured, kidney histopathology  was evaluated., and α-smooth muscle actin (α-SMA) expression  was detected by immunohistochemistry. Interleukin-1ß (IL-1ß),  interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content,  inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were  assessed. Meanwhile, cell viability, inflammatory cytokines content,  α-SMA expression, IKBα and P65 phosphorylation were detected  in vitro experiment.  Results. SQP exhibited reno-protective effect by decreasing SCr  and BUN content, improving renal interstitial damage, blunting  fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after  the treatment with SQP-containing serum, viability and α-SMA  expression were remarkably decreased in TGFß1-stimulated HK-2  cell. Furthermore, SQP markedly down-regulated IL-1ß, IL-6, and  TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro.  Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa  B (NF-κB) pathway related inflammatory response, which indicates  that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.

Analyzing chemical composition of Sargentodoxae caulis water extract and their hypouricemia effect in hyperuricemic mice.

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.

A novel method for automated crystal visualization and quantification in murine folic acid-induced acute kidney injury.

Folic acid (FA)-induced acute kidney injury (FA-AKI) is an increasingly prevalent rodent disease model involving the injection of a high dose of FA that culminates in renal FA crystal deposition and injury. However, the literature characterizing the FA-AKI model is sparse and dated in part due to the absence of a well-described methodology for the visualization and quantification of renal FA crystals. Using widely available materials and tools, we developed a straightforward and crystal-preserving histological protocol that can be coupled with automated imaging for renal FA crystal visualization and generated an automated macro for downstream crystal content quantification. The applicability of the method was demonstrated by characterizing the model in male and female C57BL6/JRj mice after 3 and 30 h of FA treatment. Kidneys from both sexes and timepoints showed a bimodal distribution of FA crystal deposition in the cortical and medullary regions while, compared with males, females exhibited higher renal FA crystal content at the 30-h timepoint accompanied by greater kidney weight and higher plasma urea. Despite comparable plasma phosphate concentrations, FA-AKI resulted in a substantially more elevated plasma intact fibroblast growth factor 23 (FGF23) in females, reflected by a similar pattern in osseous Fgf23 mRNA expression. Therefore, the presented method constitutes a valuable tool for the quantification of renal FA crystals, which can aid the mechanistic characterization of the FA-AKI model and serves as a means to control for confounding changes in FA crystallization when using the model for investigating early and prophylactic AKI therapeutic interventions.NEW & NOTEWORTHY Here, we describe a novel method for the visualization and quantification of renal folic acid (FA) crystals in the rodent FA-induced acute kidney injury (FA-AKI) model. The protocol involves a straightforward histological approach followed by fully automated imaging and quantification steps. Applicability was confirmed by showing that the FA-AKI model is sex-dependent. The method can serve as a tool to aid in characterizing FA-AKI and to control for studies investigating prophylactic therapeutic avenues using FA-AKI.

Blood urea nitrogen to creatinine ratio and long-term survival in patients with chronic heart failure.

OBJECTIVES: To explore the correlation between Blood urea nitrogen to creatinine ratio (BUN/Scr ratio) and prognosis of patients with chronic heart failure complicated with renal injury. METHODS: A retrospective analysis of 504 patients hospitalized in Guang 'anmen Hospital, Chinese Academy of Traditional Chinese Medicine from March 2006 to June 2014 was conducted. The baseline data were analyzed, and the cutoff value was obtained by receiver operator characteristic curve (ROC) analysis, according to the cutoff value, all the participants were divided into two groups, BUN/Scr < 19.37 group (280 cases) and BUN/Scr ≥ 19.37 group (224 cases). The main end point was defined as all-cause death. The long-term mortality of the two groups was evaluated, and Kaplan-Meier survival curve was drawn. Univariate analysis was performed on all the variables affecting the patient's prognosis, and the variables with P < 0.05 were put into Cox regression model, and subgroup analysis was performed on the variables that might affect the patient's prognosis. RESULTS: The baseline data of 504 patients were analyzed and found that the median follow up was 683. Through ROC analysis of 504 subjects, the cutoff value of BUN/Scr was 19.37. The results of Kaplan-Meier survival curve showed that the mortality rate of patients with ratio ≥ 19.37 was higher than that of patients with ratio < 19.37. After multivariate analysis, COX regression model showed that the mortality of patients with BUN/Scr ≥ 19.37 was 1.885 times that of patients with BUN/Scr < 19.37 [HR = 1.885 (1.298-2.737), P = 0.001]. Subgroup analysis showed that the relationship between BUN/Scr and the prognosis of CHF was influenced by NYHA and eGRF (P < 0.05). CONCLUSIONS: BUN/Scr ratio is related to the poor prognosis of patients with CHF, and is an independent predictor of all-cause death.

Effects of Shenkang Decoction on Creatinine and Blood Urea Nitrogen in Chronic Renal Failure Hemodialysis Patients: A Randomized Controlled Trial.

Objective: To explore the clinical effect of Shenkang Decoction in chronic renal failure (CRF) patients with hemodialysis (HD). Methods: From November 2020 to December 2021, a total of 160 patients with CRF, who received HD, were included as the research objects, and they were divided into a reference group and a treatment group by random number table method (80 cases in each group). The former group was given basic drug treatment, and the latter group was given Shenkang decoction treatment at the same time as basic drug treatment. The renal function indexes, Traditional Chinese Medicine (TCM) syndrome scores, nutritional status, dialysis adequacy, treatment efficiency, and adverse reactions, were compared between the two groups. Results: After treatment, the patients in the treatment group had lower levels of creatinine and blood urea nitrogen, lower TCM syndrome scores, and higher levels of various nutritional status indicators than the reference group (p < 0.05). After treatment, the effective rate of the treatment group was higher compared with the reference group (p < 0.05). There was no significant difference between the two groups of dialysis adequacy index (p > 0.05). No adverse reaction was found in the two groups of patients in routine urine, blood, stool, liver, and kidney function tests, and electrocardiogram monitoring. Conclusions: Shenkang decoction applied to CRF and HD patients can significantly improve clinical symptoms and renal function, maintain a good nutritional status and little impact on dialysis adequacy, and improve life quality with significant curative effect, high safety, and little adverse reactions.

Expression and Clinical Significance of Serum sST2, BDNF, CTnI, and BUN/Cr in Patients With Heart Failure.

Context: Of the 26-million people suffering from heart failure worldwide, 80% require hospitalization for treatment every year. Biomarkers for clinical diagnosis and prognostic evaluation of heart failure may include: (1) growth-stimulating expression gene 2 protein (sST2), (2) blood urea nitrogen (BUN) and creatinine (Cr), (3) cardiac troponin I (CTnI), and (4) brain-derived neurotrophic factor (BDNP). At present, few studies have occurred on the expression of those biomarkers in patients with heart failure. Objective: The study intended to investigate the expression and clinical significance of serum- soluble sST2, BDNF, CTnI, and BUN/Cr in patients with heart failure. Design: The research team designed a prospective controlled study. Setting: The study took place at Renmin Hospital at the Hubei University of Medicine in Shiyan, Hubei, China. Participants: Participants were 108 patients with heart failure who had been admitted to the hospital between March 2020 and March 2021 and 115 healthy individuals who received physical examinations during the same period. Intervention: The intervention group included the 108 participants with heart failure, and the control group included the healthy individuals. The research team further divided the intervention group into stage II, III, and IV groups, with 23, 65, and 20 patients, respectively. Outcome Measures: The research team collected and compared the serum levels of sST2, BDNF, CTnI, BUN/Cr, and left ventricular ejection fraction (LVEF) between the groups. The team used the Pearson correlation analysis to analyze the correlation between each parameter and participants' cardiac function and multivariate logistic regression analysis to analyze the factors influencing heart failure. Results: No significant differences existed in age, gender, or disease course between the combined intervention groups and the control group at baseline (P > .05). The sST2, CTnI, and BUN/Cr levels of the combined intervention groups were significantly higher than those of the control group postintervention. In addition, the sST2, CTnI, and BUN/Cr levels significantly increased as the disease stage progressed (all P < .05). The levels of BDNF and LVEF in the combined intervention group were significantly lower than those in the control group postintervention, with the two parameters having significantly decreased in the intervention groups as the disease stage progressed (all P < .05). The Pearson correlation analysis found that the sST2, CTnI, and BUN/Cr were positively correlated with cardiac function, with r = 0.483, P = .017; r = .521, P = .011; r = 0.321, P = .021; r = 0.271, = .032; and r = 0.632, P = .007, respectively. The BDNF and LVEF were negatively correlated with cardiac function, with r = -0.43, P < .001 and r = -0.39, P < .001, respectively. With heart failure as the dependent variable, the logistic regression analysis showed that the sST2, CTnI, BUN, Cr, and BUN/Cr were the risk factors for heart failure, and the BDNF and LVEF were the protective factors against heart failure. Conclusions: The serum sST2, CTnI, and BUN/Cr were highly expressed in patients with heart failure, while the expression of BDNF was low. Medical practitioners should pay attention to the risk factors sST2, CTnI, and BUN/Cr, and a higher BNDF indicates a better condition in patients with heart failure.

Esculetin alleviates murine lupus nephritis by inhibiting complement activation and enhancing Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Esculetin is a bioactive compound of medicinal herb Hydrangea paniculata, and has showed anti-oxidation and anti-inflammation bioactivities. Renal local oxidative stress and inflammation are import contributors for progression of lupus nephritis (LN). AIM OF THE STUDY: In the present study, the renal protective effect of esculetin against LN was evaluated using MRL/lpr mice. MATERIALS AND METHODS: MRL/lpr mice were orally administrated with esculetin (20 mg/kg and 40 mg/kg) from 10 to 20 weeks and then renal function and kidney pathology were analyzed. RESULTS: Esculetin significantly attenuated renal impairment in MRL/lpr mice by reducing blood urea nitrogen (BUN), serum creatinine (Scr) and albuminuria, and ameliorated the glomerular hypertrophy, tubular interstitial fibrosis and mononuclear cell infiltration into interstitium. mRNA microarray suggested that esculetin could significantly down-regulate complement cascade, inflammation and fibrosis pathway, and up-regulate Nrf2-related anti-oxidation genes. Most surprising finding in the current study was that esculetin could inhibit the complement activation both in classical and alternative pathway using in vitro hemolysis assay, further enzyme assay suggested that esculetin blocked the C3 convertase (C4b2a) to exert this inhibitory capability. Molecular docking predicted that esculetin had four conventional hydrogen bonds interacting with C4b2a, and CDOCKER energy is relatively lower. Luciferase reporter gene demonstrated that esculetin could activate Nrf2 signaling pathway, and further flow cytometry confirmed that anti-oxidation bioactivity of esculetin was dependent on Nrf2 activation. On the other hand, esculetin could inhibit NFκB nuclear translocation and TGFß-smad3 profibrosis pathway. CONCLUSION: Esculetin shows beneficial effect on LN progression, and it may be a good natural leading compound for design of chemical compounds to treat LN.

Intraperitoneal exposure of iron oxide nanoparticles causes dose-dependent toxicity in Wistar rats.

Nanoparticles of iron oxide, with diameters beteween 1 to 100 nm, have notable implications for human health and well being. In the current study, we have investigated the effects of iron oxide nanoparticles (IONP) exposure on general physiology and health of adult Wistar rats. IONP used in the study had spherical shape and average size in the range of 15-20 nm. A total of eight groups of rats were repeatedly injected with 0 (control), 20, 40, and 80 mg IONP per kg body weight intraperitoneally under two different exposure schemes (sub-acute and sub-chronic). IONP exposure caused significant changes in lungs, liver, and kidney indices in both exposure schemes. Sub-acute exposure did not affect body weight gain in treated rats, but longer duration exposure was responsible for significant reduction in body weight. Mesenteries, visceral fatty tissues, and visceral peritoneal membranes demonstrated apparent accumulations of IONP in a dose and time-dependent manner. Hematological analysis showed that total RBC count, hemoglobin content, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) were not affected by IONP exposure. Total lymphocyte count, however, was elevated in low- and mid-dose treated rats, but not in high-dose group. Serum lactate dehydrogenase (LDH) increased significantly in rats treated with mid and high doses as compared to control. Serum creatinine and blood urea nitrogen levels were also significantly altered in treated rats. Histological study found significant hepatic damage and mild spleen toxicity. Our report suggests that IONP exhibit significant toxicity in rats.

Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction.

In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon's effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-ß1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-ß1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-ß1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.

Dietary intake of n-3 polyunsaturated fatty acids alters the lipid mediator profile of the kidney but does not attenuate renal insufficiency.

The efficacy of n-3 polyunsaturated fatty acids (PUFAs) in improving outcomes in a renal ischemia-reperfusion injury (IRI) model has previously been reported. However, the underlying mechanisms remain poorly understood and few reports demonstrate how dietary n-3 PUFAs influence the composition of membrane phospholipids in the kidney. Additionally, it has not been elucidated whether perilla oil (PO), which is mainly composed of the n-3 alpha-linolenic acid, mitigates renal IRI. In this study, we investigated the effect of dietary n-3 PUFAs (PO), compared with an n-6 PUFA-rich soybean oil (SO) diet, on IRI-induced renal insufficiency in a rat model. Levels of membrane phospholipids containing n-3 PUFAs were higher in the kidney of PO-rich diet-fed rats than the SO-rich diet-fed rats. Levels of blood urea nitrogen and serum creatinine were significantly higher in the ischemia-reperfusion group than the sham group under both dietary conditions. However, no significant differences were observed in blood urea nitrogen, serum creatinine, or histological damage between PO-rich diet-fed rats and SO-rich diet-fed rats. In the kidney of PO-rich diet-fed rats, levels of arachidonic acid and arachidonic acid-derived pro-inflammatory lipid mediators were lower than SO-rich diet-fed rats. Eicosapentaenoic acid and eicosapentaenoic acid-derived lipid mediators were significantly higher in the kidney of PO-rich than SO-rich diet-fed rats. These results suggest that dietary n-3 PUFAs alter the fatty acid composition of membrane phospholipids and lipid mediators in the kidney; however, this does not attenuate renal insufficiency or histological damage in a renal IRI model.

Yuquan pill enhance the effect of Western medicine in treatment diabetic nephropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy is glomerular sclerosis caused by diabetic microvascular disease, which is one of the most serious complications of diabetes. At present, the traditional treatment of diabetic nephropathy is mainly based on the control of blood pressure, blood sugar, blood lipids, and other basic treatments using angiotensin converting enzyme inhibitor/angiotensin receptor blocker, the clinical reports of relying solely on angiotensin converting enzyme inhibitor/ angiotensin receptor blocker to delay the course of diabetic nephropathy are not optimistic. Yuquan pill (YQP), a classic traditional Chinese medicine prescription, has clinical reports that it can effectively assist in the treatment of diabetic nephropathy with minimal side effects. However, there has been no systematic review of the YQP in the treatment of diabetic nephropathy. This article systematically evaluated the effectiveness and safety of YQP clinical applications. METHODS: The database search include seven databases, including PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wanfang database. The search date was set as a randomized controlled trial from the establishment of the database to April 21, 2021. The main outcome indicators include urinealbumin excretion rate, serum creatinine, urea nitrogen, Total effective rate. The analysis software uses Stata 15. RESULTS: This study will analyze multiple outcome indicators such as clinical efficacy, urinary albumin excretion rate, blood creatinine value, urea nitrogen, and symptom scores. Provides a the latest evidence for YQP in the treatment of diabetic nephropathy (DN). CONCLUSION: The results of this study will provide evidence for the efficacy of YQP in the treatment of DN. INPLASY REGISTRATION NUMBER: INPLASY202150030.

Effects of prebiotic oligofructose-enriched inulin on gut-derived uremic toxins and disease progression in rats with adenine-induced chronic kidney disease.

Recent studies suggest that dysbiosis in chronic kidney disease (CKD) increases gut-derived uremic toxins (GDUT) generation, leads to systemic inflammation, reactive oxygen species generation, and poor prognosis. This study aimed to investigate the effect of oligofructose-enriched inulin supplementation on GDUT levels, inflammatory and antioxidant parameters, renal damage, and intestinal barrier function in adenine-induced CKD rats. Male Sprague-Dawley rats were divided into control group (CTL, n = 12) fed with standard diet; and CKD group (n = 16) given adenine (200 mg/kg/day) by oral gavage for 3-weeks to induce CKD. At the 4th week, CKD rats were subdivided into prebiotic supplementation (5g/kg/day) for four consecutive weeks (CKD-Pre, n = 8). Also, the control group was subdivided into two subgroups; prebiotic supplemented (CTL-Pre, n = 6) and non-supplemented group (CTL, n = 6). Results showed that prebiotic oligofructose-enriched inulin supplementation did not significantly reduce serum indoxyl sulfate (IS) but did significantly reduce serum p-Cresyl sulfate (PCS) (p = 0.002) in CKD rats. Prebiotic supplementation also reduced serum urea (p = 0.008) and interleukin (IL)-6 levels (p = 0.001), ameliorated renal injury, and enhanced antioxidant enzyme activity of glutathione peroxidase (GPx) (p = 0.002) and superoxide dismutase (SOD) (p = 0.001) in renal tissues of CKD rats. No significant changes were observed in colonic epithelial tight junction proteins claudin-1 and occludin in the CKD-Pre group. In adenine-induced CKD rats, oligofructose-enriched inulin supplementation resulted in a reduction in serum urea and PCS levels, enhancement of the antioxidant activity in the renal tissues, and retardation of the disease progression.

Effect of hyperbaric oxygen combined with alprostadil in the treatment of elderly diabetic nephropathy and effects on serum miR-126 and miR-342 levels.

This study aims to investigate the effect of hyperbaric oxygen combined with alprostadil in the treatment of elderly diabetic nephropathy (DN) and its effect on serum miR-126 and miR-342 levels. The total effective rate of the study group was 91.53% after treatment, which was higher than that (74.58%) of the control group (p<0.05); the levels of UAER, Scr, BUN and HbA1c, FPG, 2h PG were lowered in the two groups after treatment, and the levels of these indexes were lower in the study group than those in the control group (p<0.05); the levels of vWF, ET-1, CD8+, miR-342 were lowered after treatment for the two groups, and the levels of these indexes were lower in the study group than those in the control group; the levels of NO, CD3+, CD4+ and miR-126 were increased after treatment and the levels were higher in the study group than those in the control group (p<0.05). The application of hyperbaric oxygen combined with alprostadil in the treatment of elderly DN patients can improve renal function, lower blood glucose, improve vascular endothelial function and immune function, adjust serum miR-126 and miR-342 levels, thereby increasing curative effect.

Xianling Gubao Capsule Prevents Cadmium-Induced Kidney Injury.

Xianling Gubao Capsule (XGC), a kind of capsule preparation of Chinese herbal officially approved for sale by the National Medical Products Administration (NMPA), has the effect of tonifying kidney and strengthening bones. Although the impact of XGC in treating bone diseases has been widely studied, the effect of XGC in kidney injury is unknown yet. The kidney injury model is established by intraperitoneal injection with cadmium chloride (CdCl2). Before model establishment, each XGC group was pregavaged with XGC for 10 d. After 10 d, CdCl2 was injected intraperitoneally into the model group and each XGC group, each XGC group continued to be gavaged with XGC for 4 weeks, and the control group was gavaged with equal doses of distilled water once daily. The level of serum urea nitrogen (BUN) and serum creatinine (Cr) is evaluated by kit. The effect of XGC on protecting kidney injury in mice with kidney injury is analyzed by histopathology (HE stain), immunohistochemistry (IHC), and real-time fluorescence quantitative PCR (RT-qPCR). The results show that CdCl2 significantly increases the level BUN and Cr in serum and results in remarkable pathological changes in the nephron, including tubule edema, congestion, and necrosis. While oral administration of XGC can significantly decrease BUN and Cr in serum and prevent and protect the kidney from the above injuries. In addition, the protein expression of p-mTOR was remarkably reduced, and the ratio of LC3II/LC3I protein and mRNA was significantly increased in mice with oral administration of XGC. Our findings suggest that XGC can prevent and protect kidney injury by improving the state of renal tubular hyperemia and necrosis and reduce the level of BUN and Cr in cadmium poisoning mice.

Efficacy of tripterygium glycosides for diabetic nephropathy: a meta-analysis of randomized controlled trials.

BACKGROUNDS: Diabetic nephropathy (DN) is one of the most important clinical complications of diabetes mellitus (DM) and is the most common cause of end-stage renal disease. Currently, there is no highly effective medicine that can prevent, halt, or reverse the progressive course of DN. Initial clinical data showed that Tripterygium glycosides (TGs), a traditional Chinese medicine, can decrease proteinuria in patients with DN. OBJECTIVES: The objective of the present study is to investigate the efficacy and safety of TGs for the treatment of DN through meta-analysis of randomized controlled trials (RCTs). METHODS: All RCTs of TGs for DN were collected from The China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, Wanfang Data, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP) by setting the study inclusion and elimination standards. Two reviewers evaluated the quality of the trials and extracted the data independently. RevMan 5.4 software was used for meta-analyses. The primary outcome was a change in 24-hours urinary total protein (24 h TUP). RESULTS: 26 RCTs with 1824 participants were identified. Studies were assessed using the Cochrane risk of bias tool. The overall effects showed that TGs was compared with the controls, TGs showed significant effects in reducing 24 h TUP [WMD = -0.84, 95 % CI (-1.09, -0.59)], elevating serum albumin [WMD = 2.88, 95 % CI (1.87, 3.90)], and the total efficiency [OR = 4.08, 95 % CI (2.37, 7.04)]. This effect was consistent across the subgroups of period of intervention. CONCLUSIONS: The present research showed that TGs was significantly associated with improvement of renal function in patients with DN. TGs offers a novel approach to the treatment of DN, more high-quality RCTs are needed for a better understanding of the role of TGs in DN therapy.

Effects of calcitriol on peripheral endothelial progenitor cells and renal renovation in rats with chronic renal failure.

BACKGROUND: The role of calcitriol (1,25-dihydroxyvitamin D3 or 1,25-(OH)2D3) in physiological processes, such as anti-fibrosis, anti-inflammation, and immunoregulation is known; however, its role in the remodeling of the glomerular capillary endothelium in rats with chronic renal failure (CRF) remains unclear. METHODS: Here, we analyzed the role/number of endothelial progenitor cells (EPCs), renal function, and pathological alterations in rats with CRF, and compared the results before and after supplementation with calcitriol in vivo. RESULTS: Amongst the three experimental groups (sham group, CRF group, and calcitriol-treated group (0.03 µg/kg/d), we observed substantially elevated cell adhesion and vasculogenesis in vivo in the calcitriol-treated group. Additionally, lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN) was recorded in the calcitriol-treated group than the CRF group (p > 0.05). Calcitriol treatment also resulted in an improvement in renal pathological injury. CONCLUSIONS: Thus, calcitriol could ameliorate the damage of glomerular arterial structural and renal tubules vascular network integrity, maybe through regulating the number and function of EPCs in the peripheral blood of CRF rats. Treatment with it may improve outcomes in patients with renal insufficiency or combined cardiac insufficiency. Calcitriol could ameliorate CRF-induced renal pathological injury and renal dysfunction by remodeling of the glomerular capillary endothelium, thus, improving the function of glomerular endothelial cells.

Nelore females along a new Brazilian agricultural frontier: hematological and clinical-biochemical approaches / [Abordagens hematológicas e bioquímicas clínicas de fêmeas Nelore na nova fronteira agrícola brasileira]

The Nelore breed is the second largest bovine breed in the world and has actively participated in the expansion of new Brazilian agricultural frontiers. In this context, the purpose of this study was to determine the hematological and biochemical reference intervals of healthy Nelore matrices raised under an extensive regime without supplementation along southwest of Piauí state. Blood samples were collected from fifty-five multiparous female of the Nelore breed. Biochemical and hematological parameters were analyzed using a parametric statistical method with 95% CI of reference limits. The average values of red blood cells, hemoglobin as well as hematimetric indices showed reference ranges similar to reference standards. The hematocrit as well as granulocytes and agranulocytes presented alterations typical of animals raised in environments with higher temperatures. Mineral, enzymatic, protein and metabolic profiles were similar to other bovine breeds but with a narrower range of values. However, lower mean values were observed for levels of ionized calcium, total protein and urea. Nelore females present slightly different biochemical and hematological profiles from other breeds, which might result from the environmental and nutritional management applied and the natural deficiency of nitrogen, phosphorus and calcium in the region's pastures.(AU)

Nelore é a segunda maior raça bovina do mundo e tem participado ativamente da expansão das novas fronteiras agrícolas brasileiras. Nesse contexto, o objetivo do presente estudo foi determinar os intervalos de referência hematológicos e bioquímicos de matrizes Nelore criadas em regime extensivo sem suplementação, ao longo do sudoeste do estado do Piauí. Amostras de sangue foram coletadas de 55 fêmeas multíparas da raça Nelore. Os parâmetros bioquímicos e hematológicos foram analisados por método estatístico paramétrico com IC 95% para os limites de referência. Os valores médios de hemácias, hemoglobina e índices hematimétricos apresentaram intervalos de referência semelhantes aos padrões de referência. Tanto o hematócrito quanto os granulócitos e os agranulócitos apresentaram alterações típicas de animais criados em ambientes com temperaturas mais elevadas. Os perfis mineral, enzimático, proteico e metabólico foram semelhantes aos de outras raças bovinas, mas com uma faixa de valores mais estreita. No entanto, valores médios mais baixos foram observados para os níveis de cálcio ionizado, proteína total e ureia. Fêmeas Nelore apresentam perfis bioquímicos e hematológicos ligeiramente diferentes de outras raças, o que pode resultar dos manejos ambiental e nutricional aplicados e da deficiência natural de nitrogênio, fósforo e cálcio nas pastagens da região.(AU)

Ameliorative effect and mechanism of Yi-Suan-Cha against hyperuricemia in rats.

BACKGROUND: This study aimed to evaluate the urate-lowering effects of Yi-Suan-Cha and explore its underlying mechanisms in experimental hyperuricemia induced in rats. METHODS: Forty-eight male SD rats were randomly allocated into normal control, model, allopurinol, benzbromarone, low-dose Yi-Suan-Cha (0.2 g/ml), and high-dose Yi-Suan-Cha (0.4 g/ml) groups (n = 8 rats per group). Rat models of hyperuricemia were established through intragastric administration of adenine 25 mg/kg + potassium oxalate 300 mg/kg for 3 weeks. After the last administration, serum uric acid, creatinine, and urea nitrogen levels were measured. Renal histopathology was observed by hematoxylin-eosin staining. Xanthine oxidase level in serum and liver homogenates was measured by ELISA. The protein and mRNA expression of URAT1, ABCG2, OAT1, and GLUT9 in the kidney was detected by Western blotting and RT-PCR, respectively. RESULTS: The serum uric acid levels were significantly lowered in all medication groups than in the model group. The benzbromarone and both Yi-Suan-Cha groups showed clear kidney structures with no obvious abnormalities. Compared with the normal control group, the model group showed increased URAT1/GLUT9 protein expression and decreased ABCG2/OAT1 protein expression. Compared with the model group, both Yi-Suan-Cha groups showed decreased URAT1/GLUT9 protein expression and increased ABCG2/OAT1 protein expression. Compared with that in the normal control group, URAT1/GLUT9 mRNA expression increased in the model group. Compared with the model group, the low-dose and high-dose Yi-Suan-Cha groups showed decreased URAT1/GLUT9 mRNA expression and increased ABCG2/OAT1 mRNA expression. CONCLUSION: Yi-Suan-Cha may lower uric acid level by downregulating URAT1/GLUT9 expression and upregulating ABCG2/OAT1 expression.

The nephroprotective properties of taurine-amikacin treatment in rats are mediated through HSP25 and TLR-4 regulation.

Amikacin (AMK) is one of the most effective aminoglycoside antibiotics. However, nephrotoxicity is a major deleterious and dose-limiting side effect associated with its clinical use especially in high dose AMK-treated patients. The present study assessed the ability of taurine (TAU) to alleviate or prevent AMK-induced nephrotoxicity if co-administrated with AMK focusing on inflammation, apoptosis, and fibrosis. Male Sprague Dawley rats were assigned to six equal groups. Group 1: rats received saline (normal control), group 2: normal rats received 50 mg kg-1 TAU intraperitoneally (i.p.). Groups 3 and 4: received AMK (25 or 50 mg kg-1; i.p.). Groups 5 and 6: received TAU (50 mg kg-1; i.p.) concurrently with AMK (25 or 50 mg kg-1; i.p.) for 3 weeks. AMK-induced nephrotoxicity is evidenced by elevated levels of serum creatinine (CRE), blood urea nitrogen (BUN), and uric acid (UA). Histopathological investigations provoked damaging changes in the renal tissues. Heat shock proteins (HSP)25 and Toll-like receptor-4 (TLR-4) elevated levels were involved in the induction of inflammatory reactions and focal fibrosis. The improved activation of TLR-4 may stimulate monocytes to upgrade Interleukin (IL)-18 production rather than IL-10. TAU proved therapeutic effectiveness against AMK-induced renal toxicity through downregulation of HSP25, TLR-4, caspase-3, and IL-18 with up-regulation of IL-10 levels.