Association of dietary live microbe intake with diabetic kidney disease in patients with type 2 diabetes mellitus in US adults: a cross-sectional study of NHANES 1999-2018.

AIMS: Several studies have reported dietary microorganisms' beneficial effects on human health. We aimed to detect the potential association between dietary live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 1999 to 2018. METHODS: According to the Sanders classification system of dietary live microbes, the study participants were divided into three groups: low, medium, and high live microbe groups. In patients with T2DM, DKD was assessed by glomerular filtration rate (< 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration algorithm), proteinuria (urinary albumin to creatinine ratio ≥ 30 mg/g), or both. Weighted univariate and multivariate logistic regression and subgroup analyses were conducted to investigate the independent association between dietary live microbe and DKD. RESULTS: The study included 3836 participants, of whom 1467 (38.24%) had DKD for the diagnosis. Our study demonstrated that participants in the high dietary live microbe group were more likely to be older, female, non-Hispanic White, have higher education levels, have a lower prevalence of smoking, have a high poverty-income ratio, have higher energy intake, lower haemoglobin (HbA1c) and serum creatinine levels, and lower risk of progression. After adjustment for covariates, patients in the high dietary live microbe group had a low prevalence of DKD, whereas no significant association with DKD was found between the medium and low dietary live microbe groups. No statistically significant interaction was observed in all subgroup analyses except for HbA1c (p for interaction < 0.05). CONCLUSIONS: Our results indicate that high dietary live microbe intake was associated with a low DKD prevalence.

MYCT1 attenuates renal fibrosis and tubular injury in diabetic kidney disease.

Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in in vitro and in vivo DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-ß1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-ß1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD.

Association between the composite dietary antioxidant index and chronic kidney disease: evidence from NHANES 2011-2018.

Objectives: There is growing evidence that antioxidant-rich diets protect against chronic kidney disease (CKD). However, the relationship between the Composite Dietary Antioxidant Index (CDAI), an important measure of an antioxidant diet, and CKD has received little attention. Therefore, here we investigated the relationship between the CDAI and CKD through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data. Methods: The CDAI was calculated based on the intake of six dietary antioxidants. A survey-based multivariate linear regression analysis was performed to analyze the independent relationship between the CDAI and CKD. Weighted multivariate regression and subgroup analyses were conducted to explore the relationship between the CDAI and CKD. Results: A total of 6874 NHANES participants represented 181.9 million non-institutionalized US residents (mean age, 46.43 ± 0.38 years; 49.87% female; 40.62% non-Hispanic white; 20.24% non-Hispanic black; and 13.94% Mexican American). The weighted linear regression model with full adjustment for confounding variables was -0.0155 (-0.0417, 0.0107) for Q2 (P for trend <0.0001), -0.0052 (-0.0346, 0.0242) for Q3 (P for trend <0.0001), and -0.0305 (-0.0491, -0.0120) for Q4 (P for trend = 0.0094) upon comparison with the lowest quartile of the CDAI. None of the interactions in any subgroup analysis were statistically significant except for individuals with a history of diabetes or the aged population (≥60 years) (P for interaction <0.05). Conclusions: The CDAI was positively associated with a lower prevalence of CKD in adults in the United States. Further large-scale prospective studies are required to analyze the role of the CDAI in CKD.

YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosis via aberrant glycolysis associated with EGFR/PKM2/HIF-1α pathway.

Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD. Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis. Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis. Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments.

Genetically predicted body fat mass and distribution with diabetic kidney disease: A two-sample Mendelian randomization study.

The aim of this study is to apply a Mendelian randomization (MR) design to investigate the potential causal associations between the body mass index (BMI), body fat mass such as trunk fat mass and waist circumference (WC), and diabetic kidney disease (DKD). A two-sample MR study was conducted to obtain exposure and outcome data from previously published studies. The instrumental variables for BMI, trunk fat mass, and WC were selected from genome-wide association study datasets based on summary-level statistics. The random-effects inverse-variance weighted (IVW) method was used for the main analyses, and the weighted median and MR-Egger approaches were complementary. In total, three MR methods suggested that genetically predicted BMI, trunk fat mass, and WC were positively associated with DKD. Using IVW, we found evidence of causal relationships between BMI [odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.47-2.69; p = 7.89 × 10-6], trunk fat mass (OR = 1.80; 95% CI, 1.28-2.53; p = 6.84 × 10-4), WC (OR = 2.48; 95% CI, 1.40-4.42; p = 1.93 × 10-3), and DKD. MR-Egger and weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts showed no directional pleiotropic effects involving the aforementioned variables and DKD. Our MR analysis supported the causal effect of BMI, trunk fat mass, and WC on DKD. Individuals can substantially reduce DKD risk by reducing body fat mass and modifying their body fat distribution.

LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway.

AIM: More than half of microRNAs are located in genes. LncRNAs are host genes of intronic microRNAs that regulate intracellular splicing to form pre-miRNAs that are processed to mature miRNAs. MicroRNAs work as partners or antagonists of their host lncRNAs by fine-tuning their target genes. However, whether lncRNA-MIR503HG (miR-503 host gene) is co-transcribed with miR-503 and affects miR-503 splicing, thereby affecting its target gene Bcl-2 expression and cell mitochondrial apoptotic pathway in diabetic nephropathy (DN) is currently unknown. METHODS: Human proximal tubular (HK-2) cells cultured in high glucose were transfected with lncRNA MIR503HG overexpression/inhibition plasmid and miR-503 mimics/inhibitor. Real-time quantitative PCR was used to measure the expression levels of lncRNA MIR503HG, pre-miR-503, miR-503 and Bcl-2. Western blot was used to measure the protein expressions of Bcl-2, Bax, Cytc and cleaved-caspase 9/3. Annexin V/PI flow cytometry was used to measure apoptosis. RESULTS: Host lncRNA MIR503HG was co-transcribed with miR-503. MIR503HG regulated the expression of miR-503 by affecting miR-503 splicing synthesis. In the presence of high glucose, the expression levels of lncRNA MIR503HG and miR-503 were up-regulated in HK-2 cells cultured in high glucose. Bcl-2 expression was inhibited and levels of apoptosis-related proteins Cytc and Bax were increased in HK-2 cells cultured in high glucose, all of which promoted the caspase cascade reaction, leading to increased caspase-9 and caspase-3 shear fragments inducing apoptosis of the mitochondrial pathway. Inhibition of MIR503HG led to a reduction in miR-503 expression, up-regulated its target gene Bcl-2, inhibited the expression levels of Bax and other apoptosis-related proteins and attenuated HK-2 cell apoptosis induced by high glucose. Co-transfection of miRNA-503 partially offset the effect of MIR503HG-siRNA. CONCLUSION: MIR503HG indirectly regulates Bcl-2 by promoting the co-transcription of miRNA-503 to participate high-glucose-induced proximal tubular cell apoptosis, providing a new target for diabetic nephropathy treatment.

LncRNA ARAP1-AS2 promotes high glucose-induced human proximal tubular cell injury via persistent transactivation of the EGFR by interacting with ARAP1.

The persistent transactivation of epidermal growth factor receptor (EGFR) causes subsequent activation of the TGF-ß/Smad3 pathway, which is closely associated with fibrosis and cell proliferation in diabetic nephropathy (DN), but the exact mechanism of persistent EGFR transactivation in DN remains unclear. ARAP1, a susceptibility gene for type 2 diabetes, can regulate the endocytosis and ubiquitination of membrane receptors, but the effect of ARAP1 and its natural antisense long non-coding RNA (lncRNA), ARAP1-AS2, on the ubiquitination of EGFR in DN is not clear. In this study, we verified that the expression of ARAP1 and ARAP1-AS2 was significantly up-regulated in high glucose-induced human proximal tubular epithelial cells (HK-2 cells). Moreover, we found that overexpression or knockdown of ARAP1-AS2 could regulate fibrosis and HK-2 cell proliferation through EGFR/TGF-ß/Smad3 signalling. RNA pulldown assays revealed that ARAP1-AS2 directly interacts with ARAP1. Coimmunoprecipitation, dual-immunofluorescence and ubiquitination assays showed that ARAP1 may maintain persistent EGFR activation by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding. Taken together, our results suggest that the lncRNA ARAP1-AS2 may promote high glucose-induced proximal tubular cell injury via persistent EGFR/TGF-ß/Smad3 pathway activation by interacting with ARAP1.

Caspase-3 Promotes Diabetic Kidney Disease Through Gasdermin E-Mediated Progression to Secondary Necrosis During Apoptosis.

BACKGROUND: Apoptosis has been repeatedly linked with diabetic kidney disease (DKD), which is a programmed cell death mediated by effector caspases-3, 6 and 7, targeting >600 substrates. However, the pathophysiologic correlations of this process remain obscure. As a putative tumor suppressor, gasdermin E (GSDME) was recently reported to be cleaved by caspase-3 to produce a GSDME-N fragment which targets the plasma membrane to switch apoptosis to secondary necrosis. However, it remains elusive whether GSDME is involved in the regulation of DKD. METHODS: To evaluate the therapeutic potential of caspase-3 inhibition in DKD, we administered caspase-3 inhibitor Z-DEVD-FMK to STZ-induced diabetic mice for eight weeks. Albuminuria, renal function, pathological changes, and indicators of secondary necrosis and fibrosis were evaluated. In vitro, human tubule epithelial cells (HK-2 cells) were subjected to high-glucose treatment. Secondary necrosis was determined by LDH release, GSDME cleavage, and morphological feature under confocal microscopy. Z-DEVD-FMK and GSDME inhibition by shRNA were administered to suppress the cleavage and expression of GSDME. Flow cytometry, cytotoxicity assay and immunoblot were used to assess cell death and fibrogenesis. RESULTS: Caspase-3 inhibition by Z-DEVD-FMK ameliorated albuminuria, renal function, and tubulointerstitial fibrosis in diabetic mice. The nephroprotection mediated by Z-DEVD-FMK was potentially associated with inhibition of GSDME. In vitro, molecular and morphological features of secondary necrosis were observed in glucose-stressed HK-2 cells, evidenced by active GSDME cleavage, ballooning of the cell membrane, and release of cellular contents. Here we showed that caspase-3 inhibition prevented GSDME activation and cell death in glucose-treated tubular cells. Specifically, knocking down GSDME directly inhibited secondary necrosis and fibrogenesis. CONCLUSION: These data suggest GSDME-dependent secondary necrosis plays a crucial role in renal injury, and provides a new insight into the pathogenesis of DKD and a promising target for its treatment.

Machine learning in nephrology: scratching the surface.

Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases. With the development of data preservation and processing, as well as the advancement of machine learning algorithms, machine learning is expected to make remarkable breakthroughs in nephrology. Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields, including analysis of renal pathological images, diagnosis and prognosis of chronic kidney diseases and acute kidney injury, as well as management of dialysis treatments. However, it is just scratching the surface of the field; at the same time, machine learning and its applications in renal diseases are facing a number of challenges. In this review, we discuss the application status, challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction, detection, and care quality in kidney diseases.

Ursolic Acid Treatment Alleviates Diabetic Kidney Injury By Regulating The ARAP1/AT1R Signaling Pathway.

PURPOSE: This study aimed to investigate whether ursolic acid (UA) mitigates renal inflammation, oxidative stress and fibrosis by regulating the angiotensin II type 1 receptor-associated protein (ARAP1)/angiotensin II type 1 receptor (AT1R) signaling pathway and subsequently alleviating renal damage. METHODS: db/db mice were divided randomly into a diabetic nephropathy (DN) group and a UA treatment group. Light microscopy and electron microscopy were used to observe pathological changes in renal tissues. Immunohistochemistry (IHC) was employed to examine changes in the expression of ARAP1, AT1R, 8-hydroxydeoxyguanosine (8-OHdG), NADPH oxidase 2 (NOX2), the extracellular matrix protein fibronectin (FN), IL-1ß and IL-18 in renal tissues. Western blotting and RT-qPCR were used to detect the respective changes in the protein and mRNA levels of ARAP1, AT1R, NOX4, NOX2, transforming growth factor-ß1 (TGF-ß1), FN, collagen IV, IL-1ß and IL-18 in renal tissues and mesangial cells. In addition, immunofluorescence staining was employed to examine changes in FN and NOX2 expression in mesangial cells. RESULTS: UA treatment effectively reduced the body weights and blood glucose levels of db/db mice (p<0.05) as well as the urinary albumin/creatinine ratio (p<0.05). In addition, the renal tissue lesions and glomerulosclerosis index of the db/db mice were significantly improved after treatment (p<0.01). Histochemical analysis results showed significantly lower expression levels of ARAP1, AT1R, FN, NOX2, 8-OHdG, IL-1ß and IL-18 in renal tissues in the UA treatment group than in the DN group. Western blotting and RT-qPCR data also revealed UA-induced decreases in the renal levels of the ARAP1, AT1, NOX4, NOX2, TGF-ß1, FN, collagen IV, IL-1ß and IL-18 proteins in vivo and/or in vitro (p<0.01). ARAP1 knockdown effectively reduced the expression of NOX2 and FN in vitro. CONCLUSION: UA alleviated renal damage in type 2 diabetic db/db mice by downregulating proteins in the ARAP1/AT1R signaling pathway to inhibit extracellular matrix accumulation, renal inflammation, fibrosis and oxidative stress.

Ursolic Acid Attenuates High Glucose-Mediated Mesangial Cell Injury by Inhibiting the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR) Signaling Pathway.

BACKGROUND To investigate the protective effect of ursolic acid (UA) on high glucose (HG)-induced human glomerular mesangial cell injury and to determine whether UA inhibits cell proliferation and reactive oxygen species (ROS) production by suppressing PI3K/Akt/mTOR pathway activation. MATERIAL AND METHODS Human mesangial cells were cultured with normal glucose (NG group), high glucose (HG group), mannitol (mannitol hypertonic control group), or high glucose with different concentrations (0.5, 1.0, and 2.0 mmol/L) of UA (HG+UA groups). Cell proliferation and intracellular ROS levels were assessed by methyl thiazolyl tetrazolium (MTT) and dichloro-dihydro-fluorescein diacetate (DCFH-DA) flow cytometry assays, respectively. Western blotting was used to detect mesangial cell expression of PI3K/Akt/mTOR pathway components, including Akt, p-Akt, mTOR, and p-mTOR, and proteins related to cell injury, including TGF-ß1 and fibronectin (FN). mRNA expression of TGF-ß1 and FN were evaluated using real-time quantitative polymerase chain reaction (PCR). RESULTS Abnormal proliferation was observed in human glomerular mesangial cells at 48 h after treatment with HG, and UA suppressed the HG-induced proliferation of mesangial cells in a dose-dependent manner. UA inhibited ROS generation and oxidative stress in mesangial cells and mitigated mesangial cell injury. Treatment with UA reduced Akt and mTOR phosphorylation levels in mesangial cells exposed to HG (p<0.05 vs. HG) and downregulated protein and mRNA expression of TGF-ß1 and FN in these cells (p<0.05 vs. HG). CONCLUSIONS UA attenuated mesangial cell proliferation and ROS generation by inhibiting HG-mediated PI3K/Akt/mTOR pathway activation, thereby ameliorating mesangial cell damage.

Sucrose fed-batch strategy enhanced biomass, polysaccharide, and ganoderic acids production in fermentation of Ganoderma lucidum 5.26.

Ganoderma, as a Chinese traditional medicine, has multiple bioactivities. However, industrial production was limited due to low yield during Ganoderma fermentation. In this work, sucrose was found to greatly enhance intracellular polysaccharide (IPS) content and specific extracellular polysaccharide (EPS) production rate. The mechanism was studied by analyzing the activities of enzymes related to polysaccharide biosynthesis. The results revealed that sucrose regulated the activities of phosphoglucomutase and phosphoglucose isomerase. When glucose and sucrose mixture was used as carbon source, biomass, polysaccharide and ganoderic acids (GAs) production was greatly enhanced. A sucrose fed-batch strategy was developed in 10-L bioreactor, and was scaled up to 300-L bioreactor. The biomass, EPS and IPS production was 25.5, 2.9 and 4.8 g/L, respectively, which was the highest biomass and IPS production in pilot scale. This study provides information for further understanding the regulation mechanism of Ganoderma polysaccharide biosynthesis. It demonstrates that sucrose fed-batch is a useful strategy for enhancing Ganoderma biomass, polysaccharide and GAs production.

The role of CD44-hyaluronic acid interaction in exogenous mesenchymal stem cells homing to rat remnant kidney.

BACKGROUND/AIMS: The aim of our study was to reveal the role of CD44-Hyaluronic acid (HA) in the homing and improving renal function of systemically transplanted MSCs in chronic renal failure. METHODS: First, a remnant kidney model was established in rats and the expression of HA was determined using immunohistochemistry (IHC) and western blotting. Next, chemotaxis assay using flow cytometry, and cell migration assay of MSCs were performed in vitro. Then, MSCs were transplanted into rats, thus, sprague-Dawley (SD) rats were randomly divided into sham group, 5/6 nephrectomy (5/6 Nx) group, MSC group and MSC/Anti-CD44 group (n = 8 for all groups). Migration of MSCs to the kidney in these rats was assessed by using cell tracking experiments, and tissue damage was evaluated by morphological analysis using Masson's trichrome staining and periodic acid Schiff staining. RESULTS: HA was significantly observed in 5/6 Nx group, but not in sham group. Meanwhile, HA was discovered induced MSCs migration remarkably (p < 0.05) and anti-CD44 antibody inhibited the migration significantly (p < 0.05) in vitro. In vivo, the GFP-MSCs were observed in MSC group and the cells reduced in MSC/Anti-CD44 groups, especially, in the tubulointerstitium. CONCLUSION: Our findings reveal that CD44-HA has the potential to induce MSCs homing to injured tissue, while its effect on the ability of MSCs, improving tissue function, is not significant.

Effect of losartan on the glomerular protein expression profile of type 2 diabetic KKAy mice.

BACKGROUND: To investigate the pathogenesis of diabetic nephropathy (DN) and to search for novel therapeutic targets, the glomerular protein expression profile of KKAy mice treated by losartan was analyzed by two-dimensional differential gel electrophoresis (2D-DIGE). METHODS: The eight-week-old KKAy mice were divided into the losartan treatment group and the non-treatment group, and C57BL/6 mice were used as the control group. After 12 weeks treatment, glomeruli were isolated by abdominal perfusion with magnetic beads, and the glomerular proteins were extracted. The glomerular protein expression profiles were investigated using 2D-DIGE and MALDI-TOF mass spectrometry. Western blot analysis was used to confirm the results of proteomics. RESULTS: Losartan treatment improved albuminuria and renal pathologic lesion of KKAy mice. A total of 62 glomerular proteins were differentially expressed between the KKAy losartan treatment mice and KKAy non-treatment mice. Among them, the expression of 28 proteins were up-regulated, including glycerokinase, sulfite oxidase, glycine amidinotransferase, and adenosylhomocysteinase. The expression of 13 proteins were down-regulated, including 3-mercaptopyruvate sulfurtransferase, ATP synthase subunit d, 60 kDa heat shock protein, and 75 kDa glucose-regulated protein(GRP75). A total of six proteins were found to be differentially expressed between the KKAy non-treatment mice and C57BL/6 mice glomeruli, and their differential expression was suppressed by losartan treatment, including mitochondrial ATP synthase subunit d, GRP75, and selenium-binding protein 1 et al. CONCLUSIONS: Treatment with losartan suppresses the differential expression of mitochondrial ATP synthase subunit d, GRP75, selenium-binding protein 1 etc. In diabetic KKAy mice glomeruli, may play a renoprotective role by reducing glomerular mitochondrial ROS genesis and inhibiting oxidative stress.

Iridoid glycosides and glycosidic constituents from Eriophyton wallichii Benth.

C9-iridoid glycosides, wallichiisides A-C, and four dimers, wallichiisides D-G, together with 13 known glycosidic compounds, were isolated from whole plants of Eriophyton wallichii Benth. Their structures were elucidated by spectroscopic methods and comparison with literature values. Four of these compounds showed moderate DPPH free radical scavenging activity.

Successful treatment of patients with systemic lupus erythematosus complicated with autoimmune thyroid disease using double-filtration plasmapheresis: a retrospective study.

INTRODUCTION: Systemic lupus erythematosus (SLE) associated with autoimmune thyroid disease (AITD) is a complex and well recognized autoimmune disorder. Careful monitoring/surveillance of thyroid gland functioning and active treatment of SLE patients with coexisting AITD, typically using medications, are critically important. The role of apheresis in this setting remains to be fully explored. Here we examine the use of double-filtration plasmapheresis (DFPP), as an adjuvant therapy in the treatment of patients with SLE complicated with AITD and report our experiences using this apheresis methodology. METHODS: We performed a retrospective chart review of 11 patients with SLE complicated with AITD who had received DFPP in our blood purification center between 2004 and 2008. Levels of thyroid hormones, antithyroid autoantibodies, SLE disease activity, proteinuria, glomerular filtration rate (GFR), and response to therapy were analyzed. RESULTS: AITD, SLE, and lupus nephritis improved after DFPP. Except for one patient who died of severe pneumonia in the second month after completion of DFPP, all surviving patients continued to show clinical improvements or remained stable during the follow-up periods. CONCLUSION: DFPP can effectively remove autoantibodies and may have an important adjuvant role in therapeutic options in the treatment of SLE patients with AITD complications.

The modifier protein of glyceraldehyde-3-phosphate dehydrogenase reduces free radical-mediated renal damage in a rat model of acute kidney injury.

BACKGROUND: The modifier protein (MP) of glyceraldehyde-3-phosphate dehydrogenase has been shown to promote growth of renal epithelial cells in vitro. The aim of this study was to show the in vivo effects of MP in a rat model of gentamicin-induced acute kidney injury (AKI). METHOD: MP was purified from monkey renal tubular epithelial cell line BSC-1 and confirmed by amino acid sequencing. Male Sprague-Dawley rats were divided into the following groups: normal control, gentamicin-treated, epidermal growth factor (EGF) plus gentamicin-treated, and MP plus gentamicin-treated, as well as control groups for EGF and MP alone. Levels of serum creatinine (SCr), serum and tissue lipid peroxide, nitric oxide and glutathione-S-hydrogenase for each group were measured on the 7th and 14th days of treatment. Tissue sections were studied with light microscopy. RESULTS: The gentamicin-treated group showed a marked increase in SCr compared to the normal control group. Co-treatment of gentamicin with MP and/or EGF produced similar significant decreases preventing the increase in SCr. There were also significant reductions in serum and tissue homogenate levels of lipid peroxide and nitric oxide, accompanied by an increase in the level of glutathione-S-hydrogenase, in the MP co-treated groups compared to the gentamicin-treated group. AKI was confirmed histologically in the gentamicin-treated group, with damage to the tubular epithelium recorded. This was attenuated by MP co-treatment. There were also reductions in the expression of intercellular adhesion molecule-1 and proliferating cell nuclear antigen in the MP co-treated groups. CONCLUSION: Using a gentamicin model of AKI, MP was able to reduce free radical production in kidney tissue and in the circulation, thus preventing oxidant injury and minimizing damage in renal epithelial cells.

[Studies on phenylpropanoids from herbs of Eriophyton wallichii].

OBJECTIVE: To study the chemical constituents of Eriophyton wallichii. METHOD: Compounds were separated and purified by column chromatographic methods, and their structures were elucidated by spectroscopic methods. RESULT: Eight phenylpropanoids were isolated and identified as martynoside (1), leucosceptoside A (2), citrusin B (3), (+)-dehydrodiconiferyl alcohol-4, 9-beta-D-glucopyranoside (4), liriodendrin (5), velutinoside 11[ (6), jionoside B, (7), stachysoside D (8), respectively. CONCLUSION: The eight compounds were firstly isolated from E. wallichii.

Effects of shark hepatic stimulator substance on the function and antioxidant capacity of liver mitochondria in an animal model of acute liver injury.

This study was carried out to investigate whether shark hepatic stimulator substance (HSS) can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide (TAA)-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA (400 mg/kg) in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS (80 mg/kg) 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.

[Research progress in space plant breeding].

A brief introduction of the advances in study of space mutation of plants is given in this article. It includes: factors influencing plants in space flight, different levels of biological effects of space mutation and researches on space mutation breeding. Prospects are also put forward in this article.