Peritoneal dialysis in an end-stage renal disease patient with massive ascites and primary liver cancer.

End-stage renal disease (ESRD) coexisted with cirrhosis, ascites, and primary liver cancer represents an extraordinarily rare clinical condition that typically occurs in very late-stage decompensated cirrhosis and is associated with an extremely poor prognosis. We present a case of a 68-year-old male patient with ESRD who experienced various decompensated complications of liver cirrhosis, particularly massive ascites and hepatic space-occupying lesions. Peritoneal dialysis (PD) catheter insertion and continuous ambulatory peritoneal dialysis (CAPD) treatment were successfully performed. During meticulous follow-up, the patient survived for one year but ultimately succumbed to complications related to liver cancer. PD can serve as an efficacious therapeutic approach for such late-stage patients afflicted together with severe cirrhosis, massive ascites and primary liver cancer.

ANGPT2/CAV1 regulates albumin transcytosis of glomerular endothelial cells under high glucose exposure and is impaired by losartan / ANGPT2/CAV1 regula la transcitosis de la albúmina de las células endoteliales glomerulares bajo exposición a hiperglucemia, alterándose con la intervención de losartan

Background Microalbuminuria is a common clinical symptom that manifests in the early stages of diabetic kidney disease (DKD) and is also the main feature of glomerular endothelial cells (GECs) injury. There is increasing evidence that the transcytosis of albumin across GECs is closely related to the formation of albuminuria. Our previous studies have shown that angiopoietin 2 (ANGPT2) can inhibit albumin transcytosis across renal tubular epithelial cells by activating caveolin 1 (CAV1) phosphorylation during high glucose (HG) exposure. The role of ANGPT2 in albumin transcytosis across GECs remains unclear. Losartan significantly reduces albuminuria, but the mechanism has not been clarified. Methods We established an in vitro albumin transcytosis model to investigate the change in albumin transcytosis across human renal glomerular endothelial cells (hrGECs) under normal glucose (NG), high glucose (HG) and losartan intervention. We knocked down ANGPT2 and CAV1 to evaluate their roles in albumin transcytosis across hrGECs and verified the relationship between them. In vivo, DKD mouse models were established and treated with different doses of losartan. Immunohistochemistry and Western blot were used to detect the expression of ANGPT2 and CAV1. Results In vitro, the transcytosis of albumin across hrGECs was significantly increased under high glucose stimulation, and losartan inhibited this process. The expression of ANGPT2 and CAV1 were both increased in hrGECs under HG conditions and losartan intervention reduced the expression of them. Moreover, ANGPT2 downregulation reduced albumin transcytosis in hrGECs by regulating CAV1 expression. In vivo, the expression of ANGPT2 and CAV1 in the glomerulus was both increased significantly in DKD mice. Compared with DKD mice, losartan treatment reduced albuminuria and decreased the expression of ANGPT2 and CAV1 in a dose-dependent manner (AU)

Antecedentes La microalbuminuria es un síntoma clínico común que se manifiesta en las fases tempranas de la enfermedad renal diabética (ERD), y también es característica del daño de las células endoteliales glomerulares (GEC). Existe evidencia creciente en cuanto a que la transcitosis de la albúmina a través de las GEC está estrechamente relacionada con la formación de albuminuria. Nuestros estudios previos reflejaron que angiopoyetina 2 (ANGPT2) puede inhibir la transcitosis de la albúmina a través de las células epiteliales tubulares renales activando la fosforilación de caveolina 1 (CAV1) durante la exposición a hiperglucemia (HG). El rol de ANGPT2 en la transcitosis de la albúmina a través de las GEC resulta incierto. Losartan reduce considerablemente la albuminuria, aunque no se ha esclarecido el mecanismo. Métodos Establecimos un modelo in vitro de transcitosis de la albúmina para investigar el cambio de dicho mecanismo a través de las células endoteliales glomerulares renales humanas (hrGEC) en condiciones de glucosa normal (GN), hiperglucemia (HG) e intervención de losartan. Realizamos breakdown de ANGPT2 y CAV1 para evaluar sus roles en la transcitosis de la albúmina a través de las hrGEC, y verificamos la relación entre ellas. Se establecieron modelos in vivo de ratones con ERD, tratados con diferentes dosis de losartan. Se utilizaron pruebas de inmunohistoquímica e inmunotransferencia para detectar la expresión de ANGPT2 y CAV1. Resultados In vitro, la transcitosis de la albúmina a través de hrGEC se incrementó considerablemente en condiciones de estimulación de la hiperglucemia, inhibiendo losartan este proceso. La expresión de ANGPT2 y CAV1 se incrementó en las hrGEC en condiciones de HG, reduciendo la intervención de losartan la expresión de ambas (AU)

ANGPT2/CAV1 regulates albumin transcytosis of glomerular endothelial cells under high glucose exposure and is impaired by losartan.

BACKGROUND: Microalbuminuria is a common clinical symptom that manifests in the early stages of diabetic kidney disease (DKD) and is also the main feature of glomerular endothelial cells (GECs) injury. There is increasing evidence that the transcytosis of albumin across GECs is closely related to the formation of albuminuria. Our previous studies have shown that angiopoietin 2 (ANGPT2) can inhibit albumin transcytosis across renal tubular epithelial cells by activating caveolin 1 (CAV1) phosphorylation during high glucose (HG) exposure. The role of ANGPT2 in albumin transcytosis across GECs remains unclear. Losartan significantly reduces albuminuria, but the mechanism has not been clarified. METHODS: We established an in vitro albumin transcytosis model to investigate the change in albumin transcytosis across human renal glomerular endothelial cells (hrGECs) under normal glucose (NG), high glucose (HG) and losartan intervention. We knocked down ANGPT2 and CAV1 to evaluate their roles in albumin transcytosis across hrGECs and verified the relationship between them. In vivo, DKD mouse models were established and treated with different doses of losartan. Immunohistochemistry and Western blot were used to detect the expression of ANGPT2 and CAV1. RESULTS: In vitro, the transcytosis of albumin across hrGECs was significantly increased under high glucose stimulation, and losartan inhibited this process. The expression of ANGPT2 and CAV1 were both increased in hrGECs under HG conditions and losartan intervention reduced the expression of them. Moreover, ANGPT2 downregulation reduced albumin transcytosis in hrGECs by regulating CAV1 expression. In vivo, the expression of ANGPT2 and CAV1 in the glomerulus was both increased significantly in DKD mice. Compared with DKD mice, losartan treatment reduced albuminuria and decreased the expression of ANGPT2 and CAV1 in a dose-dependent manner. CONCLUSIONS: ANGPT2 exacerbated albumin transcytosis across GECs by increasing CAV1 expression during HG exposure, thereby increasing albuminuria. Losartan reduces albumin transcytosis and albuminuria formation in DKD by inhibiting the upregulation of ANGPT2 under HG conditions. Our findings suggest that ANGPT2 and CAV1 may be novel therapeutic targets for diabetic albuminuria. In addition, we provide new evidence to elaborate on the mechanism of losartan in the development of DKD.

Minimizing early catheter failure using a risk stratification model for peritoneal dialysis.

BACKGROUND: Early catheter failure is the main reason for peritoneal dialysis (PD) failure, which often causes patients to withdraw from PD. Reducing the early catheter failure is critical to increase the acceptance of PD. The purpose of our study was to establish a risk stratification model to minimize early catheter failure. METHODS: A retrospective study with patients underwent PD catheter placement from January 2013 to March 2022 was conducted. The primary outcome event was early catheter failure. Univariate and multivariable logistic regression were performed to select potential risk predictors. A risk stratification model and a clinical procedure were established. The effectiveness of the model was evaluated by external validation. RESULTS: A total of 432 patients were finally enrolled in the study. The risk for early catheter failure was associated with younger age (odds ratio [OR], 0.930; 95% confidence interval [95% CI], 0.884 to 0.972; p = 0.002), lower body mass index (BMI) (OR, 0.797; 95% CI, 0.629 to 0.964; p = 0.036), and lower albumin (ALB) levels (OR, 0.881; 95% CI, 0.782 to 0.985; p = 0.036). The risk stratification model was established and performed great discrimination capability with AUC of 0.832 (cut-off value: 0.061, sensitivity: 0.853, specificity: 0.812). The model proved to be effective in external validation; the rate of early catheter failure was dropped off from 4.1% to 0%. CONCLUSIONS: We established an effective risk stratification model, by which patients with high risk of early catheter failure could be precisely identified. The clinical procedure based on the model was proved to be helpful to minimize early catheter failure.

Isolated scaphoid dislocation: A case report and review of literature.

BACKGROUND: Isolated dislocations of the scaphoid are extremely rare types of injuries, commonly associated with severe ligament disruptions, and are occasionally misdiagnosed. Treatment options for dislocations of the scaphoid mainly include closed reduction, with or without internal fixation, and open reduction with ligament repair. CASE SUMMARY: A 59-year-old male worker sustained a twisting trauma of his right wrist, caused by a moving belt while he was operating a machine. When he presented at our emergency department, the patient complained of swelling, tenderness, and restriction of movement of the right wrist. Radiographs confirmed a primary complex partial radial dislocation of the scaphoid and some chip fractures of the capitate and hamate. Closed reduction with K-wire internal fixation was performed with the assistance of arthroscopy, and an excellent prognosis was achieved. CONCLUSION: Arthroscopy-assisted reduction is a minimally invasive method to reduce the dislocated scaphoid and maintain the blood supply.

MicroRNA-185 modulates CYP7A1 mediated cholesterol-bile acid metabolism through post-transcriptional and post-translational regulation of FoxO1.

BACKGROUND AND AIMS: Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate limiting enzyme of the bile acid biosynthetic pathway to convert cholesterol to bile acids, which is a major output pathway for cholesterol catabolism. In this study, we aimed to assess the potential regulatory mechanisms of microRNA-185 (miR-185) in cholesterol and bile acid homeostasis. METHODS: Eight-week-old male ApoE KO mice fed a high-fat diet (HFD) were injected with lentiviruses encoding antisense miR-185 (miR-185-inh). Microarrays were applied to profile miR-185-regulated genes involved in bile acid metabolism. The expression of potential targets of miR-185 was validated using qPCR and Western blotting assay in human hepatoma HepG2 cells. RESULTS: The administration of miR-185-inh correlated with decreased serum total bile acids levels in ApoE KO mice. Microarray gene profiling revealed that inhibition of miR-185 upregulated hepatic CYP7A1 expression in vivo, which was further validated in HepG2 cells and primary hepatic cells in vitro by overexpression or inhibition of miR-185. Furthermore, it was revealed that miR-185 regulated CYP7A1 expression via a FoxO1-involved indirect pathway and that miR-185 directly modulated FoxO1 expression by binding to its mRNA 3'UTR in a traditional post-transcriptional manner. Besides, we also observed that miR-185 regulated CYP7A1 expression by increasing p-AKT/AKT level, which induced the phosphorylation of FoxO1 and promoted FoxO1 degradation at a post-translational level. CONCLUSIONS: This study provides convincing evidence on the critical role of miR-185 in FoxO1 modulation at both post-transcriptional and post-translational levels, which accounts for the effects on CYP7A1 gene and its mediated cholesterol-bile acid metabolism. These results suggest an important role of miR-185 as a novel atherosclerosis-protective target for drug discovery.

Our 15-year experience of complications of Chow's technique for endoscopic carpal tunnel releasing.

PURPOSE: Our objective in this study was to summarize our 15-year experience treating carpal tunnel syndrome released with Chow technique, focusing on the complications and how to avoid them. METHOD: We systematically evaluated the postoperative complications in 211 patients who underwent endoscopic carpal tunnel release (ECTR) with Chow technique. We recorded the incidence of complex regional pain syndrome type I (CRPS I), median nerve and digital nerve injury, superficial palmar arch injury, and tendon injury. RESULT: The overall incidence of complications was 5.6%, and involved 10 cases of CRPS I, 1 case of median nerve trunk injury, and 1 case of superficial palmar arch injury. No other complication occurred. We used oral pregabalin and neurotropin to relieve CRPS I symptoms, and performed second operations for the other two complications. CONCLUSIONS: Our study revealed that ECTR could reduce structural and cutaneous complications, but increase the incidence of nerve injury. we speculated that the incidence of CRPS I may be higher in the Asian population.

Ulnar nerve injury associated with displaced distal radius fracture: Two case reports.

BACKGROUND: Ulnar nerve injury subsequent to a fracture of the distal radius is extremely rare compared to median nerve injury. Treatment of ulnar nerve injury after closed distal radial fracture is controversial. Reasonable surgical planning and careful postoperative management can improve the prognosis of patients. CASE SUMMARY: We report two cases of ulnar nerve injury subsequent to fracture of the distal radius. Both patients were admitted to hospital. Both patients had persistent ulnar nerve compression syndromes. The first patient achieved rapid recovery by early nerve decompression surgery, while the second patient had no recovery at 2-3 mo after injury and had more severe symptoms. At 10 wk after injury, the second patient agreed to nerve decompression surgery. The second patient finally achieved a successful outcome after nerve decompression and neurolysis, although she still has residual symptoms. CONCLUSION: For patients with ulnar nerve compression syndrome related to acute wrist fracture, if symptoms persist and signs of recovery are not observed, early release is necessary to prevent permanent neurological damage.

Identification of Novel Compounds Enhancing SR-BI mRNA Stability through High-Throughput Screening.

Atherosclerosis is the pathological basis of most cardiovascular diseases. Reverse cholesterol transport (RCT) is a main mechanism of cholesterol homeostasis and involves the direct transport of high-density lipoprotein (HDL) cholesteryl ester by selective cholesterol uptake. Hepatic scavenger receptor class B member 1 (SR-BI) overexpression can effectively promote RCT and reduce atherosclerosis. SR-BI may be an important target for prevention or treatment of atherosclerotic disease. In our study, we inserted human SR-BI mRNA 3' untranslated region (3'UTR) downstream of the luciferase reporter gene, to establish a high-throughput screening model based on stably transfected HepG2 cells and to screen small-molecule compounds that can significantly enhance the mRNA stability of the SR-BI gene. Through multiple screenings of 25 755 compounds, the top five active compounds that have similar structures were obtained, with a positive rate of 0.19%. The five positive compounds could enhance the SR-BI expression and uptake of DiI-HDL in the hepatocyte HepG2. E238B-63 could also effectively extend the half-life of SR-BI mRNA and enhance the SR-BI mRNA and protein level and the uptake of DiI-HDL in hepatocytes in a time-dependent and dose-dependent manner. The structure-activity relationship analysis showed that the structure N-(3-hydroxy-2-pyridyl) carboxamide is possibly the key pharmacophore of the active compound, providing reference for acquiring candidate compounds with better activity. The positive small molecular compounds obtained in this study might become new drug candidates or lead compounds for the treatment of cardiovascular diseases and contribute to the further study of the posttranscriptional regulation mechanism of the SR-BI gene.

The human nephrin Y1139RSL motif is essential for podocyte foot process organization and slit diaphragm formation during glomerular development.

Nephrin is an immunoglobulin-type cell-adhesion molecule with a key role in the glomerular interpodocyte slit diaphragm. Mutations in the nephrin gene are associated with defects in the slit diaphragm, leading to early-onset nephrotic syndrome, typically resistant to treatment. Although the endocytic trafficking of nephrin is essential for the assembly of the slit diaphragm, nephrin's specific endocytic motifs remain unknown. To search for endocytic motifs, here we performed a multisequence alignment of nephrin and identified a canonical YXXØ-type motif, Y1139RSL, in the nephrin cytoplasmic tail, expressed only in primates. Using site-directed mutagenesis, various biochemical methods, single-plane illumination microscopy, a human podocyte line, and a human nephrin-expressing zebrafish model, we found that Y1139RSL is a novel endocytic motif and a structural element for clathrin-mediated nephrin endocytosis that functions as a phosphorylation-sensitive signal. We observed that Y1139RSL motif-mediated endocytosis helps to localize nephrin to specialized plasma membrane domains in podocytes and is essential for normal foot process organization into a functional slit diaphragm between neighboring foot processes in zebrafish. The importance of nephrin Y1139RSL for healthy podocyte development was supported by population-level analyses of genetic variations at this motif, revealing that such variations are very rare, suggesting that mutations in this motif have autosomal-recessive negative effects on kidney health. These findings expand our understanding of the mechanism underlying nephrin endocytosis and may lead to improved diagnostic tools or therapeutic strategies for managing early-onset, treatment-resistant nephrotic syndrome.

A New Pathogenesis of Albuminuria: Role of Transcytosis.

Transcytosis is an important intracellular transport process by which multicellular organisms selectively move cargoes from apical to basolateral membranes without disrupting cellular homeostasis. In kidney, macromolecular components in the serum, such as albumin, low-density lipoprotein and immunoglobulins, pass through the glomerular filtration barrier (GFB) and proximal tubular cells (PTCs) by transcytosis. Protein transcytosis plays a vital role in the pathology of albuminuria, which causes progressive destruction of the GFB structure and function. However, the pathophysiological consequences of protein transcytosis in the kidney remain largely unknown. This article summarizes recent researches on the regulation of albumin transcytosis across the GFB and PTCs in both physiological and pathological conditions. Understanding the mechanism of albumin transcytosis may reveal potential therapeutic targets for prevention or alleviation of the pathological consequences of albuminuria.

Antero-lateral minimally invasive plate osteosynthesis (MIPO) with the radial nerve exploration for extra-articular distal-third diaphyseal fractures of the humerus.

INTRODUCTION: Traditional open reduction and internal fixation (ORIF) of extra-articular distal humerus fractures has a risk of iatrogenic radial nerve injury, extensive soft tissue stripping, and long incision scar. We performed an antero-lateral minimally invasive plate osteosynthesis (MIPO) technique with the radial nerve exploration for distal-third diaphyseal fractures of the humerus and evaluated clinical and radiographic outcomes through this respective study. METHODS: From April 2010 to June 2016, 28 cases of extra-articular distal-third diaphyseal fractures were treated with an antero-lateral MIPO procedure. Patient demographics, Disabilities of the Arm, Shoulder and Hand (DASH) Score, Mayo Elbow Performance (MEP) Score, elbow range of motion, scars and post-operative complications were recorded and analyzed. RESULTS: All fractures were united with a mean time of 3.5 months. One patient exhibited delayed union (3.6%). The mean DASH Score was 6.6, and all patients had excellent or good MEP Score values. The average scar length was 6.8 cm, and the shortest was 4.5 cm. CONCLUSIONS: The MIPO technique via an antero-lateral approach for extra-articular distal-third diaphyseal fractures of the humerus results in satisfactory clinical outcomes. LEVEL OF EVIDENCE: Level IV, case series, treatment study.

Role and Association of Inflammatory and Apoptotic Caspases in Renal Tubulointerstitial Fibrosis.

BACKGROUND/AIMS: Caspases, an evolutionary conserved family of aspartate-specific cystein proteases, play pivotal roles in apoptotic and inflammatory signaling. Thus far, 14 mammalian caspases are identified and categorized into 3 distinct sub-types: inflammatory caspases, apoptotic initiator and apoptotic executioner. Caspase-1 is an inflammatory caspase, while caspase-7 belongs to apoptotic executioner. The roles and association of these two distinct types of caspases in renal tubulointerstitial fibrosis (TIF) have not been well recognized. METHODS: Caspase-1 inhibitor Z-YVAD-FMK and caspase-7 siRNA were used in tubular epithelial cell line NRK-52E (TECs) to test their effects on transforming growth factor-beta1 (TGF-ß1) stimulation. In vivo, Unilateral ureteral obstruction (UUO) animal model was employed in wild-type (WT) and caspase-1 knock out (KO) (caspase-1-/-) mice. RESULTS: In current study, we found that caspase-7 was obviously activated in cultured TECs stimulated by TGF-ß1 and in UUO model of WT mice. While in UUO model of caspase-1 KO mice, the increased caspase-7 activation was suppressed significantly along with reduced trans-differentiation and minimized extracellular matrix (ECM) accumulation, as demonstrated by western blot, Masson trichrome staining and immunohistochemistry. In addition, pharmacological inhibition of caspase-1 dampened caspase-7 activation and TECs' transdifferentiation induced by TGF-ß1 exposure, which was consistent with in vivo study. Notably, caspase-7 gene knock down by specific siRNA abrogated TGF-ß1 driven TECs' trans-differentiation and reduced ECM accumulation. CONCLUSIONS: Our study associated inflammatory and apoptotic caspases in TIF for the first time and we further confirmed that caspase-1 activation is an upstream event of apoptotic caspase-7 induction in TIF triggered by UUO and in TECs mediated by TGF-ß1 induced transdifferentiation.

MAD2B-mediated SnoN downregulation is implicated in fibroblast activation and tubulointerstitial fibrosis.

MAD2B, an anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase ζ, is indispensible for mitotic checkpoint control and DNA repair. Previously, we established that MAD2B is expressed in glomerular and tubulointerstitial compartments and participates in high glucose-induced podocyte injury. However, its role in other renal diseases remains elusive. In the present study, we aim to illustrate the potential role of MAD2B in the pathogenesis of renal fibrosis. By immunofluorescence and Western blotting, we found MAD2B expression is obviously increased in tubulointerstitial fibrosis (TIF) patients and unilateral ureteral obstruction (UUO) mice. It is widely accepted that resident fibroblasts are the major source of collagen-producing myofibroblasts during TIF. Therefore, we evaluated the level of MAD2B in fibroblasts (NRK-49F) exposed to transforming growth factor (TGF)-ß1 by immunoblotting and revealed that MAD2B is upregulated in a time-dependent manner. Intriguingly, SnoN, a transcriptional repressor of the TGF-ß1/Smad signaling pathway, is decreased in TGF-ß1-treated fibroblasts as well as the kidney cortex from TIF patients and UUO mice. Either in vitro or in vivo, local genetic depletion of MAD2B by lentiviral transfection could preserve SnoN abundance and suppress Smad3 phosphorylation, which finally dampens fibroblast activation, ECM accumulation, and alleviates the severity of TIF. However, the ubiquitin ligase APC/C is not involved in the MAD2B-mediated SnoN decline, although this process is ubiquitination dependent. In conclusion, our observation proposes that besides cell cycle management, MAD2B has a profibrotic role during fibroblast activation and TIF by suppressing SnoN expression. Targeting the MAD2B-SnoN pathway is a promising intervention for TIF.

microRNA-185 modulates low density lipoprotein receptor expression as a key posttranscriptional regulator.

OBJECTIVE: Low-density lipoprotein receptor (LDLR) mediates endocytosis of LDL particles and is important in maintaining plasma cholesterol levels, thus its expression is under extensive regulation at multiple levels, including transcriptional and posttranscriptional regulation by transcription factors (TFs) and RNA-binding proteins (RBPs). Here, we identified microRNA-185 (miR-185) as a novel direct posttranscriptional regulator of LDLR and an indirect LDLR modulator through KSRP in hepatic cells. METHODS AND RESULTS: Using quantitative real-time PCR (qPCR), we detected the effect of predicted LDLR-targeting miRNAs and found that overexpression of miR-185 repressed LDLR expression and LDL uptake in HepG2 cells by 62.4 ± 6.0% (p = 7.0 × 10(-5)) and 32.5 ± 6.0% (p = 7.7 × 10(-4)) respectively, through directly targeting LDLR 3'UTR. Unexpectedly, the antisense inhibitor of miR-185 had similar repression effect on LDLR although it reduced the association of endogenous miR-185 with LDLR mRNA. Further experiments revealed that KH-type splicing regulatory protein (KSRP), one of the LDLR-destabilizing RBPs, is also a target of miR-185. KSRP silencing reversed the repression effects of miR-185-inhibitor on LDLR. Thus miR-185 regulates LDLR expression not only through directly targeting but also by a RBP-involved indirect pathway. Finally, the in vivo results showed that miR-185-inhibitor upregulated hepatic LDLR expression and correlated with a decrease in plasma cholesterol level and arterial plaque area in ApoE KO mice. CONCLUSIONS: These findings reveal that miR-185 controls cholesterol homeostasis as a key posttranscriptional LDLR modulator in hepatic cells, providing novel insight into the regulatory mechanism for LDLR expression and the anti-atherosclerosis effect of miR-185-inhibitor.

Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria.

BACKGROUND/AIMS: We previously showed that urine and serum Angiopoietin-2 (Ang-2) levels increased significantly with the degree of albuminuria in diabetes patients, but the reasons remain unclear. Consequently we aimed to determine whether there was an association between Ang-2, inflammatory cytokines (TNF-α and IL-18) and reactive oxygen species (8-OHdG and SOD) in type 2 diabetes patients with albuminuria. METHODS: This retrospective study evaluated 113 patients with type 2 diabetes and normoalbuminuria, microalbuminuria, or macroalbuminuria and 30 healthy controls. Serum and urine TNF-α, IL-18 and 8-OHdG levels were measured by ELISA. Superoxide dismutase (SOD) activity was determined by spectrophotometry. RESULTS: Serum and urine TNF-α, IL-18 and 8-OHdG levels increased significantly with the degree of albuminuria, and were positively correlated with increased Ang-2. In contrast, SOD activity decreased with the degree of albuminuria and was negatively correlated with Ang-2. Multivariable linear regression analysis revealed that serum Ang-2 level was independently associated with serum levels of TNF-α (P<0.001), 8-OHdG (P=0.001), and IL-18 (P=0.003). Urinary Ang-2 level was independently associated with urinary TNF-α (P<0.001) and 8-OHdG (P=0.004) levels. CONCLUSION: TNF-α and 8-OHdG are associated with elevated urinary Angiopoietin-2 levels in type 2 diabetic patients with albuminuria.

Pure sensory Guillain-Barré syndrome: A case report and review of the literature.

Sensory Guillain-Barré syndrome (GBS) is an acute demyelinating neuropathy that presents clinically with involvement of the sensory peripheral nerve only. To date, <10 cases of pure sensory GBS have been reported; thus, the clinical and pathological features of sensory variant GBS are yet to be well characterized. The current study reports the case of a 43-year-old female that presented with acute, symmetric and monophasic sensory neuropathy, without motor weakness. Patient history, clinical examination, routine nerve conduction studies and sural nerve biopsy were reviewed. All the observations were consistent with a diagnosis of pure sensory GBS. In particular, the pathological features of the sural nerve biopsy revealed that the form of regenerated nerve fibers have complete structure of myelinated nerve fascicles, and these myelinated nerve fibers are thicker than other parts of the biopsy. The patient received small-dose (20 mg/day) prednisone initially, but without any benefit. Satisfactory improvements were observed with one course of intravenous immunoglobulin.

Dorsal root ganglion-derived Schwann cells combined with poly(lactic-co-glycolic acid)/chitosan conduits for the repair of sciatic nerve defects in rats.

Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and purification of Schwann cells are complicated by contamination with fibroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly purified Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells (> 95%) using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly(lactic-co-glycolic acid)/chitosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were significantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental findings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly(lactic-co-glycolic acid)/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.

MicroRNAs 185, 96, and 223 repress selective high-density lipoprotein cholesterol uptake through posttranscriptional inhibition.

Hepatic scavenger receptor class B type I (SR-BI) plays an important role in selective high-density lipoprotein cholesterol (HDL-C) uptake, which is a pivotal step of reverse cholesterol transport. In this study, the potential involvement of microRNAs (miRNAs) in posttranscriptional regulation of hepatic SR-BI and selective HDL-C uptake was investigated. The level of SR-BI expression was repressed by miRNA 185 (miR-185), miR-96, and miR-223, while the uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-HDL was decreased by 31.9% (P < 0.001), 23.9% (P < 0.05), and 15.4% (P < 0.05), respectively, in HepG2 cells. The inhibition of these miRNAs by their anti-miRNAs had opposite effects in these hepatic cells. The critical effect of miR-185 was further validated by the loss of regulation in constructs with mutated miR-185 target sites. In addition, these miRNAs directly targeted the 3' untranslated region (UTR) of SR-BI with a coordinated effect. Interestingly, the decrease of miR-96 and miR-185 coincided with the increase of SR-BI in the livers of ApoE KO mice on a high-fat diet. These data suggest that miR-185, miR-96, and miR-223 may repress selective HDL-C uptake through the inhibition of SR-BI in human hepatic cells, implying a novel mode of regulation of hepatic SR-BI and an important role of miRNAs in modulating cholesterol metabolism.