Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis.

Diabetic nephropathy (DN) is one of the common microvascular complications in diabetic patients. Marrow mesenchymal stem cells (MSCs) have attracted attention in DN therapy but the underlying mechanism remains unclear. Here, we show that MSC administration alleviates high glucose (HG)-induced human kidney tubular epithelial cell (HK-2 cell) injury and ameliorates renal injury in DN mice. We identify that Smad2/3 is responsible for MSCs-regulated DN progression. The activity of Smad2/3 was predominantly upregulated in HG-induced HK-2 cell and DN mice and suppressed with MSC administration. Activation of Smad2/3 via transforming growth factor-ß1 (TGF-ß1) administration abrogates the protective effect of MSCs on HG-induced HK-2 cell injury and renal injury of DN mice. Smad2/3 has been reported to interact with methyltransferase of N6-methyladenosine (m6A) complex and we found a methyltransferase, Wilms' tumor 1-associating protein (WTAP), is involved in MSCs-Smad2/3-regulated DN development. Moreover, WTAP overexpression abrogates the improvement of MSCs on HG-induced HK-2 cell injury and renal injury of DN mice. Subsequently, α-enolase (ENO1) is the downstream target of WTAP-mediated m6A modification and contributes to the MSCs-mediated regulation. Collectively, these findings reveal a molecular mechanism in DN progression and indicate that Smad2/3/WTAP/ENO1 may present a target for MSCs-mediated DN therapy.

A Superparamagnetic Composite Hydrogel Scaffold as In Vivo Dynamic Monitorable Theranostic Platform for Osteoarthritis Regeneration.

Osteoarthritis (OA) is a prevalent disease, characterized by subchondral fractures in its initial stages, which has no precise and specific treatment now. Here, a novel multifunctional scaffold is synthesized by photopolymerizing glycidyl methacrylate-modified hyaluronic acid (GMHA) as the matrix in the presence of hollow porous magnetic microspheres based on hydroxyapatite. In vivo subchondral bone repairing results demonstrate that the scaffold's meticulous design has most suitable properties for subchondral bone repair. The porous structure of inorganic particles within the scaffold facilitates efficient transport of loaded exogenous vascular endothelial growth factor (VEGF). The Fe3O4 nanoparticles assembled in microspheres promote the osteogenic differentiation of bone marrow mesenchymal stem cells and accelerate the new bone generation. These features enable the scaffold to exhibit favorable subchondral bone repair properties and attain high cartilage repair scores. The therapy results prove that the subchondral bone support considerably influences the upper cartilage repair process. Furthermore, magnetic resonance imaging monitoring demonstrates that Fe3O4 nanoparticles, which are gradually replaced by new bone during osteochondral defect repair, allow a noninvasive and radiation-free assessment to track the newborn bone during the OA repair process. The composite hydrogel scaffold (CHS) provides a versatile platform for biomedical applications in OA treatment.

The avBNSTGABA-VTA and avBNSTGABA-DRN pathways are respectively involved in the regulation of anxiety-like behaviors in parkinsonian rats.

The anteroventral bed nucleus of stria terminalis (avBNST) is a key brain region which involves negative emotional states, such as anxiety. The most neurons in the avBNST are GABAergic, and it sends GABAergic projections to the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN), respectively. The VTA and DRN contain dopaminergic and serotonergic cell groups in the midbrain which regulate anxiety-like behaviors. However, it is unclear the role of GABAergic projections from the avBNST to the VTA and the DRN in the regulation of anxiety-like behaviors, particularly in Parkinson's disease (PD)-related anxiety. In the present study, unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, and decreased level of dopamine (DA) in the basolateral amygdala (BLA). Chemogenetic activation of avBNSTGABA-VTA or avBNSTGABA-DRN pathway induced anxiety-like behaviors and decreased DA or 5-HT release in the BLA in sham and 6-OHDA rats, while inhibition of avBNSTGABA-VTA or avBNSTGABA-DRN pathway produced anxiolytic-like effects and increased level of DA or 5-HT in the BLA. These findings suggest that avBNST inhibitory projections directly regulate dopaminergic neurons in the VTA and serotonergic neurons in the DRN, and the avBNSTGABA-VTA and avBNSTGABA-DRN pathways respectively exert impacts on PD-related anxiety-like behaviors.

Transcranial direct current stimulation of the prefrontal cortex improves depression-like behaviors in rats with Parkinson's disease.

Depression associated with Parkinson's disease (PD) seriously affects patients, and there is a lack of effective treatments. Transcranial direct current stimulation (tDCS) is increasingly used as a new non-invasive neuromodulation technique in the treatment of neuropsychiatric diseases. However, there is a paucity of research on tDCS for PD-related depression. Our study used PD model rats established with unilateral destruction of the medial forebrain bundle (MFB) to observe the modulatory effects of tDCS acting on the mPFC on depression-like behaviors. We found that tDCS acting on the mPFC improved depression-like behaviors in PD model rats by increasing sucrose intake in sucrose preference test (n = 7-10 rats/group) and shortening immobility time in forced swimming test (n = 7-8 rats/group). Meanwhile, tDCS decreased the expression of c-Fos protein (n = 8-11 rats/group) and the excitation of glutamatergic neurons (n = 6-8 rats/group) in the PrL and LHb of PD model rats. Western blots showed that tDCS decreased the overexpression of serine 845 phosphorylation site of AMPA receptor GluR1 (p-GluR1-S845) in the PrL and LHb of PD model rats (n = 8-11 rats/group), and the overexpression of p-GluR1-S831 in the LHb (n = 8-11 rats/group). The results of this study show that tDCS acting on the mPFC helps to improve PD-related depression, which involves the modulation of excitability and AMPA receptor phosphorylation on the PrL and LHb neurons.

Long-term intermittent theta burst stimulation enhanced hippocampus-dependent memory by regulating hippocampal theta oscillation and neurotransmitter levels in healthy rats.

Intermittent theta burst stimulation (iTBS), an updated pattern of high-frequency repetitive transcranial magnetic stimulation, is a potential candidate for improving memory. The hippocampus has been shown to be involved in the memory-enhancing effect induced by iTBS. However, it remains largely unknown whether this effect is achieved by regulating hippocampal theta oscillation and neurotransmitters gamma-aminobutyric acid (GABA) and glutamate, which are strongly related to memory. Thus, we investigated the effect of 14 days of iTBS on hippocampus-dependent memory and further explored the roles of hippocampal theta oscillation and neurotransmitters GABA and glutamate in this effect. We found that compared to sham iTBS, real iTBS enhanced hippocampus-dependent memory measured by hole-board test and object place recognition test. Further, real iTBS increased the density of c-Fos positive neurons and normalized power of theta oscillation in the dorsal hippocampus (dHip) compared to sham iTBS. Interestingly, we observed a decrease in the level of extracellular GABA and an increase in the level of extracellular glutamate in the dHip after real iTBS. Our results suggest that long-term iTBS improved hippocampus-dependent memory, which may be attributed to the enhancement of theta oscillation and altered levels of extracellular GABA and glutamate in the dHip.

Flatband polaritonic router in twisted bilayer van der Waals materials.

In recent years, van der Waals (vdW) polaritons excited by the hybrid of matter and photons have shown great promise for applications in nanoimaging, biosensing, and on-chip light guiding. In particular, polaritons with a flatband dispersion allow for mode canalization and diffractionless propagation, which showcase advantages for on-chip technologies requiring long-range transportation of optical information. Here, we propose a flatband polaritonic router based on twisted α-MoO3 bilayers, which allows for on-chip routing of highly confined and low-loss phonon polaritons (PhPs) along multichannel propagating paths under different circular polarized dipole excitations. Our work combines flatband physics and optical spin- orbit coupling, with potential applications in nanoscale light propagation, on-chip optical switching, and communication.

Dose and time-dependence of acute intermittent theta-burst stimulation on hippocampus-dependent memory in parkinsonian rats.

Background: The treatment options for cognitive impairments in Parkinson's disease (PD) are limited. Repetitive transcranial magnetic stimulation has been applied in various neurological diseases. However, the effect of intermittent theta-burst stimulation (iTBS) as a more developed repetitive transcranial magnetic stimulation paradigm on cognitive dysfunction in PD remains largely unclear. Objective: Our aim was to explore the effect of acute iTBS on hippocampus-dependent memory in PD and the mechanism underlying it. Methods: Different blocks of iTBS protocols were applied to unilateral 6-hydroxidopamine-induced parkinsonian rats followed by the behavioral, electrophysiological and immunohistochemical analyses. The object-place recognition and hole-board test were used to assess hippocampus-dependent memory. Results: Sham-iTBS and 1 block-iTBS (300 stimuli) didn't alter hippocampus-dependent memory, hippocampal theta rhythm and the density of c-Fos- and parvalbumin-positive neurons in the hippocampus and medial septum. 3 block-iTBS (900 stimuli) alleviated 6-hydroxidopamine-induced memory impairments, and increased the density of hippocampal c-Fos-positive neurons at 80 min post-stimulation but not 30 min compared to sham-iTBS. Interestingly, 3 block-iTBS first decreased and then increased normalized theta power during a period of 2 h following stimulation. Moreover, 3 block-iTBS decreased the density of parvalbumin-positive neurons in the medial septum at 30 min post-stimulation compared to sham-iTBS. Conclusion: The results indicate that multiple blocks of iTBS elicit dose and time-dependent effects on hippocampus-dependent memory in PD, which may be attributed to changes in c-Fos expression and the power of theta rhythm in the hippocampus.

Intestinal prolapse and exposure after peritoneal dialysis in low-birth-weight preterm infants with acute renal failure: a case report.

Background: The mortality rate of acute kidney injury (AKI) in low-birth-weight premature infants with acute renal failure is extremely high. Since small hemodialysis catheters do not exist, peritoneal dialysis (PD) is the most suitable dialysis method. At present, only a few studies have reported cases of PD in low-birth-weight newborns. Case Description: On September 8, 2021, a 10-day-old, low-birth-weight preterm infant, who presented with neonatal respiratory distress syndrome and acute renal failure, was admitted to the Second Affiliated Hospital of Kunming Medical University, China. The patient was the elder of twins and had experienced acute renal failure, hyperkalemia, and anuria following the onset of respiratory distress syndrome. During the initial PD catheterization operation, a double Tenckhoff adult PD catheter cut short by 2 cm was used, with the inner cuff placed in the skin. However, the surgical incision was relatively large, and PD fluid leakage occurred. Later, the incision tore, and the intestines prolapsed when the patient cried. The intestines were returned to the abdominal cavity in an emergency operation, and the PD catheter was placed again. This time, the inner Tenckhoff cuff was placed outside the skin, and PD fluid leakage did not reoccur. However, the patient also experienced a decrease in heart rate and blood pressure, as well as severe pneumonia and peritonitis. Following an active rescue, the patient recovered well. Conclusions: The PD method effectively treats low-birth-weight preterm neonates with AKI. An adult Tenckhoff catheter was shortened by 2 cm and successfully used in the PD treatment of a low-birth-weight preterm infant. However, the catheter placement should be outside the skin, and the incision should be as small as possible to avoid leakage and incision tears.

Oxidative stress-related patterns determination for establishment of prognostic models, and characteristics of tumor microenvironment infiltration.

Oxidative stress-mediated excessive accumulation of ROS in the body destroys cell homeostasis and participates in various diseases. However, the relationship between oxidative stress-related genes (ORGs) and tumor microenvironment (TME) in gastric cancer remains poorly understood. For improving the treatment strategy of GC, it is necessary to explore the relationship among them. We describe the changes of ORGs in 732 gastric cancer samples from two data sets. The two different molecular subtypes revealed that the changes of ORGs were associated with clinical features, prognosis, and TME. Subsequently, the OE_score was related to RFS, as confirmed by the correlation between OE_score and TME, TMB, MSI, immunotherapy, stem cell analysis, chemotherapeutic drugs, etc. OE_score can be used as an independent predictive marker for the treatment and prognosis of gastric cancer. Further, a Norman diagram was established to improve clinical practicability. Our research showed a potential role of ORGs in clinical features, prognosis, and tumor microenvironment of gastric cancer. Our research findings broaden the understanding of gastric cancer ORGs as a potential target for individualized treatment of gastric cancer and a new direction to evaluate the prognosis.

Comprehensive Diagnostics of Diabetic Nephropathy by Transcriptome RNA Sequencing.

Background: Diabetic nephropathy (DN) is a primary driver of end-stage renal disease. Given the heterogeneity of renal lesions and the complex mechanisms of DN, the present-day diagnostic approach remains highly controversial. We aimed to design a diagnostic model by bioinformatics methods for discriminating DN patients from normal subjects. Methods: In this study, transcriptome sequencing was performed on 6 clinical samples (3 from DN patients and 3 from healthy volunteers) from the Second Affiliated Hospital of Kunming Medical University. Construction of a competing endogenous RNA (ceRNA) network based on differentially expressed (DE)-mRNAs and -long noncoding RNAs (lncRNAs). Subsequently, the CytoHubba plugin was used to identify hub genes from DE-mRNAs in the ceRNA network and to perform functional enrichment analysis on them. The least absolute shrinkage and selection operator (LASSO) regression analysis was responsible for screening the diagnostic biomarkers from hub genes and assessing their diagnostic power using ROC curves. The pathways involved in hub genes were revealed by single-gene Gene Set Enrichment Analysis (GSEA). Moreover, we verified the expression levels of diagnostic biomarkers by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results: A total of 10 hub genes were screened from the ceRNA network, which appeared to be associated with the viral infection, kidney development, and regulation of immune and inflammatory responses. Subsequently, LASSO regression analysis established a diagnostic model consisting of DDX58, SAMD9L, and TLR6 with a robust diagnostic potency (AUC = 1). Similarly, single-gene GSEA showed a strong association of these diagnostic biomarkers with the viral infection. Furthermore, PCR and Western blot demonstrated showed that DDX58, SAMD9L, and TLR6 were upregulated in DN patients at both transcriptome and protein levels compared to healthy controls. Conclusion: We confirmed that differentially expressed hub genes may be novel diagnostic biomarkers in DN.

A bioinformatics analysis of the contribution of m6A methylation to the occurrence of diabetes mellitus.

N6-methyladenosine (m6A) methylation has been reported to play a role in type 2 diabetes (T2D). However, the key component of m6A methylation has not been well explored in T2D. This study investigates the biological role and the underlying mechanism of m6A methylation genes in T2D. The Gene Expression Omnibus (GEO) database combined with the m6A methylation and transcriptome data of T2D patients were used to identify m6A methylation differentially expressed genes (mMDEGs). Ingenuity pathway analysis (IPA) was used to predict T2D-related differentially expressed genes (DEGs). Gene ontology (GO) term enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions of mMDEGs. Gene set enrichment analysis (GSEA) was performed to further confirm the functional enrichment of mMDEGs and determine candidate hub genes. The least absolute shrinkage and selection operator (LASSO) regression analysis was carried out to screen for the best predictors of T2D, and RT-PCR and Western blot were used to verify the expression of the predictors. A total of 194 overlapping mMDEGs were detected. GO, KEGG, and GSEA analysis showed that mMDEGs were enriched in T2D and insulin signaling pathways, where the insulin gene (INS), the type 2 membranal glycoprotein gene (MAFA), and hexokinase 2 (HK2) gene were found. The LASSO regression analysis of candidate hub genes showed that the INS gene could be invoked as a predictive hub gene for T2D. INS, MAFA,and HK2 genes participate in the T2D disease process, but INS can better predict the occurrence of T2D.

Diminution of microRNA-98 alleviates renal fibrosis in diabetic nephropathy by elevating Nedd4L and inactivating TGF-ß/Smad2/3 pathway.

MicroRNAs (miRNAs) have already been documented to function in diabetic nephropathy (DN), yet little research has focused on the role of miR-98 in this disease. Here, we discuss the mechanism of miR-98 on the renal fibrosis in DN. Recombinant adeno-associated virus carrying miR-98 inhibitor or Nedd4L overexpression plasmid was injected into DN modeled rats to explore their roles in DN. Renal tubular epithelial cell injury models (NRK-52E cells) were induced by high glucose (HG). HG-treated NRK-52E cells were transfected with miR-98 inhibitor or Nedd4L overexpression plasmid for further verification. MiR-98 was upregulated, Nedd4L was downregulated and TGF-ß/Smad2/3 signaling was activated in kidney tissues of DN rats and HG-treated NRK-52E cells. miR-98 targeted Nedd4L mRNA 3'UTR. MiR-98 depletion and Nedd4L overexpression inactivated TGF-ß/Smad2/3 signaling pathway, alleviated pathological damage and fibrosis, ameliorated inflammation, and depressed cell apoptosis of kidney tissues of DN rats. MiR-98 depletion and Nedd4L overexpression inactivated TGF-ß/Smad2/3 signaling pathway, strengthened viability, and limited apoptosis of HG-treated renal tubular epithelial cells. Nedd4L overexpression reversed the effect of up-regulating miR-98 on DN rats and HG-treated renal tubular epithelial cells. Altogether, we find that miR-98 is upregulated in kidney tissues of DN rats, and miR-98 diminution and Nedd4L elevation attenuate renal fibrosis through inactivation of the TGF-ß/Smad2/3 pathway, which provides a novel therapy for DN.

Propagation properties of partially coherent modified Bessel-Gauss beams through the gradient-index medium.

Based on the ABCD matrix method and Collins diffraction integral formula, the general analytical expression for the partially coherent modified Bessel-Gauss beam propagating in a gradient-index medium is derived. The propagation trajectory, intensity, and phase distribution of such a beam are numerically investigated. The effects of the topological charge, the coherence parameter, and the coefficient of the gradient refractive index on propagation properties are considered. Results show that the propagation trajectory of such beam focuses and diverges periodically, which is different from free-space propagation. The period of intensity distribution is consistent with that of phase distribution under different cases. As propagation distance increases, the dark core always exists and the phase singularities remain stable and do not split. The dark core can be modulated by topological charge and coherence parameter, and the periodical distance can be modulated by the coefficient of the gradient refractive index. These results will help to explore such beams and find applications in optical communication and optical trapping.

Properties of a Tightly Focused Circularly Polarized Anomalous Vortex Beam and Its Optical Forces on Trapped Nanoparticles.

The characteristics of a circularly polarized anomalous vortex beam (CPAVB), focused by an objective lens with a high numerical aperture (NA), are studied analytically and theoretically. It shows that the topological charge can affect the beam profile significantly and a flat-topped (FT) beam can be obtained by modulating the NA and topological charge. It is interesting to find that spin-to-orbital angular momentum conversion can occur in the longitudinal component after tight focusing. Furthermore, optical forces of the tightly focused CPAVB on nanoparticles are analyzed in detail. It can be expected to trap two kinds of nanoparticles using such beam near the focus.

Mesenchymal Stem Cells Reverse Diabetic Nephropathy Disease via Lipoxin A4 by Targeting Transforming Growth Factor ß (TGF-ß)/smad Pathway and Pro-Inflammatory Cytokines.

BACKGROUND Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Mesenchymal stem cells (MSCs) treatment has been proved to be effective in DN models by protecting renal function and preventing fibrosis. However, the underlying mechanism is unclear. Previous research indicated diabetes and associated complications may be attributed to failed resolution of inflammation, which is deliberately regulated by pro-resolving lipids, including lipoxins (LXs), resolvins (Rv) D and E series, protectins, and maresins. In this study, we monitored pro-resolving mediators in a DN model to explore the mechanism of MSCs treatment. MATERIAL AND METHODS The DN model was induced by STZ injection in SD rats. UPLC-MS/MS was performed to determine pro-resolving lipids in kidney tissue and serum of DN model before and after MSCs treatment, as well as in supernatants of HBZY-1-MSCs co-culture. RESULTS LXA4 was highly accumulated in renal tissue of DN rats with MSCs treatment; ex vivo, LXA4 was significantly increased in the supernatants of HBZY-1 cells co-cultured with MSCs in a high-glucose (HG) medium. Western blot analysis indicated that ALX/FPR2, the receptor of LXA4, was markedly expressed in renal tissue of the DN-MSC group and HBZY-1 after incubating with MSCs in HG. Intraperitoneal injection of LXA4 inhibited renal fibrosis by targeting TGF-ß/Smad signaling and downregulated serum TNF-alpha, IL-6, IL-8, and IFN-γ in DN rats. Notably, all the protective effects induced by MSCs or LXA4 were abolished by ALX/FRP2 blocking. CONCLUSIONS Our results demonstrate that MSCs intervention prevented DN procession via the LXA4-ALX/FPR2 axis, which inhibited glomerulosclerosis and pro-inflammatory cytokines, eventually contributing to kidney homeostasis.

The BVAS is an independent predictor of cardiovascular events and cardiovascular disease-related mortality in patients with ANCA-associated vasculitis: A study of 504 cases in a single Chinese center.

BACKGROUND: Cardiovascular diseases (CVD) are the major causes of death in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) during long-term follow-up. This study investigated risk factors for cardiovascular events (CVE) and CVD-related mortality in Chinese AAV patients. METHODS: Five hundred and four AAV patients in our center were retrospectively included. The predictive value of variables associated with CVE- and CVD-related mortality were analyzed. RESULTS: During follow-up of a median duration of 38 (range 1-228) months, 117 out of 504 patients had CVE. Independent predictors of CVE were age [increase by 10 years, hazard ratio (HR) 1.436, 95% confidence interval (CI) 1.187-1.736, p = 0.000], systolic blood pressure (increase by 10mmHg, HR = 1.171, 95% CI: 1.038-1.321, p = 0.010), estimated glomerular filtration rate (eGFR) (increase by 1mL/min/1.73m2, HR = 0.992, 95% CI: 0.984-0.999, p = 0.020), high-density lipoprotein level (HR = 0.530, 95% CI: 0.303-0.926, p = 0.026) and the Birmingham Vasculitis Activity Score (BVAS) (HR = 1.039, 95% CI: 1.011-1.067, p = 0.006). Forty-one patients died from CVD. Independent predictors of CVD-related mortality were age (increase by 10 years; HR = 1.732, 95% CI: 1.237-2.426, p = 0.001), eGFR (increase by 1mL/min/1.73m2, HR = 0.984, 95% CI: 0.970-0.997, p = 0.016), pre-existing CV disease (HR = 2.872, 95% CI: 1.503-5.487, p = 0.001) and BVAS (HR = 1.064, 95% CI: 1.018-1.113, p = 0.006). We further analyzed CVE- and CVD-related mortality after 2 years since diagnosis, and found BVAS were still an independent predictor of CVE- and CVD-related mortality. CONCLUSION: Besides the traditional risk factors, BVAS at presentation was an independent predictor of CVE- and CVD-related mortality in patients with AAV.

Clinical observation of umbilical cord mesenchymal stem cell transplantation for treating patients receiving peritoneal dialysis.

BACKGROUND: This study aims to observe the outcome and safety of umbilical cord-mesenchymal stem cell (UC-MSC) treatment for continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: A total of 24 CAPD patients, who underwent UC-MSC treatment from June 2011 to December 2012, were selected for this study. These patients were followed up until June 2015. RESULTS: Results revealed a significant increase in hemoglobin, erythropoietin and albumin levels, a decrease in C-reactive protein levels, and marked improvement in cystatin C and urine volume within three months after UC-MSC transplantation; and the difference was statistically significant (P<0.05). However, the difference in residual glomerular filtration rate, serum creatinine, peritoneal KT/V and remnant kidney KT/V was not statistically significant (P>0.05). CONCLUSIONS: Clinical indicators of patients with CAPD can be partially improved through UC-MSC treatment.

Influence of mesenchymal stem cells on expression of AQP1 and AQP2 in rats with nephropathy induced by adriamycin.

This study aims to explore the therapeutic effect of bone marrow mesenchymal stem cells on adriamycin nephrosis, and the potential mechanism. The rat experimental nephropathy model was established by unilateral nephrectomy combined repeated injecting adriamycin (ADR). Thirty adriamycin nephrosis rats were randomly divided into three groups, including ADR (n=10), MSCs transplantation through peripheral veins groups (M-V, n=10), and MSCs transplantation through right renal artery groups (M-A, n=10), and there was another normal control group (N, n=10). This study lasted 8 weeks, 24 hours urine was collected through simple metabolic cage to measure urinary volume and urine protein quantitation in 24 hours. The levels of plasma albumin (ALB), sodium were measured by biochemical analysis. The expressions of AQP1-2 were measured by immuno-histochemistry assay. Kidney medulla ultramicroscopic structure was observed by TEM. The results indicated that the ALB and 24 h urinary volume have significant increased in M-V and M-A group compared to the ADR group (P<0.05). Furthermore, the serum sodium and urine protein quantitation in 24 hours were decreased in M-V and M-A group compared to ADR group (P<0.05). Protein expression of AQP1-2 had been remarkably decreased (P<0.05). It showed degenerative changes of kidney ultra microscopic structures of the ADR rats, while MSCs transplantation could significantly improve the damage. In conclusion, in adriamycin nephropathy rats, MSCs transplantation exerts its therapeutic effects by decrease urinary albumin excretion, increase ALB, decrease sodium and the expression of AQP1-2 in renal tubules.

SiRNA-HMGA2 weakened AGEs-induced epithelial-to-mesenchymal transition in tubular epithelial cells.

Diabetic nephropathy as the most common cause of end-stage renal disease accounts for a significant increase in morbidity and mortality in patients. Epithelial to mesenchymal transition (EMT) of tubular cells is associated with diabetic nephropathy. Advanced glycation end products (AGEs) are thought to be involved in the pathogenesis of diabetic nephropathy via multifactorial mechanisms. However, whether AGEs could induce EMT in Tubular epithelial cells is still unknown. In this study, we found that AGEs induced EMT and accompanied by reduced expression of the epithelial markers E-cadherin and enhanced expression of the mesenchymal markers vimentin and alpha-smooth muscle actin. Furthermore, the expression of HMGA2 was upregulated by AGEs. Far more interesting, its knockdown by short interfering RNA (siRNA) effectively reversed AGEs-induced EMT. Meanwhile, we also found that knockdown of HMGA2 inhibited high AGEs-induced generation of reactive oxygen species (ROS) and the activation of p38 MAPK. Collectively, these studies suggest that HMGA2 plays a important role in EMT during Diabetic nephropathy and more study toward HMGA2 should be played in renal pathogenesis.