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Obstructive renal fibrosis is the consequence of abnormal extracellular matrix assembly, which eventually results in renal failure, acute, and end‑stage renal infection. MicroRNAs (miRNAs), a particular category of small RNAs, modulate the expression of genes post-transcriptionally and regulate biological activities, including fibrogenesis. The study probed to estimate the key functions of miR-4709-3p in obstructive renal fibrosis. This investigation used TGF-β1 stimulated HK-2 in-vitro model, unilateral ureteral occlusion (UUO) mice model, and human Diabetic nephropathy (DN) and Renal interstitial fibrosis (RIF) specimens to depict the abundance of the miR-4709-3p level using FISH and RT-qPCR. MiR-4709-3p mimics and inhibitors were utilized to evaluate the functions of miR-4709-3p in-vitro. Luciferase assay was exploited to verify miR-4709-3p and LATS2 3ʹUTR binding. Finally, to depict the functions of miR-4709-3p in-vivo, the UUO model was injected with miR-4709-3p inhibitors. Results exhibited the upregulation of miR-4709-3p in UUO-induced in-vivo model, TGF-β1 stimulated HK-2, and human RIF and DN samples. Moreover, it was determined that modulating miR-4709-3p regulated the level of fibrosis markers. Luciferase assay miR-4709-3p modulates renal fibrosis by targeting LATS2. Finally, it was found that miR-4709-3p regulates obstructive renal fibrosis through the Hippo signaling pathway. Overall, the study concludes that aberrant miR-4709-3p expression plays an essential function in the renal fibrosis progression, and miR-4709-3p overexpression could advance obstructive renal fibrosis via LATS2 targeting in Hippo signaling pathway. Therefore, miR-4709-3p inhibition may be a potential renal fibrosis therapy target.

Background Kidney damage often develops into renal fibrosis. Apoptosis and inflammatory response are the main factors driving the process of renal fibrosis. Here we showed that lncRNA XIST/ miR-19b / SOX6 signal axis regulated apoptosis and inflammation of renal fibrosis. Methods HK-2 cells were treated with TGF-β1 to construct cell fibrosis model, and UUO surgery was performed to construct mouse renal fibrosis model. The expression of XIST, miR-19b and SOX6 were examined by qPCR. And levels of fibrosis-related proteins were detected by western blotting. Levels of IL-1β and TNF-α were assessed by qPCR and ELISA, respectively. Renal pathology and fibrosis were evaluated by HE and Masson staining. Flow cytometry and TUNEL staining were employed to evaluate cell apoptosis in cell fibrosis model and mouse renal fibrosis model, respectively. Besides, dual luciferase reporter assay was employed to verify whether XIST had a binding site to miR-19b, and whether miR-19b had a binding site to SOX6. Results Here we showed that XIST and SOX6 were upregulated in both HK-2 cells treatment of TGF-β1 and kidneys of UUO mice, while miR-19b was downregulated. Dual luciferase reporter assay displayed that XIST directly bound to miR-19b, and SOX6 was the target of miR-19b. Knockdown of XIST inhibited apoptosis, inflammation and fibrosis in HK-2 cells treatment of TGF-β1 via miR-19b-mediated downregulation of SOX6, while inhibition of miR-19b reversed the effect. Similarly, knockdown of XIST in vivo inhibited apoptosis, inflammation and fibrosis in kidneys of UUO mice via miR-19b-mediated downregulation of SOX6. Discussion These results provided evidence that knockdown of XIST inhibited apoptosis and inflammation of renal fibrosis via miR-19b-mediated downregulation of SOX6.

Renal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis is a form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It is currently unknown whether ferroptosis is initiated during unilateral ureteral obstruction (UUO)-induced renal fibrosis and its role has not been determined. In this study, we demonstrated that ureteral obstruction induced ferroptosis in renal tubular epithelial cells (TECs) in vivo. The ferroptosis inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, cell death, lipid peroxidation, and inhibited the downregulation of GPX4 expression induced by UUO, ultimately inhibiting ferroptosis in TECs. We found that Lip-1 significantly attenuated UUO-induced morphological and pathological changes and collagen deposition of renal fibrosis in mice. In addition, Lip-1 attenuated the expression of profibrotic factors in the UUO model. In vitro, we used RSL3 treatment and knocked down of GPX4 level by RNAi in HK2 cells to induce ferroptosis. Our results indicated HK2 cells secreted various profibrotic factors during ferroptosis. Lip-1 was able to inhibit ferroptosis and thereby inhibit the secretion of the profibrotic factors during the process. Incubation of kidney fibroblasts with culture medium from RSL3-induced HK2 cells promoted fibroblast proliferation and activation, whereas Lip-1 impeded the profibrotic effects. Our study found that Lip-1 may relieve renal fibrosis by inhibiting ferroptosis in TECs. Mechanistically, Lip-1 could reduce the activation of surrounding fibroblasts by inhibiting the paracrine of profibrotic factors in HK2 cells. Lip-1 may potentially be used as a therapeutic approach for the treatment of UUO-induced renal fibrosis.

Pericarpium Citri Reticulatae (PCR) is used in food and medical herbal formula, and its quality is determined by its age. Raman spectroscopy is a laser technology for molecular fingerprinting. The feasibility of using surface-enhanced Raman spectroscopy (SERS) to determine the PCR age was investigated. The Raman peaks were acquired using a Raman spectrometer with a 785 nm diode laser and were analyzed using principal component analysis (PCA) followed by linear discriminant analysis (PCA-LDA). There were six major peaks at 600, 730, 990, 1370, 1607, and 1742 cm

Bladder cancer (BC) is one of the most prevalent and life-threatening cancers among the male population worldwide. Sex determining region Y-box protein 5 (SOX5) plays important roles in a variety of human cancers. However, little research has been conducted on the function and underlying mechanism of SOX5 in BC. In the present study, we first reveal the increased expression of SOX5 in BC tissues and

This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT

BACKGROUND: The pathogenesis of Crohn’s disease (CD) is unknown; however, angiogenesis is known to play an important role in the disease. The present research suggests that microRNA-21 (miR-21) may play a positive regulatory role in disordered angiogenesis in CD. METHODS: C57 wild-type mice were divided into 6 groups. On day 0, all mice in the 2,4,6-trinitrobenzenesulfonic acid (TNBS) group were given an enema at the concentration of TNBS 100 mg/kg mouse body weight (solvent 50% alcohol). In the control group, the enema was performed with 50% alcohol. On day 0, 2, 4, and 6, the mice of the agomir-21 + TNBS group and the agomir control + TNBS group were injected with 200 µL, 5 nmol agomir-21 or agomir control [dissolved in ribonuclease (RNase)-free water] by tail vein injection, while the antagomir-21 + TNBS group and the antagomir control + TNBS group were injected with 200 µL, 20 nmol antagomir-21 or antagomir control (dissolved in RNase-free water). The body weight and disease activity index (DAI) score were recorded daily. The colons were obtained to assess macro and microscopic colon damage. The inferior vena cava and the accompanying abdominal aorta were chosen to detect the protein expression of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT)/vascular endothelial growth factor (VEGF) axis through western blotting. Serum interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The distribution and expression of neovascularization were demonstrated by cluster of differentiation 31 (CD31) immunohistochemistry. RESULTS: Compared with the only-TNBS group, the agomir-21 + TNBS group showed significantly severer colitis symptoms and more abnormal vascular hyperplasia, while the antagomir-21 + TNBS group showed symptom relief and reduced vascular hyperplasia. In addition, agomir-21 obviously inhibited the expression of PTEN and activated the PI3K/AKT/VEGF pathway in mice induced by TNBS, while antagomir-21 effectively antagonized this effect. CONCLUSIONS: miR-21 can promote the progression of colitis in mice induced by TNBS and aggravate the disordered angiogenesis by regulating the PTEN/PI3K/AKT axis. Intravenous injection of miR-21 antagonists can effectively relieve the symptoms of colitis and inhibit colonic angiogenesis.

BACKGROUND: Metabolic reprogramming has been identified as a hallmark of cancer, influencing the immunity in the tumor microenvironment. Because of the high-heterogeneity of cervical carcinoma, we aim to figure out the metabolic subtypes of cervical carcinoma indicating the prognosis. METHODS: We profiled the distinct metabolic signatures using data from transcriptomes obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Bioinformatics analyses were conducted to identify the possible biomarkers of overall survival and chemotherapy resistance. RESULTS: Immune infiltration was closely related to metabolic pathways, especially in the carbohydrate pathway and the lipid and energy pathway. Two distinct clusters of differentially expressed genes were identified. Six genes were selected as possible indicators of prognosis, including ELK3, BIN2, MEI1, CCR7, CYP4F12, and DUOX1, relating to the immune status of tumor microenvironment. Under the risk score model based on metabolic genes, the high-risk group showed significantly lower survival (HR =6.802, with 95% CI: 3.637−12.721, P

Background Acute pyelonephritis (APN), an acute and severe kidney infection, is usually treated with antibiotics. However, APN treatment has become increasingly challenging because of bacterial resistance. Adiponectin, an adipokine, has recently been reported to exhibit profound anti-inflammatory and anti-apoptotic effects. However, the effect of adiponectin on the outcomes of APN treatment remains unclear. In this study, we aimed to investigate the effects of adiponectin on APN and the mechanisms underlying these effects. Methods Wild-type C57 mice and adiponectin-knockout (KO) mice were divided into 6 groups: the wild-type control group, the wild-type model group, the wild-type adiponectin intervention group, the KO control group, the KO model group, and the adiponectin-KO intervention group. We measured white blood cell (WBC) and neutrophil counts (NC) using a multispecies hematology analyzer; tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) using enzyme-linked immunosorbent assay (ELISA); blood urea nitrogen (BUN) and serum creatinine (SCr) levels using colorimetry; and the protein levels of JAK2, STAT3, p-JAK2, p-STAT3, Bcl-2, and Bax in renal tissues using western blot analysis. Apoptotic cells were detected using the transferase-mediated dUTP nick end labelling (TUNEL) assay. Results Compared to the wild-type mice, the KO mice showed a more severe inflammatory response and kidney damage after Escherichia coli infection. After treatment with exogenous adiponectin injection, the inflammatory response, oxidative stress, and kidney damage were partly alleviated. Adiponectin KO led to JAK2/STAT3 signaling activation, and exogenous adiponectin administration inactivated JAK2/STAT3 signaling in the APN model. APN can lead to an increase in the level of the protein Bax and a decrease in the level of the bcl-2 protein, thereby increasing apoptosis; this effect was inhibited by adiponectin. Conclusions Through use of a pyelonephritis mouse model, we demonstrated that adiponectin might alleviate renal cell apoptosis and inflammatory response by inactivating the JAK2/STAT3 signaling pathway.

Renal fibrosis, the ultimate common pathway of progressive nephropathy, is characterized by excess accumulation and deposition of extracellular matrix (ECM) within the renal interstitium and glomeruli, finally resulting in end-stage kidney failure. TGFβ1 is not only abnormally increased during fibrosis but also involved in ECM induction and accumulation. Based on the bioinformative analyses, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and focal adhesion kinase (FAK) signaling pathway might be involved in TGFβ1 functions on renal fibrosis development. In the present study, fibrosis was induced in HK-2 cells using TGFβ1 and PTEN expression was significantly suppressed by 24 or 48 hours TGFβ1 treatment. PTEN overexpression in HK-2 cells improved TGFβ1-induced fibrosis within α-SMA and E-cadherin. According to the KEGG signaling pathway annotation analyses on microarray profiles (GSE23338 and GSE20247) and immunoblotting validation, FAK signaling might be involved in PTEN functions in TGFβ1-induced fibrosis. PTEN overexpression significantly inhibited TGFβ1- or unilateral ureteral obstruction (UUO)-induced FAK signaling pathway activation both in vitro and in vivo; more importantly, PTEN silence enhanced TGFβ1- or UUO-induced fibrosis, while FAK inhibitor PF567721 significantly reversed the effects of PTEN silence, indicating that PTEN exerted its effects on TGFβ1- and UUO-induced fibrotic development in vitro and in vivo via inhibiting FAK signaling pathway. In summary, these findings indicate that PTEN could improve cellular fibrotic changes and renal fibrosis via inhibiting FAK/AKT signaling pathway. Restoring PTEN expression to target FAK/AKT signaling pathway might be a potent strategy for renal fibrosis treatment.

Renal fibrosis (RF) is a pathological process that culminates in terminal renal failure in chronic kidney disease (CKD). Fibrosis contributes to progressive and irreversible decline in renal function. However, the molecular mechanisms involved in RF are complex and remain poorly understood. Long non-coding RNAs (lncRNAs) are a major type of non-coding RNAs, which significantly affect various disease processes, cellular homeostasis, and development through multiple mechanisms. Recent investigations have implicated aberrantly expressed lncRNA in RF development and progression, suggesting that lncRNAs play a crucial role in determining the clinical manifestation of RF. In this review, we comprehensively evaluated the recently published articles on lncRNAs in RF, discussed the potential application of lncRNAs as diagnostic and/or prognostic biomarkers, proposed therapeutic targets for treating RF-associated diseases and subsequent CKD transition, and highlight future research directions in the context of the role of lncRNAs in the development and treatment of RF.

Rotator cuff tear (RCT) is among the most common shoulder injuries and is prone to rerupture after surgery. Selecting suitable subpopulations of stem cells as a new specific cell type of mesenchymal stem cells has been increasingly used as a potential therapeutic tool in regenerative medicine. In this study, murine adipose-derived SSEA-4+CD90+PDGFRA+ subpopulation cells were successfully sorted, extracted, and identified. These cells showed good proliferation and differentiation potential, especially in the direction of tendon differentiation, as evidenced by qRT-PCR and immunofluorescence. Subsequently, we established a murine rotator cuff injury model and repaired it with subpopulation cells. Our results showed that the subpopulation cells embedded in a fibrin sealant significantly improved the histological score, as well as the biomechanical strength of the repaired tendon enthesis at four weeks after surgery, compared with the other groups. Hence, these findings indicated that the subpopulation of cells could augment the repaired enthesis and lead to better outcomes, thereby reducing the retear rate after rotator cuff repair. Our study provides a potential therapeutic strategy for rotator cuff healing in the future.

Aims Renal fibrosis is the most common final stage of progressive renal disease, characterized by fibroblast proliferation, fibroblast-to-myofibroblast differentiation and excessive accumulation of extracellular matrix. Dihydroartemisinin (DHA) exerts antitumor, antibacterial, and antifibrotic effects. The aim of this study was to determine whether DHA has beneficial effects on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice and to examine explore the underlying possible mechanisms. Materials and methods Eight-week-old male C57BL/6 mice were intragastrically administered DHA for 14 consecutive days after UUO operation. Afterward, interstitial collagen deposition, expression of collagen I and III, fibronectin, α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), and S100 calcium-binding protein A4 (S100A4) were assessed in the kidneys. Transforming growth factor beta 1 (TGF-β1)-induced primary human kidney fibroblasts were treated with DHA to further investigate the mechanism underlying its action. Key findings In vivo, DHA reduced UUO-induced morphological and pathological changes and the degree of renal fibrosis. In addition, DHA mitigated fibroblast proliferation and differentiation in kidney tissue induced by UUO. In vitro, DHA significantly attenuated the TGF-β1-induced primary human kidney fibroblast proliferation and fibroblast-to-myofibroblast differentiation. Moreover, treatment with DHA attenuated the up-regulation of phosphorylation of phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) in UUO model and TGF-β1-induced primary human kidney fibroblasts. Significance We provide in vivo and in vitro evidence that DHA may relieve renal fibrosis through regulation of fibroblast proliferation and differentiation by mitigating the PI3K/AKT pathway. DHA may potentially be used as a therapeutic antifibrotic agent for the treatment of renal fibrosis.