Thymosin β4 (Tβ4) is closely associated with the cytoskeleton, inflammation, wound healing, angiogenesis, apoptosis, and myocardial regeneration, but the effects of Tβ4 treatment on chronic renal tubular interstitial fibrosis (CRTIF) are poorly known. This study aimed to examine the effects of Tβ4 on the renal apoptosis and the expression of transforming growth factor (TGF-β), E-cadherin, and α-smooth muscle actin (α-SMA) in CRTIF rat models. Male SD rats were randomized into four groups (sham group, unilateral ureteral obstruction (UUO) group, UUO + low-dose Tβ4 group, and UUO + high-dose Tβ4 group). The pathological changes of kidney tissue and its function were assessed two weeks after UUO. In renal interstitial tissue,TGF-β, E-cadherin and α-SMA expression was detected by western blot. In tubular epithelial cells, E-cadherin and α-SMA expression was detected using Real-time qPCR and western blot. Cell apoptosis of rat renal interstitial tissue and tubular epithelial cells was evaluated by immunofluorescence and western blot. Two weeks after UUO, no differences in blood urea nitrogen and creatinine were observed between the four groups (P > 0.05). Compared to the UUO group, Tβ4 treatment decreased the 24-h proteinuria (P < 0.001) and reduced the area of pathological change (P < 0.01); this effect was more apparent in the UUO + high-dose Tβ4 group. Compared to the UUO group, a significant decrease in TGF-β and α-SMA protein expression was observed in the high-dose Tβ4 group. The level of E-cadherin protein was lower in the UUO group than the Tβ4 groups, and high-dose Tβ4 treatment further increased E-cadherin expression and improved cell apoptosis in the renal interstitial tissue. Analysis of in vitro tubular epithelial cells showed that α-SMA mRNA and protein expression decreased, while E-cadherin mRNA and protein expression increased by Tβ4 treatment. Similarly, these changes were more significant in the UUO + high-dose Tβ4 group. Tβ4 treatment improved the apoptosis of In vitro tubular epithelial cells compared with pure TGF-β stimulation, and equally, the decrease of apoptosis was more apparent in the TGF-β + high-dose Tβ4 group. Tβ4 treatment might alleviate the renal fibrosis and apoptosis of tubular epithelial cells through TGF-β pathway inhibition in UUO rats with CRTIF.

Obesity is a well-established risk factor for atherosclerosis. However, it is unknown which measure of adiposity best relates to atherosclerosis in relatively lean maintenance hemodialysis (MHD) patients. We aimed to explore and compare the associations between different adiposity indices reflecting general, abdominal, visceral adiposity and arteriosclerosis risk with atherogenic index of plasma(AIP) in relatively lean MHD patients. We conducted a multicenter, cross-sectional study in Guizhou Province, Southwest China. General/abdominal adiposity indices like body mass index (BMI), waist circumference(WC), waist-height ratio(WHtR), conicity index (Ci) and visceral obesity indices including visceral adiposity index (VAI), lipid accumulation product (LAP) and the hypertriglyceridemic waist phenotype (HW phenotype) were recorded. Univariate and multivariate linear regression models were used. All adiposity indices correlated positively with AIP in univariate analysis both in men and women except for Ci. After adjustment for age and traditional atherosclerosis risk factors, BMI, WC, WHtR, VAI and LAP still had associations with AIP both in men (β = 0.265, 0.153, 0.16, 0.788 and 0.74, respectively, all P < 0.001) and women (β = 0.34,0.199, 0.21, 0.83 and 0.74, respectively, all P < 0.001). After further adjustment for BMI, associations between AIP and VAI, LAP remained significant, but associations between WC, WHtR and AIP disappeared. The HW phenotype, VAI, and LAP, validated and convenient markers of visceral obesity, were superior to classical anthropometric general/ abdominal adiposity indices for atherosclerosis risk assessment, especially in relatively lean MHD patients aged 40 years or older.

Objective: Immune inflammatory cells and cytokines play an important role in the occurrence and development of diabetic nephropathy (DN). Acteoside has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of acteoside on the expressions of MCP-1 and TGF-β₁ on nephropathy in diabetic mice. Methods: C57BL/6J mice in the model group were given a single intraperitoneal injection of STZ (150 mg/kg). Model mice were divided randomly into two groups: 5 without treatment, 5 treated with acteoside. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected, then, ralated biochemical parameters, pathological characteristics and MCP-1 and TGF-β1 mRNA or protein were detected. The NRK-52E cells were divided into three groups as follows: the normal control group (NC group), the high glucose group (HS group), the high glucose+acteoside group (HS+ACT group). The expressions of MCP-1 and TGF-β₁ in the mRNA and protein levels were assessed with RT-PCR, western blot and ELISA. Results: The expressions of MCP-1 and TGF-β₁ were significantly enhanced in DN group and dramatically reduced after acteoside treatment. Compared with those in NC group, the expressions of MCP-1 and TGF-β₁ in NRK-52E cell of HS group were significantly enhanced, while both were significantly decreased in HS+ACT group compared with HS group. Conclusion: Our findings indicate that Acteoside has protective effects on DN via inhibiting the expressions of MCP-1 and TGF-β₁.

Objective: Acteoside (ACT) has been reported to regulate the inflammation and immune response. The study aims to explore the effect of ACT on renal fibrosis in unilateral ureteral obstruction (UUO) rats. Methods: Eighteen Sprague-Dawley rats were randomly divided into 3 groups: sham group, opened the abdominal cavity and sutured abdominal; UUO group, performed UUO surgery; and ACT + UUO group, ACT (40 mg/kg) was given by gavage every day after UUO surgery. After 2 weeks of rat model construction, urine and blood samples were collected for biochemical analysis, while kidney tissues were harvested for hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemistry staining. The expression of connective tissue growth factor (CTGF), alpha smooth muscle actin (α-SMA), collagen III, heat shock protein 47 (HSP47), and β-catenin in the renal tissue was detected and the correlation between these proteins was analyzed. Results: ACT improved the parameters of renal function in UUO rats, including decreased creatinine and urea nitrogen, and declined urinary protein. Pathological analysis suggested that ACT improved the conditions of renal tubule lesion (including structure destruction, atrophy and lumen obstruction), renal interstitial fibrosis and inflammatory cell infiltration in UUO rats. It also down-regulated the expressions of fibrin-related proteins β-catenin, CTGF, α-SMA, collagen III, and HSP47. Correlation analysis found that β-catenin and CTGF were correlated with the expressions of α-SMA, collagen III, and HSP47. Conclusions: ACT could alleviate renal fibrosis in UUO rats probably via inhibiting β-catenin/CTGF signaling pathway.

Objective(s): Acute renal ischemia may cause acute renal dysfunction due to lack of blood supply; the manifestations are renal tubular cell apoptosis, infiltration of macrophages, and microvascular destruction. Many studies have shown that erythropoietin (EPO) and vitamin D3 (VD3) can be used to prevent or treat renal ischemia-reperfusion (I/R) injury, and VD3 may interact with EPO. In the present study, the effects of the combination of VD3 and EPO in I/R acute kidney injury were studied. Materials and Methods: Rats were divided into 5 groups: sham-operated (SHAM), AKI without treatment (AKI-control), AKI treatment with VD3(AKI+VD3), AKI treatment with EPO(AKI+EPO), AKI treatment with VD3 and EPO(AKI+VD3+EPO). The effects of the combination of VD3 and EPO on AKI were assessed by histologic, inflammation, and apoptosis studies. Results: The degree of damage in renal tissue was significantly reduced in VD3, EPO, and combined groups. Combination therapy with VD3 and EPO markedly improved Creatinine clearance rate (CCr). The combined treatment group showed the lowest F4/80+ and CD68+ expressions. The expression of Bcl-2 in the combined treatment group was higher than those in VD3 group and the EPO group, while Bax's expression goes in the opposite direction. Conclusion: This provides further evidence that VD3 and EPO have beneficial effects in I/R injury via anti-inflammatory and anti-apoptosis pathways. The synergistic protective effect of VD3 and EPO is of profound significance in the development of new strategies for the prevention and treatment of acute kidney injury (AKI).

Rationale: Melanoma differentiation–associated gene 5 (MDA5)-associated rapidly progressive interstitial lung disease (RPILD) is a rare and life-threatening condition with no standardized treatment protocol. We report a case of successful treatment using a novel combination therapy. Patient concerns: A 69-year-old female presented with progressive dyspnea and chest tightness that had persisted for 1 year but significantly worsened over the 20 days before admission. The recent exacerbation was accompanied by coughing, expectoration, and fatigue. Diagnoses: Following a comprehensive evaluation including chest computed tomography imaging, laboratory tests, and autoantibody profiling, the patient was diagnosed with MDA5-associated RPILD. Interventions: The patient was treated with high-dose methylprednisolone pulse therapy, cyclophosphamide, and telitacicept (a novel TACI-Fc fusion protein). Outcomes: After treatment, the patient’s oxygenation index improved from 174 to 306 mm Hg. Follow-up chest computed tomography showed near-complete resolution of bilateral lung inflammation. Pulmonary function tests demonstrated improvement, with diffusing capacity for carbon monoxide reaching 63.6% of the predicted value at 6-month follow-up. Lessons: This case suggests that combination therapy including telitacicept may be effective for MDA5-associated RPILD. Further research is needed to confirm these findings and elucidate the underlying mechanisms of action.