Qiongdan Hu’s research while affiliated with Southwest Medical University and other places

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a systemic complication of chronic kidney disease (CKD), resulting in high morbidity and mortality. However, effective treatment strategies are lacking. The pathogenesis of CKD-MBD is unclear but involves feedback mechanisms between calcium, phosphorus, parathyroid hormone, vitamin D and other factors, in addition to FGF23, Klotho, Wnt inhibitors, and activin A. Construction of a perfect animal model of CKD-MBD with clinical characteristics is important for in-depth study of disease development, pathological changes, targeted drug screening, and management of patients. Currently, the modeling methods of CKD-MBD include surgery, feeding and radiation. Additionally, the method of CKD-MBD modeling by surgical combined feeding is worth promoting because of short time, simplicity, and low mortality. Therefore, this review based on the pathogenesis and clinical features of CKD-MBD, combined with the current status of animal models, outlines the advantages and disadvantages of modeling methods, and provides a reference for further CKD-MBD research.

The occurrence of diabetic kidney disease (DKD), a critical microvascular issue in diabetes, is progressively on the rise. In recent years, long noncoding RNAs (lncRNAs) have garnered considerable attention as a novel and critical layer of biological regulation. Our knowledge regarding the roles and underlying mechanisms of lncRNAs in various diseases, including DKD, continues to evolve. Similarly, microRNAs (miRNAs), which are small noncoding RNAs, have been recognized as crucial contributors to cellular processes and disease pathogenesis. Emerging studies have highlighted the complex interactions between lncRNAs and miRNAs, particularly in the context of DKD, underscoring their importance in complex human diseases. Renal intrinsic cell damage is an important cause of inducing DKD. Persistent high glucose stimulation leads to remodeling of renal intrinsic cells and a cascade of pathological changes. This article aims to review recent literature on the lncRNAs-mediated regulation of miRNAs affecting renal intrinsic cells in DKD and to propose novel molecular-level therapeutic strategies for DKD. Through in-depth investigation of this dynamic molecular interaction, we can gain a profound understanding of the potential mechanisms underlying diabetic nephropathy, potentially identifying new targets for therapeutic intervention and paving the way for personalized and effective treatments.

BACKGROUND Cotton phenol is a yellowish-brown polyphenol hydroxybinaphthyl aldehyde compound mainly found in the roots, stems, leaves and seeds of cotton; a plant of the mallow family that has been widely used in the study of antifertility and antitumor drugs. However, there has been no report of serious renal injuries caused by cotton phenol. We report a case of granulomatous acute interstitial nephritis caused by exposure to large amounts of cotton phenol. CASE DESCRIPTION The patient was a 56-year-old male with nausea and a blood creatinine level of 4.95 mg/dL 2 month prior to admission. He was admitted to the hospital with worsening nausea, blood creatinine level of 7.21 mg/dL, and a renal puncture biopsy suggesting granulomatous acute interstitial nephritis. The patient had no specific past medical history. Laboratory tests (double-stranded DNA, antineutrophil cytoplasmic antibody, extractable nuclear antigen, rheumatoid subunit, serum and urine protein electrophoresis, complement levels, immunoglobulin subclasses, streptococcal serology, and hepatitis B and C serology were negative, normal or undetectable. Follow-up history revealed that the patient receives large quantities of cotton phenol at work. The diagnosis was granulomatous acute interstitial nephritis induced by exposure to cotton phenol. Treatment was volume management, maintenance of a stable internal environment, and glucocorticoid activation. Blood creatinine level gradually decreased to 1.86 mg/dL after 3 month and his condition improved. CONCLUSIONS Physicians encountering patients with acute interstitial nephritis of uncertain etiology are obligated to conduct a prompt and comprehensive history review. Special attention should be given to cotton phenol and its derivatives as they may potentially act as nephrotoxic agents. The application of glucocorticoids in the treatment of acute interstitial nephritis remains a subject of debate. However, in this particular case, the patient exhibited a rapid restoration of renal function following the administration of glucocorticoids.

Background Chronic kidney disease (CKD) and its associated end-stage renal disease (ESRD) are significant health problems that pose a threat to human well-being. Renal fibrosis is a common feature and ultimate pathological outcome of various CKD leading to ESRD. The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a refined compound formulated by our research group, which has been clinically administered for over a decade and has demonstrated the ability to improve the inflammatory state of various acute or chronic kidney diseases. However, the underlying mechanism by which A&P ameliorates renal fibrosis remains unclear. Methods We established a mouse model by surgically ligating the unilateral ureter to induce renal injury in vivo. And we utilized renal in situ electroporation of a plasmid with low LncRNA A33 expression to establish the unilateral ureteral obstruction(UUO)mouse model. In vitro, we stimulated primary tubular epithelial cells(pTEC) injury using TGF-β1, siRNA-A33, and pcDNA3.1-A33 plasmids were transfected into pTECs to respectively knockdown and overexpress LncRNA A33, and both in vitro and in vivo models were intervened with A&P. Results The results demonstrated that A&P effectively alleviated renal fibrosis in mice. Subsequent findings indicated high expression of LncRNA A33 in the kidneys of UUO mice and TGF-β1-induced renal tubular cells. In situ, renal electroporation of a plasmid with reduced LncRNA A33 expression revealed that inhibiting LncRNA A33 significantly improved renal fibrosis in UUO mice. Moreover, A&P effectively suppressed LncRNA A33 expression both in vitro and in vivo. Subsequent downregulation of LncRNA A33 in renal tubular epithelial cells resulted in the downregulation of numerous fibrotic markers, a significant inhibition of LncRNA A33, and a notable reduction in downstream ferroptosis signaling. Cell experiments demonstrated that A&P improved renal fibrosis in UUO mice by inhibiting LncRNA A33 and downregulating ferroptosis signaling. Conclusion Through the inhibition of LncRNA A33 and subsequent downregulation of ferroptosis signaling, A&P showed potential as a therapeutic approach for improving renal fibrosis in UUO mice, providing a potential treatment avenue for CKD.

Background Intracerebral hemorrhage (ICH), a devastating form of stroke, is characterized by elevated morbidity and mortality rates. Neuroinflammation is a common occurrence following ICH. Mesenchymal stem cells (MSCs) have exhibited potential in treating brain diseases due to their anti-inflammatory properties. However, the therapeutic efficacy of MSCs is limited by the intense inflammatory response at the transplantation site in ICH. Hence, enhancing the function of transplanted MSCs holds considerable promise as a therapeutic strategy for ICH. Notably, the iron-quercetin complex (IronQ), a metal-quercetin complex synthesized through coordination chemistry, has garnered significant attention for its biomedical applications. In our previous studies, we have observed that IronQ exerts stimulatory effects on cell growth, notably enhancing the survival and viability of peripheral blood mononuclear cells (PBMCs) and MSCs. This study aimed to evaluate the effects of pretreated MSCs with IronQ on neuroinflammation and elucidate its underlying mechanisms. Methods The ICH mice were induced by injecting the collagenase I solution into the right brain caudate nucleus. After 24 hours, the ICH mice were randomly divided into four subgroups, the model group (Model), quercetin group (Quercetin), MSCs group (MSCs), and pretreated MSCs with IronQ group (MSCs+IronQ). Neurological deficits were re-evaluated on day 3, and brain samples were collected for further analysis. TUNEL staining was performed to assess cell DNA damage, and the protein expression levels of inflammatory factors and the cGAS-STING signaling pathway were investigated and analyzed. Results Pretreated MSCs with IronQ effectively mitigate neurological deficits and reduce neuronal inflammation by modulating the microglial polarization. Moreover, the pretreated MSCs with IronQ suppress the protein expression levels of the cGAS-STING signaling pathway. Conclusion These findings suggest that pretreated MSCs with IronQ demonstrate a synergistic effect in alleviating neuroinflammation, thereby improving neurological function, which is achieved through the inhibition of the cGAS-STING signaling pathway.

Rhabdomyolysis (RM) induced by electric blankets is exceedingly rare, with only three cases identified in our literature review. Both RM and Guillain–Barré syndrome (GBS) present with similar clinical manifestations of myalgia and muscle weakness, posing a potential challenge for accurate diagnosis in clinical settings. This report presents the case of a 22-year-old man who developed RM subsequent to the use of an electric blanket. Despite undergoing plasma exchange and renal replacement therapy, the patient continued to exhibit poor muscle strength in both lower limbs. Subsequent comprehensive evaluation revealed the presence of concurrent GBS. Following a 5-day course of intravenous gamma globulin treatment, the patient experienced rapid recovery of muscle strength and was discharged. Additionally, we reviewed seven cases from the literature of coexistent RM and GBS. This indicated that investigation of the timing of onset of muscle strength decline in RM patients could help to identify potential concurrent neurological or muscular disorders. In cases in which concurrent GBS and RM cannot be definitively ascertained during early hospitalization, prioritizing plasma exchange treatment may lead to improved patient outcomes.

Bone marrow-derived mesenchymal stem cells (MSCs) show antifibrotic activity in various chronic kidney diseases. Here, we aimed to investigate whether Calycosin (CA), a phytoestrogen, could enhance the antifibrotic activity of MSCs in primary tubular epithelial cells (PTECs) induced by TGF-β1 and in a mouse model of unilateral ureteral obstruction (UUO). We found that MSCs treatment significantly inhibited fibrosis, and CA pretreatment enhanced the effects of MSCs on fibrosis in vitro. Consistent with the in vitro studies, MSCs alleviated tubular injury and renal fibrosis in mice after UUO, and CA-pretreated MSCs resulted in more significant improvements in tubular injury and renal fibrosis than MSCs after UUO. Moreover, MSCs treatment significantly inhibited necroptosis by repressing the elevation of MLKL, RIPK1, and RIPK3 in PTECs treated by TGF-β1and in mice after UUO, and CA-pretreated MSCs were superior to MSCs in alleviating necroptosis. MSCs significantly reduced TNF-α and TNFR1 expression induced by TGF-β1 in PTECs and inhibited TGF-β1, TNF-α, and TNFR1 expression induced by UUO in mice. These effects of MSCs were significantly enhanced after CA pretreatment. Therefore, our results suggest that CA pretreatment enhances the antifibrotic activity of MSCs by inhibiting TGF-β1/TNF-α/TNFR1 signaling-induced necroptosis.

Renal tubular epithelial cell (TEC) injury and fibrosis are the key factors of the pathogenesis of chronic kidney disease. Here, we reported that tectorigenin is effectively protected against obstructive nephropathy established by unilateral ureteral obstruction (UUO). In vivo, tectorigenin administration significantly alleviated the deteriorations of renal functions including blood urea nitrogen and creatinine. Meanwhile, results from the histology suggested that renal injury characterized by tubular cell damage and fibrosis lesions of kidneys in UUO group were markedly attenuated following tectorigenin treatment. Mechanistically, we found that tectorigenin treatment greatly inhibited Smad3 phosphorylation, and the transcription and protein level of Nox4, a newly identified direct downstream molecule of Smad3 and a modulator of ferroptosis, while it indirectly restored the expression of glutathione peroxidase 4, a negative regulator of ferroptosis. Consistent with in vivo studies, treatment with tectorigenin also suppressed the ferroptosis induced by erastin/RSL3 and fibrosis stimulated by transforming growth factor β1 (TGF-β1) in primary renal TECs. What is more, treatment with ferroptosis inhibitor, ferrostatin-1, also impeded TGF-β1 stimulated the profibrotic effects in TECs, indicating that tectorigenin may relieve fibrosis by inhibiting ferroptosis in TECs. In addition, tectorigenin treatment exhibited a similar tendency, which inhibited Smad3 activation, and the docking analysis revealed that tectorigenin docked well into the Smad3 binding cavity with strong binding affinity (−7.9 kcal/mol). Thus, this study deciphers the protective effect of tectorigenin against obstructive nephropathy through inhibiting Smad3-mediated ferroptosis and fibrosis.