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Diabetic nephropathy is a serious chronic complication affecting at least 25% of diabetic patients. Hyperglycemia associated advanced glycation end-products (AGEs) increase tubular epithelial-myofibroblast transdifferentiation (TEMT) and extracellular matrix synthesis and thereby causes renal fibrosis. The chalcone isoliquiritigenin, found in many herbs of Glycyrrhiza family, is known for potential health-promoting effects. However, their effects on AGE-associated renal proximal tubular fibrosis are not known yet. In this study, the effect of isoliquiritigenin on AGE-induced renal proximal tubular fibrosis was determined in cultured HK-2 cell line. The results show that 200 μg/mL of AGE-induced TEMT and the formed myofibroblasts synthesized collagen to increase extracellular matrix formation thereby lead to renal tubular fibrosis. However, treatment with 200 nM of isoliquiritigenin considerably inhibited the TEMT and suppressed the TGFβ/STAT3 mechanism to inhibit collagen secretion. Therefore, isoliquiritigenin effectively suppressed AGE-induced renal tubular fibrosis.

Diabetes-induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin-like growth factor II receptor α (IGF-IIRα) is a cardiac risk factor. In this study, we hypothesized IGF-IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague-Dawley rat model with specific IGF-IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF-IIRα in diabetic hearts. The results showed that IGF-IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro-inflammatory factors, such as Tumor necrosis factor-alpha, Interleukin-6, Cyclooxygenase-2, Inducible nitric oxide synthase, and Nuclear factor-kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac-specific IGF-IIRα overexpression. Correspondingly, IGF-IIRα overexpression in the diabetic myocardium also reduced the PI3K-AKT survival axis and activated mitochondrial-dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac-specific IGF-IIRα overexpression. Overall, all results provid clear evidence that IGF-IIRα can enhance cardiac damage and is a harmful factor to the heart under high-blood glucose conditions. However, the pathophysiology of IGF-IIRα under different stresses and its downstream regulation in the heart still require further research.

This study reports the effect of cardiac-specific insulin-like growth factor-II receptor α (IGF-IIRα) overexpression on the development of liver dysfunction in transgenic rats via STZ-induced diabetic hepatocyte damage. The cardio-hepatic syndrome comprises a number of heart and liver illnesses in which an acute or chronic disease in one organ can lead to acute or chronic disease in the other. However, the molecular mechanism involved in such a set of conditions is unclear. In this study, we developed a transgenic rat model with cardiac-specific overexpression of IGF-IIRα, which is a supplementary splicing variant of insulin-like growth factor-II receptor (IGF-IIR), expressed in pathological hearts, to investigate the relationship between late fetal gene expression in diabetic hearts and their influence on diabetic hepatopathy. STZ (55 mg/kg) was intraperitoneally delivered into IGF-IIR overexpressed transgenic (TG) and non-transgenic (NTG) animal models developed in Sprague-Dawley (SD) rats after an overnight fast. The relationship among IGF-IIRα overexpression and hepatocyte damages have been determined based on the complexity of damage in the liver. Our findings revealed that overexpression of the cardiac-specific IGF-IIRα enhances diabetes-induced morphological alterations and hepatic inflammation in the livers. The diabetic transgenic rats demonstrated the development of pathological conditions such as thick collagen fiber deposition, bridging fibrosis, and elevation of α-SMA and MMP1 related liver fibrosis mechanisms. Our data suggest that IGF-IIRα overexpression in the heart during a pathological state may worsen diabetic hepatopathy in rats.

Neurodegenerative diseases have become increasingly prevalent in the aged population. Rheumatoid arthritis (RA) is an autoimmune disease that causes systemic inflammation, damaging the neurons. However, only a few treatment options can reduce RA-induced neurodegeneration. This study aimed to evaluate whether adipose-derived stem cells (ADSCs) pretreated with curcumin could ameliorate RA-induced neurodegenerative illness in an RA rat model. Wistar rats were randomly classified into the following four groups: control, RA, RA + ADSC (1 × 106 cells per rat), and RA + curcumin-pretreated ADSC (1 × 106 cells per rat). After treatment for two months, the effects were specifically evaluated in the brains collected from the rats. Our results demonstrated that the transplantation of curcumin-pretreated ADSCs substantially reduced inflammation and apoptosis in the cortices of RA rats compared to those of other groups. Thus, the combination of ADSCs and curcumin exerts a synergistic effect in enhancing neuronal protection in RA rats. In the future, this combination therapeutic strategy can potentially be used as a novel treatment method to reduce RA-induced neurodegenerative disorders.

Parkinson's disease (PD) is a neurodegenerative disorder involving the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Cellular clearance mechanisms, including the autophagy-lysosome pathway, are commonly affected in the pathogenesis of PD. The lysosomal CaThis study aims is to investigate the neuroprotective effects of A. argyi in promoting the TRPML1-mediated autophagy/mitophagy-enhancing effect METHODS: In this study, we used 1-methyl-4-phenyl-pyridinium (MPP+)-induced PD model established in an SH-SY5Y human neuroblastoma cell line as well as in a 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-induced PD model in C57BL/6 J mice. MTT assay was conducted to measure the cell viability and further MitoSoX and DCFDA assay were used to measure the ROS. Western blot analysis was used to access levels of TRPML1, p-DRP1 (ser616), p-AKT, PI3K, and β-catenin, Additionally, IF and IHC analysis to investigate the expression of TRPML1, LC3B, β-catenin, TH+, α-synuclein. Mitotracker stain was used to check mitophagy levels and a lysosomal intracellular activity kit was used to measure the lysosomal dysfunction. Behavioral studies were conducted by rotarod and grip strength experiments to check motor functions.In our in vitro study, A. argyi rescued the MPP+-induced loss of cell viability and reduced the accumulation of mitochondrial and total reactive oxygen species (ROS). Subsequently, it increased the expression of TRPML1 protein, thereby inducing autophagy, which facilitated the clearance of toxic accumulation of α-synuclein. Furthermore, A. argyi played a neuroprotective role by activating the PI3K/AKT/β-catenin cell survival pathway. MPP+-mediated mitochondrial damage was overcome by upregulation of mitophagy and downregulation of the mitochondrial fission regulator p-DRP1 (ser616) in SH-SY5Y cells. In the in vivo study, A. argyi ameliorated impaired motor function and rescued TH+ neurons in the SNpc region. Similar to the results of the in vitro study, TRPML1, LC3B, and β-catenin expression was enhanced in the SNpc region in the A. argyi-treated mice brain.Thus, our results first demonstrate that A. argyi can exert neuroprotective effects by stimulating TRPML1 and rescuing neuronal cells by boosting autophagy/mitophagy and upregulating a survival pathway, suggesting that A. argyi can further be exploited to slow the progression of PD.