Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

High-fat diet (HFD)-induced obesity has been involved in the development of diabetic nephropathy (DN). Tenovin-1, a potent selective SIRT1/2 inhibitor, regulates various target proteins. The present study evaluated the protective effect of Tenovin-1 against renal fibrosis in HFD-induced Zucker diabetic fatty (ZDF) rats. Rats were fed a normal chow diet or HFD. Tenovin-1 (45 mg/kg) administered to HFD-fed rats decreased inflammatory cytokine expression in the serum of the rats. The antioxidant status and oxidative damage to lipids or DNA were significantly restored by Tenovin-1. Additionally, Tenovin-1 reduced the levels of blood urea nitrogen (BUN), serum creatinine (sCr), microalbumin, and urinary protein-based biomarkers in the urine of HFD-fed rats. The abnormal architecture of the kidney and pancreas was restored by Tenovin-1 administration. Tenovin-1 also reduced apoptosis in the kidneys of the HFD-fed rats and HG-treated NRK-52E cells. It significantly lowered the levels of ECM proteins in the kidneys of HFD-fed rats and HG-treated NRK-52E cells. Additionally, Tenovin-1 markedly reduced claudin-1, SIRT1, and SIRT2, but increased SIRT3 and SIRT4 in HFD-fed rats and NRK-52E cells treated with HG. Furthermore, Tenovin-1 altered epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-β (PDGFR-β), and signal transducer and activator of transcription 3 (STAT3) levels in the kidneys of HFD-fed rats. Conclusively, this study shows that Tenovin-1 can be a potential candidate drug for the treatment of HFD-induced renal fibrosis, in vivo and in vitro models.

Our previous study demonstrated that our novel herbal remedy, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum Cassia extracts, exhibits a therapeutic effect in 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice by inhibiting the Th-2 inflammatory response upon oral administration. It also ameliorated imbalances in lipid metabolism related to the skin barrier function in keratinocytes, indicating its potential as a topical agent. This study aims to further investigate the therapeutic effects and metabolic mechanisms of its topical application. The anti-atopic effect was evaluated using dermatitis scores, histopathological analysis, and immune cell factors in DNCB-induced mice. Metabolomic profiling of serum and lesional skin was conducted to elucidate the metabolic mechanisms. The topical application significantly reduced dermatitis scores, mast cell infiltration, and serum levels of immunoglobulin E (IgE), IFN-γ, interleukin (IL)-4, IL-17, and thymic stromal lymphopoietin (TSLP), demonstrating its effectiveness in treating atopic dermatitis (AD). Serum metabolomics revealed alterations in fatty acid metabolism related to the pro-inflammatory response. In lesional skin, metabolic markers associated with oxidative stress, immune regulation, and AD symptoms were restored. This study demonstrated its potential as a topical agent in suppressing Th-2 inflammatory responses and improving metabolic abnormalities related to AD symptoms, providing crucial insights for developing natural AD treatments.

Ovarian cancer is one of the most lethal gynecological diseases owing to its poor prognosis and lack of clear symptoms. Cisplatin is commonly used as the primary chemotherapeutic drug for ovarian cancer. However, chemoresistance to cisplatin in advanced ovarian cancer is a major factor contributing to chemotherapy failure. Pyruvate kinase M2 (PKM2) is significantly upregulated in ovarian cancer tissues, thereby contributing to cisplatin resistance. Despite this, its therapeutic role remains unclear. This study aimed to evaluate whether shikonin and compound 3K, PKM2 inhibitor, could enhance anticancer effects in cisplatin-resistant ovarian cancer SKOV-3 cells by regulating autophagic pathways. Cytotoxicity assays using MTT and colony formation assays demonstrated that shikonin or compound 3K treatment significantly reduced PKM2 expression in SKOV-3 cells. Shikonin and compound 3K inhibited PKM2-mediated glycolysis and induced autophagic cell death in cisplatin-resistant ovarian cancer cells, resulting in significant suppression of cell proliferation and survival. Additionally, Shikonin and compound 3K treatment suppressed PKM2-mediated glycolysis and induced autophagic cell death in cisplatin-resistant ovarian cancer cells, as evidenced by increased LC3-II expression, autophagosome formation, and reduced cell viability. These findings strongly suggest that PKM2 overexpression plays a key role in cisplatin resistance in ovarian cancer. Thus, PKM2 inhibitors use may be a highly effective strategy for overcoming chemoresistance and improving outcomes in patients with advanced ovarian cancer.

Ovarian cancer is among the most lethal gynecological malignancies due to its poor prognosis and lack of early symptoms. Cisplatin remains the primary chemotherapeutic agent; however, resistance to cisplatin in advanced ovarian cancer is a major cause of treatment failure. Pyruvate kinase M2 (PKM2) is markedly upregulated in ovarian cancer tissues and contributes to cisplatin resistance, though its therapeutic relevance has not been fully defined. This study investigated whether shikonin and compound 3K, both PKM2 inhibitors, could enhance anticancer effects in cisplatin-resistant SKOV-3 cells by modulating autophagic pathways. Cytotoxicity assays revealed that treatment with shikonin or compound 3K significantly reduced PKM2 expression. Combination therapy with high-dose PKM2 inhibitors and cisplatin increased apoptosis compared to controls, although the modest induction suggests apoptosis is only partially responsible for the observed effects. Additionally, Shikonin and compound 3K treatment suppressed PKM2-mediated glycolysis and induced autophagic cell death in cisplatin-resistant ovarian cancer cells, as evidenced by increased LC3-II expression, autophagosome formation, and reduced cell viability. These findings indicate that PKM2 overexpression plays a central role in cisplatin resistance in ovarian cancer. Targeting PKM2 with inhibitors such as shikonin or compound 3K may represent a promising strategy to overcome chemoresistance and improve therapeutic outcomes in patients with advanced ovarian cancer. These findings strongly suggest that PKM2 overexpression plays a key role in cisplatin resistance in ovarian cancer. Thus, PKM2 inhibitors use may be a highly effective strategy for overcoming chemoresistance and improving outcomes in patients with advanced ovarian cancer.