Current Issues in Molecular Biology最新文献

Ovarian cancer, the most lethal type of tumour of the female reproductive system, severely threatens women's life and health. Despite paclitaxel being a key chemotherapeutic agent in the standard treatment for ovarian cancer, the majority of patients eventually develop resistance to paclitaxel, constituting a significant obstacle to successful treatment. KIF26B, a kinesin family protein, is involved in various cancers, but its role in ovarian cancer and chemotherapy resistance is unclear. In this study, we evaluated the role of KIF26B in drug-resistant ovarian cancer and the underlying mechanisms. Bioinformatics analysis revealed that KIF26B was highly expressed in ovarian cancer tissues and was associated with poor clinical characteristics. Moreover, KIF26B expression was consistently high in chemotherapy-resistant tissues across multiple treatment subgroups, with ROC curve analyses confirming its predictive power for chemoresistance, particularly in advanced serous ovarian cancer. To further investigate the role of KIF26B in ovarian cancer resistance, the effects of KIF26B on cell proliferation, colony formation, the cell cycle, apoptosis, and microtubule polymerization under paclitaxel treatment were assessed. KIF26B knockdown significantly reduced paclitaxel resistance in ovarian cancer cells, inhibited cell proliferation, and promoted apoptosis. Furthermore, KIF26B interference induced cell cycle arrest and altered microtubule polymerization dynamics in paclitaxel-resistant cells. Additionally, our analyses revealed a negative correlation between KIF26B and SLC7A11 in ovarian cancer, particularly in chemoresistant tissues. Combined KIF26B and SLC7A11 expression provided stronger prognostic value than either gene alone did, and functional assays demonstrated that SLC7A11 contributed to the regulation of the KIF26B-mediated paclitaxel response. Overall, our results indicate that KIF26B is crucial for ovarian cancer progression and chemotherapy resistance, likely through SLC7A11 regulation. KIF26B may serve as a potential therapeutic target for overcoming paclitaxel resistance.

Patients hospitalized with neurological disorders may be at increased risk of adverse outcomes when infected with SARS-CoV-2. We evaluated whether early routine serum inflammatory and injury markers obtained at hospital admission are associated with in-hospital mortality in this subgroup. This single-center observational cohort included 460 consecutive adult inpatients admitted for neurological disorders with SARS-CoV-2 infection confirmed on admission or during hospitalization. Serum IL-6, LDH, ferritin, hs-troponin I, CRP, procalcitonin, and D-dimers measured within 6 h of hospital admission for neurological disorder were analyzed and compared between survivors and non-survivors. Non-survivors had higher IL-6, LDH, ferritin, and hs-troponin I (all p < 0.001). In multivariable analysis, LDH, ferritin, IL-6, and hs-troponin I were independently associated with mortality. We conclude that in neurological inpatients with confirmed SARS-CoV-2 infection, elevated early IL-6, LDH, ferritin, and hs-troponin I are associated with in-hospital mortality. These markers likely reflect systemic disease severity rather than CNS-specific neuroinflammation and may support early risk stratification in this population.

Interleukin-37 (IL-37) is an anti-inflammatory cytokine with an undefined role in chronic endometritis (CE). This study aims to explore its therapeutic mechanism in CE, focusing on epithelial-mesenchymal transition (EMT) and macrophage polarization. A CE model was induced in Sprague-Dawley rats using lipopolysaccharide (LPS), followed by intervention with TAT-fused recombinant IL-37. Histological damage and fibrosis were evaluated through H&E and Masson staining. Immunofluorescence staining was performed to assess the expression of IL-37 and EMT markers (E-cadherin and vimentin) and macrophage phenotypes (M1: CD86⁺; M2: CD206⁺). In vitro, transwell, qPCR, Western blot, and flow cytometry analyses were performed to determine the effects of IL-37 on EMT and macrophage polarization. The activity of the STAT6 and Smad3 pathways was evaluated using Western blotting, dual-luciferase assays, and immunofluorescence staining. The results revealed that IL-37 accumulated in the injured uterus, alleviating inflammation, tissue damage, and collagen deposition. IL-37 reduced epithelial migration and reversed abnormal EMT by upregulating E-cadherin expression and downregulating vimentin expression. It also suppressed M1 macrophage infiltration and promoted M2 polarization. Mechanistically, IL-37 coactivated the STAT6 and Smad3 pathways, thereby increasing their phosphorylation and nuclear translocation and elevating ARG1 expression. In conclusion, IL-37 mitigates CE by suppressing EMT and promoting M2 macrophage polarization via coordinated STAT6/Smad3 activation, highlighting its therapeutic potential for CE.

DLBCLs constitute an aggressive type of lymphoma with varied clinical, molecular and genetic features. The cells are characterized by NFkB pathway disturbances and BCL-2 and mTOR protein deregulation, which significantly inhibit apoptosis. Hence, many treatment strategies have been established to target the functioning of these pathways. While early clinical trials have found mTOR, NFkB and Bcl-2 inhibitors to have activity in many hematological cancers, their activity as monotherapy agents may still be insufficient; therefore, combinations of these compounds with other molecules demonstrating activity in a given cancer subtype are under evaluation. In vitro studies were conducted on the Riva (ABC subtype) and Toledo (GCB subtype) cell lines. Three novel drugs were administered: AZD2014 (vistusertib)-an inhibitor of the serine-threonine kinase mTOR; IMD-0354-an NFκB inhibitor; and ABT-199 (venetoclax)-a highly selective inhibitor for BCL-2. Drugs were administered alone, in pairs and as a combination of all three agents. For the Riva cell line, ABT-199 had the strongest pro-apoptotic effect on cancer cells as monotherapy. As pairs, AZD2014+ABT-199 and ABT-199+IMD0354 demonstrated similar effects. The combination of the three drugs did not have a stronger effect than the drug pairs. For the Toledo cell line, no significant differences were noted between the drugs when used as monotherapy. In pairs, the strongest effect was observed for AZD2014+ABT-199; furthermore, this effect was not intensified by the combination of the three drugs. Our findings, including those for the BCL-2 and mTOR inhibitors, indicate that there is a need for further in vivo studies to evaluate these drugs as potentially effective treatments for DLBCL of the ABC and GCB subtypes.

Background: Diabetic nephropathy is characterized by metabolic dysregulation, renal fibrosis, and impaired autophagy. MicroRNA-451 (miR-451) has been implicated in metabolic and stress-response pathways, but its role in diabetic kidney disease remains unclear. This study examined the effects of systemic miR-451 overexpression on renal injury and autophagy in BTBR ob/ob mice.

Methods: Wild-type (WT) and BTBR ob/ob (OB) mice were treated with miR-451 mimics. Body weight, blood glucose, and urine albumin were assessed for three consecutive weeks. Renal miR-451 expression was measured by qRT-PCR, while protein levels of YWHAZ, mTOR, and autophagy markers were analyzed by Western blotting. Renal fibrosis was evaluated using Masson's trichrome staining.

Results: OB mice exhibited increased body weight, hyperglycemia, and albuminuria compared with WT controls. miR-451 treatment resulted in robust renal overexpression of miR-451 in OB treated mice (8.4-fold, p = 0.039) but did not normalize metabolic parameters. miR-451 overexpression significantly reduced renal expression of YWHAZ and mTOR. Histological analysis revealed increased glomerular fibrosis in OB mice, which was significantly attenuated following miR-451 treatment in WT-treated and OB-treated mice. In addition, miR-451 treatment increased expression of autophagy-related proteins ATG101 and Beclin-1 and reduced the LC3-II/I ratio, indicating altered autophagic signaling.

Conclusions: miR-451 overexpression attenuates renal fibrosis and modulates autophagy-associated pathways in diabetic kidney disease, independent of metabolic control, highlighting miR-451 as a potential therapeutic target for diabetic kidney disease.

Endothelial dysfunction induced by oxidative stress is a critical contributor to impaired microvascular homeostasis and skin aging. Blueberries are rich in polyphenolic compounds with antioxidant properties. However, whether bioconversion enhances their protective effects on endothelial function remains insufficiently explored. In this study, we investigated the beneficial effects of bioconverted blueberry extract (BBS) on human dermal microvascular endothelial cells (HDMECs). HDMECs were exposed to hydrogen peroxide (H₂O₂) to induce oxidative stress and subsequently treated with BBS. BBS significantly reduced H₂O₂-induced ROS accumulation and preserved mitochondrial membrane potential. Consistently, BBS markedly enhanced endothelial migration and tube-forming ability under oxidative stress conditions. Furthermore, BBS treatment significantly suppressed the overactivation of MAPK signaling pathways. Collectively, BBS effectively mitigated oxidative stress-induced endothelial dysfunction by restoring redox balance, preserving mitochondrial integrity, and promoting angiogenic function. Taken together, these findings suggest that bioconverted blueberry extract can be utilized as a functional ingredient for skin health and anti-aging.

The creatinine/cystatin C ratio (CCR) has emerged as a simple surrogate marker for muscle mass. This study aimed to evaluate the clinical utility of CCR in identifying sarcopenia among patients with hepatitis-C-virus-related liver cirrhosis who achieved a sustained virological response following antiviral treatment. In this retrospective study, 111 patients treated at our hospital between 2017 and 2022 were assessed for sarcopenia using the Japan Society of Hepatology criteria, which includes handgrip strength (HGS) and skeletal muscle mass index (SMI) measured via computed tomography. Sarcopenia was diagnosed in 30 patients (27.9%). The median CCR was 0.78 in males and 0.55 in females. Multivariate logistic regression analysis identified CCR < 0.56 as an independent factor associated with sarcopenia. Receiver operating characteristic curve analysis demonstrated good diagnostic performance, with an area under the curve of 0.761 for males and 0.801 for females. Furthermore, overall survival was significantly higher in patients with higher CCR values (>0.65 in males and >0.54 in females). The discriminative ability of CCR was comparable to that of HGS, SMI, and the composite diagnosis of sarcopenia. These findings suggest that CCR is a practical and reliable marker for sarcopenia in this patient population.

Neohesperidin dihydrochalcone (NHDC) is a synthetic sweetener derived from neohesperidin and can improve pathological changes in sepsis-associated acute lung injury (SALI), but the mechanism by which NHDC inhibits SALI remains unclear. We evaluated the therapeutic effect of NHDC (100 mg/kg) and its potential mechanism using bioinformatics approaches with a Lipopolysaccharide (LPS)-induced SALI model (LPS: 10 mg/kg) in mice (n = 6). Bioinformatics analysis identified 176 shared targets between NHDC and SALI, which were enriched in the MAPK signaling pathway. Further screening yielded five key targets (MAPK14, MAPK8, KDR, CASP3, and RHOA) with significant clinical expression differences (p < 0.01). Molecular docking suggested that NHDC could bind to all five targets, with binding energies <-5.0 kJ/mol, and molecular dynamics indicated stable binding between NHDC and MAPK8 (total binding energy ΔG = -181.320 kJ/mol). In vivo, NHDC reversed oxidative stress markers (catalase, superoxide dismutase, glutathione, malondialdehyde, and reactive oxygen species), decreased TNF-α and IL-6 levels, and alleviated lung pathological injury (p < 0.05 vs. model group); it also significantly decreased phosphorylation of mitogen-activated protein kinases(MAPK) pathway proteins (p < 0.001 vs. model group). In summary, our research revealed that NHDC decreased the oxidative stress and inflammatory response of SALI; its specific mechanism is associated with the MAPK pathway. NHDC has a lot of potential as a medication for anti-SALI treatment.

Cannabis seed (CS), also known as hemp seed, is a nutrient-dense plant-derived food material rich in polyunsaturated fatty acids and bioactive components with reported anti-inflammatory properties. However, potential nutritional effects of CS on acute pancreatitis (AP), an inflammation-driven disease with limited dietary management strategies, have not yet been investigated. In this study, we examined the effects of dietary CS extract in a cerulein-induced AP mouse model. CS extract (5, 10, or 50 mg/kg) or vehicle (dimethyl sulfoxide) was orally administered 1 h prior to cerulein injection, and mice were euthanized 6 h after the final challenge. Oral supplementation with CS significantly attenuated AP severity, indicated by reducing pancreatic weight-to-body weight ratio, serum amylase and lipase activities, histopathological pancreatic injury, and pancreatic myeloperoxidase activity. CS administration alleviated AP-associated acute lung injury; markedly suppressing pancreatic mRNA expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. High-performance liquid chromatography analysis identified α-linolenic acid, an omega-3 polyunsaturated fatty acid, as a major nutritional component of CS extract. Collectively, these findings suggest that CS supplementation may contribute to nutritional modulation of inflammatory responses and systemic organ injury in experimental AP, supporting its potential as a functional food ingredient in inflammation-associated pancreatic disorders.

Cancer is one of the major lethal diseases in the world, and Western medicine treatments are often affected by side effects and drug resistance. Ginseng is a commonly used Chinese medicine in clinical practice, and Ginsenoside Rh1, an important active ingredient in ginseng, has received widespread attention in recent years for its remarkable anticancer potential. In this paper, we systematically described the inhibitory effects of Ginsenoside Rh1 and its molecular mechanism in hepatocellular carcinoma, gastric carcinoma, colon carcinoma, breast carcinoma, ovarian carcinoma, cervical carcinoma, lung carcinoma and glioma. Studies have shown that Rh1 can inhibit cancer cell proliferation, migration, and invasion, and induce apoptosis by regulating multiple signaling pathways. In addition, Rh1 can inhibit MMPs expression and regulate angiogenesis and the immune microenvironment to exert synergistic anticancer effects. Although the efficacy of Rh1 has been confirmed in vitro and animal studies, the clinical translation of Rh1 requires further exploration of its in vivo pharmacokinetics, long-term safety, and precise targets. In this paper, we systematically summarize the multiple anticancer mechanisms of Rh1 and look forward to the prospect of combining Rh1 with existing therapies to provide a theoretical basis for the development of novel anticancer drugs.