General physiology and biophysics最新文献

The development of new composite materials derived from plant-based carbon for biomedical applications has posed a considerable challenge over the past decades. Herein, we successfully designed and synthesized ZnO/Meniran-C from Meniran-derived carbon (Meniran-C) decorated on zinc oxide for effective cancer treatment. These composites showed crystal microparticles and provided unique optical properties with high absorbance compared to pure Meniran and ZnO under an aqueous solution which has the potential for increased electron-hole. More importantly, in vitro analysis of MDA-MB-231 cells as breast cancer cells exhibited high toxicity after incubation with ZnO/Meniran-C for 24 h, in comparison with incubation with Meniran only. Hence, these composite materials provide a novel composite from bioactive compounds Meniran-derived carbon with excellent anticancer therapy and offer significant potential to contribute to the development of cost-effective, environmentally friendly, and widely applicable cancer therapies for future applications.

We studied the circSATB2 and PEAK1 expression in NSCLC tissues and their associations with clinicopathological features, recurrence, and metastasis. Tumor and adjacent tissues from 98 NSCLC patients (2019-2020) were analyzed using qPCR (circSATB2) and immunohistochemistry (PEAK1). Pearson correlation assessed circSATB2-PEAK1 mRNA relationships. Survival analysis compared high/low expression groups. Cox regression identified risk factors for recurrence/metastasis. circSATB2 and PEAK1 mRNA were upregulated in NSCLC tissues, correlating with lymph node metastasis and advanced TNM stage (IIIa). circSATB2 positively correlated with PEAK1 mRNA. High expression of both predicted poorer survival (Kaplan-Meier). Multivariate analysis identified high circSATB2, high PEAK1, lymph node metastasis, and stage IIIA as independent risk factors for postoperative recurrence/metastasis. In conclusion, elevated circSATB2 and PEAK1 in NSCLC are linked to aggressive clinicopathological features and poor prognosis, serving as biomarkers for recurrence/metastasis risk.

Toxic doses of chloroquine induce vasodilation, which contributes to hypotension. In this study, we aimed to investigate the involvement of endothelial nitric oxide in the vasodilatory effect of chloroquine on isolated rat aortas and elucidate the underlying mechanisms. We evaluated the effects of endothelial denudation and several inhibitors, including the nitric oxide synthase inhibitor NW-nitro-L-arginine methyl ester (L-NAME), the non-specific guanylate cyclase (GC) inhibitor methylene blue, the nitric oxide-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and the phosphoinositide-3 kinase inhibitor wortmannin, on chloroquine-induced vasodilation in endothelium-intact aortas. The effects of chloroquine and protein phosphatase 2 (PP2) on the phosphorylation of endothelial nitric oxide synthase (eNOS), Src kinase, and caveolin-1 in human umbilical vein endothelial cells were also investigated. Chloroquine-induced vasodilation was more pronounced in endothelium-intact aortas than in endothelium-denuded ones. L-NAME, methylene blue, ODQ, and wortmannin attenuated the vasodilatory effect of chloroquine in endothelium-intact aortas. Chloroquine increased cyclic guanosine monophosphate (cGMP) levels and stimulatory eNOS phosphorylation (Ser1177) while decreasing inhibitory eNOS phosphorylation (Thr495). PP2 inhibited chloroquine-induced phosphorylation of caveolin-1 and Src kinases. These findings suggest that chloroquine-induced vasodilation is mediated by the eNOS-GC-cGMP pathway, with eNOS phosphorylation regulated by caveolin-1 and Src kinase. Methylene blue may alleviate toxic-dose chloroquine-induced vasodilation.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by inflammation and oxidative stress, which is mainly caused by cigarette smoke (CS). The flavonoid myricetin was reported to exert protective effects in different diseases. This study aimed to explore the function of myricetin in COPD progression. Airway epithelial A549 cells were treated with CS extract (CSE) to establish an in vitro model, followed by the detection of inflammation, oxidative stress, and autophagy markers. Sprague-Dawley male rats were exposed to CS for 12 weeks to establish an in vivo model, followed by the evaluation of lung function parameters and lung histopathological changes. We found that myricetin relieved inflammation and oxidative stress in CSE-induced A549 cells, as demonstrated by the reduced MCP-1, IL-6, and IL-8 expression, ROS production, and MDA content and elevated SOD activity. Myricetin treatment reduced LC3B-II/LC3B-I ratio and Beclin-1 protein levels and elevated p62 protein level after CSE stimulation in A549 cells. In vivo results revealed that myricetin restored pulmonary function and ameliorated pulmonary inflammation and emphysema in CS-induced COPD rats. Collectively, the anti-inflammatory and antioxidant effects of myricetin in COPD may be attributed to its suppressive effects on autophagy.

Chemotherapeutic drug/gene nanoparticles (NPs) co-delivery system has great potential in tumor therapy. However, the role of circular RNA (circRNA) cerebellar degeneration-related 1 (CDR1) (circCDR1) and temozolomide (TMZ) NPs in the treatment of glioma remains unclear. circCDR1 was significantly low expressed in glioma tissues and cells. In the term of mechanism, circCDR1 could sponge miR-890 to regulate GJB6. The inhibition of circCDR1 on glioma progression could be reversed by miR-890, and the suppressive effect of miR-890 inhibitor on glioma progression also could be overturned by GJB6 silencing. CNPs could introduce TMZ and circCDR1 into glioma cells. The inhibitory effects of CNPs on glioma cell progression and tumor growth were much better than TMZ, TNPs and CNPs. Our study showed that circCDR1 could regulate the miR-890/GJB6 axis to inhibit glioma progression, and the constructed CNPs had a good inhibitory effect on glioma progression.

Thyroid cancer is the most prominent type of endocrine cancer. LncRNA ROR (Linc- ROR) exerts tumor regulator function in cancers. This study elucidates the action of Linc-ROR on thyroid cancer. The Linc-ROR level were investigated in 70 thyroid cancer patients. Cell viability was detected utilizing CCK-8 method. The xenograft tumor was constructed to evaluate tumor growth. The proportion of CD8+ T cells was assessed using flow cytometry. IL-10, IFN-γ, and TNF-β levels were detected utilizing ELISA assays. The Linc-ROR level was elevated in thyroid cancer patients (n = 70). The up-regulated Linc-ROR was associated with poor overall survival (p = 0.0315), lymph node metastasis (p = 0.027), and TNM stage (p = 0.016). Linc-ROR silencing restrained cell proliferation and tumor growth (p < 0.01). Additionally, silenced Linc-ROR suppressed the immune escape of thyroid cancer cells and polarization of M2 macrophages (p < 0.01). Moreover, the PI3K/ AKT signaling mediated the action of silenced Linc-ROR on thyroid cancer proliferation, immune escape, and M2 macrophage polarization (p < 0.05). Linc-ROR may be a valuable target for thyroid cancer management. The limitations of this research are that the action of Linc-ROR on the tumor microenvironment has not been investigated in the animal model.

This corrects the article DOI: 10.4149/gpb_2017058.

miR-145-5p regulates drug sensitivity in various cancer types and is also expressed at significantly low levels in pancreatic cancer (PC), but its role in PC resistance to gemcitabine is not yet clear. This study revealed low expression of miR-145-5p in the PC gemcitabine-resistant cell lines SW1990/GEM and PANC-1/GEM. The overexpression of miR-145-5p inhibited the proliferation and migration of PC drug-resistant cells. Mechanistically, miR-145-5p overexpression increased the sensitivity of PC drug-resistant cells to gemcitabine through the inhibition of CDCA3, thereby inhibiting the proliferation and migration of PC drug-resistant cells. Our study indicated that the upregulation of miR-145-5p expression might be an effective target for improving the treatment efficacy of PC.

Lung cancer, the foremost cause of cancer-related mortality worldwide, necessitates the exploration for novel anti-lung cancer therapeutics to enhance efficacy and reduce adverse effects. Targeting selenium in the tumor microenvironment has become a new strategy for the treatment of lung cancer. The objective of this study was to synthesize novel selenium nanoparticles (EBM-SeNPs) using aqueous extracts derived from Epimedium brevicornum Maxim and investigate its structural characteristics and inhibitory effects against lung cancer. The physicochemical properties of EBM-SeNPs were characterized from multiple aspects using a variety of methods. The CCK-8, flow cytometry, wound healing assay, Western blot and the cell derived xenograft model were conducted to evaluate the antitumor efficacy in vivo and in vitro. EBM-SeNPs were approximately spherical and exhibited superior dispersivity and stability in water solution. And EBM-SeNPs did not display any specific cytotoxicity against human liver cells. However, they showed outstanding capability to induce apoptosis in lung cancer cells, thereby effectively suppressing their growth and migratory potential. Furthermore, EBM-SeNPs demonstrated a reduction of tumor and an increase in immune organ index of tumor-bearing mice. Collectively, the EBM-SeNPs may be an effective and safe option for the treatment of lung cancer.

We aimed to investigate whether environmental enrichment (EE) would alter possible adverse effects of chronic unpredictable mild stress (CUMS) in elderly rats regarding corticosterone levels, stress-related gene expressions in some brain regions, and learning and memory. Wistar male rats (over 20 months) weighing 450-550 g were housed in enriched or standard cages for the duration of the study (10 weeks). After 8 weeks of CUMS application, body weight gain, adrenal weight, and corticosterone levels were measured. Morris water maze (MWM), and novel object recognition test were performed. Glucocorticoid receptor (GR), corticotropin-releasing hormone (CRH), and corticotropin-releasing hormone receptor 1 (CRHR1) expression levels were determined in the hypothalamus and hippocampus. In the stress group, body weights decreased over time. Regarding the distance swum by rats to find the platform in the MWM, while there was no significant difference between the 3rd and 4th days in the EE+CUMS group, the decrease continued until the 4th day in the standard control (SC)+CUMS group. Stress application reduced the GR and CRHR1 gene expressions in the hypothalamus. We conclude that chronic stress and EE caused brain region-specific changes, thus affecting the neurobiological and cognitive functions in the elderly. In this respect, our study will contribute to neurobiological and neurodegenerative studies on aging.