Open Life Sciences最新文献

This research examines the cytotoxic consequences of thymoquinone-loaded bovine serum albumin nanoparticles (TQ-BSA NPs) on the A549 lung cancer cell line. UV-visible (UV-Vis) spectroscopy, Fourier transform infrared spectrophotometer (FT-IR), scanning electron microscopy (SEM), and dynamic light scattering (DLS) were employed to verify the biogenic TQ-BSA NPs' size, shape, and distribution. UV-Vis spectrophotometry indicated peaks at 200-300 nm, 500-600 nm, and a prominent peak at 700-800 nm, confirming the presence of TQ-BSA NPs. The polydispersity index, as confirmed by DLS, indicated a solvent distribution in water, accompanied by a zeta potential value of 126.2 ± 46.8 mV. The average size of TQ-BSA NPs was confirmed to be 187 ± 8 nm by SEM. TQ-BSA NPs reduce colony formation in the A549 lung cancer cell line in a dose-dependent manner relative to the control group. Protein expression analysis indicated that TQ-BSA NPs promoted programmed cell death by increasing pro-apoptotic levels and decreasing anti-apoptotic levels. TQ-BSA NPs demonstrated inhibition of cancer cell proliferation and promotion of apoptosis and exhibited significant efficacy against cancer cells at low concentrations. As a result, they have the makings of a promising chemotherapeutic agent for low-dose, long-term administration.

This study evaluated the therapeutic efficacy of the gastrointestinal health anti-diarrheal mixture (GHAM) on diarrhea induced by spleen deficiency, focusing on its modulation of gut microbiota. Using specific pathogen-free Wistar rats, a spleen deficiency model was created through senna leaf gavage. Rats were divided into control, model, positive control, and GHAM treatment groups. After a 14-day treatment, fecal samples were analyzed via 16S rDNA sequencing to assess microbiota alterations. GHAM significantly mitigated diarrhea and enhanced food intake and fecal quality. It increased the abundance of beneficial bacteria, such as Romboutsia and Clostridium_sensu_stricto_1, and decreased the levels of diarrhea-associated bacteria, such as Prevotellaceae and Bacillus, thereby improving microbiota functionality. GHAM's modulation of gut microbiota structure and function effectively alleviated spleen deficiency-induced diarrhea, positioning it as a potential natural herbal treatment for gastrointestinal ailments. This study lays the groundwork for further exploration of GHAM's regulatory impact on gut health.

Nakaseomyces glabratus, previously known as Candida glabrata, has the great potential to cause systemic fungal infections despite its similarity to baker's yeast. Its pathogenicity is attributed to the production of numerous virulence factors, among which the YPS genes (YPS1-YPS11) encoding aspartyl proteases have yet to be sufficiently characterized, and limited studies suggest their involvement in cellular homeostasis. The study's novelty is an investigation of the role of YPS in N. glabratus's ability to adapt to different host environments. For this purpose, we isolated RNA from N. glabratus cells grown in both host niche-mimicking culture media, such as artificial saliva (AS) and vagina-simulating media (VS), as well as standard yeast media (RPMI 1640 and YPDA). We then performed quantitative real-time PCR to evaluate YPS gene expression at different growth phases. At the early logarithmic phase, we observed a general increase in the expression levels of YPS genes; however, at the stationary phase, high expression levels were maintained for YPS7 in RPMI 1640 and YPDA media and YPS6 in RPMI 1640 and AS media. In addition, although the VS medium does not promote the proliferation of N. glabratus, the yeast can survive in an acidic environment, and the significantly overexpressed gene is YPS7. These findings underscore the significant modulation of N. glabratus YPS gene expression in response to external environmental conditions. This research provides insights into the molecular basis of N. glabratus pathogenicity and highlights new potential targets for antifungal therapy.

In clinical practice, an increasing number of patients exhibit concurrent cardiac and renal dysfunction, known as "cardiorenal syndrome," where each condition exacerbates the other, resulting in poorer patient prognosis. Fluid and sodium retention can lead to excessive fluid overload in the body; therefore, correcting fluid and sodium metabolic disorders is crucial for alleviating patient symptoms. This study was to investigate the abnormalities in water and sodium metabolism, as well as the expression levels of arginine vasopressin receptor 1a (AVPR1a) and arginine vasopressin receptor 2 (AVPR2), in a rat model of chronic renal failure-chronic heart failure (CRF-CHF). One hundred male Sprague-Dawley rats were randomly assigned into four groups: the CG group (normal feeding), the CRF group (3/4 nephrectomy using a "two-step surgical method"), the CHF group (subcutaneous injection of isoproterenol at 100 mg/kg), and the CRF-CHF group (3/4 nephrectomy followed by a subcutaneous injection of isoproterenol at 100 mg/kg 1 week later). 4 weeks post-surgery, urine and blood samples were collected to measure 24 h urinary protein, sodium, and potassium levels. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined using assay kits. Left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) were measured via left ventricular catheterization. The heart was weighed to calculate the left ventricular weight to body weight ratio (LVW/BW). The renal cortex and medulla were isolated to assess the relative mRNA and protein expression levels of AVPR1a and AVPR2. Compared to the CG group, the CRF and CRF-CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla. The CHF and CRF-CHF groups showed significant increases in LVEDP and LVW/BW (P < 0.05). Additionally, compared to the CG group, the other three groups had significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Compared to the CRF and CHF groups, the CRF-CHF group exhibited significantly higher levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla, along with significantly increased LVEDP and LVW/BW, significantly reduced LVSP, significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Rats with CRF-CHF experienced exacerbated renal and cardiac failure, characterized by significant disturbances in water and sodium metabolism and abnormal expression of AVPR1a and AVPR2.

Diabetic nephropathy (DN) presents a significant public health challenge due to its high rate of incidence and severe health consequences. Renalase has been identified as having renal-protective properties. A key contributor to albuminuria in DN patients is podocyte loss. The function of Renalase in DN in relation to podocyte activity needs to be explored further. In this study, we assessed the therapeutic efficacy of Renalase by monitoring changes in urine protein levels and podocyte health in db/db mice. We also induced hyperglycemia (HG) to stimulate podocyte clone 5 (MPC5) cells to create a model of podocyte loss in DN. Through co-culturing these cells with Renalase or H₂O₂, we investigated the process by which Renalase prevents podocyte loss in vitro. In db/db mice, Renalase expression was significantly reduced, and adenoviral-mediated Renalase expression markedly alleviated DN symptoms and proteinuria. Furthermore, podocytopathy in db/db mice was significantly mitigated. In vitro, Renalase improved the expression of podocyte marker proteins, podocin, and nephrin, which are reduced by HG, as well as decreased oxidative stress and restrained apoptosis. Our findings suggest that Renalase can mitigate DN by reducing proteinuria through podocyte protection, potentially by inhibiting oxidative stress and apoptosis. These data suggest that Renalase may serve as a novel therapeutic agent in suppressing DN.

Fosinopril (FOS) is an angiotensin-converting enzyme inhibitor that can decrease angiotensin II (Ang II) formation, thereby reducing systemic vasoconstriction. This study investigated the impact of FOS on vascular smooth muscle cell (VSMC) phenotypic transformation in hypertension. Experiments using western blotting revealed that FOS inhibits the Ang II-induced downregulation of α-SMA and SM22α and the upregulation of OPN in VSMCs. In addition, CCK8 assays, EdU staining, and Transwell assays demonstrated that FOS reduces Ang II-induced increases in VSMC cell viability, proliferation, migration, and MMP2 and MMP9 expression. Moreover, immunofluorescence and ELISA experiments showed that FOS suppresses Ang II-induced increases in ROS levels, NAD(P)H activity, and NOX2 and NOX4 expression in VSMCs. Western blotting also indicated that FOS inhibits Ang II-induced increases in TGF-β1 and p-Smad2/3 expression in VSMCs. Finally, FOS mitigates Ang II-induced VSMC proliferation, phenotypic transformation, migration, and oxidative stress by inhibiting the TGF-β1/Smad signaling pathway. In conclusion, these results suggest that FOS could be effective in managing vascular diseases, including hypertension.

Dicranostigma leptopodum (Maxim.) Fedde, an intriguing plant of the Papaveraceae family, exhibits numerous physiological activities, including antitumor, cytotoxic, immune-boosting, antibacterial, antioxidant, insecticidal, smooth muscle modulation, antiarrhythmic, fluorescent probe capabilities, as well as hypolipidemic and hypoglycemic effects. The plant's diverse pharmacological actions are believed to be attributed to its rich reservoir of alkaloids distributed throughout the entire plant. This review encompasses an exploration of the chemical constituents, pharmacological activities, species distribution, extraction and separation methodologies, and content determination of D. leptopodum, aiming to contribute to its further advancement in medicinal development.

A 60-year-old woman with bilateral lower extremity oedema for several days was admitted to the hospital on 21 November 2023. Previously, after receiving rectal cancer resection in February 2023, she had been receiving drug chemotherapy, during which she had normal urinalysis and renal function. However, 10 days before admission, after the drug regimen was adjusted to tislelizumab + fruquintinib, she developed bilateral lower extremity oedema with foamy urine; this was later extended to facial oedema. After a histologic examination of renal biopsy, it was judged as drug-induced glomerular microangiopathy (GMA) with focal segmental glomerulosclerosis-like lesions accompanied by immune complex-mediated glomerulonephritis. The condition was controlled by stopping the anti-tumour drug, lowering glucose with linagliptin, and providing renal protection with Nephritis Rehabilitation Tablets, and the patient recovered well at the follow-up visit after 6 months. This case may be GMA induced by tislelizumab or fruquintinib and was examined in this study.

Lung cancer is considered the most ubiquitous malignant form of cancer, and the current treatment strategies do not offer effective outcomes to the patients. The present study examined the effectiveness of natural drugs delphinidin (DN) and oroxylin A (OA) in inhibiting the development of lung cancer cells (A549) through the blocking of the Signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) intervene signaling pathways. These included cytotoxicity assessments, reactive oxygen species (ROS) levels, apoptotic morphological features, mitochondrial membrane potential (ΔΨm), nuclear fragmentation, and cell cycle analysis. Furthermore, the combination of DN and OA treatments on the expression of STAT-3, FAK, and various proliferation and apoptotic proteins was studied using western blotting. The results we have obtained are that the combination of DN and OA causes significant cytotoxicity, ROS, alteration of ΔΨm, and nuclear fragmentation, resulting in apoptosis of A549 cells. Furthermore, A549 cells treated with DN and OA concurrently displayed increased cell cycle arrest at the G2/M phase. Additionally, the combined DN and OA treatment inhibited the expression of STAT3 and FAK, suppressing proliferation and the induction of pro-apoptotic protein expressions in A549 cells. Thus, a combination of DN and OA could be used as a therapeutical approach to malignant forms of lung cancer.

The expansion of Chinese spiny frog (Quasipaa spinosa) aquaculture has increased the prevalence and severity of diseases such as "skin rot" disease, which is triggered by harmful bacteria. Previous studies have mainly focused on pathogen identification and vaccine development. However, frog immune responses following pathogenic bacterial infection have hardly been investigated. We thus examined the immune response of Chinese spiny frog to skin rot disease caused by Proteus mirabilis. The liver transcriptomes of Chinese spiny frog infected with P. mirabilis were sequenced using the MGISEQ-2000 platform. We identified a total of 138,936 unigenes, of which 32.35% were known genes. After infection with P. mirabilis, 801 genes showed differential expression, with 507 upregulated and 294 downregulated genes. These differentially expressed genes were enriched in pathways related to cytokine-cytokine receptor interaction, TNF signaling, and toll-like receptor signaling, according to Kyoto Encyclopedia of Genes and Genomes analysis. Following P. mirabilis infection, immune genes, including H2-Aa, hamp1, LYZ, CXCL10, and IRAK3, were significantly upregulated, while NLRP3, ADAM19, TYK2, FETUB, and MSR1 were significantly downregulated. The results provide important information on how the immune system of Chinese spiny frog responds to P. mirabilis infection and help understand the development of skin rot in cultured frog species.