Cell Biochemistry and Biophysics最新文献

Hexavalent chromium Cr (VI), an endocrine disruptor, has been a possible risk factor for male-oriented infertility, due to its damaging effect on testes. Thus, we sought to analyze the protective effect of Aloe vera (A. vera) and their mediated silver nanoparticles on testes in mice. Sixty male mice were exposed to Cr (VI) and A. vera extract (AV) and their mediated silver nanoparticles (AV+NP) as protective agents for 60 days. The organ index, hormone analysis, enzyme analysis, metal estimation, computer assisted sperm analysis (CASA), histopathology of testes and micrometric data were assessed using one-way ANOVA. A significant reduction was found in the level of catalase (87.1 ± 7.02 mmol/mL), superoxide dismutase (61.8 ± 2.5 mmol/mL), glutathione (1.51 ± 0.9 µmol/mL), luteinizing hormone (LH) (1.6 ± 0.3 ng/mL), and testosterone (2.3 ± 0.2 ng/mL) in Cr exposed group. However, a significant increase was found in Cr exposed mice in follicle-stimulating hormone (FSH) (159.9 ± 4.98 ng/mL) level. With administration of AV and AV+NP, we found a significant increase in level of catalase (143.4 ± 2.6 mmol/mL; 134.8 ± 9.1 mmol/mL), superoxide dismutase (205.8 ± 13.0 mmol/mL; 187.3 ± 9.9 mmol/mL), glutathione (2.98 ± 0.2 µmol/mL; 3.06 ± 0.2 µmol/mL), luteinizing hormone (LH) (2.9 ± 0.2 ng/mL; 3.1 ± 0.2 ng/mL), and testosterone (3.9 ± 0.1 ng/mL; 4.58 ± 0.2 ng/mL) respectively, whereas, FSH level was decreased (84.7 ± 7.2 ng/mL; 70.4 ± 4 ng/mL). The CASA showed a noticeable decrease in sperm quantity and kinematics after Cr exposure. In AV and AV+NP exposed groups, the sperm kinematics were improved significantly. The histopathological studies showed necrosis of Leydig cells, absence of sperm tails, and destruction in the zone of mitosis and meiosis in Cr-exposed groups. The micro morphometric analysis showed a significant reduction in the size of spermatogonia (38.9 ± 0.7 µm), size of spermatocytes (26.91 ± 1.4 µm), head breadth (5.4 ± 0.7 µm), head length (19.98 ± 1.2 µm), middle piece, and tail length (0.00 ± 0.0 µm; 0.00 ± 0.0 µm) in Cr exposed mice. However, with the AV and AV+NP administration, the testis architecture was improved, exhibiting an improved zone of mitosis and meiosis. A. vera exposure induced a significant decrease in the size of spermatogonia (24.1 ± 2.4 µm), and size of spermatocytes (18.7 ± 1.2 µm), whereas a significant increase in sperm head breadth (15.1 ± 0.8 µm), and head length (34.4 ± 2.8 µm) was found. We found that AV and AV+NP can potentially reduce oxidative damage induced by Cr (VI) in testes and promote fertility.

The increasing resistance to treatments and limited effectiveness of singular medications against cancer and foodborne bacteria highlight the need for therapeutic synergy using multiple natural components. This study aimed to develop a blend nanoemulsion (NE) combining two plant essential oils, lemon (LEO) and peppermint (PEO), for anticancer and antibacterial testing. The chemical composition of PEO and LEO was analyzed by GC-MS, identifying D-limonene (77.89%) and menthol (56.63%) as their primary constituents. The NEs were prepared with droplet sizes of 57.2 (LEO), 104.2 (PEO), and 44.3 nm (blend), confirmed by FTIR. Cellular viability, DNA damage, and cell cycle progression in A549 lung cancer cells were assessed, showing a 50% reduction in viability after treatment with LEO (1.7 mg/mL), PEO (4.9 mg/mL), and the blend (2.5 mg/mL). Blend NE induced apoptosis and halted the S-phase of the cell cycle. Antibacterial activity was evaluated against Bacillus cereus, Bacillus subtilis, and Pseudomonas aeruginosa. Regarding MIC, blend NE (20 mg/mL) was more effective than LEO-NE (40 mg/mL) and PEO-NE (80 mg/mL) against B. subtilis. TEM analysis confirmed bacterial lysis, supporting the blend NE's superior antimicrobial effects. This synergy holds promise for enhanced cancer treatment and antibacterial applications.

Lysophosphatidic acid (LPA) receptors (LPA₁ to LPA₆) are implicated in cancer pathogenesis. Stromal cells within the tumor microenvironment contribute to the malignant progression of cancer cells. Given that stromal cells can contribute to the malignant behavior of tumor cells, this study investigated the role of LPA receptor-mediated signaling in modulating stromal cell-induced cancer cell growth. Lung cancer A549 cells were co-cultured with lymphatic endothelial SVEC4-10 cells and/or fibroblast 3T3 cells, or cultured in their respective supernatant. Co-culture with SVEC4-10 and/or 3T3 cells altered the expression of LPAR1, LPAR2, and LPAR5 genes in A549 cells. LPA enhanced A549 cell growth in the supernatant derived from co-cultured SVEC4-10 and 3T3 cells, exceeding the effects observed in the supernatant from SVEC4-10 or 3T3 cells alone. A549 cell growth was suppressed by AM966 (LPA₁ antagonist) and TC LPA5 4 (LPA₅ antagonist), and promoted by GRI-977143 (LPA₂ agonist). Autotaxin (ATX) expression was upregulated in A549 cells co-cultured with SVEC4-10 and/or 3T3 cells, and lysophosphatidylcholine (LPC) treatment enhanced A549 cell growth in the co-culture supernatant of both cell types. Mouse lung cancer LL/2 cells also showed increased growth in response to LPA when cultured with the co-culture supernatant, and this effect was inhibited by AM966 and TC LPA5 4, and promoted by GRI-977143. These findings suggest that co-culture of SVEC4-10 and 3T3 cells more effectively promotes lung cancer cell growth through LPA receptor signaling than either cell type alone.

Obesity and type II diabetes are independent risk factors for Endometrial cancer (EC) development. Elevated levels of insulin-like growth factor-1 (IGF-1), insulin resistance, and the increased activity of IGF-1 receptor is linked to EC development through the PI3K/AKT/mTOR pathway. The antidiabetic agent metformin is a promising repurposing drug for cancer treatment, but the mechanisms underlying its effects are not completely known. This study evaluated how metformin could act against the EC cell line Ishikawa cultured in vitro or grafted into female Balb/C nude mice. In vitro experiments demonstrated that treatment with 25 mM of metformin reduced cell viability through promoting cytotoxicity, mitochondrial dysfunction, apoptosis, and cell cycle arrest (G1 phase). Mice treatment with 250 mg/kg of metformin for 28 days did not change serum IGF-1 levels nor decreased the grafted cell-induced tumor weight and cell proliferation, but prevented its volume growth while genes of the IGF1-R and PI3K/AKT/mTOR pathways (AKT2, GAPDH, FOXO3, IGF1R, INSR, MAPK3, MTOR, and SHC1) were downregulated. Metformin treatment was more impacting for the in vitro model, but our molecular results provide valuable insights into the possible action of metformin against EC tumoral cells at physiological level. In-silico analysis using Cytoscape indicated that metformin was not described as interacting with AKT2 and SHC1 proteins. Besides interacting with metformin, mTOR and MAPK3 present the larger number of interactions with the other proteins. These four genes/proteins emerge as potential targets for deepening studies to determine the metformin's role in longer EC treatment using animal models.

Geniposide (GE), an iridoid glycoside from Gardenia jasminoides J.Ellis, exhibits anti-inflammatory, antioxidant, antidepressant, and neuroprotective properties. The excessive presence of corticosterone (CORT) can lead to neurotoxicity and inflict harm upon nerve cells. This study aimed to examine GE's neuroprotective effects on CORT-induced damage in PC12 cells. Cells were pre-treated with GE for 3 h, then exposed to CORT for 24 h. Cell viability and lactate dehydrogenase (LDH) leakage were measured, apoptosis was assessed via flow cytometry, and immunofluorescence was used to detect MAP2 and PSD95 expression. The detection of glutamate (Glu) receptor, BDNF pathway, synaptic plasticity-related protein, and apoptosis pathway were performed using Western blot. The findings indicated that GE effectively prevented the reduction in cell viability, apoptosis, and LDH release caused by CORT. In PC12 cells, the expression of MAP2 and PSD95 were significantly enhanced by GE. Furthermore, GE reduced NR1, NR2A, NR2B, and Bax levels, increased EAAT2/3, Bcl-2, and proteins linked to BDNF and synaptic plasticity, and inhibited Caspase-3 and Caspase-9. GE shows neuroprotective and anti-apoptotic properties against CORT-induced cellular damage through BDNF pathway activation and Bax/Bcl-2 pathway suppression.

This study investigates the anticancer effects and the underlying molecular mechanisms of Mimulone on human hepatoma Hep3B cells. Mimulone was found to inhibit cell proliferation and induce apoptosis in Hep3B cells, as demonstrated by annexin V-fluorescein isothiocyanate staining and flow cytometry analyses. Western blot analysis revealed that Mimulone treatment decreased the levels of procaspase-3 and PARP, while increasing the levels of cleaved caspase-3, -8, PARP, Fas, FasL, and FADD. These results suggest that Mimulone induces apoptotic cell death through the activation of the death receptor-mediated (extrinsic) pathway. Furthermore, Mimulone inactivated the extracellular signal-regulated kinase (ERK) and Akt signaling pathways, further enhancing its pro-apoptotic effects. These findings indicate that Mimulone has potential as a therapeutic agent targeting apoptosis and survival signaling pathways in hepatocellular carcinoma cells.

Inflammation is a fundamental feature of many diseases. It is part of a programmed response to threats concerning an organism's integrity. Programming is modified by the environment and is made up of complex relationships between regulating mechanisms of metabolism. In this study, S. cerevisiae were used to establish a model of reprogramming, utilizing in this case a 23-h water-only fast compared to a standard high glucose environment. Crude mitochondrial preparations were made using differential centrifugation. Pyruvate Dehydrogenase Complex (PDC) activity was approximated via an assay measuring changes in ability to produce NADH. Experiments with lipopolysaccharide (LPS) involved a procedure exposing the yeast to LPS (100 ng/ml) for 90 min prior to mitochondrial isolation. Oxygen consumption rates were measured using a Clark type electrode setup. Results suggest that fasting in water can reprogram yeast mitochondria. Mechanisms modified by this process appear to regulate the ability of the mitochondria to maintain the relationship of oxygen consumption (indicative of electron transport) to RCR (indicative of membrane potential), largely separate to ATP synthesis. Although the ADP/O may be lower in the progeny of the fasted yeast, it is the fact that it maintained a higher RCR with the same or lower ADP/O, that is the important observation. Based on estimations of PDC activity, the progeny of the high glucose exposed yeast appeared less able to readily utilize pyruvate for respiration. In addition, the LPS challenge also revealed possible changes in immune response that may be resulting from glucose toxicity. In conclusion, S. cerevisiae can be reprogrammed to metabolically respond differently to a specific environment. This includes both a high glucose environment and a high glucose environment containing LPS (a pathogen associated molecular pattern), with regard to bioenergetic changes. These changes are associated in mammalian cells with the switch to a proinflammatory and proliferative metabolic state, analogous to that of M1 macrophages (decreased OxPhos and lower RCR), seen in atherosclerosis and other conditions. This data supports the use of this model for further investigation of proinflammatory processes and potential interventions to restore proper regulation of immune responses.