Cell Biochemistry and Function最新文献

The study aimed to investigate the molecular mechanisms by which Biochanin A inhibits proliferation and induces apoptosis in breast cancer cells. Cultured MCF-7 cells were divided into four groups: Group 1-control, while Groups 2, 3, and 4 were treated with Biochanin A at different concentrations. After treatment, the cells were monitored, and morphological changes were examined after 24 h of incubation. The results showed that Biochanin A inhibited cell proliferation, increased reactive oxygen species formation, and induced apoptosis. Furthermore, western blot analysis revealed that Biochanin A-treated cells exhibited lower expression of the Bcl-2, p-PI3K and p-AKT and higher expression of proapoptotic genes, including Bax, Caspase-3, Caspase-9, and cytochrome c. Additionally, PCR array analysis indicated that the gene expression levels of cyclin D3, cyclin B1, CDK1, CDK2, and CDK4 were downregulated, while the expression levels of p21, p27, and p53 were significantly upregulated. These results suggest that Biochanin A can suppress the viability of breast cancer cells and induce apoptosis via the mitochondrial pathway, along with inhibition of the Pi3K/Akt signaling pathway and modulation of cell cycle markers.

Hepatocellular carcinoma (HCC) continues to pose a global health concern, necessitating the exploration of innovative therapeutic approaches. In the recent decade, targeting tumor stroma consisting of extracellular matrix (ECM), immune cells, vascular system, hypoxia, and also suppressive mechanisms in HCC has attracted interest in repressing tumor growth and metastasis. Phytochemicals have attained considerable attention because of their manifold biological effects and high capacity for anticancer activities. These chemical agents have shown the capability to modulate different cells and secretions within the stroma of malignancies. In recent years, the development of nanoformulations has further enhanced the therapeutic potential of phytochemicals by improving their solubility, bioavailability, and targeted delivery to tumor tissues. This review aims to provide an encyclopedic overview of the potential of phytochemicals and their nanoformulations as promising therapeutic strategies for targeting HCC. The review initially highlights the broad array of phytochemicals exhibiting potent anticancer properties, including flavonoids, alkaloids, terpenoids, and phenolic compounds, among others. Then, the nanoformulations and modification of these agents will be reviewed. Finally, we will review the latest experiments that have examined the modulation of HCC using adjuvant phytochemicals and their nanoformulations.

Perimenopausal syndrome is a significant issue that disturbs women's metabolism, mood and quality of life. Apigenin (4′,5,7-trihydroxyflavone) is a natural flavonoid that exhibits antioxidant, anti-inflammatory and anticancer effects. The present study aims to investigate the effect of apigenin on perimenopausal syndrome by combining bioinformatics analysis with in vivo experiments. The mouse model with perimenopausal syndrome was established using 4-vinylcyclohexene diepoxide (VCD) treatment. Apigenin alleviated VCD-induced disorder of estrous cycle and shrinkage of ovarian tissue. The reduction of anti-Muller hormone and the increase of follicle stimulation hormone and luteinizing hormone triggered by VCD were reversed by apigenin in a dose-dependent manner. Apigenin suppressed the VCD-induced decrease of primordial, primary, secondary and antral follicle number in ovarian tissue. Oxidative stress in ovarian tissue was activated by VCD treatment through increasing the reactive oxygen species production. High concentration of apigenin significantly reversed the alteration induced by VCD. Apigenin alleviated VCD-induced cell apoptosis through regulating Bax, Bcl-2, cleaved PARP1 and caspase-3. Furthermore, the phosphorylation of AKT and FOXO3a was inhibited by VCD and activated by apigenin in a dose-dependent manner. Collectively, apigenin effectively mitigates the ovarian dysfunction through suppressing oxidative stress and apoptosis via the AKT/FOXO3a signaling pathway.

l-cysteine is a versatile amino acid that plays a pivotal role in synthesizing critical molecules, enzymatic catalysis, regulation, and electron transport. It also has tremendous potential to act as an adjuvant for enhancing the biological efficacy of various nanoparticles in vivo. The current study is aimed to evaluate the protective efficacy of silver nanoparticles (AgNPs) decorated with l-cysteine in carbon tetrachloride (CCl₄)-induced hepatotoxicity in the Swiss albino rats as an animal model. The rats were divided into four treatment groups: Group 1 (control without any treatments), Group 2 treated with AgNPs and l-cysteine composite (5 mg/kg body weight on every third day), Group 3 (single dose of 1 mL/kg CCl₄), and Group 4 treated with AgNPs-l-cysteine composite in the rats pre-administered with CCl₄. After treatment for a month, the rats were killed, and their liver and blood samples were subjected to biochemical analysis and histological examination.: Group 2 showed all the parameters comparable to control Group 1. On the contrary, CCl₄-treated, Group 3 rats showed abnormally raised liver function markers (AST and ALT) and liver toxicity markers (GGT, LDH, and total bilirubin) concomitant with disturbed oxidative stress parameters (GSH and MDA) compared to the control. However, Group 4 rats demonstrated a significant recovery from CCl₄-induced biochemical alteration in the animals as compared to Group 3. In addition, the biochemical measurements were harmonious with the histological analysis of the liver sections of the treated rats. Hence, the proposed AgNPs-l-cysteine composite is a potent hepato-protecting agent in vivo that can be employed in regulating CCl₄-induced hepatotoxicity or any drug or potential pharmaceutical compound exerting similar toxicity.

Radiation therapy is indispensable in medical practice but often causes adverse effects on healthy tissues, necessitating the search for natural radioprotectors. This study investigates the protective effect of Biochanin A (BCA) against gamma radiation-induced oxidative stress and DNA damage in Swiss albino mice. Gamma radiation, a potent ionizing source, generates reactive oxygen species (ROS) that damage cellular biomolecules, including DNA. Antioxidants play a crucial role in neutralizing ROS and preventing oxidative damage. Swiss albino mice were divided into control, BCA control (10 mg/kg body weight), radiation alone (7 Gy), and radiation+ BCA pretreatment groups. BCA, a natural isoflavone with known antioxidant and cytoprotective properties, was administered intraperitoneally before radiation exposure. After irradiation, lipid peroxidation levels, antioxidant enzyme activities/level (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), expression levels of DNA repair genes (P53, P21, GADD45α), apoptotic markers (Bax, Bcl-2, Caspase-3, -9 and Cytochrome-C), and inflammatory marker (NF-κB) were analyzed in small intestine tissue. Our findings indicate that gamma radiation significantly elevated lipid peroxidation levels and altered antioxidant enzyme activities, indicating oxidative stress. However, BCA pretreatment mitigated these effects by bolstering antioxidant defences, reducing radiation-induced oxidative damage. Additionally, BCA altered apoptotic markers, NF-κB expression, promoting cell survival mechanisms. At the molecular level, BCA pretreatment upregulated key DNA repair genes (P53, P21, GADD45α), crucial for repairing radiation-induced DNA damage and maintaining genomic stability. These results underscore BCA potential as a radioprotector, suggesting its efficacy in mitigating radiation-induced oxidative stress and preserving cellular integrity. In conclusion, BCA demonstrates promising radioprotective properties by attenuating oxidative stress, enhancing antioxidant defences, modulating apoptotic pathways, and promoting DNA repair mechanisms following gamma radiation exposure. Further research is necessary to elucidate its precise mechanisms of action and explore its potential therapeutic applications in radiation oncology and environmental radioprotection.

Diabetes mellitus (DM) is a chronic metabolic disorder that affects most vital organs in the body. Approximately 463 million people were diagnosed with DM worldwide in 2019. The incidence of DM is estimated to increase by 700 million by 2045. Diabetic wounds (DWs) are among the most severe complications in people suffering from DM. Although diverse standard care treatment strategies are available for DWs, they are unsatisfactory because of the multifactorial pathophysiology of DWs. Cutting-edge nanoparticles are increasingly being used in treating DWs. In particular, few nanoparticles naturally act as ROS scavengers, promote angiogenesis, exhibit antimicrobial activity, and form the extracellular matrix, which is considered beneficial for DW healing. The current review focused on the pivotal potential of the present nanoparticles for DW healing, emphasizing and highlighting the use of the nanoparticles in delivering micro and macromolecules in tissue regeneration for DW healing and future perspectives.

Stress refers to an organism's response to environmental threats in normal condition to maintain homeostasis in the body. In addition, strong inflammatory reactions induced by the hypothalamic–pituitary–adrenal (HPA) axis under stress condition during a long time. Reciprocally, chronic stress can induce the irritable bowel syndrome (IBS) which is a well-known gut disorder thereby play an important role in the promotion and pathophysiology of neuropsychiatric diseases. It has been demonstrated that leaky gut is a hallmark of IBS, leads to the entrance the microbiota into the bloodstream and consequent low-grade systemic inflammation. In the current review, we will discuss the mechanisms by which stress can influence the risk and severity of IBS and its relationship with neuroinflammation. Also, the role of probiotics in IBS co-existing with chronic stress conditions is highlighted.

Staphylococcus aureus, one of the most notorious pathogens, develops antibiotic resistance by the formation of a thick layer of exopolysaccharides known as biofilms. Sortase A, a transpeptidase responsible for biofilm formation and attachment to the host surface, has emerged as an important drug target for development of anti-virulence agents. A number of sortase A inhibitors, both peptide and non-peptides are reported which involved the use of several experiments which may provide insights regarding binding affinity, specificity, safety, and efficacy of ligands. In this review, we focus on the principles, pros and cons, and the type of information obtained from biophysical (FRET assay, Microscale Thermophoresis, Surface Plasmon Resonance, CD spectroscopy etc.) and biological (cell viability assay, biofilm formation assay, CLSM, western blot analysis, in vivo characterization on mice etc.) methods for estimation of probable sortase A inhibitors, which might be helpful to the researchers who might be interested to delve into the development of sortase A inhibitors as a drug, to address the burning question of antimicrobial resistance (AMR).

Tyrosinemia type 1 (TT1) is caused by fumarylacetoacetate hydrolase activity deficiency, resulting in tissue accumulation of upstream metabolites, including succinylacetone (SA), the pathognomonic compound of this disease. Since the pathogenesis of liver and kidney damage observed in the TT1-affected patients is practically unknown, this study assessed the effects of SA on important biomarkers of redox homeostasis in the liver and kidney of adolescent rats, as well as in hepatic (HepG2) and renal (HEK-293) cultured cells. SA significantly increased nitrate and nitrite levels and decreased the concentrations of reduced glutathione (GSH) in the liver and kidney, indicating induction of reactive nitrogen species (RNS) generation and disruption of antioxidant defenses. Additionally, SA decreased the GSH levels and the activities of glutathione peroxidase, glutathione S-transferase, glutathione reductase, and superoxide dismutase in hepatic and renal cells. Noteworthy, melatonin prevented the SA-induced increase of nitrate and nitrite levels in the liver. Therefore, SA-induced increase of RNS generation and impairment of enzymatic and nonenzymatic antioxidant defenses may contribute to hepatopathy and renal disease in TT1.

Tumor immunotherapy includes bispecific antibodies (BsAbs), immune checkpoint inhibitors (ICIs), vaccines, and adoptive cell immunotherapy. BsAbs belong to the family of antibodies that can specifically target two or more different antigens and are a promising option for tumor immunotherapy. Immune checkpoints are antibodies targeting PD-1, PD-L1, and CTLA4 and have demonstrated remarkable therapeutic efficacy in the treatment of hematological and solid tumors, whose combination therapies have been shown to synergistically enhance the antitumor effects of BsAbs. In addition, the clinical efficacy of existing monoclonal antibodies targeting PD-1 (e.g., ipilimumab, nivolumab, pembrolizumab, and cemiplimab) and PD-L1 (e.g., atezolizumab, avelumab, and durvalumab) could also be enhanced by conjugation to small drugs as antibody−drug conjugates (ADCs). The development of truly effective therapies for patients with treatment-resistant cancers can be achieved by optimizing the various components of ADCs.