Cell Biochemistry and Biophysics最新文献

The hypothalamic-pituitary-gonadal axis, which regulates steroidogenesis and germ cell formation, closely regulates the reproduction process. Nonetheless, other chemical mediators, such as kisspeptin, influence this axis. Kisspeptin is a hypothalamic neuropeptide that modulates the function of this axis and also plays a central role in energy balance. The present study reviews the impact and associated mechanisms of kisspeptin on male and female reproduction based on available evidence in the literature. Kisspeptin and its neurons exert anorexigenic activity, thus maintaining adequate energy balance for optimal reproductive function. Also, they stimulate the release of GnRH, resulting in the optimal performance of gonadal physiological processes viz. production of steroid sex hormones and germ cells. However, studies linking kisspeptin to reproduction are yet scanty. Hence, studies exploring the upstream and downstream signaling pathways activated by kisspeptin concerning reproduction in an attempt to better understand the associated mechanisms of the regulatory activities of kisspeptin on reproduction are recommended. In addition, potential factors that may modulate kisspeptin activities may be useful in the management of infertility and perhaps, in the development of contraceptives for those who do not intend to achieve conception.

In male rats, the flaxseed oil (FS-oil) modulatory properties were investigated on diazinon (DZN)-induced nephrotoxicity. Adult male Wistar rats were divided randomly into five groups. To induce nephrotoxicity, animals received DZN (70 mg/kg/day, p.o.). Also, treatment groups received FS-oil (100 and 200 mg/kg/day, p.o.). The animal treatment was 28 consecutive days. On the 29th day, serum and kidney tissue samples were removed and serum levels of the creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA), glutathione peroxidase (GPx), and catalase (CAT), were measured. Also, hematoxylin and eosin (H&E) staining was applied for histological studies. DZN significantly increased the BUN, creatinine, and MDA levels compared to the control group. Besides, DZN significantly decreased the GPx and CAT activity in the kidney tissue. However, the modulatory effects of FS-oil were observed by improving renal enzyme factors, inhibiting oxidative stress, and histological change. This study demonstrated that FS-oil ameliorated DZN-induced nephrotoxicity and can be used as a preventive agent against DZN toxicity because of the FS-oil antioxidant characteristics.

RAB3 proteins, a pivotal subgroup within the Rab protein family, are known to be highly expressed in brain and endocrine gland tissues, with detectable levels also observed in exocrine glands, adipose tissue, and other peripheral tissues. They play an indispensable role in the trafficking of cellular products from the endoplasmic reticulum (ER) to the Golgi apparatus and ultimately to secretory vesicles, participating in vesicle transport, mediating cell membrane adhesion, and facilitating membrane fusion during exocytosis. Among these, Rab3B, a specific subtype of RAB3, is a low-molecular-weight (approximately 25 kD) GTP-binding protein (GTPase) characterized by its typical GTPase fold, composed of seven β-strands (six parallel and one antiparallel) surrounded by six α-helices. Previous studies have proved the significant roles of Rab3B in vesicle transport and hormone trafficking. However, its involvement in cancer remains largely unexplored. This review aims to dig into the potential mechanisms of Rab3B in various cancers, including hepatocellular cancer, lung adenocarcinoma, pancreatic cancer, breast cancer, prostate cancer, neuroblastoma and cervical cancer. Given its pivotal functions and underexplored status in oncology, Rab3B stands out as a promising target for both diagnosis and therapy in cancer treatment, with investigations into its biological mechanisms in tumorigenesis offering significant potential to advance future diagnostic and therapeutic strategies across various malignancies.

Alveolar epithelial cell injury plays a key role in acute lung injury (ALI) and is a vital determinant of its severity. Here, we aimed to assess the protective effects of cinnamaldehyde (CA) on lipopolysaccharide (LPS)-induced A549 cells and elucidate the underlying mechanisms. A549 cells were stimulated with 1 μg/mL LPS for 24 h to establish an alveolar epithelial cell injury model and subsequently treated with CA or Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and lactate dehydrogenase release assays were used to evaluate apoptosis, cell viability, and lactate dehydrogenase activity, respectively. Levels of inflammatory cytokines (interleukin-6, interleukin-1β, tumor necrosis tactor-α, and interferon-γ) and oxidative stress markers (reactive oxygen species, superoxide dismutase, catalase, and malondialdehyde) were determined using enzyme-linked immunosorbent assay and specific assay kits, respectively. Furthermore, levels of apoptosis-related proteins (cleaved caspase-3, Bcl-2-associated X, and Bcl-2) and CaMKII were assessed via western blotting. CA did not exhibit significant cytotoxicity in A549 cells. It dose-dependently improved the cell viability, suppressed apoptosis, decreased cleaved caspase-3 and Bcl-2-associated X levels, and increased Bcl-2 levels in LPS-treated A549 cells. It also inhibited inflammatory factor release and oxidative stress in LPS-induced A549 cells. Similar results were observed in the KN93- and CA-treated groups. Western blotting assay revealed that CA and KN93 inhibited CaMKII pathway activation, as indicated by the reduced p-CaMKII and p-phospholamban (PLN) levels and p-CaMKII/CaMKII and p-PLN/PLN ratios. Overall, CA alleviated alveolar epithelial cell injury by inhibiting the inflammatory response and oxidative stress and inducing cell apoptosis in LPS-induced A549 cells by regulating the CaMKII pathway, serving as a potential candidate for ALI prevention and treatment.

Differential expression patterns of growth factor (EGFR, HER-2) and hormonal (ER, PR) receptors in breast cancer (BC) remain crucial for evaluating and tailoring therapeutic interventions. This study investigates differential expression profiles of hormonal and growth factor receptors in BC patients and across age groups, major subclasses, disease stages and tumor histology and survival rates, the efficacy of emerging clinical trial drugs (Dabrafenib and Palbociclib) and elucidating their molecular interaction mechanisms for efficient therapeutic strategies. Gene and protein expression analysis in the normal vs BC and across age groups and major subclasses reveals divergent patterns as EGFR and HER-2 levels are reduced in tumors versus normal tissue, while ER and PR levels are higher, particularly in luminal subtypes. However, there was no significant difference in survival rates among high and low/medium expression levels of EGFR and PR receptors. Conversely, patients with high HER-2 and ER expression exhibited poorer survival rates compared to low or medium expression levels. The in vitro findings indicate that Dabrafenib exhibits greater effectiveness than Palbociclib in suppressing various BC cells such as MCF-7 (Luminal), MDA-MB-231 (Triple-Negative), SKBR-3 (HER-2 + ) proliferation, promoting cell death, (IC₅₀ of Dab < Pal) at 24 and 48 h, ROS production, and reduced ER and PR, elevated HER-2 with no change in EGFR expression. Molecular simulation studies revealed Dabrafenib's thermodynamically stable interactions (ΔG), tighter binding, and less structural deviation in the order EGFR > HER-2 > ER > PR as compared to Palbociclib (HER-2 > ER > PR = EGFR). These results indicate that Dabrafenib, compared to Palbociclib, more effectively regulates breast cancer cell proliferation through specific interactions with hormonal and growth factor receptors towards a repurposing approach.

The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in adipogenic differentiation of human adipose-derived stem cells (hADSCs) remain elusive. This study confirmed that ITGA2/3/5 mRNA expressions were repressed during adipogenesis. Blockade of ITGA2/3/5 enhanced adipogenic differentiation of hADSCs. Oil red O staining found that more lipid droplets were apparent in the ITGA2/3/5 inhibition group following 14 d adipogenic induction than in the control group. In addition, inhibition of ITGA2/3/5 promoted the expression of adipogenesis-related genes (PPAR-γ, C/EBPα, FABP4). Mechanistically, ITGA2/3/5 functioned by regulating the Rac1 signaling pathway, which reasonably explains ITGA2/3/5's role in adipogenic differentiation of hADSCs. Our studies suggest that blockades of ITGA2/3/5 promote the adipogenic differentiation of hADSCs.

Silene vulgaris (Moench) Garcke and Stellaria media (L.) Vill is a perennial wild weed species belonging to the Caryophyllaceae family and is widely available and abundant in the environment. The present study has aimed to evaluate the anti-inflammatory potential of two underutilized wild edible plants, Silene vulgaris (Moench) Garcke and Stellaria media (L.) Vill. fractions employing in-vitro COX inhibitory assay. Invitro COX-2 inhibitory potential of MESV and MESM fractions was carried out using BioVision^R "COX Activity Assay Kit (Fluorometric)". LC-MS analysis of selected fractions was conducted to identify bioactive compounds that were further validated for their affinity determination toward target enzymes employing molecular docking studies using the LibDock program. In-vitro COX inhibitory assay revealed that hexane fraction of S. vulgaris (HFSV) and hexane fraction of S. media (HFSM) caused impressive inhibition of COX-2 enzyme with IC₅₀ values 1.38 µg/mL and 1.51 µg/mL respectively. Further, LC-MS analysis revealed the presence of 46 compounds in HFSV and 44 compounds in HFSM respectively. Amongst identified bioactive compounds in HFSV and HFSM, sinapinic acid and syringic acid showed good docking scores with COX-2 i.e., 89.256, and 82.168 respectively. Also, the availability of chrysin in HFSM and rhamnetin in HFSV exhibited good docking scores i.e., 115.092, and 112.341 with a selective affinity towards COX-2. The findings of in-vitro COX Inhibitory Activity and molecular docking studies highlighted the impressive anti-inflammatory properties of S. vulgaris and S. media, and require further investigations to establish them as therapeutic candidates in the management of inflammation and related issues.

The current work is the first ever report on the functionalization of CoO nanoparticles (NPs) using the bio active constituents of Abies pindrow Royle (A.pindrow) leaves. An efficient phytochemical extraction method was determined by comparing different extraction strategies for extracting the biologically active compounds of A.pindrow leaves. The phytocompounds were noticed via chromatographic techniques; High-performance liquid chromatography (HPLC) as well as the Gas chromatography-mass spectroscopy (GC-MS) followed by spectroscopic analysis that is the Fourier transform infrared spectroscopy (FTIR) along with Ultraviolet-visible spectroscopy (UV-Vis). The reducing properties of the phytochemicals were investigated by efficiently synthesizing metal oxides nanoparticles (CoO NPs) by treating aqueous plant extract with Co(NO₃). 6H₂O aqueous complex. The newly synthesized NPs were characterized via X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) and field emission-scanning electron microscopy (FE-SEM). Finally, the GCMS, FTIR and UV-Vis identified the A.pindrow leaves biocomponents as capping and reducing mediator of the synthesized CoO nanoparticles. FTIR confirmed the prepartion of CoO NPs as well as the capping and stabilizing agents of A.Pindrow at 2378.31 cm^-1, 1370.11 cm^-1, 1260.57 cm^-1, 937.4 cm^-1 and 607.24 cm^-1 having carboxylic acid, alcohols, aromatics, alkenes, aromatic amines, esters as well as ethers functional groups, flavonols and flavonoids phytochemicals. Moreover GCMS analysis revealed the dominating constituents of A.pindrow leaf extracts are carbohydrates, terpenoids, alkanoids, flavonoids as well as phenols. Furthermore, the antibacterial and bioactive agent, tannis was also observed in aqueous extract. These phytochemicals noticed in this current work, has antioxidant potential, that is why they have shown biomedical applications. The present manipulation, further articulated that, maximum phytochemicals extraction of A. pindrow leaves was illustrated in the aqueous extract as compared to ethyl acetate and ethanol.

As the world grapples with the coronavirus-19 (COVID) pandemic, more reports are coming in regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endotheliopathy. It is a vascular condition in which endothelial cell injury or damage inflicts anatomical and functional changes in the endothelium, significantly impacting the physiological process and function. Previously, it was assumed that SARS-CoV-2 infects respiratory epithelial cells via spike glycoproteins present on the surface of the virus. However, severe cases and different autopsy studies described the clandestine role of this virus in infecting endothelial cells other than epithelial cells. It was observed that SARS-CoV-2 targets the pulmonary and extrapulmonary systems to damage the microvasculature and affect respiratory functioning, resulting in the onset of endotheliopathy, thrombosis, inflammation, pulmonary edema, and fibrosis. Such deleterious events are the consequence of the hyperactive immune response initiated by the SARS-CoV-2 infection, leading to pulmonary and extrapulmonary complications. However, the molecular mechanism behind endotheliopathy and other complications caused by this virus is elusive and will be unraveled by covering recent literature in this mini-review.

Osteoarthritis (OA) is a prevalent joint disease affecting orthopedic patients. Its incidence is steadily increasing, causing great economic hardship for individuals and society as a whole. OA is connected with risk factors such as genetics, obesity, and joint diseases; yet, its pathophysiology is still largely understood. At present, several cell death pathways govern the initiation and advancement of OA. It has been discovered that the onset and progression of OA are strongly associated with pyroptosis, senescence, apoptosis, ferroptosis, and autophagy. Ferroptosis and autophagy have not been well studied in OA, and elucidating their molecular mechanisms in chondrocytes is important for the diagnosis of OA. For this reason, we aim was reviewed recent national and international developments and provided an initial understanding of the molecular pathways underlying autophagy and ferroptosis in OA. We determined the reference period to be the last five years by searching for the keywords "osteoarthritis, mechanical stress, Pizeo1, ferroptosis, autophagy, ferritin autophagy" in the three databases of PUBMED, Web of Science, Google Scholar. We then screened irrelevant literature by reading the abstracts. Ferroptosis is a type of programmed cell death that is dependent on reactive oxygen species and Fe²⁺. It is primarily caused by processes linked to amino acid metabolism, lipid peroxidation, and iron metabolism. Furthermore, Piezoelectric mechanically sensitive ion channel assembly 1 (PIEZO1), which is triggered by mechanical stress, has been revealed to be intimately associated with ferroptosis events. It was found that mechanical injury triggers changes in the intracellular environment of articular chondrocytes (e.g., elevated levels of oxidative stress and increased inflammation) through PIEZO1, ultimately leading to iron death in chondrocytes. Therefore, we believe that PIEZO1 is a key initiator protein of iron death in chondrocytes. Widely present in eukaryotic cells, autophagy is a lysosome-dependent, evolutionarily conserved catabolic process that carries misfolded proteins, damaged organelles, and other macromolecules to lysosomes for breakdown and recycling. Throughout OA, autophagy is activated to differing degrees, indicating that autophagy may play a role in the development of OA. According to recent research, autophagy is a major factor in the process that leads cells to ferroptosis. Despite the notion of ferritinophagy being put forth, not much research has been done to clarify the connection between ferroptosis and autophagy in OA.