Cell Biochemistry and Function最新文献

Autophagy is a physiologically regulated cellular process orchestrated by autophagy-related genes (ATGs) that, depending on the tumor type and stage, can either promote or suppress tumor growth and progression. It can also modulate cancer stem cell maintenance and immune responses. Therefore, targeted manipulation of autophagy may inhibit tumor development by overcoming tumor-promoting mechanisms. The inflammasome is another multifunctional bioprocess that induces a form of pro-inflammatory programmed cell death, called pyroptosis. Dysregulation or overactivation of the inflammasome has been implicated in tumor pathogenesis and development. Additionally, autophagy can inhibit the NLRP3 inflammasome by removing inflammatory drivers. Recent research suggests that the NLRP3 inflammasome, in turn, affects autophagy. Understanding the complex interplay between autophagy and inflammasomes could lead to more precise and effective strategies for cancer treatments. In this review, we summarize the impact of autophagy and inflammasome dysregulation on tumor progression or suppression. We then highlight their targeting for cancer treatment as monotherapy or in combination with other therapies. Furthermore, we discuss the interaction between autophagy and tumor-promoting inflammation or the NLRP3 inflammasome. Finally, based on recent findings, we review the potential of this interaction for cancer treatment.

We hypothesized that melatonin (Mel) supplementation may offer therapeutic benefits for obesity, particularly in women. Therefore, the study evaluated Mel's effects on white adipose tissue (WAT) in diet-induced obese female mice. Four-week-old C57BL/6 females were assigned to either a control diet (C group) or a high-fat diet (HF group) for 6 weeks (n = 20/group). Following this, Mel was administered (10 mg/kg/day) for 8 weeks (n = 10/group), resulting in four groups: C, CMel, HF, and HFMel. The HF group developed obesity. HFMel displayed reduced fat pad size, lower plasma insulin, and improved glucose tolerance and insulin resistance compared to HF. In ovarian WAT (oWAT), HFMel versus HF showed reduced pro-inflammatory markers, less endoplasmic reticulum (ER) stress, and smaller adipocyte size. In subcutaneous WAT (sWAT), HFMel versus HF demonstrated increased adipocyte multiloculation, higher uncoupling protein-1 expression, and elevated thermogenic gene expression. Principal component analysis of gene expressions in oWAT and sWAT revealed significant differences: in oWAT, ER stress and inflammation markers were linked to the HF group, while HFMel and CMel clustered together, indicating a beneficial Mel effect. In sWAT, HFMel and CMel clustered on the opposite side of HF, which is associated with thermogenic gene expressions. In conclusion, the findings demonstrate that Mel supplementation in obese female mice, even when maintained on an HF diet, effectively modulated weight gain and reduced ovarian and subcutaneous fat accumulation. Mel supplementation positively influenced insulin resistance, inflammation, and ER stress while promoting thermogenesis in WAT in obese female mice.

Phospholipase A2 receptor 1 (PLA2R1) exists important role in membranous nephropathy. In this study, we evaluate a PLA2R1 in a middle-aged rat model of renal function repair to further investigate the molecular mechanisms of membranous nephropathy. We analyzed the PLA2R1 knockout (KO) model and PLA2R1 knock in (KI) model in rats, extending the time to 85 weeks of age. Urinary biochemical indicators were detected using a fully automated biochemical analyzer. The complement C3, IgG, and Nephrin were detected using the immunofluorescence method. Western blot was used to detect the expression levels of complement C3, IgA and PLA2R1 in middle-aged models. The KO model continues to display glomerular proteinuria, complement C3 aggregation, and IgA and IgG deposition. Comparing with the KO model, the deposition of complement C3 and IgA in the glomerulus of the KI chimeric model still exists and IgG expression weakened. Inserting humanized PLA2R1 into rats can continuously repair partial renal function and reduce proteinuria, which will help investigate the pathogenesis of membranous nephropathy and complement activation signaling pathways.

Rheumatoid arthritis (RA), a highly disabling autoimmune disease, is characterized by joint damage and synovial hyperplasia. This paper was designed to explore the effect and mechanisms of Aconitum diphtheria on the proliferation and apoptosis of RA fibroblast-like synoviocytes (RA-FLS). First, RA-FLS was treated with different doses of A. diphtheria extracts. Then, an inverted biological microscope was adopted to observe the RA-FLS morphology. Subsequently, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining, Cell Counting Kit-8 and western blot were utilized to analyze the apoptosis, proliferation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway-related proteins in RA-FLS, respectively. The experimental results disclosed that, after treatment of RA-FLS with A. diphtheria extracts, the cells became round and the intercellular space was increased. Besides, the RA-FLS proliferation was effectively inhibited by A. diphtheria extracts, while the apoptosis was promoted. Additionally, A. diphtheria extracts could effectively downregulate the expression levels of p-NF-κB (p50), NF-κB (p50), p-NF-κB (p65), and NF-κB (p65). Collectively, A. diphtheria can effectively inhibit RA-FLS proliferation and promote apoptosis in a dose-dependent manner. Similarly, A. diphtheria is able to downregulate p-NF-κB and NF-κB protein expression, but there is no dose–response relationship.

Combination therapy offers a promising advantage because they target multiple pathways involved in the pathogenesis and progression of Alzheimer's disease. This study aimed to investigate the synergistic effect of donepezil and each of vitamin B12, vitamin B6 and vitamin B1 on aluminium chloride (AlCl₃)-induced neurotoxicity in rats. Fifty-four rats were divided into nine groups of six. Group I received distilled water, group II—AlCl₃ (100 mg/kg), group III- AlCl₃ (100 mg/kg) + Donepezil (10 mg/kg), group IV-AlCl₃(100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B12 (5 mg/kg), group V-AlCl₃ (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B6 (5 mg/kg), group VI-AlCl₃ (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B1 (5 mg/kg), group VII-AlCl₃ (100 mg/kg) + Vitamin B12 (5 mg/kg), group VIII-AlCl₃ (100 mg/kg) + Vitamin B6 (5 mg/kg), group IX-AlCl₃ (100 mg/kg) + Vitamin B1 (5 mg/kg). Treatment lasted for 40 days. Biochemical analyses of the brain revealed that chronic administration of AlCl₃ significantly increased the level of inflammatory cytokines, caspase 9, malondialdehyde, nitric oxide and acetylcholinesterase (AChE) activity, while causing a significant decrease in superoxide dismutase (SOD) activity, Nrf2, reduced glutathione, dopamine and norepinephrine. Results also showed that AlCl₃ caused cognitive impairment as indicated by a reduction in the percentage alternation index and hypo-activity towards novel object in animals treated with AlCl₃ only. Moreover, results from biochemical evaluations indicated that treatment with donepezil, B vitamins and combination of donepezil and B vitamins attenuated the deficits in dopamine, norepinephrine, Nrf2, SOD and reduced glutathione, while also reducing the elevated levels of malondialdehyde, nitric oxide, AChE, caspase 9 and inflammatory markers. These observations were corroborated by result of histopathological evaluation. The combination of donepezil and vitamin B12, B6 and B1 proved to be more effective than donepezil monotherapy. Donepezil conferred significant protection against AlCl₃–induced neurotoxicity, however, the combination of donepezil and vitamin B12, vitamin B6 and Vitamin B1 significantly performed better in neuroprotective indices than donepezil monotherapy. The combination of donepezil and vitamin B1 was better amongst the three combination therapies in this study.

Tuberculosis (TB) remains a significant global health challenge, exacerbated by the emergence of drug-resistant strains of Mycobacterium tuberculosis (M. tb). The complex biology of M. tb, particularly its key porins, contributes to its resilience against conventional treatments, highlighting the exploration of innovative therapeutic strategies. Following with this challenges, the present study investigates the bioactivity properties of phenolic compounds derived from the terpene groups, specifically through Thymol (THY) against M. smegmatis as a surrogated model for M. tb. Furthermore, the study employed with combination of two approaches i.e., in vitro assays and computational methods to evaluate the efficacy of THY against M. smegmatis and its interaction with M. tb biofilm and efflux pump proteins, particularly Rv1258c and Rv0194. The in vitro findings demonstrated that THY exhibits inhibitory activity against M. smegmatis and shows promising interaction with a combination of isoniazid (INH) and rifampicin (RIF) of TB regimens. Furthermore, THY demonstrated significant inhibitory action towards motility and biofilm formation of M. smegmatis. The combination of THY with INH and RIF exhibited a synergistic effect, enhancing the overall antimicrobial efficacy. Additionally, THY displayed reactive oxygen species (ROS) activity and potential efflux pump inhibitory action towards M. smegmatis. The computational analysis revealed that THY interacts effectively with efflux pump proteins Rv1258c and Rv0194, showing superior binding affinity compared to verapamil, a known efflux pump inhibitor. Pharmacokinetic studies highlighted that THY possess a favourable safety profile. In conclusion, THY represents a promising inhibitory compound for tuberculosis prevention, potentially addressing challenges posed by drug resistance.

The technique of using naturally occurring light-emitting reactants (photoproteins and luciferases] that have been extracted from a wide range of animals is known as bioluminescence imaging, or BLI. This imaging offers important details on the location and functional state of regenerative cells inserted into various disease-modeling animals. Reports on gene expression patterns, cell motions, and even the actions of individual biomolecules in whole tissues and live animals have all been made possible by bioluminescence. Generally speaking, bioluminescent light in animals may be found down to a few centimetres, while the precise limit depends on the signal's brightness and the detector's sensitivity. We can now spatiotemporally visualize cell behaviors in any body region of a living animal in a time frame process, including proliferation, apoptosis, migration, and immunological responses, thanks to BLI. The biological applications of in vivo BLI in nondestructively monitoring biological processes in intact small animal models are reviewed in this work, along with some of the advancements that will make BLI a more versatile molecular imaging tool.

Autophagy is an essential intracellular degradation system responsible for delivering cytoplasmic components to lysosomes. Within this intricate process, optineurin (OPTN), an autophagy receptor, has attracted extensive attention due to its multifaceted roles in the autophagy process. OPTN is regulated by various posttranslational modifications and actively participates in numerous signaling pathways and cellular processes. By exploring the regulatory mechanism of OPTN posttranslational modification, we can further understand the critical role of protein posttranslational modification in biological progress, such as autophagy. Additionally, OPTN is implicated in many human diseases, including rheumatoid arthritis, osteoporosis, and infectious diseases. And we delve into the inflammatory pathways regulated by OPTN and clarify how it regulates inflammatory diseases and cancer. We aim to enhance the understanding of OPTN's multifaceted functions in cellular processes and its implications in the pathogenesis of inflammatory diseases and cancer.