Cellular and molecular biology最新文献

Endothelial-mesenchymal transition (EndMT) is the process by which endothelial cells transform into mesenchymal cells, driving stromatogenesis and inflammatory responses, thereby contributing to the development of atherosclerotic plaques. Spinster homolog 2 (SPNS2), a protein responsible for S1P transport, regulates sphingolipid metabolism and signaling in endothelial cells to maintain vascular homeostasis. In the present work, we investigated the involvement of SPNS2 in endothelial mesenchymal transition. Knocking down SPNS2 in endothelial cells resulted in significant phenotypic changes, marked by a decrease in endothelial markers (CD31, VE-cadherin) and an increase in mesenchymal markers (Vimentin, α-SMA), confirming the occurrence of EndMT. Notably, SPNS2 knockdown leads to alterations in sphingolipid metabolism, most prominently marked by a significant increase in sphingomyelin (SM) levels. Similar cellular alterations were observed with the exogenous addition of SM, leading to the transition of endothelial cells from a cobblestone-like morphology to a dispersed, spindle-shaped form. In contrast, the exogenous addition of sphingomyelinase, which degrades SM, was able to reverse the endothelial-to-mesenchymal transition induced by SPNS2 knockdown. Mechanistically, our study suggests that SPNS2 knockdown promotes endothelial-to-mesenchymal transdifferentiation by upregulating SMS2 expression, which subsequently enhances sphingomyelin synthesis.

Acute pancreatitis (AP) is a common but poorly understood gastrointestinal illness. One explanation for this lack of awareness is the absence of clear recommendations on the use of biochemical markers to identify this illness. This is because knowledge in this field is always expanding. Serum amylase and lipase are two extensively utilized biochemical indicators in the diagnosis of AP. The lack of agreement on the optimal use of these markers, notably amylase and lipase, has an impact on diagnostic outcomes. Through a critical study of the current literatures, this review intends to explore in depth the use of biochemical markers in the diagnosis of AP. A comprehensive review of the literature had a glance at biochemical indicators in the context of AP diagnosis, diving into topics including pancreatic anatomy, functions, pathology, mechanisms of AP, etiologies, symptoms, and also diagnostic approaches. This review revealed areas of agreement and disagreement about biochemical indicators in the diagnosis of AP, as well as potential future research directions.

Copper (Cu) is an essential element involved in numerous biochemical, metabolic and cellular processes. Excessive exposure to the pesticide copper sulfate (CuSO4) was associated with toxic effects. This study aims to evaluate the efficacy of Coenzyme Q10 (CoQ10) and its liposomal form (L-CoQ10) against myocardial injury induced by CuSO4, pinpointing the involvement of redox imbalance, TLR-4/NF-κB signaling and apoptosis. Cardiac injury in rats was induced by daily oral doses of CuSO4 for 7 days, the rats were treated orally with either CoQ10 or L-CoQ10 concurrently with CuSO4 for 7 days. Elevated serum cTnI, CK-MB and LDH were observed in CuSO4-intoxicated animals. Additionally, cellular antioxidant biomarkers were decreased and the expression levels of cardiac MDA, TLR-4, NF-κB, IL-6, IL-1β, and TNF-α were upregulated. CoQ10 and L-CoQ10 prevented myocardial injury and decreased the levels of both MDA and pro-inflammatory cytokines. CoQ10 and L-CoQ10 enhanced antioxidant capacity and Bcl-2, and downregulated caspase-3, Bax, p53, RIP3, MLKL, caspase-8 and TLR-4/NF-κB signaling. In conclusion, CoQ10 and L-CoQ10 effectively prevent CuSO4 cardiotoxicity in rats. Attenuation of redox imbalance, TLR-4/NF-κB signaling, pro-inflammatory response, and necroptosis along with enhancement of antioxidant response mediated their cardioprotective efficacy. CoQ10 could be valuable in protecting people vulnerable to Cu toxicity.

Endodontic infections, primarily caused due to microbial invasion into the root canal system, pose a significant challenge to dental health and management due to their complex etiology and resistance to conventional treatment. Porphyromonas gingivalis is a key bacterium pathogen that uses the Mfa1 fimbriae for its adhesion and biofilm formation contributing to its pathogenicity. The study explores the potential of Aegle marmelos leaf metabolites as a potential inhibitor of Mfa1 fimbriae using the molecular docking and simulation approach. We assessed the binding affinities of various metabolites with Rutin emerging as a promising candidate due to its strong and stable interactions within the Mfa1 active sites. The findings are also supported by existing literature that underscores the anti-microbial and anti-inflammatory properties of Aegle marmelos and its phytochemicals. The study also highlights the novelty of targeting Mfa1 fimbriae, a structure not addressed by current therapeutics.

Inflammation plays an important role in the pathogenesis of renal ischemia/reperfusion injury (IRI). Interleukin-38 (IL-38) is an emerging cytokine with multiple functions involved in infection and immunity. The present study aimed to determine whether IL-38 attenuates renal IR injury in an animal model and to identify the underlying mechanisms. For this purpose, the renal IRI model was induced by left renal pedicle clamping for 45 min and right nephrectomy in mice. All mice were intraperitoneally injected with vehicle or IL-38. Renal histology, function, apoptosis and inflammatory cytokines were assessed. mRNAs were detected by Real-time PCR. The proteins were measured by Western blot. Results showed that the expression of IL-38 mRNA and protein in kidney tissue was significantly increased at 6 h and reached a peak at 24 h after renal IRI, along with the kidney dysfunction. IL-38 significantly decreased renal IRI, as reflected by the attenuation of renal dysfunction, tubular damage and cellular apoptosis. Thus, IL-38 markedly ameliorated the survival rate after renal IRI. In addition, IL-38 significantly increased the level of cytoplasmic IκB-α and suppressed the nuclear translocation of NF-κB, which inhibited the expression and release of inflammatory cytokines. In conclusion, IL-38 significantly protects against renal IRI probably by inhibiting pro-inflammatory reactions.

Forty-four samples of garlic plants showing virus-like symptoms were collected, during the growing season (2021-2022) from different locations in Qassim province, Saudi Arabia. These samples were analyzed by ELISA against the important Allium allexiviruses including garlic virus A (GarV-A), garlic virus B (GarV-B), garlic virus C (GarV-C), and Shallot virus X (ShVX). The obtained results showed that 22/44 (50%) samples were found to be infected with one of the tested viruses. Mixed infections were detected in 13/22 samples (59.1%) with more than one virus. However, 13.6%, 0% and 27.2% were detected as single infection with GarV-A, GarV-B and GarV-C respectively. RT-PCR amplification with general allexiviruses primer (750 bp) and specific primers for GarV-A (1330 bp), GarV-B (1216 bp) and GarV-C (1557 bp) were used to detect the respective viruses. The phylogenetic tree and nucleotide sequence analysis of one of each GarV-A (OQ397541), GarV-B (OQ397542) and GarV-C (OQ397543) with general primer for allexiviruses while one isolate of each GarV-A (ON155441), GarV-B (OR343811) and two isolates of GarV-C (ON155445, and ON155446) with specific primers showed their similarity with their respective viruses from GenBank. In host range study, Chenopodium amaranticolor, Nicotiana benthamiana, N. tabacum and Allium cepa expressed necrotic lesions, mosaic and yellowing symptoms respectively against GarV-A, GarV-B and GarV-C. To our knowledge, this is the first report of GarV-A, GarV-B, and GarV-C in Saudi Arabia.

Pseudomonas aeruginosa is a key concern in clinical settings due to its high level of resistance to antibiotics, making infections given rise to this bacterium very problematic to treat. The rise of multidrug-resistant bacteria poses a danger to treatments and stresses the necessity to find new antimicrobial drugs. In a neoteric study, P. aeruginosa was found in a suction machine tube, affirming the importance of identifying and managing potential sources of infection in healthcare facilities-many strains of Enterococcus faecium output bacteriocins, which are antimicrobial compounds. The study aimed to produce, isolate, purify, and characterize a new bacteriocin from E. Faecium found in stool samples and to investigate the effects of E. Faecium and its bacteriocin on multidrug-resistant P. aeruginosa in laboratory conditions. E. faecium is a kind of lactic acid bacteria (LAB) set up in the intestines of both humans and animals. In a study, stool specimens from 79 healthy individuals aged 5 to 35 were collected, yielding 70 isolates of Enterococcus spp. These bacteria exhibit growth in aerobic conditions and are identified through the API20 method. A crude preparation was made to extract the E. faecium bacteriocin by combining it with n-butanol in a 1:1 ml ratio in BHIB and then refining it using an ion exchange column. Through this purification process, the final specific activity of purified enterocin GH reached 38.19 U mg with a 4761.9 purification fold. The molecular weight of the E. faecium bacteriocin was determined using ion exchange chromatography. The study also examines how temperature and pH affect the activity of pure enterocin GH using Staphylococcus aureus and P. aeruginosa Type Culture Collection. Both crude and purified enterocin GH from E. faecium exhibited significant antibacterial activity against P. aeruginosa isolates when compared to the control (p<0.05). Additionally, the antibiofilm activity of enterocin GH was found to be more effective than penicillin (p<0.05) in preventing biofilm formation on the suction machine's tube.

Antibiotics play a fundamental role in protecting millions of lives from infectious diseases. However, an important drawback of antibiotic treatment is that each advancement was followed by the development of resistance. This is due to the fact that the majority of pathogenic bacteria are capable of becoming resistant to a number of antimicrobial agents. There are a number of resistance mechanisms the microorganism may possess naturally or by acquisition from other microorganisms. The main mechanisms of resistance to a medication include altering its target, preventing its absorption, causing it to efflux actively, and rendering it inactive. Many types of gram-positive bacteria that cause serious infections in both the community and healthcare system are listed among the most dangerous bacteria according to the WHO's published list, which calls for the development of novel antibiotics to address the resistance issue. The following three strains, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and penicillin-resistant Streptococcus pneumoniae, are of special importance. Therefore, this review highlighted the main mechanisms and consequences of antibiotic resistance in Gram-positive bacterial strains.

Prostate cancer is the most common type after the age of fifty. It affects males and affects the prostate gland, which protects the function of sperm by producing semen. The current study was designed to evaluate prostate cancer infection effects on some biomarkers such as irisin, Tumor necrosis factor-TNF-α, prostate acid phosphates -PAP, Glutathione-GSH, malondialdehyde-MDA, urea, and creatinine. The study was conducted on 50 males infected with prostate cancer and 30 healthy males (control group) who attended the Baghdad Teaching Hospital -Medical City Center/Baghdad, Iraq, from 20/6/2024 to 1/8/2024. The results of the current research showed a significant elevation in (Irisin, TNF-α, PAP, MDA, urea, and creatinine) concentration and a significant decrease in (GSH) concentration in the serum of patients compared to the healthy subjects in the probability of P≤0.05. Irisin and some variables are important physiological biomarkers that can support the diagnosis of prostate cancer.

Liaoning cashmere goat is an outstanding breed in China primarily for cashmere production, with strict controls against genetic outflow. Melatonin(MT) is a key factor affecting cashmere growth, and preliminary transcriptome sequencing indicated that melatonin upregulates the expression of the PIP5K1A gene in skin fibroblasts. To predict the physicochemical properties of PIP5K1A in Liaoning cashmere goats, ascertain the tissue localization of PIP5K1A in their skin, and explore the role and mechanism of PIP5K1A in the proliferation of skin fibroblasts. This aims to provide new insights into improving the yield and quality of cashmere. Bioinformatics software was used to predict the physicochemical properties, hydrophobicity, signal peptides, transmembrane regions, secondary structure, subcellular localization, and conserved sites of PIP5K1A, and to construct a phylogenetic tree for the PIP5K1A gene across different species. siRNA technology was employed to interfere with PIP5K1A in skin fibroblasts; lentiviral vector construction techniques were used to overexpress PIP5K1A in skin fibroblasts; Western blot analysis detected changes in protein expression in cells; RT-qPCR was used to detect changes in gene expression; cell viability was assessed using the CCK-8 method; hair follicle structure was observed by HE staining; and immunohistochemistry was used to detect the distribution of PIP5K1A in skin hair follicles. The PIP5K1A gene in Liaoning cashmere goats encodes 573 amino acids, classified as a soluble unstable protein without signal peptides or transmembrane regions; its secondary structure is primarily random coil; it contains one conserved domain - PIPKc superfamily. Phylogenetic analysis of the PIP5K1A gene from different species shows that goats have the closest kinship with sheep. Immunohistochemistry confirmed that PIP5K1A is specifically expressed in the outer root sheath of hair follicles; melatonin promotes the expression of the PIP5K1A gene and protein level; overexpression of PIP5K1A can promote cell proliferation, whereas interference with PIP5K1A significantly reverses melatonin-induced cell proliferation; after overexpressing PIP5K1A, the expression levels of chi-miR-34c-5p and chi-miR-novel-86 are downregulated. Conclusion: PIP5K1A is located in the outer root sheath of skin hair follicles in Liaoning Cashmere Goats. Overexpression of PIP5K1A can promote the proliferation of skin fibroblasts, interference with PIP5K1A can significantly reverse cell proliferation induced by melatonin, and PIP5K1A can regulate the expression of chi-miR-34c-5p and chi-miR-novel-86 in skin fibroblasts of Liaoning cashmere goats.