Cellular and molecular biology最新文献

This study investigated the genetic diversity, phylogeny, and evolutionary dynamics of Tomato yellow leaf curl virus (TYLCV) across seven regions in Saudi Arabia. Analyzing 28 full-length TYLCV genomes, phylogenetic analysis revealed two distinct clades: one predominantly comprised of isolates from the Ahsa (Eastern province) region and the other encompassing isolates from Northern and Western regions. The Ahsa region exhibited significantly higher TYLCV prevalence and genetic diversity, harboring the most divergent isolates with high haplotype (Hd = 1.00) and nucleotide (π = 0.079) diversity. Conversely, regions like Jeddah and Hadasham showed lower diversity, suggesting less or stable viral populations. Genetic diversity analyses revealed high variation in coding regions like CP and Rep, which are under strong selective pressures and prone to recombination. Conversely, V2 displayed lower diversity, indicating purifying selection. Selection pressure analysis using dN/dS ratios indicated diversifying selection in C4 (2.20) and Rep (1.28). Single Likelihood Ancestor Counting identified one positively selected site in Rep. In contrast, Fast Unconstrained Bayesian AppRoximation identified multiple sites in C4 (8), TrAP (7), REn (6), and V2 (1), suggesting roles in host adaptation and immune evasion. A total of 32 credible recombination events, predominantly in Ahsa isolates, were identified using RDP and confirmed by GARD analysis. These events, involving both inter- and intraspecies recombination, play a crucial role in enhancing TYLCV genetic diversity and adaptability. The conservation of motifs in V2 and C4 indicated their essential roles in TYLCV function. In contrast, variations in ORFs like CP, Rep, TrAP, and REn among specific isolates may promote viral diversity and adaptation. This study demonstrates the crucial role of geographic and genetic factors, with Ahsa as a key hub for TYLCV diversity, in driving viral evolution and diversification. The findings emphasize the need to monitor regions with high viral diversity, like Ahsa, and develop strategies to manage TYLCV's swift spread.

Lysosomes are an important intracellular organelle that regulates cellular degradation. Dysfunctional lysosomes disrupt this process, leading to the accumulation of toxic proteins that are meant to be degraded inside the cell, leading to cellular stress and potential toxicity. One of the proteins is beta-amyloid which is associated with conditions like cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). To identify its effects on the vascular compartment, the current study explored lysosomal dysfunction's impact on cytosolic vacuole formation and amyloid beta 40 (Aß40) levels in human brain endothelial cells (HBEC-5i). Cells treated with the lysosomotropic compound chloroquine (70.5 µM) exhibited morphological changes, including prominent cytosolic vacuole formation. The vacuole density was recorded at 11.86 ± 1.907 vacuoles per cell (p < 0.05), and its diameter was significantly increased (3.76 ± 0.182 µm, p < 0.05) compared to the negative control group. However, the average cell size remained unchanged despite the vacuole formation in CQ-treated cells. ELISA tests on lysate and supernatant revealed no significant differences between treatment and control groups in intracellular and extracellular Aß40 levels. This suggested that while lysosomal dysfunction induced cytosolic vacuole changes, it did not significantly alter Aß40 levels. Further research is needed to elucidate the pathways involved in Aß40.

Di(2-ethylhexyl) phthalate (DEHP), an endocrine-disrupting chemicals (EDCs), is commonly used as a plasticizer to improve the flexibility and durability of plastics. On a daily basis, we are exposed to varying amounts of this compound. Several studies have demonstrated that exposure to DEHP and its metabolite, mono(2-ethylhexyl) phthalate (MEHP), leads to testosterone deficiency (TD) in both humans and animals. However, the precise mechanism that causes DEHP-induced TD is still not completely understood. This study aims to determine the effects of DEHP on testosterone levels and elucidate the underlying mechanisms. C57BL/6 mice and Leydig cells were exposed to various doses of DEHP (0, 0.5, and 5 mg/kg/day) for 9 weeks and MEHP (0, 0.05, 0.5, and 5 μM) for 24 hours, respectively. Both in vivo and in vitro results indicated significant reductions in testosterone levels due to DEHP and MEHP. Additionally, DEHP and MEHP increased the expression of aromatase, a gene that converts testosterone to estradiol and induced an increase in the expression of inflammatory cytokines such as IL-6, IL-1β, and TNF-α. Moreover, DEHP activated NF-κB, a key transcription factor regulating numerous genes associated with inflammation. These results suggest that sustained exposure to DEHP increases inflammatory factors, which may elevate aromatase activity and result in decreased testosterone levels in the body. Furthermore, this study provides a basis for discussing the potential correlation between persistent DEHP exposure and TD characterized by low testosterone levels in the body.

Adult stem cells (ASCs) have great applicative potential in tissue regeneration. Comparative analyses of ASCs derived from various niches are essential for comprehending the unique traits of each population and evaluating their potential for therapeutic use. In this study, the proliferation ability, stem cell marker expressions, and differentiation potential of skin-derived ASCs were compared between hair follicle dermal papilla cells (HFDPCs) and human dermal stem/progenitor cells (hDSPCs). The cell division capacity of hDSPCs was significantly increased compared with HFDPCs, and the differentiation capacity into adipocytes, chondrocytes, and osteoblasts was significantly increased in hDSPCs. On the contrary, HFDPCs showed significantly increased expression of dermal papilla-related markers (SOX2, S100β, CORIN and Snai2) compared with hDSPCs. To analyze why these two types of ASCs have different properties, I analyzed intracellular signaling by protein kinase assay. Protein kinase assays showed that the phosphorylation of ERK1/2, c-JUN, CREB, YES, and GSK3α/β is significantly changed in HFDPCs and hDSPCs compared with dermal fibroblasts. HFDPCs have increased expression of markers related to hair regeneration compared with hDSPCs, on the other hand, hDSPCs are more multipotent than HFDPCs. The five above-mentioned phosphorylated signaling proteins (ERK1/2, c-JUN, CREB, YES, and GSK3α/β) are responsible for the characterization of HFDPCs and hDSPCs. The different characteristics of each skin-derived ASC might be a major factor influencing their effective use for tissue regeneration and therapeutics.

This study investigated the association between Chronic Myeloid Leukemia (CML), Interleukin-18 (IL-18), and blood components. A case-control, multi-center trial was conducted from November 12, 2023, to August 8, 2024, including 134 CML patients and 44 healthy controls. Results indicated a statistically significant difference between the control group and CML patients in IL-18 levels, platelet count (PLT), and white blood cell count (WBC) (p = 0.048, 0.033, and 0.029, respectively). A significant age difference was also observed between the control group and patients (p = 0.0441). Furthermore, there was a highly significant difference in age distribution (>40, 40-60, <60 years) between the two groups (p = 0.0001). Significant differences were also found in PDW, RBC, MCHC, RDW-CV, MCH, HCT, and PCT levels (p = 0.0001). MPV and RDW-SD also showed significant differences between groups (p = 0.0006 and 0.0498, respectively). Finally, a significant difference was observed in age distribution (less than 40, 40-60, and more than 60 years) between the two groups (p=0.048). These findings suggest that IL-18 and specific blood components may play a role in the pathogenesis of CML.

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a critical process in various diseases. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are increasingly recognized as key modulators of ferroptosis pathways. This systematic review aims to provide a comprehensive overview of the current knowledge regarding miRNAs implicated in ferroptosis across a spectrum of diseases. We conducted a systematic search of EMBL-EBI, PubMed, Scopus, and Web of Science databases to identify relevant studies published up to October 31, 2022. Our search strategy identified 127 articles encompassing 107 distinct miRNAs that influence ferroptosis. This review synthesizes the findings of these studies, highlighting the specific miRNAs that act as either inhibitors or inducers of ferroptosis in different disease contexts, including various cancers (e.g., lung, breast, colorectal) and degenerative conditions (e.g., acute renal failure, diabetic retinopathy). We discuss the molecular mechanisms by which these miRNAs regulate ferroptosis, often by targeting key genes involved in iron metabolism, lipid peroxidation, and antioxidant defense. Furthermore, we explore the potential of these miRNAs to serve as diagnostic biomarkers and therapeutic targets in ferroptosis-related disorders, offering insights into novel strategies for disease management.

Immodulins are synthetic peptides that efficiently utilize iron-mediated cellular uptake, importin-mediated nuclear translocation and binding to retinoid X receptor to mediate transcriptional effects. The possible use of side-chain derivatized immodulins (SCDI) as tunable therapeutic agents is explored in this work. Rat biodistribution studies show that, when applied transdermally to rats using a nanoemulsion, immodulin peptides rapidly partition to skin tissue resulting in a 9X enrichment in skin relative to plasma, even at skin locations distant from the site of application. We show that optimized side-chain derivatization of immodulins with selected ligands of RXR heterodimeric partners can stimulate by one to three orders of magnitude: [a] CD169+CCL22+ macrophage differentiation (RARα/β ligand); [b] IL-19, IL-22 and IL-24 production by HaCaT keratinocytes (RARγ agonist); and [c] FGF7/KGF-1, TGFβ and COL1A1 by dermal fibroblasts (partial PPARγ ligand); all p<0.01. Differentiated CD169+ macrophages, in turn, drive the conversion of FoxP3 CD4+Tcells into iTregs (>4-fold, p<0.01) while reducing IL-17 levels >4-fold (p<0.01). In addition, myoblast differentiation is stimulated >10X by a PPARα ligand (p<0.01). These processes resemble key features of paracrine circuitry in skin known to be involved in wound healing. Versatile SCDI scaffolds hold promise for the rapid and inexpensive development of safe, targeted, self-administered therapeutic agents for skin.

Schiff bases compounds were synthesized by reaction of the Benzidine with different aldehydes and ketones by using microwave method to obtain compounds (N1-N5). Thiazolidine 4-one compounds were prepared by the cyclization of Schiff bases with thioglycolic acid to obtain thiazolidine 4-one compounds (N6-N10). The prepared compounds were characterized by physical methods, through melting points and color, as well as by spectroscopic methods such as FT-IR and 1H-NMR. The purity of the prepared compounds was evaluated using TLC. The bioactivity of these compounds was tested on the growth of one type of a fungus of the yeast variety Candida was studied and type of bacterial isolates of Bacillus pumilus and the standard fungicide (Nystatin) of the fungus was used and the standard antibiotic (neomycin sulfate) of bacteria and the results indicate that the synthesized compounds have the ability to inhibit the fungus and bacteria used by using different concentrations. Molecular docking studies were conducted to examine how some of the synthesized compounds bind to the putative target, Protein structures i.e. HER2 (PDB ID: 1N8Z), Carcinoembryonic antigen (PDB ID; 2VER), BRCA1 (PDB ID 4OFB), BRCA2 (PDB ID 1MJE).

Gfi-1B is a hematopoietic transcription factor essential for growth and differentiation of the erythroid/megakaryocytic lineages, and PU.1 is a master regulator for myeloid development. Herein, we demonstrate that PU.1 interacted with Gfi-1B in vivo by immunoprecipitation assay. GST pull-down assays showed that the binding sites were located in the Ets domain of PU.1 and the zinc finger domain of Gfi-1B. Luciferase reporter assays revealed that PU.1 and Gfi-1B antagonized each other's transcriptional activity in a dose-dependent manner. The transduction of Gfi-1B alone in human cord blood progenitor cells strongly enhanced erythroid colony formation. However, the transduction of PU.1 along with Gfi-1B in the progenitors significantly inhibited erythroid colony formation. Co-expression of Gfi-1B with a mutant PU.1, which bound to Gfi-1B but not to GATA1, another erythroid master regulator, also inhibited Gfi-1B-induced erythroid colony formation. Our results suggest that the function of Gfi-1B in the growth and differentiation of erythroid cells is antagonized by the expression of PU.1.

 The study aims to identify and quantify the phytochemical components of Ocimum basilicum, Teucrium polium, Cleome amblyocarpa, and Caralluma arabica extracts and to evaluate the antimicrobial activities of these Omani plants. The total phenolic content, flavonoid content, and tannin levels were quantified in both water and absolute ethanol extracts. The bioactive compounds present in the aerial parts of these plants were identified and characterized using liquid chromatography coupled with electrospray ionization mass. The antimicrobial properties were explored via the agar diffusion approach. The absolute ethanol extracts demonstrated higher phytochemical content compared to the water extracts for all plants. Ocimum basilicum revealed the highest quantities of total phenolic acids and flavonoids, followed by Teucrium polium, Cleome amblyocarpa, and Caralluma arabica. Quinic acid was detected in substantial quantities across all extracts, while three flavonoid compounds-1,3-di-O-caffeoylquinic acid, acacetin, and naringenin-were identified in all extracts, albeit in varying concentrations. Furthermore, the ethanolic extracts exhibited potent antimicrobial activity on the tested bacterial and fungal species. Staphylococcus aureus showed the highest sensitivity to Caralluma arabica extracts (22±0.1 mm). Staphylococcus aureus and Escherichia coli were the most vulnerable strains to Ocimum basilicum extracts (21±0.2 mm and 20±0.2 mm, respectively). Ocimum basilicum extracts demonstrated the best minimum inhibitory concentration (MIC: 1.28 mg/ml against Staphylococcus aureus and Salmonella enteritidis) and minimum bactericidal concentration (33.5 mg/ml against Salmonella enteritidis). Additionally, the Teucrium polium extract exhibited the lowest MIC (3.25 mg/ml) and minimum fungicidal concentration (17.28 mg/ml) against Fusarium spp. In conclusion, the aerial parts of Ocimum basilicum and Teucrium polium were rich in bioactive compounds, exhibited strong antimicrobial activity, and hold great potential for ethnomedicinal applications, warranting further investigation.