Cellular and molecular biology最新文献

Current research reveals a complex relationship between blood cells(BC) and neuropathic pain(NP), though the underlying biological mechanisms remain unclear. This study applies Mendelian randomization (MR) to investigate causal relationships between BC and three major types of NP: diabetic peripheral neuropathy(PDPN), postherpetic neuralgia(PHN), and trigeminal neuralgia(TN). We also explore the potential mediating role of immune cells in these associations. We employed a two-sample, two-step Mendelian randomization study using the inverse variance weighted method to investigate the causal effect of BC on three major types of NP, as well as the mediating role of immune cells in the association between BC and NP. Additionally, we utilized a two-step Mendelian randomization design to explore the mediating effect of immune cells. We identified 13 distinct blood cell phenotypes under various perturbation conditions that have a significant causal relationship with NP. Additionally, we discovered 127 immune cells that exhibit a notable causal connection with NP. Through Mendelian Randomization (MR) and two-step Mendelian Randomization analyses, we found the following results: Three blood cell phenotypes were associated with PDPN, three with PHN, and seven with TN, with platelet, red blood cell, monocyte, and neutrophil responses showing significant correlations with NP risks. Immune cell analyses revealed 36 phenotypes increasing and 31 decreasing PDPN risk, 16 increasing and 21 decreasing PHN risk, and 18 increasing and 13 decreasing TN risk, with HLA DR on DCs, PB/PC AC, and CD39+ CD4+ %T cell showing the strongest associations, respectively. Mediation analysis identified immune cells, such as CD39+ resting Treg and HLA DR+ CD4+ %lymphocyte, mediating PBC effects on NP risks. Sensitivity analyses confirmed no significant heterogeneity or pleiotropy, and reverse MR analyses found no reverse causal relationships. This study provides new evidence for the causal relationship between blood cell phenotypes and neuropathic pain and proposes immune factors with potential mediating effects. However, this finding needs to be further demonstrated by more extensive clinical studies.

Pompe disease which is glycogen storage disease type II, is an autosomal recessive lysosomal storage disorder where GAA gene mutations cause deficiency of acid alpha-glucosidase leading to deposition of glycogen in various tissues. Chromosome 17q25.2-25.3 is the location of GAA gene. This study aims to collect information on the Pompe disease symptoms' severity and genotypes of 18 children who represented all infant patients with Pompe disease until March 1st, 2024. For diagnosis tandem mass spectrometry and genetic study were used. Muscle strength was assessed by hand-held dynamometry. Cardiac assessment was by echocardiography and electrocardiography. The feeding and swallowing difficulties in the patients were addressed. Statistical analysis was used P<0.05 was considered significant. Fifty percent had normal mental development, 27.8% had delayed mile stones 55.6% had weakness of extremities, 50% had heart problems in the first month,38.8% had respiratory problems in the first month and 12(66.6%) had feeding difficulties. The level of the enzyme alpha-1,4 Glucosidase level was Zero in two patients 66.7% and was 0.1µmol/L/h in 33.3% of the alive patients while it was 0.1 µmol/L/h in 73.3% and 0.2 µmol/L/h in 13.3% of the dead with a significant correlation. The genetic mutations were   c. [258dupC]; [258dup] in 6 (33.3%) of the patients, c.258dup in 3(16.6%) and c.2237G>A in 11.1% of all the patients. Childhood Pompe disease course varies widely. It is important to consider Pompe disease in the differential diagnosis of patients with unexplained fatigue and weakness and cardiorespiratory involvement.

The liver is the second largest organ in the body, playing a crucial role in maintaining homeostasis and regulating metabolism. However, the prevalence of liver diseases has been rising steadily due to an increase in both infectious and non-infectious factors. Medicinal plants offer a remarkable opportunity to enhance our healthcare system by addressing various diseases through their ability to control oxidative stress and support metabolic processes. This revision improves readability while retaining the original meaning. In the present study, purified methanol extracts of Martynia annua and Polygonum viviparum at different concentrations were used to explore the antioxidant and hepatoprotective potential against abiotic stress on liver cells.  Firstly total flavonoids and total phenolic contents of both plants were measured and then their antioxidant activities were determined through DPPH radical scavenging activity and FRAP assay. Moreover, bioactive compounds and in vitro hepatoprotective potential among these plants were determined through LC-MS and Liver Slice Culture assay respectively. In P. viviparum high amounts of TPC and TFC were observed with maximum antioxidant potential in terms of DPPH inhibition at 84% and high ferric-reducing ability at 240 mg/mL. The presence of different phytoconstituents like Myricetin, Gallic acid, Ferulic acid, Chlorogenic acid, Sweroside, Morroniside, Echonoside, Swertiamarin and Protocatechuic acid were confirmed in M. annua and P. viviparum in LC-MS study. The maximum hepatoprotective potential in terms of minimum cytotoxicity 6% and 9% were observed in M. annua and P. viviparum respectively. It was revealed that both plants have stunning hepatoprotective properties to prevent liver from toxicants and their related complications due to high antioxidant potential and active metabolites.

Dendrimers are chemical compounds that have functional groups on their surface and a hyperbranched structure. It is simple to promote the functionality of dendrimers and produce a variety of biocompatible products by altering their terminal groups. These materials have exceptional physicochemical characteristics that make them more beneficial in the administration of medications. They have a vigorous amount of potential as agents for nanomedicine applications because of their rare properties, which compose internal cavities, strong reactivity, globular form, solubility in water, and nanoscale size. They might also be synthesized easily. In-depth information about dendrimer composition and classifications, synthesis, and applications in nanomedicine, particularly drug delivery, is mentioned in this paper. Dendrimers are chiefly categorized by their functional groups, which permit for concise encapsulation of active compounds and structural imitatively of biomaterials. A rare property not often seen in other polymers serves to stabilize the surface of dendrimers to broaden their solubility in water. Dendritic molecules own a different variety of applications, such as dendrimers, dendrons, dendronized polymers, and hyperbranched polymers, which are organized based on their molecular weight. The role-play of dendrimers' is the capability to attach a broad range of chemical entities and their ability to shift pharmacokinetic and pharmacodynamic features through tailored drug delivery. To sum up, this study bolded how dendrimers' intricate structure and versatility make them excellent drug delivery vehicles since they may exactly modify their properties to reach special requirements. Drugs can be aimed at neuroinflammatory disorders and made more soluble and stable by dendrimers, which also deliver for a diversity of modes of delivery.  Additionally, they show attractive ability in gene transfection and sensor production, drawing near their potential for a difference of usages in industries including pesticide delivery and medicine. With the potential to send out gene therapy, medicine delivery, and other specialties of science and medicine, dendrimers are becoming a huge crucial in the pharmaceutical and medical industries through the next research and clinical investigations.

Helicobacter pylori is a pathogen that infects the gastric mucosa of the stomach and can be asymptomatic or lead to disorders ranging from gastric inflammation to gastric adenocarcinoma. This study aimed to find the association of H. pylori virulence factors and their combinations with severity of the disease caused by the bacterium. This cross-sectional study involved 203 patients admitted to the gastroenterology units of the Rizgary Hospital, Erbil, Iraq from July 2021 to May 2022. Biopsy samples were taken, cultured and identified as H. pylori using biochemical and molecular approaches. PCR was employed to amplify virulence genes cagA, vacA s1/s2, iceA1, iceA2, babA2, sabA, and oipA. The most common allelic combination found among the isolates was s2/m1 detected in 33 (36.26%), followed by s1/m1 which was detected in 17 (18.68%). Other genotypes s2/m2 and s1/m2 were recorded in 15 (16.48%) and 12 (13.18%) of the total samples respectively. While the cagA gene was present in 55/91 (60.43%), iceA1 and iceA2 were found in 70 (76.92%) and 54 (59.34%) of the tested isolates respectively. Furthermore, results showed that only four isolates were positive for all virulence factor genes (4.39%). In conclusion, data produced from this study confirmed that the rate of the isolates with all virulence factors was very low. The presence of different virulence factors combination could be used to identify patients who are at high risk for the disease caused by the pathogen and its severity.

One of the most common forms of dementia and a neurodegenerative illness is Alzheimer's disease (AD), which is distinguished by impaired memory and cognitive dysfunction. Decades of research have been devoted to determining its etiology, pathogenic processes, and biomarkers to facilitate early identification and clinical investigations for therapy. Neural atrophy and broken connections between neurons are the outcomes of the illness. The amyloid beta (Aβ) cascade is among the most widely recognized and important hypotheses of the numerous hypotheses regarding the pathogenesis of AD. This theory suggests that the breakdown of the amyloid precursor protein (APP) produces Aβ monomers. These monomers are then converted into hazardous oligomers, which in turn form β-sheets, fibrils, and plaques after being formed. The amyloid cascade theory was covered in this review, along with a summary of how it is used to diagnose and treat Alzheimer's. Specifically, we covered the drawbacks, potential, and significant unsolved issues with the anti-Aβ therapy that is now in use, as well as plans for more research and the creation of more workable Aβ-targeted methods to optimize AD early detection and management.

This study investigates the association between interleukin polymorphisms (IL-6, IL-10, IL-12A, and IL-18), inflammatory markers, and COVID-19 severity in Type 1 diabetes (T1D) patients. A prospective observational study enrolled 80 female T1D patients hospitalized with COVID-19 and a control group of 30 females without COVID-19. Significantly higher cytokine levels were observed in COVID-19 patients (IL-6: 64.1 ± 30.1 pg/mL, IL-10: 11.7 ± 5.8 pg/mL, IL-12A: 6.7 ± 2.9 pg/mL, IL-18: 195.4 ± 60.7 pg/mL) compared to controls (all p < 0.001). Genotype analysis revealed that the IL-6 GG and IL-18 TG genotypes were associated with elevated cytokine levels, prolonged hospitalization, and increased mortality risk (hazard ratios [HR]: IL-6 GG: 1.25, IL-18 TG: 1.30). ROC analysis indicated IL-18 (AUC: 0.88) and IL-6 (AUC: 0.84) as strong predictors of hospitalization. Cox regression showed that IL-6 and IL-18 levels significantly affected hospitalization duration and survival, while IL-12A displayed a protective effect (HR: 0.92). Kaplan-Meier analysis confirmed shorter survival for the IL-6 GG and IL-18 TG genotypes, supporting the prognostic role of cytokine levels and genotypes in COVID-19 management. This study highlights the potential of interleukin polymorphisms as biomarkers for COVID-19 severity in T1D patients.

The gut microbiota plays a huge role in human health regarding immunity, metabolism, and nutrient absorption. In this work, the gut microbiota, with its bacterial community structure, is studied using whole genome shotgun (WGS) sequencing for populations from two different geographical regions in Egypt: Cairo (urban) and Ismailia (rural). Fecal samples were obtained from six healthy individuals, three from Cairo and three from Ismailia, of ages ranging from 43 to 52 years. Alpha diversity, measured as Shannon, inverse Simpson, and OTUs, showed no significant differences between the two cities. However, beta diversity analysis by Principal Coordinate Analysis (PCoA) revealed diverse microbial compositions. Thus, only the Ismailia samples contained higher levels of butyrate-producing bacteria involved in maintaining intestinal health, such as Faecalibacterium prausnitzii and Akkermansia muciniphila. On the other hand, there was a higher prevalence in Cairo of bacteria associated with protein and fat metabolism, like Bacteroides thetaiotaomicron. Such findings explain the influence of environmental factors in shaping gut microbiota and show that to get a comprehensive understanding of regional differences, many wider-ranging studies need to be conducted.

Endodontic infections, often involving multispecies bacterial communities, present significant challenges in treatment due to their complex pathogenic mechanisms and resistance to conventional therapies. Enterococcus faecalis is a facultative anaerobic gram-positive bacterium that has been frequently recovered from secondary or persistent endodontic infections. This study investigates the population structure, resistome, mobilome, and virulome of E. faecalis isolated from oral cavity sources, focusing on 22 genomes sequenced from saliva and root canal samples. The genome sequence analysis revealed a diversity of 14 sequence types (STs), highlighting genetic variability within oral E. faecalis populations. Virulence profiling identified 39 genes involved in adherence, biofilm formation, toxin production, stress response, and immune evasion. Antimicrobial resistance (AMR) genes, including lsa(A), efrA, and tetM, were prevalent across all genomes, indicating potential multidrug resistance. Mobile genetic elements (MGEs), such as insertion sequences, transposons, prophages, and plasmids, were also identified, facilitating genetic exchange within and between species. Network analyses identified central virulence genes (e.g., asa1, gelE) and AMR genes (e.g., ANT (6)-Ia, dfrE) crucial for pathogenicity and resistance, highlighting their pivotal roles in E. faecalis infections. This study provides comprehensive insights into the genomic characteristics, AMR genes, virulence factors, and genetic mobile elements associated with E. faecalis isolates from the oral cavity, offering implications for dental health and potential strategies for infection control and treatment.

In the pursuit of more effective breast cancer therapies, the investigation of interactions between novel compounds and established chemotherapeutics has become increasingly important. This study investigates the combinatory effects of alpha-mangostin (α-MG) and nab-paclitaxel on MCF-7 and MDA-MB-231 cell lines, utilizing the xCELLigence RTCA system for continuous real-time cellular analysis, BrdU incorporation assays for proliferation assessment, and the quantification of mitotic activity and caspase-3/7 levels to elucidate apoptotic mechanisms. Our findings demonstrate that both α-MG and nab-paclitaxel independently induce significant inhibition of cellular proliferation and modulate cell cycle dynamics over a 24 to 72-hour period. Notably, when combined, these agents exhibit a pronounced enhancement of cell cycle inhibition and apoptosis, surpassing the effects observed with monotherapy. This potentiation effect suggests that α-MG augments the therapeutic efficacy of nab-paclitaxel, potentially allowing for reduced dosages in clinical applications. The study underscores the potential of α-MG as an adjuvant in breast cancer treatment, offering a promising strategy to optimize therapeutic regimens, minimize adverse effects, and improve patient outcomes in clinical oncology.