International Journal of Molecular and Cellular Medicine最新文献

The increasing prevalence of Alzheimer's disease (AD) has led to a health crisis. According to official statistics, more than 55 million people globally have AD or other types of dementia, making it the sixth leading cause of death. It is still difficult to diagnose AD and there is no definitive diagnosis yet; post-mortem autopsy is still the only definite method. Moreover, clinical manifestations occur very late in the course of disease progression; therefore, profound irreversible changes have already occurred when the disease manifests. Studies have shown that in the preclinical stage of AD, changes in some biomarkers are measurable prior to any neurological damage or other symptoms. Hence, creating a reliable, fast, and affordable method capable of detecting AD in early stage has attracted the most attention. Seeking clinically applicable, inexpensive, less invasive, and much more easily accessible biomarkers for early diagnosis of AD, blood-based biomarkers (BBBs) seem to be an ideal option. This review is an inclusive report of BBBs that have been shown to be altered in the course of AD progression. The aim of this report is to provide comprehensive insight into the research status of early detection of AD based on BBBs.

Glioblastoma multiforme (GBM) is incurable with routine treatments. Ascorbic acid (Asc) has antioxidant and anti-cancer properties. However, its specific anti-cancer mechanisms are only partially understood. In this study, the effect of Asc on the c-Myc, HIF-1α, and lnc-SNHG16 genes in GBM cells and their exosomes was investigated. Cells isolated from the tissue were characterized by the immunocytochemistry method (GFAP⁺). The cell-doubling time was determined, and FBS-free medium supplemented with Asc (5 mM) was added to the cells. The extracted exosomes in the cell culture medium were scanned by electron microscopy, Zetasizer, and BCA assay. The expression of lnc-SNHG16 in the exosomes and c-Myc and HIF-1α in the treated and control cells was evaluated by real-time PCR. The interactions between Asc and the c-Myc and HIF-1α proteins were studied using the molecular docking method. The cells showed 90-100% GFAP⁺ in passage 4, with a cell-doubling time of 4.8 days. Exosomal vesicles measuring 98.25-105.9 were observed. Zetasizer results showed a sharp pick at 90 nm. Protein quantitation showed 3.812 µg/ml protein in the exosomes. Lnc-SNHG16 expression was reduced (P = 0.041), and c-Myc was upregulated (P = 0.002). The expression of HIF-1α was not significant in the treated cells. Also, Asc was able to interact and affect c-Myc and HIF-1α. Asc exerts its effect by reducing lnc-SNHG16 expression in exosomes, upregulating c-Myc in GBM cells, and interacting with HIF-1α and c-Myc. Further research is necessary to achieve a full understanding of these findings.

Stem cell therapy is going to become the most widely used type of therapy in regenerative medicine. The stem cell therapy market has grown at an exponential rate in recent years. The purpose of the present paper is to review the stem cell market and the factors affecting it. The methods used included a literature review across reputable databases, and identifying articles and trusted financial reports related to the stem cell therapy market. Results show that the stem cell market growth rate is increasing, so that, the global stem cell market size was valued at US$297 million in 2022 and is anticipated to grow at a compound annual growth rate of 16.8% from 2022 to 2027, driven by factors such as clinical trials with promising results, increasing funding for stem cell research, growing number of technologies and facilities for cell therapy, and rising demand for regenerative medicine. However, the market also faces some challenges such as ethical concerns, regulatory hurdles, and the high cost of stem cell therapies and products. To enhance the development of the market further, policymakers and regulatory bodies must simplify the complicated process of obtaining regulatory approvals for clinical use. However, there are growing concerns about the increasing number of unapproved treatments using stem cells.

Triploidy is a lethal chromosomal abnormality. Fetuses with triploid condition have a tendency to die in early conception and very few survive to term. In this study, we report the prenatal diagnosis of fetal triploidy with unexpected chromosomal translocation. A 27 years old women was referred to our clinical cytogenetic department due to history of previous conceptus with intrauterine growth retardation at 21-22 weeks of gestation and in present pregnancy, the quadruple marker screen test had suggested a high risk for Trisomy 18 with the risk >1:50. The study was performed on the amniotic fluid and peripheral blood samples received at the clinical cytogenetics department. The interphase FISH and conventional karyotype methods were followed. The prenatal diagnosis using an amniotic fluid sample found a triploid fetus with unexpected balanced chromosomal translocation: 69, XXX,t(2;9)(q11.2;p22)x2. Later the origin of translocation was confirmed by parental chromosomal study. Cytogenetic analysis showed the presence of translocation involving chromosome 2 and 9 in the mother which confirms the maternal origin of translocation in fetal triploidy. Prenatal diagnosis of fetal triploidy with balanced translocation of maternal origin is a rare finding. In present study, the triploidy arises from the failure to expel the second polar body. It is important to perform prenatal fetal imaging with ultrasound at 18-22 weeks to identify any fetal anomalies or intrauterine growth retardation which is associated with triploidy.

The link between the autonomic nervous system and tumor biology is being unfold. We aim to study the contribution of genes of the adrenergic (ADBR2 - rs1042713, NM_000024.6:c.46G>A, NP_000015.2:p. Gly16Arg), cholinergic (CHRNA5 - rs16969968, NM_000745.3:c.1192G>A, NP_000736.2:p.Asp398Asn), and serotonergic systems (SLC6A4 - 5-HTTVNTR-intron2, HTR2A - rs6313, NM_000621.5:c.102C>T, NP_ 001365853 .1: p. Ser 34=) to gynecological tumorigenesis and their treatment by embolization. A total of 517 DNA samples from women were analyzed. Samples were genotyped by PCR, PCR-RFLP and EndPoint genotyping. Results show a statistically significant association between the AA genotype of the ADBR2 gene and GG genotype of the CHRNA5 gene with leiomyoma (OR = 2.311; p = 0.003 and OR = 2.165; p = 0.001, respectively), and the epistatic interaction between genotypes increases the risk (OR = 2.458; p= 0.043). The GG genotype (CHRNA5) shows a lower reduction of the volume of the main leiomyoma after treatment (p=0.015). Combination of the genotypes 12/12-AA (SLC6A4 - ADBR2) increases the risk to leiomyoma (OR = 2.540, p= 0.030). TT genotype of HTR2A gene in combination with any of the two risk genotypes (of ADBR2 or CHRNA5) increases substantially the risk (OR = 5.266, p = 0.006; OR = 6.364, p=0.007, respectively). We conclude that ADBR2 and CHRNA5 genes have a relevant role that is enhanced by the epistatic relationship with the genes HTR2A and SLC6A4. CHRNA5 gene may also be a modulator of the success of embolization. We confirm the contribution of the genetics of Autonomous Nervous System to tumor biology.

This study observed in vitro screening, purification and identification of cholinesterase inhibitors from the microalgae Phormidium retzii. Mixed microalgal culture was screened from freshwater samples for Phormidium sp. Single colony was purified and authenticated as P. retzii. Acetylcholinesterase (AChE) enzyme was purified from hRBC ghost. Sequential extraction of P. retzii was performed using organic solvents. Cholinesterase enzyme activity and its inhibition by various extracts were then tested. The active fractions were then subjected to partial purification and characterization. Petroleum ether extract of P. retzii showed maximum inhibition of 68.6 % against AChE while other solvent extracts showed no inhibition. Seven fractions were obtained from the active extract using thin layer chromatography. Among which fraction no. 5 showed maximum inhibition of 86.37 % towards AChE. Fraction no. 5 when subjected to GC-MS led to determination of the active principle as stigmasterol. The maximum inhibition of stigmasterol (0.45µM) was 81.2±0.08% with IC50 value of 0.214. Stigmasterol from P. retzii inhibited AChE projecting itself as safer drug for Alzheimer's disease with minimal side effects.

E. faecium is the third most common cause of nosocomial infections. Linezolid (LNZ) is a reserve antibiotic recommended for infections caused by vancomycin resistant E. faecium (VREfm).  The aim of the present study was to investigate the prevalence of optrA gene among linezolid resistant E. faecium (LREfm) and to study the molecular epidemiology using pulse field gel electrophoresis (PFGE). Clinically significant LREfm were identified and antimicrobial susceptibility was performed by disc diffusion. Minimum inhibitory concentration (MIC) of linezolid, vancomycin, daptomycin and quinupristin/dalfopristin was determined by E-test. PCR and PCR-RFPL were performed for the detection of optrA/cfr gene and G2576T mutation respectively. Molecular epidemiology was studied by PFGE. A total of 1081 clinically significant Enterococci species were isolated which included E. faecium 63.5% (n=687) and E. faecalis 36.5% (n=394). LREfm (30/687) were further studied. Multidrug resistance and vancomycin resistance was 100% and 80%, respectively. Linezolid MIC range was 8-256µg/ml and the most common mechanism of resistance was optrA gene (83.3%) followed by G2576T mutation (33.3%). PFGE analysis demonstrated 4 major clones. The optrA gene mediated linezolid resistance was high and PFGE suggests resistance was emerging in the different background strains irrespective of resistance mechanism. Studies are required to investigate factors driving the emergence of linezolid resistance. The review suggests that this is the first report of optrA-mediated resistance in E. faecium from India.

The present study investigated the suitability of nanocomposite foams of fluorapatite and bioactive glass (FA /BG) in different weight ratios as scaffolds for bone tissue in rat tibia regeneration to determine the optimal composition. FA and BG nano powders with a weight ratio of 25% FA/75% BG (compound 1) and 75% FA/25% BG (compound 2) were used as precursors for gel casting to produce nanocomposite foams. Thirty rats were randomly divided into two equal groups. Disk-shaped samples of each compound were implanted into the tibias of 15 rats. After 15, 30, or 60 days, five rats from each group were sacrificed and subjected to radiological, histopathological, and histomorphometrical examination. Data were analyzed using SPSS software. No foreign body reaction was observed in either group at all intervals, and the bone-biomaterial junction was direct. Overall, the inflammation rate, and the number of blood vessels, osteoblasts, and osteoclasts decreased over time in both groups. However, the number of osteocytes, trabecular bone thickness, and the percentage of new bone formation increased, in contrast to the remaining biomaterial percentage. Most of the changes in the group implanted with compound 2 were significantly more significant and faster than in the other group. Although the composite with the higher percentage of FA was superior to the composite with the higher percentage of BG, considering the results of our previous similar studies, the composite with the same percentage of FA and BG is more favorable to be used as a substitute for bone tissue in the body.

Helicobacter pylori as a common gastrointestinal (GI) pathogen must possess certain virulence characteristics to colonize the stomach, evade host immune responses, and subsequently induce GI diseases. This research aimed to investigate the expression level of two important genes, the sialic acid-binding adherence (SabA) and the blood group antigen-binding adhesion (BabA) in H. pylori strains isolated from adult patients living in the northern part of Iran, and their association with peptic ulcer disease (PUD) and gastric cancer (GC). This cross-sectional study was carried out on adult patients referring to the GI clinic of the hospitals affiliated to Babol University of Medical Sciences, Iran. New cases diagnosed with gastritis, peptic ulcer or gastric cancer were included. Endoscopic-guided gastric biopsies were examined and H. pylori positive colonies were analyzed to determine the expression of babA and sabA genes, utilizing specific primers and the SYBR Green dye. Among 175 patients with mean age of 51.6±15.6 years, 101 (57.7%) of the individuals tested positive for H. pylori infection. Statistical analysis revealed a significant correlation between sabA (P=0.003) and babA (P=0.002) gene expression and development of PUD and GC. Smoking (P=0.052), gender (P=0.004) and positive babA gene expression (P=0.009) had the greatest association with occurrence of PUD or GC in H. pylori positive patients.  In summary, the presence of the sabA gene in people infected with H. pylori increased the risk of GC compared to gastritis, while, the presence of the babA gene was significantly increased in gastric ulcer patients. Considering the diversity of H. pylori isolates and the varying results observed in different geographical regions, further comprehensive studies are required to evaluate the function of these genes in H. pylori pathogenesis and their relationship with clinical outcomes.

Dysregulation of brain cholesterol homeostasis causes the accumulation of extracellular protein deposits called amyloid plaques in the hippocampus which eventually leads to neuronal death, memory and learning deficits. The aim of the present study was to investigate the effect of beta amyloid on miRNAs regulating HMGCR and ABCA1 as cholesterol synthesis and homeostasis genes. Primary astrocytes were isolated from C57BL/6J mice, and were treated with 0.5 μM amyloid beta (Aβ). Expression levels of genes and miRNAs were measured by real-time PCR. In comparison to control, Aβ treatment resulted in a significant decrease in miR-96-5p expression as a positive and negative regulator of HMGCR and ABCA1, respectively. There was no significant increase in miR-27a-3p expression as a negative regulator of HMGCR. miR- 106b- 5p and miR-143-3p expressions were also dramatically decreased as ABCA1 negative regulators. Amyloid beta can alter the expression of major genes in the cholesterol homeostasis pathway via their regulatory miRNAs.