جستجوی مقالات مرتبط با کلیدواژه "gene expression" در نشریات گروه "پزشکی"

Glycation is one of the primary underlying processes attributed to senescence and related diseases. No medicine currently targets this harmful manifestation. Drug repurposing is an efficient and cost-effective way of developing drugs. The present study evaluated meloxicam, a clinically used NSAID, for its ability to offer protection against glycative stress.

Methylglyoxal (MGO; 17.25 mg/kg) was administered for two weeks to create a rat model of glycative stress. Aminoguanidine (AG; 50 mg/kg) and Meloxicam (MEL; 0.15, 0.3, and 0.6 mg/kg) were used as standard and test agents, respectively. Afterward, the cognitive (Morris Water Maze), liver (LFT), and kidney (Creatinine) functioning were evaluated. The expression of genes of interest (TNF-α, RAGE, BACE, Glyoxalase, and VEGF) were estimated (qPCR) in the liver, brain, and kidney along with histopathology (H&E staining). Carboxymethyllysine (CML) levels in rat plasma were evaluated via ELISA.

MEL treatment has significantly (P<0.05) protected the MGO-induced cognitive (duration in target quadrant, time taken to get to target quadrant, and the frequency of crossings via platform location), hepatic, and renal impairment. The qPCR data revealed that MEL prevented MGO-induced enhancement in the expression of genes of interest. Additionally, the CML levels were significantly (P<0.005) normalized by concomitant administration of MEL. Histopathological examination did not reveal any remarkable outcomes.

MEL has significantly mitigated the rats’ MGO-induced cognitive, liver, and kidney impairments. Hence, it appears to be a potential molecule for repurposing as an antiglycation agent.

Statement of the Problem: 

Oral squamous cell carcinoma (OSCC) is the eighth leading cause of cancer-related death worldwide. JAK2 and STAT3 primarily influence intrinsic tumor cell behavior, and CTLA4 impacts the interplay between the tumor and the host immune system in the context of cancers. There is scarce information regarding the involvement and roles of JAK2, STAT3, and CTLA4 genes in OSCC; however, the molecular mechanisms are still unclear.

This study examined the relationship between JAK2, STAT3, and CTLA4 gene expression levels and OSCC in a group of patients in the southeast of Iran.

This cross-sectional study was conducted in which the relative gene expression levels of JAK2, STAT3, and CTLA4 were compared between 23 oral paraffin tissue blocks collected from OSCC patients and 20 fresh gingival tissues collected from healthy individuals. The Real-Time quantitative PCR (RT-qPCR) assay was employed to assess relative gene expression levels. SPSS 27 was employed to perform statistical analyses.

Significant differences were found between OSCC patients and healthy individuals concerning gene expression levels of JAK2 (2.4-fold, p< 0.0001), STAT3 (2.32-fold, p< 0.0001), and CTLA4 (4.09-fold, p< 0.0001). Additionally, there were significant positive correlations among JAK2-STAT3 (0.667, p< 0.001), JAK2-CTLA4 (0.771, p< 0.001), and STAT3-CTLA4 (0.635, p= 0.001) co-expressions. Moreover, gender, age groups, and tumor locations did not significantly correlate with the expression levels of these genes (p> 0.05). Nevertheless, significant differences occurred between histopathological grades and the gene expression levels of JAK2 (p< 0.001), STAT3 (p= 0.001), and CTLA4 (p< 0.001).

The overexpression of JAK2, STAT3, and CTLA4 can be considered triggers for OSCC development. It may be beneficial to conduct future research on OSCC by considering downstream genes involved in the JAK2/STAT3/CTLA4 axis.

Cervical cancer (CC) is the fourth most prevalent malignancy in women worldwide and a major cause of cancer-related mortality among females in developing countries. P16INK4a is a tumor suppressor protein with an inhibitory role in the proliferation of abnormal cells. The association between the expression of this protein and CC has established it as a diagnostic biomarker for CC.

This study evaluated the expression level of P16INK4a in cervical squamous cell carcinoma (CSCC).

Eighty-three formalin-fixed paraffin-embedded (FFPE) cervical tissue samples were obtained from the pathology department of Kowsar Gynecology Reference Hospital in Qazvin Province, Iran. The expression level of the P16INK4a gene was investigated using relative quantitative real-time PCR (RT-qPCR).

P16INK4a overexpression was observed in 55% (12/22) of cancerous samples, 46% (6/13) of intraepithelial squamous lesions, and 33% (8/24) of tissues with koilocytic changes, with N-fold overexpression of 6.01 (P = 0.001), 3.24 (P = 0.003), and 1.12 (P = 0.007), respectively.

The results of this study showed that the expression level of P16INK4a increased with cancer progression. Therefore, the expression level of P16INK4a can be utilized as a biomarker for diagnosis.

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in people over 65. The present research aimed to investigate the potential of different dietary supplements (DS) in preventing AD in an experimental animal model and in silico study.

Three DS containing a mixture of wheat-germ oil and black pepper extract/or turmeric extract were prepared. Total phenolic content, HPLC-phenolic profile, phytosterols content, fatty-acids profile, and anti-oxidant activity were evaluated in all DS. The protective effect of the prepared DS was assessed through their impact on cholinergic neurotransmission and the gene expression of GSK3β, APP, and Akt. Oxidative stress and inflammatory markers were evaluated. The inhibition activities against acetylcholinesterase (AChE) and reduction of amyloid-β aggregation of the major phytochemicals present in the studied DS were evaluated using in silico molecular docking study.

Molecular docking revealed that rosmarinic acid and β-Sitosterol exhibited the strongest binding affinities for AChE and Amyloid-β, respectively. The results showed that all DS reduced cholinergic neurotransmission, decreased TNF-α as an inflammatory marker, and improved oxidative stress status. All DS down-regulated the expression of GSK3β and APP while significantly up-regulating the expression of the Akt gene.

The present study concluded that all DS enhanced cholinergic neurotransmission, reduced inflammation, and improved oxidative stress status by impacting the expression of GSK3β, Akt, and APP genes. Rosmarinic acid and β-sitosterol showed promising effects for treating AD, according to an in silico molecular docking study. The studied dietary supplements were considered promising candidates for the prevention of AD.

Peri-implantitis is implant-associated inflammation that leads to irreversible loss of surrounding bone. Early diagnosis increases the success of peri-implantitis treatment. Despite various studies associated with this most common complication, early detection of the onset of peri-implantitis remains a major challenge. Molecular biomarkers are applicable detectors for the early detection of numerous diseases and monitoring their development. The present study aimed to predict interactome networks of up/down regulated proteins and analyze drug-gene interaction in peri-implantitis to identify the diagnostic and druggable genes.

In this in silico study, a suitable gene expression profile related to peri-implantitis was retrieved from Gene Expression Omnibus. Screening differentially expressed genes (DEGs) was carried out based on the cut-off criteria |log2 (fold change)|>2 and P < 0.05. Interactome networks were constructed and analyzed by the STRING database (Version: 12.0) and the Cytoscape software (version: 3.9.1). Finally, to investigate drug-gene interaction, detected hub genes were analyzed by DGIdb (version: 5.0.6).

A total of 216 genes were identified as DEGs (129 down-regulated and 87 up-regulated genes) in peri-implantitis. Regarding Cytoscape analysis, FCGR3B, CSF3R, AQP9, TREM1, and P2RY13 were the top 5 hub nodes of up-regulated DEGs, and CXCL10, OASL, IFIT1, RSAD2, and ISG15 were the top 5 hub nodes of down-regulated DEGs. Among these key nods, AQP9, CSF3R, CXCL10, IFIT1, ISG15, OASL, and, FCGR3B were therapeutic targets and had approved drugs.

In this research, seven genes have been identified as druggable genes in peri-implantitis which can be used to treat and diagnose this disease. However, these results and identified genes need to be validated by clinical or experimental methods. Key Words: Biomarkers, gene expression, peri-implantiti

Long non-coding ribonucleic acids (lncRNAs) have been implicated as possible circulating stroke indicators. This study focused on the expression status of antisense non-coding ribonucleic acid in the INK4 locus (ANRIL) and myocardial infarction associated transcript (MIAT) in patients with cerebral venous thrombosis (CVT). In this study, fifty patients with CVT and one hundred age/gender-matched individuals as controls were included. The circulating levels of ANRIL and MIAT in the first 24 hours after admission were evaluated using the quantitative real-time polymerase chain reaction (RT-PCR) method. We compared the expression levels of ANRIL and MIAT between patients and controls using the independent two-sample t-test. Subgroup analysis was used to investigate the association of lncRNAs with clinical characteristics in patients with CVT. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the diagnostic value of two lncRNAs in patient assessment. The relative expression of lncRNAs ANRIL and MIAT significantly decreased in patients compared to the control. ANRIL and MIAT were shown as potential markers for discriminating patients with CVT from the healthy controls with an area under the curve (AUC) of 0.98 and 0.99, respectively. For the first time, we found down-regulation and diagnostic potential of lncRNAs-ANRIL and MIAT in the blood of patients with CVT.

This study assessed how Silver nanoparticles (Ag NPs) and hydroalcoholic extract of Salvia officinalis (Sage) influence the expression levels of the vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP2) genes, which play a role in wound healing.

An excision wound was induced on the back of the 48 adult male mice. Wound treatments done with AgNPs and Salvia officinalis extract in separate animal groups for 14 days. On two weeks after treatment, the wound skin tissue was removed and gene expression analysis was done by real-time polymerase chain reaction.

The results showed that the expression of both target genes (VEGF and MMP2) in the wound skins treated with 0.05% Ag NPs increased significantly compared with the wound skin of control. The expression of VEGF gene increased significantly in the wound tissues treated with Sage extract compared with the Vaseline group, but the expression of MMP2 gene didn’t change significantly. The expression of two target genes increased significantly in the wound tissues treated with 0.5% Sage extract plus 0.05% Ag NPs in comparison to the wound tissues treated with 0.5% Sage extract alone. The expression of the two target genes did not significantly differ in the wound tissues treated with Sage extract and Ag NPs compared to those treated with 0.05% Ag NPs alone.

Based on the results above, it can be concluded that the combination of hydroalcoholic extract of sage and low doses of Ag NPs exhibits significant healing activity and could serve as a viable option for wound healing management.

While ketone bodies are not the main heart fuel, exercise may increase their uptake. This study aimed to investigate the effect of 6-week endurance training and Pyruvate dehydrogenase kinase 4 )PDK4( inhibition on ketone bodies metabolism in the heart of diabetic rats with emphasis on the role of Peroxisome proliferator-activated receptor-gamma coactivator PGC-1alpha (PGC-1α).

Sixty male Wistar rats were divided into eight groups: healthy control group (CONT), endurance training group (TRA), diabetic group (DM), DM + EX group, Dichloroacetate (DCA) group, DM + DCA group, TRA + DCA group, and DM + TRA + DCA group. Diabetes was induced using streptozotocin (STZ). The animals in training groups ran on the treadmill for six weeks (30–50 min running at 20–30 m/min). After the training period, molecular markers for mitochondrial biogenesis and ketone metabolism were assessed in the heart. Circulating ß-hydroxybutyrate (ßOHB) and Acetylacetonate (AcAc) levels were also measured. 

Our results showed that 6-week endurance training increased the cardiac expression of PGC-1α, 3-oxoacid CoA-transferase 1 (OXCT1), and Acetyl-CoA Acetyltransferase 1 (ACAT1) and reduced beta-hydroxybutyrate dehydrogenase1 (BDH1) expression (P≤0.05). In addition, exercise and DCA usage significantly decreased PDK4 gene expression, ßOHB, and AcAc blood levels (P≤0.05). Furthermore, the combination of 6-week endurance training and DCA supplementation led to more reduction in PDFK4 gene expression, ßOHB, and AcAc blood levels. 

Six-week endurance training and DCA supplementation could safely improve ketone body metabolism in the heart, ultimately reducing hyperketonemia/ketoacidosis in diabetic rats.

Lysophosphatidylcholine acyltransferases 1 (LPCAT1) overexpression and prognostic significance have been shown in various human solid cancers. However, the role of LPCAT1 in hematological malignancies has yet to be extensively explored. The present study primarily aimed to explore the LPCAT1 expression and prognostic significance in patients diagnosed with acute leukemia.

This cross-sectional study was conducted on 140 acute leukemia patients (70 acute myeloid leukemia (AML) and 70 acute lymphoblastic leukemia (ALL) patients) and 70 healthy controls. LPCAT1 expression levels and survival rate were evaluated. Patients' clinical data were extracted from their archived medical records, and the association between LPCAT1 expression and clinical data was determined. Statistical analyses were conducted using IBM SPSS version 21 and GraphPad Prism version 9.5.0.

The findings of this study indicated that LPCAT1 expression levels were significantly higher in AML and ALL cases as compared with the healthy controls (P = 0.038 and 0.032, respectively). Kaplan-Meier analysis demonstrated that LPCAT1 overexpression was correlated with shorter overall survival in both AML and ALL patients (P = 0.013 and 0.019, respectively). Moreover, multivariate Cox regression analysis revealed that LPCAT1 overexpression was an unfavorable prognostic factor associated with shorter overall survival in patients with AML (P = 0.02) and ALL (P = 0.04). There was no significant difference regarding clinical parameters between LPCAT1high and LPCAT1low patients (P > 0.05).

LPCAT1 overexpression is associated with poor prognosis in newly diagnosed patients with AML and ALL. As a result, further attention should be paid when considering treatment options for these patients.

Mitochondrial function is an integral part of glucose-stimulated insulin secretion in pancreatic β-cells and is a hallmark feature of cardiovascular disease. It may contribute to the pathophysiology of diabetic cardiomyopathy and atherosclerosis. This study aimed to investigate the effect of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), combined with quercetin supplementation (eight weeks), on mitochondrial gene expression in the diabetic heart.

In this study, 35 adult male rats were equally divided into seven groups (n=5): healthy sedentary, diabetic sedentary, diabetic quercetin sedentary, diabetic HIIT (DHIIT), diabetic MICT (DMICT), DHIIT with quercetin, and DMICT with quercetin. The rats were fed a high-fat diet for eight weeks and subsequently treated with a single low dose of streptozotocin to create a model of type 2 diabetes mellitus (T2DM). Eight weeks (five times a week) of HIIT and MICT, with and without quercetin, were conducted for the training groups, and quercetin was injected over eight weeks at a dose of 15 mg/kg.

Eight weeks of quercetin supplementation, HIIT, and MICT, with and without quercetin, significantly decreased blood glucose levels (P=0.001). Eight weeks of HIIT and MICT training increased nuclear respiratory factor-2 (NRF2) (P=0.001) and adipose triglyceride lipase (ATGL) (P=0.001) expression and decreased perilipin 2 (PLIN2) gene expression (P=0.001).

The training groups alone improved the gene expression of NRF2, ATGL, and PLIN2. Both training protocols, combined with quercetin, controlled blood glucose levels and improved antioxidant capacity. Thus, the reduction in blood glucose through quercetin supplementation appears to be a promising approach for managing T2DM.

Esophageal cancer is one of the most common cancers worldwide. Because this disease is usually diagnosed in advanced stages, its treatment is challenging and the survival rate of patients is relatively low. One of the parts that is disturbed in the tumor tissue of esophageal cancer is the tight connections between cells. Claudin-4 (CLDN-4) is one of the tight junction regulatory proteins whose changes are involved in cancer formation. In this systematic review, we examine the changes in CLDN-4 and the factors that affect its level in samples and cell lines related to esophageal cancer.

Scopus, PubMed, and Web of Science databases were searched for articles that examined CLDN-4 gene and protein expression in patients with esophageal cancer or cell lines related to esophageal cancer. A number of 202 manuscripts were obtained in the beginning, and after screening and applying the inclusion and exclusion criteria, six studies remained.

Six studies, including 596 patients and seven cell lines related to esophageal tissues, were included in this systematic review. The studies were related to Japan, South Korea, China, and Finland. In these studies, the level of CLDN-4 in cancer samples related to esophageal cancer and their location in esophageal tissue cells have been examined.

In summary, it can be concluded that the change in the level of CLDN-4 in the tumor tissues of esophageal cancer altered the tight junctions from the normal state in the normal esophageal tissues, leading to a change in normal barrier function. However, considering the conflicting results in the reports, more studies are needed to accurately interpret the role of CLDN-4 in esophageal cancer.

 Candida albicans is an opportunistic pathobiont that manifests as candidiasis. Drug-resistant biofilms hinder current treatment of candidiasis. The morphological control of filamentous growth and biofilm formation is vital for the pathogenicity of C. albicans. This study aimed to investigate the antifungal activity of magnetic iron oxide nanoparticles (nano-Fe3 O4 ) against C. albicans, their ability to inhibit pre-formed biofilms, and to examine the expression levels of negative regulators, transcriptional repressors thymidine uptake 1 (TUP1), the negative transcriptional regulator of glucose repressed genes (NRG1), and target of rapamycin (TOR1) in C. albicans pre-formed biofilms after treatment with nano-Fe3 O4 .

 This study examines the antifungal activity of nano-Fe3 O4 against C. albicans, its ability to inhibit pre-formed biofilms, and investigates the expression levels of negative regulators, TUP1, NRG1, and TOR1 in C. albicans pre-formed biofilms after treatment with nano-Fe3 O4 .

 Nano-Fe3 O4 at concentrations of 2× minimum inhibitory concentration (MIC), 1× MIC, and ½× MIC showed significant inhibitory effects on C. albicans pre-formed biofilm formation by 2,3-bis (2-methoxy-4-nitro-5 sulfophenyl)-5-[(phenylamino) carbonyl])-2H-tetrazolium hydroxide (XTT), crystal violet staining and light field microscopy with a MIC of 50 μg/mL. Gene expression profiling showed that nano-Fe3 O4 upregulates targets TUP1, NRG1, and TOR1 in C. albicans pre-formed biofilms.

 Our results suggest that nano-Fe3 O4 diminishes pre-formed biofilms and may subsequently reduce the pathogenicity of C. albicans, which can be responsible for biofilm-associated infections. TUP1, NRG1, and TOR1 may be possible molecular targets in C. albicans pre-formed biofilms after treatment with nano-Fe3 O4.

Iron is an essential element that works as a cofactor in mitochondrial respiration, neurotransmitter biosynthesis, and myelination enzymes. Several pieces of evidence reveal that iron accumulates in demyelinating lesions in patients with multiple sclerosis (MS), and its intracellular homeostasis is disrupted, which exacerbates inflammation and demyelination.

We reanalyzed a microarray human MS dataset from GEO DataSests, under accession number GSE108000. We examined differentially expressed genes involved in iron metabolism between different types of MS lesions and peri-lesional normal-appearing white matter (PL-NAWM). We used GEO2R for differential expression analysis and created volcano plots, Venn diagrams, and pie charts for data visualization using RStudio software.

We identified 58 genes involved in iron metabolism within the dataset. The expression of key iron-regulating genes, responsible for iron uptake, storage, and export, including CYBRD1, STEAP3, SLC39A14, FTL, FTH1, and CP were significantly changed. We also indicated significant alterations in the iron regulatory pathways in MS lesions and the PL-NAWM. The most prominent alterations were related to the iron uptake pathway, which showed enhanced activity.

Significant changes in iron regulatory gene expressions across MS lesions and the PL-NAWM may lead to dysregulation in iron homeostasis. This imbalance likely contributes to neurodegenerative processes associated with MS. The modifications in the PL-NAWM can be regarded as early-disease indicators. Recognizing these molecular changes provides valuable insights for facilitating timely MS diagnosis and developing targeted therapeutic strategies.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal types of cancer. Late diagnosis significantly decreases patient survival rates.

The study aimed to identify survival groups for patients with ESCC and find predictive biomarkers of time-to-death from ESCC using state-of-the-art deep learning (DL) and machine learning algorithms.

Expression profiles of 60 ESCC patients, along with their demographic and clinical variables, were downloaded from the GEO dataset. A DL autoencoder model was employed to extract lncRNA features. The univariate Cox proportional hazard (Cox-PH) model was used to select significant extracted features related to patient survival. Hierarchical clustering (HC) identified risk groups, followed by a decision trees algorithm which was used to identify lncRNA profiles. We used Python.3.7 and R.4.0.1 software.

Inputs of the autoencoder were 8,900 long noncoding RNAs (lncRNAs), of which 1000 features were extracted. Out of the features, 42 lncRNAs were significantly related to time-to-death using the Cox-PH model and used as input for clustering of patients into high and low-risk groups (P-value of log-rank test = 0.022). These groups were then labeled for supervised HC. The C5.0 algorithm achieved an overall accuracy of 0.929 on the test set and identified four hub lncRNAs associated with time-to-death.

Novel discovered lncRNAs lnc - FAM84A-1 , LINC01866 , lnc - KCNE4-2 and lnc - NUDT12-4 implicated in the pathogenesis of death from ESCC. Our findings represent a significant advancement in understanding the role of lncRNAs on ESCC prognosis. Further research is necessary to confirm the potential and clinical application of these lncRNAs.

Both coding and long non-coding RNAs (lncRNAs) have emerged as vital regulators in almost every cellular process, and their expression can be modulated by external stimuli, such as physical exercise.

The current research aimed to investigate the effects of different volumes of TABATA-high-intensity interval training (HIIT) exercises combined with royal jelly (RJ) supplementation on the NLRP3 inflammasome and lncRNA-H19 expression in obese males.

Forty-two healthy men [Body Mass Index (BMI) = 30 kg/m², waist-to-hip ratio = 0.95, age range: 40 - 60 years] volunteered to participate in the study. The individuals were randomly divided into five experimental groups (N = 35) and one control + placebo group (N = 7). The high-volume (HV) or low-volume (LV) TABATA exercise programs were performed twice a week for 8 weeks. Participants in the RJ supplementation groups received a 1000 mg capsule once a day for 8 weeks. The expression of NLRP3 and lncRNA-H19 genes was evaluated using the real-time PCR method.

The NLRP3 gene expression in the Bruce test, measured before and after the 8-week exercise interventions and RJ supplementation, showed insignificant changes across the different groups. However, the H19 gene expression in the Bruce test showed a significant reduction in the HV-TABATA HIIT intervention groups, which was more pronounced than in the LV groups after 8 weeks: HV group (P = 0.004), RJ group (P = 0.001), HV + RJ group (P = 0.007), and LV + RJ group (P = 0.002). After 8 weeks of non-pharmacological interventions involving exercise training and supplementation, a significant decrease in NLRP3 and a significant increase in H19 gene expression were detected in the HV group compared to the LV group (P = 0.05 and P = 0.010). Significant improvement was also found in the resting H19 levels between the RJ and LV groups (P = 0.011) and the LV + RJ group (P = 0.44). Moreover, a significant reduction in resting NLRP3 gene expression was observed between the RJ + LV and LV groups (P = 0.038).

Chronic HV TABATA HIIT exercise, when combined with RJ supplementation, is effective in attenuating inflammatory responses to acute stress.

Recently, the anti-herpetic activities of different plant species have been investigated. This study evaluated the effects of Teucrium stocksianum aqueous extract on the HSV-1 virus-infected Vero cell.

The IC50 of the aqueous extract was obtained by the maceration of the plant in boiling water and has been measured with the MTT method, also the q-PCR was used to study viral gene expression reduction.

Results of the MTT test indicated that the highest percentage of metabolic activity was observed in the 75 μg/ml concentration of Teucrium stocksianum’s aqueous extracts (IC50=45.5μg/ml). Time intervals of 24 and 48 hours after viral infection revealed that the cell viability is reduced by the viral infection time (MOI=0.1), log 10-3, p <0.001). Furthermore, the plant’s aqueous extract concentration almost avoids cell viability reduction. Through Q-PCR results; the reduction of viral proliferation revealed that the low expression of genes UL46 and US6 were significant in the presence of different treatments utilized in the experiment.

T. stocksianum, has an anti-viral property and may be considered as a remedy for anti-HSV-1 agents.