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1.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 242-247, 2024 04 28.
Article in English | MEDLINE | ID: mdl-38678597

ABSTRACT

One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000).  This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.


Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Gene Expression Regulation, Neoplastic , Isocitrate Dehydrogenase , Humans , Isocitrate Dehydrogenase/genetics , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Middle Aged , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Adult , Biopsy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Aged
2.
Immunotherapy ; 16(2): 75-97, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38112057

ABSTRACT

Lung cancer has a high morbidity rate worldwide due to its resistance to therapy. So new treatment options are needed to improve the outcomes of lung cancer treatment. This study aimed to evaluate the effectiveness of oncolytic viruses (OVs) as a new type of cancer treatment. In this study, 158 articles from PubMed and Scopus from 1994 to 2022 were reviewed on the effectiveness of OVs in the treatment of lung cancer. The oncolytic properties of eight categories of OVs and their interactions with treatment options were investigated. OVs can be applied as a promising immunotherapy option, as they are reproduced selectively in different types of cancer cells, cause tumor cell lysis and trigger efficient immune responses.


A lot of research has been done to find a cure for lung cancer. Among the methods investigated is the treatment of cancer using a type of virus called an oncolytic virus (OV). Since tumors have unique properties, OVs tend to bind to them and activate immune cells to kill them. This article reviews the combination of OVs with other common cancer treatments which improves their effectiveness, causes fewer reactions and brings better results.


Subject(s)
Lung Neoplasms , Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Lung Neoplasms/therapy , Immunotherapy
3.
Cancer Cell Int ; 23(1): 271, 2023 Nov 11.
Article in English | MEDLINE | ID: mdl-37951913

ABSTRACT

Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.

4.
Toxicology ; 500: 153660, 2023 12.
Article in English | MEDLINE | ID: mdl-37924934

ABSTRACT

One of the most frequent environmental contaminants, benzene is still widely used as an industrial solvent around the world, especially in developing nations, posing a serious occupational risk. While the processes behind the toxicity of benzene grounds are not fully understood, it is generally accepted that its metabolism, which involves one or more reactive metabolites, is crucial to its toxicity. In order to evaluate the many ways that benzene could influence gene regulation and thus have an impact on human health, new methodologies have been created. The pathophysiology of the disorder may result from epigenetic reprogramming caused by exposure to benzene, including changes in non-coding RNA (ncRNA) markers, according to recent studies. We are interested in the identification of hazardous regulatory ncRNAs, the identification of these ncRNAs' targets, and the comprehension of the significance of these interactions in the mechanisms behind benzene toxicity. Hence, the focus of recent research is on long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs), and some of the more pertinent articles are also discussed.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Humans , Benzene/toxicity , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Circular , Gene Expression Regulation
5.
Hum Genet ; 142(8): 1001-1016, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37074398

ABSTRACT

Neuronal ceroid lipofuscinoses (NCLs) are neurodegenerative lysosomal storage diseases which are considered among the most frequent causes of dementia in childhood worldwide This study aimed to identify the gene variants, molecular etiologies, and clinical features in 23 unrelated Iranian families with NCL. In total, 29 patients with neuronal ceroid lipofuscinoses (NCLs), diagnosed based on clinical manifestations, MRI neuroimaging, and electroencephalography (EEG), were recruited for this study. Through whole-exome sequencing (WES), functional prediction, Sanger sequencing, and segregation analysis, we found that 12 patients (41.3%) with mutations in the CLN6 gene, 7 patients (24%) with the TPP1 (CLN2) gene variants, and 4 patients (13.7%) with mutations in the MFSD8 (CLN7) gene. Also, mutations in each of the CLN3 and CLN5 genes were detected in 2 cases and mutations of each PPT1 (CLN1) and CLN8 gene were observed in only 1 separate patient. We identified 18 different mutations, 11 (61%) of which are novel, never have been reported before, and the others have been previously described. The gene variants identified in this study expand the number of published clinical cases and the variant frequency spectrum of the neuronal ceroid lipofuscinoses (NCLs) genes; moreover, the identification of these variants supplies foundational clues for future NCL diagnosis and therapy.


Subject(s)
Neuronal Ceroid-Lipofuscinoses , Tripeptidyl-Peptidase 1 , Humans , Iran , Neuronal Ceroid-Lipofuscinoses/genetics , Neuronal Ceroid-Lipofuscinoses/diagnosis , Mutation , Membrane Glycoproteins/genetics , Molecular Chaperones/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Membrane Transport Proteins/genetics
6.
Int J Biol Macromol ; 235: 123790, 2023 Apr 30.
Article in English | MEDLINE | ID: mdl-36822288

ABSTRACT

Exposure to air pollution has been connected to around seven million early deaths annually and also contributing to higher than 3 % of disability-adjusted lost life years. Particulate matters (PM) are among the key pollutants that directly discharged or formed due to atmospheric chemical interactions. Among these matters, due of its large surface area, PM2.5 may absorb a different harmful and toxic substances. One of the outcomes of such environmental disturbance is oxidative stress which affects cellular processes including apoptosis, inflammation, and epithelial mesenchymal transition. Non-coding RNAs (ncRNA) such as, miRNAs, lncRNAs, and circRNAs are classified as non-protein coding RNA's. Over the past few years these small molecules have been gaining so much attention since they participate in variety of physiological and pathological processes and their expression change during disease periods. Regarding epigenetic properties, ncRNAs play an important function in organism's response to environmental stimulus. In this manner, it was revealed that exposure to PM2.5 may cause epigenetic reprogramming, such as, ncRNAs signature's alteration, which can be effective concerning pathophysiology state. In this review, we describe PM2.5 impact on ncRNAs and excavate its roles in toxicity caused by PM2.5.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Humans , Particulate Matter/toxicity , RNA, Untranslated/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Inflammation
7.
Clin Transl Oncol ; 25(5): 1167-1188, 2023 May.
Article in English | MEDLINE | ID: mdl-36562927

ABSTRACT

Recently, nucleic acid drugs have been considered as promising candidates in treatment of various diseases, especially cancer. Because of developing resistance to conventional chemotherapy, use of genetic tools in cancer therapy appears inevitable. siRNA is a RNAi tool with capacity of suppressing target gene. Owing to overexpression of oncogenic factors in cancer, siRNA can be used for suppressing those pathways. This review emphasizes the function of siRNA in treatment of breast tumor. The anti-apoptotic-related genes including Bcl-2, Bcl-xL and survivin can be down-regulated by siRNA in triggering cell death in breast cancer. STAT3, STAT8, Notch1, E2F3 and NF-κB are among the factors with overexpression in breast cancer that their silencing by siRNA paves the way for impairing tumor proliferation and invasion. The oncogenic mechanisms in drug resistance development in breast tumor such as lncRNAs can be suppressed by siRNA. Furthermore, siRNA reducing P-gp activity can increase drug internalization in tumor cells. Because of siRNA degradation at bloodstream and low accumulation at tumor site, nanoplatforms have been employed for siRNA delivery to suppress breast tumor progression via improving siRNA efficacy in gene silencing. Development of biocompatible and efficient nanostructures for siRNA delivery can make milestone progress in alleviation of breast cancer patients.


Subject(s)
Breast Neoplasms , Nanoparticles , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , RNA, Small Interfering/genetics , Cell Line, Tumor , Cell Death , RNA Interference , Drug Delivery Systems
8.
Adv Biomed Res ; 12: 255, 2023.
Article in English | MEDLINE | ID: mdl-38192889

ABSTRACT

Background: TYK2 is a member of the JAK family and is known to mediate signals of multiple cytokines that play a crucial role in immune and inflammatory signaling. Activation of TYK2 in tumor cells has been linked to promote cell survival, growth, and invasion. This study aimed to investigate the expression of tyrosine kinase 2 (TYK2) in colorectal cancer (CRC) and adjacent control tissues. Materials and Methods: Quantitative Real-Time PCR (qRT-PCR) method was elaborated to examine the expression levels of TYK2 in 100 colorectal tumor tissues and adjacent tissues as a control. Furthermore, we analyzed the diagnostic power of the mentioned TYK2 by plotting the receiver operating characteristic (ROC) curve. Results: Our results revealed that the expression level of TYK2 was significantly up-regulated in CRC patients sample compared to the adjacent sample of the control group. Analysis of patient's clinic pathological features shows that expressions TYK2 were differently associated with lymph vascular invasion and TMN stage (P < 0.0001, P < 0.0006). Conclusion: These results indicated that TYK2 levels potential biomarkers for diagnosing colorectal cancer may be identified.

9.
Cell Mol Biol (Noisy-le-grand) ; 69(14): 277-285, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38279418

ABSTRACT

Breast cancer is a hormone-dependence and heterogenic disease. Drug resistance is the main reason for the failure of breast cancer treatment. Combinatory medications are methods for treatment but they are not sufficient in action. However, new approaches like molecular therapy reveal a new insight into cancer treatment. Studies show that Bcl-2 gene family inhibitors and ER blockers cause the improvement of recovery. Interfering molecules such as antisense ones can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Our team designed a new Antisense Oligonucleotide (ASO) based on Antisense oligo G3139. MCF-7 and MDA-MB-231 cell lines were used to evaluate cellular proliferation. Liposomes and cationic nano-complex (Niosome) are used to increase the cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO. The results indicated significant down-regulation of the Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all cell groups. The newly designed ASO reduced the expression of the Bcl-2 gene. It also had a synergistic effect with the Tamoxifen. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 in the cancer cells.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/metabolism , Liposomes/pharmacology , Liposomes/therapeutic use , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Apoptosis/genetics , Tamoxifen/pharmacology , Tamoxifen/therapeutic use , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/pharmacology , Cell Line , Cell Line, Tumor
10.
Iran J Allergy Asthma Immunol ; 21(5): 584-593, 2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36341566

ABSTRACT

Immune reconstitution after hematopoietic stem cell transplantation (HSCT) with a conditioning regimen has appeared to be a promising treatment for autoimmune diseases and hematologic malignancies. This study aimed to assess the T cell receptor (TCR) repertoire diversity in CD4+ cells of patients with hematological malignancies who received allogeneic or autologous HSCT. The diversity of the TCR repertoire was evaluated in 13 patients with hematologic malignancies before and four months after HSCT. Amino acid changes in the 25 Vß families were evaluated using Spectratyping and data were presented as Hamming distance (HD). HD more than 20% was considered a change in TCR repertoire after HSCT. The mean HD was significantly changed after transplantation in all Vß gene families, with most amino acid changes in p4 and p22 families. There was a strong negative correlation between the HD as the index of TCR repertoire and age (r = -0.62,). The results revealed no association between HD mean and parameters such as sex, disease, conditioning regimen, and type of transplantation. Our data revealed that commonly used conditioning regimens in Iran could successfully cause TCR repertoire diversity in patients with hematologic malignancies in the short term. The amount of change in TCR repertoire was inversely correlated with the increasing age of patients.


Subject(s)
Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Humans , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Hematologic Neoplasms/therapy , Receptors, Antigen, T-Cell/genetics , Amino Acids
11.
Sci Rep ; 12(1): 18063, 2022 10 27.
Article in English | MEDLINE | ID: mdl-36302939

ABSTRACT

Small cell lung cancer (SCLC) is a particularly lethal subtype of lung cancer. Metastatic lung tumours lead to most deaths from lung cancer. Predicting and preventing tumour metastasis is crucially essential for patient survivability. Hence, in the current study, we focused on a comprehensive analysis of lung cancer patients' differentially expressed genes (DEGs) on brain metastasis cell lines. DEGs are analysed through KEGG and GO databases for the most critical biological processes and pathways for enriched DEGs. Additionally, we performed protein-protein interaction (PPI), GeneMANIA, and Kaplan-Meier survival analyses on our DEGs. This article focused on mRNA and lncRNA DEGs for LC patients with brain metastasis and underlying molecular mechanisms. The expression data was gathered from the Gene Expression Omnibus database (GSE161968). We demonstrate that 30 distinct genes are up-expressed in brain metastatic SCLC patients, and 31 genes are down-expressed. All our analyses show that these genes are involved in metastatic SCLC. PPI analysis revealed two hub genes (CAT and APP). The results of this article present three lncRNAs, Including XLOC_l2_000941, LOC100507481, and XLOC_l2_007062, also notable mRNAs, have a close relation with brain metastasis in lung cancer and may have a role in the epithelial-mesenchymal transition (EMT) in tumour cells.


Subject(s)
Brain Neoplasms , Lung Neoplasms , RNA, Long Noncoding , Small Cell Lung Carcinoma , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Gene Regulatory Networks , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Protein Interaction Maps/genetics , Transcriptome , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Brain Neoplasms/genetics , Brain/metabolism
12.
Diabetes Res Clin Pract ; 189: 109945, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35690269

ABSTRACT

Diabetes mellitus (DM) has been the most prevalent global metabolic disease, turning into a serious risk for human health. Several researches have recorded a role for inflammation and immunity in the pathogenesis of both in T1DM and in T2DM. Lots of chemical agents are available to control and to cure diabetic patients, which are not always sufficient for euglycemia maintenance and late stage diabetic complications avoidance. Therefore, newborn therapeutic methods to refine clinical outcomes in DM are required. Nucleic-acid-based therapy also known as gene expression level regulator within the target cells has been calculated to be promising in various diseases. Thus, pronounced attempts have been dedicated to develop new targeted molecular therapy aimed at improving insulin resistance in DM. This review mainly focuses on recent progress in DM molecular therapy and whether, has potential efficacy against inflammatory mediators involved in DM.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Insulin Resistance , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Humans , Infant, Newborn , Inflammation/complications
13.
Clin Neurol Neurosurg ; 213: 107108, 2022 02.
Article in English | MEDLINE | ID: mdl-34995834

ABSTRACT

OBJECTIVE: Epilepsy is a disease of Central Nervous System (CNS) characterized by abnormal brain activity and recurrent seizures and is considered a clinically and genetically heterogeneous disease. Here, we investigated pathogenic genetic alteration and described the clinical characteristics of three Iranian family members affected by Idiopathic Generalized Epilepsy (IGE) with and without intellectual disability. METHODS: A non-consanguineous Iranian family with juvenile myoclonic epilepsy was enrolled in the study. The comprehensive neurological evaluation included motor and sensory skills, vision, hearing, speech, coordination, and mood. Whole-exome Sequencing (WES) was performed on the proband to detect probable pathogenic variant, and after the filtering process, probable variants were evaluated with familial segregation analysis using Sanger sequencing. RESULTS: Using WES, we identified a heterozygous missense substitution (NM_023035.3:c.T677G:p.Leu226Trp) in CACNA1A gene in the studied family with juvenile myoclonic epilepsy with and without intellectual disability and psychiatric phenotype. Considering the patients' clinical synopsis, familial segregation analysis, and literature review, we postulated this variant to be causative of the disease. Indeed, the resulting missense mutation of Leu226Trp affects a highly conserved residue supporting our hypothesis that this mutation is potentially pathogenic. CONCLUSION: To the best of our knowledge, this is the first report of juvenile myoclonic epilepsy related to CACNA1A gene. Our results provide evidence for expanding the clinical and molecular findings related to the CACNA1A gene.


Subject(s)
Epilepsy, Generalized , Intellectual Disability , Myoclonic Epilepsy, Juvenile , Calcium Channels/genetics , Epilepsy, Generalized/genetics , Humans , Intellectual Disability/genetics , Iran , Myoclonic Epilepsy, Juvenile/genetics , Pedigree , Exome Sequencing
14.
Cell Mol Biol (Noisy-le-grand) ; 68(10): 193-198, 2022 Sep 30.
Article in English | MEDLINE | ID: mdl-37114250

ABSTRACT

As the most common malignancy, oral squamous cell carcinoma (OSCC) is typically fatal. The survival of patients with oral cancer has not improved, and tumor recurrence remains high. During tumorigenesis, microRNAs (miRNAs) regulate gene expression. Patients' life expectancy can be determined by prognostic survival biomarkers, which can focus therapy on specific targets. This study evaluated five miRNAs associated with OSCC for their prognostic impact. It was determined through microarray analysis and quantitative reverse transcription polymerase chain reaction that there was a significant difference in the expression of miRNAs between OSCC patients and control patients in plasma. We used the unpaired t-tests and the Mann-Whitney test to conduct the statistical analysis. Based on the study's results, five miRNAs have been found to have significantly different expression levels in the plasma of patients with OSCC; in particular, miR-31 was found to have a significantly higher expression level in OSCC patients' plasma as compared with healthy controls. Aside from that, there was a significant reduction in the expression of miR-100, miR-199a, miR-203, and mir345 in the plasma of OSCC patients (P < 0.05). To better understand the importance of miRNAs in OSCC, various OSCC cases were analyzed. Detecting miRNAs in plasma may be a useful diagnostic tool for oral squamous cell carcinoma.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , MicroRNAs , Mouth Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/diagnosis , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Neoplasm Recurrence, Local , MicroRNAs/metabolism , Biomarkers , Head and Neck Neoplasms/genetics , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic
15.
Cell Mol Biol (Noisy-le-grand) ; 68(10): 8-14, 2022 Sep 30.
Article in English | MEDLINE | ID: mdl-37114277

ABSTRACT

Paspalidium flavidum (watercrown grass), a medicinal plant, is traditionally used in liver ailments and stomach problems. The hepatoprotective and gastroprotective activities of the aqueous methanol extract of Paspalidium flavidum (AMEPF) were studied in experimental animal models. Paracetamol and aspirin were used to induce hepatotoxicity and gastric ulcer in rats, respectively. Biochemical hepatic parameters, gastric pH, total acidity, ulcer index, percentage protection, nitric oxide and TNF-α were measured in AMEPF-treated groups. Moreover, GC-MS analysis of AMEPF was performed. Pretreatment with AMEPF improved the blood lipid profile and restored liver function tests in paracetamol-induced hepatotoxicity. While in aspirin-induced gastric ulcer, oral administration of AMEPF significantly reduced (P<0.05) the gastric lesions, total acidity and ulcer scoring index, TNF-α with upregulation of nitric oxide when compared with the Diseased group. AMEPF exhibited anti-lipid peroxidation activity. Histopathological studies were in good agreement with the biochemical findings. GC-MS analysis revealed the presence of anti-oxidant phyto-constituents, including oleic acid and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) in AMEPF. This study suggested that aqueous methanol extract from the leaves of P. flavidum has beneficial hepatoprotective and gastroprotective activities related to its anti-oxidant phytochemicals.


Subject(s)
Anti-Ulcer Agents , Chemical and Drug Induced Liver Injury , Stomach Ulcer , Rats , Animals , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Antioxidants/pharmacology , Antioxidants/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Gastric Mucosa , Methanol , Anti-Ulcer Agents/adverse effects , Ulcer/drug therapy , Ulcer/pathology , Acetaminophen/adverse effects , Nitric Oxide , Tumor Necrosis Factor-alpha , Disease Models, Animal , Aspirin/adverse effects , Poaceae , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/pathology , Plant Leaves , Phytotherapy
16.
Cell Mol Biol (Noisy-le-grand) ; 68(12): 74-78, 2022 Dec 31.
Article in English | MEDLINE | ID: mdl-37130177

ABSTRACT

Sentinel lymph node (SLN) biopsy is currently the recommended procedure for axillary staging in clinically node-negative early breast cancer at diagnosis. The present study aimed to identify Cytokeratin-19 (CK19) gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor samples from breast cancer patients were analyzed for the expression of the CK19 gene using quantitative PCR. Also, normal breast tissues (N = 50) were taken from the same patients that had undergone partial or total mastectomy. This gene signature was confirmed based on tumor's stage, grade, and estrogen receptor (ER) status, using conditional logistic regression. Based on these findings, the negative reported lymph nodes for metastasis had micrometastasis in significant values. There was a significant difference between normal and cancer samples in  CK19 expression. In this sentinel node evaluation, the relationship of this gene with tumor characteristics needs to be established and discussed finding a clear role for this gene in tumor outcome.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Iran , Lymphatic Metastasis , Keratin-19/genetics , Mastectomy , Neoplasm Staging , Gene Expression
17.
Orphanet J Rare Dis ; 16(1): 461, 2021 11 02.
Article in English | MEDLINE | ID: mdl-34727962

ABSTRACT

BACKGROUND: Epilepsy is a neurological disorder characterized by the potential to induce seizure and accompanied by cognitive, psychological, and social consequences. CACNA1A gene is a voltage-gated P/Q-type Cav2.1 channel that is broadly expressed in the central nervous system, and the pathogenic variants within this gene may be associated with the epileptic phenotype. In the present study, we collected clinical and molecular data related to epileptic patients with CACNA1A pathogenic variants and investigated possible meaningful relationship between age at onset, neurodevelopmental disorders, type of seizures, brain imaging abnormalities, genotype, and protein domains. RESULTS: In our retrospective literature studies, from among 890 articles reviewed, a total of 90 individuals were related to epilepsy phenotype. Our findings showed that about 90 percent of patients have shown the first symptoms in childhood and teenage years and different types of neurodevelopmental disorders, such as intellectual disability, developmental arrest, and behavioral disorders, have been common findings for these patients. Further, a wide range of abnormalities have been observed in their brain imaging, and generalized seizures have been the most type of seizures in these patients. However, our data showed no specific genotype-phenotype correlation in epileptic patients with CACNA1A pathogenic alterations. CONCLUSIONS: Our study focused on epileptic phenotype in patients with CACNA1A pathogenic variants and showed a wide range of clinical and molecular heterogeneity with no specific genotype-phenotype correlation. It seems that incomplete penetrance, de-novo variants, and modifier genes are obstacles in predicting the clinical outcome.


Subject(s)
Calcium Channels, Q-Type , Calcium Channels/genetics , Epilepsy , Adolescent , Calcium Channels, N-Type/genetics , Epilepsy/genetics , Humans , Retrospective Studies
18.
Hum Antibodies ; 29(3): 209-216, 2021.
Article in English | MEDLINE | ID: mdl-34057143

ABSTRACT

Signal Transducer and Activator of Transcription (STAT) pathway is functionally located downstream of Janus kinases proteins and can integrate signals from diverse pathways, thus regulating several aspects of immune responses. Although contribution of STAT proteins in the pathogenesis of several inflammatory conditions has been confirmed, their role in the development of periodontitis has been less appraised. Thus, we assessed levels of STAT transcripts in the periodontal tissues and circulation of affected individuals compared with the corresponding controls. Expression of STAT1 was remarkably lower in tissues samples of patients compared with control tissues (Ratio of mean expression (RME) = 0.15, SE = 0.99, P value = 0.01). Expression of STAT3 was lower in total periodontitis tissues compared with total control tissues (RME = 0.20, SE = 0.95, P value = 0.02). Expression of STAT6 was higher in total periodontitis tissues compared with total control tissues (RME = 0.5.38, SE = 0.74, P value < 0.001). Expressions of other STAT genes were statistically similar in tissues obtained from cases and controls. Moreover, blood levels of all STAT genes were statistically similar between patients and controls. Correlation analysis demonstrated significant correlations between tissues levels of individual STAT genes as well as between their blood levels. However, tissue and blood levels of each STAT gene were not correlated. The current investigation potentiates the role of certain STAT genes in the development of this immune-related condition and warrants functional assays to clarify the mechanism.


Subject(s)
Periodontitis , STAT Transcription Factors/genetics , Gene Expression Regulation , Humans , Periodontitis/genetics , Signal Transduction/genetics , Transducers
19.
Gulf J Oncolog ; 1(35): 7-13, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33716207

ABSTRACT

INTRODUCTION: Lung cancer is the most deadly and sumptuous cancer across the globe. Cancer occurrence is increasing progressively and there is no ideal cure yet. Therefore, new therapeutic areas are needed. The use of herbal extracts due to its properties such as antioxidant activity, anti-proliferative effect, and few side effects can be promising in the treatment of cancer. This study aimed to compare the effect of Echinophora platyloba DC. and Cordia myxa L extracts on apoptosis induction in A549 cancer cells. MATERIALS AND METHODS: In this experiment, the A549 cell line was first cultured in DMEM medium containing 10% FBS and then treated with different concentrations of both compounds. MTT assay was performed to determine IC50 and to compare the viability of cells treated with different concentrations of Echinophora platyloba DC. and Cordia myxa L seed on days 1, 3 and 5. QRT-PCR test was used to investigate the effects of Echinophora platyloba DC. and Cordia myxa L with IC50 on apoptosis induction. RESULTS: MTT results showed that both plant extracts resulted in cell death and decreased viability of lung cancer cells. But the percentage of viability decreased by Echinophora platyloba DC. was more. Also, Echinophora platyloba DC. significantly increased the expression of Bax, P53 and Bad apoptotic genes and decreased the expression of Bcl2 gene, which induces apoptotic death and the cytotoxic effect of Echinophora platyloba DC. over Cordia myxa L. CONCLUSION: In comparing the effects of these two extracts Echinophora platyloba DC. was more effective than Cordia myxa L and had greater cytotoxicity on A549 cancerous cells in a lesser concentration and could be an appropriate drug candidate for the treatment of lung cancer.


Subject(s)
Lung Neoplasms/genetics , Plant Extracts/chemistry , A549 Cells , Apoptosis , Humans , Lung Neoplasms/pathology
20.
Asian Pac J Cancer Prev ; 22(2): 627-632, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33639683

ABSTRACT

OBJECTIVE: Management of hyperuricemia is crucial to controlling tumor lysis syndrome (TLS) during cancer therapy. Urate oxidase (UOX) that catalyzes the enzymatic oxidation of uric acid into allantoin, is effective in lowering plasma uric acid levels and controlling hyperuricemia. Recently, we developed a new recombinant conjugate variant of UOX therapeutic drug using PASylation technology. This study was designed to evaluate the stability, plasma half-life and immunogencity of PASylated UOX. METHODS: A recombinant variant of PASylated UOX from the Aspergillus flavus was manufactured using bioinformatics and experimental techniques. Ex vivo evaluation of stability of PASylated UOX was done in 50% human serum. For half-life test, recombinant PASylated UOX and rasburicase were administered at 1.5 mg/kg to 10 rats in two different groups and samples were collected after injection Production of antibodies against PASylated drug was also assayed. RESULTS: Residual activity of PASylated UOX in 50% human serum was higher than rasburicase and native UOX. Stability of PASylated UOX at 25°C and 37°C was also higher than rasburicase and native UOX. The PASylated half-life was ~32.1 hours, whereas half-life for rasburicase and native UOX was ~25.1 and ~22.8 hours, respectively. In immunogenicity examination, there is 33% and 36% decrease in the absorbance of native UOX and rasburicase, respectively when compared with that of PASylated UOX. CONCLUSION: Our data confirmed the efficacy and stability of PASylated UOX in comparison to the rasburicase. In summary, the results indicated that PASylated UOX drug is effective at lowering plasma uric acid levels with prolonged plasma half-life and decreased cost.
.


Subject(s)
Hyperuricemia/drug therapy , Urate Oxidase/pharmacology , Animals , Drug Stability , Half-Life , Humans , Hyperuricemia/blood , Rats , Recombinant Proteins
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