Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.

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.

Lysine ε-aminolysis and incorporation of sulfhydryl groups into human brain tau 4R/1N and 306VQIVYK311 enhances the formation of beta structures and toxicity.

In the present study, we investigated the effects of N-homocysteine thiolactone (tHcy) modification on expressed and purified tau protein and the synthesized VQIVYK target peptide. The modified constructs were subjected to comprehensive validation using various methodologies, including mass spectrometry. Subsequently, in vivo, in vitro, and in silico characterizations were performed under both reducing and non-reducing conditions, as well as in the presence and absence of heparin as a cofactor. Our results unequivocally confirmed that under reducing conditions and in the presence of heparin, the modified constructs exhibited a greater propensity for aggregation. This enhanced aggregative behavior can be attributed to the disruption of lysine positive charges and the subsequent influence of hydrophobic and p-stacking intermolecular forces. Notably, the modified oligomeric species induced apoptosis in the SH-SY5Y cell line, and this effect was further exacerbated with longer incubation times and higher concentrations of the modifier. These observations suggest a potential mechanism involving reactive oxygen species (ROS). To gain a deeper understanding of the molecular mechanisms underlying the neurotoxic effects, further investigations are warranted. Elucidating these mechanisms will contribute to the development of more effective strategies to counteract aggregation and mitigate neurodegeneration.

Plasma cytokines profile in patients with Alzheimer's and Parkinson's Disease: a comparative study in terms of inflammation.

BACKGROUND: Neurodegenerative disorders such as Alzheimer's and Parkinson's disease inflict economic and health burdens on societies. Alzheimer's disease (AD), the most prevalent form of dementia, is accompanied by progressive degradation of memory, decision-making, and judgment. Parkinson's disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and loss of balance. Extensive research has pinpointed inflammation as a cause of the onset and progression of both diseases. However, it has not been confirmed which one is more formidable in terms of inflammation. METHODS: To assess the extent of inflammation that is implicated in AD and PD and answer the question of which one is more inflammatory, serum levels of inflammatory biomarkers, including cytokines, chemokines, and prostaglandin E2 (PEG2), were measured in AD and PD patients as well as a healthy group. RESULTS: Our results showed a significant increase in IL-1α, IL-1ß, IL-4, IL-6, IL-10, IL-12p70, IP-10, MCP-1, PEG2, and TNF-α in AD and PD patients compared with the control. Interestingly, IFN-γ did not manifest any significant difference in AD or PD patients compared with the control. CONCLUSION: As a hallmark of our results, it could be inferred that inflammation, as the underlying etiological cause, plays a more crucial role in PD compared with AD. Based on our results, it is proposed that anti-inflammatory remedies would be putatively more effective in PD rather than AD.

Unveiling Therapeutic Potential: A Systematic Review of Photobiomodulation Therapy and Biological Dressings for Diabetic Foot Ulcers.

Introduction: Diabetes poses a global health challenge, giving rise to various complications, including diabetic foot ulcers (DFUs). DFUs, marked by ischemic ulcers susceptible to infection and amputation, underscore the urgency for innovative treatments. This study investigated the impact of photobiomodulation therapy (PBT) and autologous platelet gel (APG) on DFUs recovery. Methods: We systematically searched Web of Science, EMBASE, MEDLINE, Cochrane Library, Scopus, and Google Scholar (2015-2023) by using pertinent terms like "photobiomodulation therapy," "low level light therapy," and "platelet gel." After meticulous data extraction and review, 57 articles were chosen and categorized. Among these, three randomized controlled trials involving 186 participants were selected for APG analysis. Results: Findings demonstrate that APG application carries minimal risk and offers promising improvements in healing time, grade, pain reduction, and granulation tissue formation. Similarly, diverse PBT modalities involving distinct probes and wavelengths exhibit the potential to enhance tissue perfusion, expedite healing, and impede wound progression, reducing the need for invasive interventions. Conclusion: PBT and APG emerge as valuable tools to augment wound healing, mitigate inflammation, and avert amputation, representing compelling therapeutic options for DFUs.

Molecular mechanisms and treatment strategies for methamphetamine­induced neurodegeneration, inflammation and neurotoxicity.

Methamphetamine (METH) is a highly addictive psychostimulant known for its profound impact on the nervous system. Chronic METH use leads to neurotoxicity characterized by various molecular and structural alterations in the brain. This review article primarily aims to elucidate the mechanisms underlying METH­induced neurotoxicity. METH's mechanism of action involves the inhibition of dopamine, serotonin, and norepinephrine reuptake, resulting in altered synaptic function. Prolonged METH exposure triggers oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, impaired axonal transport, autophagy, and programmed cell death, ultimately contributing to neurotoxicity. These neurotoxic effects manifest as increased neuronal firing rate, disruptions in intracellular ion balance (Ca2+ and Na+), energy production imbalances, and excessive reactive oxygen species production. The blood­brain barrier is compromised, leading to structural, functional, and neurochemical alterations, particularly in the fronto­striatal circuit. While our comprehensive review addresses these intricate molecular and structural changes induced by METH, we also examined the latest therapeutic strategies designed to mitigate neurotoxicity. Our investigation sheds light on the critical need to comprehend the complex pathways underlying METH­induced neurotoxicity and develop effective treatment approaches.

Low-Level Laser Therapy for Rheumatoid Arthritis: A Review of Experimental Approaches.

Introduction: Rheumatoid arthritis (RA) is an inflammatory and autoimmune disorder that is characterized by joint inflammation, pain, physical disability, and morning stiffness. In the present study, the effect of low-level laser therapy (LLLT) on RA was reviewed. Methods: "Low-level laser therapy", "rheumatoid arthritis disease", and "photobiomodulation" keywords were searched in Google Scholar, PubMed, and Medline. Results: A literature survey led to a discussion about the immunology of the RA, laser therapy, mechanism of LLLT action, and anti-inflammatory and immunomodulatory properties of LLLT. Conclusion: It was concluded that LLLT could improve RA patients' quality of life, reduce pain, and enhance physical movement.

Risk of second primary cancer among breast cancer patients: A systematic review and meta-analysis.

Objectives: The aim of this study was to estimate the extra risk of second primary cancer among breast cancer patients. Methods and materials: This is a systematic review. A comprehensive search of literature was performed in PubMed, Web of Science, Cochrane library, and Scopus. The search included all published studies up to October 2022. This systematic review included studies published in the English language that reported the risk of second primary non-breast cancer [i.e., standardized incidence ratio (SIR)] among breast cancer patients older than 15 years. After evaluating the methodological quality of the selected studies, SIRs were pooled with consideration of heterogeneity among studies. The estimates were pooled by age and time since the diagnosis of primary breast cancer for both sexes (male and female). Age was categorized based on before 50 years and after 50 years, and time was categorized as duration of less than and more than 10 years, respectively. Results: From 2,484 articles, 30 articles were eligible for inclusion in the systematic review and meta-analysis. The studies varied in terms of population, number of cases, study design, setting, and year of implementation of the research. The estimated SIR for men and women was 1.28 (95% CI: 1.18, 1.38) and 1.27 (95% CI: 1.15, 1.39), respectively. Women diagnosed with breast cancer before menopause [SIR: 1.52 (95% CI: 1.34, 1.71) vs. 1.21 (95% CI: 1.08, 1.34)] as well as women after 10 years since their breast cancer diagnosis [1.33 (95% CI: 1.22, 1.431) vs. 1.24 (95% CI: 1.10, 1.37)] were at a higher risk of developing second primary cancer. Among men, while there were no differences in risk based on age, with the increase of time, the risk of second primary cancer was reduced [SIR: 1.22 (95% CI: 1.12, 1.33) vs. 1.00 (95% CI: 0.79, 1.22)]. Conclusion: There is an extra risk of second primary cancer among breast cancer patients. The extra risk should be considered for further screening and preventive measures among this population. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336062, identifier (CRD42022336062).

The Role of Low-Level Laser Therapy in the Treatment of Multiple Sclerosis: A Review Study.

Introduction: Multiple sclerosis (MS) is an autoimmune disease. Inflammatory cells, cytokines and chemokines play a major role in the pathogenesis of the disease. Low-level laser therapy (LLLT) as a photobiostimulation approach could affect a wide range of cellular responses. LLLT inhibits the inflammatory signaling pathway, improves cell viability, inhibits apoptosis, modulates immune responses and induces the production of growth factors. Methods: In this review, we discuss the effect of LLLT on cellular responses and its application in the treatment of MS. Such keywords as "low-level laser therapy", "photobiomodulation" and "multiple sclerosis" were used to find studies related to laser therapy in MS in Google scholar, PubMed and Medline databases. Results: LLLT reduced the inflammatory immune cells and mediators. It also enhanced the regeneration of neurons. Conclusion: Investigations showed that besides current treatment strategies, LLLT could be a promising therapeutic approach for the treatment of MS.

The Screening of Critical Related Genes in Celiac Disease Based on Intraepithelial Lymphocytes Investigation: A Bioinformatics Analysis.

BACKGROUND: Celiac disease (CD) is an immunological intestinal disorder, which is characterized by response to gluten. In addition to the environmental factors and dysbiosis of the gut microbiota, genetic susceptibility has an important role in the pathogenesis of this multifactorial disorder. Therefore, this study aims to present the crucial involved genes in CD pathogenesis. MATERIALS AND METHODS: In this bioinformatics analysis study, significant differentially expressed genes of intraepithelial lymphocytes (IELs) samples of celiac patients versus normal patients from Gene Expression Omnibus (GEO) database were screened via the protein-protein interaction (PPI) network. The critical nodes based on degree values, betweenness centrality, and fold changes were determined and enriched by ClueGO to find relative biological terms. RESULTS: According to the network analysis, five central nodes including IL2, PIK3CA, PRDM10, AKT1, and SRC and eight significant differentially expressed genes (DEGs) were determined as the critical genes related to CD. Also, CD4+, CD25+, alpha-beta regulatory T cell differentiation are identified as prominent biological terms in the celiac disease patients. CONCLUSION: There is a possible biomarker panel related to CD that can be used as a therapeutic or diagnostic tool to manage the disease.

Introducing tumor necrosis factor as a prominent player in celiac disease and type 1 diabetes mellitus.

AIM: This study aimed to screen the common genes between celiac disease (CD) and type 1 diabetes mellitus to find critical ones. BACKGROUND: Celiac disease is a chronic autoimmune disorder which is correlated to type 1 diabetes mellitus (T1DM) in several molecular pathways. Understanding the clear common molecular mechanism of both diseases is of interest to scientists. METHODS: The related genes to the CD and T1DM were obtained from disease query of STRING and included in two separated PPI networks by Cytoscape software version 3.7.1. The networks were analyzed by network analyzer and the hub nodes were determined. The common hubs between the two networks were selected for further analysis and enriched via gene ontology using ClueGO plugin of Cytoscape software. Also, an action map was provided by Cluepedia application of Cytoscape software. RESULTS: Two separated networks of 2000 and 430 genes were constructed related to T1DM and CD, respectively. A total of 84 and 28 hubs were determined for T1DM and CD, respectively. There were 11 common hubs between the two networks. The first top hubs of Type 1 Diabetes Mellitus and CD networks were insulin (INS) and tumor necrosis factor (TNF), respectively. Also, 77 biological terms and pathways (in five clusters) were related to the common hubs. Action map revealed a close relationship between hubs. CONCLUSION: The result of this study indicated that TNF is key mediator of immune reactions in celiac disease and type 1 diabetes mellitus.

The roles of DNA epigenetics and clinical significance in Chronic Myeloid Leukemia: a review.

Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22) (q34;q11.2) encoding for the BCR-ABL fusion oncogene. Growing body of evidence suggests that epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukemic clone escape and disease propagation. The significant of therapeutic role in chronic myeloid leukemia (CML) depends on both genetic and epigenetic mechanisms.  This article focused on the CML and epigenetic and clinical significance. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, cancer, Google scholar, self-experience and PubMed databases. The keywords included leukemia, cancer, illness, epigenetic. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. Current progress in molecular biology and bioinformatics offer novel promising experiments namely as next generation sequencing for new development in epigenetic figures characterization and more understanding of the epigenetic mechanisms to be successfully utilized for personalized CML therapy in the next coming years.

Detection of gene expression in sentinel lymph node of primary breast cancer patients.

Sentinel lymph node (SLN) micrometstasis detection improves outcome for breast cancer follow up procedure. The aim of the present study was to identify gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor sample from breast cancer patients were analyzed for the expression of 3 genes using quantitative-PCR. Also clinical verification for recurrence to distant organs was performed. Three gene signature were confirmed based on tumor's stage, grade, ER status, using conditional logistic regression. Based on this findings, the negative reported lymph nodes for metastasis, had micro metastasis in significant values. There was a significant difference between normal and cancer samples in 3 gene expression marker and also there was meaningful relationship between three gene expression with tumor's grade, stage according to progression of tumor. A novel gene expression signature predictive of micro metastatic patients was evaluated. In this assessment, relationship between this gene with tumor's features   that finding clear role for these genes with tumor's outcome, needs to be established.

Determinants of survival of common childhood cancers in Iran.

BACKGROUND: Cancer is the second most common cause of morbidity and mortality in children. This study aimed to epidemiologically and demographically assess common cancers in children in Iran. MATERIALS AND METHODS: This cohort study was conducted on children registered in Mahak Hospital and Rehabilitation Complex (which is a non-governmental organizations (NGO)-related hospital for only malignant diseases). A total of 2232 questionnaires were filled out for cancer patients between 2007 and 2016. The factors including age, gender, race, family history, type of treatment, and type of cancer were entered into Cox regression model to examine their effect on mortality of children diagnosed with cancer. RESULTS: The Cox regression model showed that age, race, type of cancer, family history of cancer, and type of treatment had a significant effect on mortality of children diagnosed with cancer (P < 0.05). The hazard ratio (HR) of mortality in 10-15 years old was higher than that of 1-5 years old (P = 0.03, HR = 1.3). The HR of mortality in patients with brain tumor (P < 0.01, HR = 2.24), sarcoma (P < 0.01, HR = 2.32), and neuroblastoma (P < 0.01, HR = 2.56) was twice the value in patients with leukemia. The HR of mortality in patients who had a family history of cancer was higher than that of patients without it (P < 0.01, HR = 1.33). Patients who had undergone chemotherapy along with surgery and radiotherapy (P = 0.02, HR = 0.68) and patients who received chemotherapy along with surgery (P = 0.01, HR = 0.67) had a lower HR of mortality compared to the chemotherapy group. CONCLUSION: Young age, multidisciplinary approach, and absence of family history were associated with lower hazard of death in children diagnosed with cancer; brain tumor, leukemia, and sarcoma had higher hazard of mortality compared to leukemia. Children with a family history of cancer should be under regular follow-up. Treatment should be multidisciplinary and comprehensive.

Evaluation of IL-12A, IL-12B, IL-23A and IL-27 mRNA expression level genes in peripheral mononuclear cells of inflammatory bowel disease patients in an Iranian population.

AIM: Aim of this study was to compare the gene expression of Interleukin 12 members in two phase of IBD. BACKGROUND: Inflammatory bowel disease (IBD) is a well-known gastrointestinal disorder in the world that fluctuates between remission and flare-up phases. Each of these phases has an individual immune system response profile. Therefore, analyzing the interleukins (IL) expression status improves the diagnosis and the classification of the IBD cases. METHODS: In this a case-control study, among 400 patients whom admitted to the IBD clinic, forty nine IBD patients were included. Patients were divided into three categories based on 1) the phase of the disease, 2) the type of IBD, Ulcerative colitis (UC) or Crohn's disease (CD), and 3) the therapeutic pathways. Using the real-time PCR method, the expression levels of IL-12A, IL-12B, IL-23A, and IL-27 were examined in the peripheral blood mononuclear cell (PBMC) and compared to the pre-described subgroups. RESULTS: the data showed upregulation in the expression levels of IL-12A and IL-12B in the remission phase in comparison with the flare-up. However, no significant changes were obtained from the evaluation of IL-23A and IL-27. In addition, the mRNA levels of the target genes in the subgroups of Category 2 as well as Category 3 were similar. CONCLUSION: Our results showed that expression patterns of the IL-12A and IL-12B genes varied between the remission and flare-up phases for the IBD patients, and may be considered as potential biomarkers for the detection and the classification of IBD cases.

Genomic Profiling of Chronic Myelogenous Leukemia: Basic and Clinical Approach.

Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR-ABL1 fusion protein. We review the previous and recent evidence on the significance of CML in diagnostic and clinic management. The technical monitoring of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed by reciprocal chromosomal translocations between human chromosome 9 and 22, t(9:22) (q34:q11). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine kinase activity that promotes the characteristic proliferation of progenitor cells in CML and acute lymphoblastic lymphoma. The targeting of BCR-ABL1 fusion kinase is the first novel paradigm of molecularly targeted curing.

XRCC1 Gene Polymorphisms and Breast Cancer Risk: A Systematic Review and Meta- Analysis Study.

Breast cancer risk assessment has developed during years and evaluation of genetic factor affecting risk of breast cancer is an important component of this risk assessment. The aim of this meta-analysis was to investigate the role of XRCC1 polymorphisms (Arg194Trp, Arg280His and Arg399Gln) for risk of breast cancer among different population and categories of menopausal status. PubMed, Medline, Web of Science, and PubMed Central were systematically searched to identify studies evaluating association between breast cancer and XRCC1 gene polymorphisms (Arg194Trp, Arg280His and Arg399Gln). Two authors independently extracted required information. Odds Ratios were pooled for four genetic inheritance models using both fixed and the DerSimonian and Laird random-effect models. Egger's test and contour-enhanced funnel plot were used to evaluate publication bias and small study effect. Additional subgroup analysis was performed for menopausal status, ethnicity, and source of controls. After evaluation and applying inclusion criteria on extracted studies, fifty three studies were included in this meta-analysis. For polymorphisms of Arg194Trp and Arg280His, no significant association was observed in all genetic models. Arg194Trp had a protective effect in post-menopausal status only in homozygote model (OR=0.57 [0.37-0.88]). Arg399Gln showed significant association with breast cancer in homozygote (OR=1.21 [1.10-1.34]), dominant (OR=1.09 [1.03-1.15]) and recessive (OR=1.21 [1.09-1.35]) models. Arg399Gln was associated with higher risk in post-menopausal status for homozygote and heterozygote models. Our findings suggest that XRCC1 gene polymorphisms modify breast cancer risk in different populations and different categories of menopausal status.

Correlation Between Nitrogen Dioxide as an Air Pollution Indicator and Breast Cancer: a Systematic Review and Meta- Analysis.

BACKGROUND: The aim of this systematic review was to study the relationship between exposure to nitrogen dioxide (NO2) in the ambient air and breast cancer incidence. MATERIALS AND METHODS: A systematic review was performed based on the MOOSE guideline for review of observational studies. We searched five online databases (PubMed, Science Direct, Google Scholar, EBSCO, and Scopus) from their conception to June 2014. A pooled estimate of the correlation between NO2 exposure and breast cancer incidence was calculated using Pearson's correlation coefficient. RESULTS: A total of 654 titles were retrieved in the initial search of the databases. Further refinement and screening of the retrieved studies produced a total of five studies from four countries. The studies included three ecological studies (aggregate level) and two individual based studies (one prospective cohort and the other one a case-control study). The ecological studies were pooled and the meta-analysis of correlation coefficient without z transformation showed a pooled estimate of r = 0.89 with 95% CI of 0.84 to 0.95. Using z transformation, the pooled r was 1.38 with 95%CI of 1.11 to 1.59. No significant heterogeneity between studies was observed. Following a sensitivity analysis and the removal of each study from pooled analysis we did not see any significant change in the pooled estimate. CONCLUSIONS: It was concluded that there is a tendency toward a weak association between exposure to NO2 in ambient air and breast cancer at the individual level and a significant association at the aggregate level.

Introduction of inflammatory bowel disease biomarkers panel using protein-protein interaction (PPI) network analysis.

AIM: In the present study, a protein-protein interaction network construction is conducted for IBD. BACKGROUND: Inflammatory bowel diseases as serious chronic gastrointestinal disorders attracted many molecular investigations. Diverse molecular information is present for IBD. However, these molecular findings are not highlighted based on interactome analysis. On the other hand, PPI network analysis is a powerful method for study of molecular interactions in the protein level that provide useful information for highlighting the desired key proteins. METHODS: Cytoscape is the used software with its plug-ins for detailed analysis. Two centrality parameters including degree and betweenness are determined and the crucial proteins based on these parameters are introduced. RESULTS: The 75 proteins among 100 initial proteins are included in the network of IBD. Seventy-five nodes and 260 edges constructed the network as a scale free network. The findings indicate that there are seven hub-bottleneck proteins in the IBD network. CONCLUSION: More examination revealed the essential roles of these key proteins in the integrity of the network. Finally, the indicator panel including NFKB1, CD40, TNFA, TYK2, NOD2, IL23R, and STAT3 is presented as a possible molecular index for IBD.

Trends in incidence of breast cancer among women under 40 in Asia.

BACKGROUND: The aim of this study was to evaluate trends in incidence of breast cancer in women less than 40 years in Asia. MATERIALS AND METHODS: Registered cases of female breast cancer age less than 40 years and corresponding person years were ascertained from the CI5plus for 10 registries in Asia for the duration of 1970- 2002. Cases were categorized into three age groups: 16-40, 16-29, and 30-40. The 16-40 age group was adjusted to world age population structure. Joinpoint regression analysis was conducted to determine the annual percent of change (APC) and the average annual percent of change (AAPC) for each age group. RESULTS: A total of 23,661 cases of breast cancer occurred in the 10 registries during the 32 years (1970-2002) of follow-up. The overall age adjusted (16-40 group) breast cancer incidence rate increased from 2.28-4.26 cases per 100,000 population corresponding to an AAPC of 2.6% (95%CI 2.1, 3.0). The trend in incidence for the age group 16-29 increased from 0.45-1.07 corresponding to an AAPC of 2.8% (95%CI 1.9, 3.7). In age group 30 to 40, the incidence ranged from 13.3 in year 1970 to 24.8 in year 2002 corresponding to an AAPC of 2.7% (95% CI 2.3, 3.1). There were two statistically significant changing points in the regression line for the age groups 30-40 and 16-40: one point in the year 1975 with an APC of 6.1 (5.1, 7.1), and the other in 1985 with an APC of 0.4% (0.01, 0.8). CONCLUSIONS: Our study proved that: 1) the incidence of breast cancer in young women has increased in Asian population during the study period; 2) the rate of increase was very high during the period of 1980-1990.