Comprehensive Analysis of the Prognostic Marker and Immune Infiltrates of LDLR-Related Proteins Family Members in Breast Cancer.

Background & Objective: Breast cancer (BC) is one of the most frequent tumors worldwide, accounting for 15% of all cancer-related deaths. A timely diagnosis of BC is essential for optimal treatment and increasing patients' survival rates. LRP family proteins are important components of cell-surface receptors involved in numerous biological activities. Expression of LRP is related to breast malignancy. In this study, we initially studied the expression of LRPs in BC tissues compared to normal tissues-the relation of LRP expression with relapse-free survival (RFS) and overall survival (OS). Then, we investigated the association of LRPs relation and immune infiltrating abundance. Methods: We analyzed the LDLR family expression and prognostic value in BC by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. Subsequently, we explored the association of LDLR expression and immune infiltrating abundance via the TIMER database. Results: Expression levels of LRP1/2/4/9/10 were found to be higher in the cases with positive estrogen receptors. There was a positive association between LRP1/6 expression and the infiltration of CD8+ T cells, CD4+ T Cell, Macrophage, Dendritic Cell, and Neutrophil. Conclusion: Our study recommends LDLR as a potential prognostic biomarker that can be promising to improve the survival of BC patients' survival. However, further investigations are needed to evaluate the studied LDLR members in more detail.

Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review.

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic ß-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.

Comprehensive Analysis of the Expression, Prognosis, and Immune Infiltrates for Chromodomain-Helicase-DNA-Binding Proteins in Breast Tumor.

BACKGROUND: Several recent studies suggest that chromodomain-helicase -DNA-binding domains (CHDs) are linked with cancers. We explored the association between chromodomain-Helicase-DNA-binding domain proteins and breast cancer (BrCa) and introduced potential prognostic markers using various databases. MATERIALS AND METHODS: We analyzed the expression of the CHD family and their prognostic value in BrCa by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. The association of CHD expression and immune infiltrating abundance was studied via the TIMER database. In addition, microRNAs related to the CHD family were identified by using the MirTarBase online database. RESULTS: The present study indicated that compared to normal tissues, BrCa tissues showed increased mRNA levels of CHD3/4/7 but decreased CHD2/5/9 expression. Interestingly, We also found a positive correlation between CHD gene expression and the infiltration of macrophage, neutrophil, and dendritic cells in BrCa, except CHD3/5. The Kaplan-Meier Plotter analysis suggested that high expression levels of CHD1/2/3/4/6/8/9 were significantly related to shorter relapse-free survival (RFS), while higher mRNA expression of CHD1, CHD2, CHD8, and CHD9 was significantly associated with longer overall survival of BrCa patients. The miRNAs of hsa-miR-615-3p and hsa-let-7b-5p were identified as being more correlated with the CHD family. CONCLUSION: The altered expression of some CHD members was significantly related to clinical cancer outcomes, and CHD1/2/8/9 could serve as potential prognostic biomarkers to improve the survival of BrCa patients. However, to evaluate the studied CHD members in detail are needed further investigations including experimental validation.

Cell Therapies and Gene Therapy for Diabetes: Current Progress.

The epidemic of diabetes continues to be an increasing problem, and there is a need for new therapeutic strategies. There are several promising drugs and molecules in synthetic medicinal chemistry that are developing for diabetes. In addition to this approach, extensive studies with gene and cell therapies are being conducted. Gene therapy is an existing approach in treating several diseases, such as cancer, autoimmune diseases, heart disease and diabetes. Several reports have also suggested that stem cells have the differentiation capability to functional pancreatic beta cell development in vitro and in vivo, with the utility to treat diabetes and prevent the progression of diabetes-related complications. In this current review, we have focused on the different types of cell therapies and vector-based gene therapy in treating or preventing diabetes.

RNA interference-based therapies for atherosclerosis: Recent advances and future prospects.

Atherosclerosis represents a pathological state that affects the arterial system of the organism. This chronic, progressive condition is typified by the accumulation of atheroma within arterial walls. Modulation of RNA molecules through RNA-based therapies has expanded the range of therapeutic options available for neurodegenerative diseases, infectious diseases, cancer, and, more recently, cardiovascular disease (CVD). Presently, microRNAs and small interfering RNAs (siRNAs) are the most widely employed therapeutic strategies for targeting RNA molecules, and for regulating gene expression and protein production. Nevertheless, for these agents to be developed into effective medications, various obstacles must be overcome, including inadequate binding affinity, instability, challenges of delivering to the tissues, immunogenicity, and off-target toxicity. In this comprehensive review, we discuss in detail the current state of RNA interference (RNAi)-based therapies.

Curcumin as a regulator of Th17 cells: Unveiling the mechanisms.

Curcumin, a polyphenol natural product derived from turmeric, possesses diverse pharmacological effects due to its interactions with various cells and molecules. Recent studies have highlighted its immunomodulatory properties, including its impact on immune cells and mediators involved in immune responses. Th17 cells play a crucial role in promoting immune responses against extracellular pathogens by recruiting neutrophils and inducing inflammation. These cells produce inflammatory cytokines such as TNF-α, IL-21, IL-17A, IL-23, IL-17F, IL-22, and IL-26. Curcumin has been shown to significantly inhibit the proliferation of Th17 cells and reduce the production of inflammatory cytokines, including TNF-α, IL-22, and IL-17. This review aims to assess the effectiveness of curcumin and its underlying mechanisms in modulating Th17 cells.

Effect of CDH1 and CDH2 genes polymorphisms in oral squamous cell carcinoma susceptibility in a sample of Iranian population: A case-control study.

Background and Aims: Oral squamous cell carcinoma (OSCC) is a global malignant epithelial neoplasm affecting the oral cavity. Cadherins, as an adhesion molecule, are involved in cell-cell interaction. We aim to study the effect of two cadherin polymorphisms on OSCC risk in southeast of Iran. Methods: In this case-control study, 94 individuals (47 OSCC cases and 47 controls), that referred to the Department of Oral Pathology, Faculty of Dentistry, Zahedan University of Medical Sciences, Iran were included. Cadherin single nucleotide polymorphisms CDH1 (rs16260) and CDH2 (rs11564299) were genotyped by the tetra-Amplification Refractory Mutation System-PCR technique. Results: N-cadherin genotyping showed that the AA, AG, and AG + GG were presented 78.7%, 17%, 21.3% versus 66%, 29.7%, 34% in the cases and the control group, respectively. AG genotype was more common in control than case (OR = 0.47, 95% CI: 0.17-1.29, p = 0.14). G allele was more prevalent in control (19.1%) than the case group (12.8%) (OR = 0.61, 95% CI: 0.27-1.36, p = 0.23). In E-cadherin, AC, AA, and AC + AA genotypes frequency were 17%, 12.8%, and 29.8% in case versus 8.5%, 8.5%, and 17% in the control group. Allele A was more common in the case than the control group (OR = 1.84, 95% CI: 0.84-4.03, p = 0.12). Also, AA and CC, the codominant genotypes were common in CDH2 and CDH1 respectively in all histopathological grades, and no statically significant association was observed between OSCC different histopathological grades and cadherin genotypes (p = 0.39 in N-cadherin, p = 0.74 in E-cadherin). Conclusion: Our results showed a lack of association between CDH1 and CDH2 gene polymorphisms with OSCC risk in a population of Southeastern of Iran.

Gene and cell therapy approaches for familial hypercholesterolemia: An update.

Familial hypercholesterolemia (FH) is a common autosomal codominant hereditary illness marked by the heightened risk of early atherosclerotic cardiovascular disease and high blood levels of low-density lipoprotein cholesterol (LDL-C). FH patients can have homozygous or heterozygous variants. This condition has been linked to variations in the genes for the LDL receptor (LDLR), apolipoprotein B, proprotein convertase subtilisin/Kexin 9 (PCSK9), and LDLR adaptor protein 1. Drugs such as statins, ezetimibe, and PCSK9 inhibitors are currently widely available, allowing for the theoretical normalization of plasma LDL-C levels mostly in patients with heterozygous FH. However, homozygous FH patients usually have a poor response to traditional lipid-lowering therapy and may have a poor prognosis at a young age. LDL apheresis and novel pharmacological therapies such as microsomal transfer protein inhibitors or anti-angiopoietin-like protein 3 monoclonal antibodies are extremely expensive and unavailable in most regions of the world. Therefore, the unmet need persists for these patients. In this review, we discuss the numerous gene delivery, gene editing, and stem cell manipulation techniques used in this study to correct FH-causing LDLR gene variations in vitro, ex vivo, and in vivo. Finally, we looked at a variety of studies that corrected genetic defects that caused FH using the ground-breaking clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology.

Vitamin D role in hepatitis B: focus on immune system and genetics mechanism.

According to the World Health Organization (WHO) report, viral hepatitis has been a problem in human society. Vitamins play a significant role in preventing the hepatocarcinoma and liver cirrhosis. In this report, we will first focus on the vitamin D function in the immune system reactions, and then investigate its role in the viral infections and the signaling pathway of hepatitis B virus. The existence of the cytochrome P450 (CYP) 27B1 enzyme, which is involved in vitamin D synthesis in immune system cells, has drawn researchers ' attention to the field of immune system. Toll like receptor (TLR) play a significant role in the immune system, and are one of the primary receptors of the innate immune system. In addition, the synthesis of inflammatory cytokines, such as Interferon γ (IFNγ) and Interleukin-2 (IL-2) is one of the key roles of T helper type 1 (Th1) cells; these cells can suppress two cited cytokines via vitamin D. In the chronic phase of hepatitis B, Cytotoxic T lymphocytes (CTLs) cells have weaker performance than the acute phase of the disease. The association between vitamin D physiologies with viral infections is also confirmed by genetic studies, carried out on genetic variations of vitamin D receptor (VDR) R-encoding disease susceptibility gene. Vitamin D affects different phases of the disease. Therefore, further experiments in this area are proposed.

Resveratrol and endothelial function: A literature review.

Endothelial dysfunction is a major contributing factor to diseases such as atherosclerosis, diabetes mellitus, obesity, hypertension, acute lung injury, preeclampsia, among others. Resveratrol (RSV) is a naturally occurring bioactive polyphenol found in grapes and red wine. According to experimental studies, RSV modulates several events involved in endothelial dysfunction such as impaired vasorelaxation, eNOS uncoupling, leukocyte adhesion, endothelial senescence, and endothelial mesenchymal transition. The endothelial protective effects of RSV are found to be mediated by numerous molecular targets (e.g. Silent Information Regulator 1 (SIRT1), 5' AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS), nuclear factor-erythroid-derived 2-related factor-2 (Nrf2), peroxisome proliferator-activated receptor (PPAR), Krüppel-like factor-2 (KLF2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)). Herein, we present an updated review addressing pharmacological effects and molecular targets of RSV in maintaining endothelial function, and the potential of this phytochemical for endothelial dysfunction-associated disorders.

Network-Based Analysis Reveals Association of FOXE1 Gene Polymorphisms in Thyroid Cancer Patients; A Case-Control Study in Southeast of Iran.

Thyroid cancer (TC) is the mainly frequent endocrine cancer by different incidence rate in worldwide. However, early prediction of  this cancer is still challenging due to the unclear pathogenicity. In this study with the aid of systems biology approach, performed a holistic study on GSE65144 dataset containing anaplastic thyroid carcinoma tissues. Co-expression network analysis by WGCNA suggested that highly preserved turquoise module with 1,480 genes was significantly correlated to TC. Most of the top 54 hub-genes of this module are functionality correlated to thyroid hormone generation (GO:0006590). Of these 54 hub-genes, FOXE1 has been reported previously to contain mutation asosiated to TC and chosen for experimental validation step. To this end, we conducted a case-control study including 81 TC patients and 165 controls individuals to evaluate the effects of FOXE1 functional polymorphisms (rs1867277) on the development of TC in Sistan and Balouchestan province of Iran. The polymorphisms of FOXE1 gene (rs1867277) assessed by tetra-ARMS PCR technique. Homozygous (GG) and (AA) variant of rs1867277 polymorphism were detected in 26 (32.1%) and 15 (18.5 %) of TC patients, and 66 (40.0%), and 15 (9.1%) in controls, respectively (p-value= 0.03, OR= 2.53). The A allele frequency was 70 (43.2%) in TC patients and 114 (34.5%) in controls (p-value= 0.06, OR= 1.44). Overall, our results suggested that FOXE1 gene could be used as a prognostic marker in TC and also provides information related to FOXE1 functional polymorphisms (rs1867277) in Sistan and Balouchestan province of Iran.
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Anticancer and apoptotic activities of parthenolide in combination with epirubicin in mda-mb-468 breast cancer cells.

Breast cancer is the most common malignancy in women worldwide. Unfortunately, current therapeutic methods are not completely efficient. Hence, combination therapy with medicinal plants has attracted several kinds of research. In the current study, we aimed to investigate the apoptotic and anti-cancer effect of Parthenolide in combination with Epirubicin in the MDA-MB-468 breast cancer cell line. In this study,  the anti-proliferative and pro-apoptotic effect of Parthenolide in combination with Epirubicin and without it, in the MDA-MB-468 cell line have been assessed by MTT test, Hoescht staining and flow cytometry methods. Our outcomes showed that Parthenolide treatment in the present of Epirubicin led to a decrease in the minimum toxic concentration of Parthenolide and Epirubicin in comparison with individual treatments. Then, to achieve a likely molecular mechanism of mentioned drugs Bax and Bcl2 expression level evaluated by Real-time PCR and subsequently, Western blotting has been estimated the protein level of Caspase 3. Our data indicated that the treatment of cells with Parthenolide led to up-regulation of Bax and downregulation of Bcl2 at mRNA level. Moreover, Parthenolide treatment led to the obvious alternation of Caspase3 protein level. These results indicated that Parthenolide in combination with Epirubicin have significant cytotoxicity due to targeting the main regulators of apoptosis. Hence, according to lack of cytotoxicity of Parthenolide on normal cells that lead to reduction of drug side effects, it could be suggested as an adjuvant therapy with Epirubicin after complementary research on animal model and clinical trial.

Role of EGFR gene polymorphisms in oral squamous cell carcinoma patients of Southeast Iran: A case-control study.

BACKGROUND: The decisive etiology of oral squamous cell carcinoma (OSCC) is still ambiguous, but we recognize the contribution of genetic aberration and environmental agents due to OSCC initiation. In the current study, we elucidate the potential impact of EGFR gene polymorphisms on the risk of OSCC in Southeast Iran. METHODS: Forty-eight OSCC patients along with 100 healthy volunteers were included. Three polymorphisms of the EGFR gene (rs2227983, rs2293347 and rs2227984) were genotype by Tetra-ARMS PCR. Data were analyzed with a chi-square test, and p<0.05 was considered significant. RESULTS: In rs2227983, the frequency of AG and GG genotypes were 62.5%, 37.5% in cases and 42%, 57% in the control group (P=0.02, OR=2.3) and also A allele frequency was 31.3% in the case and 22% in control (P=0.08, OR=0.62). AG + AA genotype frequency was 62.5% and 43% in case and control, respectively (p=0.03, OR=2.2). In rs2227984 and rs2293347, no statistical differences showed in the distribution of genotypes between the case and control group. Also the majority of the OSCC belonged to grade I (43.8%). CONCLUSION: The present investigation indicated that rs2227983 polymorphism might contribute to OSCC susceptibility in Iran's southeast population. Although, with the inconsistent interpretation mentioned due to the various geographical residencies and populations, more studies of significant populations are suggested to validate our findings.

Positive correlation between vitamin D receptor gene TaqI variant and gastric cancer predisposition in a sample of Iranian population.

Gastric cancer is the second cause of cancer-related mortality and the fourth most common cancers worldwide. Owing to the immune modulatory effect of vitamin D in the body, the role of vitamin D receptor gene in vitamin D regulation receives a great deal of research interest. The aim of the current study was to highlight the association between two variants of TaqI and FokI in the vitamin D receptor gene and gastric cancer predisposition in a sample of South Khorasan population. The present investigation consisted of 69 patients affected with gastric cancer and 100 healthy individuals. The genomic DNA was extracted by salting out the protocol from peripheral venous blood. Genotyping of TaqI and FokI variants were performed by PCR-RFLP method. Our findings manifested that TC genotype of TaqI polymorphism was statistically significant between the case and the control groups (p = 0.002). Moreover, the frequency of TC + CC genotypes was statistically significant between the two groups (p = 0.009). Furthermore, we could not find any meaningful association between FokI variant and the participant groups. The present results declared that, in our population, TC genotype of TaqI polymorphism has an association with gastric cancer susceptibility. In addition, more investigation with greater sample sizes is needed to confirm our results.

Role of the NLRP3 inflammasome in cancer.

Inflammasomes are large intracellular multi-protein signalling complexes that are formed in the cytosolic compartment as an inflammatory immune response to endogenous danger signals. The formation of the inflammasome enables activation of an inflammatory protease caspase-1, pyroptosis initiation with the subsequent cleaving of the pro-inflammatory cytokines interleukin (IL)-1ß and proIL-18 to produce active forms. The inflammasome complex consists of a Nod-like receptor (NLR), the adapter apoptosis-associated speck-like (ASC) protein, and Caspase-1. Dysregulation of NLRP3 inflammasome activation is involved tumor pathogenesis, although its role in cancer development and progression remains controversial due to the inconsistent findings described. In this review, we summarize the current knowledge on the contribution of the NLRP3 inflammasome on potential cancer promotion and therapy.

Therapeutic potential of curcumin in diabetic complications.

Diabetes mellitus is an extremely prevalent endocrine disease and a major global public health concern. Diabetic complications, such as retinopathy, nephropathy, neuropathy and cardiovascular disease, are common and majorly impact a patient's quality of life. Curcumin, the major active component of turmeric, possesses extensive known pharmacological properties, including anti-inflammatory, antioxidant, and antitumor effects. Increasing evidence suggests that curcumin may offer protection against diabetic complications. The current review focuses on the possible molecular targets and pathways involved in diabetic complications and, in particular, the multi-target approach of curcumin in attenuating diabetic nephropathy, retinopathy, and neuropathy.

Positive correlation between vitamin D receptor gene FokI polymorphism and colorectal cancer susceptibility in South-Khorasan of Iran.

Colorectal cancer (CRC) is a global public health problem. Despite the major milestone in early diagnosis and treatment of colorectal cancer, the prevalence of CRC rates is still rising. The etiology of CRC is still unknown but we know CRC is influenced by both of environment and genetic factors. In this study, we aimed to elucidate the role of vitamin D receptor gene polymorphic regions; FokI and TaqI single nucleotide polymorphisms, in increasing the risk of colorectal cancer in Birjand population. One hundred patients with CRC and 100 healthy controls recruited to the study. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) method technique for all individuals. There were statistically significant differences between ff genotype and f allele of FokI SNP in case and control groups. Our results manifested positive correlation between ff genotype and f allele of FokI SNP with colorectal cancer predisposition (P = 0.035, P = 0.0001 respectively) in South Khorasan population. The present study showed that FokI polymorphism but not TaqI polymorphism may contribute to CRC susceptibility. In addition, ff genotype of FokI polymorphism was associated with CRC risk.

Evaluation of the protective effect of N-acetylcysteine on contrast media nephropathy.

INTRODUCTION: Intravenous contrast agents can cause acute decline in kidney function, especially in patients with risk factors. OBJECTIVES: In this study, we aimed to examine the ameliorative effect N-acetylcysteine (NAC) to reduce the incidence of contrast nephropathy. PATIENTS AND METHODS: This study was a prospective, randomized, double-blind clinical trial on 150 patients who underwent coronary angiography. The study was carried out on patients undergoing coronary angiography. Patients were randomly assigned into 2 groups of intervention group and control subjects. Intervention group took NAC 600 mg orally twice a day. It was administered one day before angiography and continued until the second day after angiography. Control subjects received saline only. Serum creatinine was measured before and three days after coronary angiography. RESULTS: There was no significant difference between intervention and control groups at baseline (P > 0.05). However, there was a significant decline in creatinine level among NAC patients (P = 0.001). Saline group had significantly higher proportion of nephropathy cases than NAC patients Conclusion: We found that the consumption of NAC is useful for contrast induced nephropathy (CIN) prevention.