Cancer immunotherapy focusing on the role of interleukins: A comprehensive and updated study.

Cytokines bind to specific receptors on target cells to activate intracellular signaling pathways that control diverse cellular functions, such as proliferation, differentiation, migration, and death. They are essential for the growth, activation, and operation of immune cells and the control of immunological reactions to pathogens, cancer cells, and other dangers. Based on their structural and functional properties, cytokines can be roughly categorized into different families, such as the tumor necrosis factor (TNF) family, interleukins, interferons, and chemokines. Leukocytes produce interleukins, a class of cytokines that have essential functions in coordinating and communicating with immune cells. Cancer, inflammation, and autoimmunity are immune-related disorders brought on by dysregulation of cytokine production or signaling. Understanding cytokines' biology to create novel diagnostic, prognostic, and therapeutic methods for various immune-related illnesses is crucial. Different immune cells, including T cells, B cells, macrophages, and dendritic cells, and other cells in the body, including epithelial cells and fibroblasts, generate and secrete interleukins. The present study's main aim is to fully understand interleukins' roles in cancer development and identify new therapeutic targets and strategies for cancer treatment.

New immunotherapeutic approaches for cancer treatment.

Neoplasms are a worldwide recognized non-contagious disease which has the most mortality rate after cardiovascular diseases. For decades, there has been a vast amount of study on treatment methods of cancer which has led to conventional therapies such as chemotherapy, radiation therapy, surgery and so on. Clinicians and researchers believed that there is an urgent need, considering the high rate of incidence and prevalence, for an alternative treatment option which is more efficacious and has less adverse effects than the above-mentioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and became one of the fastest developing therapeutic approaches. Different kinds of immunotherapies are FDA approved and available for treatment of various cancer types. In this review, we have summarized the major immunotherapy methods including checkpoint inhibitors, CAR T cell therapies and cancer vaccines. Furthermore, application of combination therapy, precision medicine, biomarker discovery, overcoming resistance and reduction of adverse effects are discussed in this study.

Dysregulation of P53 in breast cancer: Causative factors and treatment strategies.

One of the most prevalent cancers impacting women worldwide is breast cancer. Although there are several risk factors for breast cancer, the p53 gene's function has recently received much attention. The "gatekeeper" gene, or p53, is sometimes referred to as such since it is crucial in controlling cell proliferation and preventing the development of malignant cells. By identifying DNA damage and initiating cellular repair processes, p53 usually functions as a tumor-suppressor. But p53 gene alterations can result in a lack of function, allowing cells to divide out of control and perhaps triggering the onset of cancer. Various factors, such as mutation genes, signaling pathways, and hormones, can dysregulate P53 proteins and cause breast cancer. A promising strategy for individualized cancer treatment involves focusing on p53 mutations in breast cancer. While numerous techniques, including gene therapy and small compounds, have shown promise, further study is required to create safe and efficient treatments to target p53 mutations in breast cancer successfully.

The Therapeutic Applications of Exosomes in Different Types of Diseases: A Review.

Exosomes are nano-sized vesicles secreted by nearly all cells and have received massive attention recently. In addition to their roles in pathophysiological processes and diagnostic evaluations, recently, several studies have applied exosomes to design novel therapeutic applications. Exosomes can be derived from a variety of cells and tissues and based on the source, they can carry different native contents such as DNAs, non-coding small RNAs, mRNAs, and proteins. They can also be engineered by adding desirable agents including specific biomolecules or drugs. Both forms can be therapeutically used for delivering their cargoes to the target cells and desirably alter their functions. The present study aimed to provide a comprehensive review of the various studies which applied exosomes as a therapeutic tool in the treatment of different types of diseases including cancer, cardiovascular, neurologic, psychiatric, liver, and kidney diseases.

GAA gene mutation detection following clinical evaluation and enzyme activity analysis in Azeri Turkish patients with Pompe disease.

Pompe disease (PD) is a rare autosomal recessive multi-systemic lysosomal storage disorder, caused by mutations in the acid alpha-glucosidase (GAA) gene located on 17q25.2-q25.3. It is one of about 50 rare genetic diseases categorized as lysosomal storage disorders. This disease is characterized by a range of different symptoms related to acid alpha-glucosidase deficiency. Mutation recognition in the GAA gene can be very significant for purposes such as therapeutic interference, early diagnosis and genotype-phenotype relationship. In the current study, peripheral blood samples were gathered from patients with PD and healthy members of three families. Enzymatic activity of GAA was checked. Then, mutation detection was performed by polymerase chain reaction followed by direct sequencing of all exons in samples with decreased enzyme activity. The identified mutations were investigated using bioinformatics tools to predict possible effects on the protein product and also to compare the mutated sequence with near species. Three novel mutations (c.1966-1968delGAG, c.2011-2012delAT and c.1475-1481dupACCCCAC) were identified in the GAA gene. Assessment of the effects of these mutations on protein structure and function showed the possibility of harmful effects and their significant alterations in the protein structure. The three novel GAA gene mutations detected in this study expand the information about the molecular genetics of PD and can be used to helpdiagnosis and genetic counseling of affected families.

Diagnostic biomarker and therapeutic target applications of miR-326 in cancers: A systematic review.

MicroRNAs (miRNAs) are endogenous mediators of RNA interference and have key roles in the modulation of gene expression under healthy, inflamed, stimulated, carcinogenic, or other cells, and tissues of a pathological state. Many studies have proved the association between miRNAs and cancer. The role of miR-326 as a tumor suppressor miRNA in much human cancer confirmed. We will explain the history and the role of miRNAs changes, especially miR-326 in cancers and other pathological conditions. Attuned with these facts, this review highlights recent preclinical and clinical research performed on miRNAs as novel promising diagnostic biomarkers of patients at early stages, prediction of prognosis, and monitoring of the patients in response to treatment. All related publications retrieved from the PubMed database, with keywords such as epigenetic, miRNA, microRNA, miR-326, cancer, diagnostic biomarker, and therapeutic target similar terms from 1899 to 2018 with limitations in the English language. Recently, researchers have focused on the impacts of miRNAs and their association in inflammatory, autoinflammatory, and cancerous conditions. Recent studies have suggested a major pathogenic role in cancers and autoinflammatory diseases. Investigations have explained the role of miRNAs in cancers, autoimmunity, and autoinflammatory diseases, and so on. The miRNA-326 expression has an important role in cancer conditions and other diseases.

In vivo Evaluation of Anti-Hyperglycemic, Anti-hyperlipidemic and Anti-Oxidant Status of Liver and Kidney of Thymol in STZ-Induced Diabetic Rats.

AIM: The evaluation of the positive and protective effects thymol as a natural compound on the STZ -induced diabetic rats. MATERIALS AND METHODS: In this study, seven groups of the streptozotocin induced diabetic and normal rats (overall 42 males) were tested through various biochemical and histopathological factors such as: serum glucose, insulin, creatinine, lipids, lipoproteins, liver function-related enzymes, and antioxidant status in liver and kidney. RESULTS: The obtained results in this work indicated that thymol had a significant anti-hypoglycemic, anti-hypolipidemic activities on the STZ-induced diabetic rats. Further, the assessment different biochemical parameters revealed that the levels of creatinine, low-density lipoprotein cholesterol, very low density lipoprotein cholesterol, and liver function-related enzymes such as aspartate aminotransferase and alanine aminotransferase were decreased in the treated diabetes rats under 20 and 40 mg/kg thymol compared to the control diabetes group. Considerably, the anti-oxidant enzymes status that were achieved from the liver and kidney organs were modulated after treatment with thymol in the diabetic rats. CONCLUSION: The results of this research has brough a new aspect concerning the proteevtive and positive effects of thymol on the diabetic complications in the animal model.

Effects of a triplex mixture of Peganum harmala, Rhus coriaria, and Urtica dioica aqueous extracts on metabolic and histological parameters in diabetic rats.

CONTEXT: Several therapeutic effects such as antioxidant and blood glucose-lowering activities have been reported for Peganum harmala L (Zygophyllaceae) (PH) seeds, Rhus coriaria L (Anacardiaceae) (RC) fruits, and Urtica dioica L (Urticaceae) (UD) leaves. OBJECTIVE: This study investigates the effects of a triplex mixture (1:1:1) of these medicinal plants on metabolic and histological parameters in diabetic rats. MATERIALS AND METHODS: Aqueous extracts of PH, RC and UD were administered as either monotherapy or in combination at a final dose of 200 mg/kg to alloxan-induced diabetic rats by daily gavage. Biochemical parameters including blood glucose, liver function-related enzymes, lipid profile, and creatinine were estimated by spectrophotometric methods. Tissues from the liver and kidney stained with hematoxylin/eosin were histologically examined. The results obtained from the exposure groups were compared to either healthy or diabetic control groups. RESULTS: Compared with the diabetic control rats, all aqueous extracts (ED50 = 11.5 ± 2.57 mg/ml) led to significant decreases in the levels of ALP (1.39-2.23-fold, p < 0.05), low-density lipoprotein cholesterol (LDL-C) (1.79-3.26-fold, p < 0.05), and blood glucose (1.27-4.16-fold, p < 0.05). The serum concentrations of TG was decreased only by treatment with UD and triplex mixture (1.25- and 1.20-fold, respectively, p < 0.05). Among the studied parameters, alanine aminotransferase (ALT), LDL-C, TG, and creatinine recovered to healthy control levels after 4 weeks of treatment with the extract mixture. CONCLUSION: This study showed that PH, RC, and UD extracts, especially their combination, had significant antidiabetic, hypolipidemic, and liver and renal damage recovering effects.

Association of Pap smear abnormalities with autoimmune disorders.

Recently, it is hypothesized that there might be an association between immunological disorders and cervical premalignant and malignant abnormalities. Related studies have been generally focused on some particular autoimmune disease, specially the Systemic Lupus Erythematosus (SLE). This study aimed at comparing the rate of Pap smear abnormalities in female patients with autoimmune diseases and normal counterparts. In a case-control setting, 118 female patients with various autoimmune diseases (the case group) and 118 healthy female counterparts (the control group) were recruited in Tabriz Imam Reza Teaching Centre in a 24 months period of time. The two groups were matched for demographics and known risk factors of cervical malignancy. Frequencies of abnormal Pap smear testing were compared between the two groups. The autoimmune disorders were SLE (74 patients), rheumatoid arthritis or RA (32 patients), systcmic sclerosis or SS (7 patients) and ankylosing spondylitis or AS (5 patients) in the case group. Frequency of abnormal Pap smear testing was significantly higher in the case group comparing with that in the controls (7.6% vs. 1.7%; p = 0.03). Frequency of abnormal Pap smear testing was higher in the patients with SLE (8.1%) and RA (9.3%) comparing with that in the controls; However, these differences were marginally nonsignificant (p = 0.06 and p = 0.07, respectively). Frequency of cases with abnormal Pap smear testing was not statistically different between the autoimmune disorders (p = 0.99). Based on these findings and in conclusion, there might be an association between the autoimmune disorders and occurrence of premalignant or malignant lesions in cervix. Further studies with larger samples sizes are recommended.