The Roles of Autophagy-related miRNAs in Gynecologic Tumors: A Review of Current Knowledge for Possible Targeted Therapy.

Gynecological cancers are the leading cause of malignancy-related death and disability in the world. These cancers are diagnosed at end stages, and unfortunately, the standard therapeutic strategies available for the treatment of affected women [including chemotherapy, radiotherapy and surgery] are not safe and effective enough. Moreover, the unwanted side-effects lowering the patients' life quality is another problem for these therapies. Therefore, researchers should search for better alternative/complementary treatments. The involvement of autophagy in the pathogenesis of various cancers has been demonstrated. Recently, a novel crosstalk between microRNAs, small non-coding RNAs with important regulatory functions, and autophagy machinery has been highlighted. In this review, we indicate the importance of this interaction for targeted therapy in the treatment of cancers including gynecological cancers, with a focus on underlying mechanisms.

Association between TMPRSS2 rs2070788 polymorphism and COVID-19 severity: a case-control study in multiple cities of Iran.

Introduction: Host genetic variations have been identified as potential influencers of COVID-19 infection. This study aimed to examine the association between transmembrane serine protease type 2 (TMPRSS2) rs2070788 single nucleotide polymorphism (SNP) and the prognosis of COVID-19 in Iranian populations. Method: This case-control study was performed on 756 COVID-19 patients and 59 healthy individuals across Iran. Clinical data, blood samples, and the presence of the TMPRSS2 rs2070788: G>A SNP were determined using T-ARMS-PCR. Additionally, serum levels of tumor necrosis factor α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), and IL-1ß were evaluated in the collected blood samples. Results: No significant association was found between the genotypes and allele frequencies of TMPRSS2 rs2070788 SNP and susceptibility to or mortality from COVID-19 infection. However, we observed a substantial increase in IL-6 and CRP levels associated with the severity of COVID-19, while no such trend was observed for IL-1ß and TNF-α. This study showed a considerable rise in TNF-α and IL-1ß serum levels exclusively in COVID-19 patients with TT rs2070788 TMPRSS2 SNP genotype compared to healthy controls. Conclusion: In this study conducted across multiple cities in Iran, no significant association was found between the TMPRSS2 rs2070788 SNP genotypes and COVID-19 severity or mortality.

Potential applications of macrophages in cancer immunotherapy.

Immunotherapy has improved cancer treatment based on investigations of tumor immune escape. Manipulation of the immune system stimulates antitumor immune responses and blocks tumor immune escape routes. Genetically adoptive cell therapy, such as T cells, has yielded promising results for hematologic malignancies, but their application to solid tumors has been challenging. Macrophages have a wide broad of capabilities in regulating immune responses, homeostasis, and tissue development, as well as the ability to phagocyte, present antigens, and infiltrate the tumor microenvironment (TME). Given the importance of macrophages in cancer development, they could serve as novel tool for tumor treatment. Therefore, macrophages are used in different formats for direct and indirect targeting of tumor cells. This review summarized the available data on the various applications of macrophages in cancer immunotherapy.

SARS-CoV-2 Omicron (BA.4, BA.5) variant: Lessons learned from a new variant during the COVID-19 pandemic.

Background and Aim: In late 2021, the world faced the rapid spread of the SARS-CoV-2 Omicron variant, which quickly became the variant of concern. In April 2022, two new lineages of Omicron (BA.4/BA.5) emerged from Africa, where they caused the fifth wave of infection. Method: We searched PubMed, Google Scholar, and Scopus online databases up to December 2023 for founding relevant studies. Results: BA.4 and BA.5 subgroups, with changes in the spike protein, have a greater ability to escape from the immune system, which was possible with the help of L452R and F486V mutations. Epidemiologically, these evolving subtypes show similarities to seasonal influenza but with higher mortality rates. The symptoms of these subgroups are different from the previous types in the form of upper respiratory symptoms. Antiviral treatments, the use of antibodies such as bebtelovimab, and the development of vaccines are promising. Conclusion: Consequently, we must continue to be vigilant in our joint surveillance efforts against COVID-19 in diagnosis and treatment.

Immunoregulatory effects of nanocurcumin in inflammatory milieu: Focus on COVID-19.

The use of natural compounds, such as curcumin, to treat infections caused by bacteria, viruses, fungi, parasites, inflammatory diseases, and various types of cancer is an active and dynamic area of research. Curcumin has a long history of use in the food industry, and there is currently a growing interest in its therapeutic applications. Numerous clinical trials have consistently shown that curcumin, a polyphenolic compound, is safe and well-tolerated even at high doses. There is no toxicity limit. However, the clinical efficacy of curcumin has been limited by its constraints. However, scientific evidence indicates that the use of adjuvants and carriers, such as nanoparticles, exosomes, micelles, and liposomes, can help overcome this limitation. The properties, functions, and human benefits of using nanocurcumin are well-supported by scientific research. Recent evidence suggests that nanocurcumin may be a beneficial therapeutic modality due to its potential to decrease gene expression and secretion of specific inflammatory biomarkers involved in the cytokinestorm seen in severe COVID-19, as well as increase lymphocyte counts. Nanocurcumin has demonstrated the ability to improve clinical manifestations and modulate immune response and inflammation in various autoinflammatory diseases. Additionally, its efficacy, affordability, and safety make it a promising replacement for residual cancer cells after tumor removal. However, further studies are necessary to evaluate the safety and efficacy of nanocurcumin as a new therapeutic in clinical trials, including appropriate dosage, frequency, and duration.

The role of synbiotics as adjunctive agents in the treatment of allergic rhinitis: A randomized controlled trial.

Introduction: Allergic rhinitis (AR) is a prevalent chronic disease affecting a significant portion of the global population. The substantial economic burden associated with treating AR necessitates the exploration of alternative therapies. Probiotics have gained attention due to their availability, minimal adverse effects, and cost-effectiveness. The present study aims to investigate the role of synbiotics as adjunctive agents in the treatment of AR when added to standard treatment. Method: Thirty patients with persistent allergic rhinitis (PAR) were randomly assigned to receive routine diet therapy plus synbiotics or routine diet therapy plus placebo per day for 4 months. The data analysis was conducted using SPSS Version 20. Result: This study revealed a notable difference in immunoglobulin (Ig)E levels between the placebo and synbiotics groups (p = 0.035) following the intervention. Although a statistically significant difference (p = 0.039) was observed in the changes before and after the intervention (synbiotics and placebo) in the SNOT22 questionnaire, this finding was not observed for the MiniRQLQ questionnaire. For the MiniRQLQ questionnaire, the within-group analysis showed significant changes in activity variables (p = 0.023), ocular symptoms (p = 0.036), and practical problems (p = 0.043) exclusively in the synbiotics group. Additionally, changes in nasal symptoms were observed in both synbiotics (p = 0.006) and placebo (p = 0.007) groups. Conclusion: This study suggests that synbiotics supplementation for 4 months can impact IgE levels compared with placebo in individuals with PAR, while also exhibiting positive effects on symptomology.

Probiotics as a complementary treatment in systemic lupus erythematosus: A systematic review.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that primarily affects young women. SLE has no recognized etiology but it is believed to be triggered by a number of factors, including genetic predisposition, hormonal influences, and environmental conditions. Dysbiosis in the gut microbiota has emerged as a potential mechanism connecting the intestinal microbiome to the breakdown of self-tolerance and chronic inflammation. This review aims to investigate the role of probiotics in modulating the gut microbiome and their potential therapeutic benefits in managing SLE, providing insights for future research and clinical practice. Methods: We conducted a thorough search for papers published up to June 2023 in databases such as PubMed/MEDLINE, Web of Science, Scopus, and Cochrane Library. Results: The systematic review identified 22 articles examining the effects of probiotics on SLE. These studies-which include in vivo tests, in vitro research, and clinical trials-indicate that probiotics may be effective against inflammation, and improve immunological responses and metabolic profiles in SLE patients. Most in vivo studies were assessed as medium to high quality, while the randomized controlled trial was deemed of high quality. Conclusion: According to the findings of our systematic review, probiotics may be used in conjunction with other treatments to manage SLE. Nonetheless, current data is limited, and more randomized controlled trials would be required to fully examine their effectiveness.

Natural STAT3 inhibitors for cancer treatment: A Comprehensive Literature Review.

Cancer is one of the leading causes of mortality and morbidity worldwide, affecting millions of people physically and financially every year. Over time, many anticancer treatments have been proposed and studied, including synthetic compound consumption, surgical procedures, or grueling chemotherapy. Although these treatments have improved the daily life quality of patients and increased their survival rate and life expectancy, they have also shown significant drawbacks, including staggering costs, multiple side effects, and difficulty in compliance and adherence to treatment. Therefore, natural compounds have been considered a possible key to overcoming these problems in recent years, and thorough research has been done to assess their effectiveness. In these studies, scientists have discovered a meaningful interaction between several natural materials and signal transducer and activator of transcription 3 molecules. STAT3 is a transcriptional protein that is vital for cell growth and survival. Mechanistic studies have established that activated STAT3 can increase cancer cell proliferation and invasion while reducing anticancer immunity. Thus, inhibiting STAT3 signaling by natural compounds has become one of the favorite research topics and an attractive target for developing novel cancer treatments. In the present article, we intend to comprehensively review the latest knowledge about the effects of various organic compounds on inhibiting the STAT3 signaling pathway to cure different cancer diseases.

Dysregulated balance in Th17/Treg axis of Pristane-induced lupus mouse model, are mesenchymal stem cells therapeutic?

BACKGROUND: Despite advances in general and targeted immunosuppressive therapies, limiting all mainstay treatment options in refractory systemic lupus erythematosus (SLE) cases has necessitated the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have recently emerged with unique properties, including a solid propensity to reduce inflammation, exert immunomodulatory effects, and repair injured tissues. METHODS: An animal model of acquired SLE mice was induced via intraperitoneal immunization with Pristane and affirmed by measuring specific biomarkers. Bone marrow (BM) MSCs were isolated from healthy BALB/c mice and cultured in vitro, then were identified and confirmed by flow cytometry and cytodifferentiation. Systemic MSCs transplantation was performed and then several parameters were analyzed and compared, including specific cytokines (IL-17, IL-4, IFN-É£, TGF-ß) at the serum level, the percentage of Th cell subsets (Treg/Th17, Th1/Th2) in splenocytes, and also the relief of lupus nephritis, respectively by enzyme-linked immunosorbent assay (ELISA), flow cytometry analysis and by hematoxylin & eosin staining and also immunofluorescence assessment. Experiments were carried out with different initiation treatment time points (early and late stages of disease). Analysis of variance (ANOVA) followed by post hoc Tukey's test was used for multiple comparisons. RESULTS: The rate of proteinuria, anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies, and serum creatinine levels decreased with BM-MSCs transplantation. These results were associated with attenuated lupus renal pathology in terms of reducing IgG and C3 deposition and lymphocyte infiltration. Our findings suggested that TGF-ß (associated with lupus microenvironment) can contribute to MSC-based immunotherapy by modulating the population of TCD4+ cell subsets. Obtained results indicated that MSCs-based cytotherapy could negatively affect the progression of induced SLE by recovering the function of Treg cells, suppressing Th1, Th2, and Th17 lymphocyte function, and downregulating their pro-inflammatory cytokines. CONCLUSION: MSC-based immunotherapy showed a delayed effect on the progression of acquired SLE in a lupus microenvironment-dependent manner. Allogenic MSCs transplantation revealed the ability to re-establish the balance of Th17/Treg, Th1/Th2 and restore the plasma cytokines network in a pattern dependent on disease conditions. The conflicting results of early versus advanced therapy suggest that MSCs may produce different effects depending on when they are administered and their activation status.

Venous thromboembolism in viral diseases: A comprehensive literature review.

Venous thromboembolism (VTE) is known to be a common respiratory and/or cardiovascular complication in hospitalized patients with viral infections. Numerous studies have proven human immunodeficiency virus infection to be a prothrombotic condition. An elevated VTE risk has been observed in critically ill H1N1 influenza patients. VTE risk is remarkably higher in patients infected with the Hepatitis C virus in contrast to uninfected subjects. The elevation of D-dimer levels supported the association between Chikungunya and the Zika virus and the rise of clinical VTE risk. Varicella-zoster virus is a risk factor for both cellulitis and the consequent invasive bacterial disease which may take part in thrombotic initiation. Eventually, hospitalized patients infected with the coronavirus disease of 2019 (COVID-19), the cause of the ongoing worldwide pandemic, could mainly suffer from an anomalous risk of coagulation activation with enhanced venous thrombosis events and poor quality clinical course. Although the risk of VTE in nonhospitalized COVID-19 patients is not known yet, there are a large number of guidelines and studies on thromboprophylaxis administration for COVID-19 cases. This study aims to take a detailed look at the effect of viral diseases on VTE, the epidemiology of VTE in viral diseases, and the diagnosis and treatment of VTE.