Discovering the strength of immunometabolism in cancer therapy: Employing metabolic pathways to enhance immune responses.

Immunometabolism, which studies cellular metabolism and immune cell function, is a possible cancer treatment. Metabolic pathways regulate immune cell activation, differentiation, and effector functions, crucial to tumor identification and elimination. Immune evasion and tumor growth can result from tumor microenvironment metabolic dysregulation. These metabolic pathways can boost antitumor immunity. This overview discusses immune cell metabolism, including glycolysis, oxidative phosphorylation, amino acid, and lipid metabolism. Amino acid and lipid metabolic manipulations may improve immune cell activity and antitumor immunity. Combination therapy using immunometabolism-based strategies may enhance therapeutic efficacy. The complexity of the metabolic network, biomarker development, challenges, and future approaches are all covered, along with a summary of case studies demonstrating the effectiveness of immunometabolism-based therapy. Metabolomics, stable isotope tracing, single-cell analysis, and computational modeling are also reviewed for immunometabolism research. Personalized and combination treatments are considered. This review adds to immunometabolism expertise and sheds light on metabolic treatments' ability to boost cancer treatment immunological response. Also, in this review, we discussed the immune response in cancer treatment and altering metabolic pathways to increase the immune response against malignancies.

Exosomes derived from adipose stem cells in combination with hyaluronic acid promote diabetic wound healing.

Diabetic wound is one of the main challenges in dermatology. Although stem cell-based treatment has therapeutic benefits in wound repair, the clinical application is still limited. Herein we investigated whether adipose stem cells -derived exosomes (Exo) loaded on hyaluronic acid (HA) could promote healing in diabetic rats. Sixty diabetic rats were randomly planned into the control group, Exo group, HA group, and HA+Exo group. On days 7, 14, and 21, five rats from each group were sampled for stereological, molecular, and tensiometrical assessments. Our results indicated that the wound closure rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts, the length density blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were significantly higher in the treated groups than in the control group, and these changes were more obvious in the HA+Exo ones. Furthermore, the expression of TGF-ß and VEGF genes were meaningfully upregulated in all treated groups compared to the control group and were greater in the HA+Exo group. This is while expression of TNF-α and IL-1ß, as well as numerical densities of neutrophils decreased more considerably in the HA+Exo group in comparison to the other groups. Generally, it was found that using both HA injection and exosomes has more effect on diabetic wound healing.

The potential role of interleukins and interferons in ovarian cancer.

Ovarian cancer poses significant challenges and remains a highly lethal disease with limited treatment options. In the context of ovarian cancer, interleukins (ILs) and interferons (IFNs), important cytokines that play crucial roles in regulating the immune system, have emerged as significant factors influencing its development. This article provides a comprehensive review of the involvement of various ILs, including those from the IL-1 family, IL-2 family, IL-6 family, IL-8 family, IL-10 family, and IL-17 family, in ovarian cancer. The focus is on their impact on tumor growth, metastasis, and their role in evading immune responses within the tumor microenvironment. Additionally, the article conducts an in-depth examination of the oncogenic or antitumor roles of each IL in the context of ovarian cancer pathogenesis and progression. Besides, we elucidated the enhancements in the treatment of ovarian cancer through the utilization of type-I IFN and type-II IFN. Recent research has shed light on the intricate mechanisms through which specific ILs and IFNs contribute to the advancement of the disease. By incorporating recent findings, this review also seeks to inspire further investigations into unexplored mechanisms, fostering ongoing research to develop more effective therapeutic strategies for ovarian cancer. Moreover, through an in-depth analysis of IL- and IFN-associated clinical trials, we have highlighted their promising potential of in the treatment of ovarian cancer. These clinical trials serve to reinforce the significant outlook for utilizing ILs and IFNs as therapeutic agents in combating this disease.

A comprehensive insight into the role of small nucleolar RNAs (snoRNAs) and SNHGs in human cancers.

Long non-coding RNAs (lncRNAs), which comprise most non-coding RNAs (ncRNAs), have recently become a focus of cancer research. How many functional ncRNAs exist is still a matter of debate. Although insufficient evidence supports that most lncRNAs function as transcriptional by-products, it is widely known that an increasing number of lncRNAs play essential roles in cells. Small nucleolar RNAs (snoRNAs), 60-300 nucleotides in length, have been better studied than long non-coding RNAs (lncRNAs) and are predominantly present in the nucleolus. Most snoRNAs are encoded in introns of protein- and non-protein-coding genes called small nucleolar RNA host genes (SNHGs). In this article, we explore the biology and characteristics of SNHGs and their role in developing human malignancies. In addition, we provide an update on the ability of these snoRNAs to serve as prognostic and diagnostic variables in various forms of cancer.

The cross-talk between LncRNAs and JAK-STAT signaling pathway in cancer.

Long non-coding RNAs (lncRNAs) are non-coding RNAs that were transcribed from the human genome and have become important regulators in a number of cellular activities, mostly via controlling gene expression. A growing body of evidence shows that lncRNAs regulate various factors to impact various biological activities that are related to tumorigenesis, including the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. lncRNAs influence the JAK-STAT signaling pathway either by directly targeting or via indirectly modulating other upstream or downstream pathways' components like members of the suppressor of cytokine signaling (SOCS) family, and other genes that regulate cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition. Furthermore, lncRNAs can act as downstream effectors of the JAK-STAT pathway and mediates tumorigenesis. The relationship between JAK-STAT signaling and lncRNAs differs among various types of cancers. Besides, lncRNAs, as biological molecules, have been shown to play a dual role in either tumorigenesis or tumor suppression in various cancers. In this review, we focus on the reciprocated regulation and functions of lncRNAs and the JAK-STAT signaling pathway in cancer, as well as narrate the latest research progress on this association. A deeper understanding of this correlation may simplify the recognition of potential targets for clinical therapeutics.

miR-495-3p as a promising tumor suppressor in human cancers.

Noncoding RNAs are a type of cellular RNA not having the ability to translate into proteins. As an important type of ncRNA with a length of about 22 nucleotides (nt), microRNAs were revealed to contribute to regulating the various cellular functions via regulating the protein translation of target genes. Among them, available studies proposed that miR-495-3p is a pivotal player in cancer pathogenesis. These studies showed that the expression level of miR-495-3p decreased in various cancer cells, suggesting its tumor suppressor role in cancer pathogenesis. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are the important regulators of miR-495-3p via sponging it, leading to increased expression levels of its target genes. Moreover, miR-495-3p was shown to have a promising potential to be a prognostic and diagnostic biomarker in cancer. MiR-495-3p also could affect the resistance of cancer cells to chemotherapy agents. Here, we discussed the molecular mechanisms of miR-495-3p in various cancer including breast cancer. In addition, we discussed the miR-495-3p potential as a prognostic and diagnostic biomarker as well as its activity in cancer chemotherapy. Finally, we discussed the current limitations regarding the use of microRNAs in clinics and the future prospects of microRNAs.

Concanavalin A as a promising lectin-based anti-cancer agent: the molecular mechanisms and therapeutic potential.

Concanavalin A (ConA), the most studied plant lectin, has been known as a potent anti-neoplastic agent for a long time. Since initial reports on its capacity to kill cancer cells, much attention has been devoted to unveiling the lectin's exact molecular mechanism. It has been revealed that ConA can bind to several receptors on cancerous and normal cells and modulate the related signaling cascades. The most studied host receptor for ConA is MT1-MMP, responsible for most of the lectin's modulations, ranging from activating immune cells to killing tumor cells. In this study, in addition to studying the effect of ConA on signaling and immune cell function, we will focus on the most up-to-date advancements that unraveled the molecular mechanisms by which ConA can induce autophagy and apoptosis in various cancer cell types, where it has been found that P73 and JAK/STAT3 are the leading players. Moreover, we further discuss the main signaling molecules causing liver injury as the most significant side effect of the lectin injection. Altogether, these findings may shed light on the complex signaling pathways controlling the diverse responses created via ConA treatment, thereby modulating these complex networks to create more potent lectin-based cancer therapy. Video Abstract.

Intimate partner violence against pregnant women during the COVID-19 pandemic: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to estimate the pooled prevalence of (intimate partner violence) IPV against pregnant women in the COVID-19 pandemic. A literature search was conducted in PubMed, Web of Science, and Scopus for observational studies regarding the prevalence of IPV against pregnant women during the COVID-19 pandemic. The search was performed with the following keywords: intimate partner violence, domestic violence, battered women, wife assault, partner assault, wife abuse, partner abuse, femicide, domestic homicide, pregnancy, gestation, pregnant women, COVID-19, SARS-CoV-2, 2019-nCoV, Coronavirus Disease-19, 2019 Novel Coronavirus, Wuhan Coronavirus, SARS Coronavirus 2, Wuhan Seafood Market Pneumonia Virus. Heterogeneity between the studies was assessed using Cochran's Q test and I2 index. In addition, a random-effects model was used to estimate the prevalence of IPV. Data analysis was performed in Stata software version 16. Six articles met our inclusion criteria, which were conducted on 2213 pregnant women. The pooled prevalence of total IPV was estimated at 22 percent (95 percent Confidence Interval [CI]: 4-40 percent). Moreover, the pooled prevalence of psychological, physical, and sexual violence was reported to be 24 percent (95 percent CI: 13-35 percent), 14 percent (95 percent CI: 7-20 percent), and 6 percent (95 percent CI: 4-9 percent), respectively. Publication bias was significant (P = .01). According to the results, IPV against pregnant women has been relatively prevalent during the COVID-19 pandemic. Therefore, identifying the women who are at the risk of IPV is essential to preventing the consequences of maternal-fetal abuse and designing strategies to facilitate the reporting of violence during pandemics.

Mechanisms of cancer stem cells drug resistance and the pivotal role of HMGA2.

Nowadays, the focus of researchers is on perceiving the heterogeneity observed in a tumor. The researchers studied the role of a specific subset of cancer cells with high resistance to traditional treatments, recurrence, and unregulated metastasis. This small population of tumor cells that have stem-cell-like specifications was named Cancer Stem Cells (CSCs). The unique features that distinguish this type of cancer cell are self-renewing, generating clones of the tumor, plasticity, recurrence, and resistance to therapies. There are various mechanisms that contribute to the drug resistance of CSCs, such as CSCs markers, Epithelial mesenchymal transition, hypoxia, other cells, inflammation, and signaling pathways. Recent investigations have revealed the primary role of HMGA2 in the development and invasion of cancer cells. Importantly, HMGA2 also plays a key role in resistance to treatment through their function in the drug resistance mechanisms of CSCs and challenge it. Therefore, a deep understanding of this issue can provide a clearer perspective for researchers in the face of this problem.

Immunotherapy of inflammatory bowel disease (IBD) through mesenchymal stem cells.

Many pathophysiologic pathways and immune-pathologic etiologies are addressed as Inflammatory bowel disease (IBD) causes. Moreover, dysfunction of the immune system leads to inflammatory responses against intestinal components that boost disease severity. The use of routine treatments has limitations. Besides, patients may experience drug resistance. Therefore, the use of novel and effective therapies is essential. Relying on the immune regulatory functions of Mesenchymal Stem Cells (MSCs), researchers have suggested possible benefits of MSCs administration for IBD, both in experimental and clinical studies. Experimental animal models of IBD have shown effects of MSCs, MSC-derived exosomal micro RNAs, and MSC-based drug delivery systems on the regulation of the immune system (Th17 suppression versus T-regular cell biased responses). These studies have suggested MSCs' benefits on intestinal integrity, improved smooth cell function, and tissue repair. On the other hand, various clinical trials have been registered for MSCs application in IBD patients that show reliable safety in humans. Most clinical trials have used MSCs of bone marrow, umbilical cord, and adipose tissue that have been administered by intravenous or intra-tissue injection. Studies have evaluated clinical outcomes, patient symptoms, or healing processes; while immunological studies in the clinical era are missing. As we reviewed, huge shreds of experimental shreds of evidence have led to the inception of multiple clinical trials in phase I/II, showing promising results for IBD treatment. We suggest that further clinical investigation should be more focused on in-vitro/in-vivo assessed outcomes as well as the immunological endpoints to have more reliable results with more support for laboratory evidence.

Application of extracellular vesicles derived from mesenchymal stem cells as potential therapeutic tools in autoimmune and rheumatic diseases.

Mesenchymal stem cells (MSCs) have been proven to have superior potential to be used astherapeutic candidates in various disorders. Nevertheless, the clinical application of these cells have been restricted because of their tumorigenic properties. Increasing evidence has established that the valuable impacts of MSCs are mainly attributable to the paracrine factors including extracellular vesicles (EVs). EVs are nanosized double-layer phospholipid membrane vesicles contain various proteins, lipids and miRNAs which mediate cell-to-cell communications. Due to their inferior immunogenicity and tumorigenicity, as well as easier management, EVs have drawn attention as potential cell-free replacement therapy to MSCs. For that reason, herein, we reviewed the recent findings of researches on different MSC-EVs and their effectiveness in the treatment of several autoimmune and rheumatic diseases including multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, osteoporosis, and systemic lupus erythematosus as well as Sjogren's syndrome, systemic sclerosis and other autoimmune diseases.