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The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular RNAs (circRNAs), known for their covalently closed loop structures, are non-coding RNA molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, microRNAs (miRNAs) are endogenous non-coding RNAs with linear structures that regulate cellular biological processes akin to circRNAs. Both miRNAs and circRNAs exhibit aberrant expressions in various cancers. Notably, circRNAs can function as sponges for miRNAs, influencing their activity. The circRNA/miRNA interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circRNAs and miRNAs hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circRNA-miRNA circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circRNA/miRNA-based strategies.

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Cancer progression results from the dysregulation of molecular pathways, each with unique features that can either promote or inhibit tumor growth. The complexity of carcinogenesis makes it challenging for researchers to target all pathways in cancer therapy, emphasizing the importance of focusing on specific pathways for targeted treatment. One such pathway is the PI3K/Akt pathway, which is often overexpressed in cancer. As tumor cells progress, the expression of PI3K/Akt increases, further driving cancer advancement. This study aims to explore how ncRNAs regulate the expression of PI3K/Akt. NcRNAs are found in both the cytoplasm and nucleus, and their functions vary depending on their location. They can bind to the promoters of PI3K or Akt, either reducing or increasing their expression, thus influencing tumorigenesis. The ncRNA/PI3K/Akt axis plays a crucial role in determining cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), and even chemoresistance and radioresistance in human cancers. Anti-tumor compounds can target ncRNAs to modulate the PI3K/Akt axis. Moreover, ncRNAs can regulate the PI3K/Akt pathway both directly and indirectly.

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Cancer is a complex, multistep process characterized by abnormal cell growth and metastasis as well as the capacity of the tumor cells in therapy resistance development. The urological system is particularly susceptible to a group of malignancies known as urological cancers, where an accumulation of genetic alterations drives carcinogenesis. In various human cancers, Wnt singalling is dysregulated; following nuclear transfer of ß-catenin, it promotes tumor progression and affects genes expression. Elevated levels of Wnt have been documented in urological cancers, where its overexpression enhances growth and metastasis. Additionally, increased Wnt singalling contributes to chemoresistance in urological cancers, leading to reduced sensitivity to chemotherapy agents like cisplatin, doxorubicin, and paclitaxel. Wnt upregulation can change radiotherapy response of urological cancers. The regulation of Wnt involves various molecular pathways, including Akt, miRNAs, lncRNAs, and circRNAs, all of which play roles in carcinogenesis. Targeting and silencing Wnt or its associated pathways can mitigate tumorigenesis in urological cancers. Anti-cancer compounds such as curcumin and thymoquinone have shown efficacy in suppressing tumorigenesis through the downregulation of Wnt singalling. Notably, nanoparticles have proven effective in treating urological cancers, with several studies in prostate cancer (PCa) using nanoparticles to downregulate Wnt and suppress tumor growth. Future research should focus on developing small molecules that inhibit Wnt singalling to further suppress tumorigenesis and advance the treatment of urological cancers. Moreover, Wnt can be used as reliable biomarker for the diagnosis and prognosis of urological cancers.

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Immune checkpoints are a set of inhibitory and stimulatory molecules/mechanisms that affect the activity of immune cells to maintain the existing balance between pro- and anti-inflammatory signaling pathways and avoid the progression of autoimmune disorders. Tumor cells can employ these checkpoints to evade immune system. The discovery and development of immune checkpoint inhibitors (ICIs) was thereby a milestone in the area of immuno-oncology. ICIs stimulate anti-tumor immune responses primarily by disrupting co-inhibitory signaling mechanisms and accelerate immune-mediated killing of tumor cells. Despite the beneficial effects of ICIs, they sometimes encounter some degrees of therapeutic resistance, and thereby do not effectively act against tumors. Among multiple combination therapies have been introduced to date, targeting autophagy, as a cellular degradative process to remove expired organelles and subcellular constituents, has represented with potential capacities to overcome ICI-related therapy resistance. It has experimentally been illuminated that autophagy induction blocks the immune checkpoint molecules when administered in conjugation with ICIs, suggesting that autophagy activation may restrict therapeutic challenges that ICIs have encountered with. However, the autophagy flux can also provoke the immune escape of tumors, which must be considered. Since the conventional FDA-approved ICIs have designed and developed to target programmed cell death receptor/ligand 1 (PD-1/PD-L1) as well as cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) immune checkpoint molecules, we aim to review the effects of autophagy targeting in combination with anti-PD-1/PD-L1- and anti-CTLA-4-based ICIs on cancer therapeutic resistance and tumor immune evasion.

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Background: Recurrent aphthous stomatitis (RAS) is known as the most common ulcerative lesion in the oral mucosa. Aphthous has an unknown etiology and is considered a multifactorial disease. This study was conducted to investigate the relationship between iron and zinc deficiency and the occurrence of RAS. Materials and Methods: This systematic review and metaanalysis was performed according to the Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) guidelines. Data were obtained through an electronic search in international databases, including PubMed, Medline, Embase, ISI Web of Science, Scopus, Springer, ProQuest, ScienceDirect, Clinical Key, and Google Scholar, and domestic Persian databases, including SID, Magiran, and Iran Medex, until April 2021. New-castle Ottawa Scale (NOS) was used to determine the eligibility of studies by evaluating the title and summary of the articles and a partial evaluation of the full text. Comprehensive Metaanalysis (CMA) software was used for data analysis. Results: Initially, a total of 1383 articles were retrieved, of which 941 were duplicate studies. Further, 384 studies were excluded after evaluation of the title and abstract, and 36 studies were excluded after considering the inclusion and exclusion criteria. Finally, 22 articles were included in the metaanalysis. The standardized mean difference value was -0.421 (-0.623--0.20) for iron factor, -0.309 (-0.463--0.154) for iron factor in men, -0.483 (-0.375--0373) for iron factor in women, and -0.955 (-0.282--1.628) for the zinc factor. Conclusion: In general, the serum iron level (in general, in male and female patients separately) and the zinc serum level in patients with RAS were significantly lower than those of healthy people.

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Breast cancer continues to be a major global health challenge, driving the need for effective therapeutic strategies. Cisplatin, a powerful chemotherapeutic agent, is widely used in breast cancer treatment. However, its effectiveness is often limited by systemic toxicity and the development of drug resistance. This review examines the molecular factors that influence cisplatin response and resistance, offering crucial insights for the scientific community. It highlights the significance of understanding cisplatin resistance's genetic and epigenetic contributors, which could lead to more personalized treatment approaches. Additionally, the review explores innovative strategies to counteract cisplatin resistance, including combination therapies, nanoparticle-based drug delivery systems, and targeted therapies. These approaches are under intensive investigation and promise to enhance breast cancer treatment outcomes. This comprehensive discussion is a valuable resource to advance breast cancer therapeutics and address the challenge of cisplatin resistance.

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Osteoporosis, characterized by compromised bone density and microarchitecture, represents a significant global health challenge, particularly in aging populations. This comprehensive review delves into the intricate signaling pathways implicated in the pathogenesis of osteoporosis, providing valuable insights into the pivotal role of signal transduction in maintaining bone homeostasis. The exploration encompasses cellular signaling pathways such as Wnt, Notch, JAK/STAT, NF-κB, and TGF-ß, all of which play crucial roles in bone remodeling. The dysregulation of these pathways is a contributing factor to osteoporosis, necessitating a profound understanding of their complexities to unveil the molecular mechanisms underlying bone loss. The review highlights the pathological significance of disrupted signaling in osteoporosis, emphasizing how these deviations impact the functionality of osteoblasts and osteoclasts, ultimately resulting in heightened bone resorption and compromised bone formation. A nuanced analysis of the intricate crosstalk between these pathways is provided to underscore their relevance in the pathophysiology of osteoporosis. Furthermore, the study addresses some of the most crucial long non-coding RNAs (lncRNAs) associated with osteoporosis, adding an additional layer of academic depth to the exploration of immune system involvement in various types of osteoporosis. Finally, we propose that SKP1 can serve as a potential biomarker in osteoporosis.

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For the first time, a subset of small cancer cells identified in acute myeloid leukemia has been termed Cancer Stem Cells (CSCs). These cells are notorious for their robust proliferation, self-renewal abilities, significant tumor-forming potential, spread, and resistance to treatments. CSCs are a global concern, as it found in numerous types of cancer, posing a real-world challenge today. Our review encompasses research on key CSC markers, signaling pathways, and MicroRNA in three types of cancer: breast, colon, and liver. These factors play a critical role in either promoting or inhibiting cancer cell growth. The reviewed studies have shown that as cells undergo malignant transformation, there can be an increase or decrease in the expression of different Cluster of Differentiation (CD) markers on their surface. Furthermore, alterations in essential signaling pathways, such as Wnt and Notch1, may impact CSC proliferation, survival, and movement, while also providing potential targets for cancer therapies. Additionally, some research has focused on MicroRNAs due to their dual role as potential therapeutic biomarkers and their ability to enhance CSCs' response to anti-cancer drugs. MicroRNAs also regulate a wide array of cellular processes, including the self-renewal and pluripotency of CSCs, and influence gene transcription. Thus, these studies indicate that MicroRNAs play a significant role in the malignancy of various tumors. Although the gathered information suggests that specific CSC markers, signaling pathways, and MicroRNAs are influential in determining the destiny of cancer cells and could be advantageous for therapeutic strategies, their precise roles and impacts remain incompletely defined, necessitating further investigation.

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Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive form of cancer associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. The emerging field of stem cell therapies for ATLL is discussed, highlighting the potential of hematopoietic stem cell transplantation (HSCT) and genetically modified stem cells. HSCT aims to eradicate malignant T-cells and restore a functional immune system through the infusion of healthy donor stem cells. Genetically modified stem cells show promise in enhancing their ability to target and eliminate ATLL cells. The article presents insights from preclinical studies and limited clinical trials, emphasizing the need for further research to establish the safety, efficacy, and long-term outcomes of stem cell therapies for ATLL and challenges associated with these innovative approaches are also explored. Overall, stem cell therapies hold significant potential in revolutionizing ATLL treatment, and ongoing clinical trials aim to determine their benefits in larger patient populations.

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AMP-activated protein kinase (AMPK) signaling has a versatile role in Osteosarcoma (OS), an aggressive bone malignancy with a poor prognosis, particularly in cases that have metastasized or recurred. This review explores the regulatory mechanisms, functional roles, and therapeutic applications of AMPK signaling in OS. It focuses on the molecular activation of AMPK and its interactions with cellular processes like proliferation, apoptosis, and metabolism. The uncertain role of AMPK in cancer is also discussed, highlighting its potential as both a tumor suppressor and a contributor to carcinogenesis. The therapeutic potential of targeting AMPK signaling in OS treatment is examined, including direct and indirect activators like metformin, A-769662, resveratrol, and salicylate. Further research is needed to determine dosing, toxicities, and molecular mechanisms responsible for the anti-osteosarcoma effects of these compounds. This review underscores the complex involvement of AMPK signaling in OS and emphasizes the need for a comprehensive understanding of its molecular mechanisms. By elucidating the role of AMPK in OS, the aim is to pave the way for innovative therapeutic approaches that target this pathway, ultimately improving the prognosis and quality of life for OS patients.

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OBJECTIVES: Hospital-acquired infections (HAIs) are significant problems as public health issues which need attention. Such infections are significant problems for society and healthcare organizations. This study aimed to carry out a systematic review and a meta-analysis to analyze the prevalence of HAIs globally. METHODS: We conducted a comprehensive search of electronic databases including EMBASE, Scopus, PubMed and Web of Science between 2000 and June 2021. We found 7031 articles. After removing the duplicates, 5430 studies were screened based on the titles/ abstracts. Then, we systematically evaluated the full texts of the 1909 remaining studies and selected 400 records with 29,159,630 participants for meta-analysis. Random-effects model was used for the analysis, and heterogeneity analysis and publication bias test were conducted. RESULTS: The rate of universal HAIs was 0.14 percent. The rate of HAIs is increasing by 0.06 percent annually. The highest rate of HAIs was in the AFR, while the lowest prevalence were in AMR and WPR. Besides, AFR prevalence in central Africa is higher than in other parts of the world by 0.27 (95% CI, 0.22-0.34). Besides, E. coli infected patients more than other micro-organisms such as Coagulase-negative staphylococci, Staphylococcus spp. and Pseudomonas aeruginosa. In hospital wards, Transplant, and Neonatal wards and ICU had the highest rates. The prevalence of HAIs was higher in men than in women. CONCLUSION: We identified several essential details about the rate of HAIs in various parts of the world. The HAIs rate and the most common micro-organism were different in various contexts. However, several essential gaps were also identified. The study findings can help hospital managers and health policy makers identify the reason for HAIs and apply effective control programs to implement different plans to reduce the HAIs rate and the financial costs of such infections and save resources.

Assuntos