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Uncovering the complex role of interferon-gamma in suppressing type 2 immunity to cancer

Bhat AA, Goyal A, Thapa R, Almalki WH, Kazmi I, Alzarea SI, et al.

Cytokine, 2023 Nov;171:156376.
PMID: 37748333 DOI: 10.1016/j.cyto.2023.156376

Cancer involves cells' abnormal growth and ability to invade or metastasize to different body parts. Cancerous cells can divide uncontrollably and spread to other areas through the lymphatic or circulatory systems. Tumors form when malignant cells clump together in an uncontrolled manner. In this context, the cytokine interferon-gamma (IFN-γ) is crucial in regulating immunological responses, particularly malignancy. While IFN-γ is well-known for its potent anti-tumor effects by activating type 1 immunity, recent research has revealed its ability to suppress type 2 immunity, associated with allergy and inflammatory responses. This review aims to elucidate the intricate function of IFN-γ in inhibiting type 2 immune responses to cancer. We explore how IFN-γ influences the development and function of immune cells involved in type 2 immunity, such as mast cells, eosinophils, and T-helper 2 (Th2) cells. Additionally, we investigate the impact of IFN-mediated reduction of type 2 immunity on tumor development, metastasis, and the response to immunotherapeutic interventions. To develop successful cancer immunotherapies, it is crucial to comprehend the complex interplay between type 2 and type 1 immune response and the regulatory role of IFN-γ. This understanding holds tremendous promise for the development of innovative treatment approaches that harness the abilities of both immune response types to combat cancer. However, unraveling the intricate interplay between IFN-γ and type 2 immunity in the tumor microenvironment will be essential for achieving this goal.
Non-coding RNAs: Emerging biomarkers and therapeutic targets in ulcerative colitis

Kazmi I, Altamimi ASA, Afzal M, Majami AA, Abbasi FA, Almalki WH, et al.

Pathol Res Pract, 2024 Jan;253:155037.
PMID: 38160482 DOI: 10.1016/j.prp.2023.155037

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the colon's mucosal lining, leading to chronic bowel inflammation. Despite extensive research, the precise molecular mechanisms underlying UC pathogenesis remain elusive. NcRNAs form a category of functional RNA molecules devoid of protein-coding capacity. They have recently surfaced as pivotal modulators of gene expression and integral participants in various pathological processes, particularly those related to inflammatory disorders. The diverse classes of ncRNAs, encompassing miRNAs, circRNAs, and lncRNAs, have been implicated in UC. It highlights their involvement in key UC-related processes, such as immune cell activation, epithelial barrier integrity, and the production of pro-inflammatory mediators. ncRNAs have been identified as potential biomarkers for UC diagnosis and monitoring disease progression, offering promising avenues for personalized medicine. This approach may pave the way for novel, more specific treatments with reduced side effects, addressing the current limitations of conventional therapies. A comprehensive understanding of the interplay between ncRNAs and UC will advance our knowledge of the disease, potentially leading to more effective and personalized treatments for patients suffering from this debilitating condition. This review explores the pivotal role of ncRNAs in the context of UC, shedding light on their possible targets for diagnosis, prognosis, and therapeutic interventions.
The emerging role of non-coding RNAs in the Wnt/β-catenin signaling pathway in Prostate Cancer

Kazmi I, Altamimi ASA, Afzal M, Majami AA, AlGhamdi AS, Alkinani KB, et al.

Pathol Res Pract, 2024 Feb;254:155134.
PMID: 38277746 DOI: 10.1016/j.prp.2024.155134

Prostate cancer (PCa) is an important worldwide medical concern, necessitating a greater understanding of the molecular processes driving its development. The Wnt/-catenin signaling cascade is established as a central player in PCa pathogenesis, and recent research emphasizes the critical involvement of non-coding RNAs (ncRNAs) in this scenario. This in-depth study seeks to give a thorough examination of the complex relationship between ncRNAs and the Wnt/β-catenin system in PCa. NcRNAs, such as circular RNAs (circRNAs), long ncRNAs (lncRNAs), and microRNAs (miRNAs), have been recognized as essential regulators that modulate numerous facets of the Wnt/β-catenin network. MiRNAs have been recognized as targeting vital elements of the process, either enhancing or inhibiting signaling, depending on their specific roles and targets. LncRNAs participate in fine-tuning the Wnt/β-catenin network as a result of complicated interplay with both upstream and downstream elements. CircRNAs, despite being a relatively recent addition to the ncRNA family, have been implicated in PCa, influencing the Wnt/β-catenin cascade through diverse mechanisms. This article encompasses recent advances in our comprehension of specific ncRNAs that participate in the Wnt/β-catenin network, their functional roles, and clinical relevance in PCa. We investigate their use as screening and predictive indicators, and targets for treatment. Additionally, we delve into the interplay between Wnt/β-catenin and other signaling networks in PCa and the role of ncRNAs within this complex network. As we unveil the intricate regulatory functions of ncRNAs in the Wnt/β-catenin cascade in PCa, we gain valuable insights into the disease's pathogenesis. The implementation of these discoveries in practical applications holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of PCa patients. This comprehensive review underscores the evolving landscape of ncRNA research in PCa and the potential for innovative interventions in the battle against this formidable malignancy.
Fulltext Kaempferol: Paving the path for advanced treatments in aging-related diseases

Hussain MS, Altamimi ASA, Afzal M, Almalki WH, Kazmi I, Alzarea SI, et al.

Exp Gerontol, 2024 Apr;188:112389.
PMID: 38432575 DOI: 10.1016/j.exger.2024.112389

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the β-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.
Unwinding circular RNA's role in inflammatory pulmonary diseases

Bhat AA, Gupta G, Goyal A, Thapa R, Almalki WH, Kazmi I, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2024 May;397(5):2567-2588.
PMID: 37917370 DOI: 10.1007/s00210-023-02809-7

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications.
Fulltext COVID-19 Vaccine Hesitancy: Umbrella Review of Systematic Reviews and Meta-Analysis

Rahbeni TA, Satapathy P, Itumalla R, Marzo RR, Mugheed KAL, Khatib MN, et al.

JMIR Public Health Surveill, 2024 Apr 30;10:e54769.
PMID: 38687992 DOI: 10.2196/54769

BACKGROUND: The unprecedented emergence of the COVID-19 pandemic necessitated the development and global distribution of vaccines, making the understanding of global vaccine acceptance and hesitancy crucial to overcoming barriers to vaccination and achieving widespread immunization.
OBJECTIVE: This umbrella review synthesizes findings from systematic reviews and meta-analyses to provide insights into global perceptions on COVID-19 vaccine acceptance and hesitancy across diverse populations and regions.
METHODS: We conducted a literature search across major databases to identify systematic reviews and meta-analysis that reported COVID-19 vaccine acceptance and hesitancy. The AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) criteria were used to assess the methodological quality of included systematic reviews. Meta-analysis was performed using STATA 17 with a random effect model. The data synthesis is presented in a table format and via a narrative.
RESULTS: Our inclusion criteria were met by 78 meta-analyses published between 2021 and 2023. Our analysis revealed a moderate vaccine acceptance rate of 63% (95% CI 0.60%-0.67%) in the general population, with significant heterogeneity (I2 = 97.59%). Higher acceptance rates were observed among health care workers and individuals with chronic diseases, at 64% (95% CI 0.57%-0.71%) and 69% (95% CI 0.61%-0.76%), respectively. However, lower acceptance was noted among pregnant women, at 48% (95% CI 0.42%-0.53%), and parents consenting for their children, at 61.29% (95% CI 0.56%-0.67%). The pooled vaccine hesitancy rate was 32% (95% CI 0.25%-0.39%) in the general population. The quality assessment revealed 19 high-quality, 38 moderate-quality, 15 low-quality, and 6 critically low-quality meta-analyses.
CONCLUSIONS: This review revealed the presence of vaccine hesitancy globally, emphasizing the necessity for population-specific, culturally sensitive interventions and clear, credible information dissemination to foster vaccine acceptance. The observed disparities accentuate the need for continuous research to understand evolving vaccine perceptions and to address the unique concerns and needs of diverse populations, thereby aiding in the formulation of effective and inclusive vaccination strategies.
TRIAL REGISTRATION: PROSPERO CRD42023468363; https://tinyurl.com/2p9kv9cr.