Current Pharmaceutical Design - Online First

MicroRNAs (miRNAs) are the regulators of gene expression and several cellular processes related to the immune system. miRNAs during tuberculosis (TB) infection are considered regulatory factors for the host immune system. Mycobacterium tuberculosis has a great ability to survive and multiply in phagocytic cells, which makes it difficult to treat. It can replicate through various cellular pathways. To establish the infection in the host cell, M. tuberculosis changes in the miRNA expression and increases survival capacity with high infectivity. miRNAs are widely used as biomarkers and therapeutic agents for tuberculosis. During 
M. tuberculosis infection, altered miRNA expressions can cause the progression of the disease and discriminate between latent and active TB infection. Due to their active involvement in disease progression, miRNAs may be utilized as potential biomarkers. Furthermore, the involvement of miRNA in autophagy and apoptosis modulation against M. tuberculosis highlights its potential for host-directed therapy. In this review article, we attempt to summarize the expression and role of various miRNAs in TB as immune modulators, differential activators between different phases of TB, including neuronal dysfunction in the brain, as therapeutic targets and diagnostic tools against TB.

Cancer is still one of the most serious and life-threatening diseases in humans, and the conventional chemotherapies, radiation treatments, and surgical methods have yet to provide an effective resolution due to some drawbacks concerning drug resistance, general toxicity, and poor targeting to tumor sites. To surmount these challenges, some innovative approaches are under exploration; hence, the emergence of more promising solutions in the format of nanotechnology that combine with stem cell (SC)-based drug delivery systems (DDS). Its advantages include autonomous proliferative potential and the ability to clonally generate various cell types, leading to malignant transformation. Additionally, they possess an innate ability to migrate toward tumor sites, making them highly effective vectors for targeted DDS. The integration of nanotechnology with SCs offers several benefits, such as controlled release of therapeutic molecules, improved bioavailability, and reduced systemic toxicity. These advantages may provide the opportunity to improve cancer therapy with fewer side effects than those resulting from conventional treatments. This review has focused on the emerging role of SC-nanotechnology-based DDS as a new era in targeted cancer treatment and has emphasized enhancing therapeutic outcomes with a more precise approach to cancer therapy.

Oral diseases represent significant health challenges, with periodontal diseases and dental caries ranking as key preventable infectious diseases worldwide. Oral health affects overall quality of life, and inadequate oral hygiene is associated with chronic diseases. Carvacrol is a monoterpenoid phenol found in essential oils of pepperwort (Lepidium flavum), thyme (Thymus vulgaris), oregano (Origanum vulgare), wild bergamot (Citrus aurantium), and other plants. Carvacrol exhibits numerous biological activities, including antimicrobial, antioxidant, and anticancer effects. Carvacrol demonstrated the ability to inhibit the oral pathogens examined and exhibited properties that prevent biofilm formation on their oral biofilm; thus, it may be used to manage and prevent the colonization of microorganisms, which is particularly important in human oral diseases. Besides, carvacrol protects gingival tissue in periodontal disease. Knowledge of carvacrol's many actions will help develop novel treatment plans, and designing clinical studies will optimize its potential advantages for treating oral diseases.

Long noncoding RNAs (LncRNAs) represent a group of long noncoding RNA molecules exceeding 200 nt in length and lacking the capacity for protein coding. In recent years, the function and progress of lncRNA have attracted the attention of more and more researchers. Specifically, the long non-coding RNA, TSIX (TSIX transcript, XIST antisense RNA), plays a significant role in ensuring random X-chromosome inactivation. Recent investigations have highlighted the involvement of lncRNA TSIX in the development of various cancers, emphasizing its crucial functions in tumorigenesis. TSIX has emerged as a novel cancer-associated lncRNA and it is identified for its aberrant expression in diverse tumors, such as those of the breast, gastric, hepatocellular, head and neck, lung, esophageal squamous cell, and uterine smooth muscle. Furthermore, lncRNA TSIX regulates mRNA expression by binding to specific miRNAs, utilizing a competitive

endogenous RNA regulatory mechanism. This interaction significantly influences tumor cell proliferation, migration, invasion, and apoptosis. LncRNA TSIX may serve as a useful biomarker or a prospective therapeutic target in a variety of malignant cancers because of the biological functions and mechanisms associated with it.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a worldwide health crisis. In addition to its effects on liver function, MASLD intensely increases the risk of hepatocellular carcinoma (HCC) and a number of extrahepatic cancers, including breast, colorectal, and pancreatic cancers. This review explores the complex network of molecular pathways linking MASLD to cancer, emphasizing the involvement of oxidative stress, lipotoxicity, insulin resistance, chronic inflammation, and mitochondrial dysfunction. Genetic variations in important genes, including PNPLA3, TM6SF2, and MBOAT7, increase this risk by hastening the course of the disease and making a person more susceptible to cancer. By shedding light on these important pathways and genetic factors, this research not only advances knowledge of the relationship between MASLD and cancer but also opens the door for novel treatment approaches meant to reduce the risk of cancer in MASLD patients. Millions of people afflicted by this deadly but silent illness may benefit from novel therapies that target these fundamental systems.

Liver cancer, particularly Hepatocellular Carcinoma (HCC), remains a significant global health challenge owing to its high incidence and position as the fourth leading cause of cancer-related mortality. HCC represents 75-85% of all liver cancer cases and ranks as the sixth most prevalent cancer globally. Several factors, including late-stage diagnosis, limited treatment effectiveness, resistance to conventional therapies, and adverse side effects, hinder the delivery of life-prolonging care to patients with HCC. Current treatment options such as chemotherapy, immunotherapy, and adjuvant therapy are often associated with severe side effects. Consequently, there is an urgent need for improved diagnostic methods and alternative therapeutic approaches to extend life expectancy and reduce HCC-related mortalities. Artificial Intelligence (AI) is an emerging technology that offers promising advances for the early detection of HCC. In terms of alternative treatments, natural compounds have garnered significant attention because of their diverse biological activities, such as antitumor, antiviral, antimicrobial, antioxidant, anti-inflammatory, hepatoprotective, antimutagenic, and cardioprotective effects, and their relatively lower side effect profiles. These compounds exhibit hepatoprotective properties by modulating key molecular pathways involved in HCC development and progression. This article provides an overview of recent advances in the understanding of liver cancer etiology, therapeutic targets in HCC pathogenesis, the role of AI in its detection, and the potential of natural products, particularly flavonoids, as preventive and therapeutic agents against HCC, highlighting their underlying mechanisms of action.

Amyloid beta (Aβ) dyshomeostasis is considered the main biological aberration in Alzheimer’s Disease (AD) pathology. The interplay between Aβ formation and clearance is predominantly modulated by a disintegrin and a metalloproteinase 10 (ADAM10, α-secretase) and β-site APP Cleaving Enzyme 1 (BACE1), the two pivotal enzymes in both non-amyloidogenic/amyloidogenic and amyloidolytic pathways. Emerging evidence suggests that aberrations in ADAM10 and BACE1 expression, activity, and function in the brain of AD patients also manifest in peripheral fluids, suggesting their potential as blood-based biomarkers for AD diagnosis. This review provides a comprehensive overview of the literature by exploring the roles of ADAM10 and BACE1 in AD, spanning from their involvement as pathological AD drivers to their potential utility as promising biomarkers.

Saffron, derived from the Crocus sativus plant, has been revered for centuries for its culinary, medicinal, and cultural significance. This review provides a comprehensive overview of saffron's chemical constituents and phytochemistry, elucidating its rich profile of bioactive compounds. Emphasis is placed on exploring the bio-accessibility, bioavailability, and bioactivity of saffron's phytochemicals, laying the foundation for understanding its pharmaceutical significance. The pharmaceutical importance of saffron and its phytochemicals is thoroughly examined, focusing on their diverse therapeutic properties. These include anticancer, antidiabetic, antioxidant, antimicrobial, anti-inflammatory, antinociceptive, anticonvulsant, antidepressant, learning and memory enhancement, cardiovascular, and antihypertensive properties. Such multifaceted pharmacological activities underscore saffron's potential as a valuable medicinal resource. Clinical studies investigating the efficacy and safety of saffron in various health conditions are synthesized, providing insights into its clinical applications. Moreover, toxicity assessments in animal models, encompassing acute, subacute, subchronic, and developmental toxicity, are discussed to delineate the safety profile of saffron and its bioactive constituents. Finally, recent advances and future perspectives in saffron research are highlighted, underscoring emerging trends and potential avenues for further exploration. This review serves as a comprehensive resource for researchers, clinicians, and stakeholders interested in harnessing the therapeutic potential of saffron while ensuring its safe and effective utilization in healthcare settings.