From diabetes to diverse domains: the multifaceted roles of GLP-1 receptor agonists.

Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1RAs) emerged as a primary treatment for type-2 diabetes mellitus (T2DM), however, their multifaceted effects on various target organs beyond glycemic control opened a new era of treatment. We conducted a comprehensive literature search using databases including Scopus, Google Scholar, PubMed, and the Cochrane Library to identify clinical, in-vivo, and in-vitro studies focusing on the diverse effects of GLP-1 receptor agonists. Eligible studies were selected based on their relevance to the varied roles of GLP-1RAs in T2DM management and their impact on other physiological functions. Numerous studies have reported the efficacy of GLP-1RAs in improving outcomes in T2DM, with demonstrated benefits including glucose-dependent insulinotropic actions, modulation of insulin signaling pathways, and reductions in glycemic excursions. Additionally, GLP-1 receptors are expressed in various tissues and organs, suggesting their widespread physiological functions beyond glycemic control potentially include neuroprotective, anti-inflammatory, cardioprotective, and metabolic benefits. However, further scientific studies are still underway to maximize the benefits of GLP-1RAs and to discover additional roles in improving health benefits. This article sought to review not only the actions of GLP1RAs in the treatment of T2DM but also explore its effects on potential targets in other disorders.

The scaffold protein disabled 2 (DAB2) and its role in tumor development and progression.

BACKGROUND: Disabled 2 (DAB2) is a multifunctional protein that has emerged as a critical component in the regulation of tumor growth. Its dysregulation is implicated in various types of cancer, underscoring its importance in understanding the molecular mechanisms underlying tumor development and progression. This review aims to unravel the intricate molecular mechanisms by which DAB2 exerts its tumor-suppressive functions within cancer signaling pathways. METHODS AND RESULTS: We conducted a comprehensive review of the literature focusing on the structure, expression, physiological functions, and tumor-suppressive roles of DAB2. We provide an overview of the structure, expression, and physiological functions of DAB2. Evidence supporting DAB2's role as a tumor suppressor is explored, highlighting its ability to inhibit cell proliferation, induce apoptosis, and modulate key signaling pathways involved in tumor suppression. The interaction between DAB2 and key oncogenes is examined, elucidating the interplay between DAB2 and oncogenic signaling pathways. We discuss the molecular mechanisms underlying DAB2-mediated tumor suppression, including its involvement in DNA damage response and repair, regulation of cell cycle progression and senescence, and modulation of epithelial-mesenchymal transition (EMT). The review explores the regulatory networks involving DAB2, covering post-translational modifications, interactions with other tumor suppressors, and integration within complex signaling networks. We also highlight the prognostic significance of DAB2 and its role in pre-clinical studies of tumor suppression. CONCLUSION: This review provides a comprehensive understanding of the molecular mechanisms by which DAB2 exerts its tumor-suppressive functions. It emphasizes the significance of DAB2 in cancer signaling pathways and its potential as a target for future therapeutic interventions.

From Gut to Brain: Unraveling the Intricate Link Between Microbiome and Stroke.

Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively.

Biogenic metallic nanoparticles: from green synthesis to clinical translation.

Biogenic metallic nanoparticles (NPs) have garnered significant attention in recent years due to their unique properties and various applications in different fields. NPs, including gold, silver, zinc oxide, copper, titanium, and magnesium oxide NPs, have attracted considerable interest. Green synthesis approaches, utilizing natural products, offer advantages such as sustainability and environmental friendliness. The theranostics applications of these NPs hold immense significance in the fields of medicine and diagnostics. The review explores intricate cellular uptake pathways, internalization dynamics, reactive oxygen species generation, and ensuing inflammatory responses, shedding light on the intricate mechanisms governing their behaviour at a molecular level. Intriguingly, biogenic metallic NPs exhibit a wide array of applications in medicine, including but not limited to anti-inflammatory, anticancer, anti-diabetic, anti-plasmodial, antiviral properties and radical scavenging efficacy. Their potential in personalized medicine stands out, with a focus on tailoring treatments to individual patients based on these NPs' unique attributes and targeted delivery capabilities. The article culminates in emphasizing the role of biogenic metallic NPs in shaping the landscape of personalized medicine. Harnessing their unique properties for tailored therapeutics, diagnostics and targeted interventions, these NPs pave the way for a paradigm shift in healthcare, promising enhanced efficacy and reduced adverse effects.

Navigating the landscape of theranostics in nuclear medicine: current practice and future prospects.

Theranostics refers to the combination of diagnostic biomarkers with therapeutic agents that share a specific target expressed by diseased cells and tissues. Nuclear medicine is an exciting component explored for its applicability in theranostic concepts in clinical and research investigations. Nuclear theranostics is based on the employment of radioactive compounds delivering ionizing radiation to diagnose and manage certain diseases employing binding with specifically expressed targets. In the realm of personalized medicine, nuclear theranostics stands as a beacon of potential, potentially revolutionizing disease management. Studies exploring the theranostic profile of radioactive compounds have been presented in this review along with a detailed explanation of radioactive compounds and their theranostic applicability in several diseases. It furnishes insights into their applicability across diverse diseases, elucidating the intricate interplay between these compounds and disease pathologies. Light is shed on the important milestones of nuclear theranostics beginning with radioiodine therapy in thyroid carcinomas, MIBG labelled with iodine in neuroblastoma, and several others. Our perspectives have been put forth regarding the most important theranostic agents along with emerging trends and prospects.

Disable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in Breast Cancer for Therapeutic Revolution.

The Disabled-2 (DAB2) protein, found in 80-90% of various tumors, including breast cancer, has been identified as a potential tumor suppressor protein. On the contrary, some hypothesis suggests that DAB2 is associated with the modulation of the Ras/MAPK pathway by endocytosing the Grb/Sos1 signaling complex, which produces oncogenes and chemoresistance to anticancer drugs, leading to increased tumor growth and metastasis. DAB2 has multiple functions in several disorders and is typically under-regulated in several cancers, making it a potential target for treatment of cancer therapy. The primary function of DAB2 is the modulation of transforming growth factor- ß (TGF-ß) mediated endocytosis, which is involved in several mechanisms of cancer development, including tumor suppression through promoting apoptosis and suppressing cell proliferation. In this review, we will discuss in detail the mechanisms through which DAB2 leads to breast cancer and various advancements in employing DAB2 in the treatment of breast cancer. Additionally, we outlined its role in other diseases. We propose that upregulating DAB2 could be a novel approach to the therapeutics of breast cancer.

An Insight on Microfluidic Organ-on-a-Chip Models for PM2.5-Induced Pulmonary Complications.

Pulmonary diseases like asthma, chronic obstructive pulmonary disorder, lung fibrosis, and lung cancer pose a significant burden to global human health. Many of these complications arise as a result of exposure to particulate matter (PM), which has been examined in several preclinical and clinical trials for its effect on several respiratory diseases. Particulate matter of size less than 2.5 µm (PM2.5) has been known to inflict unforeseen repercussions, although data from epidemiological studies to back this are pending. Conventionally utilized two-dimensional (2D) cell culture and preclinical animal models have provided insufficient benefits in emulating the in vivo physiological and pathological pulmonary conditions. Three-dimensional (3D) structural models, including organ-on-a-chip models, have experienced a developmental upsurge in recent times. Lung-on-a-chip models have the potential to simulate the specific features of the lungs. With the advancement of technology, an emerging and advanced technique termed microfluidic organ-on-a-chip has been developed with the aim of identifying the complexity of the respiratory cellular microenvironment of the body. In the present Review, the role of lung-on-a-chip modeling in reproducing pulmonary complications has been explored, with a specific emphasis on PM2.5-induced pulmonary complications.

Interactions between integrin α9ß1 and VCAM-1 promote neutrophil hyperactivation and mediate poststroke DVT.

ABSTRACT: Venous thromboembolic events are significant contributors to morbidity and mortality in patients with stroke. Neutrophils are among the first cells in the blood to respond to stroke and are known to promote deep vein thrombosis (DVT). Integrin α9 is a transmembrane glycoprotein highly expressed on neutrophils and stabilizes neutrophil adhesion to activated endothelium via vascular cell adhesion molecule 1 (VCAM-1). Nevertheless, the causative role of neutrophil integrin α9 in poststroke DVT remains unknown. Here, we found higher neutrophil integrin α9 and plasma VCAM-1 levels in humans and mice with stroke. Using mice with embolic stroke, we observed enhanced DVT severity in a novel model of poststroke DVT. Neutrophil-specific integrin α9-deficient mice (α9fl/flMrp8Cre+/-) exhibited a significant reduction in poststroke DVT severity along with decreased neutrophils and citrullinated histone H3 in thrombi. Unbiased transcriptomics indicated that α9/VCAM-1 interactions induced pathways related to neutrophil inflammation, exocytosis, NF-κB signaling, and chemotaxis. Mechanistic studies revealed that integrin α9/VCAM-1 interactions mediate neutrophil adhesion at the venous shear rate, promote neutrophil hyperactivation, increase phosphorylation of extracellular signal-regulated kinase, and induce endothelial cell apoptosis. Using pharmacogenomic profiling, virtual screening, and in vitro assays, we identified macitentan as a potent inhibitor of integrin α9/VCAM-1 interactions and neutrophil adhesion to activated endothelial cells. Macitentan reduced DVT severity in control mice with and without stroke, but not in α9fl/flMrp8Cre+/- mice, suggesting that macitentan improves DVT outcomes by inhibiting neutrophil integrin α9. Collectively, we uncovered a previously unrecognized and critical pathway involving the α9/VCAM-1 axis in neutrophil hyperactivation and DVT.

Disabled-2, a versatile tissue matrix multifunctional scaffold protein with multifaceted signaling: Unveiling its potential in the cancer battle.

A multifunctional scaffold protein termed Disabled-2 (Dab2) has recently gained attention in the scientific community and has emerged as a promising candidate in the realm of cancer research. Dab2 protein is involved in a variety of signaling pathways, due to which its significance in the pathogenesis of several carcinomas has drawn considerable attention. Dab2 is essential for controlling the advancement of cancer because it engages in essential signaling pathways such as the Wnt/ß-catenin, epidermal growth factor receptor (EGFR), and transforming growth factor-beta (TGF-ß) pathways. Dab2 can also repress epithelial-mesenchymal transition (EMT) which is involved in tumor progression with metastatic expansion and adds another layer of significance to its possible impact on cancer spread. Furthermore, the role of Dab2 in processes such as cell growth, differentiation, apoptosis, invasion, and metastasis has been explored in certain investigative studies suggesting its significance. The present review examines the role of Dab2 in the pathogenesis of various cancer subtypes including breast cancer, ovarian cancer, gastric cancer, prostate cancer, and bladder urothelial carcinoma and also sheds some light on its potential to act as a therapeutic target and a prognostic marker in the treatment of various carcinomas. By deciphering this protein's diverse signaling, we hope to provide useful insights that may pave the way for novel therapeutic techniques and tailored treatment approaches in cancer management. Preclinical and clinical trial data on the impact of Dab2 regulation in cancer have also been included, allowing us to delineate role of Dab2 in tumor suppressor function, as well as its correlation with disease stage classification and potential therapy options. However, we observed that there is very scarce data in the form of studies on the evaluation of Dab2 role and treatment function in carcinomas, and further research into this matter could prove beneficial in the generation of novel therapeutic agents for patient-centric and tailored therapy, as well as early prognosis of carcinomas.

Single Nucleotide Polymorphisms [SNPs] in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer.

Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms [SNPs] in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma [ESCC]. These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci [eQTL] have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.

Integrated blood and organ profile analysis to evaluate ameliorative effects of kaempferol on 5-fluorouracil-induced toxicity.

Colorectal cancer (CRC) treatment strategies encompass a triad of medical interventions: surgery, radiotherapy, and chemotherapy. Among these, the use of chemotherapy, specifically 5-fluorouracil (5-FU), has become a cornerstone in CRC management. However, it is imperative to explore novel approaches that harness the synergistic potential of chemotherapy agents alongside adjunctive compounds to mitigate the severe adverse effects that often accompany treatment. In light of this pressing need, this study focuses on evaluating Kaempferol (KMP) in combination with 5-FU in a DMH-induced CRC animal model, scrutinizing its impact on haematological indices, organ health, and gastrointestinal, hepatotoxic, and nephrotoxic effects. Remarkably, KMP demonstrated haemato-protective attributes and exerted an immunomodulatory influence, effectively counteracting 5-FU-induced damage. Furthermore, organ assessments affirm the safety profile of the combined treatments while suggesting KMP's potential role in preserving the structural integrity of the intestine, and spleen. Histopathological assessments unveiled KMP's capacity to ameliorate liver injury and mitigate CRC-induced renal impairment. These multifaceted findings underscore KMP's candidacy as a promising adjunctive therapeutic option for CRC, underlining the pivotal need for personalized therapeutic strategies that concurrently optimize treatment efficacy and safeguard organ health. KMP holds tremendous promise in elevating the paradigm of CRC management.

Revolutionizing cancer treatment: comprehensive insights into immunotherapeutic strategies.

Cancer, characterized by the uncontrolled proliferation of aberrant cells, underscores the imperative for innovative therapeutic approaches. Immunotherapy has emerged as a pivotal constituent in cancer treatment, offering improved prognostic outcomes for a substantial patient cohort. Noteworthy for its precision, immunotherapy encompasses strategies such as adoptive cell therapy and checkpoint inhibitors, orchestrating the immune system to recognize and selectively target malignant cells. Exploiting the specificity of the immune response renders immunotherapy efficacious, as it selectively targets the body's immune milieu. Diverse mechanisms underlie cancer immunotherapies, leading to distinct toxicity profiles compared to conventional treatments. A remarkable clinical stride in the anticancer resources is immunotherapy. Remarkably, certain recalcitrant cancers like skin malignancies exhibit resistance to radiation or chemotherapy, yet respond favorably to immunotherapeutic interventions. Notably, combination therapies involving chemotherapy and immunotherapy have exhibited synergistic effects, enhancing overall therapeutic efficacy. Understanding the pivotal role of immunotherapy elucidates its complementary value, bolstering the therapeutic landscape. In this review, we elucidate the taxonomy of cancer immunotherapy, encompassing adoptive cell therapy and checkpoint inhibitors, while scrutinizing their distinct adverse event profiles. Furthermore, we expound on the unprecedented potential of immunogenic vaccines to bolster the anticancer immune response. This comprehensive analysis underscores the significance of immunotherapy in modern oncology, unveiling novel prospects for tailored therapeutic regimens.

Apolipoprotein E3 functionalized lipid-drug conjugated nanoparticles of Levetiracetam for enhanced delivery to the brain: In-vitro cell line studies and in-vivo study.

A significant portion of brain-tumor patients suffer from 'brain-tumor-related epilepsy (BTE)' which results in depression, anxiety and hampered quality of life. Conventional anti-epileptic drugs indicate negative interaction with other drugs augmenting the poor outcome of overall therapy. Levetiracetam (LVM) has evidenced effectiveness for BTE but its hydrophilicity restricts the passage into blood-brain barrier. The majority of lipid nanoparticles fails to load hydrophilic drug sufficiently. Therefore, lipid-drug conjugates (LDC) were synthesized using stearic acid via amide bond formation confirmed by FTIR and NMR. The nanoparticles of synthesized LDC were prepared by solvent injection method followed by functionalization with Apolipoprotein E3 (ApoE3@LDC-NP). The nanoparticles were characterized by DSC, XRD, particle size (131.6 ± 1.24 nm), zeta potential (-15.6 ± 0.09 mV), and for storage stability. In-vitro release study indicated initial burst release of 20 ± 0.63 % followed by sustained release up to 30 h (66 ± 1.40 %) for ApoE3@LDC-NP. The cell-line study on HEK293 indicated no significant cytotoxic effect and greater cell uptake through U87MG cell line. The pharmacokinetic and bio-distribution study indicated 2.5-fold greater brain-targeting of ApoE3@LDC-NP as compared to LVM solution. It proved safe in the haemolysis study and exhibited the absence of tissue necrosis. Thus, ApoE3@LDC-NP might be a promising approach for effective brain-targeting of LVM for improved clinical response in BTE.

Clinical Similarity of Biosimilars and Reference Drugs: A Comprehensive Review and New Hope for Public Health in a New Frontier.

BACKGROUND: Patents and exclusive rights on reference biologics contribute to the emergence of biosimilars. Regulatory bodies, such as the Food and Drug Administration (FDA), World Health Organization (WHO), and EMA (European Medicines Agency) for assessing clinical safety, effectiveness, and consequences between biosimilars and reference medications, have established guidelines. Since generic small molecules from reference can be easily swapped, biosimilars cannot be used interchangeably and may not always indicate interchangeability due to highly restrictive properties. It can be replaced with a reference without the healthcare provider's help under the interchangeability context. OBJECTIVE: The purpose of our study is to analyze and compare evidence-based clinical safety, therapeutic potential, and importance (outcomes) of several biosimilars with their references along with clinical uses in chronic diseases. METHODS: Through a comprehensive systemic literature review of more than 100 articles involving medicinally important drugs whose bio-similarity works optimally, safety-efficacy parameters have been analyzed. Analysis of biosimilar usage, approval, and safety-efficacy aspects are majorly focused upon herein in this review. RESULTS: From this systemic review, it can be stated that the majority of biosimilars are clinically and statistically equivalent to their originators. As biosimilars have good safety-efficacy aspects with lower prices, their utilization can be more encouraged, which was already done by the FDA with the establishment of a public online database entitled "Purple Book," which includes all information regarding biological drugs. CONCLUSION: To conclude, we suggest widespread use of high-grade biosimilars in clinical practice, maybe via changing, exchanging, or switching, with appropriate clinical monitoring and pharmacovigilance to improve patient accessibility to modern medicines, as it provides similar efficacy and safety parameters across all the accumulated clinical trials and studies.

Unveiling the genetic and epigenetic landscape of colorectal cancer: new insights into pathogenic pathways.

Colorectal cancer (CRC) is a complex disease characterized by genetic and epigenetic alterations, playing a crucial role in its development and progression. This review aims to provide insights into the emerging landscape of these alterations in CRC pathogenesis to develop effective diagnostic tools and targeted therapies. Genetic alterations in signaling pathways such as Wnt/ß-catenin, and PI3K/Akt/mTOR are pivotal in CRC development. Genetic profiling has identified distinct molecular subtypes, enabling personalized treatment strategies. Epigenetic modifications, including DNA methylation and histone modifications, also contribute to CRC pathogenesis by influencing critical cellular processes through gene silencing or activation. Non-coding RNAs have emerged as essential players in epigenetic regulation and CRC progression. Recent research highlights the interplay between genetic and epigenetic alterations in CRC. Genetic mutations can affect epigenetic modifications, leading to dysregulated gene expression and signaling cascades. Conversely, epigenetic changes can modulate genetic expression, amplifying or dampening the effects of genetic alterations. Advancements in understanding pathogenic pathways have potential clinical applications. Identifying genetic and epigenetic markers as diagnostic and prognostic biomarkers promises more accurate risk assessment and early detection. Challenges remain, including validating biomarkers and developing robust therapeutic strategies through extensive research and clinical trials. The dynamic nature of genetic and epigenetic alterations necessitates a comprehensive understanding of their temporal and spatial patterns during CRC progression. In conclusion, the genetic and epigenetic landscape of CRC is increasingly being unraveled, providing valuable insights into its pathogenesis. Integrating genetic and epigenetic knowledge holds great potential for improving diagnostics, prognostics, and personalized therapies in CRC. Continued research efforts are vital to translate these findings into clinical practice, ultimately improving patient outcomes.

Pathophysiological Aspects and Therapeutic Armamentarium of Alzheimer's Disease: Recent Trends and Future Development.

Alzheimer's disease (AD) is the primary cause of dementia and is characterized by the death of brain cells due to the accumulation of insoluble amyloid plaques, hyperphosphorylation of tau protein, and the formation of neurofibrillary tangles within the cells. AD is also associated with other pathologies such as neuroinflammation, dysfunction of synaptic connections and circuits, disorders in mitochondrial function and energy production, epigenetic changes, and abnormalities in the vascular system. Despite extensive research conducted over the last hundred years, little is established about what causes AD or how to effectively treat it. Given the severity of the disease and the increasing number of affected individuals, there is a critical need to discover effective medications for AD. The US Food and Drug Administration (FDA) has approved several new drug molecules for AD management since 2003, but these drugs only provide temporary relief of symptoms and do not address the underlying causes of the disease. Currently, available medications focus on correcting the neurotransmitter disruption observed in AD, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate (NMDA) receptor, which temporarily alleviates the signs of dementia but does not prevent or reverse the course of AD. Research towards disease-modifying AD treatments is currently underway, including gene therapy, lipid nanoparticles, and dendrimer-based therapy. These innovative approaches aim to target the underlying pathological processes of AD rather than just managing the symptoms. This review discusses the novel aspects of pathogenesis involved in the causation of AD of AD and in recent developments in the therapeutic armamentarium for the treatment of AD such as gene therapy, lipid nanoparticles, and dendrimer-based therapy, and many more.

Molnupiravir: an antiviral drug against COVID-19.

SARS-CoV-2, the virus responsible for COVID-19, has caused numerous deaths worldwide and poses significant challenges. Researchers have recently studied a new antiviral drug called molnupiravir for treating COVID-19. This review examines the causes and immunopathogenesis of COVID-19, as well as the role of molnupiravir in its treatment. Molnupiravir is a prodrug of ß-D-N4-hydroxyctytidine (NHC) and has demonstrated activity against various viruses, including MERS-CoV, SARS-CoV, SARS-CoV-2, and influenza virus. The active form of molnupiravir, NHC triphosphate, acts as a nucleoside analog that disrupts viral replication by causing mutations in the viral RNA, thereby inhibiting viral growth. This review summarizes the results of multiple clinical trials that have evaluated the effectiveness of molnupiravir against SARS-CoV-2 and its variants. Animal studies have also shown that molnupiravir significantly reduces the viral load and prevents transmission to other animals. Overall, molnupiravir has demonstrated strong efficacy and reasonable safety, reducing hospitalization rates by nearly 50% among COVID-19-positive individuals at risk of complications. Patients in clinical settings have tolerated molnupiravir well and experienced positive outcomes, such as clearance of viral RNA, decreased viral load, and reduced hospitalization rates. Additionally, compared to a placebo, molnupiravir has been associated with lower mortality rates. Therefore, molnupiravir can be a beneficial drug to treat patients suffering from SARS-CoV-2, and further studies can provide more information about its safety and efficacy.

NF-κB Pathway and Its Inhibitors: A Promising Frontier in the Management of Alzheimer's Disease.

The nuclear factor kappa B (NF-κB) pathway has emerged as a pivotal player in the pathogenesis of various diseases, including neurodegenerative illnesses like Alzheimer's disease (AD). The involvement of the NF-κB pathway in immune system responses, inflammation, oxidative stress, and neuronal survival highlights its significance in AD progression. We discuss the advantages of NF-κB pathway inhibition, including the potential to mitigate neuroinflammation, modulate amyloid beta (Aß) production, and promote neuronal survival. However, we also acknowledge the limitations and challenges associated with this approach. Balancing the fine line between dampening inflammation and preserving physiological immune responses is critical to avoid unintended consequences. This review combines current knowledge on the NF-κB pathway's intricate involvement in AD pathogenesis, emphasizing its potential as a therapeutic target. By evaluating both advantages and limitations, we provide a holistic view of the feasibility and challenges of NF-κB pathway modulation in AD treatment. As the quest for effective AD therapies continues, an in-depth understanding of the NF-κB pathway's multifaceted roles will guide the development of targeted interventions with the potential to improve AD management.

Combating relapsed and refractory Mantle cell lymphoma with novel therapeutic armamentarium: Recent advances and clinical prospects.

Mantle cell lymphoma (MCL) is a rare, aggressive subtype of non-Hodgkin's lymphoma (NHL), accounting for 5% of all cases. Due to its virulence factor, it is an incurable disease and keeps relapsing despite an intensive treatment regimen. Advancements in research and drug discovery have shifted the treatment strategy from conventional chemotherapy to targeted agents and immunotherapies. The establishment of the role of Bruton tyrosine kinase led to the development of ibrutinib, a first-generation BTK inhibitor, and its successors. A conditioning regimen based immunotherapeutic agent like ibritumumob, has also demonstrated a viable response with a favorable toxicity profile. Brexucabtagene Autoleucel, the only approved CAR T-cell therapy, has proven advantageous for relapsed/refractory MCL in both children and adults. This article reviews certain therapies that could help update the current approach and summarizes a few miscellaneous agents, which, seldom studied in trials, could alleviate the regression observed in traditional therapies. DATA AVAILABILITY: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Harnessing three-dimensional (3D) cell culture models for pulmonary infections: State of the art and future directions.

Pulmonary infections have been a leading etiology of morbidity and mortality worldwide. Upper and lower respiratory tract infections have multifactorial causes, which include bacterial, viral, and rarely, fungal infections. Moreover, the recent emergence of SARS-CoV-2 has created havoc and imposes a huge healthcare burden. Drug and vaccine development against these pulmonary pathogens like respiratory syncytial virus, SARS-CoV-2, Mycobacteria, etc., requires a systematic set of tools for research and investigation. Currently, in vitro 2D cell culture models are widely used to emulate the in vivo physiologic environment. Although this approach holds a reasonable promise over pre-clinical animal models, it lacks the much-needed correlation to the in vivo tissue architecture, cellular organization, cell-to-cell interactions, downstream processes, and the biomechanical milieu. In view of these inadequacies, 3D cell culture models have recently acquired interest. Mammalian embryonic and induced pluripotent stem cells may display their remarkable self-organizing abilities in 3D culture, and the resulting organoids replicate important structural and functional characteristics of organs such the kidney, lung, gut, brain, and retina. 3D models range from scaffold-free systems to scaffold-based and hybrid models as well. Upsurge in organs-on-chip models for pulmonary conditions has anticipated encouraging results. Complexity and dexterity of developing 3D culture models and the lack of standardized working procedures are a few of the setbacks, which are expected to be overcome in the coming times. Herein, we have elaborated the significance and types of 3D cell culture models for scrutinizing pulmonary infections, along with the in vitro techniques, their applications, and additional systems under investigation.