Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder.

The salient features of autism spectrum disorder (ASD) encompass persistent difficulties in social communication, as well as the presence of restricted and repetitive facets of behavior, hobbies, or pursuits, which are often accompanied with cognitive limitations. Over the past few decades, a sizable number of studies have been conducted to enhance our understanding of the pathophysiology of ASD. Preclinical rat models have proven to be extremely valuable in simulating and analyzing the roles of a wide range of established environmental and genetic factors. Recent research has also demonstrated the significant involvement of the endocannabinoid system (ECS) in the pathogenesis of several neuropsychiatric diseases, including ASD. In fact, the ECS has the potential to regulate a multitude of metabolic and cellular pathways associated with autism, including the immune system. Moreover, the ECS has emerged as a promising target for intervention with high predictive validity. Particularly noteworthy are resent preclinical studies in rodents, which describe the onset of ASD-like symptoms after various genetic or pharmacological interventions targeting the ECS, providing encouraging evidence for further exploration in this area.

The role of Aquaporins in tumorigenesis: implications for therapeutic development.

Aquaporins (AQPs) are ubiquitous channel proteins that play a critical role in the homeostasis of the cellular environment by allowing the transit of water, chemicals, and ions. They can be found in many different types of cells and organs, including the lungs, eyes, brain, glands, and blood vessels. By controlling the osmotic water flux in processes like cell growth, energy metabolism, migration, adhesion, and proliferation, AQPs are capable of exerting their regulatory influence over a wide range of cellular processes. Tumour cells of varying sources express AQPs significantly, especially in malignant tumours with a high propensity for metastasis. New insights into the roles of AQPs in cell migration and proliferation reinforce the notion that AQPs are crucial players in tumour biology. AQPs have recently been shown to be a powerful tool in the fight against pathogenic antibodies and metastatic cell migration, despite the fact that the molecular processes of aquaporins in pathology are not entirely established. In this review, we shall discuss the several ways in which AQPs are expressed in the body, the unique roles they play in tumorigenesis, and the novel therapeutic approaches that could be adopted to treat carcinoma.

Helicobacter pylori and Epstein-Barr virus infection in cell polarity alterations.

The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-ß/SMAD, and ß-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells.

The paradigm of miRNA and siRNA influence in Oral-biome.

Short nucleotide sequences like miRNA and siRNA have attracted a lot of interest in Oral-biome investigations. miRNA is a small class of non-coding RNA that regulates gene expression to provide effective regulation of post-transcription. On contrary, siRNA is 21-25 nucleotide dsRNA impairing gene function post-transcriptionally through inhibition of mRNA for homologous dependent gene silencing. This review highlights the application of miRNA in oral biome including oral cancer, dental implants, periodontal diseases, gingival fibroblasts, oral submucous fibrosis, radiation-induced oral mucositis, dental Pulp, and oral lichenoid disease. Moreover, we have also discussed the application of siRNA against the aforementioned disease along with the impact of miRNA and siRNA to the various pathways and molecular effectors pertaining to the dental diseases. The influence of upregulation and downregulation of molecular effector post-treatment with miRNA and siRNA and their impact on the clinical setting has been elucidated. Thus, the mentioned details on application of miRNA and siRNA will provide a novel gateway to the scholars to not only mitigate the long-lasting issue in dentistry but also develop new theragnostic approaches.

Mitochondrial Medicine: A Promising Therapeutic Option Against Various Neurodegenerative Disorders.

Abnormal mitochondrial morphology and metabolic dysfunction have been observed in many neurodegenerative disorders (NDDs). Mitochondrial dysfunction can be caused by aberrant mitochondrial DNA, mutant nuclear proteins that interact with mitochondria directly or indirectly, or for unknown reasons. Since mitochondria play a significant role in neurodegeneration, mitochondriatargeted therapies represent a prosperous direction for the development of novel drug compounds that can be used to treat NDDs. This review gives a brief description of how mitochondrial abnormalities lead to various NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We further explore the promising therapeutic effectiveness of mitochondria- directed antioxidants, MitoQ, MitoVitE, MitoPBN, and dimebon. We have also discussed the possibility of mitochondrial gene therapy as a therapeutic option for these NDDs.

Stem-Cell-Based Therapy: The Celestial Weapon against Neurological Disorders.

Stem cells are a versatile source for cell therapy. Their use is particularly significant for the treatment of neurological disorders for which no definitive conventional medical treatment is available. Neurological disorders are of diverse etiology and pathogenesis. Alzheimer's disease (AD) is caused by abnormal protein deposits, leading to progressive dementia. Parkinson's disease (PD) is due to the specific degeneration of the dopaminergic neurons causing motor and sensory impairment. Huntington's disease (HD) includes a transmittable gene mutation, and any treatment should involve gene modulation of the transplanted cells. Multiple sclerosis (MS) is an autoimmune disorder affecting multiple neurons sporadically but induces progressive neuronal dysfunction. Amyotrophic lateral sclerosis (ALS) impacts upper and lower motor neurons, leading to progressive muscle degeneration. This shows the need to try to tailor different types of cells to repair the specific defect characteristic of each disease. In recent years, several types of stem cells were used in different animal models, including transgenic animals of various neurologic disorders. Based on some of the successful animal studies, some clinical trials were designed and approved. Some studies were successful, others were terminated and, still, a few are ongoing. In this manuscript, we aim to review the current information on both the experimental and clinical trials of stem cell therapy in neurological disorders of various disease mechanisms. The different types of cells used, their mode of transplantation and the molecular and physiologic effects are discussed. Recommendations for future use and hopes are highlighted.

Molecular Insights into Therapeutic Potentials of Hybrid Compounds Targeting Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most complex progressive neurological disorders involving degeneration of neuronal connections in brain cells leading to cell death. AD is predominantly detected among elder people (> 65 years), mostly diagnosed with the symptoms of memory loss and cognitive dysfunctions. The multifarious pathogenesis of AD comprises the accumulation of pathogenic proteins, decreased neurotransmission, oxidative stress, and neuroinflammation. The conventional therapeutic approaches are limited to symptomatic benefits and are ineffective against disease progression. In recent years, researchers have shown immense interest in the designing and fabrication of various novel therapeutics comprised of naturally isolated hybrid molecules. Hybrid therapeutic compounds are developed from the combination of pharmacophores isolated from bioactive moieties which specifically target and block various AD-associated pathogenic pathways. The method of designing hybrid molecules has numerous advantages over conventional multitarget drug development methods. In comparison to in silico high throughput screening, hybrid molecules generate quicker results and are also less expensive than fragment-based drug development. Designing hybrid-multitargeted therapeutic compounds is thus a prospective approach in developing an effective treatment for AD. Nevertheless, several issues must be addressed, and additional researches should be conducted to develop hybrid therapeutic compounds for clinical usage while keeping other off-target adverse effects in mind. In this review, we have summarized the recent progress on synthesis of hybrid compounds, their molecular mechanism, and therapeutic potential in AD. Using synoptic tables, figures, and schemes, the review presents therapeutic promise and potential for the development of many disease-modifying hybrids into next-generation medicines for AD.