An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders.

Neuroinflammation is the major cause of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Currently available drugs present relatively low efficacy and are not capable of modifying the course of the disease or delaying its progression. Identifying well-tolerated and brain-penetrant agents of plant origin could fulfil the pressing need for novel treatment techniques for neuroinflammation. Attention has been drawn to a large family of flavonoids in citrus fruits, which may function as strong nutraceuticals in slowing down the development and progression of neuroinflammation. This review is aimed at elucidating and summarizing the effects of the flavonoid tangeretin (TAN) in the management of neuroinflammation-mediated neurodegenerative disorders. A literature survey was performed using various resources, including ScienceDirect, PubMed, Google Scholar, Springer, and Web of Science. The data revealed that TAN exhibited immense neuroprotective effects in addition to its anti-oxidant, anti-diabetic, and peroxisome proliferator-activated receptor-γ agonistic effects. The effects of TAN are mainly mediated through the inhibition of oxidative and inflammatory pathways via regulating multiple signaling pathways, including c-Jun N-terminal kinase, phosphoinositide 3-kinase, mitogen-activated protein kinase, nuclear factor erythroid-2-related factor 2, extracellular-signal-regulated kinase, and CRE-dependent transcription. In conclusion, the citrus flavonoid TAN has the potential to prevent neuronal death mediated by neuroinflammatory pathways and can be developed as an auxiliary therapeutic agent in the management of neurodegenerative disorders.

Heat shock protein paradigms in cancer progression: future therapeutic perspectives.

Heat-shock proteins (HSPs), also known as stress proteins, are ubiquitously present in all forms of life. They play pivotal roles in protein folding and unfolding, the formation of multiprotein complexes, the transportation and sorting of proteins into their designated subcellular compartments, the regulation of the cell cycle, and signalling processes. These HSPs encompass HSP27, HSP40, HSP70, HSP60, and HSP90, each contributing to various cellular functions. In the context of cancer, HSPs exert influence by either inhibiting or activating diverse signalling pathways, thereby impacting growth, differentiation, and cell division. This article offers an extensive exploration of the functions of HSPs within the realms of pharmacology and cancer biology. HSPs are believed to play substantial roles in the mechanisms underlying the initiation and progression of cancer. They hold promise as valuable clinical markers for cancer diagnosis, potential targets for therapeutic interventions, and indicators of disease progression. In times of cellular stress, HSPs function as molecular chaperones, safeguarding the structural and functional integrity of proteins and aiding in their proper folding. Moreover, HSPs play a crucial role in cancer growth, by regulating processes such as angiogenesis, cell proliferation, migration, invasion, and metastasis.

Novel therapeutic targets to halt the progression of Parkinson's disease: an in-depth review on molecular signalling cascades.

Recent research has focused mostly on understanding and combating the neurodegenerative mechanisms and symptoms of Parkinson's disease (PD). Moreover, developing novel therapeutic targets to halt the progression of PD remains a key focus for researchers. As yet, no agents have been found to have unambiguous evidence of disease-modifying actions in PD. The primary objective of this review is to summarize the promising targets that have recently been uncovered which include histamine 4 receptors, beta2 adrenergic receptor, phosphodiesterase 4, sphingosine-1-phosphate receptor subtype 1, angiotensin receptors, high-mobility group box 1, rabphilin-3A, purinergic 2Y type 12 receptor, colony-stimulating factor-1 receptor, transient receptor potential vanilloid 4, alanine-serine-cysteine transporter 2, G protein-coupled oestrogen receptor, a mitochondrial antiviral signalling protein, glucocerebrosidase, indolamine-2,3-dioxygenase-1, soluble epoxy hydroxylase and dual specificity phosphatase 6. We have also reviewed the molecular signalling cascades of those novel targets which cause the initiation and progression of PD and gathered some emerging disease-modifying agents that could slow the progression of PD. These approaches will assist in the discovery of novel target molecules, for curing disease symptoms and may provide a glimmer of hope for the treatment of PD. As of now, there is no drug available that will completely prevent the progression of PD by inhibiting the pathogenesis involved in PD, and thus, the newer targets and their inhibitors or activators are the major focus for researchers to suppress PD symptomatology. And the major limitations of these targets are the lack of clinical data and less number pre-clinical data, as we have majorly discussed the different targets which all have well reported for other disease pathogenesis. Thus, finding the disease-drug interactions, the molecular mechanisms, and the major side effects will be major challenges for the researchers.

Antiepileptic Drugs-Induced Enuresis in Children: An Overview.

Objective: To evaluate enuresis-induced antiepileptic drugs in children. Data Sources: A PubMed search (1917 to July 2020) was performed using the following keywords and associated medical subject headings: antiepileptic drugs, enuresis, pediatric population, drug-induced enuresis, and epilepsy. Study Selection and Data Extraction: The search was conducted to find the role of antiepileptic drugs-induced enuresis in children in studies published in English. Data Synthesis: Enuresis or bedwetting is an underreported adverse drug reaction of antiepileptic drugs. Owing to that fact, it is a condition that is outgrown with age and also could cause embarrassment. As antiepileptic drugs sometimes need to be taken for a long duration until epilepsy relapses, the occurrence of enuresis in this situation can be troublesome for both the child and the caretaker. Even though enuresis is proposed to have a significant effect on the child's psychology, it is still considered to be a condition that is outgrown with age. This article includes a review of antiepileptic drugs reported to have caused enuresis in children. Conclusions: If a child develops enuresis as an adverse drug reaction, this adds further challenges to their life. A better understanding of this potential adverse effect may help prevent unwanted stress. Though the exact mechanisms are not known, the hypothesis generated is from the occurred cases, most of which relapsed when the drug was withdrawn. Considering the gravity of epilepsy in children, more detailed studies need to be conducted on this adverse effect to ensure a safe and effective treatment in children.

A combination of resveratrol and 3,3'-diindolylmethane, a potent radioprotector.

PURPOSE: Exposure to ionizing radiation causes damage to the genomic integrity and stability of the cell. Though a large number of molecules have been studied for their radioprotective capability, no single agent is available today that meets all the requirements of a good radiprotector. In this study, we have investigated a combination of Resveratrol (RSV) and 3,3'-Diindolyl methane (DIM) for its efficacy for radioprotection. It is our hypothesis that this combination that possesses less toxicity than synthetic compounds, free radical scavenging potential, and the capacity to interfere with the several of the signaling cascades that trigger damage to cell by ionizing radiation may possess good radioprotective capability. MATERIALS AND METHODS: Mice were pre-treated with a combination of RSV and DIM and the 30-day mortality assay, endogenous antioxidant levels in intestinal mucosa, metaphase chromosomal aberrations, and micronuclei formation were assessed after exposed to ionizing radiation. RESULTS: The dose modifying factor (DRF) obtained for RSV, DIM, and the combination is 1.15, 1.17, and 1.3, respectively. Pre-treatment of mice with the combination results in significant (***p = .001) protection of the endogenous antioxidant levels, chromosomal aberrations, micronuclei formation, after exposure to ionizing radiation. CONCLUSIONS: Our findings suggest that pre-treatment with the combination of RSV and DIM protects effectively from the ionizing radiation-induced damage at the molecular, cellular, and tissue levels by counteracting both the direct and indirect effects.