Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma.

Medulloblastoma is a type of brain cancer that primarily affects children. While chemotherapy has been shown to be effective in treating medulloblastoma, the development of chemotherapy resistance remains a challenge. One potential therapeutic approach is to selectively inhibit the inducible transcription factor called STAT3, which is known to play a crucial role in the survival and growth of tumor cells. The activation of STAT3 has been linked to the growth and progression of various cancers, including medulloblastoma. Inhibition of STAT3 has been shown to sensitize medulloblastoma cells to chemotherapy, leading to improved treatment outcomes. Different approaches to STAT3 inhibition have been developed, including small-molecule inhibitors and RNA interference. Preclinical studies have shown the efficacy of STAT3 inhibitors in medulloblastoma, and clinical trials are currently ongoing to evaluate their safety and effectiveness in patients with various solid tumors, including medulloblastoma. In addition, researchers are also exploring ways to optimize the use of STAT3 inhibitors in combination with chemotherapy and identify biomarkers that can predict treatment that will help to develop personalized treatment strategies. This review highlights the potential of selective inhibition of STAT3 as a novel approach for the treatment of medulloblastoma and suggests that further research into the development of STAT3 inhibitors could lead to improved outcomes for patients with aggressive cancer.

Fluoride-Induced Mitochondrial Dysfunction and Approaches for Its Intervention.

Fluoride is present everywhere in nature. The primary way that individuals are exposed to fluoride is by drinking water. It's interesting to note that while low fluoride levels are good for bone and tooth growth, prolonged fluoride exposure is bad for human health. Additionally, preclinical studies link oxidative stress, inflammation, and programmed cell death to fluoride toxicity. Moreover, mitochondria play a crucial role in the production of reactive oxygen species (ROS). On the other hand, little is known about fluoride's impact on mitophagy, biogenesis, and mitochondrial dynamics. These actions control the growth, composition, and organisation of mitochondria, and the purification of mitochondrial DNA helps to inhibit the production of reactive oxygen species and the release of cytochrome c, which enables cells to survive the effects of fluoride poisoning. In this review, we discuss the different pathways involved in mitochondrial toxicity and dysfunction induced by fluoride. For therapeutic approaches, we discussed different phytochemical and pharmacological agents which reduce the toxicity of fluoride via maintained by imbalanced cellular processes, mitochondrial dynamics, and scavenging the ROS.

The fluorosis conundrum: bridging the gap between science and public health.

Fluorosis, a chronic condition brought on by excessive fluoride ingestion which, has drawn much scientific attention and public health concern. It is a complex and multifaceted issue that affects millions of people worldwide. Despite decades of scientific research elucidating the causes, mechanisms, and prevention strategies for fluorosis, there remains a significant gap between scientific understanding and public health implementation. While the scientific community has made significant strides in understanding the etiology and prevention of fluorosis, effectively translating this knowledge into public health policies and practices remains challenging. This review explores the gap between scientific research on fluorosis and its practical implementation in public health initiatives. It suggests developing evidence-based guidelines for fluoride exposure and recommends comprehensive educational campaigns targeting the public and healthcare providers. Furthermore, it emphasizes the need for further research to fill the existing knowledge gaps and promote evidence-based decision-making. By fostering collaboration, communication, and evidence-based practices, policymakers, healthcare professionals, and the public can work together to implement preventive measures and mitigate the burden of fluorosis on affected communities. This review highlighted several vital strategies to bridge the gap between science and public health in the context of fluorosis. It emphasizes the importance of translating scientific evidence into actionable guidelines, raising public awareness about fluoride consumption, and promoting preventive measures at individual and community levels.

Role of Flavonoids in Modulation of Mitochondria Dynamics during Oxidative Stress.

BACKGROUND: Flavonoids are a widespread category of naturally occurring polyphenols distinguished by the flavan nucleus in plant-based foods and beverages, known for their various health benefits. Studies have suggested that consuming 150-500 mg of flavonoids daily is beneficial for health. Recent studies suggest that flavonoids are involved in maintaining mitochondrial activity and preventing impairment of mitochondrial dynamics by oxidative stress. OBJECTIVE: This review emphasized the significance of studying the impact of flavonoids on mitochondrial dynamics, oxidative stress, and inflammatory response. METHODS: This review analysed and summarised the findings related to the impact of flavonoids on mitochondria from publicly available search engines namely Pubmed, Scopus, and Web of Science. DESCRIPTION: Any disruption in mitochondrial dynamics can contribute to cellular dysfunction and diseases, including cancer, cardiac conditions, and neurodegeneration. Flavonoids have been shown to modulate mitochondrial dynamics by regulating protein expression involved in fission and fusion events. Furthermore, flavonoids exhibit potent antioxidant properties by lowering the production of ROS and boosting the performance of antioxidant enzymes. Persistent inflammation is a characteristic of many different disorders. This is because flavonoids also alter the inflammatory response by controlling the expression of numerous cytokines and chemokines involved in the inflammatory process. Flavonoids exhibit an impressive array of significant health effects, making them an effective therapeutic agent for managing various disorders. Further this review summarised available mechanisms underlying flavonoids' actions on mitochondrial dynamics and oxidative stress to recognize the optimal dose and duration of flavonoid intake for therapeutic purposes. CONCLUSION: This review may provide a solid foundation for developing targeted therapeutic interventions utilizing flavonoids, ultimately benefiting individuals afflicted with various disorders.

Neuroprotective effect by naringin against fluorosis-induced neurodegeneration in adult Wistar rats.

Fluorosis is widespread in several areas of the world and including India leading to dental and skeletal fluorosis as well as neurological manifestations. With a limited number of treatment options available, we have tried to address the issue with a nutraceutical such as naringin which is an alkaloid derived from the citrus fruit. Naringin is a potent antioxidant and has neuroprotective action which can counteract the redox imbalance induced by sodium fluoride ingestion. Neurological effects of fluorosis were evaluated in Wistar rats by open field test (OFT) and novel object recognition test (NORT) along with lipid peroxidation (LPO) and glutathione estimation in brain homogenate and cresyl violet staining of CA3 neurons in the hippocampus. Animals were divided into groups namely, normal, vehicle, fluoride, naringin 100 mg/kg bd.wt group and fluoride with naringin (FLU-NAR) group. Fluorosis was induced by providing 100 ppm of sodium fluoride ad libitum in drinking water for 30 days and prophylactic treatment of naringin for 15 days per oral. OFT, NORT and forced swim test showed significant (P ≤ 0.05) changes in the FLU-NAR group as compared to the fluoride group indicating behavioral changes in the fluoride group and positive changes in the FLU-NAR group with attenuation of stress, fear, hyperactivity and memory impairment. The decrease in LPO and increase in glutathione levels in the treatment group compared to the fluoride group were supported by histological improvement as compared to the fluoride group. Prophylactic treatment of naringin showed its possible neuroprotective effect, thus giving an alternative treatment strategy to deal with neurological manifestations of fluorosis.