Profile of diseases prevalent in Datia District of Madhya Pradesh, India.

Background and objectives: Exploring the disease profile in a defined area helps policymakers to understand local health issues. It is essential to collect such information in countries, like India, which have a wide range of socioeconomic, geographic, and cultural diversity. Madhya Pradesh is the second largest state of India and has diversified populations living in urban, rural, and tribal areas. In this study, we performed a hospital record-based analysis to find out the status of different diseases in various outpatient departments (OPDs) of the District Hospital where patients from both rural and urban areas are treated. Materials and methods: The retrospective data was collected from medical records available for the period September 2018 to September 2020. These datasets were analyzed to determine the most common presentations among patients. Results and conclusions: A total of 138,756 records of patients were available for this study, whose department-wise analysis revealed that most records were related to respiratory tract infection, superficial dermatophytosis, anemia among women, suppurative otitis media, and pneumonia. This study provides a broad overview of the overall health issues of people living in rural and urban areas of Datia. However, a major limitation of the study was that other correlations with age and gender were not established due to the absence of such information. Nonetheless, these findings will help policymakers and researchers to set the agenda for interventions and set goals for achieving better health for all people including those living in rural and tribal regions.

Repurposing antipsychotics of the diphenylbutylpiperidine class for cancer therapy.

The recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium channel. A correlation has been found that patients treated for schizophrenia have lower incidences of certain types of cancer, such as respiratory, prostate, and bladder cancers. These compounds have also been shown to inhibit cancer proliferation in a variety of cancer cells, including melanoma, lung carcinoma, breast cancer, pancreatic cancer, glioma, and prostate cancer, among others. Antipsychotic drugs induce apoptosis and suppress metastasis in in vitro and in vivo models through mechanisms involving p53, STAT3, STAT5, protein phosphatase 2A, cholesterol homeostasis, integrins, autophagy, USP1, wnt/ß-catenin signaling, and DNA repair. Additionally, pre-clinical evidence suggests that penfluridol and pimozide act synergistically with existing chemotherapeutic agents, such as dasatinib, temozolomide, and cisplatin. Some studies have also reported that the cytotoxic activity of the antipsychotics is selective for dividing cells. Based on this growing body of evidence and the availability and previous FDA-approval of the drugs, the compounds appear to be promising anti-cancer agents.

Low Dose of Penfluridol Inhibits VEGF-Induced Angiogenesis.

: Metastasis is considered a major burden in cancer, being responsible for more than 90% of cancer-related deaths. Tumor angiogenesis is one of the main processes that lead to tumor metastasis. Penfluridol is a classic and commonly used antipsychotic drug, which has a great ability to cross the blood-brain barrier. Recent studies have revealed that penfluridol has significant anti-cancer activity in diverse tumors, such as metastatic breast cancer and glioblastoma. Here, we aim to identify the effect of low doses of penfluridol on tumor microenvironment and compare it with its effect on tumor cells. Although low concentration of penfluridol was not toxic for endothelial cells, it blocked angiogenesis in vitro and in vivo. In vitro, penfluridol inhibited VEGF-induced primary endothelial cell migration and tube formation, and in vivo, it blocked VEGF- and FGF-induced angiogenesis in the matrigel plug assay. VEGF-induced VEGFR2 phosphorylation and the downstream p38 and ERK signaling pathways were not affected in endothelial cells, although VEGF-induced Src and Akt activation were abrogated by penfluridol treatment. When cancer cells were treated with the same low concentration of penfluridol, basal Src activation levels were mildly impaired, thus impacting their cell migration and wound healing efficiency. The potential of cancer-induced paracrine effect on endothelial cells was explored, although that did not seem to be a player for angiogenesis. Overall, our data demonstrates that low penfluridol levels, similar to the ones clinically used for anti-psychotic conditions, suppress angiogenic efficiency in the tumor microenvironment.

Role of Phytochemicals in Cancer Prevention.

The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.