Alkaloid-based modulators of the PI3K/Akt/mTOR pathway for cancer therapy: Understandings from pharmacological point of view.

This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.

Polyphenols Targeting MAP Kinase Signaling Pathway in Neurological Diseases: Understanding Molecular Mechanisms and Therapeutic Targets.

Polyphenols are a class of secondary metabolic products found in plants that have been extensively studied for how well they regulate biological processes, such as the proliferation of cells, autophagy, and apoptosis. The mitogen-activated protein kinase (MAPK)-mediated signaling cascade is currently identified as a crucial pro-inflammatory pathway that plays a significant role in the development of neuroinflammation. This process has been shown to contribute to the pathogenesis of several neurological conditions, such as Alzheimer's disease (AD), Parkinson's disease (PD), CNS damage, and cerebral ischemia. Getting enough polyphenols through eating habits has resulted in mitigating the effects of oxidative stress (OS) and lowering the susceptibility to associated neurodegenerative disorders, including but not limited to multiple sclerosis (MS), AD, stroke, and PD. Polyphenols possess significant promise in dealing with the root cause of neurological conditions by modulating multiple therapeutic targets simultaneously, thereby attenuating their complicated physiology. Several polyphenolic substances have demonstrated beneficial results in various studies and are presently undergoing clinical investigation to treat neurological diseases (NDs). The objective of this review is to provide a comprehensive summary of the different aspects of the MAPK pathway involved in neurological conditions, along with an appraisal of the progress made in using polyphenols to regulate the MAPK signaling system to facilitate the management of NDs.

Epidemiological Profile of Helicobacter pylori Infection in Patients with Digestive Symptoms in Algeria.

BACKGROUND: The purpose of this study was to assess the prevalence of Helicobacter pylori infection in Algerian patients with peptic disorders and evaluate the impact of different epidemiological factors (age, sex, sampling site, presence or absence of H. pylori, and type of pathology related to this bacterium). METHODS: We undertook a retrospective and descriptive study on a series of 735 symptomatic patients identified in the laboratory of pathological anatomy at Hassani Abdelkader University Hospital Center of Sidi Bel Abbes, Algeria, over a period of 16 years from January 2002 to December 2017. All patients had benefited from a high gastroscopic fibroscopy and the diagnosis was made by histological examination (hematoxylin-eosin staining). The epidemiological factors, as well as the main gastric diseases related to this bacterium, were studied. RESULTS: The prevalence of H. pylori infection was 66.12%. The infection was more important in the age group 60-69 years (71.43%). The prevalence of H. pylori infection was statistically higher in women than in men (69.3% vs. 60.7%, p < 0.01).The antral region was most colonized by H. pylori (71.73%). In addition, the infection was associated mainly with atrophic gastritis (69.65%). CONCLUSION: In this context, the identification of epidemiological data would be of great value in guiding strategies to control the spread of this bacterium.