Role of Phytonutrients in Nutrigenetics and Nutrigenomics Perspective in Curing Breast Cancer.

Breast cancer (BC) is one of the most common type of cancer and an important contributor to female mortality. Several genes and epigenetic modifications are involved in the development and progression of BC. Research in phytochemistry, nutrigenomics, and nutrigenetics has provided strong evidence that certain phytonutrients are able to modulate gene expression at transcriptional and post-transcriptional levels. Such phytonutrients may also be beneficial to prevent and treat BC. In this review, we will focus on the nutrigenomic effects of various phytochemicals including polyphenols, phytosterols, terpenoids, alkaloids, and other compounds from different sources. Overall, these phytonutrients are found to inhibit BC cell proliferation, differentiation, invasion, metastasis, angiogenesis, and induce apoptotic cell death by targeting various molecular pathways. They also alter epigenetic mechanisms and enhance the chemosensitivity and radiosensitivity of cancer cells. Such phytochemicals may be used for the effective management of BC patients in the clinical setting in the future. The present article aims to summarize the specific molecular pathways involved in the genetic effects of phytochemicals in BC.

Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives.

Withaferin A (WA), a manifold studied, C28-steroidal lactone withanolide found in Withania somnifera. Given its unique beneficial effects, it has gathered attention in the era of modern science. Cancer, being considered a "hopeless case and the leading cause of death worldwide, and the available conventional therapies have many lacunae in the form of side effects. The poly pharmaceutical natural compound, WA treatment, displayed attenuation of various cancer hallmarks by altering oxidative stress, promoting apoptosis, and autophagy, inhibiting cell proliferation, reducing angiogenesis, and metastasis progression. The cellular proteins associated with antitumor pathways were also discussed. WA structural modifications attack multiple signal transduction pathways and enhance the therapeutic outcomes in various diseases. Moreover, it has shown validated pharmacological effects against multiple neurodegenerative diseases by inhibiting acetylcholesterinases and butyrylcholinesterases enzyme activity, antidiabetic activity by upregulating adiponectin and preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ), cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis. The current review is an extensive survey of various WA associated disease targets, its pharmacokinetics, synergistic combination, modifications, and biological activities.

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-ß Cascade in Alzheimer's Disease.

One of the most commonly occurring neurodegenerative disorders, Alzheimer's disease (AD), encompasses the loss of cognitive and memory potential, impaired learning, dementia and behavioral defects, and has been prevalent since the 1900s. The accelerating occurrence of AD is expected to reach 65.7 million by 2030. The disease results in neural atrophy and disrupted inter-neuronal connections. Amongst multiple AD pathogenesis hypotheses, the amyloid beta (Aß) cascade is the most relevant and accepted form of the hypothesis, which suggests that Aß monomers are formed as a result of the cleavage of amyloid precursor protein (APP), followed by the conversion of these monomers to toxic oligomers, which in turn develop ß-sheets, fibrils and plaques. The review targets the events in the amyloid hypothesis and elaborates suitable therapeutic agents that function by hindering the steps of plaque formation and lowering Aß levels in the brain. The authors discuss treatment possibilities, including the inhibition of ß- and γ-secretase-mediated enzymatic cleavage of APP, the immune response generating active immunotherapy and passive immunotherapeutic approaches targeting monoclonal antibodies towards Aß aggregates, the removal of amyloid aggregates by the activation of enzymatic pathways or the regulation of Aß circulation, glucagon-like peptide-1 (GLP-1)-mediated curbed accumulation and the neurotoxic potential of Aß aggregates, bapineuzumab-mediated vascular permeability alterations, statin-mediated Aß peptide degradation, the potential role of ibuprofen and the significance of natural drugs and dyes in hindering the amyloid cascade events. Thus, the authors aim to highlight the treatment perspective, targeting the amyloid hypothesis, while simultaneously emphasizing the need to conduct further investigations, in order to provide an opportunity to neurologists to develop novel and reliable treatment therapies for the retardation of AD progression.

Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson's Disease: A Perspective on Associated Therapeutic Interventions.

Current pharmacotherapy of Parkinson's disease (PD) is symptomatic and palliative, with levodopa/carbidopa therapy remaining the prime treatment, and nevertheless, being unable to modulate the progression of the neurodegeneration. No available treatment for PD can enhance the patient's life-quality by regressing this diseased state. Various studies have encouraged the enrichment of treatment possibilities by discovering the association of the effects of the endocannabinoid system (ECS) in PD. These reviews delineate the reported evidence from the literature on the neuromodulatory role of the endocannabinoid system and expression of cannabinoid receptors in symptomatology, cause, and treatment of PD progression, wherein cannabinoid (CB) signalling experiences alterations of biphasic pattern during PD progression. Published papers to date were searched via MEDLINE, PubMed, etc., using specific key words in the topic of our manuscript. Endocannabinoids regulate the basal ganglia neuronal circuit pathways, synaptic plasticity, and motor functions via communication with dopaminergic, glutamatergic, and GABAergic signalling systems bidirectionally in PD. Further, gripping preclinical and clinical studies demonstrate the context regarding the cannabinoid compounds, which is supported by various evidence (neuroprotection, suppression of excitotoxicity, oxidative stress, glial activation, and additional benefits) provided by cannabinoid-like compounds (much research addresses the direct regulation of cannabinoids with dopamine transmission and other signalling pathways in PD). More data related to endocannabinoids efficacy, safety, and pharmacokinetic profiles need to be explored, providing better insights into their potential to ameliorate or even regress PD.

Psychosocial profile of the patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, disabling entity of unknown aetiology, with negative impact on the patient's life, including psychological patterns. This study assessed multiple psychosocial factors (satisfaction with life, coping mechanisms, emotional profile, mental recognition of the disease and cognition schemes related to patients' demographic characteristics, clinical picture, form and duration of the disease, therapeutic plans) in IBD patients vs. a healthy group. This non-interventional study comprised 60 participants who attended for medical advice/check-up as an ambulatory visit or during hospitalization. The patients completed questionnaires after receiving explanations from the psychologist. Statistical analyses (Kolmogorov-Smirnov test, Independent-Samples t-test, One-Way ANOVA and Post Hoc Multiple Comparisons) were conducted using IMB for the Social Sciences (SPSS), version 20 (P≤0.05). IBD patients (G1) are more hostile when compared to the healthy group (G2). Those who experience abdominal pain are more likely to use active coping mechanisms and those who experience fatigue are more likely to use acceptance, emotional venting, behavioural disengagement and mental disengagement. G1 have higher levels of others-downing vs. G2. Regarding negative emotions, IBD patients generally experience more negative emotions compared to healthy participants (who have higher levels of life satisfaction). Regarding the perception of illness, there are no differences between patients in terms of illness coherence, personal or treatment control, consequences, timeline, or emotional representations. Results indicate that psychological factors and different characteristics of IBD patients play a relevant role in the way these patients deal with their disease.