Pesticides and the Gut Microbiota: Implications for Parkinson's Disease.

Parkinson's disease (PD) affects more people worldwide than just aging alone can explain. This is likely due to environmental influences, genetic makeup, and changes in daily habits. The disease develops in a complex way, with movement problems caused by Lewy bodies and the loss of dopamine-producing neurons. Some research suggests Lewy bodies might start in the gut, hinting at a connection between these structures and gut health in PD patients. These patients often have different gut bacteria and metabolites. Pesticides are known to increase the risk of PD, with evidence showing they harm more than just dopamine neurons. Long-term exposure to pesticides in food might affect the gut barrier, gut bacteria, and the blood-brain barrier, but the exact link is still unknown. This review looks at how pesticides and gut bacteria separately influence PD development and progression, highlighting the harmful effects of pesticides and changes in gut bacteria. We have examined the interaction between pesticides and gut bacteria in PD patients, summarizing how pesticides cause imbalances in gut bacteria, the resulting changes, and their overall effects on the PD prognosis.

Antibacterial and Antioxidant Compounds from the Root Extract of Aloe debrana.

This study was conducted to isolate and identify the chemical compounds from the roots of Aloe debrana (L.) and evaluate their antioxidant and antibacterial activities. From the acetone (99.5%) extract of the roots of this plant, four anthraquinones, such as chrysophanol (1), asphodeline (2), aloesaponarin I (5), and laccaic acid D-methyl ester (6), and a new catechol derivative, 5-allyl-3-methoxybenzene-1,2-diol (3), were isolated and elucidated by different chromatographic and spectroscopic methods together with linoleic acid (4), respectively. Compounds 2, 3, and 4 were reported here for the first time from this plant and compound 3 from the genus Aloe. The compounds were evaluated for their antioxidant activity using H2O2 and DPPH assays and bactericidal activity against S. aureus and E. coli. Compounds 3 and 6 showed highest antioxidant activities with IC50 values of 19.38 ± 0.64 and 32.81 ± 0.78 µg/mL in DPPH, and 28.52 ± 1.08 and 27.31 ± 1.46 µg/mL in H2O2, respectively. The isolated compounds also demonstrated considerable activity towards S. aureus. Among these compounds, compound 3 exhibited the highest activity (91.20 ± 0.12% and 9.14 ± 0.93 mm at 1.0 mg/mL) against this bacterium. The overall results suggest that the isolated compounds may be considered as potential sources of the bioactive agents to be used in the pharmacological, food, and other industries. Moreover, their high sensitivity against S. aureus may also support the use of A. debrana plant in the traditional medicine to treat wounds. Therefore, the isolated compounds are responsible for medicinal properties of this plant.

The Emerging Role of Natural Products in Cancer Treatment.

The exploration of natural products as potential agents for cancer treatment has garnered significant attention in recent years. In this comprehensive review, we delve into the diverse array of natural compounds, including alkaloids, carbohydrates, flavonoids, lignans, polyketides, saponins, tannins, and terpenoids, highlighting their emerging roles in cancer therapy. These compounds, derived from various botanical sources, exhibit a wide range of mechanisms of action, targeting critical pathways involved in cancer progression such as cell proliferation, apoptosis, angiogenesis, and metastasis. Through a meticulous examination of preclinical and clinical studies, we provide insights into the therapeutic potential of these natural products across different cancer types. Furthermore, we discuss the advantages and challenges associated with their use in cancer treatment, emphasizing the need for further research to optimize their efficacy, pharmacokinetics, and delivery methods. Overall, this review underscores the importance of natural products in advancing cancer therapeutics and paves the way for future investigations into their clinical applications.

Reprogramming of urea cycle in cancer: Mechanism, regulation and prospective therapeutic scopes.

Hepatic urea cycle, previously known as ornithine cycle, is the chief biochemical pathway that deals with the disposal of excessive nitrogen in form of urea, resulted from protein breakdown and concomitant condensation of ammonia. Enzymes involved in urea cycle are expressed differentially outside hepatic tissue and are mostly involved in production of arginine from citrulline in arginine-depleted condition. Inline, cancer cells frequently adapt metabolic rewiring to support sufficient biomass production in order to sustain tumor cell survival, multiplication and subsequent growth. For the accomplishment of this aim, metabolic reprogramming in cancer cells is set in way so that cellular nitrogen and carbon repertoire can be utilized and channelized maximally towards anabolic reactions. A strategy to meet such outcome is to cut down unnecessary catabolic reactions and nitrogen elimination. Thus, transfigured urea cycle is a hallmark of neoplasia. During oncogenesis, altered expression and regulation of enzymes involved in urea cycle is a revolutionary approach meet to maximum incorporation of nitrogen for sustaining tumor specific biogenesis. Currently, we have reviewed neoplasm-specific deregulations of urea cycle-enzymes in different types and stages of cancers suggesting its context-oriented dynamic nature. Considering such insight to be valuable in terms of prospective cancer diagnosis and therapeutics adaptive evolution of deregulated urea cycle has been enlightened.

Molecular mechanism of nanomaterials induced liver injury: A review.

The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.

A review on the new age methodologies for early detection of Alzheimer's and Parkinson's disease.

BACKGROUNDS: Neurodegenerative diseases (NDDs) such as Alzheimer's (AD) and Parkinson's (PD) are often diagnosed late, impeding effective treatment; therefore, early detection is imperative. Modern methodologies can serve a pivotal role in fulfilling the crucial need for timely detection and intervention in this context. OBJECTIVES: Evaluate early detection's significance and summarize key technologies (biomarkers, neuroimaging, AI/ML, genetics, digital health) for enhanced diagnostic strategies in AD and PD. METHODS: This study employs a focused descriptive review approach, encompassing analysis of peer-reviewed articles and clinical trials from existing literature, to provide a nuanced exploration of the subject matter. FINDINGS: This review underscores the efficacy of non-invasive biomarkers, biosensors and emerging promising technologies for advancing early diagnosis of AD and PD. CONCLUSION: The landscape of early NDD detection has been reshaped by technology, yet challenges persist, encompassing the domains of validation and ethics. A collaborative effort between medical professionals, researchers and technologists is imperative to effectively address and combat NDDs.

Multifaceted antineoplastic curative potency of novel water-soluble methylimidazole-based oxidovanadium (IV) complex against triple negative mammary carcinoma.

A bunch of complexes harboring vanadium as metal centers have been reported to exhibit a wide array of antineoplastic properties that come under non­platinum metallodrug series and emerge to offer alternative therapeutic strategies from the mechanistic behaviors of platinum-drugs. Though antineoplastic activities of vanado-complexes have been documented against several animal and xenografted human cancers, the definite mechanism of action is yet to unveil. In present study, a novel water soluble 1-methylimidazole substituted mononuclear dipicolinic acid based oxidovanadium (IV) complex (OVMI) has been evaluated for its antineoplastic properties in breast carcinoma both in vitro and in vivo. OVMI has been reported to generate cytotoxicity in human triple negative breast carcinoma cells, MDA-MB-231 as well as in mouse 4T1 cells by priming them for apoptosis. ROS-mediated, mitochondria-dependent as well as ER-stress-evoked apoptotic death seemed to be main operational hub guiding the cytotoxicity of OVMI in vitro. Moreover, OVMI has been noticed to elicit antimetastatic effect in vitro. Therapeutic application of OVMI has been extended on 4T1-based mammary tumor of female Balb/c mice, where it has been found to reduce tumor size, volume and restore general tissue architecture successfully to a great extent. Apart from that, OVMI has been documented to limit 4T1-based secondary pulmonary metastasis along with being non-toxic and biocompatible in vivo.

Formulation of Carnosic-Acid-Loaded Polymeric Nanoparticles: An Attempt to Endorse the Bioavailability and Anticancer Efficacy of Carnosic Acid against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is considered to be one of the most difficult subtypes of breast cancer (BC) to treat. The sheer absence of certain receptors makes it very tough to target, leaving high-dose chemotherapy as probably the sole therapeutic option at the cost of nonspecific toxic effects. Carnosic acid (CA) has been established as a potential chemotherapeutic agent against a range of cancer cells. However, its in vivo chemotherapeutic potential is significantly challenged due to its poor pharmacokinetic attributes. In this study, poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were formulated to circumvent the biopharmaceutical limitations of CA. CA-loaded polymeric NPs (CA-PLGA NPs) have been evaluated as a potential therapeutic option in the treatment of TNBC. Different in vitro studies exhibited that CA-PLGA NPs significantly provoked oxidative-stress-mediated apoptotic death in MDA-MB-231 cells. The improved anticancer potential of CA-PLGA NPs over CA was found to be associated with improved cellular uptake of the nanoformulation by TNBC cells. In vivo studies also established the improvement in the chemotherapeutic efficacy of CA-nanoformulation over that of free CA without showing any sign of systemic toxicity. Thus, CA-PLGA NPs emerge as a promising candidate to fix two bugs with a single code, resolving biopharmaceutical attributes of CA as well as introducing a treatment option for TNBC.

Correction: Mangiferin ameliorates collateral neuropathy in tBHP induced apoptotic nephropathy by inflammation mediated kidney to brain crosstalk.

Correction for 'Mangiferin ameliorates collateral neuropathy in tBHP induced apoptotic nephropathy by inflammation mediated kidney to brain crosstalk' by Sukanya Saha et al., Food Funct., 2019, 10, 5981-5999, https://doi.org/10.1039/C9FO00329K.

Genetic Underpinnings of Pulmonary Fibrosis: An Overview.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disorder, in which genetic and environmental factors are involved in disease onset. Although, by definition, the disease is considered idiopathic in nature, evidence-based studies have indicated familial cases of pulmonary fibrosis, in which genetic factors contribute to IPF pathogenesis. METHODS: Both common as well as rare genetic variants are associated with sporadic as well as familial forms of IPF. Although clinical inferences of the genetic association have still not been explored properly, observation-based studies have found a genotypic influence on disease development and outcome. RESULTS: Based on genetic studies, individuals with a risk of IPF can be easily identified and can be classified more precisely. Identification of genetic variants also helps to develop more effective therapeutic approaches. CONCLUSION: Further comprehensive research is needed to get a blueprint of IPF pathogenesis. The rapidly evolving field of genetic engineering and molecular biology, along with the bioinformatics approach, will possibly explore a new horizon very soon to achieve this goal.

Recent Contributions of Mass Spectrometry-Based "Omics" in the Studies of Breast Cancer.

Breast cancer (BC) is one of the most heterogeneous groups of cancer. As every biotype of BC is unique and presents a particular "omic" signature, they are increasingly characterized nowadays with novel mass spectrometry (MS) strategies. BC therapeutic approaches are primarily based on the two features of human epidermal growth factor receptor 2 (HER2) and estrogen receptor (ER) positivity. Various strategic MS implementations are reported in studies of BC also involving data independent acquisitions (DIAs) of MS which report novel differential proteomic, lipidomic, proteogenomic, phosphoproteomic, and metabolomic characterizations associated with the disease and its therapeutics. Recently many "omic" studies have aimed to identify distinct subsidiary biotypes for diagnosis, prognosis, and targets of treatment. Along with these, drug-induced-resistance phenotypes are characterized by "omic" changes. These identifying aspects of the disease may influence treatment outcomes in the near future. Drug quantifications and characterizations are also done regularly and have implications in therapeutic monitoring and in drug efficacy assessments. We report these studies, mentioning their implications toward the understanding of BC. We briefly provide the MS instrumentation principles that are adopted in such studies as an overview with a brief outlook on DIA-MS strategies. In all of these, we have chosen a model cancer for its revelations through MS-based "omics".

Corrigendum to "Curcumin protects rat liver from streptozotocin-induced diabetic pathophysiology by counteracting reactive oxygen species and inhibiting the activation of p53 and MAPKs mediated stress response pathways" [Toxicol. Rep. 2 (2015) 365-376].

[This corrects the article DOI: 10.1016/j.toxrep.2014.12.017.].