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.

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.

A Review on the Recent Applications of Deep Learning in Predictive Drug Toxicological Studies.

Drug toxicity prediction is an important step in ensuring patient safety during drug design studies. While traditional preclinical studies have historically relied on animal models to evaluate toxicity, recent advances in deep-learning approaches have shown great promise in advancing drug safety science and reducing animal use in preclinical studies. However, deep-learning-based approaches also face challenges in handling large biological data sets, model interpretability, and regulatory acceptance. In this review, we provide an overview of recent developments in deep-learning-based approaches for predicting drug toxicity, highlighting their potential advantages over traditional methods and the need to address their limitations. Deep-learning models have demonstrated excellent performance in predicting toxicity outcomes from various data sources such as chemical structures, genomic data, and high-throughput screening assays. The potential of deep learning for automated feature engineering is also discussed. This review emphasizes the need to address ethical concerns related to the use of deep learning in drug toxicity studies, including the reduction of animal use and ensuring regulatory acceptance. Furthermore, emerging applications of deep learning in drug toxicity prediction, such as predicting drug-drug interactions and toxicity in rare subpopulations, are highlighted. The integration of deep-learning-based approaches with traditional methods is discussed as a way to develop more reliable and efficient predictive models for drug safety assessment, paving the way for safer and more effective drug discovery and development. Overall, this review highlights the critical role of deep learning in predictive toxicology and drug safety evaluation, emphasizing the need for continued research and development in this rapidly evolving field. By addressing the limitations of traditional methods, leveraging the potential of deep learning for automated feature engineering, and addressing ethical concerns, deep-learning-based approaches have the potential to revolutionize drug toxicity prediction and improve patient safety in drug discovery and development.

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.

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.

Modifying skin flaps for achieving very large decompressive craniectomies in malignant middle cerebral artery territory infarcts: A technical note.

INTRODUCTION: Decompressive craniectomy is a well described treatment to salvage life in large middle cerebral artery (MCA) territory infarcts. The size of the craniectomy is limited by the size of the skin incision and very large craniectomies need large skin flaps that are prone to necrosis at the wound margins. MATERIAL AND METHODS: We describe two modifications in the skin flap that we have used in 7 patients to achieve very large bony decompressions in malignant MCA infarctions without compromising on flap vascularity. One consists of a linear extension posteriorly from the question mark or reverse question mark incision while the other is an "n" shaped incision. RESULTS: With these modifications we achieved craniectomies of size 15.6-17.8 cm in the anteroposterior and 10.7-12 cm in vertical axis of the bone flap removed in our patients. There were no additional procedural or wound related complications in a 6-month follow up. CONCLUSIONS: Removal of a standard size bone flap may achieve suboptimal decompression in cases of large MCA territory infarctions. Imaginative tailoring of skin flaps helps to remove larger volumes of skull with no added procedural morbidity.

Spinal Subdural Hematoma following Epidural Anesthesia.

The spinal subdural space is an avascular, potential space and is a rare location for intraspinal hematomas. Compared to spinal epidural hematomas, spinal subdural hematomas are uncommonly described complications of lumbar puncture for spinal or epidural anesthesia, particularly in patients who have no pre-existing bleeding disorders or history of antiplatelet or anticoagulant intake. We describe a 19-year-old girl who had a large thoracolumbar spinal subdural hematoma following epidural anesthesia for elective cholecystectomy with no pre-existing bleeding diathesis that caused rapidly developing paraplegia that evolved over the next 2 days following surgery. Nine days after the initial surgery she underwent multilevel laminectomy and surgical evacuation with eventual satisfactory recovery. Even epidural anesthesia without thecal sac violation can result in bleeding in the spinal subdural space. The possible sources of bleed in this space may be from injury to an interdural vein or extravasation of subarachnoid bleed into the subdural space. When neurological deficits occur, prompt imaging is mandatory and early evacuation yields gratifying results.

Postoperative Salvage Decompressive Craniotomy: Usefulness of The Simple Posteriorly Directed Release Incision in Adequately Expanding Frontotemporal Flaps.

Salvage decompressive craniotomies performed following complications after initial planned craniotomies may be inadequate if they are only restricted to removal of the small previously replaced bone flap with some additional nibbling of bone from the surrounding craniotomy margins by retracting the skin. To achieve the aim of adequately decreasing intracranial pressure without affecting wound healing, fresh incisions need to be placed to expand the craniotomy adequately while not compromising vascularity of the scalp. The rationale and safety of the simple posteriorly placed release incision to expand frontotemporal flaps is described.

Formulation and Characterization of Chia (Salvia hispanica) Seed Spread with Incorporation of Sesame (Sesamum indicum) Seed, Watermelon (Citrullus lanatus) Seed, and Pumpkin (Cucurbita pepo) Seed.

The work aims at the production and formulation of plant-based nutritionally enriched butter-like spread products using chia seed, sesame seed, watermelon seed, and pumpkin seed in different ratios, with incorporation of olive oil. The formulated spread butters COB (chia + olive oil), CSOB (chia + sesame + olive oil), CWOB (chia + watermelon + olive oil), and CPOB (chia + pumpkin + olive oil) are of superior quality due to its antioxidant and nutrient content. The antioxidant property of all the formulated spread butter is characterized by total phenolic content (TPC), DPPH free radical scavenging activity, and FRAP assay and the results indicated that CSOB has the highest TPC value of 68.73 ± 0.01 µg GAE/ml and CWOB has the highest DPPH and FRAP activity of 52.30 ± 0.01% and 51.01 ± 0.01 µg of AAE/ml, respectively. The physicochemical properties of all the formulated butter was also analyzed via acid value, peroxide value, and totox value and the results were satisfactory with CPOB having the lowest Totox value of 2.25 ± 0.01. Functional properties of the spread butter are also investigated and the results were satisfactory. All the formulated butters are medicinally and nutritionally beneficial, and it can be used as an alternative to the conventional one.

Segmental Neurofibromatosis.

Segmental neurofibromas are the rarest variant of neurofibromatosis. We describe one such case in a 34-year-old man with multiple subcutaneous swellings in the posterior aspect of the left lower limb.

Coronavirus Disease 2019: A Wake-Up Call for Neurosurgeons to Learn Percutaneous Tracheostomy.

Tracheostomy is a commonly performed operation in neurosurgical patients. It is an aerosol generating procedure and is considered a high-risk operation in times of the coronavirus disease 2019 pandemic. Though percutaneous tracheostomy has been around for some time, many neurosurgeons still perform open surgical tracheostomy as they have been trained in doing so and are well versed with the procedure. However, this pandemic is a wake-up call for them to learn a new skill that is simple, quick, and has several advantages over the traditional method.

Everted Pedicled Temporalis Fascial Flap to Augment Pedicled Pericranial Flap for Lax Duraplasty in Decompressive Craniotomy: A Cost-Effective Procedure.

Decompressive craniotomy is a commonly performed surgery to relieve raised intracranial pressure. At the end of the procedure, it is the convention to cover the exposed brain by performing a lax duraplasty which allows for both brain expansion and provides protection to the underlying parenchyma. Various commercially available dural substitutes are used for this purpose. These have the drawback of being both expensive and nonvascularized. We propose a technique of using pericranium along with everted temporalis fascia (both being locally harvested vascularized pedicle flaps) that can suffice in a vast majority of cases for covering the brain.

Alterations of thyroidal status in brain regions and hypothalamo-pituitary-blood-thyroid-axis associated with dopaminergic depletion in substantia nigra and ROS formation in different brain regions after MPTP treatment in adult male mice.

MPTP produces oxidative stress, damages niagrostriatal dopaminergic neurons and develops Parkinsonism in rodents. Due to paucity of information, the thyroidal status in brain regions and peripheral tissues during different post-treatment days in MPTP-induced mice had been executed in the present study. MPTP depleted tyrosine hydroxylase protein expressions that signify the dopaminergic neuronal damage in substantia nigra. MPTP elevated ROS formation differentially in brain regions (cerebral cortex, hippocampus, substantia nigra) with maximal elevation at hippocampus. The changes in thyroid hormone (T4 and T3) levels indicate that brain regions might combat the adverse situation by keeping the levels of thyroid hormones either unchanged or in the elevated conditions in the latter phases (day-3 and day-7), apart from the depletion of thyroid hormones in certain brain regions (T4 in SN and hippocampus, T3 in hippocampus) as the immediate (day-1) effects after MPTP treatment. MPTP caused alterations of cellular morphology, RNA:Protein ratio and TPO protein expression, concomitantly depleted TPO mRNA expression and elevated TSH levels in the thyroid gland. Although T4 levels changed differentially, T3 levels remained unaltered in thyroid gland throughout the post-treatment days. Results have been discussed mentioning the putative role of T4 and TSH in apoptosis and/or proliferation/differentiation of thyrocytes. In blood, T4 levels remained unchanged while the changes in T3 and TSH levels did not signify the clinical feature of hypo/hyperthyroidism of animals. In the pituitary, both T4 and T3 levels remained elevated where TSH differentially altered (elevated followed by depletion) during post-treatment days. Notably, T4, T3 and TSH levels did not alter in hypothalamus except initial (day-1) depletion of the T4 level. Therefore, the feedback control mechanism of hypothalamo-pituitary-blood-thyroid-axis failed to occur after MPTP treatment. Overall, MPTP altered thyroidal status in the brain and peripheral tissues while both events might occur in isolation as well.

TNFR2 mediated TNF-α signaling and NF-κB activation in hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice.

1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) -induced neuroinflammation and its impact in hippocampus remain elusive till date. Our present study includes the time dependent changes of inflammatory molecules in mouse hippocampus during MPTP treatment. MPTP treatment increased level of TNF-α, enhanced expression of TNFR2 along with PI3 kinase (PI3K) induced phosphorylation of Akt resulting in persistent nuclear factor-κB (NF-κB) activation. The expressions gradually increased from Day1 post-MPTP treatment, maximally at Day3 post-treatment. MPTP induced translocation of p65 and p52, two subunits of NF-κB family, to nucleus where they had been found to dimerize. Therefore, MPTP induced TNF-α signaling through TNFR2 mediated pathway and recruited p65-p52 dimer in hippocampal nucleus which is reported to have protective effect on hippocampal neurons indicated by unchanged neuronal count in hippocampus in treated groups with respect to control. Our finding suggests that this unique NF-κB dimer plays some role in providing inherent protection to hippocampus during MPTP-treatment.

Sustaining immunity during starvation in bivalve mollusc: A costly affair.

Complete or partial depletion of resource in a freshwater habitat is a common phenomenon. As a consequence, aquatic fauna including bivalve molluscs may be exposed to dietary stress on a seasonal basis. Haemocyte based innate immune profile of the freshwater mollusc Lamellidens marginalis (Bivalvia: Eulamellibranchiata) was evaluated under starvation induced stress for a maximum period of 32 days in a controlled laboratory condition. During starvation, the bivalve haemocytes maintained a homeostasis in phagocytic efficacy and nitric oxide generation ability with respect to the control. The mollusc maintained a significantly high protein content in its haemolymph and tissues under the nutritional stress with respect to the control. The dietary stress had no significant impact on the activity of digestive tissue derived α-amylase till sixteenth day but by 32 days the enzyme activity went down significantly. The histopathological profile revealed that the bivalve was adapted to maintain a steady immune profile by incurring degeneration of its own tissue structure. The total haemocyte count surged significantly till 16 days but differed insignificantly with respect to the control at 32 days implying probable haematopoietic exhaustion. The study reflects the instinctive urge of the bivalve to maintain immune physiology at heavy metabolic cost under nutrient limited condition.

Alteration of nuclear factor-kappaB pathway promote neuroinflammation depending on the functions of estrogen receptors in substantia nigra after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment.

The simultaneous role of neuroprotective estrogen and neurodegenerative inflammation during the progression of Parkinson's disease (PD) is still remaining elusive. The novel importance of the present study in MPTP mediated mouse model of Parkinson's disease (PD) is-to investigate the status of neuronal and glial cells in a time chase experiment; to explore which pathway of NF-kappaB exist to proceed the neuroinflammation; to investigate the status of estrogen and the activation pattern of nuclear or cytosolic estrogen receptors in either sexes of Swiss albino mice during MPTP mediated progressive neurodegeneration in the substantia nigra. After MPTP intoxication, the nigral molecular anatomy was changed differently in separate time interval during the progression of neurodegeneration with/without association of glial cells and functional (via its nuclear and cytosolic receptors) estrogen level. Both the canonical and/or non-canonical pathways of NF-kappaB exist in the substantia nigra of both the sexes after MPTP treatment that is why inspite of presence of estrogen, neuroinflammation progresses. The homodimeric or heterodimeric form of ER-beta binds with NF-kappaB molecules p65 and RelB differently, but the canonical or non-canonical pathways of NF-kappaB molecules could not be stopped or may be promoted.