PRAME Expression in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Risk factors include extensive sun damage, infection with Merkel cell polyomavirus, and an immunocompromised state. PRAME, also known as preferentially expressed antigen in melanoma, is a cancer-testis antigen recently found to be a useful diagnostic tool in the workup of melanocytic neoplasms. However, the expression pattern of PRAME in Merkel cell carcinoma is unknown. In this study, we examine PRAME expression in Merkel cell carcinoma and explore its prognostic implications. The institutional archives at the University of Virginia were used to search for tumors classified as Merkel cell carcinoma from 2004 to 2022. All potential cases were reviewed to confirm the diagnosis, and electronic medical records were searched for clinical and demographic data. Tumors were subsequently immunostained for PRAME and Merkel cell polyomavirus. Cox proportional hazards regression models were used to estimate relative (all-cause) survival of PRAME positivity and MCPyV positivity in our study as well as MCC-specific survival of PRAME positivity. Univariate and multivariable models were created for each outcome related to all-cause survival. A total of 39 cases were included in the study. Twenty-eight percent (11 cases) demonstrated strong PRAME expression, and 27% of cases were positive for Merkel cell polyomavirus. There was no statistically significant correlation between PRAME expression and virus positivity. With respect to PRAME, the adjusted all-cause mortality hazard ratio was 11.4 (95% CI: 1.8, 70.8). The unadjusted MCC-specific hazard ratio was 4.6 (95% CI: 0.8, 27.5). The adjusted hazard ratio pertaining to Merkel cell polyomavirus infection was 0.25 (95% CI: 0.02, 2.96). In this limited cohort, PRAME expression appears to correlate with worse outcomes in Merkel cell carcinoma.

Clarifying the Dominant Role of Crystallinity and Molecular Orientation in Differently Processed Thin Films of Regioregular Poly(3-hexylthiophene).

Conjugated polymers (CPs) offer the potential for sustainable semiconductor devices due to their low cost and inherent molecular self-assembly. Enhanced crystallinity and molecular orientation in thin films of solution-processable CPs have significantly improved organic electronic device performance. In this work, three methods, namely spin coating, dip coating, and unidirectional floating-film transfer method (UFTM), were utilized with their parametric optimization for fabricating RR-P3HT films. These films were then utilized for their characterization via optical and microstructural analysis to elucidate dominant roles of molecular orientation and crystallinity in controlling charge transport in organic field-effect transistors (OFETs). OFETs fabricated by RR-P3HT thin films using spin coating and dip coating displayed field-effect mobility (µ) of 8.0 × 10-4 cm2V-1s-1 and 1.3 × 10-3 cm2V-1s-1, respectively. This two-time enhancement in µ for dip-coated films was attributed to its enhanced crystallinity. Interestingly, UFTM film-based OFETs demonstrated µ of 7.0 × 10-2 cm2V-1s-1, >100 times increment as compared to its spin-coated counterpart. This superior device performance is attributed to the synergistic influence of higher crystallinity and molecular orientation. Since the crystallinity of dip-coated and UFTM-thin films are similar, ~50 times improved µ of UFTM thin films, this suggests a dominant role of molecular orientation as compared to crystallinity in controlling the charge transport.

Developing In2S3 upon modified MgTiO3 anchored on nitrogen-doped CNT for sustainable sensing and removal of toxic insecticide clothianidin.

Herein, the study introduces a novel bifunctional In2S3/MgTiO3/TiO2@N-CNT (IMTNC) nanocomposite, which is poised to revolutionize the detection and removal of clothianidin (CLD) from aquatic environments by synergistic adsorption and photodegradation. Confirmation of the material's synthesis was done using structural, optical, morphological, and chemical characterizations. An outstanding sensitivity of 2.168 µA/nM.cm2 with a linear range of 4-100 nM and a LOD of 0.04 nM, along with an exceptional elimination efficiency of 98.06 ± 0.84% for about 10 ppm CLD within 18 min was demonstrated by the IMTNC nanocomposite. Extensive studies were carried out to appraise the material's effectiveness in the presence of various interfering species, such as cations, anions, organic compounds, and different water matrices, and a comprehensive assessment of its stability throughout several cycles was made. Response Surface Methodology (RSM) study was used to determine the ideal removal conditions for improved performance. In addition, the catalytic performance in removing various other pollutants was also analyzed. Adding In2S3 and developing N-doped Carbon Nanotubes (N-CNT) increased conductivity and higher electrochemical sensing skills, improving charge transfer and increasing photocatalytic activity. This research underscores the potential of the IMTNC nanocomposite as a promising candidate for advanced environmental sensing and remediation applications.

Upper Extremity Surgeon Recommendations for Imaging Do Not Correspond with Imaging Appropriateness Guidelines.

Background: Utilization of magnetic resonance imaging (MRI) and computed tomography (CT) increases annually, raising concerns about overuse. Imaging appropriateness guidelines have the potential to standardize decisions regarding imaging based on best evidence, which might reduce unhelpful or potentially misleading imaging. We studied expert use of advanced imaging for musculoskeletal illness compared to published appropriateness recommendations. Methods: First, 15 imaging guidelines with recommendations for advanced imaging of the upper extremity were collated. Next, members of the Science of Variation Group (SOVG) were invited to participate in a survey of 11 patient scenarios of common upper extremity illnesses and asked whether they would recommend MRI or CT. Guideline recommendations for imaging were compared with surgeon recommendations using Fisher's exact tests. We used Fleiss' kappa to measure the interobserver agreement among surgeons. Results: For the 11 scenarios, most imaging appropriateness guidelines suggested that MRI or CT is useful, while most surgeons (n = 108) felt it was not. There was no correlation between surgeons and guidelines recommendations for imaging (ρ = 0.28; p = 0.40). There was slight agreement among surgeons regarding imaging recommendations (kappa: 0.17; 95% confidence interval: 0.023-0.32). Conclusion: The available imaging appropriateness guidelines appear to be too permissive and therefore seem to have limited clinical utility for upper extremity surgeons. The notable surgeon-to-surgeon variation (unreliability) in recommendations for advanced imaging in this and other studies suggests a role for strategies to ensure that patient decisions about imaging are consistent with their values (what matters most to them) and not unduly influenced by patient misconceptions about imaging or by surgeon beliefs and habits. Level Of Evidence: II, diagnostic.

Recycling Functional Fillers from Waste Tires for Tailored Polystyrene Composites: Mechanical, Fire Retarding, Electromagnetic Field Shielding, and Acoustic Insulation Properties-A Short Review.

Polymer waste is currently a big and challenging issue throughout the world. Waste tires represent an important source of polymer waste. Therefore, it is highly desirable to recycle functional fillers from waste tires to develop composite materials for advanced applications. The primary theme of this review involves an overview of developing polystyrene (PS) composites using materials from recycled tires as fillers; waste tire recycling in terms of ground tire rubbers, carbon black, and textile fibers; surface treatments of the fillers to optimize various composite properties; and the mechanical, fire retarding, acoustic, and electromagnetic field (EMI) shielding performances of PS composite materials. The development of composite materials from polystyrene and recycled waste tires provides a novel avenue to achieve reductions in carbon emission goals and closed-loop plastic recycling, which is of significance in the development of circular economics and an environmentally friendly society.

Hematoxylin and Eosin Architecture Uncovers Clinically Divergent Niches in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the only cancers with an increasing incidence rate and is often associated with intra- and peri-tumoral scarring, referred to as desmoplasia. This scarring is highly heterogeneous in extracellular matrix (ECM) architecture and plays complex roles in both tumor biology and clinical outcomes that are not yet fully understood. Using hematoxylin and eosin (H&E), a routine histological stain utilized in existing clinical workflows, we quantified ECM architecture in 85 patient samples to assess relationships between desmoplastic architecture and clinical outcomes such as survival time and disease recurrence. By utilizing unsupervised machine learning to summarize a latent space across 147 local (e.g., fiber length, solidity) and global (e.g., fiber branching, porosity) H&E-based features, we identified a continuum of histological architectures that were associated with differences in both survival and recurrence. Furthermore, we mapped H&E architectures to a CO-Detection by indEXing (CODEX) reference atlas, revealing localized cell- and protein-based niches associated with outcome-positive versus outcome-negative scarring in the tumor microenvironment. Overall, our study utilizes standard H&E staining to uncover clinically relevant associations between desmoplastic organization and PDAC outcomes, offering a translatable pipeline to support prognostic decision-making and a blueprint of spatial-biological factors for modeling by tissue engineering methods.

Thermal inactivation kinetics of Salmonella and Campylobacter in chicken livers.

Salmonella and Campylobacter are major foodborne pathogens that cause outbreaks associated with contaminated chicken liver. Proper cooking is necessary to avoid the risk of illness to consumers. This study tested the thermal inactivation of a 4-strain Salmonella cocktail and a 3-strain Campylobacter cocktail in chicken livers separately at temperatures ranging from 55.0 to 62.5°C. Inoculated livers were sealed in aluminum cells and immersed in a water bath. The decimal reduction time (D-values) of Salmonella in chicken livers were 9.01, 2.36, 0.82, and 0.23 min at 55.0, 57.5, 60.0, and 62.5°C, respectively. The D-values of Campylobacter ranged from 2.22 min at 55.0°C to 0.19 min at 60.0°C. Salmonella and Campylobacter had similar z-values in chicken livers of 4.8 and 4.6°C, respectively. Chicken livers can be heated to internal temperatures of 70.0 to 73.9°C for at least 1.6 to 0.2 s to achieve a 7-log reduction of Salmonella. Validation tests demonstrated that heating chicken livers to internal temperatures of 70.0 to 73.9°C for 2 to 0 s resulted in a reduction of Salmonella exceeding 7 logs. Collectively, these data show that Salmonella exhibits higher heat resistance than Campylobacter in chicken livers. Therefore, Salmonella could be considered as the target pathogen when designing thermal treatments or cooking instructions for liver products. These findings will aid in designing effective thermal processing for both industrial and home cooking to eliminate Salmonella and Campylobacter, ensuring consumer safety when consuming chicken liver products.

Modulation of Paracellular Permeability in SARS-CoV-2 Blood-to-Brain Transcytosis.

SARS-CoV-2 primarily infects the lungs via the ACE2 receptor but also other organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to the brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it affects the molecular functions of the BBB are unclear. In this study, we investigated the roles of the receptors ACE2 and DPP4 in the SARS-CoV-2 infection of the discrete cellular components of a transwell BBB model comprising HUVECs, astrocytes, and pericytes. Our results demonstrate that direct infection on the BBB model does not modulate paracellular permeability. Also, our results show that SARS-CoV-2 utilizes clathrin and caveolin-mediated endocytosis to traverse the BBB, resulting in the direct infection of the brain side of the BBB model with a minimal endothelial infection. In conclusion, the BBB is susceptible to SARS-CoV-2 infection in multiple ways, including the direct infection of endothelium, astrocytes, and pericytes involving ACE2 and/or DPP4 and the blood-to-brain transcytosis, which is an event that does not require the presence of host receptors.

Clinical Significance of MUC4 and Associated Proteins in Pancreatic and Periampullary Cancers.

OBJECTIVE: This study primarily aimed to assess the expression of MUC4 in patients with pancreatic ductal adenocarcinoma (PDAC) as compared with controls and assess its clinical relevance. MATERIALS AND METHODS: Serum MUC4 levels and MUC4 gene expression in snap-frozen tissue were analyzed through surface plasmon resonance and quantitative polymerase chain reaction, respectively. Tumor tissues and control tissues were analyzed for MUC4 and other mucins through immunohistochemistry. RESULT: MUC4 expression in tumor tissue was found to be significantly elevated in PDAC patients as compared with chronic pancreatitis tissues and normal pancreatic tissues. Periampullary carcinoma and cholangiocarcinoma tissue also showed increased expression of MUC4 and other mucins. CONCLUSIONS: Differential expression of MUC4 in pancreatic tumor tissues can help to differentiate PDAC from benign conditions.

7-amino carboxycoumarin 2 inhibits lactate induced epithelial-to-mesenchymal transition via MPC1 in oral and breast cancer cells.

Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta-analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA-MB-231) with sodium L-lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L-lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings.

Potential Misinformation in the Official Disability Guidelines About the Diagnosis and Treatment of Rotator Cuff Tendinopathy.

OBJECTIVE: We selected statements in the Official Disability Guidelines (ODG) that had the potential to reinforce misconceptions regarding symptoms from rotator cuff tendinopathy (RCT). These statements were revised and presented with the original statement to specialists. METHODS: Twelve statements regarding RCT were identified as deviating from principles based on ethics, values, and the evidence regarding both pathophysiology and human illness behavior. One hundred fifteen upper extremity surgeons reviewed both original and revised versions of the statements and indicated their preference. RESULTS: We found that upper extremity surgeons preferred 3 revised statements, 4 ODG statements, and 5 were rated as neutral between the 2 statements. CONCLUSION: Statements revised for evidence, ethics, and healthy mindset were not preferred by specialists, which may indicate limited awareness about how negative thoughts and distressing symptoms impact human illness.

HOMER1 Polymorphism and Parkinson's Disease-Psychosis: Is there an Association?

Objective: Homer1, a postsynaptic protein coded by the HOMER1 gene, presumably has a role in homeostatic plasticity that dampens neuronal responsiveness when the input activity is too high. HOMER1 polymorphism has been studied in major psychiatric disorders such as schizophrenia. The objective of this study is to investigate if polymorphisms of the HOMER1 gene are associated with psychosis in Parkinson's disease (PD-P). Methods: One hundred patients with Parkinson's disease (PD) and 100 healthy controls were enrolled consecutively in a PD-P biomarker study at the National Institute of Mental Health and Neurosciences, Bangalore, India. Of the 100 PD patients, 50 had psychosis (PD-P) and 50 did not have psychosis (PD-NP). Two single-nucleotide polymorphisms of HOMER1 (rs4704559 and rs4704560) were analyzed from the DNA isolated from peripheral blood. The allele and genotype frequencies in the PD-P and PD-NP groups were compared. Results: Analysis of HOMER1 rs4704560 revealed a significant difference in both genotype and allele levels between PD-P and PD-NP groups. There was an overrepresentation of T-allele (42% vs. 16%; P < 0.001) and TT genotype (24% vs. 6%; P < 0.001) in the PD-P group compared to PD-NP group. There was no significant difference between PD-P and PD-NP groups when various genotypes and allele frequencies related to HOMER1 rs4704559 were compared. Conclusion: PD-P is probably associated with overrepresentation of T-allele of HOMER1 rs4704560, and larger studies are warranted to confirm our results.

Emerging technologies in citizen science and potential for insect monitoring.

Emerging technologies are increasingly employed in environmental citizen science projects. This integration offers benefits and opportunities for scientists and participants alike. Citizen science can support large-scale, long-term monitoring of species occurrences, behaviour and interactions. At the same time, technologies can foster participant engagement, regardless of pre-existing taxonomic expertise or experience, and permit new types of data to be collected. Yet, technologies may also create challenges by potentially increasing financial costs, necessitating technological expertise or demanding training of participants. Technology could also reduce people's direct involvement and engagement with nature. In this perspective, we discuss how current technologies have spurred an increase in citizen science projects and how the implementation of emerging technologies in citizen science may enhance scientific impact and public engagement. We show how technology can act as (i) a facilitator of current citizen science and monitoring efforts, (ii) an enabler of new research opportunities, and (iii) a transformer of science, policy and public participation, but could also become (iv) an inhibitor of participation, equity and scientific rigour. Technology is developing fast and promises to provide many exciting opportunities for citizen science and insect monitoring, but while we seize these opportunities, we must remain vigilant against potential risks. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Trends in the incidence of colorectal cancer in sub-Saharan Africa: A population-based registry study.

In sub-Saharan Africa, colorectal cancer (CRC) has historically been considered a rare disease, although some previous studies have suggested that the incidence is increasing. We examine time trends in the incidence of CRC using data from 12 population-based cancer registries in 11 countries of sub-Saharan Africa that were able to provide time series data for periods of 12 or more years, or with earlier data with which recent rates may be compared. Age-standardized incidence rates were highest in the higher-income countries, and were increasing in all of the populations studied, and these increases were statistically significant in all but three. Current evidence has suggested a link between the increased adoption of western lifestyle habits with colorectal cancer, and along with increasing urbanization of African populations, there is an increase in body weight, as well as evidence of increasing consumption of meat, sugars, and alcohol.

High-Density, Nonvolatile, Flexible Multilevel Organic Memristor Using Multilayered Polymer Semiconductors.

Nonvolatile organic memristors have emerged as promising candidates for next-generation electronics, emphasizing the need for vertical device fabrication to attain a high density. Herein, we present a comprehensive investigation of high-performance organic memristors, fabricated in crossbar architecture with PTB7/Al-AlOx-nanocluster/PTB7 embedded between Al electrodes. PTB7 films were fabricated using the Unidirectional Floating Film Transfer Method, enabling independent uniform film fabrication in the Layer-by-Layer (LbL) configuration without disturbing underlying films. We examined the charge transport mechanism of our memristors using the Hubbard model highlighting the role of Al-AlOx-nanoclusters in switching-on the devices, due to the accumulation of bipolarons in the semiconducting layer. By varying the number of LbL films in the device architecture, the resistance of resistive states was systematically altered, enabling the fabrication of novel multilevel memristors. These multilevel devices exhibited excellent performance metrics, including enhanced memory density, high on-off ratio (>108), remarkable memory retention (>105 s), high endurance (87 on-off cycles), and rapid switching (∼100 ns). Furthermore, flexible memristors were fabricated, demonstrating consistent performance even under bending conditions, with a radius of 2.78 mm for >104 bending cycles. This study not only demonstrates the fundamental understanding of charge transport in organic memristors but also introduces novel device architectures with significant implications for high-density flexible applications.

A minimal presynaptic protein machinery mediating synchronous and asynchronous exocytosis and short-term plasticity.

Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic Ca2+ influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically-relevant conditions to delineate the minimal protein machinery sufficient to account for different modes of Ca2+-triggered vesicle fusion and short-term facilitation. We find that Synaptotagmin-1, Synaptotagmin-7, and Complexin, synergistically restrain SNARE complex assembly, thus preserving vesicles in a stably docked state at rest. Upon Ca2+ activation, Synaptotagmin-1 induces rapid vesicle fusion, while Synaptotagmin-7 mediates delayed fusion. Competitive binding of Synaptotagmin-1 and Synaptotagmin-7 to the same SNAREs, coupled with differential rates of Ca2+-triggered fusion clamp reversal, govern the kinetics of vesicular fusion. Under conditions mimicking sustained neuronal activity, the Synaptotagmin-7 fusion clamp is destabilized by the elevated basal Ca2+ concentration, thereby enhancing the synchronous component of fusion. These findings provide a direct demonstration that a small set of proteins is sufficient to account for how nerve terminals adapt and regulate the Ca2+-evoked neurotransmitter exocytosis process to support their specialized functions in the nervous system.

Design and Synthesis of Novel Squaraine-Based Fluorescent Probe for Far-Red Detection of Chymotrypsin Enzyme.

Chymotrypsin, a crucial enzyme in human digestion, catalyzes the breakdown of milk proteins, underscoring its significance in both health diagnostics and dairy quality assurance. Addressing the critical need for rapid, cost-effective detection methods, we introduce a groundbreaking approach utilizing far-red technology and HOMO-Förster resonance energy transfer (FRET). Our novel probe, SQ-122 PC, features a unique molecular design that includes a squaraine dye (SQ), a peptide linker, and SQ moieties synthesized through solid-phase peptide synthesis. Demonstrating a remarkable quenching efficiency of 93.75% in a tailored H2O:DMSO (7:3) solvent system, our probe exhibits absorption and emission properties within the far-red spectrum, with an unprecedented detection limit of 0.130 nM. Importantly, our method offers unparalleled selectivity towards chymotrypsin, ensuring robust and accurate enzyme detection. This pioneering work underscores the immense potential of far-red-based homo-FRET systems in enabling the sensitive and specific detection of chymotrypsin enzyme activity. By bridging the gap between cutting-edge technology and biomedical diagnostics, our findings herald a new era of enzyme sensing, promising transformative advancements in disease diagnosis and dairy quality control.

Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis.

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

Ion Channels and Metal Ions in Parkinson's Disease: Historical Perspective to the Current Scenario.

Parkinson's disease (PD) is a neurodegenerative condition linked to the deterioration of motor and cognitive performance. It produces degeneration of the dopaminergic neurons along the nigrostriatal pathway in the central nervous system (CNS), which leads to symptoms such as bradykinesias, tremors, rigidity, and postural instability. There are several medications currently approved for the therapy of PD, but a permanent cure for it remains elusive. With the aging population set to increase, a number of PD cases are expected to shoot up in the coming times. Hence, there is a need to look for new molecular targets that could be investigated both preclinically and clinically for PD treatment. Among these, several ion channels and metal ions are being studied for their effects on PD pathology and the functioning of dopaminergic neurons. Ion channels such as N-methyl-D-aspartate (NMDA), γ-aminobutyric acid A (GABAA), voltage-gated calcium channels, potassium channels, HCN channels, Hv1 proton channels, and voltage-gated sodium channels and metal ions such as mercury, zinc, copper, iron, manganese, calcium, and lead showed prominent involvement in PD. Pharmacological agents have been used to target these ion channels and metal ions to prevent or treat PD. Hence, in the present review, we summarize the pathophysiological events linked to PD with an emphasis on the role of ions and ion channels in PD pathology, and pharmacological agents targeting these ion channels have also been listed.