Label-free detection of Aß-42: a liquid crystal droplet approach for Alzheimer's disease diagnosis.

This study introduces a biosensor based on liquid crystals (LC) designed to detect the Aß-42 biomarker, commonly associated with Alzheimer's disease. The sensor utilizes LC droplets created using a PEI/Tween-20 surfactant mixture, arranged radially in an aqueous solution. These droplets are coated with the Aß1-16 antibody, enabling the detection of the Aß1-42 biomarker. The key advantage of this biosensor lies in its ability to directly translate the antigen-antibody interaction into a change in the molecular orientation of the LC droplets, simplifying the detection process by removing additional procedural steps. Specifically, this immunoassay induces a transformation in the nematic droplets orientation from radial to bipolar upon successful antigen binding. When only the Aß1-16 antibody coated the LC droplets, no change in orientation was detected, confirming the reaction's specificity. The orientation shift in the LC droplets indicates the formation of an immunocomplex between the Aß1-16 antibody and the Aß1-42 antigen. The LC droplet immunoassay effectively detected Aß1-42 antigen concentrations ranging from 45 to 112.5 µM, with the Aß1-16 antibody immobilized on the droplets at a concentration of 1 µg mL-1. These findings suggest that the LC microdroplets' orientational behavior can be harnessed to develop a biosensor for the in vivo detection of various proteins or pathogens in a PBS aqueous medium. Owing to its label-free nature and distinct optical signaling, this LC droplet-based immunoassay holds promise for further development into a cost-effective, portable diagnostic tool.

Corrigendum to 'Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics' [Genes & Diseases 10 (2023) 1367-1401].

[This corrects the article DOI: 10.1016/j.gendis.2022.02.007.].

Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics.

Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year. With the new understanding of the molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers. Targeted drug therapy, immunotherapy, and personalized medicines are now largely being employed, which were not common a few years back. The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies, extending patients' disease-free survival thereafter. Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine, chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient's physical and psychological health. Chemotherapeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons. The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals; it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.

Clinical Strategies and Therapeutics for Human Monkeypox Virus: A Revised Perspective on Recent Outbreaks.

An enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus Orthopoxviridae, a family of notorious smallpox viruses, and so it shares similar clinical pathophysiological features. The recent multicountry HMPX outbreak (May 2022 onwards) is recognized as an emerging global public health emergency by the World Health Organization, shunting its endemic status as opined over the past few decades. Re-emergence of HMPX raises concern to reassess the present clinical strategy and therapeutics as its outbreak evolves further. Keeping a check on these developments, here we provide insights into the HMPX epidemiology, pathophysiology, and clinical representation. Weighing on its early prevention, we reviewed the strategies that are being enrolled for HMPX diagnosis. In the line of expanded MPXV prevalence, we further reviewed its clinical management and the diverse employed preventive/therapeutic strategies, including vaccines (JYNNEOS, ACAM2000, VIGIV) and antiviral drugs/inhibitors (Tecovirimat, Cidofovir, Brincidofovir). Taken together, with a revised perspective of HMPX re-emergence, the present report summarizes new knowledge on its prevalence, pathology, and prevention strategies.

Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies.

Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, in addition to apparent coronary heart disease, ischemia, and hypertension-related complications, has created a more challenging situation. Diabetes, as a predominant cardio-renal metabolic syndrome, is related to severe vascular risk factors, and it underlies various complex pathophysiological pathways at the metabolic and molecular level that progress and converge toward the development of diabetic cardiomyopathy (DCM). DCM involves several downstream cascades that cause structural and functional alterations of the diabetic heart, such as diastolic dysfunction progressing into systolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, and subsequent heart failure over time. The effects of glucagon-like peptide-1 (GLP-1) analogues and sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular (CV) outcomes in diabetes have shown promising results, including improved contractile bioenergetics and significant cardiovascular benefits. The purpose of this article is to highlight the various pathophysiological, metabolic, and molecular pathways that contribute to the development of DCM and its significant effects on cardiac morphology and functioning. Additionally, this article will discuss the potential therapies that may be available in the future.

Altered glucose metabolism in Alzheimer's disease: Role of mitochondrial dysfunction and oxidative stress.

Increasing evidence suggests that abnormal cerebral glucose metabolism is largely present in Alzheimer's disease (AD). The brain utilizes glucose as its main energy source and a decline in its metabolism directly reflects on brain function. Weighing on recent evidence, here we systematically assessed the aberrant glucose metabolism associated with amyloid beta and phosphorylated tau accumulation in AD brain. Interlink between insulin signaling and AD highlighted the involvement of the IRS/PI3K/Akt/AMPK signaling, and GLUTs in the disease progression. While shedding light on the mitochondrial dysfunction in the defective glucose metabolism, we further assessed functional consequences of AGEs (advanced glycation end products) accumulation, polyol activation, and other contributing factors including terminal respiration, ROS (reactive oxygen species), mitochondrial permeability, PINK1/parkin defects, lysosome-mitochondrial crosstalk, and autophagy/mitophagy. Combined with the classic plaque and tangle pathologies, glucose hypometabolism with acquired insulin resistance and mitochondrial dysfunction potentiate these factors to exacerbate AD pathology. To this end, we further reviewed AD and DM (diabetes mellitus) crosstalk in disease progression. Taken together, the present work discusses the emerging role of altered glucose metabolism, contributing impact of insulin signaling, and mitochondrial dysfunction in the defective cerebral glucose utilization in AD.

Probiotics: Evolving as a Potential Therapeutic Option against Acetaminophen-Induced Hepatotoxicity.

Acetaminophen (APAP) is the most common prescription medicine around the world for the treatment of pain and fever and is considered to be a safe drug at its therapeutic dose. However, a single overdose or frequent use of APAP can cause severe acute liver injury. APAP hepatotoxicity is a prevalent cause of acute liver disease around the world and the lack of suitable treatment makes it a serious problem. In recent years, there has been a surge in interest in using probiotics and probiotic-derived products, known as postbiotics, as health and disease negotiators. A growing body of evidence revealed that they can be equally effective against APAP hepatotoxicity. Different probiotic bacteria were found to be pre-clinically effective against APAP hepatotoxicity. Different postbiotics have also shown exciting results in preclinical models of APAP hepatotoxicity. This review summarized the protective roles and mechanisms of the different probiotic bacteria and postbiotics against APAP hepatotoxicity, with critical discussion. A brief discussion on potential novel probiotics and postbiotics for oxidative liver injury was also included. This review was written in an attempt to pique the interest of researchers in developing a safe therapeutic option against oxidative liver damage using probiotics and/or postbiotics as dietary supplements.

COVID-19 and Rheumatoid Arthritis Crosstalk: Emerging Association, Therapeutic Options and Challenges.

Hyperactivation of immune responses resulting in excessive release of pro-inflammatory mediators in alveoli/lung structures is the principal pathological feature of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cytokine hyperactivation in COVID-19 appears to be similar to those seen in rheumatoid arthritis (RA), an autoimmune disease. Emerging evidence conferred the severity and risk of COVID-19 to RA patients. Amid the evidence of musculoskeletal manifestations involving immune-inflammation-dependent mechanisms and cases of arthralgia and/or myalgia in COVID-19, crosstalk between COVID-19 and RA is often debated. The present article sheds light on the pathological crosstalk between COVID-19 and RA, the risk of RA patients in acquiring SARS-CoV-2 infection, and the aspects of SARS-CoV-2 infection in RA development. We also conferred whether RA can exacerbate COVID-19 outcomes based on available clinical readouts. The mechanistic overlapping in immune-inflammatory features in both COVID-19 and RA was discussed. We showed the emerging links of angiotensin-converting enzyme (ACE)-dependent and macrophage-mediated pathways in both diseases. Moreover, a detailed review of immediate challenges and key recommendations for anti-rheumatic drugs in the COVID-19 setting was presented for better clinical monitoring and management of RA patients. Taken together, the present article summarizes available knowledge on the emerging COVID-19 and RA crosstalk and their mechanistic overlaps, challenges, and therapeutic options.

Counting on COVID-19 Vaccine: Insights into the Current Strategies, Progress and Future Challenges.

The emergence of a novel coronavirus viz., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 and its subsequent substantial spread produced the coronavirus disease 2019 (COVID-19) pandemic worldwide. Given its unprecedented infectivity and pathogenicity, the COVID-19 pandemic had a devastating impact on human health, and its clinical management has been a great challenge, which has led to the development and speedy trials of several vaccine candidates against SARS-CoV-2 at an exceptional pace. As a result, several COVID-19 vaccines were made commercially available in the first half of 2021. Although several COVID-19 vaccines showed promising results, crucial insights into their epidemiology, protective mechanisms, and the propensities of reinfection are not largely reviewed. In the present report, we provided insights into the prospects of vaccination against COVID-19 and assessed diverse vaccination strategies including DNA, mRNA, protein subunits, vector-based, live attenuated, and inactivated whole/viral particle-based vaccines. Next, we reviewed major aspects of various available vaccines approved by the World Health Organization and by the local administrations to use against COVID-19. Moreover, we comprehensively assessed the success of these approved vaccines and also their untoward effects, including the possibility of reinfection. We also provided an update on the vaccines that are under development and could be promising candidates in the future. Conclusively, we provided insights into the COVID-19 vaccine epidemiology, their potency, and propensity for SARS-CoV-2 reinfection, while a careful review of their current status, strategies, success, and future challenges was also presented.

Potential Biomarkers Associated with Multiple Sclerosis Pathology.

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and promptly measured, their specificity, and their reproducibility. Biomarkers are classified into several categories depending on whether they address personal or predictive susceptibility, diagnosis, prognosis, disease activity, or response to treatment in different clinical courses of MS. The identified members indicate a variety of pathological processes of MS, such as neuroaxonal damage, gliosis, demyelination, progression of disability, and remyelination, among others. The present review analyzes biomarkers in cerebrospinal fluid (CSF) and blood serum, the most promising imaging biomarkers used in clinical practice. Furthermore, it aims to shed light on the criteria and challenges that a biomarker must face to be considered as a standard in daily clinical practice.

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most prominent neurodegenerative diseases, which impairs cognitive function in afflicted individuals. AD results in gradual decay of neuronal function as a consequence of diverse degenerating events. Several neuroimmune players (such as cytokines and growth factors that are key players in maintaining CNS homeostasis) turn aberrant during crosstalk between the innate and adaptive immunities. This aberrance underlies neuroinflammation and drives neuronal cells toward apoptotic decline. Neuroinflammation involves microglial activation and has been shown to exacerbate AD. This review attempted to elucidate the role of cytokines, growth factors, and associated mechanisms implicated in the course of AD, especially with neuroinflammation. We also evaluated the propensities and specific mechanism(s) of cytokines and growth factors impacting neuron upon apoptotic decline and further shed light on the availability and accessibility of cytokines across the blood-brain barrier and choroid plexus in AD pathophysiology. The pathogenic and the protective roles of macrophage migration and inhibitory factors, neurotrophic factors, hematopoietic-related growth factors, TAU phosphorylation, advanced glycation end products, complement system, and glial cells in AD and neuropsychiatric pathology were also discussed. Taken together, the emerging roles of these factors in AD pathology emphasize the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

The Emerging Role of HDACs: Pathology and Therapeutic Targets in Diabetes Mellitus.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into four different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate ß cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting novel interventional strategies for metabolic disorders/complications.

Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic.

The unremitting coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked a year-long phase of public health adversaries and has severely compromised healthcare globally. Early evidence of COVID-19 noted its impact on the pulmonary and cardiovascular functions, while multiple studies in recent time shed light on its substantial neurological complications, though a comprehensive understanding of the cause(s), the mechanism(s), and their neuropathological outcomes is scarce. In the present review, we conferred evidence of neurological complications in COVID-19 patients and shed light on the SARS-CoV-2 infection routes including the hematogenous, direct/neuronal, lymphatic tissue or cerebrospinal fluid, or infiltration through infected immune cells, while the underlying mechanism of SARS-CoV-2 invasion to the central nervous system (CNS) was also discussed. In an up-to-date manner, we further reviewed the impact of COVID-19 in developing diverse neurologic manifestations associated with CNS, peripheral nervous system (PNS), skeletal muscle, and also pre-existing neurological diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and myasthenia gravis. Furthermore, we discussed the involvement of key factors including age, sex, comorbidity, and disease severity in exacerbating the neurologic manifestations in COVID-19 patients. An outlook of present therapeutic strategies and state of existing challenges in COVID-19 management was also accessed. Conclusively, the present report provides a comprehensive review of COVID-19-related neurological complications and emphasizes the need for their early clinical management in the ongoing COVID-19 pandemic.

Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy.

Association of diabetes with an elevated risk of cardiac failure has been clinically evident. Diabetes potentiates diastolic and systolic cardiac failure following the myocardial infarction that produces the cardiac muscle-specific microvascular complication, clinically termed as diabetic cardiomyopathy. Elevated susceptibility of diabetic cardiomyopathy is primarily caused by the generation of free radicals in the hyperglycemic milieu, compromising the myocardial contractility and normal cardiac functions with increasing redox insult, impaired mitochondria, damaged organelles, apoptosis, and cardiomyocytes fibrosis. Autophagy is essentially involved in the recycling/clearing the damaged organelles, cytoplasmic contents, and aggregates, which are frequently produced in cardiomyocytes. Although autophagy plays a vital role in maintaining the cellular homeostasis in diligent cardiac tissues, this process is frequently impaired in the diabetic heart. Given its clinical significance, accumulating evidence largely showed the functional aspects of autophagy in diabetic cardiomyopathy, elucidating its intricate protective and pathogenic outcomes. However, etiology and molecular readouts of these contrary autophagy activities in diabetic cardiomyopathy are not yet comprehensively assessed and translated. In this review, we attempted to assess the role of autophagy and its adaptations in the diabetic heart. To delineate the molecular consequences of these events, we provided detailed insights into the autophagy regulation pieces of machinery including the mTOR/AMPK, TFEB/ZNSCAN3, FOXOs, SIRTs, PINK1/Parkin, Nrf2, miRNAs, and others in the diabetic cardiomyopathy. Given the clinical significance of autophagy in the diabetic heart, we further discussed the potential pharmacotherapeutic strategies towards targeting autophagy. Taken together, the present report meticulously assessed autophagy, its adaptations, and molecular regulations in diabetic cardiomyopathy and reviewed the current autophagy-targeting strategies.

Mitochondrial dysfunction, mitophagy, and role of dynamin-related protein 1 in Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia and progressive neurodegenerative disease. The presence of ß-amyloid (Aß) plaques and phosphorylated Tau tangles are considered to be the two main hallmarks of AD. Recent findings have shown that different changes in the structure and dynamics of mitochondria play an important role in AD pathology progression. Mitochondrial changes in AD are expressed as enhanced mitochondrial fragmentation, altered mitochondrial dynamics, and changes in the expression of mitochondrial biogenesis genes in vitro and in vivo models. Therefore, targeting mitochondria and associated mitochondrial proteins seems to be a promising alternative instead of targeting Aß and Tau in the prevention of Alzheimer's disease. The dynamin-related protein (Drp1) is one such protein that plays an important role in the regulation of mitochondrial division and maintenance of mitochondrial structures. Few researchers have shown that inhibition of Drp1 GTPase activity in neuronal cells rescues excessive mitochondrial fragmentation. In addition, the growing evidence revealed that Drp1 can interact with both Aß and Tau protein in human brain tissues and mouse models. In this review, we would like to update existing knowledge about various changes in and around mitochondria related to the pathogenesis of Alzheimer's disease, with particular emphasis on mitophagy and autophagy.

Current Status of Multiple Drug Molecules, and Vaccines: An Update in SARS-CoV-2 Therapeutics.

The coronavirus disease of 2019 (COVID-19) is a pandemic disease that has taken the lives of many around the world. It is caused by severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). To date, the USA, Italy, Spain, France, Russia, and the UK have been hit the hardest by the virus. However, death counts are still rising. Some nations have managed to "flatten" the death rate via protective measures such physical distancing, quarantine measures, and therapeutic management. The structure of the SARS-CoV-2 virus comprises of S proteins, M proteins, E proteins, hemagglutinin esterases, nucleocapsid proteins, and a 30-kb RNA genome. Viral proteases cleave these polyproteins and RNA-dependent polymerases replicate the genome. Currently, there are no effective therapies against this new disease. Numerous investigators are developing novel protease inhibitors, some of which have made it into clinical trials. Researchers are also attempting to develop a vaccine. In this review paper, we discuss the latest therapeutic developments against COVID-19. Graphical Abstract.

SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets.

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.

Liquid Crystals: A Novel Approach for Cancer Detection and Treatment.

Liquid crystals are defined as the fourth state of matter forming between solid and liquid states. Earlier the applications of liquid crystals were confined to electronic instruments, but recent research findings suggest multiple applications of liquid crystals in biology and medicine. Here, the purpose of this review article is to discuss the potential biological impacts of liquid crystals in the diagnosis and prognosis of cancer along with the risk assessment. In this review, we also discussed the recent advances of liquid crystals in cancer biomarker detection and treatment in multiple cell line models. Cases reviewed here will demonstrate that cancer diagnostics based on the multidisciplinary technology and intriguingly utilization of liquid crystals may become an alternative to regular cancer detection methodologies. Additionally, we discussed the formidable challenges and problems in applying liquid crystal technologies. Solving these problems will require great effort and the way forward is through the multidisciplinary collaboration of physicists, biologists, chemists, material-scientists, clinicians, and engineers. The triumphant outcome of these liquid crystals and their applications in cancer research would be convenient testing for the detection of cancer and may result in treating the cancer patients non-invasively.

Defect transitions in nematic liquid-crystal capillary bridges.

We use experiment and computational modeling to understand the defect structure and director configuration in a nematic liquid crystal capillary bridge confined between two parallel plates. We find that tuning of the aspect ratio of the bridge drives a transition between a ring defect and a point defect. This transition exhibits hysteresis, due to the metastability of the point-defect structure. In addition, we see that the shape of the capillary-bridge surface determines whether the defect is hyperbolic or radial, with waistlike bridges containing hyperbolic defects and barrel-like bridges containing radial defects.

Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration.

In the previous study, we demonstrated that dichlorvos induces oxidative stress in dopaminergic neuronal cells and subsequent caspase activation mediates apoptosis. In the present study, we evaluated the effect and mechanism of dichlorvos induced oxidative stress on cell cycle activation in NGF-differentiated PC12 cells. Dichlorvos exposure resulted in oxidative DNA damage along with activation of cell cycle machinery in differentiated PC12 cells. Dichlorvos exposed cells exhibited an increased expression of p53, cyclin-D1, pRb and decreased expression of p21suggesting a re-entry of differentiated cells into the cell cycle. Cell cycle analysis of dichlorvos exposed cells revealed a reduction of cells in the G0/G1 phase of the cell cycle (25%), and a concomitant increase of cells in S phase (30%) and G2/M phase (43.3%) compared to control PC12 cells. Further, immunoblotting of cytochrome c, Bax, Bcl-2 and cleaved caspase-3 revealed that dichlorvos induces a caspase-dependent cell death in PC12 cells. These results suggest that Dichlorvos exposure has the potential to generate oxidative stress which evokes activation of cell cycle machinery leading to apoptotic cell death via cytochrome c release from mitochondria and subsequent caspase-3 activation in differentiated PC12 cells.