Molecular Fingerprinting and Phytochemical Investigation of Syzygium cumini L. from Different Agro-Ecological Zones of India.

Syzygium cumini L. (ver Jamun; BlackBerry) is a native, evergreen multipurpose tree species of India. Besides being a fruit tree and for agroforestry in different regions, it is medicinally important too. This study aimed to determine genetic diversity using molecular and phytochemical markers in sixteen genotypes of Indian S. cumini from different agro-ecological zones. The present study used a combination of ISSR markers and the HPLC technique to explore these genotypes. The results showed a wide genetic diversity range based on the similarity coefficient values observed in S. cumini sixteen accessions from different sites. Four primary phenolic acids were discovered in all the accessions; caffeic acid (CA) was found in high concentrations. The intraspecific association between molecular and phytochemical characteristics was the primary goal of this investigation. By employing gene-specific markers for the route of secondary metabolites (polyphenols) production, it further investigated the progressive research of diversity analysis of polyphenol content in S. cumini accessions, which may also expand its nutraceutical and pharmaceutical utilization.

Central macular thickness change after uneventful small-incision cataract surgery - An observational study.

Purpose: The purpose of this study was to diagnose CME with the help of optical coherence tomography (OCT) after uneventful cataract surgery to prevent visual deterioration. Methods: This study was conducted on 120 patients, who underwent manual small-incision cataract surgery with posterior chamber intra-ocular lens implantation. Follow-up was performed after the first week, sixth week, and 12th week post-operatively. Detailed examination was performed at each visit along with measurements of central macular thickness using OCT. Statistical analysis was performed using SPSS 22.0. Result: The mean age of the patients was 61.85 ± 11.41 years having female preponderance. The pre-operative mean best corrected visual acuity (BCVA) was found to be 0.05 ± 0.04, whereas the mean post-operative BCVA was found to be 0.65 ± 0.17 at the first week, 0.66 ± 0.17 at the sixth week, and 0.67 ± 0.17 at the 12th week follow-up. The post-operative mean macular thicknesses at the first week, sixth week, and 12th week post-operatively were documented to be 221.66 ± 8.49 µm, 224.60 ± 8.75 µm, and 219.17 ± 8.22 µm, respectively. Conclusion: A sub-clinical increase in macular thickness occurs even after uncomplicated cataract surgery. The maximum increase was observed after 6 weeks of surgery, which returns to near normal values within 3 months. Comparison of central macular thicknesses pre-operatively and post-operatively at the first week, sixth week, and 12th week suggests a significant correlation.

Isoflurane Disrupts Postsynaptic Density-95 Protein Interactions Causing Neuronal Synapse Loss and Cognitive Impairment in Juvenile Mice via Canonical NO-mediated Protein Kinase-G Signaling.

BACKGROUND: Inhalational anesthetics are known to disrupt PDZ2 domain-mediated protein-protein interactions of the postsynaptic density (PSD)-95 protein. The aim of this study is to investigate the underlying mechanisms in response to early isoflurane exposure on synaptic PSD-95 PDZ2 domain disruption that altered spine densities and cognitive function. The authors hypothesized that activation of protein kinase-G by the components of nitric oxide (NO) signaling pathway constitutes a mechanism that prevents loss of early dendritic spines and synapse in neurons and cognitive impairment in mice in response to disruption of PDZ2 domain of the PSD-95 protein. METHODS: Postnatal day 7 mice were exposed to 1.5% isoflurane for 4 h or injected with 8 mg/kg active PSD-95 wild-type PDZ2 peptide or soluble guanylyl cyclase activator YC-1 along with their respective controls. Primary neurons at 7 days in vitro were exposed to isoflurane or PSD-95 wild-type PDZ2 peptide for 4 h. Coimmunoprecipitation, spine density, synapses, cyclic guanosine monophosphate-dependent protein kinase activity, and novel object recognition memory were assessed. RESULTS: Exposure of isoflurane or PSD-95 wild-type PDZ2 peptide relative to controls causes the following. First, there is a decrease in PSD-95 coimmunoprecipitate relative to N-methyl-d-aspartate receptor subunits NR2A and NR2B precipitate (mean ± SD [in percentage of control]: isoflurane, 54.73 ± 16.52, P = 0.001; and PSD-95 wild-type PDZ2 peptide, 51.32 ± 12.93, P = 0.001). Second, there is a loss in spine density (mean ± SD [spine density per 10 µm]: control, 5.28 ± 0.56 vs. isoflurane, 2.23 ± 0.67, P < 0.0001; and PSD-95 mutant PDZ2 peptide, 4.74 ± 0.94 vs. PSD-95 wild-type PDZ2 peptide, 1.47 ± 0.87, P < 0.001) and a decrease in synaptic puncta (mean ± SD [in percentage of control]: isoflurane, 41.1 ± 14.38, P = 0.001; and PSD-95 wild-type PDZ2 peptide, 50.49 ± 14.31, P < 0.001). NO donor or cyclic guanosine monophosphate analog prevents the spines and synapse loss and decline in the cyclic guanosine monophosphate-dependent protein kinase activity, but this prevention was blocked by soluble guanylyl cyclase or protein kinase-G inhibitors in primary neurons. Third, there were deficits in object recognition at 5 weeks (mean ± SD [recognition index]: male, control, 64.08 ± 10.57 vs. isoflurane, 48.49 ± 13.41, P = 0.001, n = 60; and female, control, 67.13 ± 11.17 vs. isoflurane, 53.76 ± 6.64, P = 0.003, n = 58). Isoflurane-induced impairment in recognition memory was preventable by the introduction of YC-1. CONCLUSIONS: Activation of soluble guanylyl cyclase or protein kinase-G prevents isoflurane or PSD-95 wild-type PDZ2 peptide-induced loss of dendritic spines and synapse. Prevention of recognition memory with YC-1, a NO-independent activator of guanylyl cyclase, supports a role for the soluble guanylyl cyclase mediated protein kinase-G signaling in countering the effects of isoflurane-induced cognitive impairment.

Dentinogenic Ghost Cell Tumor of Mandible in a Pediatric Patient with Dysplastic Changes.

Dentinogenic ghost cell tumor (DGCT) is a very rare entity with controversies in its terminology and classification. It is the neoplastic solid counterpart of the calcifying odontogenic cyst (COC), which was first reported by Gorlin et al. in 1962. There are around 31 cases reported in the literature. The mean age of occurrence is 40.27 years, although very rarely is it associated with the pediatric age group. We are reporting a case of DGCT with dysplastic changes in an 11-year-old child which is very rare. The present case deals with the clinical, radiological, and histopathological aspects of the disease and the importance of an appropriate diagnosis. How to cite this article: Natani A, Borah S, Borah M, et al. Dentinogenic Ghost Cell Tumor of Mandible in a Pediatric Patient with Dysplastic Changes. Int J Clin Pediatr Dent 2020;13(S-1):S119-S121.

Glutathione S-transferases promote proinflammatory astrocyte-microglia communication during brain inflammation.

Astrocytes and microglia play critical roles in brain inflammation. Here, we report that glutathione S-transferases (GSTs), particularly GSTM1, promote proinflammatory signaling in astrocytes and contribute to astrocyte-mediated microglia activation during brain inflammation. In vivo, astrocyte-specific knockdown of GSTM1 in the prefrontal cortex attenuated microglia activation in brain inflammation induced by systemic injection of lipopolysaccharides (LPS). Knocking down GSTM1 in astrocytes also attenuated LPS-induced production of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) by microglia when the two cell types were cocultured. In astrocytes, GSTM1 was required for the activation of nuclear factor κB (NF-κB) and the production of proinflammatory mediators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and C-C motif chemokine ligand 2 (CCL2), both of which enhance microglia activation. Our study suggests that GSTs play a proinflammatory role in priming astrocytes and enhancing microglia activation in a microglia-astrocyte positive feedback loop during brain inflammation.

Neonate with urinary ascites but no hydronephrosis: unusual presentation of posterior urethral valves.

Posterior urethral valves (PUV) are an important cause of paediatric obstructive uropathy. PUV are usually diagnosed by prenatal ultrasonography (US) revealing hydronephrosis and bladder distention. We describe a 17-day-old male infant with abdominal distention who had no hydronephrosis on prenatal US. Laboratory investigations showed serum creatinine of 12 mg/dL, hyperkalaemia and metabolic acidosis. Abdominal US showed large amount of ascites, normal-sized kidneys without hydronephrosis and incompletely distended bladder. Paracentesis revealed clear, yellow ascitic fluid with creatinine level of 27 mg/dL compatible with urinary ascites. Voiding cystourethrogram (VCUG) demonstrated PUV with a dilated posterior urethra, grade 5 right vesicoureteral reflux and a ruptured kidney fornix with peritoneal extravasation of contrast. Foley decompression resulted in normalisation of creatinine within 72 hours. Transurethral resection of PUV was performed, and a repeat VCUG showed recovery of forniceal rupture. This case illustrates an unusual presentation of a potentially life-threatening but treatable cause of urinary tract obstruction.

Hormone Replacement Therapy: Would it be Possible to Replicate a Functional Ovary?

BACKGROUND: Throughout history, menopause has been regarded as a transition in a woman's life. With the increase in life expectancy, women now spend more than a third of their lives in menopause. During these years, women may experience intolerable symptoms both physically and mentally, leading them to seek clinical advice. It is imperative for healthcare providers to improve the quality of life by reducing bothersome menopausal symptoms and preventing disorders such as osteoporosis and atherosclerosis. The current treatment in the form of hormone replacement therapy (HRT) is sometimes inadequate with several limitations and adverse effects. Objective and rationale: The current review aims to discuss the need, efficacy, and limitations of current HRT; the role of other ovarian hormones, and where we stand in comparison with ovary-in situ; and finally, explore towards the preparation of an HRT model by regeneration of ovaries tissues through stem cells which can replicate a functional ovary. SEARCH METHODS: Four electronic databases (MEDLINE, Embase, Web of Science and CINAHL) were searched from database inception until 26 April 2018, using a combination of relevant controlled vocabulary terms and free-text terms related to 'menopause', 'hormone replacement therapy', 'ovary regeneration', 'stem cells' and 'ovarian transplantation'. OUTCOMES: We present a synthesis of the existing data on the efficacy and limitations of HRT. HRT is far from adequate in postmenopausal women with symptoms of hormone deprivation as it fails to deliver all hormones secreted by naïve ovarian tissue. Moreover, the pharmacokinetics of synthetic hormones makes them substantially different from natural ones. Not only does the number and type of hormones given in HRT matter, but the route of delivering and their release in circulation are also imperative. The hormones are delivered either orally or topically in a non-physiological uniform manner, which brings along with it several side effects. These identify the need for a hormone delivery system which replicates, integrates and reacts as per the requirement of the female body. Wider implications: The review outlines the strengths and weaknesses of HRT and highlights the potential areas for future research. There is a tremendous potential for research in this field to understand the collective roles of the various ovarian hormones and to devise an auto-regulated hormone delivery system which replicates the normal physiology. Its clinical applications can prove to be transformative for postmenopausal women helping them to lead a healthy and productive life.

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation.

The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU- and ß-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPA-mediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp-1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus.

Presumed isotretinoin-induced extraocular myopathy.

Isotretinoin a synthetic analogue of vitamin A is primarily used for cystic acne not responding to conventional treatment. Several ocular side effects including blurring of vision, decreased dark adaptation, corneal opacities and meibomian gland atrophy have been reported with prolonged use of isotretinoin. There have been reports of muscular damage caused by isotretinoin. Extra ocular myopathy as an adverse effect of long term used of isotretinoin has never been mentioned in literature. We report a case of a young male who presented to us with complaints of diplopia after using isotretinoin for a prolonged period. He was diagnosed as a case of presumed isotretinoin extraocular myopathy after imaging and other blood investigations.

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway.

Bisphenol A (BPA) is an environmental xenoestrogenic endocrine disruptor, utilized for production of consumer products, and exerts adverse effects on the developing nervous system. Recently, we found that BPA impairs the finely tuned dynamic processes of neurogenesis (generation of new neurons) in the hippocampus of the developing rat brain. Curcumin is a natural polyphenolic compound, which provides neuroprotection against various environmental neurotoxicants and in the cellular and animal models of neurodegenerative disorders. Here, we have assessed the neuroprotective efficacy of curcumin against BPA-mediated reduced neurogenesis and the underlying cellular and molecular mechanism(s). Both in vitro and in vivo studies showed that curcumin protects against BPA-induced hippocampal neurotoxicity. Curcumin protects against BPA-mediated reduced neural stem cells (NSC) proliferation and neuronal differentiation and enhanced neurodegeneration. Curcumin also enhances the expression/levels of neurogenic and the Wnt pathway genes/proteins, which were reduced due to BPA exposure in the hippocampus. Curcumin-mediated neuroprotection against BPA-induced neurotoxicity involved activation of the Wnt/ß-catenin signaling pathway, which was confirmed by the use of Wnt specific activators (LiCl and GSK-3ß siRNA) and inhibitor (Dkk-1). BPA-mediated increased ß-catenin phosphorylation, decreased GSK-3ß levels, and ß-catenin nuclear translocation were significantly reversed by curcumin, leading to enhanced neurogenesis. Curcumin-induced protective effects on neurogenesis were blocked by Dkk-1 in NSC culture treated with BPA. Curcumin-mediated enhanced neurogenesis was correlated well with improved learning and memory in BPA-treated rats. Overall, our results conclude that curcumin provides neuroprotection against BPA-mediated impaired neurogenesis via activation of the Wnt/ß-catenin signaling pathway.

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-ß Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/ß-Catenin Pathway.

Neurogenesis involves generation of new neurons through finely tuned multistep processes, such as neural stem cell (NSC) proliferation, migration, differentiation, and integration into existing neuronal circuitry in the dentate gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis is involved in cognitive functions and altered in various neurodegenerative disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizures. However, the effects of ETH on adult hippocampal neurogenesis and the underlying cellular and molecular mechanism(s) are yet unexplored. Herein, we studied the effects of ETH on rat multipotent NSC proliferation and neuronal differentiation and adult hippocampal neurogenesis in an amyloid ß (Aß) toxin-induced rat model of AD-like phenotypes. ETH potently induced NSC proliferation and neuronal differentiation in the hippocampus-derived NSC in vitro. ETH enhanced NSC proliferation and neuronal differentiation and reduced Aß toxin-mediated toxicity and neurodegeneration, leading to behavioral recovery in the rat AD model. ETH inhibited Aß-mediated suppression of neurogenic and Akt/Wnt/ß-catenin pathway gene expression in the hippocampus. ETH activated the PI3K·Akt and Wnt·ß-catenin transduction pathways that are known to be involved in the regulation of neurogenesis. Inhibition of the PI3K·Akt and Wnt·ß-catenin pathways effectively blocked the mitogenic and neurogenic effects of ETH. In silico molecular target prediction docking studies suggest that ETH interacts with Akt, Dkk-1, and GSK-3ß. Our findings suggest that ETH stimulates NSC proliferation and differentiation in vitro and adult hippocampal neurogenesis via the PI3K·Akt and Wnt·ß-catenin signaling.

Mechanism of Nanotization-Mediated Improvement in the Efficacy of Caffeine Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonism.

The study aimed to measure the neuroprotective efficacy of caffeine-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles over bulk and to delineate the mechanism of improvement in efficacy both in vitro and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinsonism. Caffeine-encapsulated PLGA nanoparticles exhibited more pronounced increase in the endurance of dopaminergic neurons, fibre outgrowth and expression of tyrosine hydroxylase (TH) and growth-associated protein-43 (GAP-43) against 1-methyl-4-phenylpyridinium (MPP+)-induced alterations in vitro. Caffeine-encapsulated PLGA nanoparticles also inhibited MPP(+)-mediated nuclear translocation of nuclear factor-kappa B (NF-κB) and augmented protein kinase B phosphorylation more potentially than bulk counterpart. Conversely, MPTP reduced the striatal dopamine and its metabolites and nigral TH immunoreactivity whereas augmented the nigral microglial activation and nigrostriatal lipid peroxidation and nitrite content, which were shifted towards normalcy by caffeine. The modulations were more evident in caffeine-encapsulated PLGA nanoparticles treated animals as compared with bulk. Moreover, the striatal caffeine and its metabolites were found to be significantly higher in caffeine-encapsulated PLGA nanoparticles-treated mice as compared with bulk. The results thus suggest that nanotization improves the protective efficacy of caffeine against MPTP-induced Parkinsonism owing to enhanced bioavailability, inhibition of the nuclear translocation of NF-κB and activation of protein kinase B phosphorylation.

Root amputation and perio-esthetics in salvaging a premolar.

A 32-year-old patient with complete denudation of buccal root of tooth no. 14 was referred from the Department of Oral Surgery for opinion, as he was not willing for extraction. Patient's persistent urge to save the tooth, put forth a challenge, which motivated us to tweak the established techniques. The unusual presentation of the case and unexpected par-operative condition of the surgical site required out-of-box measures to deal with the situation. Though, the tooth no. 14 was having Grade-I mobility, it was endodontically treated, buccal root was resected, osseous graft was applied over the deficient ridge area and lateral pedicle flap was displaced over the short root-trunk area to cover the surgical site. To our astonishment, the tooth survived, mobility was reduced and complete coverage with soft-tissue was observed. Uneventful healing with stable gingival margin was observed at 3-month interval, which remained stationary at 1-year follow-up.

Richter type of incarcerated obturator hernia; misery still continues.

Obturator hernia is a rare type of hernia which accounts for only 0.07-1.4% of all intra-abdominal hernias and 0.2-5.8% of small-intestinal obstructions. It develops predominantly in elderly underweight women. It has nonspecific early symptoms, so these hernias are usually discovered only after they have become incarcerated. Incarcerated obturator hernias are usually discovered on abdominal computed tomography scan or emergency surgery due to bowel obstruction. Here we present a case of a 65-year-old female who presented with intermittent abdominal pain, distension and nausea for last 3 days. She was a known case of hypothyroidism, taking Levothyroxine in inadequate dose. Her intial abdominal Xray was showing few air-fluid level with air present in rectum. She was initially managed conservatively but later developed features of peritonitis for which she was operated. In laparotomy, Richter type of right-sided incarcerated obturator hernia was discovered with a small necrotic area and perforation of small bowel. Bowel resection was performed and obturator hernia was closed with interrupted sutures. The patient recovered without complications. Obturator hernia, due to its rarity and nonspecific early symptoms, can still be misleading even to the most experienced clinicians. Delay in diagnosis of obturator hernia can lead to bowel necrosis and perforation with significant postoperative morbidity and mortality.

Pulmonary Tumourlets: Case Report and Review of Literature.

We report a case of tumourlets of the lung associated with carcinoid and neuroendocrine cell hyperplasia, found incidentally in a 30-year-old woman, who underwent bullectomy for pneumothorax. These lesions are histologically similar to carcinoid, but differ in molecular pathogenesis about which little is known. Their nature and significance is debated. Here, we point out the importance of histological, clinical, and diagnostic aspects and follow-up to have evidence of eventual malignant evolution.

Mediastinal Teratoma with Coexisting Adenocarcinoma and Carcinoid Tumor (Somatic-Type Malignancy): A Case Report with a Review of the Literature.

Germ cell tumors constitute 10% to 15% of anterior mediastinal neoplasms. Of these, mature teratoma is the most common. Somatic malignant transformation in mature teratoma is a very rare phenomenon. In the anterior mediastinum, few cases of malignant transformation in the form of carcinoma, sarcoma, or neuroendocrine tumors have been described. We present the case of a mature mediastinal teratoma in a 24-year-old female, diagnosed on computed tomography, where both carcinoid tumor and adenocarcinoma were seen. To the best of our knowledge, this is the first report of such a case. Malignant transformation in a mature teratoma confers a significantly worse prognosis and is difficult to diagnose only on clinical and radiological evaluation. As these lesions are so rare, the treatment options for these lesions are also not clearly defined. Extensive sampling and careful microscopic examination are needed when teratomas are submitted for pathological evaluation.

Phacoemulsification without preoperative topical mydriatics: induction and sustainability of mydriasis with intracameral mydriatic solution.

CONTEXT: Intracameral mydriatic solution can eliminate the disadvantages of repeated eye drop instillation regimen and provide adequate mydriasis for phacoemulsification with added advantages. AIMS: Evaluating the role of intracameral irrigating solution (0.5% lignocaine + 0.001% epinephrine) in initiating and maintaining the pupillary mydriasis during phacoemulsification. Secondary aims were to observe the effect of surgical time, nucleus density and ultrasound time on mydriasis during the procedure. SETTINGS AND DESIGN: The study is a prospective interventional case series, conducted at tertiary care institution. MATERIALS AND METHODS: Thirty patients underwent phacoemulsification under topical anesthesia for visually significant cataract. Pupillary dilatation was achieved by intracameral irrigation of mydriatic solution alone. Pupillary diameter was measured serially during surgery and ultrasound time and total surgical time were noted. STATISTICAL ANALYSIS USED: Paired samples student-t test was done to compare means. Spearman correlation coefficient was used to study the effect of various parameters on mydriasis. RESULTS: Thirty eyes completed the study. The pupil size increased from 2.1 mm (Range 2-3.5 mm SD ± 0.32) to 6.9 mm (Range 5-9 mm SD ± 1.02) in 30 seconds time after intracameral mydriatic solution delivery, and was 7.0 mm (Range 3.5 - 9 mm SD ± 0.20) at the end of surgery. Duration of surgery, grade of nucleus and ultrasound time had statistically insignificant effect on mydriasis. CONCLUSIONS: Intracameral solution containing 0.5% lignocaine and 0.001% epinephrine provides rapid mydriasis which is adequate for safe phacoemulsification and is unaffected by other parameters.

Nicotine-encapsulated poly(lactic-co-glycolic) acid nanoparticles improve neuroprotective efficacy against MPTP-induced parkinsonism.

For some instances of Parkinson disease (PD), current evidence in the literature is consistent with reactive oxygen species being involved in the etiology of the disease. The management of PD is still challenging owing to its ambiguous etiology and lack of permanent cure. Because nicotine offers neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, the neuroprotective efficacy of nicotine-encapsulated poly(lactic-co-glycolic) acid (PLGA) nanoparticles and the underlying mechanism of improved efficacy, if any, over bulk nicotine were assessed in this study. The selected indicators of oxidative stress, dopaminergic neurodegeneration and apoptosis, were measured in both in vitro and rodent models of parkinsonism in the presence or absence of "nanotized" or bulk nicotine. The levels of dopamine and its metabolites were measured in the striatum, nicotine and its metabolite in the nigrostriatal tissues while the immunoreactivities of tyrosine hydroxylase (TH), metallothionein-III (MT-III), inducible nitric oxide synthase (iNOS) and microglial activation were checked in the substantia nigra of controls and treated mice. GSTA4-4, heme oxygenase (HO)-1, tumor suppressor protein 53 (p53), caspase-3, lipid peroxidation (LPO), and nitrite levels were measured in the nigrostriatal tissues. Nicotine-encapsulated PLGA nanoparticles improved the endurance of TH-immunoreactive neurons and the number of fiber outgrowths and increased the mRNA expression of TH, neuronal cell adhesion molecule, and growth-associated protein-43 over bulk against 1-methyl-4-phenyl pyridinium ion-induced degeneration in the in vitro model. MPTP reduced TH immunoreactivity and levels of dopamine and its metabolites and increased microglial activation, expression of GSTA4-4, iNOS, MT-III, HO-1, p53, and caspase-3, and levels of nitrite and LPO. Whereas both bulk nicotine and nicotine-encapsulated PLGA nanoparticles modulated the changes toward controls, the modulation was more pronounced in nicotine-encapsulated PLGA nanoparticle-treated parkinsonian mice. The levels of nicotine and cotinine were elevated in nicotine-encapsulated PLGA nanoparticle-treated PD mouse brain compared with bulk. The results obtained from this study demonstrate that nanotization of nicotine improves neuroprotective efficacy by enhancing its bioavailability and subsequent modulation in the indicators of oxidative stress and apoptosis.