Publications by authors named "Parul Dubey"

16 Publications

  • Page 1 of 1

Direct physical interaction of active Ras with mSIN1 regulates mTORC2 signaling.

BMC Cancer 2019 Dec 19;19(1):1236. Epub 2019 Dec 19.

Division of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh, 226031, India.

Background: The mechanistic (or mammalian) target of rapamycin (mTOR), a Ser/Thr kinase, associates with different subunits forming two functionally distinct complexes, mTORC1 and mTORC2, regulating a diverse set of cellular functions in response to growth factors, cellular energy levels, and nutrients. The mechanisms regulating mTORC1 activity are well characterized; regulation of mTORC2 activity, however, remains obscure. While studies conducted in Dictyostelium suggest a possible role of Ras protein as a potential upstream regulator of mTORC2, definitive studies delineating the underlying molecular mechanisms, particularly in mammalian cells, are still lacking.

Methods: Protein levels were measured by Western blotting and kinase activity of mTORC2 was analyzed by in vitro kinase assay. In situ Proximity ligation assay (PLA) and co-immunoprecipitation assay was performed to detect protein-protein interaction. Protein localization was investigated by immunofluorescence and subcellular fractionation while cellular function of mTORC2 was assessed by assaying extent of cell migration and invasion.

Results: Here, we present experimental evidence in support of the role of Ras activation as an upstream regulatory switch governing mTORC2 signaling in mammalian cancer cells. We report that active Ras through its interaction with mSIN1 accounts for mTORC2 activation, while disruption of this interaction by genetic means or via peptide-based competitive hindrance, impedes mTORC2 signaling.

Conclusions: Our study defines the regulatory role played by Ras during mTORC2 signaling in mammalian cells and highlights the importance of Ras-mSIN1 interaction in the assembly of functionally intact mTORC2.
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http://dx.doi.org/10.1186/s12885-019-6422-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921532PMC
December 2019

Prevalence, Demographic Profile, and Psychological Aspects of Epilepsy in North-Western India: A Community-Based Observational Study.

Ann Neurosci 2018 Dec 12;25(4):177-186. Epub 2018 Jun 12.

Professor Preventive and Social Medicine, SMS Medical College, Jaipur, India.

Aims: This study was undertaken to determine the prevalence of active epilepsy, assess the sociodemographic profile, and psychological aspects of epilepsy in the Jaipur district of Rajasthan, India.

Methods: We conducted a community-based, cross-sectional observational study covering both rural ( = 165,660) and urban ( = 179,142) populations of Jaipur district using a house-to-house survey. An adapted, pre-designed World Health Organization screening questionnaire was used to identify the cases. Those confirmed by neurologists as true seizures were included in the study. Cases were classified as per the International League against Epilepsy recommendation. Global Mental Health Assessment Tool electronic questionnaire was used to analyze psychological aspects of cases. The caregivers of the patients participated in the knowledge, attitude, and practice (KAP) survey.

Results: A total of 380 patients (258 men, 122 women) were identified with active epilepsy. The estimated prevalence of active epilepsy was 1.1/1,000 population and 71% of cases belonged to low socioeconomic classes. Primary treatment gap was documented in 18.8% of cases in our study, 38% of cases were non-compliant to treatment with poorer compliance in those on pol-therapy, 76% had some psychiatric disorder, anxiety and depression being the commonest, and positive family history of epilepsy was found in 4.7%. KAP survey revealed that only 15% of the respondents believed that epilepsy is non-curable, 74% denied its infectious nature, 26% believed that epilepsy occurs due to past sins, and 81% said that they would not marry persons with epilepsy.

Conclusion: A relatively low prevalence (1.1/1,000) of active epilepsy and a smaller primary treatment gap (18.8%) was found in our study population. Almost three-fourth of cases had an associated psychological problem, Though caregivers were aware of the nature of disease, majority would not prefer to marry a person suffering from epilepsy.
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http://dx.doi.org/10.1159/000487072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470329PMC
December 2018

M2 polarization of macrophages by Oncostatin M in hypoxic tumor microenvironment is mediated by mTORC2 and promotes tumor growth and metastasis.

Cytokine 2019 06 3;118:130-143. Epub 2018 Apr 3.

Division of Toxicology and Experimental Medicine, Central Drug Research Institute (CSIR), Lucknow, Uttar Pradesh 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India. Electronic address:

Oncostatin M (OSM), an inflammatory cytokine belonging to the interleukin-6 (IL-6) superfamily, plays a vital role in multitude of physiological and pathological processes. Its role in breast tumor progression and metastasis to distant organs is well documented. Recent reports implicate OSM in macrophage M2 polarization, a key pro-tumoral phenomenon. M2 polarization of macrophages is believed to promote tumor progression by potentiating metastasis and angiogenesis. In the current study, we delineated the mechanism underlying OSM induced macrophage M2 polarization. The findings revealed that OSM skews macrophages towards an M2 polarized phenotype via mTOR signaling complex 2 (mTORC2). mTORC2 relays signals through two effector kinases i.e. PKC-α and Akt. Our results indicated that mTORC2 mediated M2 polarization of macrophages is not dependent on PKC-α and is primarily affected via Akt, particularly Akt1. In vivo studies conducted on 4T1/BALB/c mouse orthotropic model of breast cancer further corroborated these observations wherein i.v. reintroduction of mTORC2 abrogated monocytes into orthotropic mouse model resulted in diminished acquisition of M2 specific attributes by tumor associated macrophages. Metastasis to distant organs like lung, liver and bone was reduced as evident by decrease in formation of focal metastatic lesions in mTORC2 abrogated monocytes mice. Our study pinpoints key role of mTORC2-Akt1 axis in OSM induced macrophage polarization and suggests for possible usage of Oncostatin-M blockade and/or selective mTORC2 inhibition as a potential anti-cancer strategy particularly with reference to metastasis of breast cancer to distant organs such as lung, liver and bone.
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http://dx.doi.org/10.1016/j.cyto.2018.03.032DOI Listing
June 2019

Anti-proliferative effect of novel primary cetyl alcohol derived sophorolipids against human cervical cancer cells HeLa.

PLoS One 2017 18;12(4):e0174241. Epub 2017 Apr 18.

Biochemical Sciences Division, National Chemical Laboratory, Pune, India.

Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to display anticancer activity. In the present study, we report anti-proliferative studies on purified forms of novel SLs synthesized using cetyl alcohol as the substrate (referred as SLCA) and their anticancer mechanism in human cervical cancer cells. Antiproliferative effect of column purified SLCA fractions (A, B, C, D, E and F) was examined in panel of human cancer cell lines as well as primary cells. Among these fractions, SLCA B and C significantly inhibited the survival of HeLa and HCT 116 cells without affecting the viability of normal human umbilical vein endothelial cells (HUVEC). The two fractions were identified as cetyl alcohol sophorolipids with non-hydroxylated tail differing in the degree of acetylation on sophorose head group. At an IC50 concentration SLCA B (16.32 μg ml-1) and SLCA C (14.14 μg ml-1) blocked the cell cycle progression of HeLa cells at G1/S phase in time-dependent manner. Moreover, SLCA B and SLCA C induced apoptosis in HeLa cells through an increase in intracellular Ca2+ leading to depolarization of mitochondrial membrane potential and increase in the caspase-3, -8 and -9 activity. All these findings suggest that these SLCAs could be explored for their chemopreventive potential in cervical cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174241PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395175PMC
May 2017

The death wish and motor neuron disease! The chameleons and new research optimism.

Neurol India 2017 Jan-Feb;65(1):14-15

Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India.

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http://dx.doi.org/10.4103/0028-3886.198179DOI Listing
July 2019

Silk Fibroin-Sophorolipid Gelation: Deciphering the Underlying Mechanism.

Biomacromolecules 2016 10 29;17(10):3318-3327. Epub 2016 Sep 29.

Solid State Physics Division, Bhabha Atomic Research Centre , Mumbai, India.

Silk fibroin (SF) protein, produced by silkworm Bombyx mori, is a promising biomaterial, while sophorolipid (SL) is an amphiphilic functional biosurfactant synthesized by nonpathogenic yeast Candida bombicola. SL is a mixture of two forms, acidic (ASL) and lactonic (LSL), which when added to SF results in accelerated gelation of silk fibroin. LSL is known to have multiple biological functionalities and hence hydrogels of these green molecules have promising applications in the biomedical sector. In this work, SANS, NMR, and rheology are employed to examine the assembling properties of individual and mixed SLs and their interactions with SF to understand the mechanism that leads to rapid gelation. SANS and NMR studies show that ASL assembles to form charged micelles, while LSL forms micellar assemblies and aggregates of a mass fractal nature. ASL and LSL together form larger mixed micelles, all of which interact differently with SF. It is shown that preferential binding of LSL to SF causes rapid unfolding of the SF chain leading to the formation of intermolecular beta sheets, which trigger fast gelation. Based on the observations, a mechanism for gelation of SF in the presence of different sophorolipids is proposed.
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http://dx.doi.org/10.1021/acs.biomac.6b01069DOI Listing
October 2016

Commentary.

J Neurosci Rural Pract 2014 Jul;5(3):307-8

Department of Neurology, Goa Medical College, Goa, India.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078629PMC
July 2014

Clinicodiagnostic features of tuberculous meningitis and the role of CSF PCR in early diagnosis: a study from north-west India.

J Indian Med Assoc 2013 May;111(5):309-12, 314

The objective of this study was to study the clinical features and laboratory profile including acid fast bacillus microscopy, cerebrospinal fluid (CSF) culture and M. tuberculosis polymerase chain reaction (PCR) for an early diagnosis of tuberculous meningitis. Fifty consecutive patients, fulfilling the clinical criteria of tuberculous meningitis, were included in the study. All patients were subjected to detailed clinical and laboratory evaluation and radiological tests. CSF acid fast bacillus microscopy, culture and PCR were carried out in all and results were analysed. Majority of the patients presented with fever, headache, vomiting and signs of meningeal Irritation. Ziehl-Neelsen staining for acid-fast bacillus was positive in 4% cases, culture in 18% cases and CSF PCR for Mycobacterium tuberculosis was positive in 68%. Miliary pattern on chest x-ray was seen in 16% and CNS tuberculomas were seen in 14% cases. The CSF PCR estimation in clinically suspected cases of tuberculous meningitis may be an extremely valuable test for early diagnosis and institution of specific therapy.
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May 2013

Combination of AIDP and pyramidal signs associated with antecedent hepatitis A infection: a rare (co)occurrence.

BMJ Case Rep 2013 Jun 12;2013. Epub 2013 Jun 12.

Department of Neurology, SMS Medical College Hospital, Jaipur, Rajasthan, India.

Guillain-Barré syndrome (GBS) is a postinfectious illness and commonly occurs in association with infective agents such as Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, HIV, shigella, clostridium, Haemophilus influenzae; occasionally with acute hepatitis B, C, E; and more rarely with hepatitis A, as documented in various case reports. Classically, GBS presents with hyporeflexia or areflexia, but preserved and brisk reflexes have been described in context with GBS variant, AMAN (acute motor axonal neuropathy), in approximately 33% of the cases. Preserved or exaggerated tendon reflexes with extensor plantar response is not usually seen in patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP). We report a rare case of AIDP with upper motor neuron signs in association with an antecedent hepatitis A infection.
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http://dx.doi.org/10.1136/bcr-2013-009530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702957PMC
June 2013

Combination of Steven-Johnson syndrome and neuroleptic malignant syndrome following carbamazepine therapy: a rare occurrence.

BMJ Case Rep 2013 Jun 11;2013. Epub 2013 Jun 11.

Department of Neurology, SMS Medical College Hospital, Jaipur, Rajasthan, India.

Stevens-Johnson syndrome (SJS) is a severe, episodic, acute mucocutaneous reaction that is most often elicited by drugs and occasionally by infections. The drugs commonly implicated as the cause of SJS are anticonvulsants, sulfonamides, non-steroidal anti-inflammatory drugs and antibiotics. Carbamazepine (CBZ) has been commonly implicated in SJS. Neuroleptic malignant syndrome (NMS) is a rare, life-threatening but potentially treatable condition. Among the neuroleptics, haloperidol (parenteral) is implicated as a most common drug for NMS. Though rare, association of NMS with CBZ and association of NMS with toxic epidermal necrolysis (TEN) in a single patient after administration of neuroleptics has been reported in the literature before. However, a combination of NMS and SJS in a single patient after administration of CBZ has not been reported so far. We present a patient with seizure who developed SJS and NMS following administration of CBZ.
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http://dx.doi.org/10.1136/bcr-2013-008908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702838PMC
June 2013

Ophthalmoplegic migraine with trigeminal nerve involvement.

BMJ Case Rep 2013 May 27;2013. Epub 2013 May 27.

Department of Neurology, SMS Medical College Hospital, Jaipur, Rajasthan, India.

We report a 25-year-old man with a history of uncontrolled migrainous headaches who developed third nerve palsy and sensory loss over V1 distribution of trigeminal nerve, during an attack of severe migraine. Gadolinium-enhanced MRI of the brain and cavernous sinus was normal and did not disclose nerve enhancement. CT angiogram was also normal. The patient recovered uneventfully in 2 weeks on oral steroids. The commonest cranial nerve implicated in ophthalmoplegic migraine is the occulomotor nerve. Involvement of the fifth nerve has never been reported.
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http://dx.doi.org/10.1136/bcr-2013-009630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669997PMC
May 2013

A rare case of alcoholic pellagra encephalopathy with startle myoclonus and marked response to niacin therapy: time for a new dictum?

BMJ Case Rep 2013 Apr 22;2013. Epub 2013 Apr 22.

Department of Neurology, SMS Medical College Hospital, Jaipur, Rajasthan, India.

We report a case of 56-year-old man, chronic alcoholic, presented to us with progressive weakness in all the four limbs with stiffness and gait disturbance since 1-year associated with cognitive impairment. On examination he had mild confusion, spastic quadriparesis with brisk reflexes, extensor plantars and cerebellar features. During the hospital stay myoclonus was noticed in the patient, which was startle in nature. He did not have dermatitis, ascites or any stigmata of liver failure. MRI of brain revealed bilateral subdural effusion, left focal subarachnoid haemorrhage at perisylvian area and diffuse cortical atrophy. He was treated with supportive measures including thiamine with which his condition worsened. His serum niacin was low. With a possibility of alcoholic pellagra encephalopathy (APE) the patient was treated with niacin. His clinical condition improved drastically over next 1 week and startle myoclonus disappeared, favouring the diagnosis of APE though multiple confounding factors were present.
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http://dx.doi.org/10.1136/bcr-2013-008906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645309PMC
April 2013

Reversible neurological syndromes with atypical pneumonia.

Ann Indian Acad Neurol 2011 Apr;14(2):127-9

Department of Neurology, SMS Medical College & Attached Hospitals, Jaipur, Rajashthan, India.

Simultaneous or sequential involvement of lungs is frequently encountered with neurological syndromes like meningoencephalitis, cerebellitis, aseptic meningitis, transverse myelitis, or multiple cranial nerve palsies. However, pulmonary involvement is frequently overlooked when all the attention of physician is diverted to neurological disorder. Prompt and early recognition of such potentially treatable association is required to improve diagnostic and therapeutic outcome. We report six patients presenting with various neurological manifestations like meningitis, meningoencephalitis, and myelits associated with atypical pneumonia. With proper clinical correlation and relevant investigations, all of them were diagnosed in time and had remarkable recovery with appropriate treatment.
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http://dx.doi.org/10.4103/0972-2327.82806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141478PMC
April 2011

The Global Mental Health Assessment Tool-validation in Hindi: A validity and feasibility study.

Indian J Psychiatry 2010 Oct;52(4):316-9

Cheshire and Wirral Partnership NHS Foundation Trust, Wirral, Cheshire, UK.

Background: A computer-assisted interview, the Global Mental Health Assessment Tool-validation (GMHAT/PC) has been developed to assist general practitioners and other health professionals to make a quick, convenient, yet reasonably comprehensive standardized mental health assessment. GMHAT/PC has been translated into various languages including Hindi. This is the first study conducted in India, using the Hindi version GMHAT/PC of the series of studies assessing its validity in different cultures.

Aim: The study aims to assess the feasibility of using a computer assisted diagnostic interview by health professionals and to examine the level of agreement between the Hindi version GMHAT/PC diagnosis and psychiatrists' ICD-10 based clinical diagnosis.

Design: Cross-sectional validation study.

Setting: Psychiatric clinic of a General Hospital and an out patient (Neurology) clinic in the Teaching General Hospital in Jaipur, India.

Materials And Methods: All consecutive patients attending the psychiatric out patient clinic were interviewed using GMHAT/PC and psychiatrists made a diagnosis applying ICD-10 criteria for a period of six weeks. A small sample of subjects was interviewed in a similar way in a Neurology clinic for four weeks.

Results: The mean duration of interview was under 17 minutes. Most patients were pleased that they were asked about every aspect of their mental health. The agreement between psychologists' GMHAT/PC interview diagnoses and psychiatrists' clinical diagnoses was excellent (Kappa 0.96, sensitivity 1.00, and specificity 0.94).

Conclusion: GMHAT/PC Hindi version detected mental disorders accurately and it was feasible to use GMHAT/PC in Indian settings.
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http://dx.doi.org/10.4103/0019-5545.74305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025156PMC
October 2010

Newer forms of unclassified headaches.

Headache 2011 Jan 1;51(1):163. Epub 2010 Oct 1.

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http://dx.doi.org/10.1111/j.1526-4610.2010.01769.xDOI Listing
January 2011

Subarachnoid hemorrhage with transient ischemic attack: another masquerader in cerebral venous thrombosis.

Indian J Med Sci 2010 Feb;64(2):85-9

Department of Neurology, SMS Medical College, Jaipur, India.

Cerebral venous thrombosis has a wide spectrum of clinical manifestations that may mimic many other neurological disorders and lead to frequent misdiagnoses or delay in diagnosis. The most frequent symptoms and signs are headache, seizures, focal deficits, and papilledema. A number of rare atypical manifestations have been described. Cerebral venous thrombosis may present with an isolated intracranial hypertension type picture, thunderclap headache, attacks of migraine with aura, isolated psychiatric disturbances, pulsatile tinnitus, isolated or multiple cranial nerve involvement, and occasionally as subarachnoid hemorrhage (SAH) or transient ischemic attack. Our patient presented with thunderclap headache and transient ischemic attack like episode with obvious SAH on CT scan. Acute SAH suggests the presence of a vascular lesion, such as ruptured aneurysm, and CVT is not generally considered in the diagnostic workup of SAH. The case emphasizes the importance of cerebral venous study in nonaneurysmal cases of SAH. It is important to have a high index of suspicion in such atypical cases to avoid delay in diagnosis.
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http://dx.doi.org/10.4103/0019-5359.94405DOI Listing
February 2010