Browsing by Author "Manpreet Kaur"

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Assessment of genetic and environmental risk factor association with amyotrophic lateral sclerosis diseases
(Science and Engineering Research Support Society, 2020) Nitish Kumar Singh; Abhay Kumar Yadav; Manpreet Kaur; Ashish; Royana Singh
Amyotrophic lateral sclerosis (ALS) is a type of progressive neurodegenerative disease of motor neurons, resulting in a worsening weakness of voluntary muscles until death from respiratory failure occurs after about 3 to 5 years. Although highly significant mobility have been made in our understanding of the genetic causes of ALS, the contribution of environmental factors has been more challenging to assess. Extensive studies of the clinical patterns of ALS, individual family histories preceding the onset of ALS, and the rates of ALS in different populations and groups have led to improved patient care, but have not yet revealed a replicable, definitive environmental risk factor. In this review, we outline what is currently known of the environmental and genetic epidemiology of ALS, describe the current state of the art concerning the different types of ALS, and explore whether ALS should be considered a single disease or a syndrome. We examine the relationship between genetic and environmental risk factors and propose a disease model in which ALS is considered to be the result of environmental risks and time acting on a pre-existing genetic load, followed by an automatic, self-perpetuating decline to death. ⓒ 2019 SERSC.
BCR-ABL kinase domain mutations in CML patients, experience from a tertiary care center in North India
(Elsevier Ltd, 2024) Akhilesh S; Arunim shah; Ashish Ashish; Nitish kumar Singh; Manpreet Kaur; Abhay kumar Yadav; Royana singh
Background: Chronic Myeloid Leukemia is characterized by the presence of the Philadelphia Chromosome (Ph) which contains the BCR::ABL1 fusion gene that occurs due to a reciprocal translocation between chromosomes 9 and 22. This accounts for up to 15 % of all adult leukemias [1]. Most patients treated with first line tyrosine kinase inhibitor (TKI) imatinib achieve durable response but may undergo relapse at some stage [2]. The most important mechanism that may confer imatinib resistance is point mutation within BCR::ABL kinase domain. Other generation ABL tyrosine kinase inhibitors such as dasatinib, nilotinib, bosutinib and ponatinib help to overcome imatinib resistance [3]. Sensitivity of the patient to each of the above TKIs depends upon the individual candidate mutation present. Thus, it is important to perform mutation analysis for effective therapeutic management of CML patients once they show imatinib resistance. We used direct sequencing to identify the different types of mutations responsible for resistance of imatinib treatment from north India. Methods: In this study, the patient resistance for the imatinib were analyzed for BCR::ABL kinase domain mutation by direct sequencing and the detected mutations along with their percentage prevalence were reported. Results: 329 patients with CML-CP were analyzed for BCR::ABL kinase domain mutation. Total 66 (20.06 %) patients out of 329 had mutation in at least one of the domains of BCR::ABL conferring resistance to different generations of TKI. Mutations in BCR::ABL kinase domain was observed in different domain of BCR::ABL. ATP binding P-Loop (42.42 %), Direct binding site (36.36 %), C-Loop (10.60 %), A-Loop (6.06 %), SH2 contact (3.03 %), SH3 contact (1.51 %). Conclusion: Total 20.06 % patients (66/329) show mutation in at least one of the structural motifs of BCR-ABL kinase domain, which further confer the resistance to a particular generation of TKI. © 2023 The Author(s)
Copper (I) complexes based on novel N, N′-disubstituted thiocarbamides: Synthesis, spectroscopic, in vitro cytotoxicity, DNA damage and G0/G1 cell cycle arrest studies
(Elsevier S.A., 2019) Sunil K. Pandey; Seema Pratap; Sandeep Pokharia; Hirdyesh Mishra; Gaetano Marverti; Manpreet Kaur; Jerry P. Jasinski
Four trigonal planar copper (I) complexes with novel N, N′-disubstituted isobutoxycarbonyl thiocarbamide ligands were synthesized and characterized by elemental analysis, spectroscopic (FT–IR, 1H and 13C NMR, UV–Visible), TG analysis and single crystal X-ray studies of ligands 1 and 2. The synthesized copper (I) complexes (1a–4a) bear the general formula [Cu(ROCONHCSNHR1)2Cl] where R = –CH2CH(CH3)2 and R1 = 2, 4-dichlorophenyl (1), 2-chloro 4-nitrophenyl (2), 2-methoxyphenyl (3), 4-chloro-2-nitrophenyl (4). All the complexes are mononuclear coordinating through thione sulfur only. Coordination through carbonyl oxygen would have not been possible owing to the presence of strong intramolecular hydrogen bonding (N–H⋯O[dbnd]C) in the ligands. The proposed trigonal planar geometry of complexes has been validated by density functional theory (DFT) study of complex 1a. Computational details of theoretical calculations (DFT) of complex have been discussed. Cyclic voltammogram of complexes 1a–4a displayed quasireversible redox behaviour corresponding to Cu(I)/Cu(II) couple. In vitro cytotoxicity results of ligands and complexes against five human cancer cell lines indicated that all the complexes displayed stronger inhibitory properties than the ligands. The most effective were complexes 3a, 4a and 5a. All the complexes exhibit IC50 values even lower than cisplatin against C13* cell line (cisplatin resistant). The comet assay test of all the complexes against 2008, C13* and IGROV-1 cell lines indicated significant damage to the DNA structure. All the complexes induce apoptosis in 2008, C13* and IGROV-1 cells by blocking cell cycle progression of these cells in G0/G1 phase. © 2019 Elsevier B.V.
Development of a multiplex MethyLight assay for he detection of DAPK1 and SOX1 methylation in epithelial ovarian cancer in a north Indian population
(2016) Manpreet Kaur; Alka Singh; Manisha Sachan; Kiran Singh; Sameer Gupta
Ovarian cancer is the fourth most common cancer in women worldwide. It is very heterogeneous at the clinical, histopathological and molecular levels and is caused by the accumulation of genetic and epigenetic changes in regulatory genes. More than 90% of ovarian cancers are epithelial in origin. Ovarian cancer is typically asymptomatic in its early stages, and due to difficulties in early detection, most ovarian cancers are diagnosed at an advanced stage. The positive predictive value of CA-125, a routinely used serum protein marker is < 30%; therefore, for effective screening, there is a need to develop a marker with high sensitivity for early detection. Development of blood-based biomarkers that detect DNA methylation in cellfree tumor-specific DNA is now being considered as a potential approach for the early diagnosis of cancer. Our objective in this study was to develop an absolute quantitative method, the MethyLight assay, to detect the promoter methylation status of two tumor suppressor genes. We analyzed the methylation level of the promoter regions of these genes in 42 tumor samples using the MethyLight assay. SOX1 promoter methylation was significantly higher in cancer samples than in normal samples (P = 0.011), whereas this difference between cancer and normal samples was not significant for DAPK1 promoter methylation (P = 0.18), when analyzed separately in a singleplex assay, whereas the detection frequency and significance level increased several-fold when these genes were analyzed together in a multiplex assay (P = 0.0004).The sensitivity was found to be 62% and 83% for DAPK1 and SOX1, respectively, when analyzed separately in the singleplex assay, but increased to 90% in the multiplex assay when either the SOX1 or the DAPK1 gene promoters showed methylation. © 2016, The Genetics Society of Japan. All rights reserved.
Effects of SARS-Cov-2 infection and rhino-orbital mucormycosis on concentrations of inflammatory biomarkers in Indian populations
(IP Innovative Publication Pvt. Ltd., 2022) Ajay Kumar Yadav; Shivam Tiwari; Bhupendra Kumar; Abhay Kumar Yadav; Ashish Ashish; Nitish Kumar Singh; Manpreet Kaur; Shivani Mishra; Shani Vishwakarma; Surendra Pratap Mishra; Rajendra Prakash Maurya; Nargis Khanam; Pooja Dubey; Janhavi Yadav; Royana Singh; Sayeed Mehbub Ul Kadir
Rhino-orbital mucormycosis is a rare life threatening invasive fungal infection that has recently shown a very high mortality rate in India during COVID-19 pandemic. We have designed the present study to find out associations between COVID-19 induced rhino-orbital mucormycosis and concentrations of inflammatory markers, i.e. D-dimer, Ferritin, IL-6, CRP and PCT, in blood serum of Indian population. There were four groups in the study, viz. control group with healthy subjects, treatment group-1 with patients suffering from SARS-COV-2 infection, treatment group-2 with patients suffering from both SARS-COV-2 infection and rhino-orbital mucormycosis, and treatment group-3 with patients suffering from rhino-orbital mucormycosis after SARS-COV-2 infection recovery. Inflammatory markers were quantified with standard protocols, and recorded data were subjected to statistical analyses. We found that patients suffering from SARS-COV-2 infection were more susceptible to rhino-orbital mucormycosis, as they had higher concentrations of inflammatory markers in their blood than the other subjects. Diabetes mellitus, hypertension, cardiovascular diseases and renal disorders were the associated comorbidities with the patients. We also found higher concentrations of inflammatory markers in males than the females, indicating towards their higher susceptibility in developing rhino-orbital mucormycosis than females. Present study therefore suggests that the frequent occurrence of rhino-orbital mucormycosis in India during second wave of COVID-19 was possibly due to indiscriminate use of corticosteroids by COVID-19 patients. Subjects with previous history of comorbidities like diabetes mellitus, hypertension, cardiovascular disorders and renal diseases are the most susceptible population groups for developing infection. Moreover, males are at higher risk of developing mucormycosis than the females. © 2022 Innovative Publication, All rights reserved.
Genetic Analysis of Recurrent Pregnancy Loss: Role of Karyotyping in Understanding Pathogenesis and Management
(Jaypee Brothers Medical Publishers (P) Ltd, 2025) Shivani Mishra; Royana Singh; Sangeeta Rai; Ashish Ashish; Nitish Kumar Singh; Manpreet Kaur; Nargis Khanam; Janhavi Yadav; Chetan Sahni
Introduction: Recurrent pregnancy loss (RPL) is defined as two or more spontaneous pregnancy losses within 20–24 weeks of the gestational period, which typically occur in the early stages of pregnancy. Various factors can contribute to RPL, including genetic factors, hormonal imbalances, uterine abnormalities, autoimmune disorders, infections, and lifestyle factors. Materials and methods: This study involved the conventional karyotyping of women facing RPL with the G-banding method and the culture procedure of leukocytes. The statistical analysis was done by IBM SPSS 20 after the biochemical data collection and karyotyping results. Results: The total samples were collected from 160 couples, out of which only 130 were successfully done with conventional karyotyping. It was noted in this study that the genetic rearrangement in female partners was found to be 11.5%, excluding the anatomical, immunogenic, and hormonal factor dysfunctions. The advanced maternal age and primary RPL were found to be more actively causing recurrent miscarriages. Conclusion: These investigations emphasize the importance of genetic analysis in RPL cases, biochemical, and cytogenetic analysis. The karyotyping must be done to rule out any chromosomal rearrangement in male and female partners. The previous family history may indicate the likelihood of carrying chromosomal rearrangements; thus, further study needs to be done in large populations. © (2025), (Jaypee Brothers Medical Publishers (P) Ltd). All rights reserved.
Ovotesticular Disorder of Sex Development in a Tertiary Care Center in North India: A Single‑center Analysis over a 5‑year Period
(Wolters Kluwer Medknow Publications, 2023) Sarita Chowdhary; Maneesha Upadhayaya; Gunjan Rai; Manpreet Kaur; Nitish Kumar Singh; Kanika Sharma; Ritesh Yadav; Bitan Naik; Shiv Prasad Sharma; Royana Singh
Background: Disorders of sexual development (DSD) encompass a group of congenital conditions characterized by diverse genotypic and phenotypic variations. Ovotesticular (OT) DSD is a distinctive subtype within this spectrum. Among the array of DSD, OT-DSD stands as one of the most infrequent anomalies, with reported prevalence rates as scarce as 1 in 83,000. This study aims to elucidate the clinical, hormonal, cytogenetic, surgical, and histopathological characteristics of OT disorder of sex development (OT-DSD) within a tertiary center in North India. Methodology: A retrospective analysis was conducted, involving a comprehensive review of records pertaining to OT-DSD patients from the years 2018 to 2022, all of whom were incorporated into the study. Results: The mean age of presentation in this study was 10 years, spanning from 6 to 15 years. Predominantly, the affected individuals were male, with a solitary patient representing the female category. Clinical manifestations displayed a spectrum encompassing genital ambiguity, inguinal swelling, and primary amenorrhea. The karyotypes observed were 46,XX in four patients and 46,XY in one patient. A holistic assessment, inclusive of clinical evaluation, hormonal assays, pelvic ultrasonography, and surgical intervention when necessary, was administered to all patients. Among these cases, three patients were reared as males, their gender assignment driven by external genital appearance and sociocultural influences. Notably, none of the patients manifested gonadal tumors during the course of the study. Conclusion: In cases of ambiguous genitalia, the consideration of OT-DSD should be integral to the differential diagnosis, underscoring the significance of heightened clinical awareness and informed decision-making. © 2023 National Journal of Clinical Anatomy | Published by Wolters Kluwer - Medknow.
Synthesis, characterisation, Hirshfeld surface and in vitro cytotoxicity evaluation of new N-aryl-N′-Alkoxycarbonyl thiocarbamide derivatives
(Elsevier B.V., 2020) Sunil K. Pandey; Seema Pratap; Sunil K. Rai; Gaetano Marverti; Manpreet Kaur; Jerry P. Jasinski
Four new compounds N-(4-nitrophenyl)-N’-(isobutoxycarbonyl) thiocarbamide (1), N-(2, 4-nitrophenyl)-N’-(isobutoxycarbonyl) thiocarbamide (2), N-(4-nitrophenyl)-N’-(ethoxycarbonyl) thiocarbamide (3) and N-(2-Chloro- 4-nitrophenyl)-N’-(ethoxycarbonyl) thiocarbamide (4) were prepared and their structures confirmed by using various spectroscopic (FT-IR, UV–Visible, 1H and 13C NMR) and single crystal X-ray studies of 1 and 3. The presence of intramolecular (N–H⋯O[dbnd]C) hydrogen bond in the crystal structure of both the compounds causes planarity of carbonyl thiocarbamide unit and trans orientation of C[dbnd]O and C[dbnd]S group. The intermolecular contacts (C–H⋯S, C–H⋯O and N–H⋯S) present in crystal structures have been examined by Hirshfeld surface analysis and their associated 2D fingerprint plots. All the compounds were assessed for their in vitro cytotoxic properties against a panel of seven human cancer cells such as cervical carcinoma (2008, C13*), colorectal (HT29 and HCT116) and ovarian carcinoma (A2780, A2780/CP and IGROV-1). Among them, compounds 2 and 4 exhibited better activity than 1 and 3 against all the cell lines tested. © 2019 Elsevier B.V.
Synthesis, characterization, Hirshfeld surface, cytotoxicity, DNA damage and cell cycle arrest studies of N, N-diphenyl-N’-(biphenyl-4-carbonyl/4-chlorobenzoyl) thiocarbamides
(Elsevier B.V., 2019) Sunil K. Pandey; Seema Pratap; Sunil K. Rai; Gaetano Marverti; Manpreet Kaur; Jerry P. Jasinski
The condensation reaction of biphenyl-4-carbonyl isothiocyanate/4-chlorobenzoyl isothiocyanate with diphenylamine yielded two new compounds; N-diphenyl-N’-(biphenyl-4-carbonyl) thiocarbamide (1) and N, N-diphenyl-N’-(4-chlorobenzoyl) thiocarbamide (2). Structure of the compounds were determined by analytical, spectroscopic (UV–Visible, FT−IR, 1 H, & 13 C NMR), powder and single-crystal X-ray diffraction methods. Hirshfeld surface analysis and their associated two dimensional fingerprint plots of compounds were used as theoretical approach to assess driving force for crystal structure formation via the intermolecular interactions in their crystal lattices. The compounds were screened for their in vitro cytotoxicity activity against a panel of five human cancer cell lines namely; cervical (2008 and C13*) and ovarian carcinoma (A2780, A2780/CP and IGROV-1). Both the compounds exhibited promising activity against cervical and IGROV-1 cancer cells whereas for the other two cell lines appreciable activities were observed. The cell cycle arrest at G 0 /G 1 phase is supported by the DNA damage and apoptosis studies of the compounds against 2008, C13* and IGROV-1 cell lines. © 2019 Elsevier B.V.
Synthesis, spectroscopic, crystal structure and in vitro cytotoxicity studies of N-thiophenoyl-N′-substituted phenyl thiocarbamide derivatives
(Elsevier B.V., 2019) Sunil K. Pandey; Seema Pratap; Gaetano Marverti; Manpreet Kaur; Jerry P. Jasinski
A series of eight biologically active N, N′-disubstituted thiocarbamide compounds (1–8) have been prepared from thiophene-2-carbonyl isothiocyanate and various substituted aromatic primary amines (2,4-dichlorophenyl aniline, 4-chloro-3-nitrophenyl aniline, 4-methoxycarbonylphenyl aniline, 3-methoxycarbonylphenyl aniline, 2-methoxycarbonylphenyl aniline, 4-methoxyphenyl aniline, 2-methoxyphenyl aniline and 2-nitrophenyl aniline). Their structures were confirmed by elemental analyses, various spectroscopic techniques ((FT–IR, 1 H and 13 C NMR) and single crystal X-ray analysis of compound (1). In the molecular structure of compound (1) twisted confirmation of the carbonyl and thiocarbonyl group across C–N bond of thiocarbamide moiety and an offset face-to-face π–π stacking between two thiophene and two benzene ring of two molecules is observed. In vitro cytotoxicity assay of all the above compounds and five more (9–13) were carried out using seven human cancer cell lines; cervical (2008 and C13*), colorectal (HT29 and HCT116) and ovarian carcinoma (A2780, A2780/CP and IGROV-1). The results revealed that compounds 1, 11, 12 and 13 displayed promising inhibitory activity against all the cell lines tested. © 2018
The Morphological Features of Anencephaly in North Indian Population
(Wolters Kluwer Medknow Publications, 2023) Rashmi; Nitish Kumar Singh; Ashish; Abhay Kumar Yadav; Manpreet Kaur; Royana Singh
Background: Anencephaly occurs due to the complete absence of cranial vault and subsequent disruption of the cerebral cortex with a severely damaged brain. In anencephaly, the forebrain and brain stem are exposed. Forebrain either does not develop or is destroyed, leading to the absence of cerebrum and cerebellum. Methodology: Neural tube defects were taken in the study group. During the autopsy, clinical findings, external examination, internal examination, and photography were done along with the histopathology of the specimens to confirm the anomalies at microscopic level using hematoxylin and eosin staining. Results: In our study, we observed a simian crease in 4 out of 5 (80%) cases. Furthermore, there was presence of tooth which was not seen in previous studies. Central nervous system anomalies like spina bifida, gastro intestinal tract (GIT) anomalies like cleft palate, intestinal obstruction of megacolon, and malrotation of gut were some of the common anomalies which were observed in our study. Conclusion: It may be suggested that Anencephaly shows a female predisposition and the cases seems to be associated more in the primigravida females.The classical phenotypic presentation of anencephaly having absent cranial vault, low set ears, protruding eyes were present in all subjects studied. In our study, we observed a simian crease in 4 out of 5 (80%) cases. Furthermore, there was presence of tooth which was not seen in previous studies. Central nervous system anomalies like spina bifida, GIT anomalies like cleft palate, intestinal obstruction of megacolon, and malrotation of gut were some of the common anomalies which were observed in our study. © 2023 Journal of the Anatomical Society of India.