Browsing by Author "Munshi, Anjana"

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Advanced molecular therapies for neurological diseases: focus on stroke, alzheimer's disease, and parkinson's disease
(Springer-Verlag Italia s.r.l., 2022-09-06T00:00:00) Katta, Madhumitha; Mathew, Blessy Aksa; Chaturvedi, Pragya; Ludhiadch, Abhilash; Munshi, Anjana
Neurological diseases (NDs) are one of the leading causes of disability and the second leading cause of death globally. Among these stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are the most common NDs. A rise in the absolute number of individuals affected with these diseases indicates that the current treatment strategies in management and prevention of these debilitating diseases are not effective sufficiently. Therefore, novel treatment strategies are being explored to cure these diseases by addressing the causative mechanisms at the molecular level. Advanced therapies like gene therapy (gene editing and gene silencing) and stem cell therapies aim to cure diseases by gene editing, gene silencing and tissue regeneration, respectively. Gene editing results in the deletion of the aberrant gene or insertion of the corrected gene which can be executed using the CRISPR/Cas gene editing tool a promising treatment strategy being explored for many other prevalent diseases. Gene silencing using siRNA silences the gene by inhibiting protein translation, thereby silencing its expression. Stem cell therapy aims to regenerate damaged cells or tissues because of their ability to divide into any type of cell in the human body. Among these approaches, gene editing and gene silencing have currently been applied in vitro and to animal models, while stem cell therapy has reached the clinical trial stage for the treatment of NDs. The current status of these strategies suggests a promising outcome in their clinical translation. � 2022, Fondazione Societ� Italiana di Neurologia.
Analysis of pro‐ and anti‐inflammatory cytokine gene variants and serum cytokine levels as prognostic markers in breast cancer
(Wiley online Library, 2018) Kaur, R; P., Vasudeva, K.; Singla, H; Benipal, R. P. S; Khetarpal, Preeti; Munshi, Anjana
Analysis of pro‐ and anti‐inflammatory cytokine gene variants and serum cytokine levels as prognostic markers in breast cancer
(Wiley, 2018) Kaur, Raman Preet; Vasudeva, Kanika; Singla, Heena; Benipal, Raja Paramjeet Singh; Khetarpal, Preeti; Munshi, Anjana
The aim of current study was to evaluate the genetic variation in all the genes encoding pro‐ and anti‐inflammatory cytokines in association with breast cancer development in patients from Malwa region of Punjab. The importance of the levels of interleukin (IL)‐17, tumor necrosis factor, interferon γ, IL‐10, IL‐6, IL‐4, and IL‐2 with respect to clinicopathological data, prognosis, and disease‐free survival was also determined in these patients. Two hundred and fifty female breast cancer patients and 250 age‐matched controls were screened for variations in cytokine‐encoding genes using global screening array microchip and PCR‐RFLP. The level of cytokines was estimated in 150 patients and 60 age‐matched controls using BD™ Cytometric Bead Array (CBA) Human Th1/Th2/Th17 cytokine kit by BD Accuri flow cytometer. The difference in cytokine levels was evaluated by Mann–Whitney test. No significant variation in the genes encoding various cytokines was found between patients and controls. Out of the seven cytokines evaluated, the levels of IL‐6 and IL‐17a were found to be significantly high in patients in comparison with controls ( p = 0.001 and 0.02, respectively). The elevated levels of these cytokines are also associated significantly with poor outcome. We did not find any specific variation in the genes encoding various cytokines between patients and controls. However, there was a significant difference in the serum levels of IL‐6 and IL‐17a between patients and controls, and the elevated levels of these two cytokines associated significantly with poor outcome in breast cancer patients and, therefore, can be used as prognostic markers.
Apert's syndrome: Study by whole exome sequencing
(Chongqing yi ke da xue, di 2 lin chuang xue yuan Bing du xing gan yan yan jiu suo, 2018) Munshi, Anjana; Khetarpal, Preeti; Das, Satrupa; Rao, Venkateshwar; Valecha, Monica; Bansal, Manita; Kumar, Roshan
In the present study we attempted a parent-child trio, whole exome sequencing (WES) approach to study Apert's syndrome. Clinical characteristics of the child were noted down and WES was carried out using Ion Torrent System that revealed the presence of previously reported P253R mutation in FGFR2 gene. Presence of two SNPs rs1047057 and rs554851880 in FGFR2 gene with an allelic frequency of 0.5113 and 0.001176 respectively and 161 complete damaging mutations were found. This study is the first reported case of exome sequencing approach on an Apert's syndrome patient aimed at providing better genetic counselling in a non-consanguineous relationship. - 2017 Chongqing Medical University
Apert’s syndrome: study by whole exome sequencing
(Elsevier, 2017) Munshi, Anjana; Khetarpal, Preeti; Das, Satrupa; Rao, Venkateshwar; Valecha, Monica; Bansal, Vanita; Kumar, Roshan
In the present study we attempted a parent-child trio, whole exome sequencing (WES) approach to study Apert’s syndrome. Clinical characteristics of the child were noted down and WES was carried out using Ion Torrent System that revealed the presence of previously reported P253R mutation in FGFR2 gene. Presence of two SNPs rs1047057 and rs554851880 in FGFR2 gene with an allelic frequency of 0.5113 and 0.001176 respectively and 161 complete damaging mutations were found. This study is the first reported case of exome sequencing approach on an Apert’s syndrome patient aimed at providing better genetic counseling in a non-consanguineous relationship.
Apolipoprotein C3 gene polymorphisms in Southern Indian patients with nonalcoholic fatty liver disease
(Springer, 2014) Munshi, Anjana
Aim Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today. A previous study has suggested an association of apolipoprotein C3 (APOC3) gene variants with the risk of NAFLD in Asian Indian men living in the Western regions. The present study was carried out with an aim to evaluate the association of demographic features, serum lipid profile and APOC3 gene variants (C-482T and T-455C) NAFLD. Methods One hundred and fifty NAFLD patients and 150 age and gender-matched controls were included in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect the genotypes of APOC3. Serum lipid profile was analyzed. Results In the present study, body mass index was not a predictive demographic marker for NAFLD. Serum triglycerides were higher in patients (mean 155.95 ± 59.0) with NAFLD compared to the control group (mean 133.75 ± 44.71) (p = 0.016). APOC3 gene polymorphism T-455C (rs2854116) was significantly associated with NAFLD (p = 0.001). However, we did not find a significant association of C-482T polymorphism (rs2854117) of APOC3 gene with NAFLD. Genotype -455C/C of the SNP, rs2854116 associated significantly with the elevated serum triglycerides in patients. Conclusions The polymorphism T-455C in APOC3 gene and elevated serum triglycerides were associated with NAFLD.
Assessment of Resting-state functional Magnetic Resonance Imaging Connectivity Among Patients with Major Depressive Disorder: A Comparative Study
(SAGE Publications Inc., 2023-08-29T00:00:00) Singh, Paramdeep; Singh, Jawahar; Peer, Sameer; Jindal, Manav; Khokhar, Sunil; Ludhiadch, Abhilash; Munshi, Anjana
Background: Resting-state functional connectivity analysis has a potential to unearth the putative neuronal underpinnings of various disorders of the brain. Major depressive disorder (MDD) is regarded as a disorder arising from alterations in functional networks of the brain. Purpose: There is paucity of literature on resting-state functional magnetic resonance imaging (Rs-fMRI) in MDD, especially from the Indian subcontinent. The purpose of our study was to elucidate the differences in Rs-fMRI connectivity between MDD patients and age and gender matched healthy controls (HC). Methods: In this prospective single institute-based study, the patients were recruited consecutively based on Hamilton depression rating scale (HAM-D). Age and gender matched HC were also recruited. Rs-fMRI and anatomical MRI images were acquired for all the subjects (MDD and HC group) and subsequent analysis was done using the CONN toolbox. Results: A total of 49 subjects were included in the final analysis (MDD = 28 patients, HC = 21). HAM-D score was noted to be 24.4 � 4.8 in the MDD group. There was no significant difference between MDD and HC groups as far as age, gender, employment status, and level of education is concerned. Region-of-interest-based analysis of Rs-fMRI data showed a significantly lower connectivity between the left insula and left nucleus accumbens and between left paracingulate gyrus and bilateral posterior middle temporal gyri in MDD group as compared to HC group. Conclusion: There is reduced connectivity between certain key regions of the brain in MDD patients, that is, between the left insular cortex and the left nucleus accumbens and between the left paracingulate gyrus and the bilateral posterior middle temporal gyrus. These findings could explain the basis of clinical features of MDD such as anhedonia, rumination of thoughts, reduced visuo-spatial comprehension, reduced language function, and response to external stimuli. � 2023 Indian Academy of Neurosciences (IAN).
Association between PDE4D gene and ischemic stroke: recent advancements
(Taylor and Francis Ltd, 2016) Das, Satrupa; Roy, Sitara; Munshi, Anjana
Stroke is a severe complication and a leading cause of death worldwide and genetic studies among different ethnicities has provided the basis for involvement of phosphodiesterase 4D (PDE4D) gene in cerebrovascular diseases. Recent advancements have evaluated the role of this gene in stroke and these studies have provided a stronger support for the involvement of this gene in stroke development and few studies also suggest that it may influence outcome. Furthermore, case-control studies and meta-analysis studies have provided strong evidence for certain variants in PDE4D to predispose to stroke only among certain ethnicities. Thus, this review focuses on recent progress made in PDE4D gene research involving genetic, molecular and pharmacological aspect. A strong conclusion has emerged that clearly indicates a pivotal role played by this gene in ischemic stroke globally. Studies have also noticeably highlighted that PDE4D gene/pathway can be a suitable drug target for managing stroke; however, a more comprehensive research is still required to understand the molecular and cellular intricacies this gene plays in stroke development, progression and its outcome. ? 2015 Taylor and Francis.
Association of -1382A>G CCL11 gene variant with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population
(Medknow Publications, 2014) Roy, Sitara; Das, Satrupa; Munshi, Anjana; Kaul, Subhash; Jyothy, Akka
Conclusion: The results of the present study show that the GG genotype is a significant risk factor for ischemic as well as hemorrhagic stroke. Further, the frequency of the GG genotype was observed to be higher in hemorrhagic stroke patients in comparison with ischemic stroke. Evaluating the association with ischemic stroke subtypes, a significant association was observed with intracranial large artery atherosclerosis and lacunar stroke.Background: CCL11 (Eotaxin-1) is an important inflammatory cytokine belonging to the CC family of chemokines associated with a number of infection or inflammation-related diseases such as atherosclerosis and stroke. We investigated the association of CCL11 gene polymorphism rs4795895-1382A>G with ischemic and hemorrhagic stroke.Materials and Methods: Six hundred and twenty ischemic stroke patients, 620 age- and sex-matched healthy controls, and 220 hemorrhagic stroke patients, 220 age- and sex-matched healthy controls were included in the present study. The CCL11 gene polymorphism rs4795895-1382A>G was determined using PCR-RFLP technique.Results: We found a statistically significant difference in the genotypic distribution between ischemic stroke patients and controls (For GG vs. AA, ?2= 7.604; P < 0.001, Odds ratio = 2.793; 95% CI = 1.308-5.9). For GG vs. AA + AG, ?2= 44.8, P < 0.001, Odds ratio = 2.382 (95% CI = 1.842-3.081). A significant difference was observed in the frequency of G and A alleles in patients and controls (For G vs. A, ?2= 43.26; P < 0.001, Odds ratio = 2.127; 95% CI = 1.693-2.672). Statistically significant difference was observed in the genotypic distribution between hemorrhagic stroke patients and controls (For GG vs. AG, ?2= 26.78; P = 0.001, Odds ratio = 3.5; 95% CI = 2.162-5.824). A significant difference was observed in the frequency of G and A alleles in patients and controls (For G vs. A, ?2= 41.98; P = 0.001, Odds ratio = 4.1; 95% CI = 2.61-6.44).
Association of ACE gene I/D polymorphism and ACE levels with hemorrhagic stroke: comparison with ischemic stroke
(Springer-Verlag Italia s.r.l., 2015) Das, Satrupa; Roy, Sitara; Sharma,Vandana; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
In the present study, we investigated the association of insertion/deletion polymorphism of ACE gene with genetic predisposition to hemorrhagic stroke and also determined the mean ACE activity levels in ischemic and hemorrhagic stroke patients. Two hundred hemorrhagic stroke, 200 ischemic stroke patients and 200 gender and age matched controls were recruited for the study. We found statistically significant difference in the genotypic distribution between hemorrhagic patients and controls for dominant, co-dominant and recessive models. Significant difference was observed in the allelic frequencies between hemorrhagic patients and controls. Multiple logistic regression analysis confirmed these findings [adjusted OR for DD genotype was 2.46 (95?% CI 1.43?4.21) and p?=?0.001] and [adjusted OR for ID genotype was 5.45 (95?% CI 2.6?10.4) and p?=?0.001]. We have already established the association of this polymorphism in ischemic stroke patients. Comparing hemorrhagic with ischemic stroke, we found a significant difference in genotypic distribution between the two [for II vs. DD, ?2?=?4.75; p?=?0.03, OR?=?0.5 (95?% CI 0.27?0.93) and for DD vs. ID, ?2?=?5.1; p?=?0.02, OR?=?1.8 (95?% CI 1.1?3.3)]. Our results indicate that DD genotype and D allele are important risk factors for the development of stroke. Individuals harboring DD genotype of ACE I/D polymorphism are more predisposed to hemorrhagic stroke than ischemic stroke. Further, the mean ACE activity level was found to be significantly higher in hemorrhagic and ischemic stroke in comparison with controls, but there was no significant difference in the levels found between the two types of stroke. ? 2014, Springer-Verlag Italia.
Association of APOE (E2, E3 and E4) gene variants and lipid levels in ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population
(Elsevier Ireland Ltd, 2016) Das, Satrupa; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
In the present study we evaluated the association of APOE (E2/E3/E4) polymorphism with ischemic stroke (n = 620), its subtypes and hemorrhagic stroke (n = 250) in a South Indian population from Telangana. The genotypes were determined using PCR-RFLP while lipid levels were measured using commercially available kits. We found significant difference in the genotypic distribution between hemorrhagic stroke patients and controls for certain genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3; E4/E4 vs.E2/E4 and E3 vs. E4]. However, no significant difference was observed in genotypic distribution between ischemic stroke patients and controls. On analysing the genotypic distribution between ischemic and hemorrhagic stroke patients, statistically significant difference was observed in specific genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3 and E4/E4 vs. E2/E4]. In ischemic stroke subtypes analysing for alleles E3 vs. E2 and E3 vs. E4, we found significant association with intracranial large artery (p = 0.01), cardioembolic stroke (p = 0.001 and p = 0.0004) and lacunar stroke (p = 0.02). Analysing the association of various genotypes with different lipid levels significant association was observed for VLDL (P = 0.000) and for triglyceride (P = 0.000) levels with E2/E4 and E3/E4 genotypes in ischemic stroke but not in hemorrhagic stroke. In conclusion, our results suggest that APOE polymorphism does seem to play a role in hemorrhagic stroke and also in the development of specific subtypes of ischemic stroke. Further, in ischemic stroke VLDL and triglycerides levels were found to be significantly associated with E2/E4 and E3/E4 genotypes. ? 2016 Elsevier Ireland Ltd.
Association of BCL11A genetic variant (Rs11886868) with severityin β-thalassaemia major & sickle cell anaemia
(Indian Council of Medical Research, 2016) Dadheech S.; Madhulatha D.; Jain S.; Joseph J.; Jyothy A.; Munshi, Anjana
Background & objectives: The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including ?-thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse ?-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of ?-thalassaemia major and SCA. Methods: A total of 620 samples (420 ?-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with ?-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. ?-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of ?-thalassaemia major as well as SCA was evaluated. Results: There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P<0.001) difference was observed in the mean HbF levels between the three genotypes in different severity groups. HbF levels were found to be high in CC genotype bearing individuals followed by TC and TT in ?-thalassaemia major as well as SCA. Interpretation & conclusions: This study confirms that the T/C variant (rs11886868) of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of ?-thalassaemia as well as SCA.
Association of COX-2 (rs20417) polymorphism with aspirin resistance and adverse drug reactions (if any) in ischemic stroke patients in Malwa region of Punjab.
(Central University of Punjab, 2018) Kaur, Sukhvir; Munshi, Anjana
Ischemic stroke pathology involves the formation of a thrombus over an unstable atherosclerotic plaque through various inflammatory and clotting cascades. Aspirin is the oldest antiplatelet agent with well-established efficacy in stroke prevention. COX2 gene with rs20417 polymorphism has been found to be associated with ischemic stroke as well as aspirin resistance. We aimed to study the demographic profile of ischemic stroke patients from Malwa region of Punjab and check the frequency of rs20417 variant of COX 2 gene and correlate it with aspirin resistance and ADRs (if any) in ischemic stroke patients. We collected 30 samples from confirmed stroke patients from Malwa region of Punjab. DNA was isolated from blood and subjected to PCR and RFLP to evaluate rs20417 in COX 2 gene in the patients. Their mRS score was used to classify patients as aspirin responders or aspirin non-responders. 96.66% patients were aspirin responders and 3.33% were non-responders. Twenty-nine patients were carriers of CC genotype, of which 27 were responders and 2 were non-responders. Only 1 patient with CG genotype was a non-responder. A larger number of samples need to be screened for the COX-2 G765C polymorphism before coming to a conclusion. This preliminary study indicates that COX-2 G765C variant of COX-2 gene may not be a risk factor for aspirin resistance in ischemic stroke patients from Malwa region of Punjab
Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening array
(Springer Verlag, 2018) Kalra, Sourav; Kaur, Raman Preet; Ludhiadch, Abhilash; Shafi, Gowhar; Vashista, Rajesh; Kumar, Raj; Munshi, Anjana
Purpose: Cyclophosphamide and doxorubicin (adjuvant chemotherapy) are commonly used to treat breast cancer patients. Variation in the genes involved in pharmacodynamics and pharmacokinetics of these drugs plays an important role in prediction of drug response and survival. The present study was carried out with an aim to evaluate the variation in all the genes involved in pharmacokinetic and pharmacodynamics pathways of cyclophosphamide and doxorubicin, and correlate specific variants with disease outcome in breast cancer patients from the Malwa region of Punjab. Methods: A total of 250 confirmed breast cancer patients were involved in the study. Genotyping was performed on an Illumina Infinium HD assay platform using a Global Screening Array (GSA) microchip. GenomeStudio (Illumina, Inc.) was used for data preprocessing and a p value less than or equal to 5 ? 10?8 was considered statistically significant. To rule out the influence of confounding risk factors, a step-wise multivariate regression analysis was carried out to evaluate the association of genotype with overall clinical outcome. Results: Two gene variants, CYP2C19 (G681A) and ALDH1A1*2 (17 bp deletion), were found to be significantly associated with the disease outcome, including overall survival, recurrence and metastasis, in breast cancer patients on adjuvant therapy. Both these genes are involved in the pharmacokinetics of cyclophosphamide. However, none of the variants in the genes involved in pharmacokinetics and pharmacodynamics of doxorubicin were found to have any significant impact on disease outcome in the studied group. Conclusion: CYP2C19 (G681A) variant and ALDH1A1*2 emerged as two important biomarkers associated with bad outcome in breast cancer patients on adjuvant therapy. ? 2018 Springer-Verlag GmbH Germany, part of Springer Nature
Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening array.
(Springer, 2018) Kalra, Sourav; Ludhiadch Abhilash; Shafi, Gowhar; Vashista, Rajesh; Kumar, Raj; Munshi, Anjana
Cyclophosphamide and doxorubicin (adjuvant chemotherapy) are commonly used to treat breast cancer patients. Variation in the genes involved in pharmacodynamics and pharmacokinetics of these drugs plays an important role in prediction of drug response and survival. The present study was carried out with an aim to evaluate the variation in all the genes involved in pharmacokinetic and pharmacodynamics pathways of cyclophosphamide and doxorubicin, and correlate specific variants with disease outcome in breast cancer patients from the Malwa region of Punjab.
Association of elevated levels of C-reactive protein with breast cancer, breast cancer subtypes, and poor outcome
(Mosby Inc., 2018) Kaur, R.P.; Rubal, Banipal,; Vashistha, R.; Dhiman, Monisha; Munshi, Anjana
Background and Purpose: Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared. Material and Methods: Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients. Results: Elevated levels of CRP were found among the diseased in comparison with controls (P < 0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)]. Conclusion: Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high. ? 2018
Association of Serum Trace Elements and Minerals with Genetic Generalized Epilepsy and Idiopathic Intractable Epilepsy
(Springer New York LLC, 2014) Prasad, D.K.V.; Shaheen,Uzma; Satyanarayana,U.; Prabha, T. Surya; Jyothy, Akka|Munshi, Anjana; Prasad, D.K.V.; Shaheen, U.; Satyanarayana, U.; Surya Prabha, T.; Jyothy, A.; Munshi, Anjana
Certain minerals and trace elements are essential for the development of healthy nervous system. Altered serum levels of these elements may lead to the development of various diseases including epilepsy. The present study was designed to evaluate the association of serum calcium, magnesium, zinc and copper in the development of genetic generalized epilepsy [GGE; erstwhile known as idiopathic generalized epilepsy (IGE)] as well as idiopathic intractable epilepsy (IIE), in which seizures persist despite treatment with at least two or three antiepileptic drugs tolerated at reasonable dosage. 200 GGE patients and equal number of healthy controls were recruited for study with their written informed consent. The patients were further divided into responders and non-responders based on their response to antiepileptic drugs. Copper and zinc levels were assayed by atomic absorption spectrophotometer whereas calcium and magnesium were analyzed by Human Star 600 fully automated biochemistry analyzer. The patients with GGE had significant low levels of calcium, magnesium and zinc (1.85???0.33, 0.69???0.13?mmol/L and 11.33???3.32??mol/L respectively) and the corresponding values for controls were 2.27???0.22, 0.89???0.15, 12.71???3.24 (p?
Association of the genetic variants of insulin receptor substrate 1 (IRS-1) with type 2 diabetes mellitus in a Saudi population
(Humana Press Inc., 2014) Alharbi, Khalid Khalaf; Khan, Imran Ali; Munshi, Anjana; Alharbi, Fawiziah Khalaf; Al-Sheikh, Yazeed; Alnbaheen, May Salem
Type 2 diabetes mellitus (T2DM) is a chronic degenerative disease, phenotypically and genetically heterogeneous, characterized by high levels of glucose and metabolic complications. Insulin receptor substrate 1 (IRS-1) plays a key role in the insulin-stimulated signal transduction pathway. A glycine-to-arginine substitution at codon 972 (G972R) (rs1801278) in the IRS-1 gene has been associated with impaired insulin action. Another SNP rs2943641 in the IRS-1 gene has been found to be associated with T2DM and insulin resistance in genome-wide association studies. The aim of the present study was to evaluate whether rs1801278 and rs2943641 are associated with increased risk of T2DM in the Saudi population. The study included 376 T2DM cases and 380 healthy controls. Genomic DNA was isolated using a commercially available kit supplied by Norgen Biotech Corp. Genotyping was performed by PCR and RFLP analysis. There was a significant difference in the genotypic distribution as well as allelic frequency between the T2DM cases and controls in case of both the polymorphisms for rs1801278 (1.752, 95?% CI 1.002?3.121; p?=?0.04), and for rs2943641 (OR?=?1.482, 95?% CI 1.176?1.867; p?=?0.001). In conclusion, both the (rs1801278 and rs2943641) polymorphisms are associated with T2DM in the Saudi population. ? 2014, Springer Science+Business Media New York.
Association of Xmn1 -158 γG variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia
(Springer Netherlands, 2014) Dadheech,Sneha; Jain,Suman; Madhulatha,D.; Sharma,Vandana; Joseph,James; Jyothy, Akka.; Munshi, Anjana
Haemoglobinopathies including ?-thalassemia and sickle cell anaemia (SCA) are considered to be classical monogenic diseases. There is considerable clinical variability between patients inheriting identical ?-globin mutations. The reasons for this variability are not well understood. Previous studies have suggested that a variety of genetic determents influence different clinical phenotypes. The genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study 6,500 blood samples from suspected cases were analysed using HPLC, ARMS-PCR, RDB techniques. Patients with ?-thalassemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. Patients with ?-thalassemia and SCA were analysed for Xmn1 polymorphism and association between this polymorphism and severity of ?-thalassemia and SCA was evaluated. We found a significant difference in genotypic and allelic frequencies of Xmn1 polymorphism between mild and moderate and mild and severe cases. There was a significant difference in high and low percentage of HbF in CC, CT and TT bearing individuals. The TT bearing individuals were found to have a high percentage of HbF in ?-thalassemia as well as SCA. This study confirms that increased ?G-globin expression associated with Xmn1 polymorphism ameliorates the clinical severity in ?-thalassemia as well as SCA in the study population. ? 2014, Springer Science+Business Media Dordrecht.
Brain metastasis in breast cancer: focus on genes and signaling pathways involved, blood�brain barrier and treatment strategies
(Springer Science and Business Media Deutschland GmbH, 2023-03-10T00:00:00) Chhichholiya, Yogita; Ruthuparna, Malayil; Velagaleti, Harini; Munshi, Anjana
Breast cancer�(BC) is one of the most prevalent types of cancer in women. Despite advancement in early detection and efficient treatment, recurrence and metastasis continue to pose a significant risk to the life of BC patients. Brain metastasis�(BM) reported in 17�20 percent of BC patients is considered as a major cause of mortality and morbidity in these patients. BM includes various steps from primary breast tumor to secondary tumor formation. Various steps involved are primary tumor formation, angiogenesis, invasion, extravasation, and brain colonization. Genes involved in different pathways have been reported to be associated with BC cells metastasizing to the brain. ADAM8 gene, EN1 transcription factor, WNT, and VEGF signaling pathway have been associated with primary breast tumor; MMP1, COX2, XCR4, PI3k/Akt, ERK and MAPK pathways in angiogenesis; Noth, CD44, Zo-1, CEMIP, S0X2 and OLIG2 are involved in invasion, extravasation and colonization, respectively. In addition, the blood�brain barrier is also a key factor in BM. Dysregulation of cell junctions, tumor microenvironment and loss of function of microglia leads to BBB disruption ultimately resulting in BM. Various therapeutic strategies are currently used to control the BM in BC. Oncolytic virus therapy, immune checkpoint inhibitors, mTOR-PI3k inhibitors and immunotherapy have been developed to target various genes involved in BM in BC. In addition, RNA interference (RNAi) and CRISPR/Cas9 are novel interventions in the field of BCBM where research to validate these and clinical trials are being carried out. Gaining a better knowledge of metastasis biology is critical for establishing better treatment methods and attaining long-term therapeutic efficacies against BC. The current review has been compiled with an aim to evaluate the role of various genes and signaling pathways involved in multiple steps of BM in BC. The therapeutic strategies being used currently and the novel ones being explored to control BM in BC have also been discussed at length. � 2023, The Author(s), under exclusive licence to Federaci�n de Sociedades Espa�olas de Oncolog�a (FESEO).