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Article: ALS plasma reduces the viability of NSC34 cells via altering mRNA expression of VEGF: A short report.

Khosla, Radhika / Bhagat, Hemant / Lal, Parth / Anand, Akshay

2023 Volume 9, Issue 7, Page(s) e18287

Abstract: Introduction: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder that progressively leads to motor neuron degeneration at the neuromuscular junctions, resulting in paralysis in the patients. The clinical diagnosis of ALS is ... ...

Abstract	Introduction: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder that progressively leads to motor neuron degeneration at the neuromuscular junctions, resulting in paralysis in the patients. The clinical diagnosis of ALS is time taking and further delays the therapeutics that can be helpful if the disease is diagnosed at an early stage. Changes in plasma composition can be reflected upon CSF composition and hence, can be used to study the diagnosis and prognosis markers for the disease. Aim: To develop a simple model system using motor neuron like cell line after plasma induction. Method: Neuroblastoma × Spinal Cord hybridoma cell line (NSC34) was cultured under appropriate conditions. 10% ALS patients' plasma was added to the media, and cells were conditioned for 12 h. Cell survival analysis and differential gene expression of a panel of molecules (published previously, VEGF, VEGFR2, ANG, OPTN, TDP43, and MCP-1) were done. Results: ALS patients' plasma impacted the life of the cells and reduced survival to nearly 50% after induction. VEGF was found to be significantly down-regulated in the cells, which can be explained as a reason for reduced cell survival. Conclusion: ALS plasma altered the expression of an essential neuroprotective and growth factor VEGF in NSC34 cells leading to reduced viability.
Language	English
Publishing date	2023-07-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e18287
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Amyotrophic Lateral Sclerosis (ALS) prediction model derived from plasma and CSF biomarkers.

Khosla, Radhika / Rain, Manjari / Sharma, Suresh / Anand, Akshay

PloS one

2021 Volume 16, Issue 2, Page(s) e0247025

Abstract: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of motor neurons which leads to complete loss of movement in patients. The only FDA approved drug Riluzole provides only symptomatic relief to patients. Early Diagnosis of the disease ... ...

Abstract	Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of motor neurons which leads to complete loss of movement in patients. The only FDA approved drug Riluzole provides only symptomatic relief to patients. Early Diagnosis of the disease warrants the importance of diagnostic and prognostic models for predicting disease and disease progression respectively. In the present study we represent the predictive statistical model for ALS using plasma and CSF biomarkers. Forward stepwise (Binary likelihood) Logistic regression model is developed for prediction of ALS. The model has been shown to have excellent validity (94%) with good sensitivity (98%) and specificity (93%). The area under the ROC curve is 99.3%. Along with age and BMI, VEGF (Vascular Endothelial Growth Factor), VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) and TDP43 (TAR DNA Binding Protein 43) in CSF and VEGFR2 and OPTN (Optineurin) in plasma are good predictors of ALS.
MeSH term(s)	Amyotrophic Lateral Sclerosis/blood ; Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers/blood ; Biomarkers/cerebrospinal fluid ; Disease Progression ; Early Diagnosis ; Female ; Humans ; Male ; Middle Aged ; Models, Statistical ; Prognosis ; ROC Curve
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0247025
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Article ; Online: Health risks of extreme heat.

Khosla, Radhika / Jani, Anant / Perera, Rafael

BMJ (Clinical research ed.)

2021 Volume 375, Page(s) n2438

MeSH term(s)	Extreme Heat/adverse effects ; Global Health ; Heat Stress Disorders/prevention & control ; Humans ; Sustainable Development
Language	English
Publishing date	2021-10-07
Publishing country	England
Document type	Editorial
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.n2438
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Article: Association of Plasma Biomarkers for Angiogenesis and Proteinopathy in Indian Amyotrophic Lateral Sclerosis Patients.

Modgil, Shweta / Khosla, Radhika / Tiwari, Abha / Sharma, Kaushal / Anand, Akshay

Journal of neurosciences in rural practice

2020 Volume 11, Issue 4, Page(s) 573–580

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2020-08-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2601242-X
ISSN	0976-3155 ; 0976-3147
ISSN (online)	0976-3155
ISSN	0976-3147
DOI	10.1055/s-0040-1714314
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Article: The International conference on Neuroscience and 36

Mehra, Priya / Kanupriya / Battu, Priya / Khosla, Radhika / Modgil, Shweta

Annals of neurosciences

2019 Volume 26, Issue 1, Page(s) 45–46

Language	English
Publishing date	2019-01-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2576191-2
ISSN	0976-3260 ; 0972-7531
ISSN (online)	0976-3260
ISSN	0972-7531
DOI	10.5214/ans.0972.7531.260109
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Article: Angiogenesis-Centered Molecular Cross-Talk in Amyotrophic Lateral Sclerosis Survival: Mechanistic Insights.

Thakur, Keshav / Tiwari, Abha / Sharma, Kaushal / Modgil, Shweta / Khosla, Radhika / Anand, Akshay

Critical reviews in eukaryotic gene expression

2020 Volume 30, Issue 2, Page(s) 137–151

Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized with progressive muscle atrophy. We have attempted to establish the link between angiogenesis and cellular survival in the pathogenesis of ALS by compiling evidence ... ...

Abstract	Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized with progressive muscle atrophy. We have attempted to establish the link between angiogenesis and cellular survival in the pathogenesis of ALS by compiling evidence described in various scientific reports. The phenotypes of human ALS have earlier been captured in the mutant SOD1 mice as well as by targeted deletion of the hypoxia response element (HRE) from the promoter of the mouse gene for vascular endothelial growth factor (VEGF). Indirect evidence shows that angiogenesis can help prevent oxidative stress, and hence, enhance cell survival. VEGF and angiogenin chiefly regulate the process of angiogenesis. Transactive response DNA-binding protein 43 (TDP-43) is usually found inside the nucleus, but in large number of cases of ALS, it accumulates in the cytoplasm (TDP-43 proteinopathy). Interestingly, TDP-43 proteinopathy is found to be aggravated in the presence of the OPTN mutation, which is the genetic factor that is responsible for such accumulation. Interaction of TDP-43 with progranulin can further affect the angiogenesis in ALS patients by regulating activity of VEGF receptors, but conclusive evidence is needed to establish its role in pathogenesis of ALS. Certain mutations in UBQLN2 and UBQLN4 indicate that ubiquitination has a role in ALS pathobiology, but its link to angiogenesis has not been adequately studied. Recent studies have shown that several mutations in RNA-binding proteins (RBPs) can also cause ALS. Conclusively, in this review, we have attempted to argue the role of angiogenesis in enhanced ALS survival rate is probably regulated with the activation of NF-κβ. Additionally, interaction between OPTN and TDP-43 can also impact the transcription of various angiogenic molecules. Whether targeting angiogenic substances or TDP-43 can provide clues about extending ALS survival rate, in combination with current treatments, can only be evaluated after additional studies.
Language	English
Publishing date	2020-06-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	1071345-1
ISSN	1045-4403
ISSN	1045-4403
DOI	10.1615/CritRevEukaryotGeneExpr.2020031020
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Article: Association of Plasma Biomarkers for Angiogenesis and Proteinopathy in Indian Amyotrophic Lateral Sclerosis Patients

Modgil, Shweta / Khosla, Radhika / Tiwari, Abha / Sharma, Kaushal / Anand, Akshay

Journal of Neurosciences in Rural Practice

2020 Volume 11, Issue 04, Page(s) 573–580

Abstract: Background: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease with progressive degeneration of motor neurons. Various molecules have been explored to provide the early diagnostic/prognostic tool for ALS without getting much success in ... ...

Abstract	Background: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease with progressive degeneration of motor neurons. Various molecules have been explored to provide the early diagnostic/prognostic tool for ALS without getting much success in the field and miscellaneous reports studied in various population. Objective: The study was aimed to see the differential expression of proteins involved in angiogenesis (angiogenin [ANG], vascular endothelial growth factor [VEGF], vascular endothelial growth factor receptor 2 [VEGFR2], etc), proteinopathy (transactive response DNA binding protein-43 [TDP-43] and optineurin [OPTN]), and neuroinflammation (monocyte chemoattractant protein-1[MCP-1]) based on the characteristics of ALS pathology. Though, suitable panel based on protein expression profile can be designed to robust the ALS identification by enhancing the prognostic and diagnostic efficacy for ALS. Methods: A total of 89 ALS patients and 98 nonneurological controls were analyzed for the protein expression. Expression of angiogenic (VEGF, VEGFR2, and ANG), neuroinflammation (MCP-1), and proteinopathy (TDP-43 and OPTN) markers were estimated in plasma of the participants. Proteins were normalized with respective value of total protein before employing statistical analysis. Results: Analysis has exhibited significantly reduced expression of angiogenic, proteinopathy, and neuroinflammation biomarkers in ALS patients in comparison to controls. Spearman’s correlation analysis has showed the positive correlation to each protein. Conclusion: Altered expression of these proteins is indicating the prominent function in ALS pathology which may be interdependent and may have a synergistic role. Hence, a panel of expression can be proposed to diagnose ALS patient which may also suggest the modulation of therapeutic strategy according to expression profile of patient.
Keywords	amyotrophic lateral sclerosis ; angiogenic markers (VEGF, VEGFR2, angiogenin) ; TDP-43 ; optineurin ; MCP-1/ CCL-2
Language	English
Publishing date	2020-08-20
Publisher	Thieme Medical and Scientific Publishers Pvt. Ltd.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	2601242-X
ISSN	0976-3155 ; 0976-3147 ; 0976-3155
ISSN (online)	0976-3155
ISSN	0976-3147 ; 0976-3155
DOI	10.1055/s-0040-1714314
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Article ; Online: Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?

Khosla, Radhika / Banik, Avijit / Kaushal, Sushant / Battu, Priya / Gupta, Deepti / Anand, Akshay

Current Alzheimer research

2019 Volume 16, Issue 4, Page(s) 344–352

Abstract: Background: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell ... ...

Abstract	Background: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell cycle events. A recent data suggests that there is a strong inverse association between cancer and neurodegenerative disorders. There is indirect evidence to postulate Brain-derived Neurotrophic Factor (BDNF) as a potential molecular link in this association. Discussion: The BDNF levels are found to be downregulated in many neurodegenerative disorders and are found to be upregulated in various kinds of cancers. The lower level of BDNF in Alzheimer's and Parkinson's disease has been found to be related to cognitive and other neuropsychological impairments, whereas, its higher levels are associated with the tumour growth and metastasis and poor survival rate in the cancer patients. Conclusion: In this review, we propose that variance in BDNF levels is critical in determining the course of cellular pathophysiology and the development of cancer or neurodegenerative disorder. We further propose that an alternative therapeutic strategy that can modulate BDNF expression, can rescue or prevent above said pathophysiological course. Larger studies that examine this link through animal studies are imperative to understand the putative biochemical and molecular link to wellness and disease.
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Humans ; Neoplasms/metabolism ; Neurodegenerative Diseases/metabolism
Chemical Substances	Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2019-04-05
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2205170-3
ISSN	1875-5828 ; 1567-2050
ISSN (online)	1875-5828
ISSN	1567-2050
DOI	10.2174/1567205016666190408123947
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Article: Integrative Approach to COVID-19: An Indian Facebook Recipe for Mental Health.

Anand, Akshay / Tyagi, Rahul / Khosla, Radhika / Bali, Parul / Rain, Manjari / Maity, Kalyan / Verma, Prashant / Gupta, Sheetal J / Nadholta, Pooja / Kaur, Navneet / Sharma, Kiran / Tripathi, Satyam / Avti, Pramod / Singh, Amit

Annals of neurosciences

2022 Volume 28, Issue 3-4, Page(s) 183–190

Abstract: Background: The COVID-19 pandemic has given the world a big blow and has forced the entire world to develop a new thought process. To cope with the stress of lockdown, it was important for people to indulge in educational and health activities to save ... ...

Abstract	Background: The COVID-19 pandemic has given the world a big blow and has forced the entire world to develop a new thought process. To cope with the stress of lockdown, it was important for people to indulge in educational and health activities to save them from the threats being caused by the news and social media. Summary: A Facebook page named Yoga scholars Post Graduate Institute of Medical Education and Research (PGIMER) was created where three sessions were held per day for 225 days regularly. This activity resulted in people adopting an integrative approach towards alternative medicine. Key message: This also made possible a trial of Ashwagandha for COVID-19 treatment by the Ayurveda, Yoga, Naturopathy, Unani, Siddha and Homeopathy (AYUSH) ministry.
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2576191-2
ISSN	0976-3260 ; 0972-7531
ISSN (online)	0976-3260
ISSN	0972-7531
DOI	10.1177/09727531211052971
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Article ; Online: Higher Perceived Stress and Poor Glycemic Changes in Prediabetics and Diabetics Among Indian Population.

Mishra, Amit / Podder, Vivek / Modgil, Shweta / Khosla, Radhika / Anand, Akshay / Nagarathna, Raghuram / Malhotra, Rama / Nagendra, Hongasandra Ramarao

Journal of medicine and life

2020 Volume 13, Issue 2, Page(s) 132–137

Abstract: Diabetes mellitus (DM) is a chronic metabolic disorder with significant co-morbidities and healthcare burdens. Many large studies have investigated the association between perceived stress and DM; however, none investigated this in a larger Indian ... ...

Abstract	Diabetes mellitus (DM) is a chronic metabolic disorder with significant co-morbidities and healthcare burdens. Many large studies have investigated the association between perceived stress and DM; however, none investigated this in a larger Indian population. We hypothesized stress as one of the reasons for the progression of people with prediabetes into DM. The present study was, therefore, planned to report on associations between perceived stress and blood glucose markers stratified by diabetic status. The current descriptive study was a subset analysis of the nationwide cross-sectional survey, conducted in all Indian zones under the National Multicentric Diabetes Control Program. The study examined the perceived stress levels using a perceived stress scale (PSS-10) in people with prediabetes (n=649) and DM (n=485) and then segregated them into three categories (minimum, moderate, and severe). Blood glucose markers (fasting blood glucose, postprandial blood glucose, and HbA1c) were evaluated to report their association with the perceived stress. The study revealed a significantly higher HbA1c level in people with prediabetes, particularly those with severe perceived stress (6.12 ± 0.27) compared to other categories. Those with DM had a higher fasting blood glucose level, particularly with severe perceived stress (239.28 ± 99.52). An increased HbA1c level is noted in severely stressed people with prediabetes, requiring a comprehensive analysis with a longitudinal study of the role of perceived stress in the progression of prediabetes into DM. Additionally, higher fasting blood glucose levels in patients with DM and severe perceived stress suggests the need for establishing comprehensive diabetic care inclusive of stress management.
MeSH term(s)	Blood Glucose/metabolism ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/psychology ; Humans ; India ; Prediabetic State/blood ; Prediabetic State/psychology ; Stress, Psychological/blood
Chemical Substances	Blood Glucose
Language	English
Publishing date	2020-06-03
Publishing country	Romania
Document type	Journal Article
ZDB-ID	2559353-5
ISSN	1844-3117 ; 1844-3109 ; 1844-122X
ISSN (online)	1844-3117 ; 1844-3109
ISSN	1844-122X
DOI	10.25122/jml-2019-0055
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