1.Breast Cancer Selective Disruption of Actin Cytoskeleton by Diallyl Trisulfide
Eun-Ryeong HAHM ; Sivapar V. MATHAN ; Rana P. SINGH ; Shivendra V. SINGH
Journal of Cancer Prevention 2022;27(2):101-111
Diallyl trisulfide (DATS) is an attractive anti-cancer phytochemical with in vitro and in vivo growth inhibitory effects against different solid tumors including breast cancer. We have shown previously that an immortalized mammary epithelial cell line (MCF-10A) is resistant to growth inhibition by DATS. In this study, we performed RNA-seq analysis using a breast cancer cell line (SK-BR-3) and MCF-10A cells to gain insights into cancer selective effects of DATS. The Gene Ontology analysis revealed upregulation of genes associated with actin cytoskeleton but downregulation of mitochondria-related genes in the SK-BR-3 human breast cancer cell line but not in the non-oncogenic MCF-10A cell line upon treatment with DATS. Quantitative real-time reverse transcription polymerase chain reaction confirmed DATS-mediated upregulation of several actin cytoskeleton-related genes in the SK-BR-3 cell line. The DATS treatment dose-dependently disrupted actin cytoskeleton in the SK-BR-3 cell line, whereas the MCF-10A cell line was more resistant to this effect. The DATS treatment caused a marked increase in phosphorylation of dynamin-1-like (DRP1) protein in the SK-BR-3 cell line. However, the DATS-mediated apoptosis was not affected by genetic deletion of DRP1 protein. The Reactome pathway analysis showed downregulation of genes associated with citric acid cycle in the SK-BR-3 cell line but not in the MCF-10A cells. However, expression of aconitase 2 or dihydrolipoamide S-succinyltransferase was not affected by DATS treatment. In conclusion, this study reveals that actin cytoskeleton is a novel target of DATS in the SK-BR-3 cell line, which may explain its inhibitory effect on breast cancer cell migration.
2.Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis
Eun-Ryeong HAHM ; Su-Hyeong KIM ; Sivapar V. MATHAN ; Rana P. SINGH ; Shivendra V. SINGH
Journal of Cancer Prevention 2021;26(2):128-136
Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.
3.Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis
Eun-Ryeong HAHM ; Su-Hyeong KIM ; Sivapar V. MATHAN ; Rana P. SINGH ; Shivendra V. SINGH
Journal of Cancer Prevention 2021;26(2):128-136
Diallyl trisulfide (DATS), a metabolic by-product of processed garlic, is highly effective in inhibiting growth of human breast cancer cells in vitro and in vivo, but the underlying mechanisms are still not fully understood. In this study, we performed RNA-seq analyses using luminal-type (MCF-7) and basal-like (MDA-MB-231) human breast cancer cells to identify mechanistic targets of DATS. The Reactome Pathway Analysis revealed upregulation of genes associated with SLIT/ROBO tumor suppressor signaling following DATS treatment in both MCF-7 and MDA-MB-231 cells. However, the expression of SLIT2 and ROBO1 proteins or their downstream target C-X-C motif chemokine receptor 4 was not affected by DATS treatment in both cell lines. The Reactome as well as the Gene Ontology Pathways Analyses of the RNA-seq data from DATS-treated cells indicated downregulation of genes associated with G2 /M phase cell cycle arrest in comparison with vehicle-treated control cells. Consistent with the RNA-seq data, DATS treatment caused a significant increase in the fraction of the G2 /M population in both cell lines when compared to corresponding control cells. In addition, Ser10 phosphorylation of histone H3, a mitotic marker, was also increased significantly following DATS treatment in MCF-7 and MDA-MB-231 cells. These results indicate that while SLIT/ROBO signaling is not affected by DATS treatment, cell cycle arrest likely contributes to the antitumor effect of this phytochemical.
4.Antihyperglycemic and antihyperlipidemic activity of ethyl acetate fraction of Rhododendron arboreum Smith flowers in streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolism.
Neeraj VERMA ; G AMRESH ; P K SAHU ; Ch V RAO ; Anil Pratap SINGH
Asian Pacific Journal of Tropical Biomedicine 2012;2(9):696-701
<p>OBJECTIVETo explore and identify the most potent antihyperglycemic fraction from the ethanol extract of Rhododendron arboreum (R. arboreum) flowers.p><p>METHODSNormal and streptozotocin induced diabetic rats were treated with all four fractions of R. arboreum flowers for short term and with fraction 3 for long term study. On completion of the treatment, a range of indicators were tested including fasting blood glucose, plasma protein, haemoglobin A1C, insulin secretion, body weight, blood lipid profile and carbohydrate metabolism regulating enzymes of liver.p><p>RESULTSIn short term study, the fraction 3 (Active fraction) produced a significant (P<0.000 1) reduction (73.6%) in blood glucose level at a dose of 200 mg/kg after the treatment in the diabetic rats. Administration of active fraction (200 and 400 mg/kg) once daily for 30 d in streptozotocin diabetic rats resulted in a significant (P<0.001 to P<0.000 1) fall in blood glucose level, hemoglobin A1C, serum urea and creatinine with significant but a increase in insulin level similar to standard drug glybenclamide. Further, the active fraction showed antihyperlipidemic activity as evidenced by significant (P<0.001 to P<0.000 1) decreases in serum serum total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density cholesterol levels coupled together with elevation of high density lipoprotein cholesterol in the diabetic rats.p><p>CONCLUSIONSThe active fraction of R. arboreum flowers decreases streptozotocin induced hyperglycemia by promoting insulin secretion and glycolysis and by decreasing gluconeogenesis.p>
Animals
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Blood Glucose
;
drug effects
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Carbohydrate Metabolism
;
drug effects
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Diabetes Mellitus, Experimental
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drug therapy
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metabolism
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Disease Models, Animal
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Flowers
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chemistry
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Hypoglycemic Agents
;
chemistry
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pharmacology
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Hypolipidemic Agents
;
chemistry
;
pharmacology
;
Lipids
;
blood
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Male
;
Phytochemicals
;
chemistry
;
Plant Extracts
;
chemistry
;
pharmacology
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Rats
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Rhododendron
;
chemistry
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Toxicity Tests, Acute
5.Psychiatric, Somatic and Other Functional Gastrointestinal Disorders in Patients With Irritable Bowel Syndrome at a Tertiary Care Center.
Prashant SINGH ; Abhishek AGNIHOTRI ; Manish K PATHAK ; Asef SHIRAZI ; Rajeew P TIWARI ; V SREENIVAS ; Rajesh SAGAR ; Govind K MAKHARIA
Journal of Neurogastroenterology and Motility 2012;18(3):324-331
BACKGROUND/AIMS: To study the prevalence of somatic and psychiatric co-morbidities in the patients of irritable bowel syndrome (IBS) and to assess the quality of life (QOL) of these patients. METHODS: One hundred and eighty-four IBS patients and 198 controls were included. Diagnosis of IBS, its sub-classification and assessment of other functional gastrointestinal disorders (FGIDs) was made on basis of Rome III criteria. Severity of IBS was assessed using IBS severity scoring system. Psychiatric evaluation was done using Patient Heath Questionnaire. QOL was evaluated using WHO QOL-BREF. RESULTS: One hundred and forty-seven (79.9%) and 158 (85.9%) patients with IBS had at least one other FGID or at least one somatic co-morbidity, respectively. Higher number of patients had at least one psychiatric co-morbidity compared to controls (79.9% vs 34.3%; P < 0.001). Major depressive syndrome (47.3% vs 5.1%; P < 0.001), somatoform disorder (50% vs 14.6%; P < 0.001) and panic syndrome (44% vs 11.6%; P < 0.001) were more common in IBS than controls. Only 14 (7.6%) patients were receiving drug treatment for their psychiatric illness. Severe IBS symptoms were present in significantly higher number of patients with constipation predominant IBS than diarrhea predominant IBS. Those with severe disease had higher prevalence of psychiatric (95.1%) and somatic (96.7%) co-morbidities compared with mild disease. QOL of IBS patients was significantly lower in all four domains compared to controls. Presence of at least one other FGID was significantly associated with presence of one or more psychiatric co-morbidity (P < 0.001). CONCLUSIONS: Majority of IBS patients presenting to a tertiary care center had associated psychiatric, somatic co-morbidities and reduced QOL. Very few of them received specific psychiatric treatment.
Anxiety Disorders
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Constipation
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Depression
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Depressive Disorder
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Diarrhea
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Gastrointestinal Diseases
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Humans
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Irritable Bowel Syndrome
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Panic
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Prevalence
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Quality of Life
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Surveys and Questionnaires
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Rome
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Somatoform Disorders
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Tertiary Care Centers
;
Tertiary Healthcare
6.Pontomedullary white epidermoid: a rare cause of tinnitus.
Shambanduram Somorendra SINGH ; Kanchan GUPTA ; Sunitha P KUMARAN ; Nandita GHOSAL ; Sunil V FURTADO
Singapore medical journal 2012;53(8):e179-81
Intracranial epidermoid cysts are relatively rare congenital inclusion cysts. They are the third most common cerebellopontine angle cistern mass after vestibular schwannoma and meningioma. White epidermoid is a rare variant. We present the first case, to our knowledge, of a white epidermoid cyst anterior to the pontomedullary junction, emphasising its imaging appearance, location and the importance of pre-operative diagnosis, which may reduce operative complications.
Adolescent
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Cerebellar Diseases
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complications
;
diagnosis
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Cerebellopontine Angle
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diagnostic imaging
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Epidermal Cyst
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complications
;
diagnosis
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Humans
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Male
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Tinnitus
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etiology
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Tomography, X-Ray Computed
7.Cadavers as teachers in medical education: knowledge is the ultimate gift of body donors.
Prakash ; L V PRABHU ; R RAI ; S D'COSTA ; P J JIJI ; G SINGH
Singapore medical journal 2007;48(3):186-quiz 190
In most of the medical colleges in India, unclaimed bodies from various mortuaries reach the dissection hall; and here, the body donors club has yet to gain the desired dimensions. In spite of all the adverse circumstances, the cadaver and the dissection both have survived the most rigorous test of pedagological fitness--the test of time. Today, many of the Western countries have long donor waiting lists where cadavers are acquired as anatomical gifts or through body donor programmes. Thailand's approach to body donors offers a role model for resolving the present situation. The spirit of volunteerism reflects the drastic shift in public perception and a global change in approach is needed in the present time.
Anatomy
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education
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Cadaver
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Dissection
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Education, Medical, Undergraduate
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Humans
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India
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Tissue Donors
8.Effect of 1-corydalmine,an Alkaloid Isolated from Corydalis chaerophylla Roots on Spore Germination of Some Fungi.
S Ameer BASHA ; R N JHA ; V B PANDEY ; U P SINGH
Mycobiology 2007;35(2):69-71
1-Corydalmine,an alkaloid isolated from roots of Corydalis chaerophylla inhibited spore germination of some plant pathogenic as well as saprophytic fungi e.g. Alternaria brassicae, A. brassicicola, A. solani, Curvularia lunata, C. maculans, C. sp., C. pallscens, Erysiphe pisi, Fusarium udum, Helminthosporium species,H. penniseti and a Heterosporium species. 1-Corydalmine significantly inhibited spore germination of all the fungi at 100 to 1500 ppm. It was effective against all the fungi at 1500 ppm. C. lunata was highly sensitive to this chemical even at 250 ppm.
Alternaria
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Brassica
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Corydalis*
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Fungi*
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Fusarium
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Germination*
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Helminthosporium
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Plants
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Spores*
9.Chopstick splinter: A rare cause of bilateral frozen orbits
Bin Lieh O. ; Ong Lee C. ; Tet Min C. ; Raja Selva V. ; Liza-Sharmini AT ; Balaravi P. ; Singh Gurdeep M.
Philippine Journal of Ophthalmology 2006;31(1):42-43
OBJECTIVE: To report an unusual case of frozen orbit caused by an unsuspected intraorbital foreign body.
METHOD: This is a case report.
RESULTS: A 31-year old Chinese man presented with a 6-month history of painless progressive right caruncular growth with mucoid discharge. He also had bilateral progressive reduction in ocular movements. His best-corrected vision was 6/9 bilaterally. A conjunctival granuloma arising from the right caruncle and extending to the cornea and associate with ophthalmoplegia was also present. Orbital computed tomography showed a dense rod-like structure traversing the nasal area, extending from the superomedial wall of the right orbit to the apex of the left orbit with surrounding inflammatory reaction but sparing the optic nerve. The intraorbital foreign body, a 6 cm chopstick splinter, was successfully removed via right lateral rhinotomy.
CONCLUSION: Intraorbital foreign bodies are not uncommonly seen and, generally, the diagnosis is straightforward. Nevertheless, diagnosis, could be missed if it is not suspected.
Human
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Male
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Adult
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WOUNDS AND INJURIES
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EYE FOREIGN BODIES
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EYE DISEASES
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10.Antifungal Activity of Narceine Methyl Ester and Narceine Isolated from Corydalis longipes Against Some Phytopathogenic Fungi.
Dibyendu CHOWDHURY ; S MAURYA ; M B PANDEY ; V B PANDEY ; B K SARMA ; U P SINGH
Mycobiology 2005;33(4):206-209
Narceine methyl ester and narceine are potent alkaloids which were isolated from Corydalis longipes were found effective in vitro at very low concentration, i.e., 100~500 ppm against spore germination of some test plant pathogenic fungi (Alternaria solani, A. tagetica, Cercospora abelmoschi, Curvularia maculans, Erysiphe cichoracearum, E. pisi, Fusarium udum, Helminthosporium oryzae, H. penniseti, Ustilago cynodontis). Among the test, phytopathogens the spores of F. udum, C. maculans and H. penniseti were highly sensitive at 200 ppm. However, spores of E. pisi, A. solani and A. tagetica were less sensitive at low concentration followed by other test fungi. Most of the fungi showed zero or nearly zero percent spore germination at 400 and 500 ppm.
Alkaloids
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Corydalis*
;
Fungi*
;
Fusarium
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Germination
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Helminthosporium
;
Oryza
;
Plants
;
Spores
;
Ustilago

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