Regeneration of Anti-Hypoxic Myocardial Cells by Transduction of Mesenchymal Stem Cell-Derived Exosomes Containing Tat-Metallothionein Fusion Proteins

Qurrat ul ain,우영선,정지영,김용희 한국고분자학회 2018 Macromolecular Research Vol.26 No.8

Stem cells secrete many extracellular vesicles such as micro vesicles, exosomes and membrane particles. Exosomes represent characteristics similar to their native cells and exosomes secreted from human mesenchymal stem cells (hMSCs) have demonstrated cardio protective effects. In this study, we examined the synergistic effects of exosomes derived from hMSCs expressing metallothionein (MT), a wellknown therapeutic protein to treat myocardial infarction, for recovery of cell viability in vitro in hypoxic conditions. Tat-metallothionein (Tat-MT) recombinant fusion proteins were prepared by a recombinant method to increase the transduction of metallothionein into exosomes via Tat’s transduction characteristic. Exosomes from hMSCs were transduced with Tat-MT, and characterized by transmission electron microscopy and immunoblotting. Cellular uptake of exosomes and protein was analyzed by confocal microscopy. The cytoprotective effects of exosomes transfected with Tat-MT (Exo/Tat-MT) on cardiomyocytes were evaluated by accessing cell viability. Exo/Tat-MT significantly upregulated cell viability and downregulated apoptosis in cardiomyocytes. The therapeutic potential of exosome-mediated therapeutic protein delivery was demonstrated by strong cell viability (70-80%) under in vitro hypoxic conditions. This study reveals the dual benefits of exosomes derived from hMSCs and highlights a new method of intercellular stem cells mediation for the stem cell-derived treatment of myocardial infarction.

A Clinico-epidemiological Profile of Dyslipidaemia and its Association with Temperament - A Cross Sectional Study

Qurratulain, Qurratulain,Nawab, Mohammad,Kazmi, M.H. Cellmed Orthocellular Medicine and Pharmaceutical 2020 셀메드 (CellMed) Vol.10 No.4

Introduction: Dyslipidaemia is directly associated with cardiovascular diseases. Temperament, the unique constitutional make-up of an individual, is responsible for one's personality traits, physical appearances, and disease predispositions. The rising prevalence of dyslipidaemia becomes a challenge to control morbidity and mortality due to cardiovascular diseases. Objective: To study clinical patterns and risk factors of dyslipidaemia and its association with temperament at the individual level was the main objective of this study. Materials and Methods: It was a descriptive and analytical cross sectional study. The participants (n=88) were screened on the basis of raised serum lipid profile from the outpatient department of National Research Institute of Unani Medicine for Skin Disorders, Hyderabad. The data were collected on a case record form designed for this study and analyzed retrospectively. Results: In this study, there were 57% participants (n=50) of phlegmatic temperament in which mean total cholesterol, triglycerides, low density lipoprotein- cholesterol and high density lipoprotein-cholesterol were 230.92 (±49.48) mg/dl, 182.34 (±110.61) mg/dl, 153.24 (±50.21) mg/dl and 46.3 (±10.83) mg/dl respectively. Discussion: This study showed the prevalence of different clinical patterns of dyslipidaemia in the population and the phlegmatic participants were dyslipidaemic in a higher percentage. The prevalence of dyslipidaemia in phlegmatic participants may be linked to the constitutional make-up of the individual. The temperament of an individual may be considered as one of the risk factors for dyslipidaemia. Conclusion: It was concluded that the temperament of an individual may be used as a screening tool to predict the individual's tendency to develop dyslipidaemia.

TRAIL Mediated Signaling in Pancreatic Cancer

Nogueira, Daniele Rubert,Yaylim, Ilhan,Aamir, Qurratulain,Kahraman, OzlemTimirci,Fayyaz, Sundas,Naqvi, Syed Kamran-Ul-Hassan,Farooqi, Ammad Ahmad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced by findings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites.

Role of Human papilloma virus Infection and Altered Methylation of Specific Genes in Esophageal Cancer

Mohiuddin, Mohammed Khaliq,Chava, Srinivas,Upendrum, Pavani,Latha, Madhavi,Zubeda, Syeda,Kumar, Ajith,Ahuja, Yog Raj,Hasan, Qurratulain,Mohan, Vasavi Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Background: Evaluation of Human papilloma virus (HPV) and its association with promoter methylation of candidate genes, p53 and Aurora A in esophageal cancer. Materials and Methods: One hundred forty-one esophageal tissue samples from different pathologies were evaluated for HPV infection by PCR, while the promoter methylation status of p53 and Aurora A was assessed by methylation-specific restriction based PCR assay. Statistical analyses were performed with MedCalc and MDR software. Results: Based on endoscopy and histopathology, samples were categorized: cancers (n=56), precancers (n=7), esophagitis (n=19) and normals (n=59). HPV infection was found to be less common in cancers (19.6%), whereas its prevalence was relatively high in precancers (71.4%), esophagitis (57.8%) and normals (45.7%). p53 promoter methylation did not show any significant difference between cancer and normal tissues, whereas Aurora A promoter methylation demonstrated significant association with disease (p=0.00016, OR:5.6452, 95%CI:2.18 to 14.6) when compared to normals. Aurora A methylation and HPV infection was found in a higher percentages of precancer (66.6%), esophagitis (54.5%) and normal (45.2%) when compared to cancers (14.2%). Conclusions: Aurora A promoter methylation is significantly associated with esophageal cancer, but the effect of HPV infection on this epigenetic alteration is not significant. However MDR analysis showed that the hypostatic effect of HPV was nullified when the cases had Aurora methylation and tobacco exposure. Further HPV sub-typing may give an insight into its reduced prevalence in esophageal cancer verses normal tissue. However, with the present data it is difficult to assign any significant role to HPV in the etiopathology of esophageal cancer.

Molecular Analysis of CAG Repeats at Five Different Spinocerebellar Ataxia loci: Correlation and Alternative Explanations for Disease Pathogenesis

Ravindra Alluri,Sreelatha Komandur,Avinash Wagheray,Jaydip Chaudhuri,Sitajayalakshmi ,Angmuthu Meena,Afshan Jabeen,Kamalesh Chawda,Kaul Subhash,Alladi Krishnaveni,Qurratulain Hasan 한국분자세포생물학회 2007 Molecules and cells Vol.24 No.3

HER-2/neu Status: A Neglected Marker of Prognostication and Management of Breast Cancer Patients in India

Zubeda, Syeda,Kaipa, Prabhakar Rao,Shaik, Noor Ahmad,Mohiuddin, Mohammed Khaliq,Vaidya, Sireesha,Pavani, Boddana,Srinivasulu, Mukta,Latha, Manolla Madhavi,Hasan, Qurratulain Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Background: Categorizing breast tumors based on the ER, PR and HER/Neu 2 receptor status is necessary in order to predict outcome and assist in management of breast cancer. Herfe we assessed this question in South Indian patients. Materials and Methods: A total of 619 formalin fixed paraffin embedded breast tumor tissues were collected from pathology archives after receipt of ethical clearance. With the help of primary and secondary conjugated antibodies, expression status of ER, PR and HER2/neu was determined. All the experimental data were assessed for correlations with histopathological features of tumors and clinical presentation of the subjects. Results: In the present study, the ages ranged from 20-87 years with a mean of $50.0{\pm}12.q$ years, and majority of the tumors (84%) were of infiltrating duct cell carcinoma type. Assessment of ER, PR and Her-2/neu expression showed that 46% were triple negative. Interestingly, an inverse relation between ER, PR and HER-2/neu was apparent in 41.2% (p<0.0001) of the tumors, of which 24.5% (p<0.0001) were ER and PR co-negative but HER-2 positive. Conclusions: ER and PR positive tumors are less common (i.e<30%) compared to HER-2/neu positive tumors (i.e>50%) in Indian breast cancer patients, underlining the need for effective diagnostic screening and specific therapeutic managements in order to improve the survival rate of patients in low resource countries such as India.