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991.
Shubham Srivastava Bhanwar Singh Choudhary Manish Sharma Ruchi Malik 《Medicinal chemistry research》2016,25(6):1140-1147
P-gp transporter regulates key ADME of drugs in MDR condition. In the present work, a pharmacophore-based 3D-QSAR model was generated for a series of galloyl benzamides analogs possessing P-gp inhibitory activity. Developed pharmacophore model contains two hydrogen-bond acceptors (A), one hydrophobic (H), one hydrogen-bond donor (D) and two aromatic rings (R). These are crucial molecular fingerprints which predict binding efficacy of high-affinity and low-affinity ligands to the P-gp efflux pump. These pharmacophoric features point toward key structural requirements of galloyl benzamides for potent P-gp inhibition. Furthermore, a biological correlation 3D-QSAR variants and functional fingerprints of P-gp responsible for the receptor binding were observed. Alignment of the developed model with P-gp crystal structure indicated importance of A2 and A4 H-bond acceptor sites, which are involved in the important interactions with Glu530 and His690 residues of the active site. Excellent statistical results of QSAR model such as good correlation coefficient (r 2 > 0.95), higher F value (F > 205) and excellent predictive power (Q 2 > 0.6) with low standard deviation (SD < 0.2) strongly suggest that the developed model is good for the future prediction of P-gp inhibitory activity of new galloyl benzamide analogs. 相似文献
992.
Ghulam Abbas Ahmed Sulaiman Al-Harrasi Hidayat Hussain Javid Hussain Rehana Rashid M. Iqbal Choudhary 《Pharmaceutical biology》2016,54(2):198-206
Context: During diabetes mellitus, non-enzymatic reaction between amino groups of protein and carbonyl of reducing sugars (Millard reaction) is responsible for the major diabetic complications. Various efforts have been made to influence the process of protein glycation.Objectives: This review article provides an extensive survey of various studies published in scientific literature to understand the process of protein glycation and its measurement. Moreover, evaluation and identification of potential inhibitors (antiglycation agents) of protein glycation from natural and synthetic sources and their mechanism of action in vitro and in vivo are also addressed.Method: In this review article, the mechanism involved in the formation of advanced glycation end products (AGEs) is discussed, while in second and third parts, promising antiglycation agents of natural and synthetic sources have been reviewed, respectively. Finally, in vivo studies have been addressed. This review is mainly compiled from important databases such as Science, Direct, Chemical Abstracts, SciFinder, and PubMed.Results: During the last two decades, various attempts have been made to inhibit the process of protein glycation. New potent inhibitors of protein glycation belonging to different classes such as flavonoids, alkaloids, terpenes, benzenediol Schiff bases, substituted indol, and thio compounds have been identified.Conclusion: Antiglycation therapy will be an effective strategy in future to prevent the formation of AGEs for the management of late diabetic complications Current review article highlighted various compounds of natural and synthetic origins identified previously to inhibit the protein glycation and formation of AGEs in vitro and in vivo. 相似文献
993.
Sriram Krishamurthy V. S. Venkateswaran K. M. Adhikari Kannan Venkatnarayan Shyama Choudhary Satyendra Khichar Amitabh Singh Rahul Jain Sushil Kumar Amit Garg Ira Shah Pradeep Kumar Sharma Neeraj Awasthy Arijit Bhowmik Tamoghna Biswas Aniruddha Ghosh Arunaloke Bhattacharya S. Kalpana B. Sarath Balaji 《Indian pediatrics》2016,53(10):928-936
994.
Pesona Grace Lucksom Rekha Upadhya Latha Kharka Swati Dubey Nishi Choudhary Ruby Yadav 《Journal of obstetrics and gynaecology of India》2016,66(1):55-59
Background
This study was conducted to determine whether antenatal mothers in Sikkim have adequate knowledge about awareness, attitude, and preventive practices regarding HIV infection.Methods
Cross-sectional study using structured questionnaire. 220 Antenatal mothers attending the outpatient department of Central Referral Hospital of Sikkim were taken for the study for a period of 1 year from April 2011 to April 2012. Questionnaire form filled by pregnant women during their first antenatal visit was the source of data for this study. Systematic sampling technique was used where every alternate pregnant women registering for ANC visit were voluntarily recruited into the study.Results
2.27 % (5) women had not heard about HIV. 84 % (38) women had the knowledge that HIV was related to STI, while 50 % (110) did not. Television was the best method of increasing the knowledge (48 %). 68 % (150) of the women were aware about mother-to-child transmission (MTCT) of HIV during antenatal period. Only 2.66 % (6) women knew that HIV can be transmitted to child through breast milk. 90 % (198) knew that HIV is spread by having unsafe sex, 48 % (106) women knew using condoms would protect against it. 69.4 % (153) women wanted partner testing, and 84 % (185) of women consented that all pregnant women should be tested for HIV.Conclusions
The current study revealed high levels of knowledge, positive attitude, and preventive practices regarding HIV; however, this population lacked knowledge about MTCT and its prevention.995.
Human parainfluenza virus type 3 (HPIV3) causes bronchiolitis, pneumonia, and croup in newborns and infants. Several studies have implicated intercellular adhesion molecule-1 (ICAM-1) in inflammation during infection by viruses. In this study, we investigated the potential for HPIV3 to induce ICAM-1 in HT1080 cells. FACS analysis showed that HPIV3 strongly induced ICAM-1 expression in these cells. The ICAM-1 induction was significantly reduced when the virions were UV inactivated prior to infection, indicating that ICAM-1 induction was mostly viral replication dependent. Culture supernatant of HPIV3-infected cells induced ICAM-1 at an extremely low level, indicating that virus-induced cytokines played only a minor role in the induction process. Consistent with this, potent inducers of ICAM-1 such as IFN-gamma, TGF-beta, and TNF-alpha were absent in the culture supernatant, but a significant amount of IFN type 1 was present. By using U2A cells, which are defective in IFN type I signaling, we confirmed that ICAM-1 induction by HPIV3 occurred in a JAK/STAT signaling-independent manner. These data strongly indicate that HPIV3 induces ICAM-1 directly by viral antigens in a cytokine-independent manner; this induction may play a role in the inflammation during HPIV3 infection. 相似文献
996.
Suzy V. Hope Bridget A. Knight Beverley M. Shields Anita V. Hill Pratik Choudhary W. David Strain Timothy J. McDonald Angus G. Jones 《Diabetologia》2018,61(1):66-74
Aims/hypothesis
The aim of this study was to determine whether random non-fasting C-peptide (rCP) measurement can be used to assess hypoglycaemia risk in insulin-treated type 2 diabetes.Methods
We compared continuous glucose monitoring-assessed SD of blood glucose and hypoglycaemia duration in 17 patients with insulin-treated type 2 diabetes and severe insulin deficiency (rCP < 200 pmol/l) and 17 matched insulin-treated control patients with type 2 diabetes but who had preserved endogenous insulin (rCP > 600 pmol/l). We then assessed the relationship between rCP and questionnaire-based measures of hypoglycaemia in 256 patients with insulin-treated type 2 diabetes and a comparison group of 209 individuals with type 1 diabetes.Results
Continuous glucose monitoring (CGM)-assessed glucose variability and hypoglycaemia was greater in individuals with rCP < 200 pmol/l despite similar mean glucose. In those with low vs high C-peptide, SD of glucose was 4.2 (95% CI 3.7, 4.6) vs 3.0 (2.6, 3.4) mmol/l (p < 0.001). In the low-C-peptide vs high-C-peptide group, the proportion of individuals experiencing sustained hypoglycaemia ≤ 4 mmol/l was 94% vs 41% (p < 0.001), the mean rate of hypoglycaemia was 5.5 (4.4, 6.7) vs 2.1 (1.4, 2.9) episodes per person per week (p = 0.004) and the mean duration was 630 (619, 643) vs 223 (216, 230) min per person per week (p = 0.01). Hypoglycaemia ≤ 3 mmol/l was infrequent in individuals with preserved C-peptide (1.8 [1.2, 2.6] episodes per person per week vs 0.4 [0.1, 0.8] episodes per person per week for low vs high C-peptide, p = 0.04) and only occurred at night. In a population-based cohort with insulin-treated type 2 diabetes, self-reported hypoglycaemia was twice as frequent in those with rCP < 200 pmol/l (OR 2.0, p < 0.001) and the rate of episodes resulting in loss of consciousness or seizure was five times higher (OR 5.0, p = 0.001). The relationship between self-reported hypoglycaemia and C-peptide was similar in individuals with type 1 and type 2 diabetes.Conclusions/interpretation
Low rCP is associated with increased glucose variability and hypoglycaemia in patients with insulin-treated type 2 diabetes and represents a practical, stable and inexpensive biomarker for assessment of hypoglycaemia risk.997.
Phase II Study of Irinotecan Plus Panitumumab as Second‐Line Therapy for Patients with Advanced Esophageal Adenocarcinoma
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998.
999.
Bidhan Chandra Bera Mamta Choudhary Taruna Anand Nitin Virmani Karthik Sundaram Binod Choudhary Bhupendra Nath Tripathi 《Transboundary and Emerging Diseases》2020,67(3):1062-1067
Porcine circovirus type 3 (PCV3), a novel circovirus, has been reported recently from major swine growing countries globally, and the virus is associated with diseases like porcine dermatitis, nephropathy syndrome and reproductive failure. This report describes the identification of PCV3 associated with reproductive failure in sows and piglet mortality and circulation of the virus in healthy pigs in India. The pathological changes in various tissues from stillborn piglet and characterization of the virus genomes were reported. The genome sequences of Indian PCV3 strains showed 91.4%–99.8% nucleotide identity with other sequences of PCV3 strains circulating worldwide. The phylogenetic analysis showed clustering of Indian strains into a separate group with the isolate from USA (MN/2016) under PCV3a genotype. The results confirmed the circulation of PCV3 in Indian pigs and its association with clinical cases. This study speculates emergence of PCV3 as an important pig pathogen in the country, which warrants the thorough investigation on PCV3 epidemiology, pathogenesis and to implement the control measures. 相似文献
1000.
Choudhary M Zhang X Stojkovic P Hyslop L Anyfantis G Herbert M Murdoch AP Stojkovic M Lako M 《Stem cells (Dayton, Ohio)》2007,25(12):3045-3057
Human embryonic stem cells (hESC) promise tremendous potential as a developmental and cell therapeutic tool. The combined effort of stimulatory and inhibitory signals regulating gene expression, which drives the tissue differentiation and morphogenetic processes during early embryogenesis, is still very poorly understood. With the scarcity of availability of human embryos for research, hESC can be used as an alternative source to study the early human embryogenesis. Hyaluronan (HA), a simple hydrating sugar, is present abundantly in the female reproductive tract during fertilization, embryo growth, and implantation and plays an important role in early development of the mammalian embryo. HA and its binding protein RHAMM regulate various cellular and hydrodynamic processes from cell migration, proliferation, and signaling to regulation of gene expression, cell differentiation, morphogenesis, and metastasis via both extracellular and intracellular pathways. In this study, we show for the first time that HA synthase gene HAS2 and its binding receptor RHAMM are differentially expressed during all stages of preimplantation human embryos and hESC. RHAMM expression is significantly downregulated during differentiation of hESC, in contrast to HAS2, which is significantly upregulated. Most importantly, RHAMM knockdown results in downregulation of several pluripotency markers in hESC, induction of early extraembryonic lineages, loss of cell viability, and changes in hESC cycle. These data therefore highlight an important role for RHAMM in maintenance of hESC pluripotency, viability, and cell cycle control. Interestingly, HAS2 knockdown results in suppression of hESC differentiation without affecting hESC pluripotency. This suggests an intrinsic role for HAS2 in hESC differentiation process. In accordance with this, addition of exogenous HA to the differentiation medium enhances hESC differentiation to mesodermal and cardiac lineages. Disclosure of potential conflicts of interest is found at the end of this article. 相似文献