Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 267
Filtrar
1.
Diabetes ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409493

RESUMO

Exercise seems to enhance the beneficial effect of bariatric surgery (RYGB) on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underly these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB or standard of care (RYGB). Insulin sensitivity was assessed by OGTT. Muscle biopsies were obtained at baseline, and 3 and 9 months after surgery and subjected to comprehensive phenotyping, transcriptome profiling, molecular pathway identification and validation in vitro Exercise training improved insulin sensitivity beyond surgery alone (e.g, Matsuda index - RYGB: +123% vs. RYGB + ET: +325%; P ≤ 0.0001). ECM remodeling was reduced by surgery alone, with an additive benefit of surgery and exercise training (e.g., collagen I - RYGB: -41% vs. RYGB + ET: -76%; P ≤ 0.0001). Exercise and RYGB had an additive effect on enhancing insulin sensitivity, but surgery alone did not resolve insulin resistance and ECM remodeling. We identified candidates modulated by exercise training that may become therapeutic targets for treating insulin resistance, in particular, the transforming growth factor-beta 1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle extracellular matrix remodeling. Clinicaltrial.gov: NCT02441361.

2.
Analyst ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400815

RESUMO

Lab-on-a-chip technology offers an ideal platform for low-cost, reliable, and easy-to-use diagnostics of key biomarkers needed for early screening of diseases and other health concerns. In this work, a graphene field-effect transistor (GFET) functionalized with target-binding aptamers is used as a biosensor for the detection of thrombin protein biomarker. Furthermore, this GFET is integrated with a microfluidic device for enhanced sensing performances in terms of detection limit, sensitivity, and continuous monitoring. Under this platform, a picomolar limit of detection was achieved for measuring thrombin; in our experiment measured as low as 2.6 pM. FTIR, Raman and UV-Vis spectroscopy measurements were performed to confirm the device functionalization steps. Based on the concentration-dependent calibration curve, a dissociation constant of KD = 375.8 pM was obtained. Continuous real-time measurements were also conducted under a constant gate voltage (VGS) to observe the transient response of the sensor when analyte was introduced to the device. The target selectivity of the sensor platform was evaluated and confirmed by challenging the GFET biosensor with various concentrations of lysozyme protein. The results suggest that this device technology has the potential to be used as a general diagnostic platform for measuring clinically relevant biomarkers for point-of-care applications.

3.
Indian J Dent Res ; 31(1): 26-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32246677

RESUMO

Aim: The study was conducted to assess knowledge and awareness of biomedical waste management (BMWM) among undergraduate students, residents, and nursing staff in a tertiary care dental facility in Delhi. Materials and Methods: A questionnaire survey (using ten close ended questions) was conducted regarding various aspects of BMWM among undergraduate students, residents, and nursing staff in a tertiary care dental facility. In each group, scores were determined depending upon the correct responses, the participants marked. The data were compiled and subjected to statistical analysis. Results: Only 33.3% undergraduate students gave over 70% correct answers as compared to nursing staff (100%) and residents (62.2%). Undergraduate students showed various lacunae in terms of knowledge regarding BMWM. The difference between the knowledge of the 3 groups i.e., nursing staff, residents, and undergraduate students was statistically significant (P = 0.001). Residents exhibited better awareness regarding BMWM as compared to undergraduate students (P = 0.003). Conclusion: The pertinence of the issue of BMWM and lack of adequate preparation of the trainee dentists at undergraduate level reflects the urgent need to fill the lacunae in the dental undergraduate curriculum.


Assuntos
Atitude do Pessoal de Saúde , Gerenciamento de Resíduos , Instituições Odontológicas , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Índia , Atenção Terciária à Saúde
5.
Diabetes Ther ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916214

RESUMO

AIM: The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management. BACKGROUND: The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations. REVIEW RESULTS: After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most. CONCLUSION: Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.

6.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 129(2): e204-e211, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31606423

RESUMO

OBJECTIVE: Microcephalic osteodysplastic dwarfism (MOPD) type II (OMIM 210720) is a rare autosomal recessive form of primordial dwarfism, characterized by intrauterine and postnatal growth restriction, microcephaly, distinctive facial features, and osteodysplastic skeletal changes. The dental literature describing the oral manifestations of this syndrome is scarce. STUDY DESIGN: The aim of this article is to report the case of an 8-year-old male of Indian origin with MOPD type II and to describe his oral and dental manifestations. Genetic analysis was performed to confirm the diagnosis. RESULTS: The patient presented with interesting dental findings, including oligodontia, enamel hypoplasia, early exfoliation of primary dentition, accelerated eruption of permanent teeth with generalized grade II mobility, histopathologic features suggestive of dentin dysplasia, and a new mutation in the Pericentrin gene, which has not been documented earlier. CONCLUSIONS: This is the first report from India of a case with this syndrome. The article presents various dentomaxillofacial features that have not been documented in dental literature earlier with sufficient evidence.

7.
J Cytol ; 36(4): 200-204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741578

RESUMO

Background: The Bethesda system of reporting thyroid cytopathology (BSRTC) was introduced in 2007. The third category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) poses difficulties for the pathologist, and different papers have been published varying the risks of malignancy. Aims: (1) Evaluation of the cytological features of thyroid lesions according to BSRTC. (2) After resection, correlation with histopathological report to evaluate the risk of malignancy (ROM) and the risk of neoplasm (RON). (3) Division of category III into six subgroups based on cytological findings and assessment of ROM and RON. Materials and Methods: A total of 282 patients with diagnosed thyroid lesions underwent fine-needle sampling under ultrasound guidance. Smears were prepared and stained with May-Grunwald-Giemsa stain and Papanicolaou stain. Results: Of 282 cases, there were 9 cases (3.1%) of category I, 157 cases (55.8%) of category II, 24 cases (8.5%) of category III, 20 cases (7.1%) of category IV, 14 cases (4.8%) of category V, and 58 cases (20.7%) of category VI. The RON was 60, 17.1, 63.1, 77.7, 91.7, and 98.2% and the ROM was 60, 14.3, 26.3, 38.9, 91.7, and 96.3% in categories I, II, III, IV, V, and VI, respectively. The RON was 0, 75, 50, 100, 66.6, and 100% and the ROM was 0, 25, 50, 100, 16.6, and 0% in subgroups 1, 2, 3, 4, 5, and 6, respectively. We have proposed a system of subgrouping AUS/FLUS that may help to dispel the confusion generated by an AUS/FLUS report, and provide with a more exact and reproducible diagnostic and prognostic tool.

8.
Indian J Endocrinol Metab ; 23(4): 400-406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741896

RESUMO

As the first biologics produced by recombinant deoxyribonucleic acid (DNA) technology were approved in the late 1980s and consequently the exclusive marketing rights of most of these biological medicinal products have expired or will expire very shortly, it is quite evident that biosimilars are being developed and marketed in developed as well as developing countries in line with these expiries. Hence, there is an explosion of published papers and scientific programs on biological medicinal products and biosimilar insulins in the last decade or so. Each of these papers or scientific programs generated more questions than providing clinically useful answers. The specific aim of the medical literature or scientific programs were blurred due to lot of attention (created by the innovators) directed towards confusing terminologies, past mishaps with biosimilars (in the era with the absence of regulatory guidelines for biosimilars) diverting our attention from the matters relevant to clinicians and patients. One of the principle reason behind this phenomenon has been our poor understanding of the manufacturing process, regulatory pathways, and study endpoints involved in developing a biosimilar in the present era. This drawback resulted in a nonsystematic approach in analyzing the biosimilars and apparently resulting in confusion. This review attempts at demystifying certain facets of frequently encountered information on biosimilars and acquire a personal understanding on the same, rather than depending on conflicting versions floated at different continuing medical educations (CMEs) and Diabetes Congresses.

9.
Indian J Endocrinol Metab ; 23(4): 422-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741900

RESUMO

Context: There is no consensus about the inflection point for 25 hydroxy vitamin D below which the intact PTH level increases. Objective: Determine the relationship/inflection point between 25 hydroxy vitamin D and parathormone levels. Materials and Methods: We performed a population-based analysis on a nonobese cohort (n = 405). Results: Prevalence of vitamin D deficiency was 58.76% (n = 228). Vitamin D insufficiency was found in 34.56% (n = 140). An inverse relationship between 25 hydroxy vitamin D (25(OH)D) and intact PTH exist, but strength of such relationship is weak (r = -0.16, P = 0.018). With respect to the 25(OH)D cut-off of 16 ng/mL by IOM (EAR linked), proportion of persons with high intact PTH was higher in the group with lower 25(OH)D compared with higher 25(OH)D group (P = 0.005) and it was similar for RDA linked cut-off of 20 ng/mL also (P = 0.017). LOWESS method revealed two inflection points at which PTH levels change. A less conspicuous inflection point was found at 32 ng/mL (95% CI, 27-36), which reasonably corroborates with the current cutoff of definition of vitamin D sufficiency, and the second, steeper inflection point was found at 16.5 ng/ml (95% CI, 14.9-18.8) which corroborates with the IOM supported EAR linked value of 25(OH)D level in general population and possible definition of vitamin D deficiency. Conclusions: There are possibly two inflection points at which PTH levels change in relation to 25(OH)D levels.

10.
Indian J Endocrinol Metab ; 23(4): 438-445, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741903

RESUMO

Background: Data on prevalence and burden of end-organ damage in fibrocalculous pancreatic diabetes (FCPD) from eastern India is scant. This study investigated the burden of end-organ damage and exocrine pancreatic defect in FCPD patients in Eastern India. Materials and Methods: Consecutive FCPD patients underwent evaluation of glycemic control, C-peptide, fecal elastase, body fat percent, tests for cardiac autonomic neuropathy (CAN), neuropathy, nephropathy, and retinopathy which were compared with data from type-1 diabetes (T1DM) and type-2 diabetes (T2DM). Results: Data from 101 FCPD, 41 T1DM, 40 T2DM, and 40 controls were analyzed. Body fat percent was lowest in FCPD and T1DM. Similarly, fasting and stimulated C-peptide was significantly lowest in T1DM, followed by FCPD. Significant elevations in stimulated C-peptide were observed in FCPD. Fecal elastase was lowest in FCPD. Exocrine pancreas defect in FCPD, T1DM, and T2DM was 100%, 53.66%, 27.5%, respectively. HbA1c was worst in FCPD. About 40% of FCPD patients had CAN while 13.33% had borderline CAN. Isolated parasympathetic dysfunction was the commonest (66.67%) among them. FCPD patients with CAN had lower fecal elastase, higher HbA1c, microalbuminuria, steatorrhea, neuropathy, retinopathy, and nephropathy, compared to those without CAN. On binary logistic regression, diabetes duration was a significant predictor of end-organ damage in FCPD. Fecal elastase and body fat percent were independent predictors for insulin therapy in FCPD. Conclusion: CAN is common in FCPD while exocrine pancreas defect is most severe in FCPD followed by T1DM and T2DM. Fecal elastase has an important prognostic role for insulinization in FCPD. Role of pancreatic enzyme replacement on glycemic control in diabetes with exocrine pancreas defect needs investigation.

11.
Sci Transl Med ; 11(518)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723038

RESUMO

The gut microbiota evolves as the host ages, yet the effects of these microbial changes on host physiology and energy homeostasis are poorly understood. To investigate these potential effects, we transplanted the gut microbiota of old or young mice into young germ-free recipient mice. Both groups showed similar weight gain and skeletal muscle mass, but germ-free mice receiving a gut microbiota transplant from old donor mice unexpectedly showed increased neurogenesis in the hippocampus of the brain and increased intestinal growth. Metagenomic analysis revealed age-sensitive enrichment in butyrate-producing microbes in young germ-free mice transplanted with the gut microbiota of old donor mice. The higher concentration of gut microbiota-derived butyrate in these young transplanted mice was associated with an increase in the pleiotropic and prolongevity hormone fibroblast growth factor 21 (FGF21). An increase in FGF21 correlated with increased AMPK and SIRT-1 activation and reduced mTOR signaling. Young germ-free mice treated with exogenous sodium butyrate recapitulated the prolongevity phenotype observed in young germ-free mice receiving a gut microbiota transplant from old donor mice. These results suggest that gut microbiota transplants from aged hosts conferred beneficial effects in responsive young recipients.

12.
J Biol Chem ; 294(48): 18192-18206, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31636124

RESUMO

GNA13, the α subunit of a heterotrimeric G protein, mediates signaling through G-protein-coupled receptors (GPCRs). GNA13 is up-regulated in many solid tumors, including prostate cancer, where it contributes to tumor initiation, drug resistance, and metastasis. To better understand how GNA13 contributes to tumorigenesis and tumor progression, we compared the entire transcriptome of PC3 prostate cancer cells with those cells in which GNA13 expression had been silenced. This analysis revealed that GNA13 levels affected multiple CXC-family chemokines. Further investigation in three different prostate cancer cell lines singled out pro-tumorigenic CXC motif chemokine ligand 5 (CXCL5) as a target of GNA13 signaling. Elevation of GNA13 levels consistently induced CXCL5 RNA and protein expression in all three cell lines. Analysis of the CXCL5 promoter revealed that the -505/+62 region was both highly active and influenced by GNA13, and a single NF-κB site within this region of the promoter was critical for GNA13-dependent promoter activity. ChIP experiments revealed that, upon induction of GNA13 expression, occupancy at the CXCL5 promoter was significantly enriched for the p65 component of NF-κB. GNA13 knockdown suppressed both p65 phosphorylation and the activity of a specific NF-κB reporter, and p65 silencing impaired the GNA13-enhanced expression of CXCL5. Finally, blockade of Rho GTPase activity eliminated the impact of GNA13 on NF-κB transcriptional activity and CXCL5 expression. Together, these findings suggest that GNA13 drives CXCL5 expression by transactivating NF-κB in a Rho-dependent manner in prostate cancer cells.

13.
ACS Nano ; 13(11): 13413-13420, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31661261

RESUMO

The existence of an exquisite phenomenon such as a metal-insulator transition (MIT) in two-dimensional (2D) systems, where completely different electronic functionalities in the same system can emerge simply by regulating parameters such as charge carrier density in them, is noteworthy. Such tunability in material properties can lead to several applications where precise tuning of function specific properties are desirable. Here, we report on our observation on the occurrence of MIT in the 2D material system of copper indium selenide (CuIn7Se11). Clear evidence of the metallic nature of conductivity (σ) under the influence of electrostatic doping via the gate, which crosses over to an insulating phase upon lowering the temperature, was observed by investigating the temperature and gate dependence of σ in CuIn7Se11 field-effect transistor devices. At higher charge carrier densities (n > 1012 cm-1), we found that σ ∼ (n)α with α ∼ 2, which suggests the presence of bare Coulomb impurity scattering within the studied range of temperature (280 K > T > 20 K). Our analysis of the conductivity data following the principles of percolation theory of transition where σ ∼ (n - nC)δ show that the critical percolation exponent δ(T) has average values ∼1.57 ± 0.27 and 1.02 ± 0.35 within the measured temperature range for the two devices and it is close to the 2D percolation exponent value of 1.33. We believe that the 2D MIT seen in our system is due to the charge density inhomogeneity caused by electrostatic doping and unscreened charge impurity scattering that leads to a percolation driven transition. The findings reported here for CuIn7Se11 system provide a different material platform to investigate MIT in 2D and are crucial in order to understand the fundamental basis of electronic interactions and charge-transport phenomenon in other unexplored 2D electron systems.

14.
Indian J Endocrinol Metab ; 23(3): 273-277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31641626

RESUMO

Objective: New-onset diabetes after transplantation (NODAT) develops frequently after renal transplant. The study aims at the prevalence of NODAT, predictors for developing it and therapeutic glycemic responses in NODAT. Materials and Methods: Consecutive renal transplant recipients excluding Diabetic Kidney Disease (DKD) or pretransplant diabetes were evaluated. Forty-three out of 250 persons were found to have NODAT. Ninety age-matched transplant recipients from the rest were recruited as control. Fasting blood sugar (FBS), HbA1c, lipid profile, and trough tacrolimus level (T0) were examined in all. HOMA IR C-peptide and HOMA-beta C-peptide were calculated. Results: Prevalence of NODAT in renal transplant recipients was 17.2% (43/250). Twenty-four (55.8%) developed early NODAT (<1 year) and 19 (44.2%) developed late NODAT (>1 year). Significantly higher pretransplant body mass index (BMI) (kg/m2) (P < 0.001), waist circumference (WC) (cm) (P < 0.001), pretransplant cholesterol (mg%) (P = 0.04), triglyceride (mg%) (P < 0.001), and FBS (mg%) (P < 0.001) were found in NODAT compared with non-NODAT. Trough tacrolimus (ng/mL) was found to be higher in NODAT (10.2 vs. 5.37, P < 0.001). Though HOMA IR was not found to be different between groups, HOMA-beta C-peptide was low in NODAT compared with non-NODAT (P = 0.03). Predictors of NODAT were WC [odds ratio (OR) = 01.15] and trough tacrolimus level (OR = 1.316). Best cut-off of WC for predicting NODAT was 87.5 cm for male and 83.5 cm for female. Best cut-off of T0 was 8.5 ng/mL. In NODAT, 9.3% were treated by lifestyle modification, 67.4% by oral hypoglycemic agents, 11.6% by insulin, and 11.6% by combined insulin and oral antidiabetic agents with HbA1c <7%. Conclusion: NODAT in renal transplant recipients is more common in those with higher pretransplant BMI, WC, pretransplant total cholesterol, triglyceride, and FBS. Beta-cell secretory defect is more relevant as etiological factor rather than insulin resistance. Higher WC and trough tacrolimus level above 8.5 ng/mL may be important factors for predicting NODAT.

15.
Pituitary ; 22(6): 594-600, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556012

RESUMO

PURPOSE: Hypopituitarism frequently develops following vasculotoxic snake bite complicated by acute kidney injury (AKI). Well defined prospective studies of prevalence of hypopituitarism and its predictors in vasculotoxic snake bites complicated by AKI are unavailable. METHODS: Fifty-one consecutive patients of AKI following vasculotoxic snake bite were evaluated for various clinical/biochemical parameters (including Free T4, TSH, Cortisol, ACTH, total testosterone, FSH, LH, prolactin, and IGF-1). Diabetes insipidus was evaluated in relevant cases. Twenty minutes whole blood clotting time (WBCT) at presentation was measured in all. MRI of hypothalamo-pituitary region was done at 3 months in subjects with hypopituitarism to rule out structural lesion. RESULTS: 21.6% (11/51) patients developed hypopituitarism at baseline (within 7 days), 39.3% (13 /33) at 3 months developed hypopituitarism. Cortisol deficiency was the commonest abnormality. Subjects who developed hypopituitarism at baseline were younger compared to those without hypopituitarism (35.67 years vs. 46.59 years, p = 0.032) and required more sessions of hemodialysis (8 vs. 3, p = 0.041). Binary logistic regression confirmed that development of hypopituitarism could be predicted by increased number of sessions of hemodialysis (OR 1.51, p = 0.008) and 20 min WBCT (OR 1.2, p = 0.038). CONCLUSION: Hypopituitarism is common following vasculotoxic snake bite in subjects who develop AKI requiring hemodialysis. Hypopituitarism can develop as early as 7 days following snake bite and should be evaluated for particularly in younger subjects, especially those requiring increasing number of sessions of hemodialysis and in subjects with abnormal 20 min WBCT at presentation.

16.
Pan Afr Med J ; 33: 147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558944

RESUMO

Pleomorphic Adenoma (PA) is the most common salivary gland tumor and accounts for about 60% of all salivary gland neoplasms. Intraorally, the hard palate is the most common presenting site (50-60%) followed by upper lip (15-20%) and rarely buccal mucosa (8-10%). Histopathologically, PA shows diverse morphology resulting from amalgamation of cellular and stromal components. The PA may show changes in the stromal and epithelial components, such as sebaceous, lipocytic and oncocytic metaplasia. A rare characteristic of PA is to show extensive squamous and mucous differentiation which poses diagnostic dilemma to the pathologist. Here, we present an unusual case of PA of buccal minor salivary gland with squamous and mucous metaplasia. The localization, gender and microscopic features of the presented case are unusual.


Assuntos
Adenoma Pleomorfo/diagnóstico , Mucosa Bucal/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Glândulas Salivares Menores/patologia , Adenoma Pleomorfo/patologia , Adulto , Humanos , Masculino , Metaplasia , Neoplasias das Glândulas Salivares/patologia
17.
mSphere ; 4(5)2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533998

RESUMO

Dengue is caused by infection with any one of four dengue viruses (DENV); the risk of severe disease appears to be enhanced by the cross-reactive or subneutralizing levels of antibody from a prior DENV infection. These antibodies opsonize DENV entry through the activating Fc gamma receptors (FcγR), instead of infection through canonical receptor-mediated endocytosis, to result in higher levels of DENV replication. However, whether the enhanced replication is solely due to more efficient FcγR-mediated DENV entry or is also through FcγR-mediated alteration of the host transcriptome response to favor DENV infection remains unclear. Indeed, more efficient viral entry through activation of the FcγR can result in an increased viral antigenic load within target cells and confound direct comparisons of the host transcriptome response under antibody-dependent and antibody-independent conditions. Herein, we show that, despite controlling for the viral antigenic load in primary monocytes, the antibody-dependent and non-antibody-dependent routes of DENV entry induce transcriptome responses that are remarkably different. Notably, antibody-dependent DENV entry upregulated DENV host dependency factors associated with RNA splicing, mitochondrial respiratory chain complexes, and vesicle trafficking. Additionally, supporting findings from other studies, antibody-dependent DENV entry impeded the downregulation of ribosomal genes caused by canonical receptor-mediated endocytosis to increase viral translation. Collectively, our findings support the notion that antibody-dependent DENV entry alters host responses that support the viral life cycle and that host responses to DENV need to be defined in the context of its entry pathway.IMPORTANCE Dengue virus is the most prevalent mosquito-borne viral infection globally, resulting in variable manifestations ranging from asymptomatic viremia to life-threatening shock and multiorgan failure. Previous studies have indicated that the risk of severe dengue in humans can be increased by a specific range of preexisting anti-dengue virus antibody titers, a phenomenon termed antibody-dependent enhancement. There is hence a need to understand how antibodies augment dengue virus infection compared to the alternative canonical receptor-mediated viral entry route. Herein, we show that, besides facilitating viral uptake, antibody-mediated entry increases the expression of early host dependency factors to promote viral infection; these factors include RNA splicing, mitochondrial respiratory chain complexes, vesicle trafficking, and ribosomal genes. These findings will enhance our understanding of how differences in entry pathways can affect host responses and offer opportunities to design therapeutics that can specifically inhibit antibody-dependent enhancement of dengue virus infection.


Assuntos
Anticorpos Antivirais/imunologia , Vírus da Dengue/fisiologia , Interações entre Hospedeiro e Microrganismos , Receptores de IgG/imunologia , Internalização do Vírus , Anticorpos Facilitadores , Antígenos Virais/imunologia , Linhagem Celular , Células Cultivadas , Dengue/virologia , Humanos , Monócitos/imunologia , Monócitos/virologia , Análise de Sequência de RNA , Transcriptoma , Replicação Viral
18.
Artigo em Inglês | MEDLINE | ID: mdl-31402899

RESUMO

Background: Increase in circulating dipeptidyl peptidase-4 (DPP4) activity and levels has been reported to associate both with hyperglycemia and obesity. Here we aim to decipher the role of enhanced plasma DPP4 activity in obese type 2 diabetes (T2DM) patients. Materials and methods: Plasma DPP4 levels and activity were measured in obese and non-obese newly diagnosed T2DM patients (n = 123). Visceral and subcutaneous adipose tissue DPP4 expression and activity were determined in 43 obese subjects (T2DM = 21 and non-T2DM = 22). 20 subjects undergoing Mini-Gastric Bypass (MGB) surgery were followed up over 4-6 weeks for plasma DPP4. Results: Plasma DPP4 levels and activity both were increased in T2DM patients compared to control group. However, DPP4 levels and not DPP4 activity were increased in obese T2DM patients compared to non-obese T2DM (62.49 ± 26.27 µg/ml vs. 48.4 ± 30.98 µg/ml, respectively, p = 0.028). DPP4 activity in visceral adipose tissue (VAT) from obese T2DM and obese non-T2DM groups were similar (5.05 ± 3.96 nmol/min/ml vs. 5.83 ± 4.13 nmol/min/ml respectively, p = 0.548) in spite of having increased DPP4 expression in the obese T2DM group. Moreover, in obese patients, plasma DPP4 levels and activity did not show any significant change after weight reduction and glycemic control following MGB surgery. Conclusion: Enhanced plasma DPP4 activity in T2DM occurs independently of obesity. Thus, adipose derived DPP4 may not be playing any significant role in glycemic deregulation in obese T2DM patients.

19.
ACS Chem Neurosci ; 10(8): 3575-3589, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31313908

RESUMO

Guanabenz (GBZ), an α2-adrenergic agonist, demonstrated off-target effects that restored protein homeostasis and ameliorated pathobiology in experimental models of neurodegenerative disease. However, GBZ did not directly activate the integrated stress response (ISR), and its proposed mode of action remains controversial. Utilizing an iterative in silico screen of over 10,000 GBZ analogues, we analyzed 432 representative compounds for cytotoxicity in Wild-type, PPP1R15A-/-, and PPP1R15B-/- mouse embryonic fibroblasts. Nine compounds clustering into three functional groups were studied in detail using cell biological and biochemical assays. Our studies demonstrated that PromISR-6 is a potent GBZ analogue that selectively activated ISR, eliciting sustained eIF2α phosphorylation. ISRIB, an ISR inhibitor, counteracted PromISR-6-mediated translational inhibition and reduction in intracellular mutant Huntingtin aggregates. Reduced protein synthesis combined with PromISR-6-stimulated autophagic clearance made PromISR-6 the most efficacious GBZ analogue to reduce Huntingtin aggregates and promote survival in a cellular model of Huntington's disease.

20.
ACS Appl Mater Interfaces ; 11(30): 27279-27287, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31265242

RESUMO

This work introduces a piezoelectric-pyroelectric nanogenerator (P-PNG) based on methylammonium lead iodide (CH3NH3PbI3) incorporated electrospun poly(vinylidene fluoride) (PVDF) nanofibers that are able to harvest mechanical and thermal energies. During the application of a periodic compressive contact force at a frequency of 4 Hz, an output voltage of ∼220 mV is generated. The P-PNG has a piezoelectric coefficient (d33) of ∼19.7 pC/N coupled with a high durability (60 000 cycles) and quick response time (∼1 ms). The maximum generated output power density (∼0.8 mW/m2) is sufficient to charge up a variety of capacitors, with the potential to replace an external power supply to drive portable devices. In addition, upon exposure to cyclic heating and cooling at a temperature of 38 K, a pyroelectric output current of 18.2 pA and a voltage of 41.78 mV were achieved. The fast response time of 1.14 s, reset time of 1.25 s, and pyroelectric coefficient of ∼44 pC/m2 K demonstrate a self-powered temperature sensing capability of the P-PNG. These characteristics make the P-PNG suitable for flexible piezoelectric-pyroelectric energy harvesting for self-powered electronic devices.


Assuntos
Fontes de Energia Elétrica , Metilaminas/química , Nanofibras/química , Iodetos/química , Chumbo/química , Transição de Fase , Polivinil/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA