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1.
Lab Invest ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350405

RESUMO

The mechanisms which underlie defects in learning and memory are a major area of focus with the increasing incidence of Alzheimer's disease in the aging population. The complex genetically-controlled, age-, and environmentally-dependent onset and progression of the cognitive deficits and neuronal pathology call for better understanding of the fundamental biology of the nervous system function. In this study, we focus on nuclear receptor binding factor-2 (NRBF2) which modulates the transcriptional activities of retinoic acid receptor α and retinoid X receptor α, and the autophagic activities of the BECN1-VPS34 complex. Since both transcriptional regulation and autophagic function are important in supporting neuronal function, we hypothesized that NRBF2 deficiency may lead to cognitive deficits. To test this, we developed a new mouse model with nervous system-specific knockout of Nrbf2. In a series of behavioral assessment, we demonstrate that NRBF2 knockout in the nervous system results in profound learning and memory deficits. Interestingly, we did not find deficits in autophagic flux in primary neurons and the autophagy deficits were minimal in the brain. In contrast, RNAseq analyses have identified altered expression of genes that have been shown to impact neuronal function. The observation that NRBF2 is involved in learning and memory suggests a new mechanism regulating cognition involving the role of this protein in regulating networks related to the function of retinoic acid receptors, protein folding, and quality control.

2.
Mol Cell Biochem ; 459(1-2): 215-217, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31325012

RESUMO

In the original publication of the article, the wrong ß-actin blots were pasted in Figs. 1b and 2c. The correct versions of Figs. 1b and 2c are given in this correction.

3.
J Orthod ; 46(3): 220-224, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31195913

RESUMO

INTRODUCTION: Infection control in dentistry is a major concern due to risk of transmission of communicable diseases. The aim of this study is to evaluate and compare the efficacy of various pre-cleaning methods for the tried-in orthodontic bands. MATERIAL AND METHODS: An in-vitro experimental study was conducted at the Central Sterilization Services Department (Dental Clinic) and the Microbiology lab at our university hospital. A total of 130 bands were included in our study which comprised 10 controls and the rest were equally divided into three groups according to the pre-cleaning methods, i.e. manual scrubbing, enzymatic solution and a combination of both. The orthodontic bands were incubated in the brain heart infusion broth at 37 °C for five days after pre-cleaning and sterilisation in a steam autoclave and were assessed for any bacterial growth. The chi-square test was applied to determine any significant association between the various pre-cleaning methods and the frequency of bands that showed growth. Effect size was calculated using the phi coefficient. RESULTS: The enzyme method revealed 5% of the sample to exhibit bacterial growth, whereas manual scrubbing and the combination of both showed no growth. There was no statistically significant difference among the three methods (P = 0.131). Further investigations showed the presence of Staphylococcus non-aureus bacterial species in contaminated bands from group II. CONCLUSIONS: All pre-cleaning methods were found to be equally effective in the decontamination of bands. Hence, the tried-in bands can be safely reused after pre-cleaning and sterilisation.


Assuntos
Ortodontia , Esterilização , Descontaminação , Contaminação de Equipamentos , Centros de Atenção Terciária
4.
Toxicol Lett ; 312: 204-213, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047999

RESUMO

Phosgene (Carbonyl Chloride, COCl2) remains an important chemical intermediate in many industrial processes such as combustion of chlorinated hydrocarbons and synthesis of solvents (degreasers, cleaners). It is a sweet smelling gas, and therefore does not prompt escape by the victim upon exposure. Supplemental oxygen and ventilation are the only available management strategies. This study was aimed to delineate the pathogenesis and identify novel biomarkers of acute lung injury post exposure to COCl2 gas. Adult male and female C57BL/6 mice (20-25 g), exposed to COCl2 gas (10 or 20 ppm) for 10 min in environmental chambers, had a dose dependent reduction in PaO2 and an increase in PaCO2, 1 day post exposure. However, mortality increased only in mice exposed to 20 ppm of COCl2 for 10 min. Correspondingly, these mice (20 ppm) also had severe acute lung injury as indicated by an increase in lung wet to dry weight ratio, extravasation of plasma proteins and neutrophils into the bronchoalveolar lavage fluid, and an increase in total lung resistance. The increase in acute lung injury parameters in COCl2 (20 ppm, 10 min) exposed mice correlated with simultaneous increase in oxidation of red blood cells (RBC) membrane, RBC fragility, and plasma levels of cell-free heme. In addition, these mice had decreased plasmalogen levels (plasmenylethanolamine) and elevated levels of their breakdown product, polyunsaturated lysophosphatidylethanolamine, in the circulation suggesting damage to cellular plasma membranes. This study highlights the importance of free heme in the pathogenesis of COCl2 lung injury and identifies plasma membrane breakdown product as potential biomarkers of COCl2 toxicity.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Substâncias para a Guerra Química/toxicidade , Hemólise/efeitos dos fármacos , Fosgênio/toxicidade , Administração por Inalação , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosgênio/administração & dosagem
5.
JCI Insight ; 3(21)2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30385726

RESUMO

Pulmonary fibrosis and emphysema are irreversible chronic events after inhalation injury. However, the mechanism(s) involved in their development remain poorly understood. Higher levels of plasma and lung heme have been recorded in acute lung injury associated with several insults. Here, we provide the molecular basis for heme-induced chronic lung injury. We found elevated plasma heme in chronic obstructive pulmonary disease (COPD) (GOLD stage 4) patients and also in a ferret model of COPD secondary to chronic cigarette smoke inhalation. Next, we developed a rodent model of chronic lung injury, where we exposed C57BL/6 mice to the halogen gas, bromine (Br2) (400 ppm, 30 minutes), and returned them to room air resulting in combined airway fibrosis and emphysematous phenotype, as indicated by high collagen deposition in the peribronchial spaces, increased lung hydroxyproline concentrations, and alveolar septal damage. These mice also had elevated pulmonary endoplasmic reticulum (ER) stress as seen in COPD patients; the pharmacological or genetic diminution of ER stress in mice attenuated Br2-induced lung changes. Finally, treating mice with the heme-scavenging protein, hemopexin, reduced plasma heme, ER stress, airway fibrosis, and emphysema. This is the first study to our knowledge to report elevated heme in COPD patients and establishes heme scavenging as a potential therapy after inhalation injury.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Estresse do Retículo Endoplasmático/genética , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/veterinária , Idoso , Animais , Enfisema/induzido quimicamente , Enfisema/patologia , Feminino , Fibrose/induzido quimicamente , Fibrose/patologia , Heme/metabolismo , Humanos , Hidroxiprolina/metabolismo , Inalação , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumaça/efeitos adversos
6.
Indian J Clin Biochem ; 33(4): 429-437, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30319189

RESUMO

Osteoporosis is a systemic disease with a strong genetic component. Vitamin D receptor (VDR) has been suggested as a candidate gene for osteoporosis. Therefore the present study was aimed to investigate the pattern of allelic variants of VDR gene polymorphism (FokI and BsmI), its influence on vitamin D levels and bone mineral density (BMD) in North Indian postmenopausal women with osteoporosis for possible genetic association. 254 postmenopausal osteoporotic women and 254 postmenopausal non osteoporotic women were included in the study. VDR FokI and BsmI gene polymorphism gene were assessed by the PCR-RFLP method. Serum 25-hydroxyvitamin D was measured by the ELISA. BMD at the L1-L4 lumbar spine, hip, forearm and femoral neck was assessed by dual energy X-ray absorptiometry. The average BMD at spine and hip in postmenopausal women with bb and spine, hip, femoral neck and forearm with ff genotype had significantly low BMD. The frequency of ff genotype and f allele was significantly higher in postmenopausal osteoporotic women when compared with postmenopausal non osteoporotic women. However, no significant association was found between the genotypes and vitamin D levels. Our study reveals that VDR gene FokI and BsmI polymorphism is significantly associated with low bone mineral density. Therefore the ff genotype and f allele of VDR FokI gene may be used as an important risk factor for osteoporosis.

7.
Am J Physiol Lung Cell Mol Physiol ; 315(5): L787-L798, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30188746

RESUMO

Allergic asthma is a major cause of morbidity in both pediatric and adult patients. Recent research has highlighted the role of hyaluronan (HA), an extracellular matrix glycosaminoglycan, in asthma pathogenesis. Experimental allergic airway inflammation and clinical asthma are associated with an increase of shorter fragments of HA (sHA), which complex with inter-α-inhibitor heavy chains (HCs) and induce inflammation and airway hyperresponsiveness (AHR). Importantly, the effects of sHA can be antagonized by the physiological counterpart high molecular weight HA (HMWHA). We used a mouse model of house dust mite-induced allergic airway inflammation and demonstrated that instilled HMWHA ameliorated allergic airway inflammation and AHR, even when given after the establishment of allergic sensitization and after challenge exposures. Furthermore, instilled HMWHA reduced the development of HA-HC complexes and the activation of Rho-associated, coiled-coil containing protein kinase 2. We conclude that airway application of HMWHA is a potential treatment for allergic airway inflammation.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Modelos Animais de Doenças , Ácido Hialurônico/administração & dosagem , Inflamação/prevenção & controle , Pyroglyphidae/patogenicidade , Hipersensibilidade Respiratória/prevenção & controle , Animais , Feminino , Inflamação/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Hipersensibilidade Respiratória/etiologia
8.
Pak J Med Sci ; 34(3): 525-529, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034409

RESUMO

Background & Objectives: Terrorist attack in Army Public School Peshawar, Pakistan left behind more than hundred children dead. It was the highest death toll of children in the world in a single terrorists attack. The attack dominated national and international news, high level security measures have been adopted in all school throughout Pakistan, which created fear and stress in children. The objective of the study was to determine post-traumatic stress disorder among children after six month of terrorist attack inspite of rigorous psychosocial support and rehabilitation. Methods: We wanted to determine Post Traumatic Stress Disorder (PTSD) among children of Army Public School of age range 10 to 18 years after 5 months of intervention and rehabilitation following terrorists attack. For this a self-report questionnaire, Child PTSD Symptom Scale (CPSS), which assess and identify symptoms matching DSM (Diagnostic and Statistical Manual of Mental Disorders) IV criteria for post-traumatic stress disorder of children, was filled. Informed consent was taken from school Principal and responders. Results: A total 205 students of age range 10 to 18 years participated in the study. The most frequent age group of the study were 16 years and 14 years students with frequency 58 (28.3%) and 46 (22.4%) respectively. Among 205 participated school children PTSD were found in 154 (75.2%) children while only 24.8% students had no PTSD symptoms. In more than 50% PTSD positive school children had functional impairment for each category of fun and hobbies, friendship, school work, family relation, doing chores, general happiness and saying prayers. Conclusion: Study found a very high prevalence of PTSD among 10 to 18 years age group students of Army Public School inspite of five months continuous intervention and rehabilitation services. Study showed that this age group needs long term psychosocial treatment in case of trauma.

9.
Int J Pharm ; 547(1-2): 582-592, 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-29859925

RESUMO

Mitochondria are considered the power house of cells where ATP is generated for cellular metabolism, and they also act as a crucial regulator of the intrinsic apoptosis pathway. During ATP synthesis, reactive oxygen species (ROS) are produced as secondary products. Overproduction of ROS can promote mitochondrial DNA mutation, dysfunction and depolarization of the mitochondrial membrane, ultimately resulting in cell death. Therefore, the destruction of mitochondria would be an effective therapeutic approach to kill malignant tumors. Herein, we formulated a PEGylated α-TOS polymeric micellar system loaded with 10-hydroxycamptothecin (HCPT) drug to inhibit the nuclear topoisomerase I enzyme and disrupt the mitochondrial membrane to induce apoptosis. In addition, tumor-penetrating CRGDK peptide-functionalized TPGS2k specifically bound to the Nrp-1 receptor to facilitate higher cell uptake of polymeric micelles by tumor cells. Experimental studies confirmed that HCPT-loaded and peptide-functionalized TPGS2k-TOS micelles (HLPFTTM) showed an enhanced anti-cancer effect in A549 cancer cells.


Assuntos
Camptotecina/análogos & derivados , Portadores de Fármacos/química , Neoplasias/tratamento farmacológico , Neuropilina-1/metabolismo , Inibidores da Topoisomerase I/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Camptotecina/farmacologia , Núcleo Celular/metabolismo , DNA Topoisomerases Tipo I/metabolismo , Sinergismo Farmacológico , Células Hep G2 , Humanos , Concentração Inibidora 50 , Células MCF-7 , Micelas , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/química , Peptídeos/química , Peptídeos/farmacologia , Polímeros/química , Espécies Reativas de Oxigênio/metabolismo , Vitamina E/química , Vitamina E/farmacologia
10.
Gene ; 659: 123-127, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29559350

RESUMO

Vitamin D receptor (VDR) gene has an important role as a candidate gene for the regulation of bone mass in osteoporosis. However, its association with bone mineral density (BMD) is controversial and has not been established in different ethnic populations. To enhance the understanding of VDR gene polymorphism in the context of BMD, we investigated the plausible genetic association of TaqI and ApaI polymorphism with BMD in North Indian postmenopausal women with osteoporosis.254 osteoporotic women (Age 55.82 ±â€¯6.91) and 254 postmenopausal non osteoporotic women (Age 54.76 ±â€¯6.26) were included in the study. VDR TaqI and ApaI polymorphism were determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). BMD was assessed by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L1-L4), hip, forearm and femoral neck. The average BMD with TT genotype was significantly lower at lumbar spine, hip and forearm. The Frequency of TT genotype and t allele was significantly high in osteoporotic women when compared with controls. The average BMD with Aa genotype was higher in ApaI. Furthermore, comparison of frequency distribution of genotype and allele for VDR ApaI between osteoporotic patients and controls did not show any significant difference. Our findings revealed that TaqI gene TT genotype was associated with low BMD in North Indian osteoporotic women. Moreover, TT genotype and t allele associated significantly with osteoporosis in postmenopausal women. Therefore, VDR TaqI gene is an important determinant of risk factor for osteoporosis.


Assuntos
Antebraço/diagnóstico por imagem , Estudos de Associação Genética/métodos , Quadril/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Osteoporose Pós-Menopausa/diagnóstico por imagem , Polimorfismo Genético , Receptores de Calcitriol/genética , Absorciometria de Fóton , Idoso , Densidade Óssea , Estudos de Casos e Controles , Feminino , Humanos , Índia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/genética , Pós-Menopausa
11.
Am J Physiol Lung Cell Mol Physiol ; 314(5): L808-L821, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29368549

RESUMO

Acid (HCl) aspiration during anesthesia may lead to acute lung injury. There is no effective therapy. We hypothesized that HCl instilled intratracheally in C57BL/6 mice results in the formation of low-molecular weight hyaluronan (L-HA), which activates RhoA and Rho kinase (ROCK), causing airway hyperresponsiveness (AHR) and increased permeability. Furthermore, instillation of high-molecular weight hyaluronan (H-HA; Yabro) will reverse lung injury. We instilled HCl in C57BL/6 wild-type (WT), myeloperoxidase gene-deficient (MPO-/-) mice, and CD44 gene-deficient (CD44-/-) mice. WT mice were also instilled intranasally with H-HA (Yabro) at 1 and 23 h post-HCl. All measurements were performed at 1, 5, or 24 h post-HCl. Instillation of HCl in WT but not in CD44-/- resulted in increased inflammation, AHR, lung injury, and L-HA in the bronchoalveolar lavage fluid (BALF) 24 h post-HCl; L-HA levels and lung injury were significantly lower in HCl-instilled MPO-/- mice. Isolated perfused lungs of HCl instilled WT but not of CD44-/- mice had elevated values of the filtration coefficient ( Kf). Addition of L-HA on the apical surface of human primary bronchial epithelial cell monolayer decreased barrier resistance ( RT). H-HA significantly mitigated inflammation, AHR, and pulmonary vascular leakage at 24 h after HCl instillation and mitigated the increase of Kf and RT, as well as ROCK2 phosphorylation. Increased H- and L-HA levels were found in the BALF of mechanically ventilated patients but not in healthy volunteers. HCl instillation-induced lung injury is mediated by the L-HA-CD44-RhoA-ROCK2 signaling pathway, and H-HA is a potential novel therapeutic agent for acid aspiration-induced lung injury.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Barreira Alveolocapilar/efeitos dos fármacos , Receptores de Hialuronatos/fisiologia , Ácido Hialurônico/farmacologia , Ácido Clorídrico/toxicidade , Peroxidase/fisiologia , Pneumonia/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Barreira Alveolocapilar/metabolismo , Barreira Alveolocapilar/patologia , Líquido da Lavagem Broncoalveolar/química , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Pneumonia/patologia , Troca Gasosa Pulmonar , Viscossuplementos/farmacologia
12.
JAMA Dermatol ; 153(10): 983-989, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28832880

RESUMO

Importance: Protective effects of UV-B radiation against nonmelanoma skin cancer (NMSC) are exerted via signaling mechanisms involving the vitamin D receptor (VDR). Recent studies have examined single-nucleotide polymorphisms (SNPs) in the VDR, resulting in contradictory findings as to whether these polymorphisms increase a person's risk for NMSC. Objective: To examine whether the polymorphisms in the VDR gene are associated with the development of NMSC and the demographic characteristics of the participants. Design, Setting, and Participants: This case-control study recruited 100 individuals who received a diagnosis of and were being treated for basal cell carcinoma or squamous cell carcinoma (cases) and 100 individuals who were receiving treatment of a condition other than skin cancer (controls) at the dermatology clinics at the Kirklin Clinic of the University of Alabama at Birmingham Hospital between January 1, 2012, and December 31, 2014. All participants completed a questionnaire that solicited information on skin, hair, and eye color; skin cancer family history; and sun exposure history, such as tanning ability and number of severe sunburns experienced throughout life. Blood samples for DNA genotyping were collected from all participants. Main Outcomes and Measures: Polymorphisms in the VDR gene (ApaI, BsmI, and TaqI) were assessed to determine the association of polymorphisms with NMSC development and demographic characteristics. χ2 Analysis was used to determine whether genotype frequencies deviated significantly from Hardy-Weinberg equilibrium. Logistic regression was used to calculate odds ratios (ORs) and associated 95% CIs for the identification of factors associated with NMSC diagnosis. A model was created to predict NMSC diagnoses using known risk factors and, potentially, VDR SNPs. Results: A total of 97 cases and 100 controls were included. Of the 97 cases, 68 (70%) were men and 29 (30%) were women, with a mean (SD) age of 70 (11) years. Of the 100 controls, 46 (46%) were men and 54 (54%) were women, with a mean (SD) age of 63 (9) years. All participants self-identified as non-Hispanic white. A model including age, sex, and skin color was created to most effectively predict the incidence of skin cancer. Risk factors that significantly increased the odds of an NMSC diagnosis were light skin color (OR, 5.79 [95% CI, 2.79-11.99]), greater number of severe sunburns (OR, 2.59 [95% CI, 1.31-5.10]), light eye color (OR, 2.47 [95% CI, 1.30-4.67]), and less of an ability to tan (OR, 2.35 [95% CI, 1.23-4.48]). The risk factors of family history of NMSC (OR, 1.66 [95% CI, 0.90-3.07]) and light hair color (OR, 1.17 [95% CI, 0.51-2.71]) did not reach statistical significance. Participants with the BsmI SNP were twice as likely to develop NMSC than participants with no mutation (OR, 2.04 [95% CI, 1.02-4.08]; P = .045). Conclusions and Relevance: The results of this study are especially useful in the early treatment and prevention of NMSC with chemopreventive agents (for those with the BsmI SNP). A screening for the BsmI SNP may emphasize the importance of sun protection and facilitate skin cancer prevention and, therefore, decrease the skin cancer burden.

13.
Colloids Surf B Biointerfaces ; 159: 540-545, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28846964

RESUMO

Inhibiting amyloid ß (Aß) aggregation has drawn much attention because it is one of the main reasons for the cause of Alzheimer's disease (AD). Here we have synthesized a nanocomposite of graphene oxide-iron oxide (GOIO) and demonstrated its ability of modulating Aß aggregation. The inhibition effects of the GOIO nanocomposite on Aß aggregates was studied by Thioflavin T fluorescence assay, circular dichroism and transmission electron microscopy, respectively. Furthermore, the cell viability study revealed that the GOIO nanocomposite can reduce the toxicity of Aß fibrils to neuroblastoma cells. Our results demonstrated that the combination of GO and IO as a nanocomposite material has a potential use for the design new therapeutic agents for the treatment of Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/química , Compostos Férricos/química , Grafite/química , Nanocompostos/química , Óxidos/química , Fragmentos de Peptídeos/química , Amiloide/química , Benzotiazóis , Linhagem Celular Tumoral , Dicroísmo Circular , Humanos , Microscopia Eletrônica de Transmissão , Tiazóis/química
15.
Exp Dermatol ; 26(11): 1018-1025, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28418604

RESUMO

The CDKN2A locus encodes for tumor suppressor genes p16INK4a and p14Arf which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation-induced skin tumors. Panels of INK4a/Arf-/- mice and wild-type (WT) mice were treated with a single dose of UVB (200 mJ/cm2 ). For long-term studies, these mice were irradiated with UVB (200 mJ/cm2 ) three times weekly for 30 weeks. At the end of the experiment, tissues were harvested from mice and assayed for inflammatory biomarkers and cytokines. A single dose of UVB resulted in a significant increase in reactive oxygen species (ROS) and 8-dihydroxyguanosine (8-oxo-dG) lesions in INK4a/Arf-/- mice compared to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf-/- mice had tumors, whereas there were no tumors in WT controls after 24 weeks of UVB exposure. The increase in tumor development correlated with a significant increase in nuclear factor (NF)-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2 ) and its receptors both in UVB-exposed skin and in the tumors. A significant increase was seen in inflammatory cytokines in skin samples of INK4a/Arf-/- mice following treatment with chronic UVB radiation. Furthermore, significantly more CD11b+ Gr1+ myeloid cells were present in UVB-exposed INK4a/Arf-/- mice compared to WT mice. Our data indicate that by targeting UVB-induced inflammation, it may be possible to prevent UVB-induced skin tumors in individuals that carry CDKN2A mutation.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Radiodermatite/etiologia , Neoplasias Cutâneas/etiologia , Raios Ultravioleta/efeitos adversos , Animais , Antígenos Ly/metabolismo , Núcleo Celular/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citoplasma/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Dinoprostona/metabolismo , Feminino , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Knockout , Células Mieloides/metabolismo , Células Mieloides/patologia , Inibidor de NF-kappaB alfa/metabolismo , Radiodermatite/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Prostaglandina E/metabolismo , Neoplasias Cutâneas/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
PLoS One ; 12(2): e0171896, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28192466

RESUMO

BACKGROUND: This paper presents the first quantitative ethnobotanical study of the flora in Toli Peer National Park of Azad Jammu and Kashmir, Pakistan. Being a remote area, there is a strong dependence by local people on ethnobotanical practices. Thus, we attempted to record the folk uses of the native plants of the area with a view to acknowledging and documenting the ethnobotanical knowledge. The aims of the study were to compile an inventory of the medicinal plants in the study area and to record the methods by which herbal drugs were prepared and administered. MATERIALS AND METHODS: Information on the therapeutic properties of medicinal plants was collected from 64 local inhabitants and herbalists using open ended and semi-structured questionnaires over the period Aug 2013-Jul 2014. The data were recorded into a synoptic table comprising an ethnobotanical inventory of plants, the parts used, therapeutic indications and modes of application or administration. Different ethnobotanical indices i.e. relative frequencies of citation (RFC), relative importance (RI), use value (UV) and informant consensus factor (Fic), were calculated for each of the recorded medicinal plants. In addition, a correlation analysis was performed using SPSS ver. 16 to check the level of association between use value and relative frequency of citation. RESULTS: A total of 121 species of medicinal plants belonging to 57 families and 98 genera were recorded. The study area was dominated by herbaceous species (48%) with leaves (41%) as the most exploited plant part. The Lamiaceae and Rosaceae (9% each) were the dominant families in the study area. Among different methods of preparation, the most frequently used method was decoction (26 species) of different plant parts followed by use as juice and powder (24 species each), paste (22 species), chewing (16 species), extract (11 species), infusion (10 species) and poultice (8 species). The maximum Informant consensus factor (Fic) value was for gastro-intestinal, parasitic and hepatobiliary complaints (0.90). Berberis lycium Ajuga bracteosa, Prunella vulgaris, Adiantum capillus-veneris, Desmodium polycarpum, Pinus roxburgii, Albizia lebbeck, Cedrella serrata, Rosa brunonii, Punica granatum, Jasminum mesnyi and Zanthoxylum armatum were the most valuable plants with the highest UV, RFC and relative importance values. The Pearson correlation coefficient between UV and RFC (0.881) reflects a significant positive correlation between the use value and relative frequency of citation. The coefficient of determination indicated that 77% of the variability in UV could be explained in terms of RFC. CONCLUSION: Systematic documentation of the medicinal plants in the Toli Peer National Park shows that the area is rich in plants with ethnomedicinal value and that the inhabitants of the area have significant knowledge about the use of such plants with herbal drugs commonly used to cure infirmities. The results of this study indicate that carrying out subsequent pharmacological and phytochemical investigations in this part of Pakistan could lead to new drug discoveries.


Assuntos
Ecossistema , Etnobotânica/métodos , Medicina Tradicional/métodos , Parques Recreativos , Plantas Medicinais/química , Conhecimentos, Atitudes e Prática em Saúde , Lamiaceae/química , Lamiaceae/classificação , Paquistão , Fitoterapia/métodos , Folhas de Planta/química , Preparações de Plantas/administração & dosagem , Preparações de Plantas/química , Preparações de Plantas/uso terapêutico , Plantas Medicinais/classificação , Plantas Medicinais/fisiologia , Rosaceae/química , Rosaceae/classificação , Especificidade da Espécie , Inquéritos e Questionários
17.
Photochem Photobiol ; 93(4): 1025-1033, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28120514

RESUMO

Basal cell carcinomas (BCCs) account for majority of skin malignancies in the United States. The incidence of BCCs is strongly associated with exposure of ultraviolet (UV) radiation. Nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome plays an important role in innate immune responses. Different stimuli such as toxins, microorganisms and particles released from injured cells activate the NLRP3 inflammasome. Activated NLRP3 results in activation of caspase-1, which cleaves pro-IL-1ß to active IL-1ß. In this study, we have shown that NLRP3 is expressed in human basal cell carcinomas. The proximal steps in activation of NLRP3 inflammasome are not well understood. Here, we have attempted to elucidate a critical role for Ca2+ mobilization in activation of the NLRP3 inflammasome by UVB exposure using HaCaT keratinocytes. We have demonstrated that UVB exposure blocks Ca2+ mobilization by downregulating the expression of sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA2), a component of store-operated Ca2+ entry that leads to activation of the NLRP3 inflammasome.


Assuntos
Cálcio/metabolismo , Carcinoma Basocelular/metabolismo , Regulação para Baixo/efeitos da radiação , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neoplasias Induzidas por Radiação/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta , Carcinoma Basocelular/patologia , Linhagem Celular , Homeostase , Humanos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Neoplasias Induzidas por Radiação/patologia , Neoplasias Cutâneas/patologia
18.
Cell Mol Biol (Noisy-le-grand) ; 63(12): 63-67, 2017 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-29307344

RESUMO

Gram-positive bacteria, particularly Staphylococcus aureus is a significant pathogen, not only in the hospital setting but the community also. S. aureus is a major cause of serious hospital and community-acquired infections, particularly in the colonized individuals. The emergence of vancomycin-resistant S. aureus (VRSA) strains has led to global concerns about treatments for staphylococcal infections. Until now, few strains of VRSA have been reported worldwide. The conventional disk diffusion method for determination of vancomycin sensitivity often misclassifies intermediately susceptible isolates to fully sensitive. However, non-automated minimum inhibitory concentration (MIC) detection methods are the gold standards. Hence there is a dire need of some advanced methods for rapid detection of VRSA strains. In the present study, Gram-positive clinical isolates were collected from different wards of K.G.M.U.  Hospital, among them, 12 bacterial isolates were identified as Staphylococcus aureus and 18 isolates as Klebsiella spp. Genomic DNA of S. aureus was isolated and used as template in PCR for detection of the presence of van A and van X gene based on a given protocol. Nosocomial infections have an impact on morbidity and probably on mortality as well, and pose a significant economic burden. Rapid molecular identification of antibiotic-resistant strains undoubtedly helps to prevent the hospital-induced infections.


Assuntos
Cateteres/microbiologia , Staphylococcus aureus/genética , Resistência a Vancomicina/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Infecção Hospitalar/microbiologia , Genes Bacterianos , Humanos , Klebsiella/efeitos dos fármacos , Fenótipo , Staphylococcus aureus/efeitos dos fármacos
19.
Arch Iran Med ; 19(12): 866-869, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27998162

RESUMO

BACKGROUND: Septicemia plays an important role in neonatal morbidity and mortality, especially in developing countries. OBJECTIVE: To investigate the bacterial pathogens causing neonatal sepsis and their antibiotic susceptibility profile. METHODOLOGY: A total of 2,685 neonates aged 0-28 days were included in the study. Blood from each neonate was cultured and isolates were identified using standard biochemical tests. Antibiotic sensitivity pattern was analyzed using modified Kirby-Bauer disc diffusion method. RESULTS: Blood culture positivity was observed in 1,534 (57.1%) samples. Most of the cases (1089 counts - 71%) were of early onset sepsis while 445 (29%) were of late onset sepsis. The incidence of sepsis was higher in males 856 (55.8%) than females 678 (44.2%) with a 1:2 ratio. Similarly, 58.3% of septicemic patients were neonates with low birth weights. Twelve hundred and six (78.6%) isolates were gram negative while 328 (23.4%) were gram positive bacteria. E. coli was the dominant pathogen seen in 811 (52.8%) followed by Staphylococcus aureus 300 (19.5%), Pseudomonas 199 (13%), Klebsiella 102 (6.7%), Proteus 87 (5.7%), Staphylococcus epidermidis 28(1.8%) and Salmonella in 7 (0.5%) samples. All bacterial isolates showed high sensitivity to Imipenem, Enoxacin, Ofloxacin and Ciprofloxacin while low sensitivity was observed for other antibiotics (n = 16). The Proteus species showed high level of multiple resistances to all antibiotics (5.9%). CONCLUSION: Imipenem, Enoxacin, Ofloxacin and Ciprofloxacin can be used as an effective antibiotic regimen for treatment of bacterial sepsis in neonates.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Sepse Neonatal/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Ciprofloxacino/farmacologia , Farmacorresistência Bacteriana , Enoxacino/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Infecções por Escherichia coli/microbiologia , Feminino , Bactérias Gram-Negativas/fisiologia , Humanos , Imipenem/farmacologia , Recém-Nascido de Baixo Peso , Recém-Nascido , Klebsiella/efeitos dos fármacos , Klebsiella/fisiologia , Infecções por Klebsiella/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Ofloxacino/farmacologia , Paquistão , Proteus/efeitos dos fármacos , Proteus/fisiologia , Infecções por Proteus/microbiologia , Pseudomonas/efeitos dos fármacos , Pseudomonas/fisiologia , Infecções por Pseudomonas/microbiologia , Staphylococcus aureus/fisiologia , Staphylococcus epidermidis/fisiologia
20.
J Environ Biol ; 37(2): 221-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27097441

RESUMO

Mango (Mangifera indica L.) has been cultivated and conserved in different agro-ecologies including Malihabad region in northern part of India, that is well known for housing diverse types (heirloom and commercial varieties). In the present study, 37 mango types comprising of 27 heirloom varieties from Malihabad region and 10 commercial varieties grown in North and Eastern India were assessed for morphological attributes and molecular diversity. The employed SSR markers amplified 2-13 alleles individually, cumulatively amplifying 124 alleles. These were studied for allelic diversity and genetic dissimilarity ranged from 0.035 to 0.892 arranging the varieties in three major clusters. The results revealed that majority of unique heirloom mangoes from Malihabad were different from the eastern part of the country. It is interesting to note Dashehari, a commercial variety from Malihabad was not aligned with heirloom varieties. Commercial varieties like Gulabkhas and Langra were placed in a separate group including Bombay Green, Himsagar, Dashehari, etc., indicating their dissimilarity with heirloom varieties at molecular level and thus, indicating importance for later from conservation point of view. Furthermore, the hierarchical clustering of varieties based on fruit morphology, assembled these into four groups largely influenced by fruit size. The maximum agreement subtree indicated seemingly good fit as thirteen varieties were arrayed in common grouping pattern. Appreciable dissimilarity among the heirloom varieties demonstrated by molecular analysis, underlines the importance for their on-farm conservation.


Assuntos
Agricultura , Variação Genética , Mangifera/genética , Conservação dos Recursos Naturais , DNA de Plantas/genética , Índia , Filogenia
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