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1.
Oncogene ; 41(2): 147-158, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34689178

RESUMO

G12 proteins comprise a subfamily of G-alpha subunits of heterotrimeric GTP-binding proteins (G proteins) that link specific cell surface G protein-coupled receptors (GPCRs) to downstream signaling molecules and play important roles in human physiology. The G12 subfamily contains two family members: Gα12 and Gα13 (encoded by the GNA12 and GNA13 genes, respectively) and, as with all G proteins, their activity is regulated by their ability to bind to guanine nucleotides. Increased expression of both Gα12 and Gα13, and their enhanced signaling, has been associated with tumorigenesis and tumor progression of multiple cancer types over the past decade. Despite these strong associations, Gα12/13 proteins are underappreciated in the field of cancer. As our understanding of G protein involvement in oncogenic signaling has evolved, it has become clear that Gα12/13 signaling is pleotropic and activates specific downstream effectors in different tumor types. Further, the expression of Gα12/13 proteins is regulated through a series of transcriptional and post-transcriptional mechanisms, several of which are frequently deregulated in cancer. With the ever-increasing understanding of tumorigenic processes driven by Gα12/13 proteins, it is becoming clear that targeting Gα12/13 signaling in a context-specific manner could provide a new strategy to improve therapeutic outcomes in a number of solid tumors. In this review, we detail how Gα12/13 proteins, which were first discovered as proto-oncogenes, are now known to drive several "classical" hallmarks, and also play important roles in the "emerging" hallmarks, of cancer.


Assuntos
Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Neoplasias/genética , Oncogenes/genética , Animais , Humanos , Camundongos , Transdução de Sinais
3.
Sci Rep ; 11(1): 10751, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031472

RESUMO

We aimed to isolate Acinetobacter baumannii (A. baumannii) from wound infections, determine their resistance and virulence profile, and assess the impact of Silver nanoparticles (AgNPs) on the bacterial growth, virulence and biofilm-related gene expression. AgNPs were synthesized and characterized using TEM, XRD and FTIR spectroscopy. A. baumannii (n = 200) were isolated and identified. Resistance pattern was determined and virulence genes (afa/draBC, cnf1, cnf2, csgA, cvaC, fimH, fyuA, ibeA, iutA, kpsMT II, PAI, papC, PapG II, III, sfa/focDE and traT) were screened using PCR. Biofilm formation was evaluated using Microtiter plate method. Then, the antimicrobial activity of AgNPs was evaluated by the well-diffusion method, growth kinetics and MIC determination. Inhibition of biofilm formation and the ability to disperse biofilms in exposure to AgNPs were evaluated. The effect of AgNPs on the expression of virulence and biofilm-related genes (bap, OmpA, abaI, csuA/B, A1S_2091, A1S_1510, A1S_0690, A1S_0114) were estimated using QRT-PCR. In vitro infection model for analyzing the antibacterial activity of AgNPs was done using a co-culture infection model of A. baumannii with human fibroblast skin cell line HFF-1 or Vero cell lines. A. baumannii had high level of resistance to antibiotics. Most of the isolates harbored the fimH, afa/draBC, cnf1, csgA and cnf2, and the majority of A. baumannii produced strong biofilms. AgNPs inhibited the growth of A. baumannii efficiently with MIC ranging from 4 to 25 µg/ml. A. baumannii showed a reduced growth rate in the presence of AgNPs. The inhibitory activity and the anti-biofilm activity of AgNPs were more pronounced against the weak biofilm producers. Moreover, AgNPs decreased the expression of kpsMII , afa/draBC,bap, OmpA, and csuA/B genes. The in vitro infection model revealed a significant antibacterial activity of AgNPs against extracellular and intracellular A. baumannii. AgNPs highly interrupted bacterial multiplication and biofilm formation. AgNPs downregulated the transcription level of important virulence and biofilm-related genes. Our findings provide an additional step towards understanding the mechanisms by which sliver nanoparticles interfere with the microbial spread and persistence.


Assuntos
Acinetobacter baumannii/fisiologia , Antibacterianos/administração & dosagem , Biofilmes/crescimento & desenvolvimento , Prata/administração & dosagem , Infecções por Acinetobacter , Acinetobacter baumannii/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Chlorocebus aethiops , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Humanos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Tamanho da Partícula , Prata/química , Prata/farmacologia , Células Vero , Virulência/efeitos dos fármacos
4.
Nanomaterials (Basel) ; 11(4)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921234

RESUMO

In this work, we developed a sandwich DNA-immunosensor for quantification of the methylated tumour suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT), which is a potential biomarker for brain tumours and breast cancer. The biosensor is based on aminated reduced graphene oxide electrode, which is achieved by ammonium hydroxide chemisorption and anti-5-methylcytosine (anti-5mC) as a methylation bioreceptor. The target single-strand (ss) MGMT oligonucleotide is first recognised by its hybridisation with complementary DNA to form double-stranded (ds) MGMT, which is then captured by anti-5mC on the electrode surface due to the presence of methylation. Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Scanning electron microscopy (SEM) techniques were used to characterise the electrode surface. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques were used for electrochemical measurements. Under optimised conditions, the proposed biosensor is able to quantify a linear range of concentrations of the MGMT gene from 50 fM to 100 pM with a limit of detection (LOD) of 12 fM. The sandwich design facilitates the simultaneous recognition and quantification of DNA methylation, and the amination significantly improves the sensitivity of the biosensor. This biosensor is label-, bisulfite- and PCR-free and has a simple design for cost-efficient production. It can also be tailor-made to detect other methylated genes, which makes it a promising detection platform for DNA methylation-related disease diagnosis and prognosis.

5.
Bioprocess Biosyst Eng ; 44(2): 417-427, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33034739

RESUMO

Combustion of coal create many harmful gases which effect on human health as well as on environment. The sulfur in coal limits its own use, and bio-desulfurization (BDS) shows enormous development potential and the prospects for the application of coal desulfurization. Present study highlights the bioprocess strategies for reduction of sulfur content from coal before combustion. The bioprocess involved the use of Airlift Bioreactor along with Rhodococcus sp. ATCC55309 as biocatalyst. Different nutritional and operational parameters involved to promote sulfur reduction at maximum level. The parameters were investigated are different carbon source, temperature, pH, Agitation speed, and pulp density. The impact of these parameters shows that sulfur removal can be enhanced though optimized conditions. The amount of total sulfur and organic sulfur present in coal were reduced by 33 ± 1.7% and 71 ± 1.5%, respectively, compared to untreated coal at controlled condition of various parameters are 20% (w/v) pulp density, 30 °C, 170 rpm, glucose as carbon source and pH 7. Whereas organic sulfur degrades from coal using Rhodococcus sp. ATCC55309 about 0.36 mM DBT (Di-benzothiophene) within 8 days via 4S-pathway. The maximum conversion of DBT compound into 2-HBP(2-hydroxybiphenyl) by utilizing 30 °C, 170 rpm, 20 pulp density and glucose as carbon source.


Assuntos
Biocatálise , Reatores Biológicos , Carvão Mineral , Rhodococcus/metabolismo , Enxofre/metabolismo
6.
Environ Sci Pollut Res Int ; 28(5): 5005-5019, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33241504

RESUMO

Petroleum, coal, and natural gas reservoir were depleting continuously due to an increase in industrialization, which enforced study to identify alternative sources. The next option is the renewable resources which are most important for energy purpose coupled with environmental problem reduction. Microbial fuel cells (MFCs) have become a promising approach to generate cleaner and more sustainable electrical energy. The involvement of various disciplines had been contributing to enhancing the performance of the MFCs. This review covers the performance of MFC along with different wastewater as a substrate in terms of treatment efficiencies as well as for energy generation. Apart from this, effect of various parameters and use of different nanomaterials for performance of MFC were also studied. From the current study, it proves that the use of microbial fuel cell along with the use of nanomaterials could be the waste and energy-related problem-solving approach. MFC could be better in performances based on optimized process parameters for handling any wastewater from industrial process.


Assuntos
Fontes de Energia Bioelétrica , Purificação da Água , Eletricidade , Eletrodos , Águas Residuárias
7.
Mikrochim Acta ; 187(6): 338, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32430539

RESUMO

The published version of this article, unfortunately, contains errors. Corrections in references were incorrectly carried out. Also, the reduction of graphene oxide was carried out between the potential of -1.5 and 0.5 V, instead of 0.5 and 1.5 V.

8.
Mikrochim Acta ; 187(5): 288, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32333119

RESUMO

A label-free biosensor is developed for the determination of plasma-based Aß1-42 biomarker in Alzheimer's disease (AD). The platform is based on highly conductive dual-layer of graphene and electrochemically reduced graphene oxide (rGO). The modification of dual-layer with 1-pyrenebutyric acid N-hydroxysuccinimide ester (Pyr-NHS) is achieved to facilitate immobilization of H31L21 antibody. The effect of these modifications were studied with morphological, spectral and electrochemical techniques. The response of the biosensor was evaluated using differential pulse voltammetry (DPV). The data was acquired at a working potential of ~ 180 mV and a scan rate of 50 mV s-1. A low limit of detection (LOD) of 2.398 pM is achieved over a wide linear range from 11 pM to 55 nM. The biosensor exhibits excellent specificity over Aß1-40 and ApoE ε4 interfering species. Thus, it provides a viable tool for electrochemical determination of Aß1-42. Spiked human and mice plasmas were used for the successful validation of the sensing platform in bio-fluidic samples. The results obtained from mice plasma analysis concurred with the immunohistochemistry (IHC) and magnetic resonance imaging (MRI) data obtained from brain analysis. Graphical abstract Schematic representation of the electrochemical system proposed for Aß1-42 determination: (a) modification of graphene screen-printed electrode (SPE) with monolayer graphene oxide (GO) followed by its electrochemical reduction generating graphene/reduced graphene oxide (rGO) dual-layer (b), modification of dual-layer with linker (c), Aß1-42 antibody (H31L21) (d), bovine serum albumin (BSA) (e) and Aß1-42 peptide (f).


Assuntos
Peptídeos beta-Amiloides/sangue , Técnicas Biossensoriais , Técnicas Eletroquímicas , Grafite/química , Fragmentos de Peptídeos/sangue , Animais , Biomarcadores/sangue , Humanos , Camundongos , Estrutura Molecular , Oxirredução
9.
J Indian Soc Periodontol ; 24(2): 122-126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189839

RESUMO

BACKGROUND: Various medications are used in the treatment of chronic systemic diseases that affect the periodontium. Antidepressants in mentally depressed patients are prescribed for a long term, but their effect on the periodontium has not been studied adequately. A case-control study was conducted to know the effect of two commonly prescribed antidepressants - venlafaxine (serotonin-norepinephrine reuptake inhibitor [SNRI]) and fluoxetine (selective serotonin reuptake inhibitor [SSRI]). These drugs have been shown to possess anti-inflammatory properties but do not protect the periodontium from insults caused by these medications, which are significantly associated with the presence of destruction of the periodontium. The aim of this study was to clinically evaluate the effect of antidepressants on various periodontal parameters. MATERIALS AND METHODS: The study sample consisted of 182 depressed patients divided into three study groups: Group I - the control group diagnosed as depressed on the first visit, Group II - depressed patients taking fluoxetine 20 mg/day, and Group III - patients taking venlafaxine 75 mg/day. Patients in Groups II and III were on isolated antidepressant medication at least for a period of 3 or more months. Mental depression in patients was assessed with the Patient Health Questionnaire-based Hamilton Depression Rating Scale with scoring of ≤16. All the depressed patients were assessed for periodontal health on the basis of the clinical periodontal parameters. RESULTS: The commonly prescribed antidepressants such as fluoxetine and venlafaxine do not protect the periodontium from destruction in spite of possessing anti-inflammatory properties; therefore, these drugs may be considered as a risk factor for periodontal health. The comparative periodontal indices on nonusers of antidepressants or control group (Group I), users of SSRI (fluoxetine) (Group II), and users of antidepressants-SNRI (venlafaxine) (Group III) showed increased periodontal parameters, especially debris index (DI), calculus index (CI), gingival index (GI), periodontal pocket depth (PD), and loss in clinical attachment level. There was no significant difference for CI and GI, probing PD, and clinical attachment levels except DI which was significantly different (P ≤ 0.001). CONCLUSION: The depressed patients receiving fluoxetine or venlafaxine should be regularly evaluated for periodontal health status as these drugs are risk factors for normal periodontal tissues. Further, these medications did not protect the periodontium from periodontal inflammation, although possessing anti-inflammatory properties.

10.
J Biol Chem ; 294(48): 18192-18206, 2019 11 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.


Assuntos
Quimiocina CXCL5/metabolismo , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Ativação Transcricional , Quimiocina CXCL5/genética , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Humanos , Masculino , Proteínas de Neoplasias/genética , Células PC-3 , Neoplasias da Próstata/genética , Fator de Transcrição RelA/genética
11.
Cell Death Differ ; 26(11): 2223-2236, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30737477

RESUMO

Cancer cells frequently boost nucleotide metabolism (NM) to support their increased proliferation, but the consequences of elevated NM on tumor de-differentiation are mostly unexplored. Here, we identified a role for thymidylate synthase (TS), a NM enzyme and established drug target, in cancer cell de-differentiation and investigated its clinical significance in breast cancer (BC). In vitro, TS knockdown increased the population of CD24+ differentiated cells, and attenuated migration and sphere-formation. RNA-seq profiling indicated repression of epithelial-to-mesenchymal transition (EMT) signature genes upon TS knockdown, and TS-deficient cells showed an increased ability to invade and metastasize in vivo, consistent with the occurrence of a partial EMT phenotype. Mechanistically, TS enzymatic activity was found essential for maintenance of the EMT/stem-like state by fueling a dihydropyrimidine dehydrogenase-dependent pyrimidine catabolism. In patient tissues, TS levels were found significantly higher in poorly differentiated and in triple negative BC, and strongly correlated with worse prognosis. The present study provides the rationale to study in-depth the role of NM at the crossroads of proliferation and differentiation, and depicts new avenues for the design of novel drug combinations for the treatment of BC.


Assuntos
Desdiferenciação Celular/fisiologia , Timidilato Sintase/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Animais , Antígeno CD24/metabolismo , Movimento Celular , Proliferação de Células/fisiologia , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica/genética , Prognóstico , Pirimidinas/metabolismo , Esferoides Celulares , Timidilato Sintase/genética , Células Tumorais Cultivadas
12.
Sensors (Basel) ; 18(1)2018 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-29361679

RESUMO

Clusterin (CLU) has been associated with the clinical progression of Alzheimer's disease (AD) and described as a potential AD biomarker in blood plasma. Due to the enormous attention given to cerebrospinal fluid (CSF) biomarkers for the past couple of decades, recently found blood-based AD biomarkers like CLU have not yet been reported for biosensors. Herein, we report the electrochemical detection of CLU for the first time using a screen-printed carbon electrode (SPCE) modified with 1-pyrenebutyric acid N-hydroxysuccinimide ester (Pyr-NHS) and decorated with specific anti-CLU antibody fragments. This bifunctional linker molecule contains succinylimide ester to bind protein at one end while its pyrene moiety attaches to the carbon surface by means of π-π stacking. Cyclic voltammetric and square wave voltammetric studies showed the limit of detection down to 1 pg/mL and a linear concentration range of 1-100 pg/mL with good sensitivity. Detection of CLU in spiked human plasma was demonstrated with satisfactory recovery percentages to that of the calibration data. The proposed method facilitates the cost-effective and viable production of label-free point-of-care devices for the clinical diagnosis of AD.


Assuntos
Clusterina/análise , Doença de Alzheimer , Biomarcadores , Técnicas Biossensoriais , Eletrodos , Humanos , Limite de Detecção , Pirenos
13.
Cancer Res ; 78(7): 1604-1618, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29343522

RESUMO

Cancer cells alter their metabolism to support their malignant properties. In this study, we report that the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) strongly correlates with epithelial-to-mesenchymal transition (EMT). This association was confirmed in samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels, and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGFß signature genes. Excess glucose was found to promote EMT through autocrine TGFß stimulation, while PP-deficient cells were refractory to glucose-induced EMT. These data show that PP represents a molecular link between glucose metabolism, cancer differentiation, and aggressiveness, and may serve as a novel therapeutic target.Significance: A glucose-transforming pathway in TGFß-driven epithelial-to-mesenchymal transition provides novel mechanistic insights into the metabolic control of cancer differentiation. Cancer Res; 78(7); 1604-18. ©2018 AACR.


Assuntos
Aldeído Redutase/genética , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal/genética , L-Iditol 2-Desidrogenase/genética , Neoplasias Pulmonares/patologia , Células A549 , Animais , Linhagem Celular Tumoral , Glucose/metabolismo , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Células MCF-7 , Camundongos , Interferência de RNA , RNA Interferente Pequeno/genética , Fator de Crescimento Transformador beta/metabolismo
14.
Oncogene ; 37(10): 1340-1353, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29255247

RESUMO

Treatment failure in solid tumors occurs due to the survival of specific subpopulations of cells that possess tumor-initiating (TIC) phenotypes. Studies have implicated G protein-coupled-receptors (GPCRs) in cancer progression and the acquisition of TIC phenotypes. Many of the implicated GPCRs signal through the G protein GNA13. In this study, we demonstrate that GNA13 is upregulated in many solid tumors and impacts survival and metastases in patients. GNA13 levels modulate drug resistance and TIC-like phenotypes in patient-derived head and neck squamous cell carcinoma (HNSCC) cells in vitro and in vivo. Blockade of GNA13 expression, or of select downstream pathways, using small-molecule inhibitors abrogates GNA13-induced TIC phenotypes, rendering cells vulnerable to standard-of-care cytotoxic therapies. Taken together, these data indicate that GNA13 expression is a potential prognostic biomarker for tumor progression, and that interfering with GNA13-induced signaling provides a novel strategy to block TICs and drug resistance in HNSCCs.


Assuntos
Transformação Celular Neoplásica/genética , Resistencia a Medicamentos Antineoplásicos/genética , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transformação Celular Neoplásica/efeitos dos fármacos , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Tumorais Cultivadas
15.
Biosensors (Basel) ; 7(3)2017 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-28704926

RESUMO

We report on a label-free immunosensor based on graphene field effect transistors (G-FETs) for the ultrasensitive detection of Human Chorionic Gonadotrophin (hCG), as an indicator of pregnancy and related disorders, such as actopic pregnancy, choriocarcinoma and orchic teratoma. Pyrene based bioactive ester was non-covalently anchored onto the graphene channel in order to retain the sp² lattice. The G-FET transfer characteristics showed repeatable and reliable responses in all surface modifying steps using a direct current (DC) readout system. The hCG concentration gradient showed a detection limit of ~1 pg·mL-1. The proposed method facilitates the cost-effective and viable production of graphene point-of-care devices for clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Gonadotropina Coriônica/isolamento & purificação , Grafite/química , Feminino , Ouro/química , Humanos , Gravidez , Transistores Eletrônicos
16.
Iran J Basic Med Sci ; 20(5): 511-515, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28656086

RESUMO

OBJECTIVES: Causality of occurrence of metformin-associated lactic acidosis (MALA) is a clinical problem. Currently, there is no drug available to prevent MALA. The present study was conducted to evaluate the protective effect of Berberine (BBR) against MALA in induced diabetic rat model. MATERIALS AND METHODS: A sample of 75 healthy male Wistar rats was randomly selected according to inclusion and exclusion criteria. 75 male Wistar rats were randomly divided into a control and 4 experimental groups. Streptozotocin (STZ) in citrate buffer (pH 4.5) at a dose of 45 mg/kg was injected for induction of diabetes mellitus and rats achieving fasting blood glucose >250 mg/dl were included. Blood samples were collected 18 hr after the last dose of metformin and berberine. Ethical approval was taken before the study was conducted. Staistix 10.0 (USA) software was used for data analysis. RESULTS: Berberine decreased MALA. Metformin, metformin + BBR 50 mg/kg bwt, and metformin + BBR 100 mg/kg bwt showed serum lactate as 1.87±0.4 mmol/lL, 1.62 ± 0.44 mmol/l and 1.47± 0.45 mmol/l, respectively (P=0.0001). Insulin resistance and liver enzymes were improved in BBR treated rats. CONCLUSION: The present study reports berberine protects against MALA in streptozocin-induced diabetes mellitus.

17.
J Res Med Sci ; 22: 49, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28567068

RESUMO

BACKGROUND: Pulmonary tuberculosis (PTB) is a chronic granulomatous disease caused by Mycobacterium tuberculosis. The present study determined the serum human enolase-2 (ENO-2), high-sensitive C-reactive protein (hs-CRP), and serum cholesterol levels as biological marker of disease activity and treatment response in smear-positive drug-naïve PTB. MATERIALS AND METHODS: This case-control study was done in the Department of Medicine, Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro/Hyderabad, Sindh, from January 2015 to April 2016. Thirty-five sputum smear-positive drug-naïve PTB patients and thirty controls were studied. MTB culture and drug sensitivity were performed at the Diagnostic and Research Laboratory of LUMHS. Serum ENO-2, hs-CRP, and serum cholesterol were estimated at baseline, 3rd and 6th month of antituberculosis (TB) therapy. RESULTS: Serum ENO-2 and hs-CRP were found raised in PTB compared to controls and showed decrease of 13% and 21.55%, 19.6% and 31.5% at 3rd and 6th month, respectively (P = 0.0001). Serum ENO-2 revealed positive correlation with hs-CRP (r = 0.734, P = 0.0001), and serum cholesterol revealed negative correlation with ENO-2 and hs-CRP (r = -0.509, P = 0.0001) and (r = -0.566, P = 0.0001), respectively. CONCLUSION: The present study reports the baseline ENO-2 and hs-CRP were raised, and serum cholesterol was low in smear-positive PTB patients and the ENO-2 and hs-CRP were reduced by anti-TB drug therapy.

18.
J Glob Infect Dis ; 9(4): 135-138, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29302147

RESUMO

Objective: The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. Study Design: This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Subjects and Methods: Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA). Results: Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female (P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii. Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. Conclusion: The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.

19.
Int Breastfeed J ; 11(1): 24, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27606000

RESUMO

BACKGROUND: Breastfeeding is considered to be an important measure to achieve optimum health outcomes for children, women's return to work has frequently been found to be a main contributor to the early discontinuation of breastfeeding. The aim of the study is to assess workplace breastfeeding support provided to working mothers in Pakistan. METHOD: A workplace based cross-sectional survey was conducted from April through December 2014. Employers from a representative sample of 297 workplaces were interviewed on pre-tested and structured questionnaire. The response rate was 93.7 %. Prevalence of workplace breastfeeding facilities were assessed in the light of World Alliance for Breastfeeding Action (WABA) guidelines. RESULTS: Among non-physical facilities, all workplaces offered 3 months paid maternity leave, 45 % of the sites were offering task adjustment to mothers during lactation period. Only 15 % of the sites were offering breastfeeding breaks to working mothers. Physical facilities that include a breastfeeding corner, refrigerator for storing breast milk, breast milk pump and nursery for childcare were provided in less than 7 % of the sites. Multinational organizations provided better support compared to national organizations. CONCLUSION: Support for continuation of breastfeeding by working women at workplaces is inadequate; hence, women discontinue breastfeeding earlier than planned. Policies need to be developed and enforced, employers and employees need to be educated and supportive environment needs to be created to encourage and facilitate breastfeeding friendly worksite environment.

20.
Cell Signal ; 28(10): 1479-88, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27424208

RESUMO

Gα13 (encoded by GNA13 gene) is the alpha subunit of a heterotrimeric G-protein that mediates signaling through specific G-protein-coupled receptors (GPCRs). Increased GNA13 expression has been observed in metastatic breast cancer cells. Recently, we have shown that enhanced GNA13 signaling in MCF-10a cells, a benign breast cancer cell line increased its invasiveness. Previous studies have reported that Kallikrein-related peptidases (KLKs 1-15) are down-regulated in breast tumors and may have a tumor protective function. However, the mechanisms that lead to the down-regulation of KLK genes in breast cancer are yet to be elucidated. We found that enhanced GNA13 signaling represses KLK gene expression in breast cancer, and undertook examination of the mechanisms involved. A microarray analysis revealed down-regulation of several members of the Kallikrein-related peptidases (KLK) gene family, namely KLK5, KLK6, KLK7, KLK8 and KLK10, in MCF-10a lines with enhanced GNA13 protein expression. Using real-time PCR and promoter analysis, we identified that the mRNA expression and promoter activities of these KLKs are suppressed upon enforced expression of GNA13 in MCF-10a cells. Using Rhotekin pull-down assays, we identified that GNA13 suppressed Rho-A activation and protein levels in MCF-10a cells. Blocking Rho-A activation using C3-toxin or by inhibiting its down-stream effector, Rho-associated kinase (ROCK), reduced the above-mentioned KLK mRNAs in MCF-10A cells. Importantly, in a metastatic breast cancer cell line MDA-MB-157, knock down of GNA13 alone was sufficient to induce the expression KLK mRNAs. Taken together, our findings suggested that enhanced GNA13 signaling down-regulates KLK gene transcription. The ability of enhanced GNA13 signaling to suppress KLK gene expression appears at least in part due to the ability of enhanced GNA13 signaling to negatively impact Rho/ROCK-signaling.


Assuntos
Neoplasias da Mama/genética , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Calicreínas/genética , Transdução de Sinais , Proteína rhoA de Ligação ao GTP/metabolismo , Toxinas Bacterianas/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Calicreínas/metabolismo , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/metabolismo
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