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1.
J Viral Hepat ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771312

RESUMO

Hepatitis C virus core antigen (HCVcAg) testing can simplify and decrease costs of HCV infection confirmation compared to molecular testing (nucleic acid testing). We piloted HCVcAg testing for the confirmation of active infection. The study was conducted during June through December 2022 among the police and the general population of Islamabad, Pakistan age 18 years and older. Initial screening for HCV antibody was conducted using a rapid diagnostic test (RDT) for all consenting participants. Those who tested positive had venous blood samples tested for HCVcAg, platelets and aspartate aminotransferase (AST). Persons with HCVcAg values ≥3 fmol/L were defined as viremic, and they were offered treatment with direct acting antiviral (DAA) medications, sofosbuvir and daclatasvir. Aspartate aminotransferase to platelet ratio index (APRI) was calculated for each HCV infected person, and those with an APRI score <1.5 received treatment for 12 weeks, while those with APRI ≥ to 1.5 received 24 weeks of treatment. A total of 15,628 persons were screened for anti-HCV using RDT and 643 (4.1%) tested positive. HCVcAg values of ≥3 fmol/L was found in 399/643 (62.1%), and all were offered and accepted treatment. Of those treated, 273/399 (68.4%) returned for a follow-up SVR and HCVcAg was not detected in 261/273, a 95.6% cure rate. The pilot study demonstrated the effectiveness of reaching and treating an urban population using RDT for screening and HCVcAg for confirmation of infection and test of cure.

2.
Nanomedicine (Lond) ; 19(9): 755-777, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38334078

RESUMO

Aim: This study aimed to develop and evaluate pH-sensitive docetaxel-loaded thiolated hyaluronic acid (HA-SH) nanoparticles (NPs) for targeted treatment of colon cancer. Materials & methods: HA-SH, synthesized via oxidation and subsequent covalent linkage to cysteamine, served as the precursor for developing HA-SH NPs through polyelectrolyte complexation involving chitosan and thiol-bearing HA. Results & conclusion: HA-SH NPs displayed favorable characteristics, with small particle sizes (184-270 nm), positive zeta potential (15.4-18.6 mV) and high entrapment efficiency (91.66-95.02%). In vitro, NPs demonstrated potent mucoadhesion and enhanced cytotoxicity compared with free docetaxel. In vivo assessments confirmed safety and biocompatibility, suggesting HA-SH NPs as promising pH-sensitive drug carriers with enhanced antitumor activity for colorectal cancer treatments.


Assuntos
Quitosana , Neoplasias do Colo , Nanopartículas , Humanos , Docetaxel , Ácido Hialurônico , Portadores de Fármacos , Polímeros , Concentração de Íons de Hidrogênio , Tamanho da Partícula
3.
BMC Pediatr ; 23(Suppl 1): 653, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38413880

RESUMO

BACKGROUND: Bangladesh significantly reduced under-5 mortality (U5M) between 2000 and 2015, despite its low economic development and projected high mortality rates in children aged under 5 years. A portion of this success was due to implementation of health systems-delivered evidence-based interventions (EBIs) known to reduce U5M. This study aims to understand how Bangladesh was able to achieve this success between 2000 and 2015. Implementation science studies such as this one provide insights on the implementation process that are not sufficiently documented in existing literature. METHODS: Between 2017 and 2020, we conducted mixed methods implementation research case studies to examine how six countries including Bangladesh outperformed their regional and economic peers in reducing U5M. Using existing data and reports supplemented by key informant interviews, we studied key implementation strategies and associated implementation outcomes for selected EBIs and contextual factors which facilitated or hindered this work. We used facility-based integrated management of childhood illnesses and insecticide treated nets as examples of two EBIs that were implemented successfully and with wide reach across the country to understand the strategies put in place as well as the facilitating and challenging contextual factors. RESULTS: Strategies which contributed to the successful implementation and wide coverage of the selected EBIs included community engagement, data use, and small-scale testing, important to achieving implementation outcomes such as effectiveness, reach and fidelity, although gaps persisted including in quality of care. Key contextual factors including a strong community-based health system, accountable leadership, and female empowerment facilitated implementation of these EBIs. Challenges included human resources for health, dependence on donor funding and poor service quality in the private sector. CONCLUSION: As countries work to reduce U5M, they should build strong community health systems, follow global guidance, adapt their implementation using local evidence as well as build sustainability into their programs. Strategies need to leverage facilitating contextual factors while addressing challenging ones.


Assuntos
Serviços de Saúde da Criança , Prestação Integrada de Cuidados de Saúde , Inseticidas , Criança , Humanos , Feminino , Bangladesh , Personalidade
4.
J Viral Hepat ; 31(3): 156-160, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38169120

RESUMO

Collection and preservation of plasma are challenging in remote or under-resourced settings. The cobas® Plasma Separation Card (PSC) is an alternative specimen type for blood-borne pathogen nucleic acid quantitation. We assessed PSC as a specimen type for HCV RNA quantitation in Pakistan. Plasma from venous blood and PSC from finger prick blood were prepared at two sites: Site 1 (in Lahore, n = 199) consisted of laboratory-based outpatient clinics. Specimens were prepared in the same facility and stored frozen. Site 2 was a catchment area within a resource-limited, semi-urban locality of Islamabad with limited access to healthcare services (n = 151). Community public health outreach staff collected blood and prepared the PSC in the participants' homes. Specimens were transported to the central hepatitis laboratory in Lahore to be stored frozen until tested. HCV RNA testing was performed using the cobas HCV RNA test in a central laboratory. Concordance with respect to RNA detectability was high at Site 1 (97.4%), but lower at Site 2 (82.4%). At Site 1, HCV viral load in plasma and PSC were well correlated across the linear range with a 0.21 log10 IU/mL mean bias toward higher concentrations in PSC. At Site 2, HCV viral load in plasma and PSC were poorly correlated. There was a 0.11 log10 IU/mL mean bias toward higher concentrations in PSC. PSC performance can be excellent in underserved settings where refrigerated transport of traditional specimens is difficult. In very challenging field settings, extra support must be provided to ensure correct specimen collection and handling.


Assuntos
Hepatite C , RNA Viral , Humanos , Carga Viral/métodos , Hepacivirus/genética , Plasma , Hepatite C/diagnóstico , Sensibilidade e Especificidade
5.
J Mater Chem B ; 11(40): 9712-9720, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37791404

RESUMO

The development of organic dyes with emission peaks in the second near-infrared window (NIR-II 1000-1700 nm) is highly desirable for in vivo imaging and imaging-guided phototheranostics. However, the lack of appropriate molecular frameworks and the challenges associated with complex synthesis critically hinder the development of new candidate fluorophores. J-Aggregation is considered as a smart and straightforward way to construct such a therapeutic agent with NIR-II fluorescence imaging properties. Here, we present the design and synthesis of an aza-BODIPY probe (TA). Upon encapsulation within the amphiphilic polymer DSPEG-PEG2000-NH2, TA underwent self-assembly and formed J-aggregates (TAJ NPs), which showed emission at 1020 nm. High spatial resolution and adequate signal-to-noise ratio of the TAJ NPs are demonstrated for noninvasive bioimaging of the vasculature, lymph nodes and bones of mice in the NIR-II region. Moreover, the TAJ NPs exhibited good tumor enrichment efficiency with reduced liver accumulation and significant imaging-guided phototherapy performance against lung cancer cells. Taken together, this work not only introduces a new NIR-II imaging and phototheranostic agent based on J-aggregates, but also provides insight into the development of versatile organic dyes for future clinical implementation.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Nanopartículas/química , Neoplasias/terapia , Compostos de Boro , Corantes Fluorescentes/química
6.
J Infect Dis ; 228(Suppl 3): S204-S210, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37703344

RESUMO

BACKGROUND: Pakistan has a high hepatitis burden for both hepatitis C virus (HCV) and hepatitis B virus (HBV). To achieve World Health Organization (WHO) 2030 targets for hepatitis elimination, there is a need to constitute progress in the country, find the barriers and strategies for HCV elimination, and take actions to address the gaps. METHODS: We collected data from (1) WHO estimates in 2020, (2) midterm review questionnaire of the WHO regional action plan, and (3) WHO estimates on immunization. We analyzed these data to inform (1) the burden defined as prevalence and mortality and (2) response in 3 thematic areas: governance, policy, and finance; strategic information; and service delivery. RESULTS: The prevalence of hepatitis B in the general population is 1.6% with 12 000 deaths/year. The prevalence of hepatitis C in the general population is 7.5% with 19 000 deaths and 545 000 new cases (incidence)/year. The selected indicators to monitor progress on viral hepatitis in Pakistan were governance and financing, policies and guidelines, and strategic information. The overall governance indicators are good with a focal point, a national hepatitis strategy, an operational plan, strategy for price reduction, and involvement of civil society but the costed action plan and the advocacy strategy are missing. The indicators on policies and guidelines are also adequately addressed. The hepatitis B and C testing and treatment guidelines are available, there is a policy to screen all blood donations, and there is an injection safety policy, but the policy for timely hepatitis B vaccine birth dose and hepatitis B vaccination for the vulnerable is missing. Both indicators regarding strategic information, that is measures of key hepatitis indicators and regular data review, are missing. The status of 5 key interventions in Pakistan show that the hepatitis B vaccination coverage is 74% and only 3% of newborn children are given the hepatitis B vaccine birth dose. Only 22% of HCV cases have been diagnosed and 2% have received treatment. Treatment response is 96%. Same-day testing and treatment of hepatitis C reduced the overall dropout rate and improved the cascade of care. Decentralization and task shifting are important tools to improve service delivery and reach communities. Finances to implement hepatitis elimination is a major barrier. CONCLUSIONS: Pakistan has the highest hepatitis disease burden. With the current pace, hepatitis elimination appears impossible. Introduction of the birth dose of hepatitis B vaccine and improving access and affordability of testing can improve the testing and treatment numbers. Finances need to be mobilized from within the country and outside to support disease elimination.


Assuntos
Hepatite A , Hepatite B , Hepatite C , Recém-Nascido , Humanos , Paquistão/epidemiologia , Vacinas contra Hepatite B , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepacivirus
7.
Adv Healthc Mater ; 12(26): e2300871, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37204046

RESUMO

Ferroptosis is a form of programmed cell death and plays an important role in many diseases. Dihydroorotate dehydrogenase (DHODH) and glutathione peroxidase 4 (GPX4) play major roles in cell resistance to ferroptosis. Therefore, inactivation of these proteins provides an excellent opportunity for efficient ferroptosis-based synergistic cancer therapy. In this study, a multifunctional nanoagent (BPNpro ) containing a GPX4 targeting boron dipyrromethene (Bodipy) probe (BP) and a DHODH targeting proteolysis targeting chimera (PROTAC) is reported. BPNpro is prepared using a nanoprecipitation method in the presence of a thermoresponsive liposome, where BP is encapsulated inside and the cathepsin B (CatB)-cleavable PROTAC peptide (DPCP) is modified on the outer surface. In the presence of near-infrared (NIR) photoirradiation, BPNpro is melted and BP is released in tumor cells. Subsequently, BP inhibits the activity of GPX4 by covalently bonding with the selenocysteine at the enzyme active site. In addition, DPCP achieves sustained degradation of DHODH upon activation by CatB overexpressed in the tumor. The synergistic deactivation of GPX4 and DHODH induces extensive ferroptosis and subsequent cell death. In vivo and in vitro studies clearly show that the proposed ferroptosis therapy provides excellent antitumor effect.


Assuntos
Di-Hidro-Orotato Desidrogenase , Ferroptose , Neoplasias , Humanos , Boro , Ferroptose/genética , Ferroptose/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia
8.
Antioxidants (Basel) ; 12(5)2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37237981

RESUMO

Recently, we reported that N-acetyltransferase 10 (NAT10) regulates fatty acid metabolism through ac4C-dependent RNA modification of key genes in cancer cells. During this work, we noticed ferroptosis as one of the most negatively enriched pathways among other pathways in NAT10-depleted cancer cells. In the current work, we explore the possibility of whether NAT10 acts as an epitranscriptomic regulator of the ferroptosis pathway in cancer cells. Global ac4C levels and expression of NAT10 with other ferroptosis-related genes were assessed via dotblot and RT-qPCR, respectively. Flow cytometry and biochemical analysis were used to assess oxidative stress and ferroptosis features. The ac4C-mediated mRNA stability was conducted using RIP-PCR and mRNA stability assay. Metabolites were profiled using LC-MS/MS. Our results showed significant downregulation in expression of essential genes related to ferroptosis, namely SLC7A11, GCLC, MAP1LC3A, and SLC39A8 in NAT10-depleted cancer cells. Further, we noticed a reduction in cystine uptake and reduced GSH levels, along with elevated ROS, and lipid peroxidation levels in NAT10-depleted cells. Consistently, overproduction of oxPLs, as well as increased mitochondrial depolarization and decreased activities of antioxidant enzymes, support the notion of ferroptosis induction in NAT10-depleted cancer cells. Mechanistically, a reduced ac4C level shortens the half-life of GCLC and SLC7A11 mRNA, resulting in low levels of intracellular cystine and reduced GSH, failing to detoxify ROS, and leading to increased cellular oxPLs, which facilitate ferroptosis induction. Collectively, our findings suggest that NAT10 restrains ferroptosis by stabilizing the SLC7A11 mRNA transcripts in order to avoid oxidative stress that induces oxidation of phospholipids to initiate ferroptosis.

9.
Anal Chim Acta ; 1260: 341173, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37121649

RESUMO

Fluorescence-based visual assays have sparked tremendous attention in on-site detection due to their obvious color gradient changes and high sensitivity. In this study, a novel emission wavelength shift-based visual sensing platform is constructed to detect glucose based on the oxidation of Rhodamine B (RhB). MnO2 nanosheets (MnO2 NS) with strong oxidizing properties were introduced to oxidize RhB, which resulted in a blue shift in the emission wavelength, and a visual color changed of the fluorescence from orange-red to green. The oxidation reaction could be inhibited via reducing and destroying MnO2 NS by H2O2, which was produced by the oxidizing procedure of glucose in the presence of glucose oxidase (GOx). A series of wavelength shifts and fluorescence color variations appeared with the addition of various amounts of glucose. A ratiometric fluorescence glucose sensor with a lowest recorded concentration of 0.25 µM was developed. Meanwhile, test paper-based assays integrated with the smartphone platform were established for the sensing of glucose by means of the significant fluorescence color changes, offering a reliable, sensitive, and portable on-site assay of glucose.


Assuntos
Glucose , Smartphone , Fluorescência , Peróxido de Hidrogênio , Compostos de Manganês , Óxidos , Corantes Fluorescentes , Limite de Detecção
10.
J Viral Hepat ; 30(4): 345-354, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36650932

RESUMO

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treatment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-HCV prevalence. In the absence of an updated national study, this analysis uses provincial data to estimate a national prevalence and the interventions needed to achieve elimination. Using a Delphi process, epidemiologic HCV data for the four provinces of Pakistan (accounting for 97% of the population) were reviewed with 21 subject-matter experts in Pakistan. Province-level estimates were inputted into a mathematical model to estimate the national HCV disease burden in the absence of intervention (Base), and if the World Health Organization (WHO) elimination targets are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated 9,746,000 (7,573,000-10,006,000) Pakistanis were living with viraemic HCV as of January 1, 2021; a viraemic prevalence of 4.3% (3.3-4.4). WHO Elimination would require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700 new infections prevented anually between 2022 and 2030. Elimination would reduce total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data, and expert panel input uncovered more HCV infections and lower treatment numbers in the provinces than estimated using national extrapolations, demonstrating the benefits of a bottom-up approach. Screening and treatment must increase 20 times and 5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination by 2030.


Assuntos
Hepatite C , Neoplasias Hepáticas , Humanos , Hepacivirus , Prevalência , Paquistão/epidemiologia , Antivirais/uso terapêutico , Hepatite C/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico
11.
BMC Public Health ; 22(1): 2417, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36550423

RESUMO

BACKGROUND: There is growing global evidence that girl child marriage (CM) increases during humanitarian crises. Norms, attitudes, and policies that sustain CM are deeply entrenched within families and communities, and may be further exacerbated by conflict and displacement. The purpose of this study is to understand how the social and normative environment influences attitudes and practices related to CM in two diverse humanitarian settings. METHODS: We held a total of eight focus group discussions, four in each country, with Syrian refugees in Jordan and Rohingya Refugees in Bangladesh. FGDs were conducted with fathers, mothers, and adolescent boys and girls. RESULTS: Similar themes emerged from both settings. Participants discussed a desire to hold onto tradition in displacement and how norms are reinforced across generations. Social influence emerged in positive and negative ways, including peer pressure and conformity and the positive influence of host communities. In both settings, girls themselves described having little agency. Participants described resistance to change, which was exacerbated by conflict and displacement, though they discussed how social influence could be an effective way to challenge existing norms that drive the practice of girl child marriage. CONCLUSIONS: Our findings represent a more robust understanding of how norms operate within the social ecological system, and how they are reinforced across social relationships, offering an opportunity to more effectively challenge norms that sustain the practice of girl child marriage.


Assuntos
Refugiados , Masculino , Feminino , Adolescente , Humanos , Criança , Casamento , Jordânia , Bangladesh , Síria , Meio Social
12.
Molecules ; 27(21)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36364431

RESUMO

Neurodegenerative diseases exert an overwhelming socioeconomic burden all around the globe. They are mainly characterized by modified protein accumulation that might trigger various biological responses, including oxidative stress, inflammation, regulation of signaling pathways, and excitotoxicity. These disorders have been widely studied during the last decade in the hopes of developing symptom-oriented therapeutics. However, no definitive cure has yet been discovered. Tea is one of the world's most popular beverages. The same plant, Camellia Sinensis (L.).O. Kuntze, is used to make green, black, and oolong teas. Green tea has been most thoroughly studied because of its anti-cancer, anti-obesity, antidiabetic, anti-inflammatory, and neuroprotective properties. The beneficial effect of consumption of tea on neurodegenerative disorders has been reported in several human interventional and observational studies. The polyphenolic compounds found in green tea, known as catechins, have been demonstrated to have many therapeutic effects. They can help in preventing and, somehow, treating neurodegenerative diseases. Catechins show anti-inflammatory as well as antioxidant effects via blocking cytokines' excessive production and inflammatory pathways, as well as chelating metal ions and free radical scavenging. They may inhibit tau protein phosphorylation, amyloid beta aggregation, and release of apoptotic proteins. They can also lower alpha-synuclein levels and boost dopamine levels. All these factors have the potential to affect neurodegenerative disorders. This review will examine catechins' neuroprotective effects by highlighting their biological, pharmacological, antioxidant, and metal chelation abilities, with a focus on their ability to activate diverse cellular pathways in the brain. This review also points out the mechanisms of catechins in various neurodegenerative and cognitive diseases, including Alzheimer's, Parkinson's, multiple sclerosis, and cognitive deficit.


Assuntos
Camellia sinensis , Catequina , Doenças Neurodegenerativas , Humanos , Chá , Catequina/farmacologia , Catequina/uso terapêutico , Doenças Neurodegenerativas/metabolismo , Peptídeos beta-Amiloides/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Quelantes/uso terapêutico , Cognição
13.
Metabolites ; 12(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36355133

RESUMO

It has been reported from the previous literature that butin restores mitochondrial dysfunction by modulation of oxidative stress and glutamate-induced neurotoxicity in mouse hippocampus HT22 cells. Butin also possesses an anti-Huntington's effect in rats. Considering the current background, this study was designed to evaluate the neuroprotective effect of butin against memory loss caused by streptozotocin (STZ). STZ (40 mg/kg) was intraperitoneally injected into rats. Three days later, diabetic rats were identified and included in the study. A total of 30 rats (12 nondiabetic and 18 diabetics) were grouped as Group A (control-non-diabetic rats) and Group B (STZ diabetic control) were treated with 1 mL of sodium CMC (0.5% w/v). Group C (STZ+ butin 25) were treated with butin 25 mg/kg. Group D (STZ+ butin 50) and Group E (butin per se) were administered with butin 50 mg/kg. Each therapy was administered orally once each day for 15-day. The Morris water maze and the Y-maze behavioural tests were run throughout the experimental programme. Animals were put to death on day 15 and their brains were removed for biochemical assays (CAT, SOD, GSH, MDA, nitrite, acetylcholinesterase (AchE), IL-1, and mitochondrial enzyme complexes). Rats with neurobehavioral impairments brought on by STZ have less spontaneous movement, learning capacity, and memory. Additionally, STZ decreased endogenous antioxidants and increased pro-inflammatory cytokines, nitrite, MDA, and AchE. Neurobehavioral deficits and metabolic markers were dramatically improved by butin.

14.
Int J Mol Sci ; 23(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36232989

RESUMO

Brain metastasis is one of the major reasons of death in breast cancer (BC) patients, significantly affecting the quality of life, physical activity, and interdependence on several individuals. There is no clear evidence in scientific literature that depicts an exact mechanism relating to brain metastasis in BC patients. The tendency to develop breast cancer brain metastases (BCBMs) differs by the BC subtype, varying from almost half with triple-negative breast cancer (TNBC) (HER2- ER- PR-), one-third with HER2+ (human epidermal growth factor receptor 2-positive, and around one-tenth with luminal subclass (ER+ (estrogen positive) or PR+ (progesterone positive)) breast cancer. This review focuses on the molecular pathways as possible therapeutic targets of BCBMs and their potent drugs under different stages of clinical trial. In view of increased numbers of clinical trials and systemic studies, the scientific community is hopeful of unraveling the underlying mechanisms of BCBMs that will help in designing an effective treatment regimen with multiple molecular targets.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias da Mama/metabolismo , Estrogênios , Feminino , Humanos , Progesterona , Qualidade de Vida , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
15.
Front Psychol ; 13: 983930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304858

RESUMO

The aim of this study is to elaborate the different factors which attract users to use social media sites. These main factors are subjective norms, image, efficiency and satisfaction along with the mediating role of perceived usefulness. Survey method was used to collect data from B2B fashion brands in Pakistan. Convenient sampling technique was used to collect data from targeted respondents. Collected data was analyzed using Smart-PLS 3.3 version. Results express that subjective norms, image, efficiency and satisfaction have positive and significant impact on perceived usefulness and intention to use social media sites in B2B context within Pakistani fashion brands. Results further reveal that perceived usefulness partially mediates the relationship between subjective norms, image, efficiency, satisfaction and intention to use social media sites. This study will enhance the available literature in the area of technology acceptance model (TAM) and will provide useful insights to B2B managers to use efficiently use social media sites for the promotion of their brands. This study is limited to fashion brands, future researchers can expand this model to other area of business.

16.
Clin Transl Med ; 12(9): e1045, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36149760

RESUMO

BACKGROUND: N-4 cytidine acetylation (ac4C) is an epitranscriptomics modification catalyzed by N-acetyltransferase 10 (NAT10); important for cellular mRNA stability, rRNA biogenesis, cell proliferation and epithelial to mesenchymal transition (EMT). However, whether other crucial pathways are regulated by NAT10-dependent ac4C modification in cancer cells remains unclear. Therefore, in this study, we explored the impact of NAT10 depletion in cancer cells using unbiased RNA-seq. METHODS: High-throughput sequencing of knockdown NAT10 in cancer cells was conducted to identify enriched pathways. Acetylated RNA immunoprecipitation-seq (acRIP-seq) and RIP-PCR were used to map and determine ac4C levels of RNA. Exogenous palmitate uptake assay was conducted to assess NAT10 knockdown cancer cells using Oil Red O staining and lipid content analysis. Gas-chromatography-tandem mass spectroscopy (GC/MS) was used to perform untargeted lipidomics. RESULTS: High-throughput sequencing of NAT10 knockdown in cancer cells revealed fatty acid (FA) metabolism as the top enriched pathway through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis in differentially downregulated genes. FA metabolic genes such as ELOLV6, ACSL1, ACSL3, ACSL4, ACADSB and ACAT1 were shown to be stabilised via NAT10-dependent ac4C RNA acetylation. Additionally, NAT10 depletion was shown to significantly reduce the levels of overall lipid content, triglycerides and total cholesterol. Further, NAT10 depletion in palmitate-loaded cancer cells showed decrease in ac4C levels across the RNA transcripts of FA metabolic genes. In untargeted lipidomics, 496 out of 2 279 lipids were statistically significant in NAT10 depleted cancer cells, of which pathways associated with FA metabolism are the most enriched. CONCLUSIONS: Conclusively, our results provide novel insights into the impact of NAT10-mediated ac4C modification as a crucial regulatory factor during FA metabolism and showed the benefit of targeting NAT10 for cancer treatment.


Assuntos
Citidina , Neoplasias , Acetiltransferases , Colesterol , Citidina/análise , Citidina/genética , Citidina/metabolismo , Transição Epitelial-Mesenquimal , Ácidos Graxos/genética , Neoplasias/genética , Palmitatos , RNA/química , Transferases , Triglicerídeos
17.
Nanotechnology ; 33(48)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-35998539

RESUMO

In this work, an electrochemical immunosensor based on black phosphorus nanosheets (BPNS)/poly(allylamine hydrochloride) (PAH) nanocomposite modified glassy carbon electrode was developed for the detection of ovarian cancer biomarker HE4. PAH has been applied to retain BPNS in its original honeycomb structure and to anchor biomolecules electrostatically on the transducer surface. The as synthesized nanocomposite was characterized by zeta potential analysis, scanning electron microscopy, x-ray photoelectron spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy. Subsequently, the performance of the electrochemical immunosensor was evaluated through cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy. Under the optimal condition, the developed electrochemical immunosensor permitted to detect HE4 with a linear range of 0.1-300 ng ml-1and a detection limit of 0.01 ng ml-1. The developed sensor exhibited good selectivity and specificity to HE4 with negligible interference effect from common biomolecules like bovine serum albumin, lysozyme, protamine, glucose, fructose, hemoglobin and fetal bovine serum. Further, practical application of developed electrochemical immunosensor was demonstrated in spiked human serum which showed satisfactory recovery percentages.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Imunoensaio/métodos , Limite de Detecção , Fósforo , Poliaminas
18.
Gels ; 8(7)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35877535

RESUMO

The second most common cause of mortality among women is breast cancer. A variety of natural compounds have been demonstrated to be beneficial in the management of various malignancies. Resveratrol is a promising anticancer polyphenolic compound found in grapes, berries, etc. Nevertheless, its low solubility, and hence its low bioavailability, restrict its therapeutic potential. Therefore, in our study, we developed a thermosensitive hydrogel formulation loaded with resveratrol nanoemulsion to enhance its bioavailability. Initially, resveratrol nanoemulsions were formulated and optimized utilizing a central composite-face-centered design. The independent variables for optimization were surfactant level, homogenization speed, and time, while the size and zeta potential were the dependent variables. The optimized nanoemulsion formulation was converted into a sensitive hydrogel using poloxamer 407. Rheological studies proved the formation of gel consistency at physiological temperature. Drug loading efficiency and in vitro drug release from gels were also analyzed. The drug release mechanisms from the gels were assessed using various mathematical models. The effect of the optimized thermosensitive resveratrol nanoemulsion hydrogel on the viability of human breast cancer cells was tested using MCF-7 cancer cell lines. The globule size of the selected formulation was 111.54 ± 4.16 nm, with a zeta potential of 40.96 ± 3.1 mV. Within 6 h, the in vitro release profile demonstrated a release rate of 80%. According to cell line studies, the produced hydrogel of resveratrol nanoemulsion was cytotoxic to breast cancer cells. Overall, the results proved the developed nanoemulsion-loaded thermosensitive hydrogel is a promising platform for the effective delivery of resveratrol for the management of breast cancer.

19.
Trends Analyt Chem ; 153: 116659, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35527799

RESUMO

Viral infections have been proven a severe threat to human beings, and the pandemic of Coronavirus Disease 2019 (COVID-19) has become a societal health concern, including mental distress and morbidity. Therefore, the early diagnosis and differentiation of viral infections are the prerequisite for curbing the local and global spread of viruses. To this end, carbon nanotubes (CNTs) based virus detection strategies are developed that provide feasible alternatives to conventional diagnostic techniques. Here in this review, an overview of the design and engineering of CNTs-based sensors for virus detection is summarized, followed by the nano-bio interactions used in developing biosensors. Then, we classify the viral sensors into covalently engineered CNTs, non-covalently engineered CNTs, and size-tunable CNTs arrays for viral detection, based on the type of CNTs-based nano-bio interfaces. Finally, the current challenges and prospects of CNTs-based sensors for virus detection are discussed.

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