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1.
Arch Craniofac Surg ; 25(2): 77-84, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38742334

RESUMO

BACKGROUND: The facial artery is an important blood vessel responsible for supplying the anterior face. Understanding the branching patterns of the facial artery plays a crucial role in various medical specialties such as plastic surgery, dermatology, and oncology. This knowledge contributes to improving the success rate of facial reconstruction and aesthetic procedures. However, debate continues regarding the classification of facial artery branching patterns in the existing literature. METHODS: We conducted a comprehensive anatomical study, in which we dissected 102 facial arteries from 52 embalmed and formaldehyde-fixed Vietnamese cadavers at the Anatomy Department, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. RESULTS: Our investigation revealed eight distinct termination points and identified 35 combinations of branching patterns, including seven arterial branching patterns. These termination points included the inferior labial artery, superior labial artery, inferior alar artery, lateral nasal artery, angular artery typical, angular artery running along the lower border of the orbicularis oculi muscle, forehead branch, duplex, and short course (hypoplastic). Notably, the branching patterns of the facial artery displayed marked asymmetry between the left and right sides within the same cadaver. CONCLUSION: The considerable variation observed in the branching pattern and termination points of the facial artery makes it challenging to establish a definitive classification system for this vessel. Therefore, it is imperative to develop an anatomical map summarizing the major measurements and geometric features of the facial artery. Surgeons and medical professionals involved in facial surgery and procedures must consider the detailed anatomy and relative positioning of the facial artery to minimize the risk of unexpected complications.

2.
Sci Rep ; 14(1): 7461, 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553482

RESUMO

The common autosomal recessive (AR) mutation carrier is still unknown in Vietnam. This study aims to identify the most common AR gene mutation carriers in women of reproductive age to build a Vietnamese-specific carrier screening panel for AR and X-linked disorders in the preconception and prenatal healthcare program. A cross-sectional study was conducted at University Medical Center-Branch 2 in Ho Chi Minh City from December 1st, 2020, to June 30th, 2023. 338 women have consented to take a 5 mL blood test to identify 540 recessive genes. The carrier screening panel was designed based on the American College of Medical Genetics and Genomics (ACMG)-recommended genes and suggestions from 104 clinical experts in Vietnam. Obstetricians and genetic experts counseled all positive testing results to discuss the possibility of recessive diseases in their offspring. The most common recessive disorders were defined at a prevalence of 1 in 60 or greater, and those were added to a Vietnamese-specific carrier screening panel. 338 non-pregnant and pregnant women underwent the expanded carrier screening (ECS). The carrier frequency was 63.6%, in which 215 women carried at least one AR gene mutation. GJB2 hearing impairment was identified as the most common chronic condition (1 in 5). The second most common AR disorder was beta-thalassemia (1 in 16), followed by cystic fibrosis (1 in 23), G6PD deficiency (1 in 28), Wilson's disease (1 in 31), Usher's syndrome (1 in 31), and glycogen storage disease (1 in 56). Seven common recessive genes were added in ethnic-based carrier screening. Women in the South of Vietnam have been carried for many recessive conditions at high frequency, such as hearing impairment, genetic anemia, and cystic fibrosis. It is necessary to implement a preconception and prenatal screening program by using seven widely popular AR genes in a Vietnamese-specific carrier screening panel to reduce the burden related to AR and X-linked disorders.


Assuntos
Fibrose Cística , Perda Auditiva , Humanos , Feminino , Gravidez , Testes Genéticos/métodos , Triagem de Portadores Genéticos/métodos , Vietnã/epidemiologia , Fibrose Cística/genética , Prevalência , Estudos Transversais , Mutação , Perda Auditiva/genética
3.
RSC Adv ; 14(8): 5264-5275, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38343997

RESUMO

Epoxy resin has been extensively used in many industrial and daily applications due to its unique properties. However, the high flammability of epoxy has limited its further development. DOPO derivatives, which are organophosphorus compounds, are highly effective components of flame retardant epoxy composites due to their good compatibility with the resin and their lower toxicity compared to halogenated compounds. This study synthesized sixteen new DOPO derivatives, characterizing their chemical structures with NMR spectroscopy. The combination of synthesized DOPO derivatives and APP-PEI (ammonium polyphosphate-polyethyleneimine) has shown a synergistic effect on enhancing the flame retardancy of epoxy resin with the UL-94 V-0 rating and the LOI value of 28.6%. Moreover, the epoxy composites displayed relatively high mechanical performance with the impact strength of 26-28 kJ m-2.

4.
BMC Health Serv Res ; 24(1): 151, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291402

RESUMO

BACKGROUND: Inpatient rehabilitation services are challenged by increasing demand. Where appropriate, a shift in service models towards more community-oriented approaches may improve efficiency. We aimed to estimate the hypothetical cost of delivering a consensus-based rehabilitation in the home (RITH) model as hospital substitution for patients requiring reconditioning following medical illness, surgery or treatment for cancer, compared to the cost of inpatient rehabilitation. METHODS: Data were drawn from the following sources: the results of a Delphi survey with health professionals working in the field of rehabilitation in Australia; publicly available data and reports; and the expert opinion of the project team. Delphi survey data were analysed descriptively. The costing model was developed using assumptions based on the sources described above and was restricted to the Australian National Subacute and Non-Acute Patient Classification (AN-SNAP) classes 4AR1 to 4AR4, which comprise around 73% of all reconditioning episodes in Australia. RITH cost modelling estimates were compared to the known cost of inpatient rehabilitation. Where weighted averages are provided, these were determined based on the modelled number of inpatient reconditioning episodes per annum that might be substitutable by RITH. RESULTS: The cost modelling estimated the weighted average cost of a RITH reconditioning episode (which mirrors an inpatient reconditioning episode in intensity and duration) for AN-SNAP classes 4AR1 to 4AR4, to be A$11,371, which is 28.1% less than the equivalent weighted average public inpatient cost (of A$15,820). This represents hypothetical savings of A$4,449 per RITH reconditioning substituted episode of care. CONCLUSIONS: The hypothetical cost of a model of RITH which would provide patients with as comprehensive a rehabilitation service as received in inpatient rehabilitation, has been determined. Findings suggest potential cost savings to the public hospital sector. Future research should focus on trials which compare actual clinical and cost outcomes of RITH for patients in the reconditioning impairment category, to inpatient rehabilitation.


Assuntos
Pacientes Internados , Humanos , Austrália , Previsões
5.
RSC Adv ; 14(3): 1838-1853, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38192320

RESUMO

Two different synthetic approaches to novel heterocyclic hybrid compounds of 4-azapodophyllotoxin were investigated. The obtained products were characterized by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. MTT protocol was then performed to examine the cytotoxic activity of these products against KB, HepG2, A549, MCF7, and Hek-293 cell lines. The cytotoxic assessment indicated that all products displayed moderate to high cytotoxicity against all tested cancer cell lines. The most active compound 13k containing the 2-methoxypyridin-4-yl group exhibited selective cytotoxicity against KB, A549, and HepG2 cell lines with the IC50 values ranging from 0.23 to 0.27 µM, which were between 5- to 10-fold more potent than the positive control ellipticine. Compounds 13a (HetAr = thiophen-3-yl) and 13d (HetAr = 5-bromofuran-2-yl) displayed high cytotoxic selectivity for A549 and HepG2 cancer cell lines when compared to the other cancer cell lines and low toxicity to the normal Hek-293 cell line. Molecular docking study was conducted to evaluate the interaction of new synthesized compounds with the colchicine-binding-site of tubulin. Besides that, physicochemical and pharmacokinetic properties of the most active compounds 13h,k were predicted.

6.
AIDS Care ; 36(5): 631-640, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37339000

RESUMO

The Human Immunodeficiency Virus (HIV) epidemic remains a major public health issue worldwide. In Vietnam, the HIV epidemic is essentially driven by people who inject drugs (PWID). This study aims to compare mortality and loss to follow-up (LTFU) between PWID and other patients. From June 2017 to April 2018, HIV-infected adults were enrolled in a prospective cohort from time of ART initiation in six provinces of North Vietnam. The end date was July 2020. Mortality and LTFU were described using competing-risk survival models. Factors associated with mortality and with LTFU were identified using Cox models with a competing-risk approach. Of the 578 participants, 261 (45.2%) were PWID and almost exclusively male. 49 patients died, corresponding to a mortality rate (95% confidence interval (CI)) of 3.7 (2.8-4.9) per 100 person-months, and 79 were lost to follow-up, corresponding to a rate (95% CI) of 6.0 (4.8-7.4) per 100 person-months. PWID were at higher risk of death but not of LTFU. Overall, LTFU was high in both groups. Latecomers to clinical visits were more at risk of both death and LTFU. Therefore, this should be a warning to clinical teams and preventive actions taken in these patients.Trial registration: ClinicalTrials.gov identifier: NCT03249493..


Assuntos
Infecções por HIV , Abuso de Substâncias por Via Intravenosa , Adulto , Humanos , Masculino , HIV , Infecções por HIV/epidemiologia , Incidência , Perda de Seguimento , Estudos Prospectivos , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Vietnã/epidemiologia , Feminino
7.
World Neurosurg ; 178: e559-e565, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37532017

RESUMO

BACKGROUND: Epilepsy surgery is traditionally difficult to pursue in resource-limited countries but is nevertheless essential in the treatment of medication-refractory, surgically amenable epilepsy. METHODS: With the help of international collaboration, a successful epilepsy program was started in Vietnam. This article comprises a retrospective chart review, combined with prospective longitudinal follow-up of 35 cases of unilateral drug-resistant epilepsy in the temporal lobe who underwent temporal lobectomy, in Viet Duc University Hospital from May 2018 to September 2022. RESULTS: The female/male ratio was 0.6:1, and focal seizures with impaired awareness accounted for 97.14% of patients. Of patients with focal awareness seizures, 51.41% were localized and detected by electroencephalography. Postoperatively, 80% of patients were seizure free (Engel I) at 1 year, and the remaining 20% had worthwhile seizure improvement (Engel II). Postoperative temporal lobe pathology was categorized as follows: mesial temporal sclerosis (48.57%), focal cortical dysplasia (25.71%), and low-grade neoplasms (25.71%). Of patients, 17.14% had postoperative complications (5 infections and 1 transient extremity paresis), and there were no deaths. CONCLUSIONS: Even in low-resource environments, effective and safe surgical care can be provided for drug-resistant epilepsy caused by temporal lobe disease. This study serves as a model of international collaboration and support for future hospitals in low-resource environments to replicate.

8.
Ann Med Surg (Lond) ; 85(8): 3852-3857, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37554863

RESUMO

Epilepsy is a prevalent neurological condition that affects individuals of all ages and genders worldwide. Surgical intervention for drug-resistant epilepsy has been found to improve quality of life, with patient independence being of utmost importance. Methods: The study was a retrospective and prospective cross-sectional study of 35 cases of drug-resistant temporal lobe epilepsy. All patients were operated on by the primary author between May 2018 and September 2022. The study evaluated various factors including clinical characteristics, electroencephalogram, magnetic resonance imaging, surgical outcomes, and histopathology. Results: The success rate of the surgeries (74.3%) is similar to those reported in high-income countries. 51.4% underwent selective amygdalohippocampectomy for cases that localized to the mesial temporal lobe. Lateral/neocortical lesions underwent lesionectomy (48.6%). Our study found a complication rate of 17.1%: meningitis (8.5%), trainset focal paralysis (2.9%), and soft tissue infection (5.7%). There were no mortalities. Conclusions: The article showcases an international collaborative effort that demonstrates the possibility of providing highly effective and safe surgical care for temporal lobe epilepsy even in low-resource environments. The authors hope that this model can be replicated in other areas with similar resource limitations.

9.
Transl Lung Cancer Res ; 12(4): 742-753, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37197627

RESUMO

Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the second/subsequent line after resistance to first- and second-generation (1/2G) EGFR-TKI. Methods: We reviewed electronic records of 202 patients who received osimertinib from July 2015 to January 2019 in the second/subsequent line after progression on prior EGFR-TKI. Of these, complete data from 193 patients were available. Clinical data including patient characteristics, primary EGFR mutation, T790M mutation status, presence of baseline brain metastases (BM), first-line EGFR-TKI use, and survival outcomes were extracted, and results retrospectively analyzed. Results: Of 193 evaluable patients, 151 (78.2%) were T790M+ (T790M positive) with 96 (49.2%) tissue confirmed; 52% of patients received osimertinib in the second line setting. After median follow up of 37 months, median progression-free survival (PFS) of the entire cohort was 10.3 [95% confidence interval (CI): 8.64-11.50] months and median overall survival (OS) was 20 (95% CI: 15.61-23.13) months. Overall response rate (ORR) to osimertinib was 43% (95% CI: 35.9-50.3%); 48.3% in T790M+ vs. 20% in T790M- (T790M negative) patients. OS in T790M+ patients was 22.6 vs. 7.9 months in T790M- patients (HR 0.43, P=0.001), and PFS was 11.2 vs. 3.1 months respectively (HR 0.52, P=0.01). Tumour T790M+ was significantly associated with longer PFS (P=0.007) and OS (P=0.01) compared to tumour T790M- patients, however this association was not seen with plasma T790M+. Of the 22 patients with paired tumor/plasma T790M testing, response rate (RR) to osimertinib was 30% for those plasma T790M+/tumour T790M-, compared to 63% and 67% for those who were plasma T790M+/tumour T790M+ and plasma T790M-/tumour T790M+, respectively. By multivariable analysis (MVA), Eastern Cooperative Oncology Group (ECOG) performance status ≥2 was associated with shorter OS (HR 2.53, P<0.001) and PFS (HR 2.10, P<0.001), whereas presence of T790M+ was associated with longer OS (HR 0.50, P=0.008) and PFS (HR 0.57, P=0.027). Conclusions: This cohort demonstrated the efficacy of osimertinib in second line/beyond for EGFR+ (EGFR mutation-positive) non-small cell lung cancer (NSCLC). Tissue T790M result appeared more predictive of osimertinib efficacy compared to plasma, highlighting potential T790M heterogeneity and the advantage with paired tumor-plasma T790M testing at TKI resistance. T790M- disease at resistance remains an unmet treatment need.

10.
BMC Health Serv Res ; 23(1): 113, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737750

RESUMO

BACKGROUND: Reconditioning for patients who have experienced functional decline following medical illness, surgery or treatment for cancer accounts for approximately 26% of all reported inpatient rehabilitation episodes in Australia. Rehabilitation in the home (RITH) has the potential to offer a cost-effective, high-quality alternative for appropriate patients, helping to reduce pressure on the acute care sector. This study sought to gain consensus on a model for RITH as hospital substitution for patients requiring reconditioning. METHODS: A multidisciplinary group of health professionals working in the rehabilitation field was identified from across Australia and invited to participate in a three-round online Delphi survey. Survey items followed the patient journey, and also included items on practitioner roles, clinical governance, and budgetary considerations. Survey items mostly comprised statements seeking agreement on 5-point Likert scales (strongly agree to strongly disagree). Free text boxes allowed participants to qualify item answers or make comments. Analysis of quantitative data used descriptive statistics; qualitative data informed question content in subsequent survey rounds or were used in understanding item responses. RESULTS: One-hundred and ninety-eight health professionals received an invitation to participate. Of these, 131/198 (66%) completed round 1, 101/131 (77%) completed round 2, and 78/101 (77%) completed round 3. Consensus (defined as ≥ 70% agreement or disagreement) was achieved on over 130 statements. These related to the RITH patient journey (including patient assessment and development of the care plan, case management and program provision, and patient and program outcomes); clinical governance and budgetary considerations; and included items for initial patient screening, patient eligibility and case manager roles. A consensus-based model for RITH was developed, comprising five key steps and the actions within each. CONCLUSIONS: Strong support amongst survey participants was found for RITH as hospital substitution to be widely available for appropriate patients needing reconditioning. Supportive legislative and payment systems, mechanisms that allow for the integration of primary care, and appropriate clinical governance frameworks for RITH are required, if broad implementation is to be achieved. Studies comparing clinical outcomes and cost-benefit of RITH to inpatient rehabilitation for patients requiring reconditioning are also needed.


Assuntos
Pessoal de Saúde , Hospitais , Reabilitação , Humanos , Austrália , Consenso , Técnica Delphi , Inquéritos e Questionários
11.
Front Plant Sci ; 14: 1125158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818833

RESUMO

Spirooxindole alkaloids feature a unique scaffold of an oxindole ring sharing an atom with a heterocyclic moiety. These compounds display an extensive range of biological activities such as anticancer, antibiotics, and anti-hypertension. Despite their structural and functional significance, the establishment and rationale of the spirooxindole scaffold biosynthesis are yet to be elucidated. Herein, we report the discovery and characterization of a cytochrome P450 enzyme from kratom (Mitragyna speciosa) responsible for the formation of the spirooxindole alkaloids 3-epi-corynoxeine (3R, 7R) and isocorynoxeine (3S, 7S) from the corynanthe-type (3R)-secoyohimbane precursors. Expression of the newly discovered enzyme in Saccharomyces cerevisiae yeast allows for the efficient in vivo and in vitro production of spirooxindoles. This discovery highlights the versatility of plant cytochrome P450 enzymes in building unusual alkaloid scaffolds and opens a gateway to access the prestigious spirooxindole pharmacophore and its derivatives.

12.
J Alzheimers Dis ; 91(3): 933-960, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36530085

RESUMO

BACKGROUND: Historically, research questions have been posed by the pharmaceutical industry or researchers, with little involvement of consumers and healthcare professionals. OBJECTIVE: To determine what questions about medicine use are important to people living with dementia and their care team and whether they have been previously answered by research. METHODS: The James Lind Alliance Priority Setting Partnership process was followed. A national Australian qualitative survey on medicine use in people living with dementia was conducted with consumers (people living with dementia and their carers including family, and friends) and healthcare professionals. Survey findings were supplemented with key informant interviews and relevant published documents (identified by the research team). Conventional content analysis was used to generate summary questions. Finally, evidence checking was conducted to determine if the summary questions were 'unanswered'. RESULTS: A total of 545 questions were submitted by 228 survey participants (151 consumers and 77 healthcare professionals). Eight interviews were conducted with key informants and four relevant published documents were identified and reviewed. Overall, analysis resulted in 68 research questions, grouped into 13 themes. Themes with the greatest number of questions were related to co-morbidities, adverse drug reactions, treatment of dementia, and polypharmacy. Evidence checking resulted in 67 unanswered questions. CONCLUSION: A wide variety of unanswered research questions were identified. Addressing unanswered research questions identified by consumers and healthcare professionals through this process will ensure that areas of priority are targeted in future research to achieve optimal health outcomes through quality use of medicines.


Assuntos
Pesquisa Biomédica , Demência , Humanos , Prioridades em Saúde , Austrália , Pessoal de Saúde , Cuidadores , Demência/tratamento farmacológico
13.
Blood Adv ; 7(15): 3846-3861, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-36322827

RESUMO

Regulation of gene expression at the RNA level is an important regulatory mechanism in cancer. However, posttranscriptional molecular pathways underlying tumorigenesis remain largely unexplored. In this study, we uncovered a functional axis consisting of microRNA (miR)-148a-3p, RNA helicase DDX6, and its downstream target thioredoxin-interacting protein (TXNIP) in acute myeloid leukemia (AML). Using a DROSHA-knockout cell system to evaluate miR-mediated gene expression control, we comprehensively profiled putative transcripts regulated by miR-148a-3p and identified DDX6 as a direct target of miR-148a-3p in AML cells. DDX6 depletion induced cell cycle arrest, apoptosis, and differentiation, although delaying leukemia development in vivo. Genome-wide assessment of DDX6-binding transcripts and gene expression profiling of DDX6-depleted cells revealed TXNIP, a tumor suppressor, as the functional downstream target of DDX6. Overall, our study identified DDX6 as a posttranscriptional regulator that is required for AML survival. We proposed the regulatory link between miR-148a-3p and DDX6 as a potential therapeutic target in leukemia.


Assuntos
Leucemia Mieloide Aguda , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Genes Supressores de Tumor , Leucemia Mieloide Aguda/genética , Diferenciação Celular/fisiologia , Proteínas Proto-Oncogênicas/genética , RNA Helicases DEAD-box/genética
14.
Arch Craniofac Surg ; 24(6): 266-272, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38176760

RESUMO

BACKGROUND: In recent years, there has been an increase in reports of perioral vascular complications resulting from filler injections, such as necrosis of the lip or alar rim, occlusion, and in severe cases, blindness. Conversely, the use of perioral arterial flaps is becoming more prevalent in the treatment of cleft lips, cancer, and trauma. A thorough understanding of perioral arteries is essential to minimize complications and maximize the success of these flaps. However, the course of the facial artery (FA) in the perioral region remains incompletely understood. The aim of this study was to describe the variations of the FA in the perioral region. METHODS: We dissected 52 embalmed and formaldehyde-fixed Vietnamese cadavers. We then studied the size and distribution of perioral arteries in 102 specimens. RESULTS: The superior labial artery (SLA) was the most common branch, occurring in 87.25% of cadavers, followed by the inferior labial artery (ILA) at 78.43%. The SLA primarily originated above the mouth corner (cheilion), accounting for 91.01% of cases, and predominantly exhibited a tortuous course within the submucosa (78.65%). The ILA's branching pattern varied, but it was primarily located below the cheilion (91.25%). The ILA also followed a twisted path, generally within the submucosa. The ILA exhibited two patterns: the typical pattern, distributed at the vermilion border of the lower lip (8.82%), and the horizontal labiomental artery pattern, which ran horizontally in the middle of the lower lip area (69.61%). At their origin, the SLA and ILA had average external diameters of 1.29 mm and 1.28 mm, respectively. CONCLUSION: Numerous anatomical variations in the FA in the perioral region were found. A detailed anatomic description, suggested landmarks, and angiography before the procedure will be useful to help doctors avoid complications.

15.
J Biol Chem ; 298(12): 102677, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36336075

RESUMO

Cytokines of the interleukin 12 (IL-12) family are assembled combinatorially from shared α and ß subunits. A common theme is that human IL-12 family α subunits remain incompletely structured in isolation until they pair with a designate ß subunit. Accordingly, chaperones need to support and control specific assembly processes. It remains incompletely understood, which chaperones are involved in IL-12 family biogenesis. Here, we site-specifically introduce photocrosslinking amino acids into the IL-12 and IL-23 α subunits (IL-12α and IL-23α) for stabilization of transient chaperone-client complexes for mass spectrometry. Our analysis reveals that a large set of endoplasmic reticulum chaperones interacts with IL-12α and IL-23α. Among these chaperones, we focus on protein disulfide isomerase (PDI) family members and reveal IL-12 family subunits to be clients of several incompletely characterized PDIs. We find that different PDIs show selectivity for different cysteines in IL-12α and IL-23α. Despite this, PDI binding generally stabilizes unassembled IL-12α and IL-23α against degradation. In contrast, α:ß assembly appears robust, and only multiple simultaneous PDI depletions reduce IL-12 secretion. Our comprehensive analysis of the IL-12/IL-23 chaperone machinery reveals a hitherto uncharacterized role for several PDIs in this process. This extends our understanding of how cells accomplish the task of specific protein assembly reactions for signaling processes. Furthermore, our findings show that cytokine secretion can be modulated by targeting specific endoplasmic reticulum chaperones.


Assuntos
Citocinas , Isomerases de Dissulfetos de Proteínas , Humanos , Interleucina-12 , Interleucina-23 , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Dobramento de Proteína , Retículo Endoplasmático
16.
Chem Biodivers ; 19(8): e202200359, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35920799

RESUMO

A convenient three-component synthetic approach was developed en route to new and significative N-arylated-dihydrobenzo[g]quinoline-5,10-diones using 2-hydroxy-1,4-naphthoquinone, a variety of aromatic aldehydes, and 4-(arylamino)furan-2(5H)-ones. A sequence of steps including Knoevenagel condensation, Michael addition, [1,3]-hydrogen shift, intramolecular cyclization and dehydration led to the formation of products. All the products were structurally characterized by spectroscopic techniques and assessed in terms of their cytotoxicity profile against four cancer cell lines (KB, HepG2, A549, and MCF7), and human embryonic kidney (Hek-293) cell lines.


Assuntos
Antineoplásicos , Quinolinas , Antineoplásicos/farmacologia , Ciclização , Células HEK293 , Humanos , Micro-Ondas , Quinolinas/química
17.
Methods Mol Biol ; 2505: 141-164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35732943

RESUMO

Monoterpene indole alkaloid (MIA) constitutes a structurally diverse plant natural product group with remarkable pharmacological activities. Many MIAs have been routinely used as potent drugs for several diseases, including leukemia (vinblastine), lung cancer (camptothecin), and malaria (quinine). Nevertheless, MIAs are biosynthesized at extremely low abundance in plants and, in many cases, require additional chemical functionalizations before their therapeutic uses. As oxygenations and oxidative rearrangements are critical throughout MIAs' structural scaffolding and modifications, the discovery and engineering of oxidative enzymes play essential roles in understanding and boosting the supplies of MIAs. Recent advances in omics technologies and synthetic biology have provided unprecedented amount of biochemical data and tools, paving a wide pathway for discovering, characterizing, and engineering enzymes involved in MIA biosynthesis. Here, we discuss the latest progress in understanding the roles of oxidative enzymes in MIA metabolism and describe a bioinformatic and biochemical pipeline to identify, characterize, and make use of these plant biocatalysts.


Assuntos
Catharanthus , Catharanthus/metabolismo , Alcaloides Indólicos/química , Alcaloides Indólicos/metabolismo , Monoterpenos/metabolismo , Estresse Oxidativo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Vimblastina
18.
Healthcare (Basel) ; 10(6)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35742177

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) infection causes gastritis, duodenal and gastric ulcers, and gastric cancer. H. pylori eradication efficacy is low worldwide, and antibiotic resistance is the leading cause of therapy failure; therefore, this study was performed to determine the characteristics of antibiotic resistance of H. pylori in children with gastritis, duodenal and gastric ulcer. METHODS: A cross-sectional study was conducted on 237 pediatric patients diagnosed with gastroduodenal inflammation and ulcer at two hospitals in Vietnam from March 2019 to April 2022. Pediatric patients with positive H. pylori tests continued to do E-tests to measure the minimum inhibitory concentration of the antibiotic so that we could prescribe effective antibiotics based on the sensitivity. RESULTS: In 237 pediatric patients (51.1% males) with a median age of 10.3 years (range 5-16 years), endoscopic images showed that inflammatory lesions and peptic ulcers accounted for 69.2% and 30.8%, respectively. Resistance rates of H. pylori were 80.6% to clarithromycin (CLR), 71.7% to amoxicillin (AMX), 49.4% to metronidazole (MTZ), 45.1% to levofloxacin (LEV), and 11.4% to tetracycline (TET); dual resistance to AMX + CLR was 64.2%, AMX + LEV 35%, AMX + MTZ 33.3%, CLR + MTZ 32.5%, and TET + MTZ 7.2%. The frequency of clarithromycin resistance was significantly increased, particularly in pediatric patients who had received prior H. pylori treatment. The percentage of amoxicillin resistance increased with age; amoxicillin resistance of H. pylori was more prevalent among pediatric patients with peptic ulcers than those with gastroduodenal inflammation and higher in males than females. CONCLUSIONS: The proportions of resistance to CLR, AMX, MTZ, and LEV were extremely high, in contrast to TET, which was lower in pediatric patients. Our study suggests that the standard triple therapy with CLR should be limited as the empiric therapy for pediatric patients, and we should consider using eradication regimens with TET for children over 8 years of age if the medical facility is not qualified to perform antibiotic susceptibility tests of H. pylori in the Mekong Delta.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36817494

RESUMO

Objective: Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infections and cervical cancer due to their high number of sexual partners. The objectives of this study were to determine the prevalence of HPV and identify risk factors for high-risk HPV infection among FSWs in Hanoi and Ho Chi Minh City (HCMC), Viet Nam. Methods: A cross-sectional study was conducted in Hanoi and HCMC between December 2017 and May 2018. We surveyed and screened 699 FSWs aged 318 years for HPV infection and abnormal cytology. A multivariable modified Cox regression model was used to determine risk factors for high-risk HPV infection. Results: The overall prevalence of any HPV, high-risk HPV and HPV-16/18 infection in the 699 FSWs was 26.3%, 17.6% and 4.0%, respectively, and were similar in both cities. Multiple infections were identified in 127 participants (69.0%). HPV-52 was the most prevalent (7%), followed by HPV-58 (6%). Abnormal cytology was detected in 91 participants (13.0%). FSWs who are divorced (adjusted prevalence ratio [aPR]: 1.96, 95% confidence interval [CI]: 1.01-3.81), widowed (aPR: 3.26, 95% CI: 1.49-7.12) or living alone (aPR: 1.85, 95% CI: 1.01-3.39) were associated with a higher prevalence of high-risk HPV infection. Discussion: Almost one in five FSWs in Viet Nam are infected with high-risk HPV. This highlights the importance of prevention strategies such as HPV vaccination and screening in this high-risk group.


Assuntos
Infecções por Papillomavirus , Profissionais do Sexo , Humanos , Feminino , Cidades , Infecções por Papillomavirus/epidemiologia , Estudos Transversais , Papillomavirus Humano , Prevalência , Vietnã/epidemiologia , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Fatores de Risco
20.
J Therm Spray Technol ; 31(1-2): 269-281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38624803

RESUMO

A typical structure of thermal spray coatings consisted of molten particles, semi-molten particles, oxides, pores, and cracks. These factors caused the porosity of sprayed coatings, leading to a significant influence on the coating properties, especially their wear-corrosion resistance. In this study, a post-spray sealing treatment of Cr3C2-NiCr/Al2O3-TiO2 plasma-sprayed coatings was carried out, and then, their corrosion properties were evaluated, before and after the treatment. For the sealing process, aluminum phosphate (APP) containing Al2O3 nanoparticles (~10 nm) was used. The permeability of APP into the sprayed coating was analyzed by SEM-EDS. The treatment efficiency for porosity and corrosion resistance of sprayed coatings was evaluated by electrochemical measurements, such as the potentiodynamic polarization and electrochemical impedance spectroscopy. The wear-corrosion resistance of the coating was examined in 3.5 wt.% NaCl circulation solution containing 0.25% SiO2 particles. The sealing efficiency was evaluated by the percentage of the treated open pores in the coating. The obtained results showed that APP penetrated deeply through the coating and the incorporation of Al2O3 nanoparticles into APP sealant improved the sealing efficiency by 20% of open pores in comparison with the sealant without nano-Al2O3. The effect of the post-treatment on corrosion protection of the sprayed coating has been discussed.

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