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1.
J Med Chem ; 67(16): 14313-14328, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39106150

RESUMO

Pancreatic cancer, one of the deadliest cancers with the lowest 5-year survival rate, often develops resistance to gemcitabine-based chemotherapies. The hypovascular nature of pancreatic tumors forces cancer cells to adapt to nutrient-depleted tumor microenvironments. Conventional anticancer agents targeting rapidly dividing cancer cells under nutrient-rich conditions are largely ineffective against adapted pancreatic cancer cells. Thus, targeting cancer cells under nutrient starvation, termed the "antiausterity strategy", may be effective for pancreatic cancer. This study examined nicolaioidesin C (Nic-C) derivatives as antiausterity agents. Among the 32 derivatives, Nic-15 (4n) exhibited superior cytotoxicity against MIA PaCa-2 and PANC-1 pancreatic cancer cells, inhibited MIA PaCa-2 cell migration and colony formation, and modulated the PI3K/Akt/mTOR pathway, while reducing the ER stress markers induced by gemcitabine. Nic-15 was found to inhibit tumor growth and enhance the efficacy of gemcitabine in an in vivo xenograft model. Nic-15 in combination with gemcitabine may be an effective strategy for the treatment of pancreatic cancer.


Assuntos
Desoxicitidina , Gencitabina , Neoplasias Pancreáticas , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Camundongos Nus , Movimento Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais
2.
Int J Emerg Med ; 17(1): 90, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014326

RESUMO

BACKGROUND: Dengue is the most common arboviral illness reported globally, endemic to most tropical and sub-tropical regions of the world. Dengue Shock Syndrome is a rare complication of severe Dengue infection resulting in haemorrhagic complications and refractory hypotension. We report on a case of severe dengue diagnosed in a patient with major trauma and illustrate some of the potential challenges and considerations in the clinical management of such cases. CASE PRESENTATION: A 49-year-old female presented following a road trauma incident with multiple abdominal injuries requiring urgent laparotomy. Her recovery in Intensive Care Unit was complicated by the development of Dengue Shock Syndrome characterised by a falling haemoglobin and platelet count, multiorgan dysfunction and prolonged hospital stay. CONCLUSIONS: Dengue Shock Syndrome may complicate fluid management and bleeding control in major trauma cases. Awareness of Dengue, particularly in endemic areas and returned travellers may help facilitate early diagnosis and management of complications.

3.
Cureus ; 16(5): e60746, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38903303

RESUMO

Telepharmacy is receiving significant attention as an innovative approach. The objective of this study is to assess the needs and evaluate the impact of telepharmacy applications in drug consultations at Thu Duc City Hospital. We used a cross-sectional research design and conducted a survey with the participation of leaders of the Faculty of Pharmacy, clinical pharmacists, dispensing pharmacists, and patients or their caregivers who receive medication at the Pharmacy of Thu Duc Hospital. We deployed a telepharmacy application for consulting on drug use and surveyed the satisfaction of patients/family members with the telepharmacy model. 60.3% of survey subjects expressed a desire to receive drug use consultations through telepharmacy if the hospital were to offer this service. One hundred percent of the pharmacists at the pharmacy and the hospital's leadership believe that telepharmacy can address patient consultation needs and improve the current physical facilities in the dispensing area. Over 90% of telepharmacy users reported being satisfied or very satisfied with the service. Telepharmacy has garnered the attention of patients, their caregivers, and the medical staff at the Outpatient Pharmacy of Thu Duc Hospital. The majority of users are satisfied with the drug use consultation service provided by telepharmacy. By expanding the good results of Thu Duc Hospital to other hospitals, more patients across Vietnam can benefit from this innovative approach.

4.
J Phys Chem B ; 128(19): 4846-4852, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38700512

RESUMO

Epoxy resins are essential for various applications, and their properties depend on the curing reactions during which epoxy and amine compounds form the network structure. We here focus on how the presence or absence of two methyl groups in common epoxy bases, diglycidyl ether of bisphenol A and F (4,4'-DGEBA and 4,4'-DGEBF), affects the curing kinetics. The chemical reactions of both 4,4'-DGEBA and 4,4'-DGEBF, when cured with the same amine, were monitored by Fourier-transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC). Despite no difference in the reactivity of epoxy groups between 4,4'-DGEBA and 4,4'-DGEBF, the initial curing reaction was slower for the latter. This delay for the 4,4'-DGEBF system was attributed to intermolecular stacking, which hindered the approach of unreacted epoxy groups to amino groups and vice versa. This conclusion was drawn from the results obtained through ultraviolet (UV) spectroscopy, wide-angle X-ray scattering (WAXS), density functional theory (DFT) calculation, and all-atom molecular dynamics (MD) simulation.

5.
EBioMedicine ; 104: 105164, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38815363

RESUMO

BACKGROUND: Dengue epidemics impose considerable strain on healthcare resources. Real-time continuous and non-invasive monitoring of patients admitted to the hospital could lead to improved care and outcomes. We evaluated the performance of a commercially available wearable (SmartCare) utilising photoplethysmography (PPG) to stratify clinical risk for a cohort of hospitalised patients with dengue in Vietnam. METHODS: We performed a prospective observational study for adult and paediatric patients with a clinical diagnosis of dengue at the Hospital for Tropical Disease, Ho Chi Minh City, Vietnam. Patients underwent PPG monitoring early during admission alongside standard clinical care. PPG waveforms were analysed using machine learning models. Adult patients were classified between 3 severity classes: i) uncomplicated (ward-based), ii) moderate-severe (emergency department-based), and iii) severe (ICU-based). Data from paediatric patients were split into 2 classes: i) severe (during ICU stay) and ii) follow-up (14-21 days after the illness onset). Model performances were evaluated using standard classification metrics and 5-fold stratified cross-validation. FINDINGS: We included PPG and clinical data from 132 adults and 15 paediatric patients with a median age of 28 (IQR, 21-35) and 12 (IQR, 9-13) years respectively. 1781 h of PPG data were available for analysis. The best performing convolutional neural network models (CNN) achieved a precision of 0.785 and recall of 0.771 in classifying adult patients according to severity class and a precision of 0.891 and recall of 0.891 in classifying between disease and post-disease state in paediatric patients. INTERPRETATION: We demonstrate that the use of a low-cost wearable provided clinically actionable data to differentiate between patients with dengue of varying severity. Continuous monitoring and connectivity to early warning systems could significantly benefit clinical care in dengue, particularly within an endemic setting. Work is currently underway to implement these models for dynamic risk predictions and assist in individualised patient care. FUNDING: EPSRC Centre for Doctoral Training in High-Performance Embedded and Distributed Systems (HiPEDS) (Grant: EP/L016796/1) and the Wellcome Trust (Grants: 215010/Z/18/Z and 215688/Z/19/Z).


Assuntos
Dengue , Aprendizado de Máquina , Fotopletismografia , Índice de Gravidade de Doença , Dispositivos Eletrônicos Vestíveis , Humanos , Feminino , Masculino , Estudos Prospectivos , Adulto , Fotopletismografia/métodos , Fotopletismografia/instrumentação , Criança , Adolescente , Dengue/diagnóstico , Adulto Jovem , Vietnã
6.
Environ Int ; 186: 108620, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579451

RESUMO

Per- and polyfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, pose significant challenges to ecosystems and human health. While cell cultures have emerged as new approach methodologies (NAMs) in ecotoxicity research, metabolomics is an emerging technique used to characterize the small-molecule metabolites present in cells and to understand their role in various biological processes. Integration of metabolomics with cell cultures, known as cell culture metabolomics, provides a novel and robust tool to unravel the complex molecular responses induced by PFAS exposure. In vitro testing also reduces reliance on animal testing, aligning with ethical and regulatory imperatives. The current review summarizes key findings from recent studies utilizing cell culture metabolomics to investigate PFAS toxicity, highlighting alterations in metabolic pathways, biomarker identification, and the potential linkages between metabolic perturbations. Additionally, the paper discusses different types of cell cultures and metabolomics methods used for studies of environmental contaminants and particularly PFAS. Future perspectives on the combination of metabolomics with other advanced technologies, such as single-cell metabolomics (SCM), imaging mass spectrometry (IMS), extracellular flux analysis (EFA), and multi-omics are also explored, which offers a holistic understanding of environmental contaminants. The synthesis of current knowledge and identification of research gaps provide a foundation for future investigations that aim to elucidate the complexities of PFAS-induced cellular responses and contribute to the development of effective strategies for mitigating their adverse effects on human health.


Assuntos
Poluentes Ambientais , Fluorocarbonos , Metabolômica , Humanos , Fluorocarbonos/toxicidade , Fluorocarbonos/metabolismo , Poluentes Ambientais/toxicidade , Técnicas de Cultura de Células/métodos , Animais
7.
Pediatr Int ; 66(1): e15770, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38641933

RESUMO

BACKGROUND: WAS gene mutational analysis is crucial to establish a definite diagnosis of Wiskott-Aldrich syndrome (WAS). Data on the genetic background of WAS in Vietnamese patients have not been reported. METHODS: We recruited 97 male, unrelated patients with WAS and analyzed WAS gene mutation using Sanger sequencing technology. RESULTS: We identified 36 distinct hemizygous pathogenic mutations, with 17 novel variants, from 38 patients in the entire cohort (39.2%). The mutational spectrum included 14 missense, 12 indel, five nonsense, four splicing, and one non-stop mutations. Most mutations appear only once, with the exception of c.37C>T (p.R13X) and c.374G>A (p.G125E) each of which occurs twice in unrelated patients. CONCLUSION: Our data enrich the mutational spectrum of the WAS gene and are crucial for understanding the genetic background of WAS and for supporting genetic counseling.


Assuntos
Síndrome de Wiskott-Aldrich , Humanos , Masculino , Análise Mutacional de DNA , Mutação , Vietnã , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Proteína da Síndrome de Wiskott-Aldrich/genética
8.
RSC Adv ; 14(17): 12081-12095, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38628478

RESUMO

Twelve compounds were isolated from Mussaenda saigonensis aerial parts through phytochemical analysis and the genus Mussaenda is the first place where the compounds 4-6 and 11-12 have been found. Based on the ability to inhibit NO production in RAW264.7 cells, compound 2 has demonstrated the strongest anti-inflammatory activity in vitro with an IC50 of 7.6 µM, as opposed to L-NMMA's IC50 of 41.3 µM. Compound 12 was found to be the most effective inhibitor of alpha-glucosidase enzyme in vitro, with an IC50 value of 42.4 µM (compared to 168 µM for acarbose). Compounds 1-12 were evaluated in vitro for antimicrobial activity using the paper dish method. Compound 11 demonstrated strong antifungal activity against M. gypseum with a MIC value of 50 µM. In silico docking for antimicrobial activity, pose 90 or compound 11 docked well to the 2VF5 enzyme, PDB, which explains why compound 11 had the highest activity in vitro. Entry 2/pose 280 demonstrated excellent anti-inflammatory activity in silico. The stability of the complex between pose 280 and the 4WCU enzyme for anti-inflammatory activity has been assessed using molecular dynamics over a simulation course ranging from 0 to 100 ns. It has been found to be stable from 60 and 100 ns. The Tyr 159 (95%, H-bond via water bridge), Asp 318 (200%, multiple contacts), Met 273 (75%, hydrophobic interaction via water bridge), and Gln 369 (75%, H-bond via water bridge) interacted well within the time range of 0 to 100 ns. It has more hydrophilic or polar pharmacokinetics.

9.
Fitoterapia ; 175: 105950, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599338

RESUMO

The inhibitory effect against 5-α reductase of the ethyl acetate (EA) extract from Physalis angulata was evaluated in vitro using mouse prostate homogenates, and the suppression of benign prostatic hyperplasia (BPH) was assessed in a mouse model of testosterone-induced BPH. The EA extract exhibited a potentially inhibitory effect on 5-α reductase with an IC50 of 197 µg/ml. In BPH mice, the EA extract at a dose of 12 mg/kg was comparable to finasteride 5 mg/kg in suppressing BPH in terms of reducing absolute enlarged prostate weight (p < 0.05 vs. BPH group) and mitigating the hypertrophy of glandular elements and prostate connective tissue. Identification of chemical ingredients in the EA extract by UPLC-QTOF-MS revealed 37 substances belonging chiefly to flavonoids and physalins. Further quantification of the EA extract by HPLC-PDA methods revealed that chlorogenic acid, and rutin were the main components. Molecular docking studies of chlorogenic acid and rutin on 5-α reductase showed their high affinity to the enzyme with binding energies of -9.3 and - 9.2 kcal/mol, respectively compared with finasteride (- 10.3 kcal/mol). Additionally, chlorogenic acid inhibited 5-α reductase with an IC50 of 12.07 µM while rutin did not. The presence of chlorogenic acid in the EA extract may explain the inhibitory effects of the EA extract on 5-α reductase, and thus the suppression of BPH.


Assuntos
Inibidores de 5-alfa Redutase , Simulação de Acoplamento Molecular , Physalis , Extratos Vegetais , Hiperplasia Prostática , Animais , Hiperplasia Prostática/tratamento farmacológico , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos , Physalis/química , Inibidores de 5-alfa Redutase/farmacologia , Inibidores de 5-alfa Redutase/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Estrutura Molecular , Ácido Clorogênico/farmacologia , Ácido Clorogênico/isolamento & purificação , Próstata/efeitos dos fármacos , Modelos Animais de Doenças
10.
JMIR Hum Factors ; 11: e44619, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38180799

RESUMO

BACKGROUND: Wearable devices have been used extensively both inside and outside of the hospital setting. During the COVID-19 pandemic, in some contexts, there was an increased need to remotely monitor pulse and saturated oxygen for patients due to the lack of staff and bedside monitors. OBJECTIVE: A prototype of a remote monitoring system using wearable pulse oximeter devices was implemented at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from August to December 2021. The aim of this work was to support the ongoing implementation of the remote monitoring system. METHODS: We used an action learning approach with rapid pragmatic methods, including informal discussions and observations as well as a feedback survey form designed based on the technology acceptance model to assess the use and acceptability of the system. Based on these results, we facilitated a meeting using user-centered design principles to explore user needs and ideas about its development in more detail. RESULTS: In total, 21 users filled in the feedback form. The mean technology acceptance model scores ranged from 3.5 (for perceived ease of use) to 4.4 (for attitude) with behavioral intention (3.8) and perceived usefulness (4.2) scoring in between. Those working as nurses scored higher on perceived usefulness, attitude, and behavioral intention than did physicians. Based on informal discussions, we realized there was a mismatch between how we (ie, the research team) and the ward teams perceived the use and wider purpose of the technology. CONCLUSIONS: Designing and implementing the devices to be more nurse-centric from their introduction could have helped to increase their efficiency and use during the complex pandemic period.


Assuntos
COVID-19 , Humanos , Vietnã , Pandemias , Pacientes , Hospitais
11.
Am J Trop Med Hyg ; 110(1): 165-169, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-37983924

RESUMO

Tetanus is a disease associated with significant morbidity and mortality. Heart rate variability (HRV) is an objective clinical marker with potential value in tetanus. This study aimed to investigate the use of wearable devices to collect HRV data and the relationship between HRV and tetanus severity. Data were collected from 110 patients admitted to the intensive care unit in a tertiary hospital in Vietnam. HRV indices were calculated from 5-minute segments of 24-hour electrocardiogram recordings collected using wearable devices. HRV was found to be inversely related to disease severity. The standard deviation of NN intervals and interquartile range of RR intervals (IRRR) were significantly associated with the presence of muscle spasms; low frequency (LF) and high frequency (HF) indices were significantly associated with severe respiratory compromise; and the standard deviation of differences between adjacent NN intervals, root mean square of successive differences between normal heartbeats, LF to HF ratio, total frequency power, and IRRR, were significantly associated with autonomic nervous system dysfunction. The findings support the potential value of HRV as a marker for tetanus severity, identifying specific indices associated with clinical severity thresholds. Data were recorded using wearable devices, demonstrating this approach in resource-limited settings where most tetanus occurs.


Assuntos
Tétano , Dispositivos Eletrônicos Vestíveis , Humanos , Frequência Cardíaca/fisiologia , Tétano/diagnóstico , Eletrocardiografia Ambulatorial , Gravidade do Paciente
12.
Heliyon ; 9(10): e20727, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37867806

RESUMO

This study aimed to investigate the occurrence, antibiotic resistance, and biofilm formation of Escherichia coli in the Vietnamese Pangasius fish processing facility. Among 144 samples including Pangasius fish, wash water, food contact surfaces, and personnel gloves, 18 E. coli isolates was detected and characterized. The E. coli was detected most frequently in wash water samples (22%, 8/36), followed by Pangasius fish (18%, 8/45). According to the antibiotic susceptibility test by the disc diffusion method, isolates showed the highest resistance against sulfamethoxazole/trimethoprim (45%), followed by tetracycline (39%), whereas all the E. coli isolates were susceptible to meropenem and fosfomycin. Notably, 39% of the isolates (7/18) were found to be multidrug resistant while no E. coli isolates were confirmed as extended-spectrum ß-lactamase producers by the double-disk synergy test. The potency to form biofilm on the polystyrene surface of E. coli isolates indicated that 44% of the isolates (8/18) were classified as weak, 39% (7/18) as moderate, and 17% (3/18) as strong biofilm formers. Interestingly, multidrug resistant E. coli isolates were observed in moderate and strong biofilm producers. Additionally, either slightly acidic hypochlorous water with 40 mg/L of available chlorine or sodium hypochlorite with 100 mg/L of available chlorine exhibited a significant reduction in biofilm mass and biofilm cells of E. coli isolates. This study may provide helpful information about the actual state of E. coli isolates for effective control in the fish processing plant.

13.
Clin Med Insights Oncol ; 17: 11795549231203503, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905233

RESUMO

Background: The B-type rafkinase (BRAF) V600E gene mutation plays an important role in the pathogenesis, diagnosis, and prognosis of thyroid carcinoma. This study was conducted to investigate the rate of the BRAF V600E mutation, the relationships between the BRAF V600E gene mutation and some immunohistochemical markers, and recurrence rate in patients with differentiated thyroid cancer. Method: The study was conducted by a descriptive and longitudinal follow-up method on 102 thyroid carcinoma patients at 103 Military Hospital, Hanoi, Vietnam. All patients were identified with the BRAF V600E gene mutation by real-time polymerase chain reaction. Results: The rate of BRAF V600E gene mutation in patients with thyroid cancer was 60.8%. Patients with BRAF V600E gene mutation had a significantly higher rate of positive cyclooxygenase 2 (COX-2) and Ki67 markers than those without the mutation (COX-2: odds ratio [OR] = 2.93; 95% confidence interval [CI] = 1.27-6.74, P = .011; Ki67: OR = 3.41; 95% CI = 1.31-8.88, P = .01). A statistically significant relationship was identified between the rate of BRAF V600E mutation and the rate of positive Hector Battifora mesothelial 1 (HBME-1) (B = -1.040; P = .037) and COX-2 (B = -1.123; P = .023) markers. The recurrence rate in patients with BRAF V600E gene mutation was significantly higher than that in those without the mutation (P = .007). The mean of the recurrence time of patients with BRAF V600E mutation was significantly lower than that in those without the mutation (P = .011). Conclusions: A high prevalence of BRAF V600E gene mutation was found in thyroid carcinoma patients. The rates of positive HBME-1, COX-2, and Ki67 markers were significantly correlated to BRAF V600E gene mutation. Patients with BRAF V600E gene mutation showed a significantly higher relapse rate and earlier relapse time than those without the mutation.

14.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37765061

RESUMO

Little is known about the chemical and biological profiles of Dicranopteris linearis and Psychotria adenophylla. No previous studies have investigated alpha-glucosidase inhibition using extracts from D. linearis and P. adenophylla. In this paper, bioactive-guided isolation procedures were applied to the plants D. linearis and P. adenophylla based on alpha-glucosidase inhibition. From the most active fractions, 20 compounds (DL1-DL13 and PA1-PA7) were isolated. The chemical structures were elucidated using spectroscopic data and compared with those available in the literature. These compounds were evaluated for alpha-glucosidase inhibition, while a molecular docking study was performed to elucidate the mechanisms involved. Consequently, D. linearis and P. adenophylla might serve as a good potential for developing new antidiabetic preparations.

15.
Cureus ; 15(5): e38691, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37292572

RESUMO

PURPOSE: The purpose of this study was to quantitatively assess changes in the subfoveal choroidal thickness (SFCT) and superficial retinal vessel density (SRVD) in acute and chronic central serous chorioretinopathy (CSCR) patients, and estimate the correlation of SFCT and SRVD with best-corrected visual acuity (BCVA), respectively, using spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). METHODS: This was a cross-sectional, case-control study. The study included CSCR patients treated at the Ho Chi Minh City Eye Hospital from May 2022 to October 2022. RESULTS: A total of 91 subjects (182 eyes) were included in this study, with 74 eyes in the unilateral acute CSCR group and 17 eyes in the unilateral chronic CSCR group; 91 eyes in the control group were patients' unaffected other eyes. The mean age was 40.78 ± 1.26 years (ranging from 31 to 45 years). The proportions of male and female patients were 78.0% and 22.0%, respectively. The major symptom was reduced vision, and the mean BCVA was 0.36 ± 0.05 logMAR. The mean SFCT of CSCR eyes was 357.2 ± 11.8 µm, which was 290.4 ± 8.5 µm in the control group (p < 0.05). The mean SRVD of chronic CSCR (24.2 ± 4.94%) and acute CSCR (28 ± 2.33%) eyes was lower compared with the control group (21.7 ± 1.87%). SFCT had a correlation with BCVA (r = -0.490, p < 0.05) in chronic CSCR; the center region of SRVD was likewise correlated with BCVA (r = -0.384, p < 0.05) and the parafoveal region of SRVD was also correlated with BCVA (r = -0.271, p < 0.05). CONCLUSION: Both altered SFCT and SRVD were identified in CSCR patients by SD-OCT and 6 x 6 mm OCT angiography scans, and both were found to be correlated with BCVA. SD-OCT along with OCTA could be a good technique for quantitatively evaluating different CSCR courses.

16.
J Med Chem ; 66(12): 8054-8065, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37257133

RESUMO

Pancreatic tumors grow in an "austerity" tumor microenvironment characterized by nutrient deprivation and hypoxia. This leads to the activation of adaptive pathways in pancreatic cancer cells, promoting tolerance to nutrition starvation and aggressive malignancy. Conventional anticancer drugs are often ineffective against tumors that grow in such austerity condition. Plumbagin, a plant-derived naphthoquinone, has shown potent preferential cytotoxicity against pancreatic cancer cells under nutrient-deprived conditions. Therefore, we synthesized a series of plumbagin derivatives and found that 2-(cyclohexylmethyl)-plumbagin (3f) was the most promising compound with a PC50 value of 0.11 µM. Mechanistically, 3f was found to inhibit the PI3K/Akt/mTOR signaling pathways, leading to cancer cell death under nutrient-deprived conditions. In vivo studies using pancreatic cancer xenograft mouse models confirmed the efficacy of 3f, demonstrating significant inhibition of tumor growth in a dose-dependent manner. Compound 3f represents a highly promising lead for anticancer drug development based on an antiausterity strategy.


Assuntos
Antineoplásicos Fitogênicos , Naftoquinonas , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Fosfatidilinositol 3-Quinases , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Microambiente Tumoral , Neoplasias Pancreáticas
17.
Int J Gen Med ; 16: 1695-1703, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187590

RESUMO

Purpose: This study was conducted to evaluate the results of conservative management of blunt splenic trauma according to the American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) in 2018 by embolization. Methods: This observational study included 50 patients (42 men and 8 women) with splenic injury who underwent multidetector computed tomography (MDCT) and embolization. Results: According to the 2018 AAST-OIS, 27 cases had higher grades than they did according to the 1994 AAST-OIS. The grades of two cases of grade II increased to grade IV; those of 15 cases of grade III increased to grade IV; and four cases of grade IV increased to grade V. As a result, all patients underwent successful splenic embolization and were stable at discharge. No patients required re-embolization or conversion to splenectomy. The mean hospital stay was 11.8±7 days (range, 6-44 days), with no difference in length of hospital stay among grades of splenic injury (p >0.05). Conclusion: Compared with the AAST-OIS 1994, the AAST-OIS 2018 classification is useful in making embolization decisions, regardless of the degree of blunt splenic injury with vascular lacerations visible on MDCT.

18.
Radiol Case Rep ; 18(6): 2073-2077, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37089968

RESUMO

Intestinal hypoganglionosis in adults is quite uncommon, and hypoganglionosis of the ileum has not been documented to date. The majority of studies on this disorder are single case reports and brief case series. We describe a 30-year-old male patient with bowel obstruction and intestinal hypoganglionosis of the ileum and we review the literature on the disorder.

19.
J Arrhythm ; 39(2): 185-191, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37021031

RESUMO

Background: Radiofrequency catheter ablation is the preferred treatment choice for ventricular arrhythmias (VAs) originating from right ventricular outflow tract (RVOT) in symptomatic patients and is usually performed under fluoroscopy guidance. Zero-fluoroscopy (ZF) ablations using 3D mapping system applied for treatment of various types of arrhythmias are trending and practiced in many centers around the world, but rarely done in Vietnam. The objective of this study was to evaluate the efficacy and safety of zero-fluoroscopy ablation of RVOT VAs, compared with fluoroscopy-guided ablation without a 3D electroanatomic mapping (EAM) system. Methods and Results: We conducted a nonrandomized, prospective single-center study including 114 patients with RVOT VAs that had electrocardiographic features of typical left bundle branch block, inferior axis QRS morphology, and a precordial transition ≥ V3, from May 2020 to July 2022. The patients were assigned (without randomization) to two different approaches of either zero-fluoroscopy ablation under the guidance of the Ensite system (ZF group) or fluoroscopy-guided ablation without a 3D EAM (fluoroscopy group) in a 1:1 ratio. After a follow-up time of 5.0 ± 4.9 months and 6.9 ± 9.3 months in the ZF and fluoroscopy groups, respectively, the results showed a higher success rate in the fluoroscopy group than in the complete ZF group (87.3% vs 86.8%), although the difference was not statistically significant. No major complication was noted in both the groups. Conclusion: ZF ablation for RVOT VAs can be done safely and effectively using the 3D electroanatomic mapping system. The results of ZF approach are comparable to that of the fluoroscopy-guided approach without a 3D EAM system.

20.
Eur Rev Med Pharmacol Sci ; 27(5): 1767-1773, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36930492

RESUMO

BACKGROUND: Primary hypokalemic periodic paralysis (HypoPP), a rare skeletal muscle channelopathy resulting in episodic muscle weakness or paralysis under hypokalemic conditions, is caused by autosomal-dominant genetic mutations. HypoPP limits physical activity, and cardiac arrhythmias during paralytic attacks have been reported. We describe a rare familial HypoPP case complicated by sinus arrest and syncope requiring urgent temporary pacemaker implantation. CASE REPORT: A 27-year-old Vietnamese man with a family history of periodic paralysis presented with his third attack of muscle weakness triggered by intense football training the previous day. Clinical and laboratory features justified a HypoPP diagnosis. During intravenous potassium replacement, the patient experienced syncopal sinus arrest requiring urgent temporary pacemaker implantation. The patient gradually improved, responding favorably to oral potassium supplements. Genetic testing revealed an Arg1132Gln mutation in the sodium ion channel (SCN4A, chromosome 17: 63947091). At discharge, the patient received expert consultation regarding nonpharmacological preventive strategies, including avoidance of vigorous exercise and carbohydrate-rich diet. CONCLUSIONS: No evidence has established a relationship between hypokalemia and sinus arrest, and no specific treatment exists for familial HypoPP due to SCN4A mutation. Clinician awareness of this rare condition will promote appropriate diagnostic approaches and management strategies for acute paralytic attacks. Treatment should be tailored according to HypoPP phenotypes and genotypes.


Assuntos
Hipopotassemia , Paralisia Periódica Hipopotassêmica , Humanos , Paralisia Periódica Hipopotassêmica/diagnóstico , Paralisia Periódica Hipopotassêmica/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Mutação , Potássio , Debilidade Muscular
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