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BACKGROUND: During the COVID-19 pandemic, health care professionals experienced high levels of depression. However, extant research has not highlighted effective internet-based psychological interventions to improve the mental health in this population during the pandemic. It remains unclear whether self-guided, internet-based cognitive behavioral therapy (iCBT) programs are effective in improving the mental health of health care workers during the COVID-19 pandemic. OBJECTIVE: The aim of this study was to evaluate the effectiveness of a smartphone-based iCBT stress management program for reducing the depression experienced by nurses in Vietnam and Thailand. METHODS: From March to April 2022, a 2-arm, parallel-group randomized controlled trial was implemented. One arm offered a 7-week self-guided iCBT program, and the other offered treatment as usual as a control arm. Full-time nurses were recruited from 6 hospitals: 2 hospitals in Vietnam and 4 hospitals in Thailand. The primary outcome of this program was the severity of depression measured by the Depression Anxiety Stress Scale-21 items. Follow-up surveys were conducted to measure the change in depression severity at 3 months (July-August 2022) and at 6 months (October-November 2022) after baseline. Mixed modeling for repeated measures was used to test the effects of the intervention compared with the control for the follow-up. RESULTS: A total of 1203 nurses were included in this study: 602 in the intervention group and 601 in the control group. The follow-up rate at 3 and 6 months ranged from 85.7% (515/601) to 87.5% (527/602). The completion rate for the program was 68.1% (410/602). The group difference in depression was significant at the 3-month follow-up (coefficient=-0.92, 95% CI -1.66 to -0.18; P=.02) and nonsignificant at the 6-month follow-up (coefficient=-0.33, 95% CI -1.11 to 0.45; P=.41). The estimated effect sizes were -0.15 and -0.06 at the 3- and 6-month follow-ups, respectively. CONCLUSIONS: Our study shows that the smartphone-based iCBT program was effective in reducing depression at the 3-month follow-up among hospital nurses in Vietnam and Thailand during the COVID-19 pandemic. However, the effect size was small, and therefore, these results may not be clinically meaningful. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000044145; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050128. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.20944/preprints202303.0450.v1.
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COVID-19 , Terapia Cognitivo-Conductual , Depresión , Teléfono Inteligente , Humanos , Vietnam , Tailandia , Adulto , Femenino , Depresión/terapia , Masculino , Terapia Cognitivo-Conductual/métodos , Personal de Enfermería en Hospital/psicología , Pandemias , SARS-CoV-2 , Estrés Psicológico/terapia , Persona de Mediana EdadRESUMEN
This study aims to investigate the use of pond apple (Annona glabra) compounds as a novel strategy to prevent and treat acute hepatopancreatic necrosis disease (AHPND) as well as to better understand the mechanism of health improvement in shrimp. The A. glabra leaf extracts were extracted using various solvents and examined for in vitro and in vivo activity against Vibrio parahaemolyticus strains. In comparison with ethanol and water extracts, methanol extract showed the strongest bactericidal effect (MBC/MIC ratio of 2.50 ± 1.00), with minimal inhibitory concentration (MIC) of 0.023 ± 0.012 mg ml-1 and minimum bactericidal concentration (MBC) of 0.065 ± 0.062 mg ml-1. White leg shrimp (P. vannamei, body weight 10.37 ± 0.27 g) fed A. glabra methanol extracts-containing diets (AMEDs) at 1 %, 1.5 %, and 2.0 % demonstrated no deleterious effects on survival and were significantly increased in length and weight after 30 days of feeding. The level of total haemocyte, hyaline haemocyte on day 15 and granulocyte on day 30 remarkably increased (p < 0.05) in shrimps fed AMEDs groups compared to those in the control group. The finding demonstrates that granulocyte was induced time dependently. In particular, the survival rate of V. parahaemolyticus challenged shrimps under medication with AMEDs at 1.5 % and 2.0 % was significantly higher (p < 0.05) than that of the control group. The decrease in bacterial load of Vibrio spp. and V. parahaemolyticus was obviously recorded in hepatopancreas shrimp given AMEDs 1.5 % and 2.0 % and may be linked to herb characteristics such as antibacterial activity, enhancing innate immunity, and its potential to maintain the integrity of hepatopancreatic tissue. Our findings suggest that A. glabra extract might be used as a health enhancer in commercial farmed shrimp.
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Annona , Hepatopáncreas , Penaeidae , Extractos Vegetales , Vibrio parahaemolyticus , Animales , Penaeidae/microbiología , Penaeidae/efectos de los fármacos , Extractos Vegetales/farmacología , Vibrio parahaemolyticus/efectos de los fármacos , Annona/química , Hepatopáncreas/efectos de los fármacos , Hepatopáncreas/patología , Antibacterianos/farmacologíaRESUMEN
Ulcerative colitis (UC) is a complex chronic inflammatory disease closely associated with gut homeostasis dysfunction. The previous studies have shown that stachyose, a functional food additive, has the potential to enhance gut health and alleviate UC symptoms. However, the underlying mechanism of its effects remains unknown. In this study, our findings showed that dietary supplements of stachyose had a significant dose-dependent protective effect on colitis symptoms, regulation of gut microbiota, and restoration of the Treg/Th17 cell balance in dextran sulfate sodium (DSS) induced colitis mice. To further validate these findings, we conducted fecal microbiota transplantation (FMT) to treat DSS-induced colitis in mice. The results showed that microbiota from stachyose-treated mice exhibited a superior therapeutic effect against colitis and effectively regulated the Treg/Th17 cell balance in comparison to the control group. Moreover, both stachyose supplementation and FMT resulted in an increase in butyrate production and the activation of PPARγ. However, this effect was partially attenuated by PPARγ antagonist GW9662. These results suggested that stachyose alleviates UC symptoms by modulating gut microbiota and activating PPARγ. In conclusion, our work offers new insights into the benefical effects of stachyose on UC and its potential role in modulating gut microbiota.
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Butiratos , Colitis Ulcerosa , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , PPAR gamma , Transducción de Señal , Linfocitos T Reguladores , Células Th17 , Animales , PPAR gamma/metabolismo , PPAR gamma/genética , Ratones , Células Th17/inmunología , Linfocitos T Reguladores/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Masculino , Transducción de Señal/efectos de los fármacos , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/terapia , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/tratamiento farmacológico , Oligosacáridos/administración & dosificación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Sulfato de Dextran/efectos adversosRESUMEN
The working conditions for teachers in Vietnam were characterized by increased workload and pressure, burdening teachers' well-being. The study aims to investigate anxiety prevalence and identify some related factors among primary and secondary school teachers in Hanoi after the first COVID-19 outbreak in 2020. This paper analyzed data of 481 teachers working at ten primary and secondary schools in Hanoi city. Anxiety was measured using the anxiety component of the Depression, Anxiety, and Stress scale 42 items. Multivariable logistics regression was performed to examine anxiety-related factors using SPSS 20.0 at a significant level p less than 0.05. The prevalence of anxiety symptoms was 42.4% and similar between primary and secondary school teachers. More secondary teachers reported moderate to severe anxiety symptoms than primary teachers did (31.6% and 27.7%). Primary school teachers who felt discomfort with their supervisor's assessment, high responsibility for student safety, and ever thinking of leaving their current job were more likely to report anxiety symptoms (OR (95%CI) = 2.8 (1.2-6.5), 3.6 (1.0-12.8), and 2.6 (1.3-5.4), respectively). Meanwhile, the discomfort of caring for many students or problematic students, repetitive work, and disagreement with coworkers were risk factors of anxiety among secondary school teachers (OR (95%CI) = 2.6 (1.2-5.8), 3.2 (1.1-9.2), 3.4 (1.3-8.8), and 3.7 (1.1-12.6), respectively). In conclusion, the prevalence of teachers with anxiety symptoms is on the rise, caused by the characteristics of the job and professional relationships. Tailored support for teachers in different grades is necessary to improve and prevent teachers' anxiety.
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INTRODUCTION AND IMPORTANCE: Laparoscopic surgery is recommended to treat recurrent inguinal hernia (IH). Single-incision laparoscopic surgery transabdominal pre-peritoneal (SILS-TAPP) has been an option for IH repair but few studies on the application of this method for recurrent IH was conducted. We aimed to report our experience of SILS-TAPP for recurrent IH and the long-term outcomes of this technique. CASE PRESENTATION: Ten patients of recurrent IH, including three multiple recurrences, were successfully treated with SILS-TAPP. Previous surgeries were Bassini and Lichtenstein's procedures. No perioperative complications were observed; neither additional trocar nor conversion to open surgery was needed. Median operation time was 65 (range: 45-95) minutes. Post-operative pain lasted for two to three days. Neither long-term complications nor recurrence was seen until the median follow-up time of 37 (range: 16-53) months. CLINICAL DISCUSSION: Although the surgical procedure of hernia repair of SILS-TAPP was the same as conventional TAPP, the manipulation of the instrument was technically challenging. This surgical method should be done by an SILS expert with application of several surgical tips to overcome difficulties adhering to single-port surgery. Also, meticulous and patient dissection of the inguinal site is suggested. CONCLUSION: SILS-TAPP is safe and feasible to repair recurrent inguinal hernia. However, it should be done by experienced surgeons.
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Major advances in the treatment of multiple myeloma (MM) have been achieved by effective new agents such as proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies. Despite significant progress, MM remains still incurable and, recently, cellular immunotherapy has emerged as a promising treatment for relapsed/refractory MM. The emergence of chimeric antigen receptor (CAR) technology has transformed immunotherapy by enhancing the antitumor functions of T cells and natural killer (NK) cells, leading to effective control of hematologic malignancies. Recent advancements in gene delivery to NK cells have paved the way for the clinical application of CAR-NK cell therapy. CAR-NK cell therapy strategies have demonstrated safety, tolerability, and substantial efficacy in treating B cell malignancies in various clinical settings. However, their effectiveness in eliminating MM remains to be established. This review explores multiple approaches to enhance NK cell cytotoxicity, persistence, expansion, and manufacturing processes, and highlights the challenges and opportunities associated with CAR-NK cell therapy against MM. By shedding light on these aspects, this review aims to provide valuable insights into the potential of CAR-NK cell therapy as a promising approach for improving the treatment outcomes of MM patients.
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Reaction of nickel and zinc triflates with the tridentate leucoverdazyl 1-isopropyl-3,5-di (2'-pyridyl)-6-oxo-2H-tetrazine (dipyvdH) and triethylamine resulted in the neutral coordination compounds M(dipyvd)2 (M = Ni,Zn). In acetonitrile, both compounds undergo two one electron oxidation processes, Zn (dipyvd)2 at -0.28 V and -0.12 V and Ni(dipyvd)2 at -0.32 V and -0.15 V vs ferrocene/ferricenium. Oxidations are ligand based resulting in an intermediate mixed valence species and a cationic bis(verdazyl) compound respectively. Oxidation of the ligand changes a localized, antiaromatic, non-planar 8π electron anion to a planar, delocalized 7π electron radical. The change in ligand structure results in an increase in the octahedral ligand field splitting from 10,500 cm-1 to â¼13,000 cm-1, suggesting an increase in the pi acceptor character of the ligand. In the mixed valence species, spectroscopic data suggests minimal interaction between ligands mediated by the metal center; i.e., these are class I-II systems in the Robin-Day classification.
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OBJECTIVES: This article examines the validity and reliability of the Vietnamese version of the Copenhagen Burnout Inventory (CBI-V) among hospital nurses in Vietnam in 2022. METHODS: This article examined data from 587 nurses in two city hospitals in Vietnam in 2022. The reliability was determined via internal consistency (Cronbach's alpha coefficient) and test-retest reliability (Intraclass correlation coefficient). Factorial and construct validity of CBI-V were explored with confirmation factor analysis (CFA), exploratory factor analysis (EFA), and correlations with other mental health outcomes (measured by the depression, anxiety, and stress scale), job performance (Work Health Performance Questionnaires), work engagement (Utrecht work engagement), and quality of life (EQ-5D-5L). Statistical analyses were performed using SPSS 20.0 and AMOS 20.0. RESULTS: Cronbach's alpha coefficients of CBI-V's three subscales showed good internal consistency (from 0.87 to 0.91). CFA showed a good fit of the three-factor model with the current data. EFA results showed that all items were loaded in accordance with the CBI's original three constructs, excluding work burnout item 7, forming the fourth factor with a single item. All of CBI-V's three subscales correlated with other constructs in expected directions. CONCLUSION: The CBI-V showed good validity and reliability among hospital nurses. It can be a reliable tool to measure burnout among nurses in a low- and middle-income country in Vietnam during such a crisis as COVID-19. Future studies should examine the construct of the Copenhagen Burnout Inventory in different occupation groups.
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Agotamiento Profesional , Psicometría , Humanos , Agotamiento Profesional/psicología , Calidad de Vida , Reproducibilidad de los Resultados , Pueblos del Sudeste Asiático , Encuestas y Cuestionarios , VietnamRESUMEN
Introduction: Artificial Intelligence (AI) and machine learning (ML) are used extensively in HICs to detect and control antibiotic resistance (AMR) in laboratories and clinical institutions. ML is designed to predict outcome variables using an algorithm to enable "machines" to learn the "rules" from the data. ML is increasingly being applied in intensive care units to identify AMR and to assist empiric antibiotic therapy. This study aimed to evaluate the performance of ML models for predicting AMR bacteria and resistance to antibiotics in two Vietnamese hospitals. Patients and Methods: A cross-sectional study combined with retrospective was conducted from 1st January 2020 to 30th June 2022. Five models were developed to predict antibiotic resistance of bacterial infections of ICU patients. Two datasets were prepared to predict AMR bacteria and antibiotics with ML models. The performance of the prediction models was evaluated by various indicators (sensitivity, specificity, precision, accuracy, F1-score, PRC, AuROC, and NormMCC) to determine the optimal time point for data selection. Python version 3.8 was used for statistical analyses. Results: The accuracy, F1-score, AuROC, and normMMC of LightGBM, XGBoost, and Random Forest models were higher than those of other models in both datasets. In both datasets 1 and 2, accuracy, F1-score, AuROC and normMCC of the XGBoost model were the highest among five models (from 0.890 to 1.000). Only Random Forest models had specificity scores higher than 0.850. High scores of sensitivity, accuracy, precision, F1-score, and normMCC indicated that the models were making accurate predictions for datasets 1 and 2. Conclusion: XGBoost, LightGBM, and Random Forest were the best-performed machine learning models to predict antibiotic resistance of bacterial infections of ICUs patients using the patients' EMRs.
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A 2'-deoxycytidin-N4-yl radical (dC·), a strong oxidant that also abstracts hydrogen atoms from carbon-hydrogen bonds, is produced in a variety of DNA damaging processes. We describe here the independent generation of dC· from oxime esters under UV-irradiation or single electron transfer conditions. Support for this σ-type iminyl radical generation is provided by product studies carried out under aerobic and anaerobic conditions, as well as electron spin resonance (ESR) characterization of dC· in a homogeneous glassy solution at low temperature. Density functional theory (DFT) calculations also support fragmentation of the corresponding radical anions of oxime esters 2d and 2e to dC· and subsequent hydrogen atom abstraction from organic solvents. The corresponding 2'-deoxynucleotide triphosphate (dNTP) of isopropyl oxime ester 2c (5) is incorporated opposite 2'-deoxyadenosine and 2'-deoxyguanosine by a DNA polymerase with approximately equal efficiency. Photolysis experiments of DNA containing 2c support dC· generation and indicate that the radical produces tandem lesions when flanked on the 5'-side by 5'-d(GGT). These experiments suggest that oxime esters are reliable sources of nitrogen radicals in nucleic acids that will be useful mechanistic tools and possibly radiosensitizing agents when incorporated in DNA.
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Ésteres , Oximas , Radicales Libres/química , Oximas/química , Electrones , ADN/química , HidrógenoRESUMEN
OBJECTIVE: To evaluate the effectiveness of cycling in combination with electroacupuncture in treatment of post-stroke hemiplegia patients at National Hospital of Acupuncture, Vietnam. METHODS: The study was designed as a single-centre, outcome-assessor-blinded parallel randomised controlled trial with 120 post-stroke hemiplegia patients randomly assigned into two groups: electroacupuncture plus cycling (CT group) and electroacupuncture (AT group). Patients were assessed before and after the treatment (using muscle grading, modified Rankin, Barthel, Orgorozo scores and electromyography). Statistical Man-Whitney U test, and Fisher's exact tests were used to compare between CT and AT groups. RESULTS: The results reported statistically significant improvement in motor function in patients suffering from hemiplegia following ischemic stroke in both CT and AT groups. Patients in CT group experienced a greater improvement compared to those in AT group including better muscle contraction (increased frequency and amplitude of electromyography and increased muscle grading scale); increased recovery (Orgogozo scale), increased independency (Barthel scale) and decreased disability (Modified Rankin scale) (< 0.01). CONCLUSIONS: Combination with cycling training significantly improves the recovery of post-stroke patients treated with electroacupuncture.
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Terapia por Acupuntura , Electroacupuntura , Accidente Cerebrovascular , Humanos , Electroacupuntura/métodos , Hemiplejía/etiología , Hemiplejía/terapia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Terapia por Acupuntura/métodos , Terapia Combinada , Resultado del TratamientoRESUMEN
@#Objective: Human respiratory syncytial virus (RSV) is a primary cause of paediatric severe acute respiratory infection (SARI) worldwide, especially in developing countries. We investigated the genetic characteristics of RSV in northern Viet Nam to determine the prevalence and distribution of subtypes as well as the diversity and transmission patterns of genotypes. Methods: In two facilities, from January 2017 to December 2020, 1563 clinical specimens were collected from paediatric patients hospitalized with SARI and tested for RSV. Selected positive samples underwent sequencing analysis targeting the second hypervariable region of the G gene using next-generation sequencing. Results: The RSV positivity rate was 28.02% (438/1563 samples), and prevalence was highest in children aged <1 year (43.84%; 192/438). Subtype RSV-A accounted for 53.42% (234/438) of cases, RSV-B for 45.89% (201/438), and there was coinfection in 0.68% (3/438). Both subtypes cocirculated and peaked during August–September in each year of the study. Phylogenetic analysis showed that RSV-A samples belonged to the ON1 genotype, which has three subgenotypes: ON1.1, ON1.2 and ON1.3. However, we did not find the 72-nucleotide duplication in the second hypervariable region of the G gene, a characteristic of genotype ON1, in any RSV-A samples. RSV-B samples belonged to genotype BA9. Discussion: Our results provide additional molecular characterization of RSV infections in Viet Nam. Specially, our study is the first to report the absence of the 72-nucleotide duplication in the G gene of RSV-A genotype ON1 in Viet Nam, which may help in understanding the genetic evolution of RSV and be useful for vaccine development in the future.
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Background: Depression is a widespread and incapacitating mental health disorder that impacts millions of people worldwide, playing a substantial role in the overall global health challenges. Depression has a big impact on a person's quality of life, cognitive and social functioning, risk of suicide, risk of heart disease and other illnesses, as well as death from all causes. Objective: It may be challenging to choose the best tools to screen for severe depression in patients with recurrent depression disorder (PRD) considering the diversity of psychological scales in Vietnam. The aim of this study was to evaluate diagnostic value for detect severe depression of four psychological scales including Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory Scale (BECK), and Zung's Self-Rating Anxiety Scale (SAS) by genders and age groups among PRD in Vietnam. Methods: This study was conducted at National Institute of Mental Health, Bach Mai Hospital, Vietnam, from 2020 to 2021. There were 109 PRD evaluated with HAM-D, HAM-A, BECK, and SAS by qualified psychiatrists. By analysing Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC) curve, we determined sensitivity, specificity and cut points of four above scales. Results: Among four scales, the BECK scale had the best diagnostic effect with the most optimal sensitivity and specificity (61.64% and 75%, respectively). We proposed the new cut-off of HAM-D, HAM-A, BECK, and SAS for detecting severe depression among PRD were 20, 34, 30, and 45, respectively. By genders, the cut points for the HAM-D, HAM-A, BECK, and SAS in males were 20, 27, 34, and 44, respectively, while those figure in females were 14, 34, 30, and 46, respectively. By age groups, adults had cut values for four above scales of 20, 34, 27, and 45, respectively, whereas those for the elderly were 16, 17, 35, and 44, respectively. Conclusion: We highly recommended that BECK is the most optimal method to screen severe depression in PRD in Vietnam. It is essential to utilize varied cut values of HAM-D, HAM-A, BECK, and SAS for different genders and age groups.
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Cancer immunotherapy has fundamentally altered cancer treatment; however, its efficacy is limited to a subset of patients in most clinical settings. The immune system plays a key role in cancer progression from tumor initiation to the metastatic state. Throughout the treatment course, communications between the immune cells in the tumor microenvironment and the immune macroenvironment, as well as interactions between the immune system and cancer cells, are dynamic and constantly evolving. To improve the clinical benefit for patients who do not respond completely to immunotherapy, the molecular mechanisms of resistance to immunotherapy must be elucidated in order to develop effective strategies to overcome resistance. In an attempt to improve and update the current understanding of the molecular mechanisms that hinder immunotherapy, we discuss the molecular mechanisms of cancer resistance to immunotherapy and the available treatment strategies.
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Inmunoterapia , Neoplasias , Humanos , Sistema Inmunológico/patología , Neoplasias/patología , Microambiente TumoralRESUMEN
Chemotherapy has been widely used as a clinical treatment for cancer over the years. However, its effectiveness is limited because of resistance of cancer cells to programmed cell death (PCD) after treatment with anticancer drugs. To elucidate the resistance mechanism, we initially focused on cancer cell-specific mitophagy, an autophagic degradation of damaged mitochondria. This is because mitophagy has been reported to provide cancer cells with high resistance to anticancer drugs. Our data showed that TRIP-Br1 oncoprotein level was greatly increased in the mitochondria of breast cancer cells after treatment with various anticancer drugs including staurosporine (STS), the main focus of this study. STS treatment increased cellular ROS generation in cancer cells, which triggered mitochondrial translocation of TRIP-Br1 from the cytosol via dephosphorylation of TRIP-Br1 by protein phosphatase 2A (PP2A). Up-regulated mitochondrial TRIP-Br1 suppressed cellular ROS levels. In addition, TRIP-Br1 rapidly removed STS-mediated damaged mitochondria by activating mitophagy. It eventually suppressed STS-mediated PCD via degradation of VDACI, TOMM20, and TIMM23 mitochondrial membrane proteins. TRIP-Br1 enhanced mitophagy by increasing expression levels of two crucial lysosomal proteases, cathepsins B and D. In conclusion, TRIP-Br1 can suppress the sensitivity of breast cancer cells to anticancer drugs by activating autophagy/mitophagy, eventually promoting cancer cell survival.
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Antineoplásicos , Neoplasias de la Mama , Antineoplásicos/farmacología , Apoptosis , Autofagia , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Mitofagia , Proteínas Oncogénicas/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Much higher risk of cancer has been found in diabetes patients. Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) have been extensively studied in both breast cancer and diabetes therapies. Interestingly, a recent study proposed that IR/IGF1R ratio is an important factor for breast cancer prognosis. Women with higher IR/IGF1R ratio showed poor breast cancer prognosis as well as hyperinsulinemia. Here, we propose a novel mechanism that oncogenic protein TRIP-Br1 renders breast cancer cells and insulin deficient mice to have higher IR/IGF1R ratio by positively and negatively regulating IR and IGF1R expression at the protein level, respectively. TRIP-Br1 repressed IR degradation by suppressing its ubiquitination. Meanwhile, TRIP-Br1 directly interacts with both IGF1R and NEDD4-1 E3 ubiquitin ligase, in which TRIP-Br1/NEDD4-1 degrades IGF1R via ubiquitin/proteasome system. TRIP-Br1-mediated higher IR/IGF1R ratio enhanced the proliferation and survival of breast cancer cells. In conclusion, current study may provide an important information in the regulatory mechanism of how breast cancer cells have acquired higher IR/IGF1R ratio.
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Neoplasias de la Mama , Factor I del Crecimiento Similar a la Insulina , Animales , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ratones , Pronóstico , Receptor IGF Tipo 1 , Receptor de Insulina , UbiquitinaRESUMEN
Acquired chemoresistance of tumor cells is an unwanted consequence of cancer treatment. Overcoming chemoresistance is particularly important for efficiently improving cancer therapies. Here, using multiple lines of evidence, we report the suppressive role of SERTAD1 in apoptosis/anoikis. Among various breast cancer cell lines, higher SERTAD1 expression was found in MCF7 and MDA-MB-231 in suspension than in adherent cell culture. We revealed an unexpected phenomenon that different types of cell deaths were induced in response to different doses of doxorubicin (Dox) in breast cancer cells, presumably via lysosomal membrane permeabilization. A low dose of Dox highly activated autophagy, while a high dose of the chemotherapy induced apoptosis. Inhibition of SERTAD1 promoted the sensitivity of breast cancer cells to Dox and paclitaxel, leading to a significant reduction in tumor volumes of xenograft mice. Simultaneously targeting cancer cells with Dox and autophagy inhibition successfully induced higher apoptosis/anoikis. The novel role of SERTAD1 in maintaining cellular homeostasis has also been suggested in which lysosomal contents, including LAMP1, LAMP2, CTSB, and CTSD, were reduced in SERTAD1-deficient cells.
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Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.
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Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.
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Quitosano , Colitis Ulcerosa , Nanopartículas , Administración Oral , Alginatos , Colitis Ulcerosa/tratamiento farmacológico , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Preparaciones FarmacéuticasRESUMEN
Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis. Polymorphism in bovine leukocyte antigen (BoLA)-DRB3 allele can influence the host immune response to pathogens, including BLV. However, association between specific BoLA-DRB3 alleles and BLV proviral load (PVL), which is a useful index for estimating disease progression and transmission risk, in Vietnamese cattle are unknown. Here, association study of BoLA-DRB3 allele frequency between cattle with high or low PVL demonstrated BoLA-DRB3*12:01 associates with high PVL in Vietnamese Holstein Friesian (HF) crossbred cattle. This is the first study to demonstrate that BoLA-DRB3 polymorphism confers susceptibility to BLV high PVL in HF crossbred kept in Vietnam. Our results may be useful in disease control and eradiation for BLV through genetic selection.