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1.
Mol Ther ; 32(9): 2803-2806, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39163859

RESUMO

Genome editing technologies are rapidly evolving, from the early zinc-finger nucleases, transcription activator-like effector nucleases (TALENs), and CRISPR-Cas9 (Figure 1, initial genome editing technologies), which generate double-strand breaks (DSBs), to base editing, which makes precise nucleobase conversion without inducing DSBs, and prime editing, which can carry out all types of edits without DSBs or donor DNA templates. The emergence of these revolutionary technologies offers us unprecedented opportunities for biomedical research and therapy development.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Edição de Genes/métodos , Humanos , Epigenoma , Animais , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Quebras de DNA de Cadeia Dupla , Terapia Genética/métodos
2.
J Biol Chem ; 299(12): 105463, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37977221

RESUMO

Ferroptosis, characterized by iron-dependent cell death, has recently emerged as a critical defense mechanism against microbial infections. The present study aims to investigate the involvement of exosomes in the induction of ferroptosis and the inhibition of bacterial infection in crustaceans. Our findings provide compelling evidence for the pivotal role of exosomes in the immune response of crustaceans, wherein they facilitate intracellular iron accumulation and activate the ferroptotic pathways. Using RNA-seq and bioinformatic analysis, we demonstrate that cytochrome P450 (CYP) can effectively trigger ferroptosis. Moreover, by conducting an analysis of exosome cargo proteins, we have identified the participation of six-transmembrane epithelial antigen of prostate 4 in the regulation of hemocyte ferroptotic sensitivity. Subsequent functional investigations unveil that six-transmembrane epithelial antigen of prostate 4 enhances cellular Fe2+ levels, thereby triggering Fenton reactions and accelerating CYP-mediated lipid peroxidation, ultimately culminating in ferroptotic cell death. Additionally, the Fe2+-dependent CYP catalyzes the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid, which activates the peroxisome proliferator-activated receptor. Consequently, the downstream target of peroxisome proliferator-activated receptor, cluster of differentiation 36, promotes intracellular fatty acid accumulation, lipid peroxidation, and ferroptosis. These significant findings shed light on the immune defense mechanisms employed by crustaceans and provide potential strategies for combating bacterial infections in this species.


Assuntos
Bactérias , Crustáceos , Exossomos , Ferroptose , Ferro , Sistema Enzimático do Citocromo P-450/metabolismo , Exossomos/metabolismo , Ferroptose/fisiologia , Ferro/metabolismo , Peroxidação de Lipídeos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Oxirredutases/metabolismo , Proteínas de Membrana/metabolismo , Antígenos CD36/metabolismo , RNA-Seq , Compostos Ferrosos/metabolismo , Crustáceos/citologia , Crustáceos/genética , Crustáceos/metabolismo , Crustáceos/microbiologia , Ácidos Hidroxieicosatetraenoicos , Ácido Araquidônico/metabolismo , Ácidos Graxos/metabolismo , Bactérias/metabolismo
3.
Circulation ; 147(1): 35-46, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36503273

RESUMO

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. METHODS: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. RESULTS: The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively. CONCLUSIONS: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Isquemia Miocárdica , Acidente Vascular Cerebral , Humanos , Temperatura Alta , Temperatura , Causas de Morte , Temperatura Baixa , Morte , Mortalidade
4.
Prostate ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39154281

RESUMO

BACKGROUND: A specific type of prostate cancer (PC) that exhibits neuroendocrine (NE) differentiation is known as NEPC. NEPC has little to no response to androgen deprivation therapy and is associated with the development of metastatic castration-resistant PC (CRPC), which has an extremely poor prognosis. Our understanding of genetic drivers and activated pathways in NEPC is limited, which hinders precision medicine approaches. L1 cell adhesion molecule (L1CAM) is known to play an oncogenic role in metastatic cancers, including CRPC. However, the impact of L1CAM on NEPC progression remains elusive. METHODS: L1CAM expression level was investigated using public gene expression databases of PC cohorts and patient-derived xenograft models. L1CAM knockdown was performed in different PC cells to study in vitro cell functions. A subline of CRPC cell line CWR22Rv1 was established after long-term exposure to abiraterone to induce NE differentiation. The androgen receptor-negative cell line PC3 was cultured under the tumor sphere-forming condition to enrich cancer stemness features. Several oxidative stress inducers were tested on PC cells to observe L1CAM-mediated gene expression and cell death. RESULTS: L1CAM expression was remarkably high in NEPC compared to CRPC or adenocarcinoma tumors. L1CAM was also correlated with NE marker expressions and associated with the adenocarcinoma-to-NEPC progression in gene expression databases and CRPC cells with NE differentiation. L1CAM also promoted cancer stemness and NE phenotypes in PC3 cells under cancer stemness enrichment. L1CAM was also identified as a reactive oxygen species-induced gene, by which L1CAM counteracted CRPC cell death triggered by ionizing radiation. CONCLUSIONS: Our results unveiled a new role of L1CAM in the acquisition of the NE phenotype in PC, contributing to the NE differentiation-related therapeutic resistance of CRPC.

5.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34891158

RESUMO

In this article, we review two challenging computational questions in protein science: neoantigen prediction and protein structure prediction. Both topics have seen significant leaps forward by deep learning within the past five years, which immediately unlocked new developments of drugs and immunotherapies. We show that deep learning models offer unique advantages, such as representation learning and multi-layer architecture, which make them an ideal choice to leverage a huge amount of protein sequence and structure data to address those two problems. We also discuss the impact and future possibilities enabled by those two applications, especially how the data-driven approach by deep learning shall accelerate the progress towards personalized biomedicine.


Assuntos
Aprendizado Profundo , Sequência de Aminoácidos , Imunoterapia , Proteínas/química
6.
J Med Virol ; 96(6): e29746, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38884391

RESUMO

Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high-risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV-driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridization and polymerase chain reaction (PCR) techniques, notably reverse transcription-quantitative PCR (RT-qPCR), offer sensitive HPV detection. Liquid-based RT-qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost-effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 16/patogenicidade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/isolamento & purificação , Papillomavirus Humano
7.
BMC Cancer ; 24(1): 442, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600473

RESUMO

Head and neck cancers, particularly oropharyngeal cancers (OPC), have been increasingly associated with human papillomavirus (HPV) infections, specifically HPV16. The current methods for HPV16 detection primarily rely on p16 staining or PCR techniques. However, it is important to note the limitations of conventional PCR, as the presence of viral DNA does not always indicate an ongoing viral infection. Moreover, these tests heavily rely on the availability of tissue samples, which can present challenges in certain situations. In this study, we developed a RT-qPCR biplex approach to detect HPV16 oncogenes E6 and E7 RNA in saliva samples from OPC patients. Salivary supernatant was used as the liquid biopsy source. We successfully obtained RNA from salivary supernatant, preserving its integrity as indicated by the detection of several housekeeping genes. Our biplex approach accurately detected E6 and E7 RNA in HPV16-positive cell lines, tissues, and finally in OPC salivary samples. Importantly, the assay specifically targeted HPV16 and not HPV18. This biplexing technique allowed for reduced sample input without compromising specificity. In summary, our approach demonstrates the potential to detect viable HPV16 in saliva from OPC patients. Since the assay measures HPV16 RNA, it provides insights into the transcriptional activity of the virus. This could guide clinical decision-making and treatment planning for individuals with HPV-related OPC.


Assuntos
Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Papillomavirus Humano 16/genética , Saliva/metabolismo , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/complicações , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/patologia , RNA , Reação em Cadeia da Polimerase , Proteínas E7 de Papillomavirus/genética
8.
Biopolymers ; : e23613, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989603

RESUMO

Hydrogels are notable for their outstanding absorbent qualities, satisfactory compatibility with biological systems, ability to degrade, and inherent safety, all of which contribute to their high demand in the field of biomedicine. This study focuses on the fabrication of hydrogels using environmentally friendly cellulosic material. Cellulose hydrogel beads were prepared by physical cross-linking in a NaOH/urea medium. Furthermore, nano polydopamine was integrated into the hydrogel matrix as functional polymers and α-mangostin was employed as an active pharmaceutical ingredient. The physicochemical properties were comprehensively analyzed using Fourier-transform infrared spectrometer, 13C cross-polarization/magic angle spinning nuclear magnetic resonance, thermogravimetric analysis, and scanning electron microscope. The drug delivery properties, including water content, swelling ratio, and drug release profiles, were evaluated. In vitro cytotoxicity against MC3T3-E1 cells was assessed using sulforhodamine B staining. All test hydrogels exhibited inhibitory activity against the growth of MC3T3-E1 cells. These results indicated the potential use of these hydrogels as a drug delivery carrier for α-mangostin in the treatment of ankylosing spondylitis.

9.
Cell Commun Signal ; 22(1): 437, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261954

RESUMO

Squalene (SQ) is a well-known antioxidant and anti-inflammatory agent that provides promising anti-aging and UV-protective roles on human skin. However, its strong hydrophobic nature, accompanied by issues such as poor solubility and limited tissue permeation, has created challenges for scientists to investigate its untapped potential in more complex conditions, including cancer progression. The present study assessed the potent anti-metastatic properties of a newly synthesized amphiphilic ethylene glycol SQ derivative (SQ-diEG) in melanoma, the most fatal skin cancer. In vitro and in vivo experiments have discovered that SQ-diEG may exert its potential on melanoma malignancy through the mitochondria-mediated caspase activation apoptotic signaling pathway. The potent anti-metastatic effect of SQ-diEG was observed in vitro using highly proliferative and aggressive melanoma cells. Administration of SQ-diEG (25 mg/kg) significantly decreased the tumor burden on the lung and inhibited the metastasis-associated proteins and gene markers in B16F10 lung colonization mice model. Furthermore, global gene profiling also revealed a promising role of SQ-diEG in tumor microenvironment. We anticipated that the amphiphilic nature of the SQ compound bearing ethylene glycol oligomers could potentially augment its ability to reach the pathology site, thus enhancing its therapeutic potential in melanoma.


Assuntos
Melanoma , Esqualeno , Animais , Camundongos , Esqualeno/química , Esqualeno/farmacologia , Humanos , Linhagem Celular Tumoral , Melanoma/patologia , Melanoma/tratamento farmacológico , Camundongos Endogâmicos C57BL , Apoptose/efeitos dos fármacos , Melanoma Experimental/patologia , Melanoma Experimental/tratamento farmacológico , Metástase Neoplásica , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Éteres/farmacologia , Éteres/química , Proliferação de Células/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química
10.
Langmuir ; 40(25): 13292-13302, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38871669

RESUMO

In this study, surface-enhanced Raman scattering substrates were investigated by the electrodeposition method to detect low concentrations of pesticides via the electrodeposition method with different agents from silver and gold precursors on APTES-modified ITO glass. A dual-potential method supplied three electrodes and was performed with a nucleation potential of 0.7 V for 2 s and a growth potential of -0.2 V for 500 s. The Ag film produced by the electrodeposition approach has great surface uniformity and good SERS signal amplification for the thiram insecticide at low concentrations. Interestingly, the ITO/APTES/Ag substrate extensively increased the sensitivity than the other investigated ones, thanks to the adequate assistance of amino groups of APTES in the denser and hierarchical deposition of Ag NPs. These observations were additionally elucidated via finite-difference time-domain (FDTD) calculation. For thiram, the detection was set at 10-8 M with an enhancement factor of up to 3.6 × 107 times. Comparing the SERS spectra of thiram at concentrations of 10-3, 10-4, and 10-5 M with a relative standard deviation (RSD) of less than 7.0% demonstrates excellent reproducibility of the ITO/APTES/Ag substrate. In addition, the special selectivity of the ITO/APTES/Ag substrate for thiram demonstrates that these nanostructures can identify pesticides with extreme sensitivity.

11.
Circ Res ; 130(2): 252-272, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34930019

RESUMO

BACKGROUND: APC (activated protein C) is a plasma serine protease with anticoagulant and anti-inflammatory activities. EPCR (Endothelial protein C receptor) is associated with APC's activity and mediates its downstream signaling events. APC exerts cardioprotective effects during ischemia and reperfusion (I/R). This study aims to characterize the role of the APC-EPCR axis in ischemic insults in aging. METHODS: Young (3-4 months) and aged (24-26 months) wild-type C57BL/6J mice, as well as EPCR point mutation (EPCRR84A/R84A) knockin C57BL/6J mice incapable of interaction with APC and its wild type of littermate C57BL/6J mice, were subjected to I/R. Wild-type APC, signaling-selective APC-2Cys, or anticoagulant-selective APC-E170A were administrated before reperfusion. RESULTS: The results demonstrated that cardiac I/R reduces APC activity, and the APC activity was impaired in the aged versus young hearts possibly attributable to the declined EPCR level with aging. Serum EPCR measurement showed that I/R triggered the shedding of membrane EPCR into circulation, while administration of APC attenuated the I/R-induced EPCR shedding in both young and aged hearts. Subsequent echocardiography showed that APC and APC-2Cys but not APC-E170A ameliorated cardiac dysfunction during I/R in both young and aged mice. Importantly, APC elevated the resistance of the aged heart to ischemic insults through stabilizing EPCR. However, all these cardioprotective effects of APC were blunted in the EPCRR84A/R84A mice versus its wild-type littermates. The ex vivo working heart and metabolomics results demonstrated that AMPK (AMP-activated protein kinase) mediates acute adaptive response while AKT (protein kinase B) is involved in chronic metabolic programming in the hearts with APC treatment. CONCLUSIONS: I/R stress causes shedding of the membrane EPCR in the heart, and administration of APC prevents I/R-induced cardiac EPCR shedding that is critical for limiting cardiac damage in aging.


Assuntos
Envelhecimento/metabolismo , Receptor de Proteína C Endotelial/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteína C/metabolismo , Animais , Cardiotônicos/uso terapêutico , Receptor de Proteína C Endotelial/sangue , Feminino , Coração/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Proteína C/uso terapêutico
12.
MMWR Morb Mortal Wkly Rep ; 73(6): 131-134, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359006

RESUMO

Correctional settings provide a high-risk environment for hepatitis A transmission because of the high proportion of homelessness and injection drug use among persons who are incarcerated. On May 30, 2023, Los Angeles County Department of Public Health informed the Communicable Disease Surveillance and Control (CDSC) unit of the Los Angeles County Jail system that a symptomatic incarcerated person had received a positive test result for acute hepatitis A. Upon learning the next day that the patient was a food handler, CDSC staff members identified 5,830 potential contacts of the index patient, 1,702 of whom had been released from the jail. During June 1-12, a total of 2,766 contacts who did not have a documented history of hepatitis A serology or vaccination that could be confirmed from the electronic health record or state immunization registry were identified. These persons were offered hepatitis A vaccination as postexposure prophylaxis; 1,510 (54.6%) accepted vaccination. Contacts who were food handlers without confirmed evidence of immunity and who declined vaccination were removed from food-handling duties for the duration of their potential incubation period. No additional cases were identified. Identifying contacts promptly and using immunization and serology records to ensure rapid delivery of postexposure prophylactic vaccine can help prevent hepatitis A transmission during exposures among incarcerated populations.


Assuntos
Hepatite A , Humanos , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Prisões Locais , Los Angeles/epidemiologia , Surtos de Doenças/prevenção & controle , Vacinação
13.
Fish Shellfish Immunol ; 146: 109385, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242262

RESUMO

The Toll pathway is crucial for innate immune responses in organisms (including Drosophila and mammals). The Spätzle protein outside of cells acts as a ligand for Toll receptors, enabling the transfer of signals from outside the cell to the inside. However, the function of Spätzle in the immune system of mud crab (Scylla paramamosain) remains unclear. This research discovered a novel Spätzle gene (Sp-Spz) in mud crab, which showed extensive expression in all the tissues that were examined. The RNA interference exhibited the correlation between Sp-Spz and the anti-lipopolysaccharide factors (ALFs). Knockdown of Sp-Spz decreased the expression of Sp-Toll2 but not Sp-Toll1. In Drosophila Schneider 2 cells, Sp-Spz was found interacted with Sp-Toll2. Moreover, the depletion of Sp-Spz caused the separation of hepatic lobules from the basement membrane, resulting in the disruption of the structural coherence of hepatopancreatic cells. Additionally, the knockdown of Sp-Spz resulted in changes to the composition of the hemolymph microbiota, specifically affecting the proportions of different phylum and family levels. The findings indicated that Sp-Spz may promote the synthesis of ALFs via Sp-Toll2, thereby influencing the homeostasis of microbiota in the hemolymph. In this study, novel insights into mud crab immunity are provided.


Assuntos
Braquiúros , Microbiota , Animais , Hemolinfa , Proteínas de Artrópodes , Homeostase , Drosophila/metabolismo , Imunidade Inata/genética , Mamíferos/metabolismo
14.
Environ Sci Technol ; 58(15): 6781-6792, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38560895

RESUMO

Predicting the hotspots of antimicrobial resistance (AMR) in aquatics is crucial for managing associated risks. We developed an integrated modeling framework toward predicting the spatiotemporal abundance of antibiotics, indicator bacteria, and their corresponding antibiotic-resistant bacteria (ARB), as well as assessing the potential AMR risks to the aquatic ecosystem in a tropical reservoir. Our focus was on two antibiotics, sulfamethoxazole (SMX) and trimethoprim (TMP), and on Escherichia coli (E. coli) and its variant resistant to sulfamethoxazole-trimethoprim (EC_SXT). We validated the predictive model using withheld data, with all Nash-Sutcliffe efficiency (NSE) values above 0.79, absolute relative difference (ARD) less than 25%, and coefficient of determination (R2) greater than 0.800 for the modeled targets. Predictions indicated concentrations of 1-15 ng/L for SMX, 0.5-5 ng/L for TMP, and 0 to 5 (log10 MPN/100 mL) for E. coli and -1.1 to 3.5 (log10 CFU/100 mL) for EC_SXT. Risk assessment suggested that the predicted TMP could pose a higher risk of AMR development than SMX, but SMX could possess a higher ecological risk. The study lays down a hybrid modeling framework for integrating a statistic model with a process-based model to predict AMR in a holistic manner, thus facilitating the development of a better risk management framework.


Assuntos
Antibacterianos , Escherichia coli , Antibacterianos/farmacologia , Ecossistema , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Combinação Trimetoprima e Sulfametoxazol , Resistência Microbiana a Medicamentos , Bactérias
15.
J Immunol ; 209(4): 710-722, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35896338

RESUMO

Exosomes, secreted by most cells, are critical antimicrobial immune factors in animals. Recent studies of certain key regulators of vesicular transport, the Rab GTPases, have linked Rab dysfunction to regulation of innate immune signaling. However, the relationship between exosomes and Rab GTPases, resulting in antimicrobial activity in vertebrates and invertebrates during pathogenic infection, has not been addressed. In this study, SpRab11a was reported to have a protective effect on the survival rate of mud crabs Scylla paramamosain after Vibrio parahaemolyticus challenge through the stimulation of exosome secretion and modulation of anti-LPS factor (ALF) expression. Furthermore, Sp14-3-3 was confirmed to be densely packaged in exosomes after V. parahaemolyticus infection, which could recruit the MyD88 and TLR by binding the Toll/IL-1R domain to the plasma membrane, promoting the translocation of Dorsal from the cytoplasm into the nucleus, and thereby regulating ALFs expression in the hemocytes of mud crab in response to the bacterial infection. The findings therefore provide, to our knowledge, a novel mechanism that underlies the cross-talk between SpRab11a-regulated exosome formation and ALFs expression in innate immune response in invertebrates, with a crustacean species, mud crab S. paramamosain, as a model study.


Assuntos
Infecções Bacterianas , Braquiúros , Exossomos , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Artrópodes/genética , Exossomos/metabolismo , Imunidade Inata , Filogenia , Proteínas rab de Ligação ao GTP/metabolismo
16.
Support Care Cancer ; 32(10): 654, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259391

RESUMO

AIMS: This qualitative study explores the experiences of women after cancer treatment in terms of habit changes and mental health impact. METHOD: The study involved 10 women who had undergone cancer treatment, recruited from three major hospitals in Hanoi, Vietnam. Data were collected through semi-structured interviews, which were transcribed and analyzed using thematic analysis. RESULTS: The findings of the study shed light on the various factors influencing lifestyle behavior and mental health changes among women after cancer treatment. Ten participants, aged 39 to 64 years, shared experiences including dietary changes, sleep disruptions, and reliance on non-scientific sources for health decisions. Initially shocked by their diagnosis, many transitioned to acceptance, adopting a "giving-in" attitude. Cultural beliefs, word-of-mouth sharing, and social support networks played significant roles in shaping post-treatment lifestyle changes, coping mechanisms, information-seeking behaviors, and mental health. CONCLUSION: The study highlights the need for accessible and scientifically verified information for women after cancer treatment to make informed decisions about their health. It emphasizes the importance of addressing traditional beliefs and promoting evidence-based practices. Moreover, the study underscores the importance of social support and relationships in coping with the challenges of post-cancer experiences.


Assuntos
Adaptação Psicológica , Estilo de Vida , Saúde Mental , Neoplasias , Pesquisa Qualitativa , Apoio Social , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Vietnã , Neoplasias/psicologia , Neoplasias/terapia , Hábitos , Entrevistas como Assunto , População do Sudeste Asiático
17.
Public Health Nutr ; : 1-37, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804077

RESUMO

OBJECTIVE: SEANUTS II Vietnam aims to obtain an in-depth understanding of the nutritional status and nutrient intake of children between 0.5-11.9 years old. DESIGN: Cross-sectional survey. SETTING: A multistage cluster systematic random sampling method was implemented in different regions in Vietnam: North Mountainous, Central Highlands, Red River Delta, North Central and Coastal Area, Southeast and Mekong River Delta. PARTICIPANTS: 4001 children between 6 months and 11.9 years of age. RESULTS: Prevalence of stunting and underweight was higher in rural than in urban children, whereas overweight and obese rates were higher in urban areas. 12.0% of the children had anemia and especially children 0.5-1-year-old were affected (38.6%). Low serum retinol was found in 6.2% of children ≥ 4 years old. Prevalence of vitamin D insufficiency was 31.1% while 60.8% had low serum zinc. For nutrient intake, overall, 80.1% of the children did not meet the estimated energy requirements. For calcium intake, ∼60% of the younger children did not meet the RNI while it was 92.6% in children >7 years old. For vitamin D intake, 95.0% of the children did not meet RNI. CONCLUSIONS: SEANUTS II Vietnam indicated that overnutrition was more prevalent than undernutrition in urban areas, while undernutrition was found more in rural areas. The high prevalence of low serum zinc, vitamin D insufficiency and the inadequate intakes of calcium and vitamin D are of concern. Nutrition strategies for Vietnamese children should consider three sides of malnutrition and focus on approaches for the prevention malnutrition.

18.
Subcell Biochem ; 103: 79-94, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37120465

RESUMO

The gap between improvements in lifespan and age-related health is widening. Globally, the demographic of ageing is increasing and there has emerged a 'diseasome of ageing', typified by a range of non-communicable diseases which share a common underlying component of a dysregulated ageing process. Within this, chronic kidney disease is an emerging global epidemic.The extensive inter-individual variation displayed in how people age and how their diseasome manifests and progresses, has required a renewed focus on their life course exposures and the interplay between the environment and the (epi)genome. Termed the exposome, life course abiotic and biotic factors have a significant impact on renal health.We explore how the exposome of renal ageing can predispose and affect CKD progression. We discuss how the kidney can be used as a model to understand the impact of the exposome in health and chronic kidney disease and how this might be manipulated to improve health span.Notably, we discuss the manipulation of the foodome to mitigate acceleration of ageing processes by phosphate and to explore use of emerging senotherapies. A range of senotherapies, for removing senescent cells, diminishing inflammatory burden and either directly targeting Nrf2, or manipulating it indirectly via modification of the microbiome are discussed.


Assuntos
Expossoma , Insuficiência Renal Crônica , Humanos , Envelhecimento , Longevidade
19.
J Couns Psychol ; 71(4): 267, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949779

RESUMO

Reports an error in "Defining racial allies: A qualitative investigation of White allyship from the perspective of people of color" by Cassandra L. Hinger, Cirleen DeBlaere, Rebecca Gwira, Michelle Aiello, Arash Punjwani, Laura Cobourne, Ngoc Tran, Madison Lord, Jordan Mike and Carlton Green (Journal of Counseling Psychology, 2023[Nov], Vol 70[6], 631-644). An additional citation was added for the structure of the definition of White allies in the second paragraph of the introduction. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2024-23216-002.) While interdisciplinary scholars and activists urge White allies to engage in racial justice work led by the voices of Black, Indigenous, and people of color (BIPOC), to date, most research on racial allyship has centered exclusively on the perspective of White allies themselves. Thus, the purpose of this study was to create a framework of racial allyship from the perspective of BIPOC. Utilizing constructivist grounded theory (Charmaz, 2014), focus groups were conducted to understand how BIPOC describe the knowledge, skills, and actions of White allies. Participants across eight focus groups described allyship as an ongoing interpersonal process that included a lifelong commitment to (a) building trust, (b) engaging in antiracist action, (c) critical awareness, (d) sociopolitical knowledge, (e) accountability, and (f) communicating and disseminating information. The findings of this study point to several avenues through which White counseling psychologists can incorporate racial allyship in their research, training, clinical, and advocacy work that align with our field's emphasis on social justice, multiculturalism, and prevention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

20.
Int J Food Sci Nutr ; 75(6): 550-561, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38946436

RESUMO

This study aims to investigate longitudinal associations between the dietary glycemic index (GI) and glycemic load (GL) and changes in glycemic and cardio-metabolic outcomes. A 28-month retrospective cohort study included 110 Vietnamese diabetic patients, collecting their dietary GI and GL values along with blood biochemical data from baseline 24-h dietary recall and medical records. Latent class growth modelling identified three distinct HbA1c trajectories during the follow-up period, with 51% of patients achieving good glycemic control. The adjusted linear mixed-effect model showed that 1 unit increase in logarithms in dietary GL was associated with a 0.14% increase in the log-HbA1c. Among poorly controlled diabetic patients, baseline GL values were positively correlated with increases in HbA1c; GI showed effects on changes in fasting plasma glucose and the triglyceride-glucose (TyG) index. No significant association was observed in patients with good glycemic control.


Assuntos
Biomarcadores , Glicemia , Dieta , Hemoglobinas Glicadas , Índice Glicêmico , Carga Glicêmica , Humanos , Masculino , Feminino , Glicemia/metabolismo , Glicemia/análise , Hemoglobinas Glicadas/análise , Biomarcadores/sangue , Idoso , Vietnã , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos Longitudinais , Diabetes Mellitus Tipo 2/sangue , Triglicerídeos/sangue , Controle Glicêmico/métodos
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