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1.
Bioorg Med Chem ; 90: 117377, 2023 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-37352576

RESUMEN

Indoleamine 2,3-dioxygenase (IDO1) is a heme-containing enzyme mainly responsible for the metabolism of tryptophan to kynurenine. To date, the IDO1 inhibitors have been developed intensively for the re-activation of the anticancer immune response. In this report, we designed, and synthesized novel 1,3-dimethyl-6-amino indazole derivatives as IDO1 inhibitors based on the structure of IDO1 active site. We further examined their anticancer activity on hypopharyngeal carcinoma cells (FaDu), squamous cell carcinoma of the oral tongue (YD-15), breast cancer cells (MCF7), and human dental pulp stem cells (HDPSC). Of them, compound N-(4-bromobenzyl)-1,3-dimethyl-1H-indazol-6-amine (7) remarkably suppressed IDO1 expression in a concentration - dependent manner. In addition, 7 was the most potential anticancer compound with inducing apoptosis activity as well as selectively activated extracellular signal-regulated kinases (ERK) in mitogen-activated protein kinase (MAPK) pathways on FaDu cells. Finally, compound 7 suppressed cell mobility in wound healing assay with the reduced expression of matrix metalloproteinase MMP9. Taken together, we believe that 7 is the most promising compound, which may be applied to treatment of hypopharyngeal carcinoma.


Asunto(s)
Antineoplásicos , Carcinoma , Humanos , Indazoles/química , Antineoplásicos/farmacología , Antineoplásicos/química , Triptófano , Indolamina-Pirrol 2,3,-Dioxigenasa , Inhibidores Enzimáticos/química
2.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36674771

RESUMEN

Nowadays, cancers and dementia, such as Alzheimer's disease, are the most fatal causes of death. Many studies tried to understand the pathogenesis of those diseases clearly and develop a promising way to treat the diseases. Matrix metalloproteinases (MMPs) have been reported to be involved in the pathology of cancers and AD through tumor cell movement and amyloid degradation. Therefore, control of the levels and actions of MMPs, especially MMP-2 and MMP-9, is necessary to care for and/or cure cancer and AD. Various molecules have been examined for their potential application as regulators of MMPs expression and activity. Among the molecules, multiple metal complexes have shown advantages, including simple synthesis, less toxicity and specificity toward MMPs in cancer cells or in the brain. In this review, we summarize the recent studies and knowledge of metal complexes (e.g., Pt-, Ru-, Au-, Fe-, Cu-, Ni-, Zn-, and Sn-complexes) targeting MMPs and their potentials for treating and/or caring the most fatal human diseases, cancers and AD.


Asunto(s)
Enfermedad de Alzheimer , Complejos de Coordinación , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Metaloproteinasas de la Matriz/metabolismo , Encéfalo/metabolismo
3.
Int J Mol Sci ; 24(23)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38069361

RESUMEN

Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these vitamins is imperative to the upkeep of various physiological processes including vision, bone health, immunity, and protection against oxidative stress. Current research highlights fat-soluble vitamins as potential therapeutics for human diseases, especially cancer. Fat-soluble vitamins exert their therapeutic effects through multiple pathways, including regulation of matrix metalloproteinases' (MMPs) expression and enzymatic activity. As MMPs have been reported to be involved in the pathology of various diseases, such as cancers, cardiovascular diseases, and neurological disorders, regulating the expression and/or activity of MMPs could be considered as a potent therapeutic strategy. Here, we summarize the properties of fat-soluble vitamins and their potential as promising candidates capable of effectively modulating MMPs through multiple pathways to treat human diseases.


Asunto(s)
Enfermedades Cardiovasculares , Vitamina A , Humanos , Vitamina A/farmacología , Metaloproteinasa 2 de la Matriz , Vitaminas/uso terapéutico , Vitamina K , Enfermedades Cardiovasculares/tratamiento farmacológico , Vitamina D/uso terapéutico , Vitamina E
4.
J Happiness Stud ; 24(5): 1729-1757, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37293325

RESUMEN

Family and intergenerational relationships are becoming increasingly important as sources of support and care for the elderly population in rapidly ageing Asian societies. However, this has also raised concerns over reinforcement of cultural preference for sons as a source of old-age security. This paper therefore revisits the question-what determines happiness in old age-by investigating the role of adult children's gender in the context of Thailand, an ageing Asian country with no legacy of sex-preference in fertility. We employ nationally representative data to examine the association between old-age happiness and presence of a co-residing child. Compared to living alone, living with at least one child is found to positively associate with older persons' happiness. However, this result is specific to daughters. Moreover, compared to older men, women systematically benefit from a "daughter effect". Co-residing daughters with university education and those who maintain a good relationship with their parents help explain the positive happiness effect on older persons. Co-residing daughters are also positively linked to  reduced loneliness; improved self-rated health; and improved economic conditions of older parents. Our findings suggest that policies that increase human capital of the girl child and enhance family solidarity are likely to have long term intergenerational wellbeing benefits.

5.
J Biosoc Sci ; 54(6): 1047-1066, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34629135

RESUMEN

This paper investigates the relationship between women's education and desire for additional children across the six economic regions of Vietnam. The study employed data from the nationally representative Vietnam Multiple Indicator Cluster Survey (MICS) 2014. Probit regression results showed that for women with one child, higher levels of education were associated with higher fertility desire in two out of six regions. Similar results were found for women with two or more children. Children's sex composition played a role in the desire for additional children, reflecting both son preference and mixed-gender preference. In Vietnam overall, among women with at least one boy, those with lower levels of education were more likely not to want another child. The results, however, differed by region. The findings suggest that the social and economic context of each region, particularly sex ratio at birth and total fertility rate, should be taken into account when designing population policies in Vietnam.


Asunto(s)
Tasa de Natalidad , Composición Familiar , Masculino , Niño , Recién Nacido , Femenino , Humanos , Vietnam , Escolaridad , Fertilidad , Núcleo Familiar , Países en Desarrollo
6.
Bull Environ Contam Toxicol ; 107(3): 475-486, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33760936

RESUMEN

Unsubstituted and methylated polycyclic aromatic hydrocarbons (22 PAHs and 17 Me-PAHs) were examined in surface sediments collected from the Red River and four inner-city rivers of Hanoi City, Vietnam. Concentrations of total PAHs and Me-PAHs ranged from 52 to 920 (median 710) and from 70 to 2600 (median 1000) ng/g dry weight in samples of dry and wet seasons, respectively. Significant correlation was observed between total PAHs and organic carbon contents (Spearman's ρ = 0.782; p < 0.05). PAHs were more abundant than Me-PAHs in all samples and dominated by 4-6 ring compounds. The most predominant PAHs were benzo[ghi]perylene, benzo[b/j]fluoranthene, chrysene, pyrene, fluoranthene, and phenanthrene. Methylated derivatives of naphthalene, phenanthrene, anthracene, and benz[a]anthracene were frequently detected. The patterns of PAHs indicated principal pyrogenic sources (notably gasoline exhaust) in this highly urbanized area. The occurrence of several PAHs were occasionally associated with adverse effects on benthic organisms of the inner-city rivers.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Sedimentos Geológicos , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo , Vietnam , Contaminantes Químicos del Agua/análisis
7.
Emerg Infect Dis ; 26(8): 1878-1881, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32687023

RESUMEN

Serologic and molecular surveillance of serum collected from 152 suspected scrub typhus patients in Myanmar revealed Orientia tsutsugamushi of genotypic heterogeneity. In addition, potential co-infection with severe fever with thrombocytopenia syndrome virus was observed in 5 (3.3%) patients. Both scrub typhus and severe fever with thrombocytopenia syndrome are endemic in Myanmar.


Asunto(s)
Coinfección , Orientia tsutsugamushi , Tifus por Ácaros , Trombocitopenia , Coinfección/epidemiología , Humanos , Mianmar/epidemiología , Orientia , Orientia tsutsugamushi/genética , Tifus por Ácaros/complicaciones , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/epidemiología
8.
Molecules ; 25(14)2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32664351

RESUMEN

10-gingerol is a major phenolic lipid found in the rhizomes of ginger (Zingiber officinale). Being amphiphilic in nature, phenolic lipids have the ability to incorporate into cell membranes and modulate membrane properties. The purpose of the present study was to evaluate the effects of 10-gingerol on lipid raft/membrane raft modulation in radio-resistant triple negative breast cancer (MDA-MB-231/IR) cells. The effects of 10-gingerol on MDA-MB-231/IR cells' proliferation, clonogenic growth, migration, and invasion were assayed using MTT, colony formation, cell migration, and invasion assays, respectively. Sucrose density gradient centrifugation was used to extract lipid rafts. Western blotting and immunofluorescence were employed to assess the effects of 10-gingerol on lipid raft/membrane raft modulation and lipid rafts-associated PI3K/Akt signaling. Cholesterol measurements were carried out using a commercially available kit. 10-gingerol suppressed the proliferation, migration, invasion, and induced apoptosis through targeting the PI3K/Akt signaling pathway in MDA-MB-231/IR cells. Moreover, 10-gingerol was found to modulate the lipid rafts of MDA-MB-231/IR cells and attenuate the key PI3K/Akt signaling components in lipid rafts. The cholesterol content of the lipid rafts and rafts-resident Akt signaling were also affected by exposure to 10-gingerol. The results of the present study highlight rafts-associated PI3K/Akt signaling as a new target of 10-gingerol in MDA-MB-231/IR cells, thus rationalizing a new rafts-mediated treatment approach for radio-resistant triple negative breast cancer cells.


Asunto(s)
Catecoles/farmacología , Alcoholes Grasos/farmacología , Microdominios de Membrana/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Zingiber officinale/química , Humanos , Microdominios de Membrana/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo
9.
Molecules ; 25(3)2020 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-32013195

RESUMEN

Arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) was originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. After that, mammalian ARD1/NAA10 expanded its' role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT and KAT activities. However, recent studies on the role of human ARD1/NAA10 (hARD1/NAA10) in lysine acetylation are contradictory, as crystal structure and in vitro acetylation assay results revealed the lack of KAT activity. Thus, the role of hARD1/NAA10 in lysine acetylation is still debating. Here, we found a clue that possibly explains these complicated and controversial results on KAT activity of hARD1/NAA10. Recombinant hARD1/NAA10 exhibited KAT activity, which disappeared soon in vitro. Size-exclusion analysis revealed that most recombinant hARD1/NAA10 formed oligomers over time, resulting in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 lost its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. We also characterized the KAT activity of hARD1/NAA10 that was influenced by several experimental conditions, including concentration of reactants and reaction time. Taken together, our study proves that recombinant hARD1/NAA10 exhibits KAT activity in vitro but only under accurate conditions, including reactant concentrations and reaction duration.


Asunto(s)
Lisina Acetiltransferasas/metabolismo , Acetiltransferasa A N-Terminal/metabolismo , Acetiltransferasa E N-Terminal/metabolismo , Acetilación , Diálisis , Escherichia coli , Humanos , Lisina/metabolismo , Acetiltransferasa A N-Terminal/genética , Acetiltransferasa A N-Terminal/aislamiento & purificación , Acetiltransferasa E N-Terminal/genética , Acetiltransferasa E N-Terminal/aislamiento & purificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo
10.
J Med Entomol ; 52(6): 1203-12, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26336261

RESUMEN

We studied the winter activity of Aedes albopictus (Skuse) from November 2008 to April 2009 in Bat Trang village of Hanoi, Vietnam. We selected 12 houses and collected: 1) adults with BG sentinel traps, 2) pupae from household water containers, and 3) eggs with ovitraps. Aedes albopictus adults, pupae, and eggs were not collected from early January to early February. Though the egg hatching probability tended to be initially high at longer day length, the maximum probability gradually shifted to shorter day length, as the observation period elapsed. When females were reared under long day length and their eggs were immersed 1 or 5 wk after oviposition, >50% of eggs hatched within 20 days. However, when females were reared under short day length and their eggs were immersed after 1 wk, hatching was suppressed for 60 days. When females were reared under short day length, the median hatching day occurred earlier in eggs kept dry for 5 and 10 wk after oviposition than in those dried for only 1 wk. This indicates that the extended dry periods accelerate egg hatching. Our results showed that hatchability gradually changed with day length, suggesting that selection for overwintering is not as strong relative to Ae. albopictus living in the temperate zone, where winter conditions are less favorable than in tropical and subtropical areas.


Asunto(s)
Aedes/fisiología , Diapausa de Insecto , Animales , Femenino , Óvulo/fisiología , Fotoperiodo , Estaciones del Año , Vietnam
11.
J Vet Med Sci ; 86(1): 96-100, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38030282

RESUMEN

Cats normally play a role of the definitive host in which the plerocercoid (sparganum), the second larval form of Spirometra spp., develops into an adult in the intestines. However, some cases of cats with visceral or subcutaneous sparganosis were sporadically reported worldwide. We herein documented the discovery of a sparganum in abdominal cavity of a domestic cat during a surgery of dystocia. The larva was molecularly identified as Spirometra mansoni, belonging to Type I, that was recently misidentified to be S. erinaceieuropaei in several Asian countries. This is the first report for sparganum of S. mansoni in the cat. The future study is necessary to provide further insights into the species of Spirometra causing sparganosis and spirometrosis in humans and other animals.


Asunto(s)
Cavidad Abdominal , Enfermedades de los Gatos , Esparganosis , Spirometra , Humanos , Animales , Gatos , Spirometra/genética , Plerocercoide/genética , Esparganosis/diagnóstico , Esparganosis/epidemiología , Esparganosis/veterinaria , Vietnam , Larva , Enfermedades de los Gatos/diagnóstico
12.
Eur J Cardiothorac Surg ; 65(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830041

RESUMEN

OBJECTIVES: Children with congenital tracheal stenosis born in the developing world face a high risk of mortality due to limited access to proper treatment. Patients who required preoperative respiratory support were suspected to have poor survival after slide tracheoplasty; however, this was not clearly demonstrated in the previous studies. This study aims to investigate the impact of preoperative respiratory conditions on outcomes of slide tracheoplasty. METHODS: From 2016 to 2022, children who underwent slide tracheoplasty were retrospectively reviewed. Patients with respiratory distress requiring emergency operations (group A) were compared with patients in stable condition who were scheduled for surgery (group B). RESULTS: Perioperative results revealed that group A (n = 43) had a longer bypass time (P < 0.001), operation time (P = 0.01), postoperative ventilation time (P < 0.001) and length of intensive care unit stay (P = 0.00125) than group B (n = 60). The early mortality rate was 7.8%, and the actuarial 5-year survival rate was 85.3%. The cumulative incidence test revealed that group A was highly significant for overall mortality [sudistribution (SHR) 4.5; 95% confidence interval (CI) 1.23-16.4; P = 0.023]. Risk factors for overall mortality were prolonged postoperative ventilation time (hazard ratio 3.86; 95% CI 1.20-12.48; P = 0.024), bronchial stenosis (hazard ratio 5.77; 95% CI 1.72-19.31; P = 0.004), and preoperative tracheal mucositis (hazard ratio 5.67; 95% CI 1.51-21.31; P = 0.01). Four patients needed reintervention during a follow-up of 28.4 months (interquartile range 15.3-47.3). CONCLUSIONS: Preoperative respiratory distress negatively affected the outcomes of patients who required slide tracheoplasty. Therefore, early detection of congenital tracheal stenosis and aggressive slide tracheoplasty are crucial and obligatory to enhance long-term survival in this lethal congenital airway disease.


Asunto(s)
Tráquea , Estenosis Traqueal , Humanos , Estudios Retrospectivos , Femenino , Masculino , Estenosis Traqueal/cirugía , Estenosis Traqueal/congénito , Estenosis Traqueal/mortalidad , Tráquea/cirugía , Tráquea/anomalías , Recién Nacido , Lactante , Resultado del Tratamiento , Procedimientos de Cirugía Plástica/métodos , Factores de Riesgo , Preescolar
13.
Front Vet Sci ; 11: 1366904, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812564

RESUMEN

Tembusu virus (TMUV) is an important infectious disease, causing economic losses in duck production. Since the first report of TMUV infection in Vietnam in 2020, the disease has persisted and affected poultry production in the country. This study conducted epidemiological and genetic characterization of the viral strains circulating in north Vietnam based on 130 pooled tissue samples collected in six provinces/cities during 2021. The TMUV genome was examined using conventional PCR. The results indicated that 21 (16.15%) samples and 9 (23.68%) farms were positive for the viral genome. The positive rate was 59.26% for ducks at ages 2-4 weeks, which was significantly higher than for ducks at ages >4 weeks and < 2 weeks. Genetic analysis of the partial envelope gene (891 bp) sequences indicated that the five Vietnamese TMUVs shared 99.55-100% nucleotide identity, while the rates were in the range 99.59-100% based on the pre-membrane gene sequences (498 bp). The five Vietnamese TMUV strains obtained formed a novel single subcluster. These strains were closely related to Chinese strains and differed from the vaccine strain, suggesting that Vietnamese TMUV strains were field viruses. It needs to be further studied on vaccine development to prevent effects of TMUV infection on poultry production across Vietnam.

14.
Sci Transl Med ; 16(735): eadk1867, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38381847

RESUMEN

Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody-based universal antivenom to treat snakebite envenoming.


Asunto(s)
Antivenenos , Mordeduras de Serpientes , Humanos , Animales , Ratones , Antivenenos/química , Mordeduras de Serpientes/tratamiento farmacológico , Neurotoxinas/toxicidad , Anticuerpos ampliamente neutralizantes , Venenos de Serpiente
15.
Nat Commun ; 15(1): 4187, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760381

RESUMEN

Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe invasive infections in Vietnam, yet data on its epidemiology, population structure and dynamics are scarce. We screened hvKp isolates from patients with bloodstream infections (BSIs) at a tertiary infectious diseases hospital in Vietnam and healthy individuals, followed by whole genome sequencing and plasmid analysis. Among 700 BSI-causing Kp strains, 100 (14.3%) were hvKp. Thirteen hvKp isolates were identified from 350 rectal swabs of healthy adults; none from 500 rectal swabs of healthy children. The hvKp isolates were genetically diverse, encompassing 17 sequence types (STs), predominantly ST23, ST86 and ST65. Among the 113 hvKp isolates, 14 (12.6%) carried at least one antimicrobial resistance (AMR) gene, largely mediated by IncFII, IncR, and IncA/C plasmids. Notably, the acquisition of AMR conjugative plasmids facilitated horizontal transfer of the non-conjugative virulence plasmid between K. pneumoniae strains. Phylogenetic analysis demonstrated hvKp isolates from BSIs and human carriage clustered together, suggesting a significant role of intestinal carriage in hvKp transmission. Enhanced surveillance is crucial to understand the factors driving intestinal carriage and hvKp transmission dynamics for informing preventive measures. Furthermore, we advocate the clinical use of our molecular assay for diagnosing hvKp infections to guide effective management.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Filogenia , Plásmidos , Secuenciación Completa del Genoma , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Klebsiella pneumoniae/aislamiento & purificación , Vietnam/epidemiología , Humanos , Plásmidos/genética , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Virulencia/genética , Adulto , Femenino , Transferencia de Gen Horizontal , Masculino , Genoma Bacteriano , Persona de Mediana Edad , Antibacterianos/farmacología , Niño , Genómica , Farmacorresistencia Bacteriana/genética
16.
mBio ; 14(1): e0154322, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36541760

RESUMEN

Scrub typhus is a mite-borne disease caused by the obligately intracellular bacterium Orientia tsutsugamushi. We previously demonstrated that ScaA, an autotransporter membrane protein of O. tsutsugamushi, is commonly shared in various genotypes and involved in adherence to host cells. Here, we identified a mixed-lineage leukemia 5 (MLL5) mammalian trithorax group protein as a host receptor that interacts with ScaA. MLL5, identified by yeast two-hybrid screening, is an alternative splicing variant of MLL5 (vMLL5) which contains 13 exons with additional intron sequences encoding a tentative transmembrane domain. Indeed, vMLL5 is expressed on the plasma membrane as well as in intracellular compartments in eukaryotic cells and colocalized with adherent O. tsutsugamushi. In addition, ScaA-expressing Escherichia coli showed significantly increased adherence to vMLL5-overexpressing cells compared with vector control cells. We mapped the C-terminal region of the passenger domain of ScaA as a ligand for vMLL5 and determined that the Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain of MLL5 is an essential and sufficient motif for ScaA binding. We observed significant and specific inhibition of bacterial adhesion to host cells in competitive inhibition assays using the C-terminal fragment of ScaA or the SET domain of vMLL5. Moreover, immunization with the C-terminal fragment of ScaA provided neutralizing activity and protective immunity against lethal challenge with O. tsutsugamushi as efficiently as vaccination with the whole passenger domain of ScaA. These results indicate that vMLL5 is a novel cellular receptor for ScaA-mediated adhesion of O. tsutsugamushi and facilitates bacterial adhesion to host cells, thereby enhancing bacterial infection. IMPORTANCE O. tsutsugamushi is a mite-borne pathogen that causes scrub typhus. As an obligately intracellular pathogen, its adhesion to and invasion of host cells are critical steps for bacterial growth. However, the molecular basis of the bacterial ligand and host receptor interaction is poorly defined. Here, we identified a splicing variant of MLL5 (vMLL5) as a cellular adhesion receptor of ScaA, an outer membrane autotransporter protein of O. tsutsugamushi. We mapped the interacting domains in the bacterial ligand and host receptor and confirmed their functional interaction. In addition, immunization with the C-terminal region of ScaA, which involves an interaction with the SET domain of vMLL5, not only induces enhanced neutralizing antibodies but also provides protective immunity against lethal challenge with O. tsutsugamushi.


Asunto(s)
Orientia tsutsugamushi , Tifus por Ácaros , Animales , Humanos , Empalme Alternativo , Ligandos , Mamíferos/metabolismo , Proteínas de la Membrana/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/metabolismo , Tifus por Ácaros/microbiología , Tifus por Ácaros/prevención & control , Sistemas de Secreción Tipo V/metabolismo , Proteínas Bacterianas/metabolismo
17.
Sci Adv ; 9(17): eadd6868, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37115927

RESUMEN

The thermo-mechanical response of shock-initiated energetic materials (EMs) is highly influenced by their microstructures, presenting an opportunity to engineer EM microstructures in a "materials-by-design" framework. However, the current design practice is limited, as a large ensemble of simulations is required to construct the complex EM structure-property-performance linkages. We present the physics-aware recurrent convolutional (PARC) neural network, a deep learning algorithm capable of learning the mesoscale thermo-mechanics of EM from a modest number of high-resolution direct numerical simulations (DNS). Validation results demonstrated that PARC could predict the themo-mechanical response of shocked EMs with comparable accuracy to DNS but with notably less computation time. The physics-awareness of PARC enhances its modeling capabilities and generalizability, especially when challenged in unseen prediction scenarios. We also demonstrate that visualizing the artificial neurons at PARC can shed light on important aspects of EM thermos-mechanics and provide an additional lens for conceptualizing EM.

18.
Nat Prod Res ; : 1-6, 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37737149

RESUMEN

Three new minor steroidal glycosides were isolated from the whole plants of Hoya parasitica (Wall. ex Hornem.) Wight. Their structures were further elucidated as 3ß,4α-dihydroxy-5ß-spirost-(25)27-en-1ß-yl O-α-L-arabinopyranoside (1), 3ß-hydroxy-5ß-spirost-25(27)-en-1ß-yl O-α-L-rhamnopyranosyl-(1→2)-ß-D-xylopyranoside (2), and (23S,24S,25S)-3ß,4α,23,24-tetrahydroxy-5ß-spirostan-1ß-yl O-α-L-rhamnopyranosyl-(1→2)-ß-D-fucopyranoside (3) through interpretation of the spectroscopic data (one-dimensional and two-dimensional) and mass spectrometry (HR-ESI-MS). To the best of our knowledge, this is the first report of the isolation of spirostane-type steroidal saponins from the Hoya genus.

19.
Asian Pac J Cancer Prev ; 24(6): 2073-2082, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37378938

RESUMEN

OBJECTIVE: Alcohol abuse can cause developing cirrhosis, even liver cancer. Several single nucleotide polymorphisms (SNPs) of ADH1B, ADH1C, and ALDH2 genes have been reported to be associated with alcohol abuse and alcoholic cirrhosis (ALC). This study investigated the association between three SNPs of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with alcohol abuse and ALC in people living in the Northeast region of Vietnam. METHODS: 306 male participants were recruited including 206 alcoholics (106 ALC, 100 without ALC) and 100 healthy non-alcoholics. Clinical characteristics were collected by clinicians. Genotypes were identified by Sanger sequencing. Chi-Square (χ2) and Fisher-exact tests were used to assess the differences in age and clinical characteristics, Child-Pugh score, frequencies of alleles and genotypes. RESULT: Our data showed that the frequency of ALDH2*1 was significantly higher in alcoholics (88.59%) and ALC groups (93.40%) than that of healthy non-alcoholics (78.50%) with p=0.0009 and non-ALC group (83.50%) with p=0.002, respectively. We detected opposite results when examined ALDH2*2. Frequency of combined genotypes with high acetaldehyde accumulation were significantly lower in alcoholics and ALC group than those of control groups with p=0.005 and p=0.008, respectively. Meanwhile, the proportion of combined genotypes with non-acetaldehyde accumulation were significantly two times higher in the ALC group (19.98%) than those of the non-ALC group (8%) with p=0.035. These combined genotypes showed a decreasing trend in the Child-Pugh score from likely phenotype causing risk for non-acetaldehyde accumulation to high acetaldehyde accumulation. CONCLUSION: The ALDH2*1 allele was found as a risk factor for alcohol abuse and ALC, and combined genotypes of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with non-acetaldehyde accumulation increase ALC risk. In contrast, ALDH2*2 and the genotype combinations related to high acetaldehyde accumulation were protective factors against alcohol abuse and ALC.


Asunto(s)
Alcoholismo , Masculino , Humanos , Alcoholismo/genética , Cirrosis Hepática Alcohólica/epidemiología , Cirrosis Hepática Alcohólica/genética , Vietnam/epidemiología , Aldehído Deshidrogenasa Mitocondrial/genética , Alcohol Deshidrogenasa/genética , Polimorfismo de Nucleótido Simple , Genotipo , Acetaldehído , Aldehído Deshidrogenasa/genética , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/genética
20.
Ann Med Surg (Lond) ; 85(5): 1358-1365, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37228979

RESUMEN

The aim of this study was to determine the accuracy of two-dimensional and three-dimensional transesophageal echocardiography (TEE) in the detection of pannus and thrombus in left mechanical valve obstruction (LMVO) compared with surgical and histopathology findings. Materials and methods: Patients with suspected LMVO on transthoracic echocardiography were enrolled consecutively. All patients underwent two-dimensional and three-dimensional TEE, and open-heart surgery to replace obstructed valves. Macroscopic and microscopic analysis of the excised masses was used as the gold standard for the diagnosis of thrombus and/or pannus. Results: Forty-eight patients [34 women (70.8%), age 49±13 years, New York Heart Association II: 68.8%, New York Heart Association III: 31.2%] were enrolled. In the diagnostic of thrombus, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of three-dimensional TEE were 89.2, 72.7, 85.4, 91.7, and 66.7%, respectively, compared with those of two-dimensional TEE (42.2, 66.7, 43.8, 95, and 7.1%, respectively). In the diagnosis of pannus, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of three-dimensional TEE were 53.3, 100, 85.4, 100, and 82.5%, respectively; compared with those of two-dimensional TEE (7.4, 90.5, 43.8, 50, and 43.2%, respectively). Receiver operating characteristic curves depict that the area under the curves of three-dimensional TEE was higher than the area under the curves of two-dimensional TEE in both diagnoses of thrombus and pannus (0.8560 vs. 0.7330, P=0.0427 and 0.8077 vs. 0.5484, P=0.005, respectively). Conclusions: This study indicated that three-dimensional TEE had a higher diagnostic value than two-dimensional TEE in the detection of thrombus and pannus in patients with LMVO, and can be a reliable imaging modality to identify the causes of LMVO.

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