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1.
Cell ; 182(5): 1328-1340.e13, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32814014

RESUMO

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.


Assuntos
Variação Genética/genética , Doenças Transmitidas por Carrapatos/microbiologia , Carrapatos/genética , Animais , Linhagem Celular , Vetores de Doenças , Especificidade de Hospedeiro/genética
2.
Proc Natl Acad Sci U S A ; 121(24): e2321619121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38833475

RESUMO

Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat-ACE2), where powered flight and bat-coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat-ACE2 and its mutant (AncBat-ACE2-mut) created by replacing the positively selected sites. Compared to AncBat-ACE2-mut, AncBat-ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.


Assuntos
Enzima de Conversão de Angiotensina 2 , Quirópteros , Seleção Genética , Quirópteros/virologia , Quirópteros/genética , Animais , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Camundongos , Pleiotropia Genética , Evolução Molecular , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/genética , Coronavirus/genética , Humanos , Filogenia
3.
Plant Cell ; 35(5): 1593-1616, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36695476

RESUMO

High salinity, an adverse environmental factor affecting about 20% of irrigated arable land worldwide, inhibits plant growth and development by causing oxidative stress, damaging cellular components, and disturbing global metabolism. However, whether and how reactive oxygen species disturb the metabolism of salt-stressed plants remain elusive. Here, we report that salt-induced hydrogen peroxide (H2O2) inhibits the activity of plastid triose phosphate isomerase (pdTPI) to promote methylglyoxal (MG) accumulation and stimulates the sulfenylation of pdTPI at cysteine 74. We also show that MG is a key factor limiting the plant growth, as a decrease in MG levels completely rescued the stunted growth and repressed salt stress tolerance of the pdtpi mutant. Furthermore, targeting CATALASE 2 into chloroplasts to prevent salt-induced overaccumulation of H2O2 conferred salt stress tolerance, revealing a role for chloroplastic H2O2 in salt-caused plant damage. In addition, we demonstrate that the H2O2-mediated accumulation of MG in turn induces H2O2 production, thus forming a regulatory loop that further inhibits the pdTPI activity in salt-stressed plants. Our findings, therefore, illustrate how salt stress induces MG production to inhibit the plant growth.


Assuntos
Peróxido de Hidrogênio , Aldeído Pirúvico , Peróxido de Hidrogênio/metabolismo , Aldeído Pirúvico/metabolismo , Estresse Salino , Estresse Oxidativo , Plantas/metabolismo , Cloroplastos/metabolismo , Estresse Fisiológico
4.
Nature ; 583(7815): 282-285, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32218527

RESUMO

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.


Assuntos
Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Eutérios/virologia , Evolução Molecular , Genoma Viral/genética , Homologia de Sequência do Ácido Nucleico , Sequência de Aminoácidos , Animais , Betacoronavirus/química , Betacoronavirus/classificação , COVID-19 , China/epidemiologia , Quirópteros/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Genômica , Humanos , Malásia , Pandemias , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Recombinação Genética , SARS-CoV-2 , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Zoonoses/virologia
5.
Mol Ther ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734897

RESUMO

Altered branched chain amino acids (BCAAs), including leucine, isoleucine, and valine, are frequently observed in patients with advanced cancer. We evaluated the efficacy of chimeric antigen receptor (CAR) T cell-mediated cancer cell lysis potential in the immune microenvironment of BCAA supplementation and deletion. BCAA supplementation increased cancer cell killing percentage, while accelerating BCAA catabolism and decreasing BCAA transporter decreased cancer cell lysis efficacy. We thus designed BCKDK engineering CAR T cells for the reprogramming of BCAA metabolism in the tumor microenvironment based on the genotype and phenotype modification. BCKDK overexpression (OE) in CAR-T cells significantly improved cancer cell lysis, while BCKDK knockout (KO) resulted in inferior lysis potential. In an in vivo experiment, BCKDK-OE CAR-T cell treatment significantly prolonged the survival of mice bearing NALM6-GL cancer cells, with the differentiation of central memory cells and an increasing proportion of CAR-T cells in the peripheral circulation. BCKDK-KO CAR-T cell treatment resulted in shorter survival and a decreasing percentage of CAR-T cells in the peripheral circulation. In conclusion, BCKDK-engineered CAR-T cells exert a distinct phenotype for superior anticancer efficiency.

6.
Nucleic Acids Res ; 51(2): 619-630, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36546827

RESUMO

Jasmonic acid (JA) signaling plays a pivotal role in plant development and defense. MYC2 is a master transcription factor in JA signaling, and was found to be phosphorylated and negatively regulated by MAP kinase and receptor-like kinase. However, the kinases that positively regulate MYC2 through phosphorylation and promote MYC2-mediated activation of JA response have not been identified. Here, we identified CK2 as a kinase that phosphorylates MYC2 and thus regulates the JA signaling. CK2 holoenzyme can interact with MYC2 using its regulatory subunits and phosphorylate MYC2 at multiple sites with its catalytic subunits. Inhibition of CK2 activity in a dominant-negative plant line, CK2mut, repressed JA response. On the other hand, increasing CK2 activity by overexpression of CKB4, a regulatory subunit gene of CK2, enhanced JA response in a MYC2-dependent manner. Substitution of the Ser and Thr residues at phosphorylation sites of MYC2 by CK2 with Ala impaired MYC2 function in activating JA response. Further investigations evidenced that CK2 facilitated the JA-induced increase of MYC2 binding to the promoters of JA-responsive genes in vivo. Our study demonstrated that CK2 plays a positive role in JA signaling, and reveals a previously undiscovered mechanism that regulates MYC2 function.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Caseína Quinase II , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Fosfotransferases/genética , Caseína Quinase II/metabolismo
7.
J Cell Mol Med ; 28(11): e18462, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847478

RESUMO

Osteosarcoma (OS) is the most common primary malignant bone tumour in children and young adults. Account for 80% of all OS cases, conventional OS are characterized by the presence of osteoblastic, chondroblastic and fibroblastic cell types. Despite this heterogeneity, therapeutic treatment and prognosis of OS are essentially the same for all OS subtypes. Here, we report that DEC2, a transcriptional repressor, is expressed at higher levels in chondroblastic OS compared with osteoblastic OS. This difference suggests that DEC2 is disproportionately involved in the progression of chondroblastic OS, and thus, DEC2 may represent a possible molecular target for treating this type of OS. In the human chondroblastic-like OS cell line MNNG/HOS, we found that overexpression of DEC2 affects the proliferation of the cells by activating the VEGFC/VEGFR2 signalling pathway. Enhanced expression of DEC2 increased VEGFR2 expression, as well as increased the phosphorylation levels at sites Y951 and Y1175 of VEGFR2. On the one hand, activation of VEGFR2Y1175 enhanced cell proliferation through VEGFR2Y1175-PLCγ1-PKC-SPHK-MEK-ERK signalling. On the other hand, activation of VEGFR2Y951 decreased mitochondria-dependent apoptosis rate through VEGFR2Y951-VARP-PI3K-AKT signalling. Activation of these two signalling pathways resulted in enhanced progression of chondroblastic OS. In conclusion, DEC2 plays a pivotal role in cell proliferation and apoptosis-resistance in chondroblastic OS via the VEGFC/VEGFR2 signalling pathway. These findings lay the groundwork for developing focused treatments that target specific types of OS.


Assuntos
Neoplasias Ósseas , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Osteossarcoma , Transdução de Sinais , Fator C de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteossarcoma/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/genética , Animais , Apoptose/genética , Fosforilação
8.
Plant J ; 114(6): 1369-1384, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36948886

RESUMO

Hydrogen sulfide (H2 S) promotes plant tolerance against various environmental cues, and d-cysteine desulfhydrase (DCD) is an enzymatic source of H2 S to enhance abiotic stress resistance. However, the role of DCD-mediated H2 S production in root growth under abiotic stress remains to be further elucidated. Here, we report that DCD-mediated H2 S production alleviates osmotic stress-mediated root growth inhibition by promoting auxin homeostasis. Osmotic stress up-regulated DCD gene transcript and DCD protein levels and thus H2 S production in roots. When subjected to osmotic stress, a dcd mutant showed more severe root growth inhibition, whereas the transgenic lines DCDox overexpressing DCD exhibited less sensitivity to osmotic stress in terms of longer root compared to the wild-type. Moreover, osmotic stress inhibited root growth through repressing auxin signaling, whereas H2 S treatment significantly alleviated osmotic stress-mediated inhibition of auxin. Under osmotic stress, auxin accumulation was increased in DCDox but decreased in dcd mutant. H2 S promoted auxin biosynthesis gene expression and auxin efflux carrier PIN-FORMED 1 (PIN1) protein level under osmotic stress. Taken together, our results reveal that mannitol-induced DCD and H2 S in roots promote auxin homeostasis, contributing to alleviating the inhibition of root growth under osmotic stress.


Assuntos
Proteínas de Arabidopsis , Sulfeto de Hidrogênio , Sulfeto de Hidrogênio/metabolismo , Raízes de Plantas/metabolismo , Pressão Osmótica , Homeostase , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
9.
Basic Res Cardiol ; 119(3): 349-369, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38683371

RESUMO

Heart failure continues to be a significant global health concern, causing substantial morbidity and mortality. The limited ability of the adult heart to regenerate has posed challenges in finding effective treatments for cardiac pathologies. While various medications and surgical interventions have been used to improve cardiac function, they are not able to address the extensive loss of functioning cardiomyocytes that occurs during cardiac injury. As a result, there is growing interest in understanding how the cell cycle is regulated and exploring the potential for stimulating cardiomyocyte proliferation as a means of promoting heart regeneration. This review aims to provide an overview of current knowledge on cell cycle regulation and mechanisms underlying cardiomyocyte proliferation in cases of heart failure, while also highlighting established and novel therapeutic strategies targeting this area for treatment purposes.


Assuntos
Ciclo Celular , Proliferação de Células , Insuficiência Cardíaca , Miócitos Cardíacos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Humanos , Animais , Regeneração
10.
Microb Pathog ; 187: 106513, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38147968

RESUMO

Since pseudorabies (PR) re-emerged and rapidly spread in China at the end of 2011, researchers have focused on effective vaccine strategies to prevent and control pseudorabies virus (PRV) infection in pig herds. Due to the extensive application of an attenuated vaccine based on the Bartha-K61 strain isolated in Hungary in 1961 and the variation of the PRV strain, it has been suggested that traditional vaccines based on the Bartha-K61 strain offer only partial protection against variant strains. It was therefore evaluated whether the Porcilis® Begonia vaccine, which is based on the NIA-3 strain with deletions in the gE and TK genes, is efficacious against experimental infection with the virulent, contemporary Chinese PRV strain ZJ01. In this study, piglets were vaccinated with Porcilis® Begonia through either the intradermal (ID) route or the intramuscular (IM) route and subsequently challenged intranasally with strain ZJ01 at 4 weeks post-vaccination. An unvaccinated challenge group and an unvaccinated/nonchallenged group were also included in the study. All animals were monitored for 14 days after challenge. Vaccinated and negative control pigs stayed healthy during the study, while the unvaccinated control animals developed lesions associated with PRV ZJ01 challenge, and 44% of these pigs died before the end of the experiment. This study demonstrated that ID or IM vaccination of pigs with a vaccine based on the NIA-3 strain Porcilis® Begonia clinically protects against fatal PRV challenge with the ZJ01 strain.


Assuntos
Begoniaceae , Herpesvirus Suídeo 1 , Doenças dos Suínos , Vacinas Virais , Suínos , Animais , Herpesvirus Suídeo 1/genética , Vacinas contra Pseudorraiva , Anticorpos Antivirais , Vacinação/veterinária , Vacinas Virais/genética
11.
Respir Res ; 25(1): 139, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521900

RESUMO

BACKGROUND: DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are "non-atopic", lacking a clear etiology. METHODS: In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman's rank correlation coefficients, multiple logistic regression, and multinomial logistic regression. RESULTS: Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified. CONCLUSION: The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.


Assuntos
Asma , Diabetes Mellitus Tipo 2 , Dietilexilftalato , Dietilexilftalato/análogos & derivados , Hipertensão , Ácidos Ftálicos , Adulto , Animais , Humanos , Dietilexilftalato/toxicidade , Dietilexilftalato/urina , Exposição Ambiental , Estudos de Casos e Controles , Asma/induzido quimicamente , Asma/diagnóstico , Asma/epidemiologia , Citocinas
12.
Hum Genomics ; 17(1): 69, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491351

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding. METHODS: The SNEEP (SNP exploration and analysis using epigenomics data) pipeline was used to identify regulatory SNPs, which alter the binding behavior of TFs and link GWAS SNPs to their potential target genes for six CVDs. The human-induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. Gene expression, cardiomyocyte size and cardiac contractility were assessed. RESULTS: By using our integrative computational pipeline, we identified 1905 regulatory SNPs in CVD GWAS data. These were associated with hundreds of genes, half of them non-coding RNAs (ncRNAs), suggesting novel CVD genes. We experimentally tested 40 CVD-associated non-coding RNAs, among them RP11-98F14.11, RPL23AP92, IGBP1P1, and CTD-2383I20.1, which were upregulated in hiPSC-CMs, MCOs and SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued expression of hypertrophic marker genes, reduced hypoxia-induced cardiomyocyte size and improved hypoxia-reduced cardiac contractility in hiPSC-CMs and MCOs. CONCLUSIONS: IGBP1P1 is a novel ncRNA with key regulatory functions in modulating cardiomyocyte size and cardiac function in our disease models. Our data suggest ncRNA IGBP1P1 as a potential therapeutic target to improve cardiac function in CVDs.


Assuntos
Doenças Cardiovasculares , Polimorfismo de Nucleotídeo Único , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estudo de Associação Genômica Ampla , Doenças Cardiovasculares/genética , Genômica , Genoma
13.
Artigo em Inglês | MEDLINE | ID: mdl-38658222

RESUMO

BACKGROUND AND AIMS: We aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk. METHODS AND RESULTS: Using data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non-MAFLD, overweight/obese (OW-MAFLD), lean/normal weight (lean-MAFLD) and diabetes (DM-MAFLD) groups. Among the participants with a median follow-up of 2.17 years, 4511 (37.2%) participants had MAFLD at baseline, among which 3954 (87.7%), 123 (2.7%), and 434 (9.6%) were OW-, lean- and DM-MAFLD, respectively. Analyses using linear regression models confirmed that compared with the non-MAFLD group, the elevated baPWV change rates (cm/s/year) were 12.87 (8.81-16.94), 25.33 (7.84-42.83) and 38.49 (27.88-49.10) in OW, lean and DM-MAFLD, respectively, while the increased change proportions (%) were 1.53 (1.10-1.95), 3.56 (1.72-5.40) and 3.94 (2.82-5.05), respectively. Similar patterns were observed when these two baPWV parameters were transformed in the form of the greatest increase using Cox proportional hazards model analyses. Furthermore, the risk of arterial stiffness progression across MAFLD subtypes presented a significant, gradient, inverse relationship in the order of DM-, lean-, OW with metabolic abnormalities (MA)-, and OW without MA-MAFLD. CONCLUSION: MAFLD, especially DM-MAFLD and lean-MAFLD, was significantly associated with arterial stiffness progression, providing evidence that stratification screening and surveillance strategies for CVD risk have important clinical implications.

14.
BMC Psychiatry ; 24(1): 370, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755597

RESUMO

BACKGROUND: Borderline personality traits play a significant role in nonsuicidal self-injury (NSSI), particularly in depressed youths. NSSI is also highly correlated with negative life events. This research aimed to explore the connections between negative life events, borderline personality traits, and NSSI. METHODS: The study included 338 depressed youth aged 13 to 25 years. Self-reported measures and clinical interviews were utilized to evaluate the depressive symptoms, borderline personality traits, negative life events, and NSSI behaviours of these participants. Identifying variables linked to NSSI was the aim of our analysis, and we also conducted a mediation analysis to look into the influence of borderline traits on the connection between negative life events and NSSI. RESULTS: Of the 338 depressed youth, approximately 59.47% (201/338) displayed NSSI, which was associated with greater clinical severity. Borderline traits had an independent influence on NSSI and it partially explained the connection between negative life events and NSSI, even when accounting for depression symptoms. Depressed youth who were more vulnerable to NSSI behaviours often experienced negative life events such as interpersonal relationships, academic pressure, being punished, and loss. CONCLUSIONS: Our research suggests that depressed youth who experience more negative life events are more likely to experience NSSI, and negative life events indirectly influence nonsuicidal self-injury through borderline personality traits. Implementing interventions focused on mitigating borderline symptoms could be a promising therapeutic approach for addressing NSSI in young people.


Assuntos
Transtorno da Personalidade Borderline , Comportamento Autodestrutivo , Humanos , Comportamento Autodestrutivo/psicologia , Adolescente , Transtorno da Personalidade Borderline/psicologia , Feminino , Masculino , Adulto Jovem , Adulto , Depressão/psicologia , Acontecimentos que Mudam a Vida
15.
BMC Psychiatry ; 24(1): 351, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730360

RESUMO

BACKGROUND: Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. METHODS: The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. RESULTS: The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P < 0.05). In females, BMI [AUC = 0.468], LAP [AUC = 0.468], and TyG index [AUC = 0.466] were weak predictors of depressive symptoms during the long-term (P < 0.05). However, ABSI cannot predict depressive symptoms in males and females during both periods (P > 0.05). CONCLUSION: The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.


Assuntos
Depressão , Obesidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Obesidade/epidemiologia , Depressão/epidemiologia , Depressão/sangue , Idoso , Estudos Longitudinais , Fatores de Risco , Índice de Massa Corporal , Lipídeos/sangue , Circunferência da Cintura , População do Leste Asiático
16.
Platelets ; 35(1): 2315037, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38372252

RESUMO

Glycosylation is a ubiquitous cellular or microenvironment-specific post-translational modification that occurs on the surface of normal cells and tumor cells. Tumor cell-associated glycosylation is involved in hematogenous metastasis. A wide variety of tumors undergo aberrant glycosylation to interact with platelets. As platelets have many opportunities to engage circulating tumor cells, they represent an important avenue into understanding the role glycosylation plays in tumor metastasis. Platelet involvement in tumor metastasis is evidenced by observations that platelets protect tumor cells from damaging shear forces and immune system attack, aid metastasis through the endothelium at specific sites, and facilitate tumor survival and colonization. During platelet-tumor-cell interactions, many opportunities for glycan-ligand binding emerge. This review integrates the latest information about glycans, their ligands, and how they mediate platelet-tumor interactions. We also discuss adaptive changes that tumors undergo upon glycan-lectin binding and the impact glycans have on targeted therapeutic strategies for treating tumors in clinical settings.


Tumor hematogenous metastasis is a serious threat to the survival and prognosis of patients, and a variety of factors help this process to occur, and platelets are also involved. During tumor cell metastasis, platelets can adhere to each other and tumor cells, a phenomenon that leads to the immunity of tumor cells from various threats in metastasis, including immune attacks, shearing forces, etc. Scientists have shown that the adhesion effect between platelets and tumor cells is often dependent on various types of sugars, which are not the sugars we ingest. These sugars often appear as glycosylation modifications on the proteins of the cells, including normal glycosylation modifications and some abnormal structures that only appear on tumor cells, and their ligands, lectins, are also present on the surface of the tumor cells or platelets. Their combination results in the better adaptation of tumor cells to the metastatic process, where proteins such as P-selectin, CLEC-2, and Galectins have been more studied. Focusing on Glycan-Lectin interactions between platelets and tumor cells, related studies help us to further understand tumor metastasis, and intervene in this binding and develop related drugs with great potential.


Assuntos
Lectinas , Neoplasias , Humanos , Lectinas/metabolismo , Neoplasias/patologia , Polissacarídeos/metabolismo , Plaquetas/metabolismo , Glicosilação , Metástase Neoplásica/patologia , Microambiente Tumoral
17.
J Nanobiotechnology ; 22(1): 360, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907233

RESUMO

Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs' function by CE-sEVs.


Assuntos
Vesículas Extracelulares , Neoplasias Pulmonares , Osteossarcoma , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Camundongos Endogâmicos BALB C , Saponinas/farmacologia , Camundongos Nus , Movimento Celular/efeitos dos fármacos , Pulmão/patologia
18.
BMC Geriatr ; 24(1): 77, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245677

RESUMO

OBJECTIVE: Hypertension refers to the persistent elevation of blood pressure above the established normal range, resulting in increased pressure exerted by blood on the walls of blood vessels during its circulation. Recent studies have identified significant associations between obesity and lipid-related indices, as well as hypertension. Nevertheless, these studies have yet to comprehensively examine the correlation between the two variables. Our objective is to identify the fat and lipid-related indices that have the strongest correlation with hypertension. METHOD: There was a total of 9488 elderly and middle-aged Chinese citizens who participated in this investigation. The participants in this research were separated into distinct gender cohorts. The participants were classified into normal and hypertensive categories according to their gender, with hypertension defined as a blood pressure level of 140/90 mmHg or higher, or a history of hypertension. Through the utilization of binary logistic regression analyses and the receiver operator curve (ROC), the optimal among fourteen indicators associated with obesity and lipids were identified. RESULTS: After adjusting for variables, statistical analysis showed that all 14 measures of obesity and lipid were risk factors for hypertension. The receiver operating characteristic (ROC) curve analysis reveals that the Chinese visceral adiposity index (CVAI) has the highest degree of relationship to hypertension. Simultaneously, a statistically significant association between hypertension and these 14 variables was observed in both males and females. CONCLUSION: There was a significant independent association between various parameters related to obesity and lipid-related index and the presence of hypertension, indicating that these factors can be considered risk factors for hypertension. CVAI and WHtR (waist height ratio) can be used to screen the high-risk groups of hypertensions in middle-aged and elderly people in China, and then take individualized health care measures to reduce the harm of hypertension.


Assuntos
Hipertensão , Obesidade , Idoso , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Índice de Massa Corporal , Obesidade/diagnóstico , Obesidade/epidemiologia , Fatores de Risco , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Obesidade Abdominal , Lipídeos , China/epidemiologia
19.
Chem Biodivers ; 21(2): e202301949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326086

RESUMO

Five new iridoids, valeralides A-E (1-5), two new acyclic monoterpenoids, valeralides F (6) and G (7), together with two known iridoids (8 and 9), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated based on 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The absolute configuration of compounds 1-4 were elucidated based on electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their inhibition on nitric oxide production, cytotoxicity and anti-influenza A virus activity.


Assuntos
Rizoma , Valeriana , Estrutura Molecular , Valeriana/química , Iridoides/química , Monoterpenos/análise , Raízes de Plantas/química
20.
BMC Med Educ ; 24(1): 118, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321409

RESUMO

BACKGROUND: Nurses play an important role in healthcare development. The increasing demands for nurses mean that nursing schools at the undergraduate level have the responsibility to ensure patient safety and quality care through a well-designed curriculum. This research aimed to evaluate the effect of the teaching method combined with situational awareness and case-based seminars in a comprehensive nursing skills practice course on the level of self-directed learning, professional identity, academic self-efficacy, theoretical scores, practical scores, teaching satisfaction, and student competence among nursing students. METHODS: The research population comprised was of the grades of 2019 and 2020 at Wannan Medical College in Anhui Province, China (n = 169, response rate 77.88%). The observation group from grade 2020 used the teaching method combined with situational awareness and case-based seminars, whereas the control group from grade 2019 used the traditional teaching mode. General information, self-directed learning, a professional identity, and academic self-efficacy were compared between the two groups. This research used means and standard deviations, chi-square, the Shapiro-Wilk test, and an independent sample t-test for statistical analyses. RESULTS: Compared with the control group, the total scores for self-directed learning, professional identity, and academic self-efficacy were higher in the observation group (78.80 ± 7.89 vs 60.21 ± 7.44, 63.39 ± 7.87 vs 52.35 ± 7.68, and 22.31 ± 3.30 vs 21.28 ± 2.31, respectively, with P < 0.05 for all scores). More significant improvements were made in the observation group on the level of theoretical scores (81.39 ± 3.32 vs 76.28 ± 5.90) and practical scores (93.32 ± 4.70 vs 90.67 ± 5.09) (P < 0.05). Meanwhile, teaching satisfaction, which includes teaching method (66/18 vs 32/53) and teacher-student interaction (72/12 vs 34/51), and student competence, which includes team cooperation (67/17 vs 39/46), critical thinking (60/24 vs 31/54), and communication skills (67/17 vs 38/47) after the intervention (P < 0.05). There was no significant difference in social persuasion (P > 0.05). CONCLUSION: The teaching method combined with situational awareness and case-based seminars in a comprehensive nursing skills practice course has the potential to improve the level of self-directed learning, professional identity, and academic self-efficacy, and it increases theoretical scores, practical scores, teaching satisfaction, and student competence.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Conscientização , Bacharelado em Enfermagem/métodos , Aprendizagem , Currículo
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