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1.
Sci Immunol ; 9(99): eadl3755, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303017

RESUMEN

Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased TFH responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of TFH priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.


Asunto(s)
Centro Germinal , Inmunidad Humoral , Centro Germinal/inmunología , Animales , Inmunidad Humoral/inmunología , Ratones , Femenino , Vacunas contra el SIDA/inmunología , Vacunas contra el SIDA/administración & dosificación , Ratones Endogámicos C57BL , Linfocitos B/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación
2.
J Med Signals Sens ; 14: 13, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100741

RESUMEN

The employees who work in infection prevention and control (IPC) are very important in the field of health-care because they are committed to protecting patients, staff, and visitors from the risk of acquiring infections while in the hospital. The complexity of infection control in hospitals is alwaysgrowing in tandem with the rapid developments that are being made in medical technology andpractices. IPC personnel are required to maintain vigilance and continually improve their monitoringof the entire health-care process due to the ongoing development of IPC guidelines and regulations, the fluctuating infection risks, and the emergence of new infectious diseases. As a result, individuals involved in the prevention and control of infections in health-care settings absolutely need to participate in continual training and professional development. This reviewemphasizes the need of relevant professionals to engage in ongoing training and professional development to maintain their skills in the area of healthcare-associated infection control and prevention. Personnel working in IPC may more effectively react to newly discovered health risks andmake certain that hospital infection (HI) management gets the appropriate attention if they have atimely and in-depth awareness of best practices. They are better able to maintain their composure, react correctly, and deliver the most effective infection control and prevention techniques for the health-care system, all while increasing awareness about the significance of effective HI management.

3.
bioRxiv ; 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-39005274

RESUMEN

Immunotherapies such as checkpoint inhibitors (CPI) are effective in treating several advanced cancers, but these treatments have had limited success in metastatic ovarian cancer (OC). Here, we engineered liposomal nanoparticles (NPs) carrying a layer-by-layer (LbL) polymer coating that promotes their binding to the surface of OC cells. Covalent anchoring of the potent immunostimulatory cytokine interleukin-12 (IL-12) to phospholipid headgroups of the liposome core enabled the LbL particles to concentrate IL-12 in disseminated OC tumors following intraperitoneal administration. Shedding of the LbL coating and serum protein-mediated extraction of IL-12-conjugated lipids from the liposomal core over time enabled IL-12 to disseminate in the tumor bed following rapid NP localization in tumor nodules. Optimized IL-12 LbL-NPs promoted robust T cell accumulation in ascites and tumors in mouse models, extending survival compared to free IL-12 and remarkedly sensitizing tumors to CPI, leading to curative treatments and immune memory.

4.
Sci Rep ; 14(1): 17045, 2024 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048616

RESUMEN

This study aimed to investigate the relationship between various prevention and control measures for nosocomial infections (NIs) in psychiatric hospitals and patients with mental disorders. This study aimed to determine the characteristics of NIs in psychiatric hospitals and provide a reference for infection prevention and control in this setting. Data from the NI monitoring system of a psychiatric hospital in southeastern China were analysed. Patients who were hospitalized for mental disorders from January 1, 2016, to November 30, 2019, were classified into the non-COVID-19 containment group (NC19C group, n = 898), while those who were hospitalized from January 25, 2020, to November 30, 2022, were classified into the COVID-19 containment group (C19C group, n = 840). The data were analysed using SPSS version 22.0, and independent sample t tests, chi-square tests, correlation analyses, and multivariate logistic regression analyses were performed. A significance level of P < 0.0024 was applied. The incidence rate of NIs was higher in autumn in the NC19C group, while no seasonal difference was detected in the C19C group (P < 0.0024). Further analysis revealed that in the C19C group, the risk of hospitalized patients with mental disorders developing hospital-acquired pneumonia in spring was 0.362 times that in winter (OR = 0.362, 95% CI = 0.200 ~ 0.656, P = 0.001), and in summer, the risk was 0.342 times that in winter (OR = 0.342, 95% CI = 0.185 ~ 0.633 P = 0.001). Patients aged 18-44 years had a 4.260 times higher risk of developing hospital-acquired upper respiratory tract infections than did those aged 60 years and older (OR = 4.260, 95% CI = 2.143 ~ 8.470; P = 0.000). The risk of acquiring urinary tract infections in the hospital was 0.324 times greater among patients aged 18-44 years than for patients aged 60 years and older (OR = 0.324, 95% CI = 0.171-0.613; P = 0.001). The NC19C group did not exhibit the aforementioned differences. During the NC19C period, differences were observed in the diagnosis of hospital-acquired infections and sex (all P = 0.000). Psychiatric hospitals exhibit distinct nosocomial infection characteristics under the context of various infection control measures. Against the backdrop of strengthened infection control, the nosocomial infection characteristics of psychiatric hospitals may be associated with the features of mental disorders.


Asunto(s)
COVID-19 , Infección Hospitalaria , Hospitales Psiquiátricos , Estaciones del Año , Humanos , China/epidemiología , Masculino , Femenino , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , COVID-19/epidemiología , COVID-19/prevención & control , Trastornos Mentales/epidemiología , Control de Infecciones/métodos , Anciano , Incidencia , Adolescente , Adulto Joven
5.
Dev Cell ; 59(16): 2254-2269.e6, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39053471

RESUMEN

Symbiotic nodules comprise two classes, indeterminate and determinate, defined by the presence/absence of apical meristem and developmental zonation. Why meristem and zonation are absent from determinate nodules remains unclear. Here, we define cell types in developing soybean nodules, highlighting the undifferentiated infection zones and differentiated nitrogen-fixation zones. Auxin governs infection zone maintenance. GRETCHEN HAGEN 3 (GH3) enzymes deactivate auxin by conjugation and promote cell differentiation. gh3 mutants increased undifferentiated cells and enlarged infection zones. The central symbiosis-transcription factor NIN2a activates GH3.1 to reduce auxin levels and facilitates cell differentiation. High auxin promotes NIN2a protein accumulation and enhances signaling, further deactivating auxin and depleting infection zones. Our findings shed light on the NIN2a-GH3-auxin module that drives soybean nodule cell differentiation. This study challenges our understanding of determinate nodule development and proposes that the regulation of nodule zonation offers valuable insights into broader mechanisms of cell differentiation across plant species.


Asunto(s)
Diferenciación Celular , Regulación de la Expresión Génica de las Plantas , Glycine max , Homeostasis , Ácidos Indolacéticos , Proteínas de Plantas , Nódulos de las Raíces de las Plantas , Transducción de Señal , Simbiosis , Glycine max/metabolismo , Glycine max/genética , Glycine max/crecimiento & desarrollo , Ácidos Indolacéticos/metabolismo , Nódulos de las Raíces de las Plantas/metabolismo , Nódulos de las Raíces de las Plantas/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Fijación del Nitrógeno
6.
Front Psychiatry ; 15: 1284559, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903641

RESUMEN

Objective: To explore the insight, treatment attitude, and related influencing factors of hospitalized elderly patients suffering from major depression. Methods: A total of 141 hospitalized elderly patients with depression were selected as the research objects. Insight was evaluated by the total score of the Insight and Treatment Attitude questionnaire (ITAQ). The data collected included sociodemographic characteristics, psychiatric symptoms, delirium status, social functioning, social support, suicide risk, and cognitive function. Results: The sample included 74.5% of female patients, and the mean age was 67.53 (sd=7.19) years. The influencing factors of inpatients with depression included alcohol consumption, length of hospitalization, admission types, and the main caregivers (P<0.05). The various factors were further analyzed by linear regression, revealing that the insight and treatment attitude of elderly depressed hospitalized patients were mainly related to the Mini-Mental State Examination (MMSE) (ß= 0.225, 95% CI 0.055-0.395, P=0.01), dependent on a caregiver (ß=-5.810, 95% CI -8.086~-3.535, P<0.001), the type of admission (involuntary admission) (ß=-3.365, 95% CI -5.448~-1.283, P=0.002), Functional Activities Questionnaire (FAQ) (ß=-0.156, 95% CI -0.303~-0.010, P=0.037), and length of stay (≤28 days) (ß=2.272, 95% CI 0.055~-4.489, P=0.045). Conclusion: The level of insight was affected by cognitive function, involuntary admission, dependent on a caregiver, social function and length of stay. Future studies should focus on cognitive function recovery, observation of admission mode, and self-care ability in elderly patients with depression.

7.
J Adv Res ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38879123

RESUMEN

INTRODUCTION: The interplay between influential factors and the incidence of subthreshold depression (SD) in young adults remains poorly understood. OBJECTIVES: This study sought to understand the dietary habits, gut microbiota composition, etc. among individuals with SD in young adults and to investigate their association with SD occurrence. METHODS: Employing a cross-sectional approach, 178 individuals with SD, aged 18-32 years, were matched with 114 healthy counterparts. SD status was evaluated using the Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Beck Depression Inventory 2nd version (BDI-II), the 17-item Hamilton Rating Scales of Depression (HAMD-17), and Pittsburgh Sleep Quality Index (PSQI). Metagenomic sequencing was utilized to identify fecal microbial profiles. Dietary patterns were discerned via factor analysis of a 25-item food frequency questionnaire (FFQ). Logistic regression analysis and mediation analysis were performed to explore the potential links between gut microbiota, dietary patterns, and incident SD. RESULTS: Data on dietary habits were available for 292 participants (mean [SD] age, 22.1 [2.9] years; 216 [73.9 %] female). Logistic regression analysis revealed that dietary patterns Ⅰ (odds ratio [OR], 0.34; 95 % CI, 0.15-0.75) and IV (OR, 0.39; 95 % CI, 0.17-0.86 and OR, 0.39; 95 % CI, 0.18-0.84) were associated with reduced risk of SD. Distinct microbial profiles were observed in young adults with SD, marked by increased microbial diversity and taxonomic alterations. Moreover, mediation analysis suggested Veillonella atypica as a potential mediator linking SDS or BDI-II scores with a healthy dietary pattern rich in bean products, coarse grains, nuts, fruits, mushrooms, and potatoes (ß = 0.25, 95 % CI: 0.02-0.78 and ß = 0.18, 95 % CI: 0.01-0.54). CONCLUSIONS: Our findings highlight the complex interplay between dietary patterns, gut microbiota, and the risk of developing SD in young adults, underscoring the potential for dietary interventions and microbiome modulation in mental health promotion.

8.
Alpha Psychiatry ; 25(1): 1-8, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38799491

RESUMEN

Objective: This study aims to assess the efficacy of mindfulness-based cognitive therapy (MBCT) in alleviating depression in older adults. Methods: A comprehensive search was conducted in 4 electronic databases and 1 registered database from inception up to July 2021 to identify relevant trials. The meta-analysis employed Hedge's g, along with its 95% CI, and associated z and P-values for the included studies, utilizing Comprehensive Meta-Analysis software. Results: Qualitative synthesis was performed on 5 eligible studies. Evaluation of methodological quality and bias risk across the papers involved scrutiny of key variables due to the heterogeneous research formats. Our findings indicated a significant moderating effect of MBCT against current depressive symptoms in older adults (g = 0.53, 95% Confidence Intervals (CI) = 0.31-0.75) and a similar effect size for anxiety (g = 0.43, 95% CI = 0.20-0.65). However, caution is warranted due to the limited number of studies and potential publication bias. Further extensive research with longer follow-up measures and larger sample sizes is essential. Conclusion: This study underscores the effectiveness of MBCT as a treatment for anxiety and despair in older individuals. Mindfulness-based cognitive therapy should be recommended for its positive impact on older adults with depression, and the involvement of authorized psychiatric nurses is crucial for conducting successful MBCT interventions. However, caution is warranted due to the limited number of studies and potential publication bias. Further extensive research with longer follow-up measures and larger sample sizes is essential.

9.
Discov Med ; 36(182): 581-590, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38531798

RESUMEN

BACKGROUND: Phentolamine is an α-adrenergic receptor blocker that can be used to treat neonatal pneumonia, but its underlying mechanism is unclear. The purpose of this study is to probe the function of phentolamine on lipopolysaccharide (LPS)-induced inflammation and cell death in an in vitro model of neonatal pneumonia. METHODS: Human MRC-5 cells were incubated with varying doses of phentolamine in vitro to evaluate cell viability. Subsequently, LPS was introduced to further investigate the combined effects of phentolamine and LPS on cell viability and apoptosis in MRC-5 cells. The effect of phentolamine/LPS treatment on the Neurotrophic Tyrosine Kinase Receptor A (TrkA)/Protein Kinase B (Akt) signaling pathway and the phosphorylation of pathway proteins in MRC-5 cells was further analyzed via western blot. Additionally, knockout of TrkA and Akt genes in MRC-5 cells was performed to explore the effects of phentolamine/LPS treatment on cell viability, apoptosis levels, and inflammatory factor levels in MRC-5 cells. RESULTS: Preincubation of MRC-5 cells with a low concentration of phentolamine (≤6 µg/mL) protected against LPS-induced cell inflammatory injury. Phentolamine promoted both TrkA and Akt phosphorylation and Akt activation induced by LPS in MRC-5 cells. The protective effect of phentolamine against LPS-induced apoptosis and inflammation was significantly reduced in response to TrkA or Akt gene knockdown in MRC-5 cells. CONCLUSIONS: Phentolamine may protect LPS-induced apoptosis and inflammation by activating the TrkA and Akt signaling pathways.


Asunto(s)
Lipopolisacáridos , Neumonía , Recién Nacido , Humanos , Lipopolisacáridos/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/farmacología , Fentolamina/farmacología , Transducción de Señal , Inflamación/metabolismo , Apoptosis
10.
BMJ Open ; 14(2): e079218, 2024 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326262

RESUMEN

INTRODUCTION: Patient-reported outcomes (PROs) are health reports that come directly from the patients themselves and represented the experience and insights of the patient's perspective on the impact of the intervention. PROs were increasingly emphasised in acupuncture randomised controlled trials (RCTs). However, the reporting quality of PROs in acupuncture RCTs has not been investigated to date. Therefore, we constructed this study to reveal the basic characteristics and reporting quality of PROs in acupuncture RCTs, and explore the relationship between concealment, blinding and RROs. We hope our findings can provide guidance for the reporting standards and future development of PROs in acupuncture RCTs in reverse. METHODS AND ANALYSIS: RCTs using acupuncture treatment as the intervention and PROs as primary outcomes or secondary outcomes will be systematically searched through seven databases MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP between 1 January 2012 and 15 October 2022. The basic characteristics, concealment, blinding design and the characteristics of PROs in included RCTs will be summarised. The reporting quality of PROs will be assessed based on the CONSORT PRO extension. Logistic analysis will be performed to identify the association between concealment, blinding and RROs. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework (OSF) Registries. The findings of this study will be submitted to a peer-reviewed academic journal.


Asunto(s)
Terapia por Acupuntura , Humanos , Estudios Transversales , Terapia por Acupuntura/métodos , Estándares de Referencia , Medición de Resultados Informados por el Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto
11.
Int J Nurs Stud ; 150: 104649, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38070229

RESUMEN

BACKGROUND: Although swallowing exercises are a fundamental treatment for dysphagia, few studies have evaluated the effectiveness of swallowing training in patients with Alzheimer's disease. METHODS: We recruited 93 patients with Alzheimer's disease from three hospitals in Guangdong, China. This was a parallel armed randomized controlled trial that randomly assigned patients to intervention (n = 48) and control (n = 45) groups. The intervention group adopted systematic stepwise swallowing training for four weeks based on routine dysphagia care. The control group implemented routine dysphagia care, including diet and posture management and health education about swallowing dysfunction. The swallowing function was the primary outcome, which was assessed using the Water Swallowing Test and Standard Swallowing Assessment. An abnormal eating behavior questionnaire was used to assess the incidence of aberrant eating behavior in patients with Alzheimer's disease. The Mini-Nutritional Assessment Short Form and Barthel index were adopted to evaluate the nutritional status and ability to carry out daily activities between groups. SPSS software was used to perform the chi-square test, t-test, and generalized estimation equation for data analysis. RESULTS: We analyzed the effects of the stepwise swallowing training program using the generalized estimating equation method. The intervention group exhibited greater improvements in their swallowing function (Water Swallowing Test: ß = -3.133, 95 % CI: -4.113, -2.154, P < 0.001; Standard Swallowing Assessment: ß = -5.813, 95 % CI: -7.782, -3.844, P < 0.001), abnormal eating behaviors (abnormal eating behavior questionnaire: ß = -13.324, 95 % CI: -21.643, -5.005, P = 0.002), daily function (Barthel index: ß = 11.280, 95 % CI: 4.021, 18.540, P = 0.002), and nutritional status (Mini-Nutritional Assessment Short Form: ß = 2.402, 95 % CI: 1.313, 3.490, P < 0.001) over time than the routine-care group in the fourth week. CONCLUSIONS: Stepwise swallowing training is a safe and effective intervention for managing dysphagia and other related symptoms in patients with Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Trastornos de Deglución , Humanos , Deglución , Trastornos de Deglución/terapia , Trastornos de Deglución/diagnóstico , Estado Nutricional , Agua
12.
bioRxiv ; 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38045401

RESUMEN

"Extended priming" immunization regimens that prolong exposure of the immune system to vaccines during the primary immune response have shown promise in enhancing humoral immune responses to a variety of subunit vaccines in preclinical models. We previously showed that escalating-dosing immunization (EDI), where a vaccine is dosed every other day in an increasing pattern over 2 weeks dramatically amplifies humoral immune responses. But such a dosing regimen is impractical for prophylactic vaccines. We hypothesized that simpler dosing regimens might replicate key elements of the immune response triggered by EDI. Here we explored "reduced ED" immunization regimens, assessing the impact of varying the number of injections, dose levels, and dosing intervals during EDI. Using a stabilized HIV Env trimer as a model antigen combined with a potent saponin adjuvant, we found that a two-shot extended-prime regimen consisting of immunization with 20% of a given vaccine dose followed by a second shot with the remaining 80% of the dose 7 days later resulted in increased total GC B cells, 5-10-fold increased frequencies of antigen-specific GC B cells, and 10-fold increases in serum antibody titers compared to single bolus immunization. Computational modeling of the GC response suggested that this enhanced response is mediated by antigen delivered in the second dose being captured more efficiently as immune complexes in follicles, predictions we verified experimentally. Our computational and experimental results also highlight how properly designed reduced ED protocols enhance activation and antigen loading of dendritic cells and activation of T helper cells to amplify humoral responses. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.

13.
Neuropsychobiology ; 82(5): 271-286, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37640020

RESUMEN

INTRODUCTION: Clozapine-induced sialorrhea (CIS) is one of the most common side effects of clozapine use, while the mechanism remains unclear. METHODS: A total of 51 schizophrenia patients taking clozapine were selected. Among them, 32 had sialorrhea, and 19 had no sialorrhea. Saliva metabolites were identified using ultra-high-performance liquid chromatography-MS/MS (UHPLC-MS/MS), and the differences in saliva metabolites in each group were analyzed through qualitatively searching HMDB, KEGG, and self-built databases, combined with multivariate statistics. After further evaluation by receiver-operating characteristic curve (ROC) analysis, the screened differential metabolites were enriched and topologically analyzed. RESULTS: The biomarkers potentially related to CIS included 37 differential metabolites involving 17 metabolic pathways, mainly histidine metabolism (p < 0.05, impact = 0.50), pyrimidine metabolism (p < 0.05, impact = 0.08), and ß-alanine metabolism (p < 0.05, impact = 0.06). CONCLUSION: Our study indicates that histidine metabolic pathway may contribute to the mechanism of CIS.


Asunto(s)
Antipsicóticos , Clozapina , Sialorrea , Humanos , Clozapina/efectos adversos , Sialorrea/inducido químicamente , Sialorrea/tratamiento farmacológico , Antipsicóticos/efectos adversos , Histidina/efectos adversos , Espectrometría de Masas en Tándem , Redes y Vías Metabólicas , Biomarcadores
14.
J Biomol Struct Dyn ; : 1-16, 2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37632305

RESUMEN

Danzhi-xiaoyao-San (DZXYS), a Traditional Chinese Medicine, plays an essential role in the clinical treatment of depression, but its mechanisms in humans remain unclear. To investigate its pharmacological effects and mechanisms as an add-on therapy for depression, we conducted a double-blind, placebo-controlled trial with depressed patients receiving selective serotonin reuptake inhibitors (SSRIs). Serum and fecal samples were collected for metabolomic and microbiome analysis using UHPLC-QTRAP-MS/MS and 16S rRNA gene sequencing technologies, respectively. Depression symptoms were assessed using the 24-item Hamilton Depression Scale. We employed network pharmacology, metabolomics, and molecular docking to identify potential targets associated with DZXYS. We also examined the correlation between gut microbes and metabolites to understand how DZXYS affects the microbiota-gut-brain axis. The results showed that DZXYS combined with SSRIs was more effective than SSRIs alone in improving depression. We identified 39 differential metabolites associated with DZXYS treatment and found seven upregulated metabolic pathways. The active ingredients quercetin and luteolin were docked to targets (AVPR2, EGFR, F2, and CDK6) associated with the enriched pathways 'pancreatic cancer' and 'phospholipase D signaling pathway', which included the metabolite lysophosphatidic acid [LPA(0:0/16:0)]. Additionally, we identified 32 differential gut microbiota species related to DZXYS treatment, with Bacteroides coprophilus and Ruminococcus gnavus showing negative correlations with specific metabolites such as L-2-aminobutyric acid and LPA(0:0/16:0). Our findings indicate that DZXYS's antidepressant mechanisms involve multiple targets, pathways, and the regulation of LPA and the microbiota-gut-brain axis. These insights from our systems pharmacology analysis contribute to a better understanding of DZXYS's potential pharmacological mechanisms in depression treatment.Communicated by Ramaswamy H. Sarma.


HIGHLIGHTSThis study presents a double-blind, randomized, placebo-controlled clinical trial comparing the clinical effects of Danzhi-xiaoyao-San (DZXYS) plus selective serotonin reuptake inhibitors (SSRIs) and SSRIs alone.This study is the first system pharmacology approach to integrate multi-omics and network pharmacology and examine the clinical pharmacological mechanisms of DZXYS as an add-on therapy for depression.This study highlights that regulation of lysophosphatidic acid (LPA) and the microbiota-gut-brain axis by DZXYS plays an essential role in its antidepressant mechanisms.

15.
Sci Total Environ ; 897: 165449, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37437642

RESUMEN

Profound growth differences such as seedling length and biomass are often observed during the cultivation of Sargassum fusiforme despite the absence of detectable variance in abiotic factors that could have affected this process. This highlights the importance of biotic factors such as epiphytic microbiota in controlling seedling growth. Yet, how, and to what extent microbial activities can affect host growth in the presence of seawater flow and continuous erosion remains debatable. Particularly, the contribution of microbial network interactions to the growth of macroalgae remains poorly understood. This study aimed to compare the physicochemical properties of S. fusiforme seedlings via 16S rRNA gene Illumina sequencing-based profiling of the epiphytic microbial communities of seedlings with different lengths. Significantly different epiphytic bacterial communities were observed among S. fusiforme seedlings of different lengths. The result showed that community from longer seedlings maintained higher bacterial diversity with the taxa Gammaproteobacteria, Burkholderiales, Alteromonadales, Vibrionaceae, Ralstonia, Colwelliaceae, and Thalassotalea being selectively enriched. More importantly, microbial interspecific interactions, which were predominantly positive, were enhanced consistently in communities of the longer seedlings, indicative of reinforced prevalent and mutually cooperative relationships among the microorganisms associated with S. fusiforme seedlings of greater length. Furthermore, longer seedlings also displayed up-regulation of microbial functional potentials involved in N fixation and mineralization, P mineralization and transportation, and ion transportation compared with shorter ones. Lastly, stochastic processes dominated the community assembly of the epiphytic microorganisms. These findings could provide new insights into the relationship between microbial communities and growth in S. fusiforme seedlings and enable us to predict the community diversity and assembly of macroalgae-associated microbial communities. This could have important implications for linking microbial community diversity and network interactions to their host productivity.


Asunto(s)
Microbiota , Sargassum , Algas Marinas , ARN Ribosómico 16S/genética , Bacterias , Plantones/genética
16.
Nat Biomed Eng ; 7(9): 1113-1128, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37291434

RESUMEN

The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cells with a CAR specific for fluorescein isothiocyanate (FITC) can be directed against solid tumours via the intratumoural administration of a FITC-conjugated lipid-poly(ethylene)-glycol amphiphile that inserts itself into cell membranes. In syngeneic and human tumour xenografts in mice, 'amphiphile tagging' of tumour cells drove tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours. In syngeneic tumours, the therapy induced the infiltration of host T cells, elicited endogenous tumour-specific T cell priming and led to activity against distal untreated tumours and to protection against tumour rechallenge. Membrane-inserting ligands for specific CARs may facilitate the development of adoptive cell therapies that work independently of antigen expression and of tissue of origin.


Asunto(s)
Neoplasias , Humanos , Ratones , Animales , Fluoresceína-5-Isotiocianato/metabolismo , Ligandos , Linfocitos T , Inmunoterapia Adoptiva
17.
BMJ Open ; 13(6): e070545, 2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37344108

RESUMEN

INTRODUCTION: Randomised controlled trials (RCTs) play an important role in evidence-based medicine. However, an article with low reporting quality may mislead both experts and the general public into an erroneous decision. Data sharing can contribute to the truthfulness and transparency of trials. Acupuncture RCTs have been increasing rapidly these years, but the reporting quality and data-sharing level of acupuncture RCTs are not clear. Thus, this study will provide the current status of the reporting quality and data-sharing level of acupuncture RCTs. METHODS AND ANALYSIS: A cross-sectional study will be conducted. The seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang Database and VIP will be searched between 1 January 2012 and 15 October 2022 to identify acupuncture RCTs. The basic characteristics of included trials will be summarised. The reporting quality for included RCTs will be assessed by the Consolidated Standards for Reporting Trials 2010 statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture. The data-sharing level will be assessed by open science practices. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework Registries. The findings of this study will be submitted to a peer-reviewed academic journal.


Asunto(s)
Terapia por Acupuntura , Humanos , Estudios Transversales , MEDLINE , Bases de Datos Factuales , Estándares de Referencia , Proyectos de Investigación , Ensayos Clínicos Controlados Aleatorios como Asunto
18.
Plant Physiol ; 192(3): 2243-2260, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37010107

RESUMEN

The primary cell wall is a fundamental plant constituent that is flexible but sufficiently rigid to support the plant cell shape. Although many studies have demonstrated that reactive oxygen species (ROS) serve as important signaling messengers to modify the cell wall structure and affect cellular growth, the regulatory mechanism underlying the spatial-temporal regulation of ROS activity for cell wall maintenance remains largely unclear. Here, we demonstrate the role of the Arabidopsis (Arabidopsis thaliana) multicopper oxidase-like protein skewed 5 (SKU5) and its homolog SKU5-similar 1 (SKS1) in root cell wall formation through modulating ROS homeostasis. Loss of SKU5 and SKS1 function resulted in aberrant division planes, protruding cell walls, ectopic deposition of iron, and reduced nicotinamide adeninedinucleotide phosphate (NADPH) oxidase-dependent ROS overproduction in the root epidermis-cortex and cortex-endodermis junctions. A decrease in ROS level or inhibition of NADPH oxidase activity rescued the cell wall defects of sku5 sks1 double mutants. SKU5 and SKS1 proteins were activated by iron treatment, and iron over-accumulated in the walls between the root epidermis and cortex cell layers of sku5 sks1. The glycosylphosphatidylinositol-anchored motif was crucial for membrane association and functionality of SKU5 and SKS1. Overall, our results identified SKU5 and SKS1 as regulators of ROS at the cell surface for regulation of cell wall structure and root cell growth.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Pared Celular , Raíces de Plantas , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pared Celular/metabolismo , Hierro/metabolismo , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Oxidación-Reducción , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo
19.
J Biophotonics ; 16(9): e202200390, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37099397

RESUMEN

BACKGROUND: To investigate the alterations in the retinal vasculature and microstructure in dry-type high myopia. METHODS: One hundred and eighty-nine dry-type high myopia eyes were classified into three groups. Group 1 consisted of 86 eyes with no myopic retinal degenerative lesion (C0). Group 2 consisted of 71 eyes with tessellated fundus (C1). Group 3 consisted of 32 eyes with diffuse chorioretinal atrophy (C2). Retinal vascular density and retinal thickness were measured with optical coherence tomography angiography. The scanning area was a 3 × 3 mm2 ring with the fovea of the macular. All data were analyzed with the SPSS 23.0 by one-way ANOVA test among comparison groups. Pearson's correlation analysis was used to determine the relations among measurements. Univariate linear regression showed a correlation between the vascular densities and retinal thicknesses. RESULTS: The microvessel density significantly decreased and significant thinning of the superior and temporal macular thickness in the C2 group. The vascular densities of macular decreased significantly with the increase of axial length (AL) and refractive diopter in the C2 group. The retinal thicknesses of the macular fovea increased significantly with the increase of vascular densities in the C0 group and C1 group. CONCLUSIONS: The impairment of retinal microstructure is more likely related to reduced oxygen and nutrients due to microvessel density decreases.


Asunto(s)
Miopía , Humanos , Miopía/diagnóstico por imagen , Miopía/patología , Retina/patología , Vasos Retinianos/diagnóstico por imagen , Fondo de Ojo , Microvasos/diagnóstico por imagen
20.
BMC Psychiatry ; 22(1): 800, 2022 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-36536383

RESUMEN

The domestic health care system has been facing a difficult task, especially in medical care, and Chinese nurses are under tremendous psychological pressure. Psychological support is a protective factor to relieve stress. This study examined the stress level and characteristics of Chinese nurses with different psychological support-seeking behaviours. Data from online questionnaires for this cross-sectional study were collected between January 2020 and February 2020 and yielded 2248 valid questionnaires for analysis with a response rate of 99.8%. General information of the respondents was also collected. The nurses' stress levels were assessed using the Perceived Stress Scale (PSS-10). T tests, chi-square tests, and linear regression were used to examine the relationships among the factors. The results of this survey showed that between January and February 2020, 26.9% of nurses received psychological counselling, and the proportion was higher among men and nurses with lower education. The PSS-10 was related to gender, age group, provincial severity, and confidence in the control of the epidemic. The results showed that psychological support can effectively improve the confidence of domestic nurses in the face of arduous work and effectively relieve the psychological pressure caused by a heavy workload.


Asunto(s)
Enfermeras y Enfermeros , Salud Pública , Masculino , Humanos , Estudios Transversales , Pueblos del Este de Asia , Estrés Psicológico/epidemiología , Consejo , Encuestas y Cuestionarios
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