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OBJECTIVE: There is ongoing debate regarding the association between epilepsy and obesity. Thus, the aim of this study was to examine the correlation between epilepsy and obesity. METHOD: This study adhered to the PRISMA guidelines for systematic reviews and meta-analyses. On The Prospero website, this study has been successfully registered (CRD42023439530), searching electronic databases from the Cochr-ane Library, PubMed, Web of Sciences and Embase until February 10, 2024.The search keywords included "Epilepsy", "Obesity", "Case-Control Studies", "cohort studies", "Randomized Controlled Trial" and "Cross-Sectional Studies". The medical subject headings(MeSH) of PubMed was utilized to search for relevant subject words and free words, and a comprehensive search strategy was developed. Two reviewers conducted article screening, data extraction and bias risk assessment in strict accordance with the predefined criteria for including and excluding studies. The predefined inclusion criteria were as follows: 1) Inclusion of case-control, cohort, randomized controlled trial, and cross-sectional studies; 2) Segregation of subjects into epileptic patients and healthy controls; 3)Obesity as the outcome measure; 4) Availability of comprehensive data; 5) Publication in English. The exclusion criteria were as follows: 1) Exclusion of animal experiments, reviews, and other types of studies; 2) Absence of a healthy control group; 3) Incomplete data; 4) Unextractable or unconvertible data; 5) Low quality, indicated by an Agency for Healthcare Research and Quality(AHRQ) score of 5 or lower,or a Newcastle-Ottawa Scale (NOS) score less than 3. The subjects included in the study included adults and children, and the diagnostic criteria for obesity were used at different ages. In this study, obesity was defined as having a body mass index(BMI) of 25 kg/m2 or higher in adults and being above the 85th percentile of BMI for age in children. We used obesity as an outcome measure for meta-analysis using RevMan, version 5.3. RESULTS: A meta-analysis was conducted on a total of 17 clinical studies, which involved 5329 patients with epilepsy and 480837 healthy controls. These studies were selected from a pool of 1497 articles obtained from four electronic databases mentioned earlier. Duplicate studies were removed based on the search strategies employed. No significant heterogeneity was observed in the outcome measure of obesity in epileptic patients compared with healthy controls(p = 0.01,I2 = 49%). Therefore, a fixed effects model was utilized in this study. The findings revealed a significant difference in obesity prevalence between patients with epilepsy and healthy controls(OR = 1.28, 95%CI: 1.20-1.38, p<0.01). CONCLUSION: The results of this meta-analysis indicate that epilepsy patients are more prone to obesity than healthy people, so we need to pay attention to the problem of post-epilepsy obesity clinically. Currently, there is a scarcity of largescale prospective studies. Additional clinical investigations are warranted to delve deeper into whether obesity is a comorbidity of epilepsy and whether obesity can potentially trigger epilepsy.
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Epilepsia , Obesidad , Humanos , Obesidad/complicaciones , Estudios de Casos y ControlesRESUMEN
Regulatory T (Treg) cells play a key role in maintaining immune tolerance and tissue homeostasis. However, in some disease microenvironments, Treg cells exhibit fragility, which manifests as preserved FoxP3 expression accompanied by inflammation and loss of immunosuppression. Fragile Treg cells are formatively, phenotypically and functionally diverse in various diseases, further complicating the role of Treg cells in the immunotherapeutic response and offering novel targets for disease treatment by modulating specific Treg subsets. In this review, we summarize findings on fragile Treg cells to provide a framework for characterizing the formation and role of fragile Treg cells in different diseases, and we discuss how this information may guide the development of more specific Treg-targeted immunotherapies.
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Homeostasis , Linfocitos T Reguladores , Humanos , Linfocitos T Reguladores/inmunología , Animales , Homeostasis/inmunología , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/inmunología , InmunoterapiaRESUMEN
Immunosuppression is a major hallmark of tumor progression in non-small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro-tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di-methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di-methylation of CD147 at Lys148 (CD147-K148me2) is identified as a common post-translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147-K148me2. Further analysis demonstrates that CD147-K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38-ZBTB32 signaling, leading to increased NSCLC cell-derived CCL5 secretion. Subsequently, CD147-K148me2-mediated CCL5 upregulation facilitates M2-like tumor-associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis-dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147-K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147-K148me2-driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM-targeted NSCLC therapy.
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Basigina , Carcinoma de Pulmón de Células no Pequeñas , Quimiocina CCL5 , Neoplasias Pulmonares , Receptores CCR5 , Microambiente Tumoral , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Basigina/metabolismo , Basigina/genética , Ratones , Animales , Receptores CCR5/metabolismo , Receptores CCR5/genética , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Microambiente Tumoral/inmunología , Macrófagos/metabolismo , Macrófagos/inmunología , Línea Celular Tumoral , Terapia de Inmunosupresión , Modelos Animales de Enfermedad , Transducción de SeñalRESUMEN
BACKGROUND: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes. AIM: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. METHODS: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort (n = 309) and validation cohort (n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year. RESULTS: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development. CONCLUSION: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.
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Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Humanos , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/complicaciones , Biomarcadores , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Receptor Activador Expresado en Células Mieloides 1RESUMEN
BACKGROUND: The potential pathogenic mechanism of idiopathic pulmonary fibrosis is widely recognized to involve immune dysregulation. However, the current pool of studies has yet to establish a unanimous agreement regarding the correlation between various types of immune cells and IPF. METHODS: By conducting a two-sample Mendelian randomization analysis using publicly available genetic data, the study examined the causal relationship between IPF and 731 immune cells. To ensure the reliability of the results, combined sensitivity analyses and inverse Mendelian analyses were conducted. Moreover, within subgroups, multivariate Mendelian randomization analyses were utilized to investigate the autonomous causal connection between immune cell characteristics and IPF. RESULTS: After adjusting for false discovery rate, it was discovered that 20 immunophenotypes exhibited a significant association with IPF. After subgrouping for multivariate Mendelian randomization analysis, there were six immunophenotypes that remained significantly associated with IPF. These included CD33 + HLA DR + CD14dim (OR = 0.96, 95% CI 0.93-0.99, P = 0.033), HLA DR + NK (OR = 0.92, 95% CI 0.85-0.98, P = 0.017), CD39 + CD8 + T cell %T cell (OR = 0.93, 95% CI 0.88-0.99, P = 0.024), CD3 on activated & secreting Treg (OR = 0.91, 95% CI 0.84-0.98, P = 0.026), PDL-1 on CD14- CD16 + monocyte (OR = 0.89, 95% CI 0.84-0.95, P = 8 × 10-4), and CD45 on CD33 + HLA DR + CD14- (OR = 1.08, 95% CI 1.01-1.15, P = 0.011). CONCLUSION: Our study reveals a noteworthy association between IPF and various immune cells, providing valuable insights for clinical research and aiding the advancement of immunologically-based therapeutic strategies.
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Fibrosis Pulmonar Idiopática , Análisis de la Aleatorización Mendeliana , Humanos , Reproducibilidad de los Resultados , Fibrosis Pulmonar Idiopática/genética , Linfocitos T CD8-positivos , Antígenos HLA-DR , Estudio de Asociación del Genoma CompletoRESUMEN
This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.
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Tumores Neuroendocrinos , Neoplasias del Recto , Humanos , Endosonografía , Relevancia Clínica , Tumores Neuroendocrinos/patología , Neoplasias del Recto/patología , Recto/diagnóstico por imagen , Recto/patologíaRESUMEN
OBJECTIVE: To investigate the expression of the precursor of brain-derived neurotrophic factor (proBDNF) and its high-affinity receptor p75NTR in neurons of emotion-related brain areas (prefrontal cortex, hippocampus, and amygdala) in rats with post-stroke depression (PSD), and to explore the expression levels of proBDNF and p75NTR in neurons of emotion-related brain areas by injecting tissue plasminogen activator (t-PA) into the lateral ventricle of PSD rats, this significantly improved the stress-induced depression-like behavior,thus further validating the above results. METHODS: Rats were randomly divided into four groups: a normal control group (n = 8), a depression group (n = 8), a stroke group (n = 8), and a PSD group (n = 8). The rat model of stroke was established by thread embolism, and the PSD animal model was induced by chronic unpredictable mild stress (CUMS) and solitary feeding. Behavioral tests were conducted, including weight measurement, open field tests, and sucrose preference tests. Immunofluorescence double labeling was used to detect the expression of proBDNF and p75NTR in neurons of emotion-related brain regions in the PSD rat model. Four weeks after CUMS treatment, the PSD group was selected. Rats were infused with t-PA (3 µg dissolved in 6 µL saline, Boehringer Ingelheim), proBDNF (3 µg dissolved in 6 µL saline, Abcam), or equal-volume NS once per day for 7 consecutive days using the syringe pump connecting to injection needles. After 7 days of continuous administration, animal behavior was assessed through scoring, and the expression of proBDNF and p75NTR in the emotion-related brain regions of the PSD rat model was detected using immunofluorescence double labeling. RESULTS: Compared with the normal control group and the stroke group, the body weight, sucrose water consumption, and vertical movement distance in the PSD group were significantly lower (P < 0.05). In contrast, when compared with the proBDNF injection group and saline injection group, the weight, sucrose water consumption, field horizontal movement, and vertical movement distance of the t-PA injection group significantly increased after PSD lateral ventricle intubation.Double immunofluorescence revealed a higher neuronal expression of proBDNF as well as p75NTR in the prefrontal cortex and hippocampus of PSD rats compared to control animals (P < 0.05). In the amygdala, the expression levels of proBDNF and P75NTR were significantly reduced in the PSD group compared to the control group (P < 0.05). The results of the expression levels of proBDNF and P75NTR in the emotion-related brain regions of PSD rats injected with t-PA showed that proBDNF and P75NTR was significantly reduced in the prefrontal cortex, hippocampus, and amygdala of PSD rats compared to those of the NS and proBDNF groups (P < 0.05). CONCLUSIONS: The increased expression of the brain-derived neurotrophic factor precursor proBDNF and its receptor p75NTR in neurons of emotion-related brain regions may play an important role in the pathogenesis of PSD.t-PA reduced the expression of proBDNF and its receptor p75NTR in neurons emotion-related brain regions and significantly improved the stress-induced depression-like behavior. Therefore, it is reasonable to assume that exogenous injection of t-PA may alleviate the depressive symptoms of PSD patients.Reducing the expression of proBDNF by injecting t-PA may provide a novel therapeutic approach for the treatment of stress-related mood disorders.
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Factor Neurotrófico Derivado del Encéfalo , Depresión , Receptor de Factor de Crecimiento Nervioso , Accidente Cerebrovascular , Animales , Ratas , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/genética , Depresión/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Neuronas/metabolismo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/metabolismo , Sacarosa/metabolismo , Activador de Tejido Plasminógeno/uso terapéutico , Receptor de Factor de Crecimiento Nervioso/genética , Receptor de Factor de Crecimiento Nervioso/metabolismoRESUMEN
Glutamatergic neurons in ventral pallidum (VPGlu) were recently reported to mediate motivational and emotional behavior, but its role in opioid addiction still remains to be elucidated. In this study we investigated the function of VPGlu in the context-dependent heroin taking and seeking behavior in male rats under the ABA renewal paradigm. By use of cell-type-specific fiber photometry, we showed that the calcium activity of VPGlu were inhibited during heroin self-administration and context-induced relapse, but activated after extinction in a new context. The drug seeking behavior was accompanied by the decreased calcium signal of VPGlu. Chemogenetic manipulation of VPGlu bidirectionally regulated heroin taking and seeking behavior. Anterograde tracing showed that the lateral habenula, one of the epithalamic structures, was the major output region of VPGlu, and its neuronal activity was consistent with VPGlu in different phases of heroin addiction and contributed to the motivation for heroin. VPGlu axon terminals in LHb exhibited dynamic activity in different phases of heroin addiction. Activation of VPGlu-LHb circuit reduced heroin seeking behavior during context-induced relapse. Furthermore, the balance of excitation/inhibition from VP to LHb was shifted to enhanced glutamate transmission after extinction of heroin seeking motivation. Overall, the present study demonstrated that the activity of VPGlu was involved in the regulation of heroin addiction and identified the VPGlu-LHb pathway as a potential intervention to reduce heroin seeking motivation.
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Prosencéfalo Basal , Ácido Glutámico , Dependencia de Heroína , Neuronas , Ratas Sprague-Dawley , Animales , Masculino , Dependencia de Heroína/metabolismo , Dependencia de Heroína/psicología , Prosencéfalo Basal/metabolismo , Ácido Glutámico/metabolismo , Neuronas/metabolismo , Comportamiento de Búsqueda de Drogas , Heroína , Ratas , Autoadministración , Habénula/metabolismoRESUMEN
Severe combined immunodeficient (SCID) mice serve as a critical model for human xenotransplantation studies, yet they often suffer from low engraftment rates and susceptibility to graft-versus-host disease (GVHD). Moreover, certain SCID strains demonstrate 'immune leakage', underscoring the need for novel model development. Here, we introduce an SCID mouse model with a targeted disruption of the dclre1c gene, encoding Artemis, which is essential for V(D)J recombination and DNA repair during T cell receptor (TCR) and B cell receptor (BCR) assembly. Artemis deficiency precipitates a profound immunodeficiency syndrome, marked by radiosensitivity and compromised T and B lymphocyte functionality. Utilizing CRISPR/Cas9-mediated gene editing, we generated dclre1c-deficient mice with an NOD genetic background. These mice exhibited a radiosensitive SCID phenotype, with pronounced DNA damage and defective thymic, splenic and lymph node development, culminating in reduced T and B lymphocyte populations. Notably, both cell lines and patient-derived tumor xenografts were successfully engrafted into these mice. Furthermore, the human immune system was effectively rebuilt following peripheral blood mononuclear cells (PBMCs) transplantation. The dclre1c-knockout NOD mice described herein represent a promising addition to the armamentarium of models for xenotransplantation, offering a valuable platform for advancing human immunobiological research.
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Endonucleasas , Huésped Inmunocomprometido , Leucocitos Mononucleares , Proteínas Nucleares , Trasplante Heterólogo , Animales , Humanos , Ratones , Endonucleasas/genética , Xenoinjertos , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Mutación , Proteínas Nucleares/genética , Huésped Inmunocomprometido/genética , Modelos AnimalesRESUMEN
BACKGROUND: RNA interference (RNAi) is the sequence-dependent suppression of gene expression by double-stranded RNA (dsRNA). This is a promising strategy for the control of insect pests because dsRNA can be rationally designed to maximize efficacy and biosafety, the latter by using sequences that are found in target pests but are safe for non-target insects. However, this has yet to be optimized in aphids, destructive sap-sucking pests that also transmit plant viruses. We used the green peach aphid (Myzus persicae) as a case study to optimize the efficiency of RNAi by applying a novel fusion dsRNA design. RESULTS: Comparative transcriptomics revealed a number of genes that are induced in feeding aphids, and eight candidate genes were chosen as RNAi targets. To improve RNAi efficiency, our fusion dsRNA design approach combined optimal gene fragments (highly conserved in several aphid species but with less homology in beneficial insects such as the predator ladybeetle Propylea japonica) from three candidate genes. We compared this RNAi-based biological control approach with conventional chemical control using imidacloprid. We found that the fusion dsRNA strategy inhibited the aphid population to a significantly greater extent than single-target RNAi and did not affect ladybeetle fitness, allowing an additive effect between RNAi and natural predation, whereas imidacloprid was harmful to aphids and ladybeetles. CONCLUSION: Our fusion dsRNA design approach enhances the ability of RNAi to control aphids without harming natural predators. © 2024 Society of Chemical Industry.
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Áfidos , Interferencia de ARN , ARN Bicatenario , Áfidos/genética , Animales , ARN Bicatenario/genética , Escarabajos/genética , Control Biológico de Vectores/métodos , Control de Insectos/métodos , Neonicotinoides/farmacología , Nitrocompuestos/farmacologíaRESUMEN
To investigate the association of systemic inflammation index (SII) with psoriasis risk and psoriasis severity. This is a retrospective cohort study based on data from the National Health and Nutrition Examination Survey database from 2009 to 2014. The psoriasis information was obtained from the questionnaire data, and the SII was calculated as neutrophilâ ×â platelet/lymphocyte. We performed matching by controlling age and gender to reach a 1:2 ratio for better statistical power. Weighted logistic regression analysis, subgroup analysis, restricted cubic spline analysis, and threshold analysis were used to evaluate the association of SII with psoriasis risk. Besides, mediation analysis was conducted to assess the possible regulatory path. Finally, the receiver operating characteristic curve was plotted to analyze the predictive value of SII for psoriasis severity. The study involved 16,466 participants including 16,020 no-psoriasis participants and 446 psoriasis participants. After matching, psoriasis and non-psoriasis individuals were 446 and 892, respectively. SII was significantly higher in the psoriasis group than the non-psoriasis group (Pâ <â .05). Additionally, white blood cells and monocytes were significantly linked to psoriasis risk and SII scores (Pâ <â .05). Besides, SII elevation was an independent predictor for upregulated psoriasis risk (Pâ <â .05). There was a nonlinear relationship between SII and psoriasis risk (P nonlinearâ <â .05), which was not mediated by white blood cells and monocytes. Unexpectedly, SII had no significance in predicting SII severity (Pâ >â .05). SII can independently predict psoriasis risk but has no impact on psoriasis severity. Further, SII serves as a potential and robust biomarker for identifying high-risk psoriasis individuals.
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Plaquetas , Psoriasis , Humanos , Encuestas Nutricionales , Estudios Retrospectivos , Inflamación/epidemiología , Psoriasis/complicaciones , Psoriasis/epidemiologíaRESUMEN
Twisted van der Waals (vdW) quantum materials have emerged as a rapidly developing field of two-dimensional (2D) semiconductors. These materials establish a new central research area and provide a promising platform for studying quantum phenomena and investigating the engineering of novel optoelectronic properties such as single photon emission, nonlinear optical response, magnon physics, and topological superconductivity. These captivating electronic and optical properties result from, and can be tailored by, the interlayer coupling using moiré patterns formed by vertically stacking atomic layers with controlled angle misorientation or lattice mismatch. Their outstanding properties and the high degree of tunability position them as compelling building blocks for both compact quantum-enabled devices and classical optoelectronics. This paper offers a comprehensive review of recent advancements in the understanding and manipulation of twisted van der Waals structures and presents a survey of the state-of-the-art research on moiré superlattices, encompassing interdisciplinary interests. It delves into fundamental theories, synthesis and fabrication, and visualization techniques, and the wide range of novel physical phenomena exhibited by these structures, with a focus on their potential for practical device integration in applications ranging from quantum information to biosensors, and including classical optoelectronics such as modulators, light emitting diodes, lasers, and photodetectors. It highlights the unique ability of moiré superlattices to connect multiple disciplines, covering chemistry, electronics, optics, photonics, magnetism, topological and quantum physics. This comprehensive review provides a valuable resource for researchers interested in moiré superlattices, shedding light on their fundamental characteristics and their potential for transformative applications in various fields.
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Seven new pentasaccharides (1-7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1-9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri.
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Rehmannia , Humanos , Rehmannia/química , Línea Celular , Raíces de Plantas/químicaRESUMEN
Two new baccharane triterpenes, 17,24-epoxy-23-en-baccharan-3-one (1) and 17,24(S)-epoxy-25-en-21-hydroxy-baccharan-3-one (2) were isolated from Rhus chinensis Mill. The structures were established on the basis of UV, IR, HR-ESI-MS, 1D and 2D NMR spectroscopy and X-ray diffraction analysis.
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Rhus , Triterpenos , Triterpenos Pentacíclicos , Rhus/química , Triterpenos/farmacología , Triterpenos/química , Extractos Vegetales , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
INTRODUCTION: Accumulative evidence suggests the associations between systemic inflammatory regulators and chronic respiratory diseases (CRDs). However, the intrinsic causation remains implicit. Therefore, this study aimed to examine causative associations by mendelian randomization (MR) and to identify valuable active factors. METHODS: Based on data from the GWAS database, we performed MR analyses of 41 serum cytokines from 8,293 Finnish and European descent cohorts from GBMI and UKBB for five major CRDs. We mainly applied inverse variance weighted regression, supplemented by MR-Egger regression, weighted median, maximum likelihood, weighted mode, and simple mode algorithms. Moreover, sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept, MR-PRESSO Global test and MR-Steiger filtering. Eventually, the consistency of MR results was assessed by leave-one-out. RESULTS: Our results suggest that 12 genetically predicted systemic inflammatory regulators probably participate in the progression of CRDs, including four risk factors (IL-1RA, IL-4, MIP-1A, PDGF-BB) and one protective factor (IL-6) in IPF, two protective factors (SCF, SDF-1A) in COPD, and two protective factors (SCF, SDF-1A) in asthma, two protective factors (GROA, IL-2RA) were also included in asthma, whereas only one factor (HGF) was protective against bronchiectasis. Additionally, two protective factors (FGF-BASIC, G-CSF) were identified in sarcoidosis. Sensitivity analyses showed no horizontal pleiotropy and significant heterogeneity. Finally, based on the findings of inverse MR analysis, no inverse causal association was uncovered, confirming the robustness of results. CONCLUSION: Our study unearths potential associations between systemic inflammatory modulators and common CRDs, providing new insights for inflammation-mediated CRD prevention and therapeutic approaches.
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Asma , Bronquiectasia , Humanos , Distribución Aleatoria , Factores de Riesgo , Algoritmos , Estudio de Asociación del Genoma CompletoRESUMEN
Four new iridoid glycosides (1-4), rehmaglutosides L-O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1-6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri.
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Glicósidos , Rehmannia , Humanos , Glicósidos/farmacología , Glicósidos/química , Rehmannia/química , Glicósidos Iridoides/farmacologíaRESUMEN
Background: This mixed methods study identified needed refinements to a telehealth-delivered cultural and linguistic adaptation of Meaning-Centered Psychotherapy for Chinese patients with advanced cancer (MCP-Ch) to enhance acceptability, comprehensibility, and implementation of the intervention in usual care settings, guided by the Ecological Validity Model (EVM) and the Practical, Robust Implementation and Sustainability Model (PRISM). Methods: 15 purposively sampled mental health professionals who work with Chinese cancer patients completed surveys providing Likert-scale ratings on acceptability and comprehensibility of MCP-Ch content (guided by the EVM) and pre-implementation factors (guided by PRISM), followed by semi-structured interviews. Survey data were descriptively summarized and linked to qualitative interview data. Three analysts independently coded the transcripts according to EVM and PRISM domains; discrepancies were resolved through discussion and consensus. Results: Quantitative findings showed high appropriateness and relevance of MCP-Ch across five EVM domains of Language, Metaphors/Stories, Goals, Content, and Concepts. Qualitative analysis yielded 23 inductive codes under the seven EVM domains: (1) Language (3 subcodes), (2) Persons (2 subcodes), (3) Metaphors/Stories (2 subcodes), (4) Methods (8 subcodes), (5) Content (2 subcodes), (6) Goals (4 subcodes), and (7) Concepts (2 subcodes). Themes based on PRISM included (1) Intervention characteristics (organizational perspective, 7 subcodes; and patient perspective, 6 subcodes) (2) External environment (2 subcodes), (3) Implementation and sustainability infrastructure (4 subcodes), and (4) Recipients (organizational characteristics, 5 subcodes; and patient characteristics, 4 subcodes). Conclusion: Recommendations for next steps include increasing the MCP-Ch protocol's flexibility and adaptability to allow interventionists to flexibly tailor MCP-Ch material to meet patients' individual needs, simplifying content to improve comprehension and acceptability, providing additional training to Chinese-serving providers to increase adoption and sustainability, and considering interpreter-assisted delivery to increase access. Findings yielded important information to maximize cultural relevance as well as the implementation and sustainability potential of MCP-Ch in real-world settings.
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RNA interference (RNAi) is a promising tool for pest control and relies on sequence-specific gene silencing. Salivary proteins are cooperatively secreted into plants to guarantee the feeding of aphids; thus they have potential to develop as selective targets for RNAi-based pest control strategy. For this purpose, we firstly analyzed 18 salivary proteomes of various aphid species, and these salivary proteins can be mainly categorized into seven functional groups. Secondly, we created a work-flow for fusion dsRNA design that can target multiple genes but were selectively safe to beneficial insects. Based on this approach, seven fusion dsRNAs were designed to feed the green peach aphid, which induced a significant reduction in aphid fitness. Among them, ingestion of dsperoxidase induced the highest mortality in aphids, which was also significantly higher than that of traditional dsRNAs in targeting three peroxidases separately. In addition, dsperoxidase-fed green peach aphids triggered the highest H2O2 content of host plants as well as the attraction to natural enemies (ladybeetle and parasitic wasp) but repellent to other control aphids. Our results indicate that the fusion dsRNA design approach can improve aphid control capacity, and the fusion dsRNA targeting salivary protein-encoding genes can enhance the direct and indirect defenses of host plants, thus providing a new strategy for RNAi-based aphid control.
Asunto(s)
Áfidos , Animales , Interferencia de ARN , Áfidos/genética , Áfidos/metabolismo , Peróxido de Hidrógeno/metabolismo , Silenciador del Gen , ARN Bicatenario/genética , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/metabolismoRESUMEN
Objective: The purpose of this study was to investigate the correlation between the deposition of M-type phospholipase A2 receptor (PLA2R) in the kidney tissues of patients with idiopathic membranous nephropathy (IMN). Method: We enrolled a total of 61 patients diagnosed with IMN in the past 8 years who were admitted at the Jinjiang Municipal Hospital and the 2nd Affiliated Hospital of Fujian Medical University. PLA2R immunofluorescence was used to stain kidney tissues, and all patients were treated with steroid combined with immunosuppressive agents or conservative regimens. The duration of follow-up was more than 48 weeks. Based on the deposition of PLA2R in kidney tissues, we divided the patients into the PLA2R Positive group and the PLA2R Negative group. Further, patients with PLA2R-positive kidney tissues were divided into "1+", "2+", and "3+" groups based on the extent of their PLA2R deposition, and we compared the therapeutic outcomes of the various groups. Results: At week 12 of follow-up, the partial remission rate of kidney tissues in the PLA2R Negative group was significantly higher than that in the Positive group (P = 0.004). Among the various deposition groups with PLA2R-positive kidney tissues, the complete remission rate of the "2+" group was higher than that of the "3+" group at weeks 24, 36, and 48 of follow-up (P < 0.05). In IMN patients treated with a combination regimen of steroid and tacrolimus, the complete remission rate in kidney tissues of the PLA2R Negative group was higher than that of the Positive group at weeks 24 and 48 of follow-up (P < 0.05). Conclusion: The overall effective rate of treatment in kidney tissues of PLA2R-negative patients was higher than that in the kidney tissues of PLA2R-positive patients. The varied levels of PLA2R deposition in kidney tissues were related to the treatment outcomes of IMN, and those with lower PLA2R deposition levels had better outcomes.
RESUMEN
Bacterial diseases caused by Vibrio spp. are prevalent in aquaculture and can lead to high mortality rates among aquatic species and significant economic losses. With the increasing emergence of multidrug-resistant Vibrio strains, phage therapy is being explored as a potential alternative to antibiotics for biocontrol of infectious diseases. Here, a new lytic phage named vB_VhaS_R21Y (R21Y) was isolated against Vibrio harveyi BVH1 obtained from seawater from a scallop-farming area in Rongcheng, China. Its morphology, infection cycle, lytic profile, phage stability, and genetic features were characterized. Transmission electronic microscopy indicated that R21Y is siphovirus-like, comprising an icosahedral head (diameter 73.31 ± 2.09 nm) and long noncontractile tail (205.55 ± 0.75 nm). In a one-step growth experiment, R21Y had a 40-min latent period and a burst size of 35 phage particles per infected cell. R21Y was highly species-specific in the host range test and was relatively stable at pH 4-10 and 4-55 °C. Genomic analysis showed that R21Y is a double-stranded DNA virus with a genome size of 82,795 bp and GC content of 47.48%. Its high tolerance and lytic activity indicated that R21Y may be a candidate for phage therapy in controlling vibriosis in aquacultural systems.