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1.
Eur J Neurol ; : e16342, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757755

RESUMO

BACKGROUND AND PURPOSE: Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). METHODS: Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). CONCLUSIONS: Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

2.
Front Psychiatry ; 15: 1398669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736623

RESUMO

Objective: This study used latent profile analysis to explore the level of depression among US adults with obstructive sleep apnea hypopnea syndrome (OSAHS) symptoms and to identify different latent categories of depression to gain insight into the characteristic differences between these categories. Methods: The data of this study were obtained from the National Health and Nutrition Examination Survey (NHANES) database, and the subjects with OSAHS symptoms were aged 18 years and older. The latent profile analysis (LPA) method was used to fit the latent depression categories in subjects with OSAHS symptoms. The chi-square test, rank sum test, and binary logistic regression were used to analyze the influencing factors of depression subgroups in subjects with OSAHS symptoms. Results: Three latent profiles were identified: low-level (83.7%), moderate-level (14.5%) and high-level (1.8%) depression. The scores of 9 items in the high-level depression group were higher than those in the other two groups. Among them, item 4 "feeling tired or lack of energy" had the highest score in all categories. Conclusion: Depression in subjects with OSAHS symptoms can be divided into low-level, moderate-level and high-level depression. There are significant differences among different levels of depression in gender, marital status, PIR, BMI, smoking, general health condition, sleep duration and OSAHS symptom severity.

3.
ACS Omega ; 9(17): 19428-19439, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38708214

RESUMO

Tailings pond accidents frequently occur during an extended period, resulting in loss of life and property, wastage of resources, and environmental pollution. Relying on tailings pond engineering, this paper carried out sample particle fragmentation experiments and settling column experiments to explore the deposition distribution pattern of tailings in both horizontal and vertical directions as well as the impact of particle size distribution on the sedimentation stratification effect. The results show that the median particle size on the dry beach surface in the horizontal direction slowly decreased with the increase in the distance from the subdam. The particle size of tailings showed great fluctuations in the vertical direction, which gradually became finer with the increase in the depth overall. At the same time, saturated sedimentation experiments suggested the inconsistent variation rule with the field test, namely, coarse on the bottom and fine at the top, and the change in particle size greatly affected the tailing sedimentation stratification effect. With the increase in fine particle content in tailings, the appearance time of the water-sand interface was shortened to within 30 min, but the sedimentation and consolidation completion times were delayed to about 1400 min. The settling column results indicate that the increase in fine particle content gradually weakened the sedimentation stratification effect, and the sedimentation pattern transformed from independent sedimentation to floc-type average sedimentation, which led to the enhanced water-retaining property of the settled layer. This may lead to an increase in the saturation line and a decrease in the length of the dry beach, seriously affecting the safe operation of the tailings pond. The research results provide some theoretical guidance and basic data for analyzing the consolidation efficiency of tailings and the stability of the tailings pond.

4.
J Phys Chem B ; 128(19): 4621-4630, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38697651

RESUMO

Thymine DNA glycosylase (TDG)-mediated excision of 5-formylcytosine and 5-carboxylcytosine (5-caC) is a critical step in active DNA demethylation. Herein, we employed a combined quantum mechanics/molecular mechanics approach to investigate the reaction mechanism of TDG-catalyzed N-glycosidic bond cleavage of 5-caC. The calculated results show that TDG-catalyzed 5-caC excision follows a concerted (SN2) mechanism in which glycosidic bond dissociation is coupled with nucleophile attack. Protonation of the 5-caC anion contributes to the cleavage of the N-glycoside bond, in which the N3-protonated zwitterion and imino tautomers are more favorable than carboxyl-protonated amino tautomers. This is consistent with the experimental data. Furthermore, our results reveal that the configuration rearrangement process of the protonated 5-caC would lower the stability of the N-glycoside bond and substantially reduce the barrier height for the subsequent C1'-N1 bond cleavage. This should be attributed to the smaller electrostatic repulsion between the leaving base and the negative phosphate group as a result of the structural rearrangement.


Assuntos
Citosina , Glicosídeos , Teoria Quântica , Timina DNA Glicosilase , Timina DNA Glicosilase/metabolismo , Timina DNA Glicosilase/química , Citosina/química , Citosina/metabolismo , Citosina/análogos & derivados , Glicosídeos/química , Glicosídeos/metabolismo , Simulação de Dinâmica Molecular
5.
Plant J ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733631

RESUMO

The jasmonic acid (JA) signaling pathway plays an important role in promoting the biosynthesis of tanshinones. While individual transcription factors have been extensively studied in the context of tanshinones biosynthesis regulation, the influence of methyl jasmonate (MeJA)-induced transcriptional complexes remains unexplored. This study elucidates the positive regulatory role of the basic helix-loop-helix protein SmMYC2 in tanshinones biosynthesis in Salvia miltiorrhiza. SmMYC2 not only binds to SmGGPPS1 promoters, activating their transcription, but also interacts with SmMYB36. This interaction enhances the transcriptional activity of SmMYC2 on SmGGPPS1, thereby promoting tanshinones biosynthesis. Furthermore, we identified three JA signaling repressors, SmJAZ3, SmJAZ4, and SmJAZ8, which interact with SmMYC2. These repressors hindered the transcriptional activity of SmMYC2 on SmGGPPS1 and disrupted the interaction between SmMYC2 and SmMYB36. MeJA treatment triggered the degradation of SmJAZ3 and SmJAZ4, allowing the SmMYC2-SmMYB36 complex to subsequently activate the expression of SmGGPPS1, whereas SmJAZ8 inhibited MeJA-mediated degradation due to the absence of the LPIARR motif. These results demonstrate that the SmJAZ-SmMYC2-SmMYB36 module dynamically regulates the JA-mediated accumulation of tanshinones. Our results reveal a new regulatory network for the biosynthesis of tanshinones. This study provides valuable insight for future research on MeJA-mediated modulation of tanshinones biosynthesis.

6.
Toxicol Lett ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734219

RESUMO

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5minutes after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20minutes. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

7.
Nanomicro Lett ; 16(1): 189, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698120

RESUMO

Monolithic textured perovskite/silicon tandem solar cells (TSCs) are expected to achieve maximum light capture at the lowest cost, potentially exhibiting the best power conversion efficiency. However, it is challenging to fabricate high-quality perovskite films and preferred crystal orientation on commercially textured silicon substrates with micrometer-size pyramids. Here, we introduced a bulky organic molecule (4-fluorobenzylamine hydroiodide (F-PMAI)) as a perovskite additive. It is found that F-PMAI can retard the crystallization process of perovskite film through hydrogen bond interaction between F- and FA+ and reduce (111) facet surface energy due to enhanced adsorption energy of F-PMAI on the (111) facet. Besides, the bulky molecular is extruded to the bottom and top of perovskite film after crystal growth, which can passivate interface defects through strong interaction between F-PMA+ and undercoordinated Pb2+/I-. As a result, the additive facilitates the formation of large perovskite grains and (111) preferred orientation with a reduced trap-state density, thereby promoting charge carrier transportation, and enhancing device performance and stability. The perovskite/silicon TSCs achieved a champion efficiency of 30.05% based on a silicon thin film tunneling junction. In addition, the devices exhibit excellent long-term thermal and light stability without encapsulation. This work provides an effective strategy for achieving efficient and stable TSCs.

8.
Int J Biol Macromol ; 269(Pt 1): 131824, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38697411

RESUMO

Maintaining wound moisture and monitoring of infection are crucial aspects of chronic wound treatment. The development of a pH-sensitive functional hydrogel dressing is an effective approach to monitor, protect, and facilitate wound healing. In this study, beet red pigment extract (BRPE) served as a native and efficient pH indicator by being grafted into silane-modified bacterial nanocellulose (BNC) to prepare a pH-sensitive wound hydrogel dressing (S-g-BNC/BRPE). FTIR confirmed the successful grafting of BRPE into the BNC matrix. The S-g-BNC/BRPE showed superior mechanical properties (0.25 MPa), swelling rate (1251 % on average), and hydrophilic properties (contact angle 21.83°). The composite exhibited a notable color change as the pH changed between 4.0 and 9.0. It appeared purple-red when the pH ranged from 4.0 to 6.0, and appeared light pink at pH 7.0 and 7.4, and appeared ginger-yellow at pH 8.0 and 9.0. Subsequently, the antioxidant activity and cytotoxicity of the composite was evaluated, its DPPH·, ABTS+, ·OH scavenging rates were 32.33 %, 19.31 %, and 30.06 %, respectively, and the cytotoxicity test clearly demonstrated the safety of the dressing. The antioxidant hydrogel dressing, fabricated with a cost-effective and easy method, not only showed excellent biocompatibility and dressing performance but could also indicated the wound state based on pH changes.

9.
J Pharm Biomed Anal ; 246: 116204, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38776584

RESUMO

Lamiophlomis Herba (LH) is a traditional Chinese and Tibetan dual-use herb with hemostatic and analgesic effects, and is widely used in the clinical treatment of traumatic bleeding and pain. In recent years, LH has been proven to treat liver fibrosis (LF), but the chemical components related to the pharmacological properties of LH in the treatment of LF are still unclear. Based on the theory of plasma pharmachemistry, the characteristic components in water extract and drug-containing plasma samples of LH were qualitatively analyzed by UPLC-Q-TOF-MS. The chemical components in plasma were screened and the targets were predicted by network pharmacology. Then, the predicted components and targets were verified in vitro by Elisa and qRT-PCR technology. Finally, the pharmacological effects of LH and its monomeric components were determined by hematoxylin-eosin staining of rat liver. A total of 50 chemical constituents were identified in LH, of which 12 were blood prototypes and 9 were metabolites. In vitro experiments showed that LH and its monomeric components luteolin, shanzhiside methyl ester, loganic acid, loganin, 8-O-acetyl shanzhiside methyl ester could increase the expression of antioxidant genes (NQO-1, HO-1) and decrease the expression of inflammatory genes (IL-6, IL-18), thereby reducing the expression of extracellular matrix-related genes and proteins (COL1A1, COL3A1, LN, α-sma, PC-III, Col-IV). In vivo experiments showed that LH could reduce the area of LF in rats in a dose-dependent manner, and shanzhiside methyl ester and 8-O-acetyl shanzhiside methyl ester may be the main components in pharmacodynamics. These effects may be mediated by LH-mediated Nrf2/NF-κB pathway. This study explored the potential pharmacodynamic components of LH in the treatment of LF, and confirmed that shanzhiside methyl ester and 8-O-acetyl shanzhiside methyl ester play a key role in the treatment of LF with LH.

10.
Sci Total Environ ; 934: 173420, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38777049

RESUMO

Toxicological studies have demonstrated the hepatic toxicity of several bisphenol analogs (BPs), a prevalent type of endocrine disruptor. The development of Adverse Outcome Pathway (AOP) has substantially contributed to the rapid risk assessment for human health. However, the lack of in vitro and in vivo data for the emerging BPs has limited the hazard assessment of these synthetic chemicals. Here, we aimed to develop a new strategy to rapidly predict BPs' hepatotoxicity using network analysis coupled with machine learning models. Considering the structural and functional similarities shared by BPs with Bisphenol A (BPA), we first integrated hepatic disease related genes from multiple databases into BPA-Gene-Phenotype-hepatic toxicity network and subjected it to the computational AOP (cAOP). Through cAOP network and conventional machine learning approaches, we scored the hepatotoxicity of 20 emerging BPs and provided new insights into how BPs' structure features contributed to biologic functions with limited experimental data. Additionally, we assessed the interactions between emerging BPs and ESR1 using molecular docking and proposed an AOP framework wherein ESR1 was a molecular initiating event. Overall, our study provides a computational approach to predict the hepatotoxicity of emerging BPs.

11.
Environ Pollut ; 352: 124082, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697246

RESUMO

Antimony (Sb) contamination in certain areas caused by activities such as antimony mining and smelting poses significant risks to human health and ecosystems. In this study, a stable composite material consisting of natural zeolite-supported nanoscale zero-valent iron (Z-ZVI) was successfully prepared. The immobilization effect of Z-ZVI on Sb in contaminated soil was investigated. Experimental results showed that Z-ZVI exhibited superior performance compared to pure nano zero-valent iron (nZVI) in terms of stability, with a lower zeta potential (-25.16 mV) at a pH of 7 and a higher specific surface area (54.54 m2/g). It can be easily applied and dispersed in contaminated soils. Additionally, Z-ZVI demonstrated a more abundant porous structure. After 60 days of treatment with 3% Z-ZVI, the leaching concentration of Sb in the contaminated soil decreased from 1.32 mg/L to 0.31 mg/L (a reduction of 76%), and the concentration of available Sb species decreased from 19.84 mg/kg to 0.71 mg/kg, achieving a fixation efficiency of up to 90%. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed the effective immobilization of Sb in the soil through reduction of antimonate to antimonite, precipitation, and adsorption processes facilitated by Z-ZVI. Moreover, the addition of Z-ZVI effectively reduced the bioavailability of Sb in the contaminated soil, thereby mitigating its toxicity to earthworms. In conclusion, Z-ZVI can be utilized as a promising material for the safe remediation and antimony and other heavy metal-contaminated soils.

12.
Pharm Biol ; 62(1): 423-435, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38757785

RESUMO

CONTEXT: Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota. OBJECTIVE: This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation. METHODS: We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD. RESULTS: Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD. CONCLUSION: This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.


Assuntos
Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Animais
13.
Pak J Pharm Sci ; 37(2): 291-296, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38767095

RESUMO

Mangiferin, a key bioactive constituent in Gentiana rhodantha, has a favorable impact on reducing blood sugar. A selective and sensitive UPLC MS/MS approach was developed for determining mangiferin in diabetic rats. Employing acetonitrile protein precipitation, chromatographic separation utilized a 2.1×50 mm, 3.5µm C18 column with a mobile phase of 0.1% formic acid aqueous and 5mM ammonium acetate (A, 45%) and acetonitrile (B, 55%) at a 0.5mL min-1 flow rate. Quantification, employing the multiple reaction monitoring (MRM) mode, focused on precursor-to-product ion transitions at m/z 447.1→271.1 for baicalin m/z and 421.0→301.0 for mangiferin. Calibration curves demonstrated linearity in the 1.00~100ng/mL range, with a lower quantification limit for rat plasma set at 1.00ng/mL. Inter- and intra-day accuracies spanned -9.1% to 8.5% and mangiferin mean recovery varied from 82.3% to 86.7%. The adeptly utilized UPLC-MS/MS approach facilitated the exploration of mangiferin pharmacokinetics in diabetic rats.


Assuntos
Diabetes Mellitus Experimental , Gentiana , Extratos Vegetais , Espectrometria de Massas em Tandem , Xantonas , Animais , Xantonas/farmacocinética , Xantonas/sangue , Xantonas/administração & dosagem , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Espectrometria de Massas em Tandem/métodos , Masculino , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/farmacocinética , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Administração Oral , Ratos , Gentiana/química , Ratos Sprague-Dawley , Estreptozocina , Reprodutibilidade dos Testes , Espectrometria de Massa com Cromatografia Líquida
14.
J Hosp Infect ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740299

RESUMO

Invasive fungal infections pose a substantial threat to patients in healthcare settings globally. Recent changes in the prevalence of fungal species and challenges in conducting reference antifungal susceptibility testing emphasize the importance of monitoring fungi and their antifungal resistance. A two-phase surveillance project was conducted in Beijing, China, involving 37 centers across 12 districts, from January 2012 to December 2013 and from January 2016 to December 2017. We found that the proportion of Candida albicans in intensive care units (ICUs) during 2016-2017 exhibited a significant decline compared to the 2012-2013 period, although it remained the most predominant pathogen. In contrast, the prevalence of Nakaseomyces glabratus (formerly Candida glabrata) and Candida tropicalis notably increased during the two-phase surveillance. The high prevalence of C. tropicalis and its resistance to azole drugs posed a serious threat to patients in ICUs. The pathogens causing invasive fungal infections in Beijing were relatively sensitive to echinocandins. While C. albicans continued to exhibit susceptibility to azoles, the resistance and growth rates of C. tropicalis towards azoles were particularly prominent. Concerns were raised due to the emergence of multiple, short-term isolates of Clavispora lusitaniae and Candida parapsilosis complex in neonatal ICUs, given their similarity in antifungal susceptibilities. Such occurrences point towards the potential for transmission and persisting presence of these pathogens within the ICU environment. Our study complements existing data on the epidemiology of invasive fungal infections. It is imperative to exercise cautious medication management for ICU patients in Beijing, paying particular attention to azole resistance in C. tropicalis.

15.
BMC Pediatr ; 24(1): 341, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755560

RESUMO

BACKGROUND: The Premonitory Urge for Tics Scale (PUTS) is a common self-report measure of premonitory urges for patients with tic disorders. This study aims to evaluate the Chinese version of the PUTS (PUTS-C) and to explore its association with psychiatric symptoms in Chinese children diagnosed with tic disorders. METHODS: The psychometric evaluation involved 204 outpatients with tic disorders, aged 7-16 years, who were divided into two age groups: (7-10 years, n = 103; 11-16 years, n = 95). RESULTS: The PUTS-C demonstrated good internal consistency (McDonald'sω = 0.84) and two-week test-retest reliability (0.76). We observed a statistically significant correlation between the total PUTS-C score and various Yale Global Tic Severity Scale (YGTSS) subscales and total tic severity scores. The PUTS-C score also showed significant correlations with the Children Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Screening Child Anxiety-Related Emotional Disorders (SCARED), and Children's Depression Inventory (CDI). Notably, premonitory urges independently predicted tic severity, beyond the influence of comorbid symptoms. A two-factor structure of the PUTS-C was identified in the total sample through factor analysis. CONCLUSIONS: The PUTS-C possesses acceptable validity and good reliability. It appears that premonitory urges in Chinese patients with tic disorders are associated with obsessive-compulsive symptoms, anxiety, and depression, but can independently predict tic severity. Specific PUTS-C factors possibly related to motor and vocal tics. Future research should continue to investigate age-related differences and the association with tics and other sensory symptoms.


Assuntos
Psicometria , Transtornos de Tique , Humanos , Criança , Transtornos de Tique/diagnóstico , Transtornos de Tique/psicologia , Masculino , Adolescente , Feminino , Reprodutibilidade dos Testes , China , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Autorrelato
16.
Plant Commun ; : 100942, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38720463

RESUMO

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop, ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and fertilization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, 915 accessions from 20 countries were gathered, comprising cultivars, major landraces, feral populations and wild progenitor. Based on whole genome resequencing of these accessions, the most comprehensive ramie genomic variation map to date was constructed. Phylogenetic, demographic, and admixture signal detection analyses indicate that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and wild progenitor or ancient landraces. Feral ramie has greater genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization are different from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches which are substantially different from the niche of the wild progenitor, and three environmental variables were associated with habitat-specific adaptation in feral ramie. Our findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature.

17.
South Afr J HIV Med ; 25(1): 1567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725705

RESUMO

Background: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing - those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance. Objectives: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance. Method: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA < 400 copies/mL), or at the point of censoring. Results: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77-1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71-5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance. Conclusion: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

18.
Int J Biol Macromol ; 269(Pt 2): 131805, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38677673

RESUMO

Endothelial repair is essential for restoring tissue fluid homeostasis following lung injury. R-spondin3 (RSPO3), a secreted protein mainly produced by endothelial cells (ECs), has shown its protective effect on endothelium. However, the specific mechanisms remain unknown. To explore whether and how RSPO3 regulates endothelial regeneration after inflammatory vascular injury, the role of RSPO3 in sepsis-induced pulmonary endothelial injury was investigated in EC-specific RSPO3 knockdown, inducible EC-specific RSPO3 deletion mice, EC-specific RSPO3 overexpression mice, systemic RSPO3-administration mice, in isolated mouse lung vascular endothelial cells (MLVECs), and in plasma from septic patients. Here we show that plasma RSPO3 levels are decreased in septic patients and correlated with endothelial injury markers and PaO2/FiO2 index. Both pulmonary EC-specific knockdown of RSPO3 and inducible EC-specific RSPO3 deletion inhibit pulmonary ECs proliferation and exacerbate ECs injury, whereas intra-pulmonary EC-specific RSPO3 overexpression promotes endothelial recovery and attenuates ECs injury during endotoxemia. We show that RSPO3 mediates pulmonary endothelial regeneration by a LGR4-dependent manner. Except for ß-catenin, integrin-linked kinase (ILK)/Akt is also identified as a novel downstream effector of RSPO3/LGR4 signaling. These results conclude that EC-derived RSPO3 mediates pulmonary endothelial regeneration by LGR4-dependent activation of ß-catenin and ILK signaling pathways after inflammatory vascular injury.

19.
Int Immunopharmacol ; 133: 112081, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38652963

RESUMO

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP.


Assuntos
Apoptose , Antígeno B7-H1 , Camundongos Endogâmicos C57BL , Neutrófilos , Pâncreas , Pancreatite , Animais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Pancreatite/imunologia , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Neutrófilos/imunologia , Neutrófilos/efeitos dos fármacos , Camundongos , Pâncreas/patologia , Pâncreas/imunologia , Masculino , Monócitos/imunologia , Monócitos/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos Knockout , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Ceruletídeo , Pessoa de Meia-Idade , Amilases/sangue , Lipase/sangue
20.
Front Psychiatry ; 15: 1354999, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38563028

RESUMO

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

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