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BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.
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Infecciones por Henipavirus , Virus Nipah , Virus Nipah/fisiología , Infecciones por Henipavirus/epidemiología , Infecciones por Henipavirus/transmisión , Humanos , Animales , Quirópteros/virología , Asia Sudoriental/epidemiología , Filogenia , Zoonosis/epidemiología , Zoonosis/virologíaRESUMEN
Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients' quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.
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Dolor Crónico , Bulbo Olfatorio , Humanos , Dolor Crónico/terapia , Animales , Bulbo Olfatorio/citología , Neuroglía , Trasplante de Células/métodosRESUMEN
Metal-organic frameworks (MOFs) have been widely studied as electrocatalysts, and the research strategy to improve their electrocatalytic oxygen evolution reaction (OER) performance is to modify their structure. In this paper, two-dimensional bimetallic MOFs were constructed to improve electrocatalytic OER performance. Using a mild electrochemical method with Ni and Co as metal sources and 4, 4 '-biphenyl dicarboxylic acid (H2 BPDC) as ligand, two-dimensional NiCo-BPDC was synthesized and then deposited on a carbon cloth electrode. The results show that NiCo-BPDC/CC possessed a low overpotential of 356â mV at a current density of 20â mA cm-2 with a small Tafel slope of 86â mV dec-1 in 1.0â M KOH solution. The two-dimensional NiCo-BPDC exhibits excellent electrocatalytic OER performance because the coordination of Ni and Co in the material and the interaction of the two-dimensional materials provide a large electrochemically active surface area and expose more metal active sites for OER, thus improving the reaction efficiency and indicating NiCo-BPDC as potential OER electrocatalyst.
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BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.
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Mpox , Humanos , Mpox/epidemiología , Filogenia , Brotes de Enfermedades , Estudios Retrospectivos , BrasilRESUMEN
Norovirus is a common cause of sporadic cases and outbreaks of gastroenteritis worldwide, although its prevalence and the dominant genotypes responsible for gastroenteritis outbreaks remain obscure. A systematic review was conducted on norovirus infection in China between January 2009 and March 2021. A meta-analysis and beta-binomial regression model were used to explore the epidemiological and clinical characteristics of norovirus infection and the potential factors contributing to the attack rate of the norovirus outbreaks, respectively. A total of 1132 articles with 155,865 confirmed cases were included, with a pooled positive test rate of 11.54% among 991,786 patients with acute diarrhea and a pooled attack rate of 6.73% in 500 norovirus outbreaks. GII.4 was the predominant genotype in both the etiological surveillance and outbreaks, followed by GII.3 in the etiological surveillance, and GII.17 in the outbreaks, with the proportion of recombinant genotypes increasing in recent years. A higher attack rate in the norovirus outbreaks was associated with age group (older adults), settings (nurseries, primary schools, etc.) and region (North China). The nation-wide pooled positive rate in the etiological surveillance of norovirus is lower than elsewhere in the global population, while the dominant genotypes are similar in both the etiological surveillance and the outbreak investigations. This study contributes to the understanding of norovirus infection with different genotypes in China. The prevention and control of norovirus outbreaks during the cold season should be intensified, with special attention paid to and enhanced surveillance performed in nurseries, schools and nursing homes from November to March.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Humanos , Anciano , Prevalencia , Filogenia , Brotes de Enfermedades , Genotipo , Gastroenteritis/epidemiología , Infecciones por Caliciviridae/epidemiología , China/epidemiología , Norovirus/genéticaRESUMEN
BACKGROUND: Human adenovirus (HAdV) is a major pathogen that causes acute respiratory tract infections (ARTI) and is frequently associated with outbreaks. The HAdV prevalence and the predominant types responsible for ARTI outbreaks remains obscure in China. METHODS: A systematic review was performed to retrieve literature that reported outbreaks or etiological surveillance of HAdV among ARTI patients in China from 2009 to 2020. Patient information was extracted from the literature to explore the epidemiological characteristics and clinical manifestations of the infection of various HAdV types. The study is registered with PROSPERO, CRD42022303015. RESULTS: A total of 950 articles (91 about outbreaks and 859 about etiological surveillance) meeting the selection criteria were included. Predominant HAdV types from etiological surveillance studies differed from those in outbreak events. Among 859 hospital-based etiological surveillance studies, positive detection rates of HAdV-3 (32.73%) and HAdV-7 (27.48%) were significantly higher than other virus types. While nearly half (45.71%) of outbreaks were caused by HAdV-7 with an overall attack rate of 22.32% among the 70 outbreaks for which the HAdVs were typed by the meta-analysis. Military camp and school were main outbreak settings with significantly different seasonal pattern and attack rate, where HAdV-55 and HAdV-7 were identified as the leading type, respectively. Clinical manifestations mainly depended on the HAdV types and patient's age. HAdV-55 infection tends to develop into pneumonia with poorer prognosis, especially in children <5 years old. CONCLUSIONS: This study improves the understanding of epidemiological and clinical features of HAdV infections and outbreaks with different virus types, and helps to inform future surveillance and control efforts in different settings.
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Infecciones por Adenoviridae , Infecciones por Adenovirus Humanos , Adenovirus Humanos , Infecciones del Sistema Respiratorio , Niño , Humanos , Preescolar , Prevalencia , Filogenia , Infecciones por Adenoviridae/epidemiología , China/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/diagnósticoRESUMEN
Ticks are important vectors of various zoonotic pathogens that can infect animals and humans, and most documented tick-borne pathogens have a strong bias towards microorganisms with strong disease phenotypes. The recent development of next-generation sequencing (NGS) has enabled the study of microbial communities, referred to as microbiome. Herein, we undertake a systematic review of published literature to build a comprehensive global dataset of microbiome determined by NGS in field-collected ticks. The dataset comprised 4418 records from 76 literature involving geo-referenced occurrences for 46 species of ticks and 219 microorganism families, revealing a total of 83 emerging viruses identified from 24 tick species belonging to 6 tick genera since 1980. The viral, bacterial and eukaryotic composition was compared regarding the tick species, their live stage and types of the specimens, or the geographic location. The data can assist the further investigation of ecological, biogeographical and epidemiological features of the tick-borne disease.
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Microbiota , Garrapatas , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metagenoma , Microbiota/genética , Revisiones Sistemáticas como Asunto , Garrapatas/microbiologíaRESUMEN
A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.
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Berberina , Fluoxetina , Animales , Cromatografía Liquida/métodos , Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos , Ratas , Espectrometría de Masas en Tándem/métodosRESUMEN
ABSTRACT: Women with labial hypertrophy may opt for labiaplasty. The aim of the study was to analyze the complications, long-term follow-up of clinical outcomes and satisfaction in this population over the past 10 years.All women who underwent labiaplasty with or without clitoral hood reduction at our center between January 2008 and August 2020 were retrospectively identified. Retrospective study was conducted, recording follow-up outcomes, motivations, techniques, postoperative complications, reasons requiring reoperation, and surgical satisfaction concerned different clinical characteristics. A concrete analysis of each specific outcome and a detailed knowledge of these procedures were performed.A total of 52.41% reported functional impairment, 20.25% cited aesthetics complains, and 27.34% were motivated by both the previously mentioned reasons. Women undergoing surgical correction sometimes mixed with various psychological aspects. A total of 91.06% reported that they were moderately (6.04%) or extremely (85.02%) satisfied with the outcomes after surgery, and 37 (8.94%) reported dissatisfied. Revision surgery was needed in a small number of patients (n = 7 of 414 patients, 1.69%) because of undesirable appearance. The most common complication in our patients was asymmetry (6.28%). Women requested labiaplasty in the last 2 reasons or procedures or without psychological distress were more likely feel satisfied with the results (satisfaction rate >90%). There was a significant difference in satisfaction among the 3 concerns as well as between the 2 kinds of psychological conditions ( P < 0.05). Satisfaction of patients with aesthetic complains compared with the other 2 worries was significantly lower ( P < 0.05). There was no significant difference among the 3 procedures in this comparison group ( P > 0.05). In addition, satisfaction in labiaplasty with or without clitoral hoodoplasty, neither of which was statistically different ( P > 0.05). Patients aged 30 to 39 years reported the lowest satisfaction in comparison with the other age groups.Labiaplasty of the labia minora is the most commonly performed genital cosmetic surgery procedure. This study on 414 patients demonstrated that it is associated with a high degree of patient satisfaction and low morbidity and provided evidence of safety and effectiveness preliminary, indicating that the procedure may be regarded as safe.
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Procedimientos de Cirugía Plástica , Vulva , China , Clítoris/cirugía , Femenino , Estudios de Seguimiento , Humanos , Satisfacción del Paciente , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Vulva/cirugíaRESUMEN
There is a lack of vaccine against human cysticercosis, thus making a huge population at the risk of infection. In this study, we chose a novel potential antigen molecule Taenia solium 14-3-3.3 (Ts14-3-3.3) and optimized it as sp-Ts14-3-3.3 (sp is immunoglobulin H chain V-region precursor, partial) in order to construct recombinant plasmids pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3. BALB/c mice were divided into four groups for immunization: pMZ-X3-Ts14-3-3.3, pMZ-X3-sp-Ts14-3-3.3, pMZ-X3 plasmid control group and PBS control group. Compared with two control groups, the proliferation level of splenic lymphocytes increased significantly in pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3 groups and reached the maximum in week 6. And the same case arose as cytokines associated with Th1 response, IFN-γ, and IL-2 while those with Th2 response, IL-4, IL-10 went up and reached the maximum in week 4. The levels of serum specific IgG, IgG1 and IgG2a rose and reached the maximum in week 6, 4 and 6, respectively. Meanwhile, the proportion of CD4+/CD8+ splenic T lymphocytes increased and reached the peak in week 6. The results indicated that the recombinant plasmids pMZ-X3-Ts14-3-3.3 and pMZ-X3-sp-Ts14-3-3.3 can induce specific cellular and humoral immune responses in BALB/c mice with immunization. Notably, the recombinant plasmid pMZ-X3-sp-Ts14-3-3.3 has a better immune effect, which proves that Ts14-3-3.3 enjoys a higher possibility as a potential antigen molecule to T. solium vaccine.
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Taenia solium , Vacunas , Animales , Anticuerpos Antihelmínticos , Inmunidad , Inmunoglobulina G , Ratones , Ratones Endogámicos BALB C , Plásmidos/genética , Taenia solium/genéticaRESUMEN
Background: Emerging vector-borne pathogens (VBPs) pose a continuous background threat to the global health. Knowledge of the occurrence, distributions and epidemiological characteristics of VBP are lacking in many countries. Outbreaks of novel VBP are of increasing global interest including those arising in China. Methods: A systematic review of published literature was undertaken to characterize the spectrum of VBPs causing human illness in China. We searched five databases for VBP-related articles in English and Chinese published between January 1980 and June 2021, that excluded those listed in the National Notifiable Diseases Surveillance System of China. The study is registered with PROSPERO, CRD42021259540. Findings: A total of 906 articles meeting the selection criteria were included in this study. A total of 44,809 human infections with 82 species of VBPs including 40 viruses, 33 bacteria (20 Rickettsiales bacteria, eight Spirochaetales bacteria, and five other bacteria) and nine parasites, were identified in China. Rickettsiales bacteria were the most common and widely distributed pathogens with 18,042 cases reported in 33 provinces by 347 reviewed articles, followed by Spirochaetales bacteria with 15,745 cases in 32 provinces (299 articles), viruses with 8455 cases in 30 provinces (139 articles), other bacteria with 2053 cases in 19 provinces (65 articles), parasites with 514 cases in 17 provinces (44 articles), and multiple pathogens with 3626 cases in 14 provinces (23 articles). Coxiella burnetii, Bartonella henselae and Rickettsia sibirica were the most frequently reported pathogens. A total of 18 new pathogens were reported in China during this period (these also represented their first identification globally). Based on 419 articles with clinical information, a meta-analysis revealed that flu-like illness was the most common manifestation among infections with VBPs. Interpretation: This review helps improve the understanding of VBPs in China, demonstrating the need to consider a wider surveillance of VBPs in many different settings, thus helping to inform future research and surveillance efforts. Funding: Natural Science Foundation of China.
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Mutator enzymes alter the nucleotide sequences of DNA or RNA molecules; immune systems utilize them to destroy the integrity of pathogen genomes and to optimize immune mediators of the host. Their dysregulation has been linked to tumorigenesis in various tissues. Defining and comparing the activities of such mutator enzymes requires a robust versatile assay that is independent of their biological context as in vivo mutation rates are typically low. Here we provide detailed protocols for two widely used E. coli-based approaches that detect the activities of ectopically expressed cytidine deaminases on two distinct reporter genes: an extrachromosomal kanamycin-resistance gene or an endogenous chromosomal substrate, the rpoB gene-encoding RNA polymerase. The generation of mutations is in both cases measured in a colony formation assay. With appropriate modifications, these assays can be extended to study other mutator enzymes.
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Escherichia coli , Citidina Desaminasa/genética , ADN , Escherichia coli/genética , Genes Reporteros , MutaciónRESUMEN
The incidence of acute myocardial infarction (AMI) is currently increasing. Early detection is important for the treatment and prognosis of patients with AMI. Heart-type fatty acid-binding protein (H-FABP) may be used as an early marker of AMI due to its high sensitivity, specificity and prognostic value. Therefore, in the present study, H-FABP was used as a biomarker in a double-antibody sandwich method and colloidal gold-based lateral flow immunoassay to develop a rapid detection kit for H-FABP with a processing time of only 5 min. The sensitivity of the kit in plasma and whole blood was 1 ng/ml and this method had good specificity, exhibiting no cross-reaction with cardiac troponin I, myoglobin or creatine kinase-Mb. The kits had good shelf life and stability, as they were able to be stored at 40ËC for 30 days. A total of 12 clinical samples were collected for detection and the coincidence rate with the ELISA method was up to 91.67%. Therefore, the present study provided a simple, rapid and economical early-detection in-home testing kit.
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The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1ß, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1ß, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1ß, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.
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Antidepresivos , Depresión , Animales , Conducta Animal , Cromatografía Liquida , Depresión/tratamiento farmacológico , Depresión/etiología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Hipocampo , Ratones , Simulación del Acoplamiento Molecular , Sirtuina 1/genética , Estrés Psicológico , Espectrometría de Masas en TándemRESUMEN
In this research, the graft modification mechanism of coupling agent vinyl triethoxysilane (KH-151) to macroporous silica gel was studied using a combination of multiple methods. SEM, FTIR, RAMAN, NMR and XPS were used to characterize the silica gel before and after grafting, determining the mechanism of the grafting reaction of the silane coupling agent. On this basis, the grafting rate of the coupling agent was accurately calculated by TGA weight loss. From the results of characterization, it can be seen that the coupling agent molecules have two connection types on the surface of silica gel, and the ratio of the two types is 43.51% and 56.49% respectively. The influences of hydration degree of the silica gel, coupling agent dosage and reaction temperature on the grafting rate were explored, and the optimal reaction conditions for the modification of macroporous silica gel were determined by the coupling agent through orthogonal experiments, that is, the hydration degree of silica gel of 10%, a coupling agent dosage of 12 mL, and a reaction temperature of 80 °C. Under optimal reaction conditions, the average grafting rate of the coupling agent vinyl triethoxysilane (KH-151) on macroporous silica gel is as high as 91.03%.
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Combination of Aconiti Lateralis Radix Praeparata (FZ) and Paeoniae Radix Alba (BS) shows a significant effect in rheumatoid arthritis (RA). This study aimed to investigate the efficacy enhancing and toxicity reducing mechanism of combination of them in adjuvant-induced arthritis (AIA) rats by metabolomics. Rats were randomly divided into seven groups, including A (healthy control), B (model control), C1 (therapy group), C2 (efficacy enhancing group), D1 (toxicity group), and D2 (toxicity reducing group), and dexamethasone group was used as positive control. The plasma biochemical indexes showed that therapeutic dose of lipid-soluble alkaloids of FZ could significantly inhibit the concentrations of IL-1ß, TNF-α, and IFN-γ in AIA rats, and combination with total glucosides of peony could further reduce the concentration of IL-1ß. Then, UPLC-LTQ/Orbitrap MS with untargeted metabolomics was performed to identify the possible metabolites and pathways. Through multivariate data analysis of therapeutic dose groups (A vs. B vs. C1 vs. C2) and multivariate data analysis of toxic dose groups (A vs. B vs. D1 vs. D2), 10 and 7 biomarkers were identified based on biomarker analysis, respectively. After inducing AIA model, the plasma contents of spermidine, vanillylmandelic acid, catechol, and linoleate were increased significantly, and the contents of citric acid, L-tyrosine, L-phenylalanine, leucine, L-tryptophan, and uridine 5'-monophosphate (UMP) were decreased significantly. High dose of lipid-soluble alkaloids of FZ could increase the plasma contents of L-lysine, L-arginine, and deoxycholic acid, while the plasma contents of UMP, carnitine, N-formylanthranilic acid, and adenosine were decreased significantly. The pathway analysis indicated that therapeutic dose of lipid-soluble alkaloids of FZ could regulate energy and amino acid metabolic disorders in AIA rats. However, toxic dose could cause bile acid, fat, amino acid, and energy metabolic disorders. And combination with total glucosides of peony could enhance the therapeutic effects and attenuate the toxicity induced by lipid-soluble alkaloids of FZ.
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Cysticercosis is a cosmopolitan zoonotic parasitic disease infected by larval of Taenia solium (T. solium). Several drugs for the treatment of cysticercosis, such as praziquantel, albendazole, and mebendazole, have certain toxicity and side effects. Considering that there is no vaccine available, we studied a new vaccine for cysticercosis in this study. The complete TSOL18 gene and the optimized SP-TSOL18 gene fragments were obtained using PCR-based accurate synthesis method. The secretory and intracellular recombinant pMG36e-SP-TSOL18/Lactococcus lactis (L. lactis) and pMG36e-TSOL18/L. lactis vaccines of T. solium were prepared. Immune responses in mice orally immunized with these two recombinant L. lactis vaccines were analyzed by the determination of specific antibodies (IgG, IgG1, IgG2a, and sIgA) in serum, spleen lymphocyte proliferation, and cytokines (IL-2, IFN-γ, IL-4, and IL-10) in spleen lymphocyte culture supernatant. Our results showed that, after the first immunization, in these two recombinant L. lactis vaccine groups, the levels of serum specific IgG, IgG2a, and IgG1 increased on 14-56 d and reached the highest level on days 42, 42, and 28, respectively. The level of specific sIgA of intestinal mucosa also increased on 14-56 d and reached the highest level on day 42. The level of spleen lymphocyte proliferation increased on 14-56 d and reached the highest level on day 42. The levels of IL-2, IFN-γ, IL-4, and IL-10 in spleen lymphocyte culture supernatant increased on 14-56 d and reached the highest level on days 42, 42, 28, and 28, respectively. These results indicated that the recombinant pMG36e-SP-TSOL18/L. lactis and pMG36e-TSOL18/L. lactis vaccines can induce specific cellular, humoral, and mucosal immune responses in mice with oral vaccination. More importantly, the recombinant pMG36e-SP-TSOL18/L. lactis vaccine has a better immune effect. In summary, these results demonstrated the possibility of using L. lactis strain as a vector to deliver protective antigens of T. solium.
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Antígenos Helmínticos/inmunología , Cisticercosis/inmunología , Mucosa Intestinal/inmunología , Lactococcus lactis/inmunología , Linfocitos T/inmunología , Taenia solium/fisiología , Vacunas/inmunología , Administración Oral , Animales , Anticuerpos Antihelmínticos/metabolismo , Antígenos Helmínticos/genética , Células Cultivadas , Femenino , Humanos , Inmunización , Inmunoglobulina A Secretora/metabolismo , Masculino , Ratones , Ratones Endogámicos , Porcinos , Vacunas SintéticasRESUMEN
In the course of both innate and adaptive immunity, cytidine deaminases within the activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) family modulate immune responses by mutating specific nucleic acid sequences of hosts and pathogens. The evolutionary emergence of these mediators, however, seems to coincide precisely with the emergence of adaptive immunity in vertebrates. Here, we show a family of genes in species within two divergent invertebrate phyla-the echinoderm Strongylocentrotus purpuratus and the brachiopod Lingula anatina-that encode proteins with similarities in amino acid sequence and enzymatic activities to the vertebrate AID/APOBECs. The expression of these invertebrate factors is enriched in tissues undergoing constant, direct interactions with microbes and can be induced upon pathogen challenge. Our findings suggest that AID/APOBEC proteins, and their function in immunity, emerged far earlier than previously thought. Thus, cytidine deamination is probably an ancient innate immune mechanism that predates the protostome/deuterostome divergence.
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Desaminasas APOBEC-1/genética , Citidina Desaminasa/genética , Inmunidad Innata/genética , Invertebrados/genética , Desaminasas APOBEC-1/metabolismo , Inmunidad Adaptativa/genética , Secuencia de Aminoácidos , Animales , Citidina Desaminasa/metabolismo , Regulación Enzimológica de la Expresión Génica , Humanos , Invertebrados/clasificación , Invertebrados/enzimología , Mutación , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Strongylocentrotus purpuratus/enzimología , Strongylocentrotus purpuratus/genéticaRESUMEN
As a large category of natural products widely present in traditional Chinese medicine, iridoid glycosides have multiple pharmacological activities. Recent researches suggest that iridoid glycosides mainly exist in vivo in the forms of original form, aglycone and a series of their â and â ¡ metabolites under the biotransformation effect, and their metabolites have been proved to have multiple pharmacological activities. The research progress on in vivo metabolism and metabolite activities of several iridoid glycosides would be reviewed in this article, to provide a theoretical basis for the further development and utilization of iridoid compounds and their metabolites.