RESUMEN
α-keratins are structural proteins in the cortex of wool fibres and assemble in an organized fashion into keratin intermediate filaments. Variation in these keratin proteins affects the structure and characteristics of wool fibre, making keratin genes ideal candidates for the development of gene markers that describe variations in wool traits. A region of KRT85 spanning exon 3-4 (including the entire exon 3, intron 3, exon 4 and part of intron 4) was investigated. Two banding patterns defining two variant sequences (A and B) were observed in this region, and these were characterised by the presence of two single nucleotide polymorphisms. The effect of this variation in the exon 3-4 region of KRT85 on wool traits was investigated in 463 Merino × Southdown-cross lambs. The frequencies of these two variants in these sheep were 55.6% and 44.4%, respectively. Three different genotypes were observed with frequencies of 32.6%, 46.1% and 21.3% for AA, AB and BB, respectively. The presence of A was associated with an increase in greasy fleece weight and clean fleece weight, while the presence of B was associated with an increased wool prickle factor. These findings should be replicated in a broader range of sheep breeds to determine whether the associations are robust and to clarify whether the observed effects are attributable to breed differences or to gene effects themselves.
RESUMEN
BACKGROUND: Non-proliferative diabetic retinopathy (NPDR) poses a significant challenge in diabetes management due to its microvascular changes in the retina. Laser photocoagulation, a conventional therapy, aims to mitigate the risk of progressing to proliferative diabetic retinopathy (PDR). AIM: To compare the efficacy and safety of multi-spot vs single-spot scanning panretinal laser photocoagulation in NPDR patients. METHODS: Forty-nine NPDR patients (86 eyes) treated between September 2020 and July 2022 were included. They were randomly allocated into single-spot (n = 23, 40 eyes) and multi-spot (n = 26, 46 eyes) groups. Treatment outcomes, including best-corrected visual acuity (BCVA), central macular thickness (CMT), and mean threshold sensitivity, were assessed at predetermined intervals over 12 months. Adverse reactions were also recorded. RESULTS: Energy levels did not significantly differ between groups (P > 0.05), but the multi-spot group exhibited lower energy density (P < 0.05). BCVA and CMT improvements were noted in the multi-spot group at one-month post-treatment (P < 0.05). Adverse reaction incidence was similar between groups (P > 0.05). CONCLUSION: While energy intensity and safety were comparable between modalities, multi-spot scanning demonstrated lower energy density and showed superior short-term improvements in BCVA and CMT for NPDR patients, with reduced laser-induced damage.
RESUMEN
BACKGROUND: Ubiquitin-conjugating enzyme E2 N (UBE2N) is recognized in the progression of some cancers; however, little research has been conducted to describe its role in prostate cancer. The purpose of this paper is to explore the function and mechanism of UBE2N in prostate cancer cells. METHODS: UBE2N expression was detected in Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data, prostate cancer tissue microarrays, and prostate cancer cell lines, respectively. UBE2N knockdown or overexpression was used to analyze its role in cell viability and glycolysis of prostate cancer cells and tumor growth. XAV939 or Axin1 overexpression was co-treated with UBE2N overexpression to detect the involvement of the Wnt/ß-catenin signaling and Axin1 in the UBE2N function. UBE2N interacting with Axin1 was analyzed by co-immunoprecipitation assay. RESULTS: UBE2N was upregulated in prostate cancer and the UBE2N-high expression correlated with the poor prognosis of prostate cancer. UBE2N knockdown inhibited cell viability and glycolysis in prostate cancer cells and restricted tumor formation in tumor-bearing mice. Wnt/ß-catenin inhibition and Axin1 overexpression reversed the promoting viability and glycolysis function of UBE2N. UBE2N promoted Axin1 ubiquitination and decreased Axin1 protein level.
Asunto(s)
Proteína Axina , Supervivencia Celular , Glucólisis , Neoplasias de la Próstata , Enzimas Ubiquitina-Conjugadoras , Ubiquitinación , Animales , Humanos , Masculino , Ratones , Proteína Axina/metabolismo , Proteína Axina/genética , Línea Celular Tumoral , Ratones Desnudos , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Vía de Señalización WntRESUMEN
Enteroendocrine cells (EECs) and vagal afferent neurons constitute functional sensory units of the gut, which have been implicated in bottom-up modulation of brain functions. Sodium oligomannate (GV-971) has been shown to improve cognitive functions in murine models of Alzheimer's disease (AD) and recently approved for the treatment of AD patients in China. In this study, we explored whether activation of the EECs-vagal afferent pathways was involved in the therapeutic effects of GV-971. We found that an enteroendocrine cell line RIN-14B displayed spontaneous calcium oscillations due to TRPA1-mediated calcium entry; perfusion of GV-971 (50, 100 mg/L) concentration-dependently enhanced the calcium oscillations in EECs. In ex vivo murine jejunum preparation, intraluminal infusion of GV-971 (500 mg/L) significantly increased the spontaneous and distension-induced discharge rate of the vagal afferent nerves. In wild-type mice, administration of GV-971 (100 mg· kg-1 ·d-1, i.g. for 7 days) significantly elevated serum serotonin and CCK levels and increased jejunal afferent nerve activity. In 7-month-old APP/PS1 mice, administration of GV-971 for 12 weeks significantly increased jejunal afferent nerve activity and improved the cognitive deficits in behavioral tests. Sweet taste receptor inhibitor Lactisole (0.5 mM) and the TRPA1 channel blocker HC-030031 (10 µM) negated the effects of GV-971 on calcium oscillations in RIN-14B cells as well as on jejunal afferent nerve activity. In APP/PS1 mice, co-administration of Lactisole (30 mg ·kg-1 ·d-1, i.g. for 12 weeks) attenuated the effects of GV-971 on serum serotonin and CCK levels, vagal afferent firing, and cognitive behaviors. We conclude that GV-971 activates sweet taste receptors and TRPA1, either directly or indirectly, to enhance calcium entry in enteroendocrine cells, resulting in increased CCK and 5-HT release and consequent increase of vagal afferent activity. GV-971 might activate the EECs-vagal afferent pathways to modulate cognitive functions.
Asunto(s)
Células Enteroendocrinas , Yeyuno , Canal Catiónico TRPA1 , Nervio Vago , Animales , Masculino , Ratones , Vías Aferentes/efectos de los fármacos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Señalización del Calcio/efectos de los fármacos , Línea Celular , Colecistoquinina/metabolismo , Modelos Animales de Enfermedad , Células Enteroendocrinas/metabolismo , Células Enteroendocrinas/efectos de los fármacos , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Yeyuno/inervación , Ratones Endogámicos C57BL , Ratones Transgénicos , Presenilina-1/genética , Serotonina/metabolismo , Canal Catiónico TRPA1/metabolismo , Nervio Vago/efectos de los fármacos , Nervio Vago/metabolismoRESUMEN
BACKGROUND AND AIMS: Although the life expectancy of women systematically and robustly exceeds that of men, specific differences and molecular mechanisms of sex in influencing longevity phenotypes remain largely unknown. Therefore, we performed transcriptome sequencing of peripheral blood samples to explore regulatory mechanisms of healthy longevity by incorporating sex data. METHODS: We selected 34 exceptional longevity (age: 98.26 ± 2.45 years) and 16 controls (age: 52.81 ± 9.78) without advanced outcomes from 1363 longevity and 692 controls recruited from Nanning of Guangxi for RNA sequencing 1. The transcriptome sequencing 1 data of 50 samples were compared by longevity and sex to screen differentially expressed genes (DEGs). Then, 121 aging samples (40-110 years old) without advanced outcomes from 355 longevity and 294 controls recruited from Dongxing of Guangxi were selected for RNA sequencing 2. The genes associated with aging from the transcriptome sequencing 2 of 121 aging samples were filtered out. Finally, the gender-related longevity candidate genes and their possible metabolic pathways were verified by cell model of aging and a real-time polymerase chain reaction (RT-PCR). RESULTS: Metabolism differs between male and female and plays a key role in longevity. Moreover, the principal findings of this study revealed a novel key gene, UGT2B11, that plays an important role in regulating lipid metabolism through the peroxisome proliferator activated receptor gamma (PPARG) signalling pathway and ultimately improving lifespan, particularly in females. CONCLUSION: The findings suggest specific differences in metabolism affecting exceptional longevity phenotypes between the sexes and offer novel therapeutic targets to extend lifespan by regulating lipid homeostasis.
Asunto(s)
Longevidad , Fenotipo , Humanos , Masculino , Femenino , Longevidad/genética , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto , Transcriptoma , Estudios de Casos y Controles , Pronóstico , Estudios de Seguimiento , Perfilación de la Expresión Génica , Biomarcadores/análisis , Factores Sexuales , Envejecimiento/genéticaRESUMEN
The transition from ordered to noisy is a significant epigenetic signature of aging and age-related disease. As a paradigm of healthy human aging and longevity, long-lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high-resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs. Importantly, we identified 38,923 genomic regions with LLI-specific lower ME (LLI-specific lower entropy regions, for short, LLI-specific LERs). These regions were overrepresented in promoters, which likely function in transcriptional noise suppression. Genes associated with LLI-specific LERs have a considerable impact on SNP-based heritability of some aging-related disorders (e.g., asthma and stroke). Furthermore, neutrophil was identified as the primary cell type sustaining LLI-specific LERs. Our results highlight the stability of epigenetic order in promoters of genes involved with aging and age-related disorders within LLI epigenomes. This unique epigenetic feature reveals a previously unknown role of epigenetic order maintenance in specific genomic regions of LLIs, which helps open a new avenue on the epigenetic regulation mechanism in human healthy aging and longevity.
Asunto(s)
Metilación de ADN , Epigénesis Genética , Envejecimiento Saludable , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Envejecimiento/genética , Metilación de ADN/genética , Pueblos del Este de Asia/genética , Entropía , Envejecimiento Saludable/genética , Longevidad/genéticaRESUMEN
MicroRNA (miRNA) is a highly conserved non-coding tiny endogenous RNA molecule that regulates various cellular functions by inhibiting mRNA translation or promoting the degradation of proteins. In this study, we identified a specific miRNA (designed as Pva-miR-2765) from Penaeus vannamei, which widely distributed in different tissues of shrimp, with the highest concentration found in the intestine. Through fluorescence in situ hybridization (FISH), we observed that Pva-miR-2765 is primarily located in the cytoplasm. Interestingly, we found that the expression of Pva-miR-2765 significantly decreased in hemocytes, hepatopancreas and gill under ammonia nitrogen stress. Furthermore, when Pva-miR-2765 was silenced, the autophagy level in shrimp significantly increased. Additionally, Pva-miR-2765 was found to promote pathological damage in the hepatopancreas of shrimp. Subsequently, correlation analysis revealed a negative relationship between the expression of Pva-miR-2765 and PvTBC1D7. To confirm this interaction, we conducted a dual luciferase reporter gene assay, which demonstrated that Pva-miR-2765 inhibit the expression of PvTBC1D7 by interacting with its 3'UTR. And the expression level of PvTBC1D7 in shrimp decreased significantly under ammonia nitrogen stress in Pva-miR-2765 overexpressed. Our findings suggest that Pva-miR-2765 can reduce autophagy in P. vannamei by inhibiting the regulation of PvTBC1D7, thereby participating in the oxidative stress of shrimp caused by ammonia nitrogen stress.
Asunto(s)
MicroARNs , Penaeidae , Animales , Amoníaco , Hibridación Fluorescente in Situ , Nitrógeno , AutofagiaRESUMEN
MicroRNAs (miRNAs) are a group of RNAs that regulate gene expression in the post-transcriptionally. miRNAs can regulate numerous processes, such as the immune response, due to their dynamic expression patterns. The giant freshwater prawn Macrobrachium rosenbergii is a major freshwater aquaculture prawn that is attacked by various bacteria, including Aeromonas hydrophila. For this study, we performed an analysis of the miRNA and mRNA transcriptome analysis of M. rosenbergii which was infected with A. hydrophila. We identified 56 differentially expressed miRNAs (DEMs) and 1542 differentially expressed mRNAs. Furthermore, an integrated analysis of miRNA-mRNA expression led to the identification of 729 differentially predicted target genes (DETGs) of the DEMs. Multiple functional categories related to immunity, apoptosis, and autophagy were found to be enriched in the DETGs. During the infection of M. rosenbergii by A. hydrophila, an elaborate regulatory network involving Toll and immune deficiency (IMD) signaling, mitogen-activated protein kinase (MAPK) signaling, lysosome, and cell apoptosis was formed by a complex interplay of 40 crucial DEMs and 22 DETGs, all associated with the immune and autophagy pathway. The findings suggest that infection with A. hydrophila triggers intricate responses in both miRNA and mRNA, significantly impacting immune and autophagy processes in M. rosenbergii.
Asunto(s)
MicroARNs , Palaemonidae , Animales , Aeromonas hydrophila/fisiología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Perfilación de la Expresión Génica/veterinaria , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
Small nucleolar RNA host gene 15 (SNHG15) plays an oncogenic role in many cancers. However, the role of SNHG15 in bladder cancer (BLCA) remains unclear. In this study, the regulation of SNHG15 on the activities of BLCA cells (T24 and RT112) was investigated. In detail, super-enhancers (SEs), differentially expressed genes, and functional enrichment were detected by bioinformatic analyses. Mutant cell lines lacking SNHG15-SEs were established using CRISPR-Cas9. Relative gene expression was detected by quantitative polymerase chain reaction (qPCR), western blot, in situ hybridization, and immunohistochemistry assays. Cell senescence, apoptosis, viability, and proliferation were measured. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter gene assays were conducted to analyze the interactions between genes. A novel super-enhancer of SNHG15 (SNHG15-SEs) was discovered in several BLCA datasets. The deletion of SNHG15-SEs resulted in a significant downregulation of SNHG15. Mechanistically, the core active region of SNHG15-SEs recruited the transcription factor FOSL1 to facilitate the SNHG15 transcription, thereby inducing the proliferation and metastasis of BLCA cells. Deletion of SNHG15-SEs inhibited the growth and metastasis of T24 and RT112 cells by inactivating the WNT/CTNNB1 pathway activation. Overexpression of FOSL1 in SNHG15-SEs restored the cell proliferation and metastasis. Next, a xenograft mouse model showed that SNHG15-SEs deletion inhibited the proliferation and metastasis of BLCA cells in vivo. Collectively, our data indicate that SNHG15-SEs recruit FOSL1 to promote the expression of SNHG15 which interacts with CTNNB1 in the nucleus to activate the transcription of ADAM12, leading to the malignance of BLCA cells.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Vía de Señalización Wnt , Humanos , Animales , Ratones , Neoplasias de la Vejiga Urinaria/genética , Vejiga Urinaria , Células Epiteliales , ApoptosisRESUMEN
Current COVID-19 vaccines are highly effective against symptomatic disease, but repeated booster doses using vaccines based on the ancestral strain offer limited additional protection against SARS-CoV-2 variants of concern (VOCs). To address this, we used antigenic distance to in silico select optimized booster vaccine seed strains effective against both current and future VOCs. Our model suggests that a SARS-CoV-1-based booster vaccine has the potential to cover a broader range of VOCs. Candidate vaccines including the spike protein from ancestral SARS-CoV-2, Delta, Omicron (BA.1), SARS-CoV-1, or MERS-CoV were experimentally evaluated in mice following two doses of the BNT162b2 vaccine. The SARS-CoV-1-based booster vaccine outperformed other candidates in terms of neutralizing antibody breadth and duration, as well as protective activity against Omicron (BA.2) challenge. This study suggests a unique strategy for selecting booster vaccines based on antigenic distance, which may be useful in designing future booster vaccines as new SARS-CoV-2 variants emerge.
Asunto(s)
COVID-19 , Animales , Humanos , Ratones , COVID-19/prevención & control , SARS-CoV-2 , Vacunas contra la COVID-19 , Vacuna BNT162 , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines demonstrate reduced protection against acquisition of BA.5 subvariant but are still effective against severe disease. However, immune correlates of protection against BA.5 remain unknown. We report the immunogenicity and protective efficacy of vaccine regimens consisting of the vector-based Ad26.COV2.S vaccine and the adjuvanted spike ferritin nanoparticle (SpFN) vaccine against a high-dose, mismatched Omicron BA.5 challenge in macaques. The SpFNx3 and Ad26 + SpFNx2 regimens elicit higher antibody responses than Ad26x3, whereas the Ad26 + SpFNx2 and Ad26x3 regimens induce higher CD8 T cell responses than SpFNx3. The Ad26 + SpFNx2 regimen elicits the highest CD4 T cell responses. All three regimens suppress peak and day 4 viral loads in the respiratory tract, which correlate with both humoral and cellular immune responses. This study demonstrates that both homologous and heterologous regimens involving Ad26.COV2.S and SpFN vaccines provide robust protection against a mismatched BA.5 challenge in macaques.
Asunto(s)
COVID-19 , Nanopartículas , Vacunas , Humanos , Animales , Macaca , Ad26COVS1 , COVID-19/prevención & control , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , FerritinasRESUMEN
OBJECTIVES: Strong evidence imply that delayed cord clamping (DCC) provides significant benefits for singleton neonates. However, there is little information about the safety or efficacy of DCC in twins to recommend for or against DCC in twins in guidelines. We aimed to determine the effect of DCC on dichorionic twins born at <32 weeks of gestation. STUDY DESIGN: This is a retrospective cohort study comparing the neonatal and maternal outcomes of immediate cord clamping (ICC) [<15 second (s)] versus DCC (at 60 s). Generalized estimating equations models were performed accounting for twin correlation. RESULTS: A total of 82 pairs of twins (DCC: 41; ICC: 41) were included in analysis. The primary outcome of death before discharge occurred in 3.66% of twins in the DCC group and 7.32% in the ICC group, without a significant difference between the groups. Compared to ICC group, DCC was associated with increased hemoglobin levels [ß1 coefficient 6.51; 95% confidence interval (CI) 0.69-12.32. ß2 coefficient 5.80; 95% CI 0.07-11.54] at 12-24 h of life. There were no significant differences between the groups in neonatal death, neonatal major morbidities and maternal bleeding complications, although DCC was associated with higher estimated maternal blood loss in the cesarean section group (p = .005). CONCLUSIONS: DCC for 60 s in dichorionic twins born at <32 weeks of gestation was associated with increased neonatal hemoglobin levels, when compared with ICC. The finding of a higher estimated maternal blood loss by cesarean section in the DCC group calls for further trials to assess maternal safety of this procedure in this patient population.
Asunto(s)
Cesárea , Clampeo del Cordón Umbilical , Recién Nacido , Embarazo , Humanos , Femenino , Estudios Retrospectivos , Cordón Umbilical , Gemelos Dicigóticos , Constricción , HemoglobinasRESUMEN
Objective: Deleted in liver cancer 1 (DLC1) is a GTPase-activating protein that is reported as a suppressor in certain human cancers. However, the detailed biological function of DLC1 is still unclear in human prostate cancer (PCa). In the present study, we aimed to explore the function of DLC1 in PCa cells. Methods: Silencing and overexpression of DLC1 were induced in an androgen-sensitive PCa cell line (LNCaP) using RNA interference and lentiviral vector transduction. The Cell Counting Kit-8 assay was performed to determine cell proliferation. The cell cycle was examined by performing a propidium iodide staining assay. Results: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of LNCaP cells. Moreover, DLC1 expression was negatively correlated with Rho-associated protein kinase (ROCK) expression in LNCaP cells. Importantly, this study showed that the ROCK inhibitor Y27632 restored the function of DLC1 in LNCaP cells and reduced the tumorigenicity of LNCaP cells in vivo. Conclusion: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of PCa cells and negatively correlated with ROCK expression in PCa cells and tissue.
RESUMEN
Glioblastoma (GBM) is one of the most aggressive forms of cancer. Although IDH1 mutation indicates a good prognosis and a potential target for treatment, most GBMs are IDH1 wild-type. Identifying additional molecular markers would help to generate personalized therapies and improve patient outcomes. Here, we used our recently developed metabolic modeling method (genome-wide precision metabolic modeling, GPMM) to investigate the metabolic profiles of GBM, aiming to identify additional novel molecular markers for this disease. We systematically analyzed the metabolic reaction profiles of 149 GBM samples lacking IDH1 mutation. Forty-eight reactions showing significant association with prognosis were identified. Further analysis indicated that the purine recycling, nucleotide interconversion, and folate metabolism pathways were the most robust modules related to prognosis. Considering the three pathways, we then identified the most significant GBM type for a better prognosis, namely N+P-. This type presented high nucleotide interconversion (N+) and low purine recycling (P-). N+P--type exhibited a significantly better outcome (log-rank p = 4.7 × 10-7) than that of N-P+. GBM patients with the N+P--type had a median survival time of 19.6 months and lived 65% longer than other GBM patients. Our results highlighted a novel molecular type of GBM, which showed relatively high frequency (26%) in GBM patients lacking the IDH1 mutation, and therefore exhibits potential in GBM prognostic assessment and personalized therapy.
RESUMEN
The Rho/ROCK pathway regulates diverse cellular processes and contributes to the development and advancement of several types of human cancers. This study investigated the role of specific Rho GTPase-activating proteins (RhoGAP), ARHGAP6, in bladder cancer (BC). In this study, ARHGAP6 expression in BC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism ARHGAP6 of in BC. The mRNA and protein levels of ARHGAP6 significantly reduced in human BC tissues and cell lines compared with corresponding adjacent non-cancerous tissues and normal urothelial cells. In vitro, ARHGAP6 overexpression markedly decreased the viability, migration, and invasion of BC cells. Interestingly, low ARHGAP6 expression in BC strongly correlated with poor patient survival and was highly associated with metastasis and ß-catenin signaling. Furthermore, ARHGAP6 expression strongly influenced the sensitivity of BC cells to mitomycin C treatment. Together, our results demonstrate that ARHGAP6 plays critical roles in regulating the proliferation, migration, invasion, and metastasis of BC cells possibly via the modulation of ß-catenin and strongly influences the chemosensitivity of BC cells.
Asunto(s)
Mitomicina , Neoplasias de la Vejiga Urinaria , Humanos , beta Catenina/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Activadoras de GTPasa/genética , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
Objective: To assess the interplay among psychopathological symptoms and real-life functioning, and to further detect their influence with violent behavior in patient with schizophrenia. Methods: A sample of 1,664 patients with post-violence assessments and their propensity score-matched controls without violence from a disease registration report system of community mental health service in Guangdong, China, were studied by network analysis. Ising-Model was used to estimate networks of psychopathological symptoms and real-life functioning. Then, we tested whether network properties indicated the patterns of interaction were different between cases and controls, and calculated centrality indices of each node to identify the central nodes. Sensitivity analysis was conducted to examine the difference of interaction patterns between pre-violence and post-violence assessments in violence cases. Results: Some nodes in the same domain were highly positive interrelations, while psychopathological symptoms were negatively related to real-life functioning in all networks. Many symptom-symptom connections and symptom-functioning connections were disconnected after the violence. The network density decreased from 23.53% to 12.42% without statistical significance (p = 0.338). The network structure, the global network strength, and the global clustering coefficient decreased significantly after the violence (p < 0.001, p = 0.019, and p = 0.045, respectively). Real-life functioning had a higher node strength. The strength of sleeping, lack of spontaneity and flow of conversation, and preoccupation were decreased in post-violence network of patients. Conclusion: The decreasing connectivity may indicate an increased risk of violence and early warning for detecting violence. Interventions and improving health state based on nodes with high strength might prevent violence in schizophrenia patients.
RESUMEN
Peripheral nerve damages take place as a result of trauma, compression or disease, resulting in sensory loss, impaired motor function and subsequent challenges. In the current study, ginkgo biloba extract was loaded into PCL/gelatin scaffolds through electrospinning method. The scaffolds were characterized in vitro using various studies. The prepared nanofibrous scaffolds were rolled up to make neural guidance channels. Then, the conduits were seeded with adipose-derived stem cells and transplanted into a rat model of sciatic nerve injury. The scaffolds were not toxic and had optimal tensile and suturability. The animals treated with the conduits that delivered adipose-derived stem cells and ginkgo biloba extract, and received the treadmill exercise, had significantly higher motor and sensory functions recovery. In addition, histopathological examinations showed beneficial role of the exercise plan on the nervous system repair.
Asunto(s)
Tejido Adiposo , Gelatina , Ginkgo biloba , Nanofibras , Traumatismos de los Nervios Periféricos , Extractos Vegetales , Poliésteres , Células Madre , Andamios del Tejido , Ginkgo biloba/química , Animales , Extractos Vegetales/farmacología , Andamios del Tejido/química , Gelatina/química , Gelatina/farmacología , Nanofibras/química , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/patología , Poliésteres/química , Poliésteres/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/citología , Células Madre/efectos de los fármacos , Células Madre/citología , Ratas , Regeneración Nerviosa/efectos de los fármacos , Condicionamiento Físico Animal , Trasplante de Células Madre/métodos , Masculino , Nervio Ciático/efectos de los fármacos , Ratas Sprague-Dawley , Extracto de GinkgoRESUMEN
@#Abstract:Objective To optimize the production process of inactivated vaccine of Aeromonas veronii(AV)CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time(2~16 h),medium(optimized fermentation medium,LB medium and NB medium)and fermentation conditions(in⁃ oculation amount of 1%,5%,10% and 15%;ventilation rate of 2,4,6 and 8 L/min and fermentation time of 6,8,10 and 12 h). The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution(0. 10%,0. 20%,0. 30% and 0. 40%),inactivation temperature(28 and 37 ℃)and inactivation time(24, 48 and 72 h). The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%,ventilation rate was 4 L/min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU/mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge,the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.
RESUMEN
Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and waning immunity call for next-generation vaccine strategies. Here, we assessed the immunogenicity and protective efficacy of two SARS-CoV-2 vaccines targeting the WA1/2020 spike protein, Ad26.COV2.S (Ad26) and Spike ferritin Nanoparticle (SpFN), in nonhuman primates, delivered as either a homologous (SpFN/SpFN and Ad26/Ad26) or heterologous (Ad26/SpFN) prime-boost regimen. The Ad26/SpFN regimen elicited the highest CD4 T cell and memory B cell responses, the SpFN/SpFN regimen generated the highest binding and neutralizing antibody responses, and the Ad26/Ad26 regimen generated the most robust CD8 T cell responses. Despite these differences, protective efficacy against SARS-CoV-2 Omicron BA.1 challenge was similar for all three regimens. After challenge, all vaccinated monkeys showed significantly reduced peak and day 4 viral loads in both bronchoalveolar lavage and nasal swabs as compared with sham animals. The efficacy conferred by these three immunologically distinct vaccine regimens suggests that both humoral and cellular immunity contribute to protection against SARS-CoV-2 Omicron challenge.
RESUMEN
The ongoing coronavirus disease 2019 pandemic has raised concerns about the risk of re-infection. Non-neutralizing epitopes are one of the major reasons for antibody-dependent enhancement. Past studies on the ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have revealed an infectivity-enhancing site on the ancestral SARS-CoV-2 spike protein. However, infection enhancement associated with the SARS-CoV-2 Omicron strain remains elusive. In this study, we examined the antibodies induced by a multiple epitope-based vaccine, which showed infection enhancement for the Omicron strain but not for the ancestral SARS-CoV-2 or Delta strain. By examining the antibodies induced by single epitope-based vaccines, we identified a conserved epitope, IDf (450-469), with neutralizing activity against ancestral SARS-CoV-2, Delta, and Omicron. Although neutralizing epitopes are present in the multiple epitope-based vaccine, other immunodominant non-neutralizing epitopes such as IDg (480-499) can shade their neutralizing activity, leading to infection enhancement of Omicron. Our study provides up-to-date epitope information on SARS-CoV-2 variants to help design better vaccines or antibody-based therapeutics against future variants.