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1.
Reprod Sci ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656424

RESUMO

Previous studies had shown that the gut microbiota of polycystic ovary syndrome (PCOS) patients had significant differences from those of healthy individuals, which may play an important role in the pathogenesis of PCOS. Lifestyle intervention, such as nutritional intervention, could improve the metabolic profiles and PCOS-like phenotypes of PCOS patients. Meanwhile, nutritional intervention could rapidly alter and reshape the distribution of gut microbiota in individuals. Therefore, we sought to investigate the differences in gut microbiota in overweight and obese PCOS patients with or without nutritional intervention. Thirty-six overweight and obese PCOS patients were finally enrolled in the study. Eighteen individuals who refused nutritional intervention (RNI) were collected as the RNI group. Eighteen individuals who received the nutritional intervention were collected as the pre-NI group before the nutritional intervention. And they were also collected as the NI group after the nutritional intervention for 4-12 weeks. Significant decreases in BMI, FBG, TC, TG, APO A1, and APO B were observed when comparing the NI group with the pre-NI and RNI groups after the nutritional intervention for 4-12 weeks. Meanwhile, the differences in the phylum Firmicutes, Bacteroidetes, and the species Eubacterium rectale, Flavonifractor plautii, and Bacteroides vulgatus between the NI and the RNI groups were observed, which may be potentially linked to the improved inflammatory state and PCOS-like phenotypes of overweight and obese PCOS individuals.

2.
Pest Manag Sci ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36606406

RESUMO

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite, which transmits various pathogens to humans, livestock and wild animals. Hexokinase (HK) is a key regulatory enzyme of the glycolytic pathway in the organisms. However, little is known about hexokinase and its functions in ticks. RESULTS: The open reading frame of the H. longicornis HK (HlHK) gene was 1425 bp and encoded a protein of 474 amino acids, containing conserved domains for glucose, glucose 6-phosphate, and adenosine triphosphate. The expression of HlHK gene was detected at different developmental stages and in different tissues of unfed female ticks. Enzyme-linked immunosorbent assay revealed that both HK protein- and DNA-based vaccines increased the antibody levels of the immunized animals. A vaccination trail on rabbits against H. longicornis infestation indicated that the rHlHK protein and HlHK DNA vaccines reduced the number of attached female ticks by 9% and 12%, egg mass weight by 36% and 34%, and egg hatching rate by 41% and 17%, respectively. Overall, protein vaccination conferred 65.6% protection against adult female ticks, whereas the DNA vaccine conferred 51.8% protection. CONCLUSION: This is the first report of the molecular characterization of the HK protein and sequencing of the HK gene from H. longicornis. Positive results from vaccination trials on rabbits of the recombinant HK protein and HK DNA suggest that these novel anti-tick vaccines potentially can be used as viable tick control tools for the management of the Asian longhorned tick. Additionally, inhibition of glucose metabolism may be a new strategy for tick control. © 2023 Society of Chemical Industry.

3.
Materials (Basel) ; 16(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36676209

RESUMO

In this work, graphene oxide@Fe3O4 (GO@Fe3O4) two-dimensional magnetically oriented nanocomposites were prepared through the co-precipitation approach using graphene oxide as the carrier and FeCl3·6H2O and FeSO4·7H2O as iron sources. The samples were characterized and tested by X-ray diffraction, a transmission electron microscope, Fourier-transform infrared spectroscopy, a vibrating-specimen magnetometer, a polarized optical microscope, an optical microscope, etc. The effects of material ratios and reaction conditions on the coating effects of Fe3O4 on the GO surface were investigated. The stable GO@Fe3O4 sol system was studied and constructed, and the optical properties of the GO@Fe3O4 sol were revealed. The results demonstrated the GO@Fe3O4 two-dimensional nanocomposites uniformly coated with Fe3O4 nanoparticles were successfully prepared. The GO@Fe3O4 two-dimensional nanocomposites exhibited superparamagnetic properties at room temperature, whose coercive force was 0. The stable GO@Fe3O4 sol system could be obtained by maintaining 1 < pH < 1.5. The GO@Fe3O4 sol showed magneto-orientation properties, liquid crystalline properties, and photonic crystal properties under the influence of the external magnetic field. The strength and direction of the magnetic field and the solid content of the GO@ Fe3O4 sol could regulate the aforementioned properties. The results suggest that GO@Fe3O4 two-dimensional magnetically oriented nanocomposites have potential applications in photonic switches, gas barriers, and display devices.

4.
Mar Drugs ; 21(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36662212

RESUMO

It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional ß-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA ß-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA ß-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet ß-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.


Assuntos
Ácidos Graxos Ômega-3 , Insulinas , Camundongos , Animais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Estreptozocina/toxicidade , Ácidos Graxos Insaturados , Ácidos Graxos , Inflamação/tratamento farmacológico , Pâncreas , Suplementos Nutricionais , Apoptose , Estresse Oxidativo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia
5.
BMC Infect Dis ; 23(1): 37, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670349

RESUMO

BACKGROUND: Acute and early HIV (AEH) infection is characterized by a high viral load and infectivity. Approximately 50% of cases of HIV-1 transmission occur during AEH. Understanding sexual behaviour trajectories would be useful for predicting changes in the risk of HIV acquisition. However, few studies have investigated sexual behaviour trajectories and their association with AEH acquisition. This study identified behaviour trajectories among men who have sex with men (MSM), determined the risk of AEH infection, and compared risk factors between different behaviour trajectories. METHODS: The study was based on an ongoing prospective open cohort of voluntary HIV counselling and testing (VHCT) among MSM in Tianjin, China. From 2011 to 2019, 1974 MSM were recruited. Group-based trajectory modelling (GBTM) was used to identify behaviour trajectories by constructing a sexual risk behaviour score. Logistic regression and generalized estimating equation (GEE) were used to compare the risk of AEH infection and risk factors for different behaviour trajectories. All data analyses were performed using SAS 9.4. RESULTS: The incidence of AEH infection was 1.76/100 person-years, with 64 AEH infections documented in 3633 person-years of follow-up. Three sexual behaviour trajectories were identified: CL (consistently low risk, 35.46%), CH (consistently high risk, 42.71%) and HTL (high to low risk, 21.83%). MSM in the HTL and CH groups had higher AEH infection rates than MSM in the CL group (6.73%, 3.08% and 1.28%, respectively), with ORs of 5.54 (2.60, 11.82) and 2.44 (1.14, 5.25), respectively. MSM aged 30-50 years old and MSM who underwent HIV testing in the last year were more likely to be in the CH group and HTL group. In addition, the HTL group was characterized by a lower likelihood of local registration and a higher likelihood of working as a MSW. CONCLUSION: MSM in the CH group and the HTL group had a higher risk of AEH infection. In the future, VHCT should be performed more often among younger MSM, and HIV counselling should be given the same priority as HIV testing. In addition, VHCT combined with PrEP may have a better preventive impact on MSM with a high risk of AEH infection.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Homossexualidade Masculina , Estudos de Coortes , Estudos Prospectivos , Infecções por HIV/prevenção & controle , Comportamento Sexual , China/epidemiologia
6.
J Affect Disord ; 323: 884-892, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36566934

RESUMO

BACKGROUND: Adverse childhood experiences (ACES) are prevalent and have long-lasting effects. This study explored how ACE exposure is associated with subsequent depression and cognitive impairment and whether sociodemographic characteristics modify that association. METHOD: This study used data on 14,484 participants of the 2015 China Health and Retirement Longitudinal Study (CHARLS) and 2014 CHARLS life history survey. Depression was assessed using the 10-item Center for Epidemiologic Studies Depression scale. Cognitive performance was evaluated via three composite measures: episodic memory, mental intactness, and global cognition. Twelve ACE indicators were measured using a validated questionnaire. Multiple regression models and stratified analyses explored the relationship between ACES and subsequent depression and cognitive impairment, as well as potential modifiers. RESULTS: Compared with individuals without ACES, those who experienced four or more ACES had a higher risk of subsequent depression (adjusted odds ratio, aOR = 2.65, 95 % confidence intervals [CIs]: 2.21 to 3.16), poorer mental intactness (ß = -0.317 [-0.508 to -0.125]), and worse global cognition (-0.437 [-0.693 to -0.181]). Trend analyses showed a dose-response association between accumulated ACES and subsequent depression and cognitive impairment. No modifications of those associations by age, sex, educational level, or family's financial status during childhood were observed. LIMITATIONS: Self-reported measures could favour recall bias. CONCLUSION: Our study suggests that ACES increase the risk of subsequent depression and cognitive impairment in Chinese adults regardless of sociodemographic characteristics. These findings provide important implications for mitigating the adverse effects of early-life stress and promoting health in adulthood.


Assuntos
Experiências Adversas da Infância , Disfunção Cognitiva , Adulto , Humanos , Depressão/epidemiologia , Depressão/psicologia , Estudos Longitudinais , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia
7.
Cell Stem Cell ; 30(1): 69-85.e7, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36574771

RESUMO

N6-methyladenosine (m6A) is a common chemical modification for mammalian mRNA and exhibits high dynamics in various biological processes. However, dynamics of m6A RNA methylome during leukemogenesis remains unknown. Here, we delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6 as a key for maintaining AML stem cells. We observe an obvious change in m6A methylome during leukemogenesis and find that protein arginine methyltransferase PRMT6 and m6A reader IGF2BP2 maintain the function of human and murine leukemia stem cells (LSCs). Genetic deletion or pharmacological inhibition of PRMT6 damages AML development and LSC function. Mechanistically, IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner, which catalyzes H3R2me2a and suppresses lipid transporter MFSD2A expression. PRMT6 loss upregulates MFSD2A expression that increases docosahexaenoic acid levels and impairs LSC maintenance. Collectively, our findings reveal a critical role of PRMT6-MFSD2A signaling axis in AML development and provide a therapeutic strategy for targeting LSCs.


Assuntos
Leucemia Mieloide Aguda , RNA , Humanos , Animais , Camundongos , RNA/metabolismo , Epigenoma , RNA Mensageiro/metabolismo , Células-Tronco Neoplásicas/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Lipídeos , Mamíferos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Nucleares/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo
8.
J Trace Elem Med Biol ; 76: 127117, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36512970

RESUMO

OBJECTIVE: To evaluate the effects of yttrium nitrate on the development of the parent, offspring and third generation of Sprague-Dawley (SD) rats by using a two-generation reproductive toxicity test. METHODS: The SD rats were randomly divided into 0 mg/kg group, 10.0 mg/kg group, 30.0 mg/kg group and 90.0 mg/kg group according to the different doses of yttrium nitrate administration. The reproductive toxicity of parent, offspring and third generation SD rats were compared. RESULTS: The weight gains of F1a female rats and F2a female rats in the low-dose groups were significantly lower than those of the control groups (p < 0.05), the weight gains of F1a male rats in the medium-dose and high-dose groups were significantly lower than those of the control groups (p < 0.05), and the weight gains of F2a male rats in the low-dose, medium-dose and high-dose groups were significantly lower than those of the control groups (p < 0.05). In F0 male rats, the absolute weight and relative weight of the liver in the low-dose, middle-dose, and high-dose groups were significantly lower than those of the control group (p < 0.05). In F1b male rats, the absolute and relative weights of the liver in the medium-dose and high-dose groups were significantly lower than those of the control group (p < 0.05). In F2b male rats, the absolute and relative weights of the liver and spleen of the medium-dose and high-dose groups were significantly lower than those of the control group (p < 0.05). In F2a female rats, the absolute weight and relative weight of oviduct in the high-dose group were significantly lower than those in the control group (p < 0.05). The absolute and relative weights of lung, spleen, brain and uterus of F2b female rats in the high-dose group were higher than those of the control group (p < 0.05). But the pathological test results showed no hepatotoxicity. There was no statistically significant difference in sperm count and sperm motility between male rats in the yttrium nitrate administration groups and the control group (p > 0.05). There was no significant correlation between F0, F1a, F1b, F2a, F2b SD rats' reproductive organ lesions and the dose of yttrium nitrate. CONCLUSION: Yttrium nitrate at a dose of 90 mg/kg has no reproductive toxicity to two generations of SD rats, but 30.0 mg/kg dose of yttrium nitrate is toxic to the liver weight of male two generations of SD rats, but no hepatotoxicity.


Assuntos
Nitratos , Motilidade Espermática , Masculino , Ratos , Feminino , Animais , Ratos Sprague-Dawley , Nitratos/farmacologia , Sêmen , Reprodução , Aumento de Peso , Peso Corporal
9.
Theriogenology ; 198: 153-163, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36586353

RESUMO

Zebrafish is an important animal model, thousands lines have been developed, thus having a great need for their preservation. However, the cryopreservation of fish oocytes is still limited and needs improvement. The sodium alginate hydrogel, in addition to providing support for the cells, has been shown to be a potential cryoprotectant. Therefore, the aim of this study was to evaluate the sodium alginate hydrogel encapsulation technique efficiency during zebrafish ovarian tissue vitrification. The encapsulation methodology was standardized in the first experiment. In Experiment 2, we evaluated four vitrified groups: standard protocol without encapsulation (VS); encapsulated with cryoprotectants (VS1-A); encapsulated with half the cryoprotectants concentration (VS2-A); encapsulated without cryoprotectants (VA). VS treatment (54.6 ± 12.3%; 23.7 ± 9.9%; 12.6 ± 5.0%) did not differ from the VS1-A and VA showed a lower membrane integrity percentage (1.2 ± 1.4%; 0.3 ± 0.6%; 0.5 ± 1.5%). Mitochondrial activity was significantly greater in non-encapsulated treatment (VS) when compared to the encapsulated treatments. VS1-A and VS obtained the lowest lipid peroxidation (39.4 ± 4.4 and 40.5 ± 3.3 nmol MDA/mg respectively) in which VS was not significantly different from the VS2-A treatment (63.6 ± 3.1 nmol MDA/mg), unlike, VA obtained the highest lipid peroxidation level (124.7 ± 7.9 nmol MDA/mg). The results obtained in this study demonstrate that the sodium alginate hydrogel encapsulation technique did not have a cryoprotective action, but maintained the membrane integrity when used the standard concentration of cryoprotectants. However, halving the cryoprotectant concentration of fragments encapsulated in alginate hydrogel did not cause an increase in lipid peroxidation. In addition, it provided support and prevented the oocytes from loosening from the tissue during the vitrification process, being an interesting alternative for later in vitro maturation.


Assuntos
Vitrificação , Peixe-Zebra , Animais , Hidrogéis , Criopreservação/métodos , Criopreservação/veterinária , Oócitos , Crioprotetores , Alginatos
10.
Blood Adv ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469551

RESUMO

B-cell activating factor receptor (BAFF-R) is a mature B-cell survival receptor which is highly expressed in a wide variety of B-cell malignancies, but with minimal expression in immature B-cells. These properties make BAFF-R an attractive target for therapy of B-cell lymphomas. We generated a novel humanized anti BAFF-R monoclonal antibody (mAb) with high specificity and potent in vitro and in vivo activity against B-cell lymphomas and leukemias. The humanized variants of an original chimeric BAFF-R mAb retained BAFF-R binding affinity and antibody-dependent cellular cytotoxicity against a panel of human cell lines and primary lymphoma samples. Furthermore, one humanized BAFF-R mAb clone and its afucosylated version, glycoengineered to optimize the primary mechanism of action, prolonged survival of immunodeficient mice bearing human tumor cell line or patient-derived lymphoma xenografts (PDX) in three separate models, compared with controls. Finally, the tissue specificity of this humanized mAb was confirmed against a broad panel of normal human tissues. Taken together, we have identified a robust lead candidate BAFF-R mAb for clinical development.

11.
Clin Lab ; 68(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36546736

RESUMO

BACKGROUND: The aim was to investigate the value of concomitant use of fecal KRAS-APC-p53-BRAF mutation test and a fecal immunochemical test (FIT) for colorectal cancer (CRC) screening. METHODS: Stool samples of 279 subjects were collected from the Fujian provincial hospital and divided into five groups: CRC (n = 82); advanced adenoma (AA, n = 76); non-advanced adenoma (NAA, n = 24); healthy control (n = 85); and interference group (n = 12). All stool samples were tested using a fecal multigene mutation (KRAS-APC-p53-BRAF) Kit and FIT. RESULTS: The sensitivity of combined use of fecal multigene mutation test and FIT for detecting CRC [84.15% (69/ 82)] was significantly higher than that of fecal multigene mutation test [47.56% (39/82), p < 0.001] or FIT [71.95% (59/82), p < 0.001] alone. The sensitivity of combined use for detection of AA [48.68% (37/76)] was also significantly higher than that of multigene mutation test [26.32% (20/76), p < 0.001] or FIT [28.95% (22/76), p < 0.001] alone. The specificity of combined use for detection of NAA and healthy control was 87.16%. CONCLUSIONS: The combination of fecal multigene (KRAS-APC-p53-BRAF) mutation test and FIT has greater sensitivity than alone and may be a useful noninvasive method for CRC screening.


Assuntos
Adenoma , Neoplasias Colorretais , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Detecção Precoce de Câncer/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Sangue Oculto , Fezes , Adenoma/diagnóstico , Adenoma/genética , Mutação , Programas de Rastreamento , Colonoscopia
12.
Antioxidants (Basel) ; 11(12)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36552574

RESUMO

Senile and disuse osteoporosis have distinct bone turnover status and lack effective treatments. In this study, senescence-accelerated mouse prone 8 (SAMP8) and hindlimb unloading mouse models were used to explore the protective effects of daphnetin on these two types of osteoporosis, and primary osteoblasts and bone marrow monocyte-derived osteoclasts, as well as pre-osteoblast MC3T3-E1, and osteoclast precursor RAW264.7 cells were used to investigate the underlying mechanisms. The results showed that daphnetin administration effectively improved bone remodeling in both senile and disuse osteoporosis, but with different mechanisms. In senile osteoporosis with low bone turnover, daphnetin inhibited NOX2-mediated ROS production in osteoblasts, resulting in accelerated osteogenic differentiation and bone formation, while in disuse osteoporosis with high bone turnover, daphnetin restored SIRT3 expression, maintained mitochondrial homeostasis, and additionally upregulated SOD2 to eliminate ROS in osteoclasts, resulting in attenuation of osteoclast differentiation and bone resorption. These findings illuminated that daphnetin has promising potential for the prevention and treatment of senile and disuse osteoporosis. The different mechanisms may provide clues and basis for targeted prevention and treatment of osteoporosis according to distinct bone turnover status.

13.
BMC Pulm Med ; 22(1): 490, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36582007

RESUMO

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with different subtypes, multidisciplinary teams-led management, and a poor prognosis. Currently, the clinical benefits of stage III NSCLC in the neoadjuvant setting are still unclear. We performed a meta-analysis of published data on neoadjuvant chemoimmunotherapy in stage III NSCLC to systematically evaluate its efficacy and safety. METHODS: We searched the databases to identify eligible studies of neoadjuvant chemoimmunotherapy for stage III NSCLC. The primary outcomes mainly included pathological and radiological response outcomes, the feasibility of surgery, and the safety of the regimen. The pathological and radiological response included the rate of major pathologic response (MPR), complete pathologic response (pCR), radiological response outcomes, and R0 resection; The feasibility included the rate of surgical resection, conversion to thoracotomy, surgical complications, pathological downstaging of clinical disease stage. The safety included the incidence of treatment-related adverse events (TRAEs) and severe adverse events (SAEs). R 4.1.3 software was conducted for data analysis, and p < 0.05 was considered statistically significant. RESULTS: Nine trials containing a total of 382 populations were eligible for the meta-analysis, with the pooled surgical resection rate of 90%. Owing to the large heterogeneity of the single-rate meta-analysis, the random effect model was adopted. The estimated pooled prevalence of MPR was 56% (95%CI 0.39-0.72) and of pCR was 39% (95%CI 0.28-0.51). The pooled rate of TRAEs was 65% (95%CI 0.17-0.99) and SAEs was 24% (95%CI 0.05-0.49). CONCLUSION: Compared to neoadjuvant chemotherapy or immunotherapy, neoadjuvant chemoimmunotherapy achieved more pathological and radiological relief, and has a high surgical resection rate and low risk of conversion to thoracotomy and surgical complications, with poor tolerance of toxicity but rarely developing life-threatening adverse events. In conclusion, neoadjuvant chemoimmunotherapy is suggested to be beneficial for stage III NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Neoadjuvante/efeitos adversos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Imunoterapia
14.
Cells ; 11(24)2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36552785

RESUMO

B and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule that mediates the escape of tumor cells from immunosurveillance. Consequently, BTLA and its ligand herpesvirus entry mediator (HVEM) are potentially immunotherapeutic targets. However, the potential effects of BTLA on tumor cells remain incompletely unknown. Here, we show that BTLA is expressed across a broad range of tumor cells. The depletion of BTLA or HVEM promotes cell proliferation and colony formation, which is reversed by the overexpression of BTLA in BTLA knockout cells. In contrast, overexpression of BTLA or HVEM inhibits tumor cell proliferation and colony formation. Furthermore, the proliferation of a subpopulation with high BTLA was also significantly slower than that of the low BTLA subpopulation. Mechanistically, the coordination of BTLA and HVEM inhibits its major downstream extracellular regulated protein kinase (ERK1/2) signaling pathway, thus preventing tumor cell growth. This study demonstrates that tumor cell-intrinsic BTLA/HVEM is a potential tumor suppressor and is likely to have a potential antagonist for immunotherapy, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.


Assuntos
Neoplasias , Receptores Imunológicos , Humanos , Proliferação de Células , Sistema de Sinalização das MAP Quinases , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores Imunológicos/metabolismo , Subpopulações de Linfócitos T/metabolismo
15.
Front Psychiatry ; 13: 996996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36424991

RESUMO

Purpose: University freshmen are particularly vulnerable as they are undergoing the transition from high school to university with a range of changes. Sleep problems among this group in the Qinghai-Tibet Plateau of China were barely studied. This study aimed to explore sleep disturbance, and its association with quality of life (QoL) and demographic and clinical characteristics among university freshmen in Qinghai-Tibet Plateau, China. Methods: A multistage stratified cluster random sampling method was performed to recruit student participants with a structured questionnaire to collect sociodemographic and clinical characteristics, and lifestyle behaviors. Sleep disturbance including three aspects of sleep disturbance (i.e., difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA)) was assessed using standardized measurement. Multiple logistic regression models were applied to analyze the data. Results: Among included 2,769 freshmen, the prevalence of sleep disturbance was 14.8% (95% CI: 14.2-15.5%), and corresponding prevalence of DIS, DMS, and EMA was 8.2% (95% CI: 7.7-8.7%), 8.3% (95% CI: 7.8-8.8%), and 4.2% (95% CI: 3.8-4.6%), respectively. Freshmen with sleeping disturbance had significantly lower QoL in physical [F (1, 2769) = 60.23, p < 0.001], psychological [F (1, 2769) = 46.18, p < 0.001], social [F (1, 2769) = 23.04, p < 0.001], and environment [F (1, 2769) = 6.07, p = 0.01] domains. Multiple logistic regression analyses revealed that having breakfast five times a week or less (less than three times, OR = 1.79, 95% CI: 1.34-2.40; 3-5 times, OR = 1.40, 95% CI: 1.09-1.79), self-perceived severe Internet dependence (OR = 1.71, 95% CI: 1.11-2.65), self-perceived poor health status (OR = 3.44, 95% CI: 2.06-5.74), high academic stress (OR = 1.42, 95% CI: 1.13-1.78), poor relationship with classmates (OR = 3.44, 95% CI: 1.53-7.71), and severe ADHD symptoms (OR = 1.08, 95% CI: 1.05-1.12) were positively associated with sleeping disturbance. Conclusion: Sleep disturbance was common among freshmen and is associated with poorer QoL. Prevention and intervention strategies should be developed and implemented, especially among the vulnerable university freshman groups.

16.
Drug Chem Toxicol ; : 1-17, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384384

RESUMO

This study was designed to evaluate the subchronic toxicity of the compound of diphenhydramine hydrochloride (DH) and caffeine in Sprague-Dawley (SD) rats and beagle dogs. A total of 180 SD rats (15/sex/group) were randomly divided into the compound low-, medium- and high-dose groups (51, 102, 204 mg/kg), DH group (60 mg/kg), caffeine group (144 mg/kg) and the vehicle control group. Sixty beagle dogs (5/sex/group) were randomly divided into the compound low-, medium- and high-dose groups (male: 14.20, 28.30, 56.60 mg/kg, female: 5.66, 14.20, 28.30 mg/kg), DH group (male: 16.60 mg/kg, female: 8.30 mg/kg), caffeine group (male: 40.00 mg/kg, female: 20.00 mg/kg) and the vehicle control group. Rats and dogs were given continuous oral administration for 28 days following a 28-day recovery period. The adverse effects of the compound on rats and beagle dogs mainly included anorexia and liver function impairment. Most adverse effects induced by administration were reversible. Under the experimental conditions, the no-observed-adverse-effect level (NOAEL) of the compound of DH and caffeine was 51 mg/kg/day for SD rats and 28.30 mg/kg/day (male) and 5.66 mg/kg/day (female) for beagle dogs.

17.
Front Public Health ; 10: 1008180, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388370

RESUMO

Background: In spite of initial widespread skepticism, city lockdown has been proved to be an effective short-term tool in containing and delaying the spread of a viral epidemic. The measures to ensure the supply of the basic necessities adequately and equitably, especially for those vulnerable ones has become a major challenge faced by all countries taking a city lockdown measure during the epidemic. Methods: Data was collected through relevant government documents, work records, policy reports, media reports and the online-work information platform designed by the research group. Based on these references, the study analyzed the mainly technical difficulties and the countermeasures of the supply process, and summarized the key characteristics of basic necessities supply strategy for vulnerable groups in Shanghai. Results: The supply strategy for vulnerable groups in Shanghai covers 16 districts, 232 streets and 6,028 neighborhood communities, which has already been in test running in April in some districts. The practical experience in Shanghai solved three key materials supply problems (lack of purchase channels, insufficient material reserves, insufficient transportation capacity) faced by government during the city lockdown, and showed three essential characteristics (overall coordination, community-centered intervention, technical support). Conclusions: The findings in this study may provide some suggestions to other countries about how to better manage the preparation, dispatch and transportation of basic necessities in shortage for those vulnerable ones during the city lockdown.


Assuntos
COVID-19 , Populações Vulneráveis , Humanos , China/epidemiologia , COVID-19/epidemiologia , Pandemias , Controle de Doenças Transmissíveis
18.
ACS Sens ; 7(11): 3560-3570, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36382569

RESUMO

Current tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detect either the constituent nucleic acids/proteins of the viral particles or antibodies specific to the virus, but cannot provide information about viral neutralization by an antibody and the efficacy of an antibody. Such information is important about individuals' vulnerability to severe symptoms or their likelihood of showing no symptoms. We immobilized online SARS-CoV-2 spike (S1) protein and angiotensin-converting enzyme 2 (ACE2) into separate surface plasmon resonance (SPR) channels of a tris-nitrilotriacetic acid (tris-NTA) chip to simultaneously detect the anti-S1 antibody and viral particles in serum samples. In addition, with a high-molecular-weight-cutoff filter, we separated the neutralized viral particles from the free antibody molecules and used a sensing channel immobilized with Protein G to determine antibody-neutralized viral particles. The optimal density of probe molecules in each fluidic channel can be precisely controlled through the closure and opening of the specific ports. By utilizing the high surface density of ACE2, multiple assays can be carried out without regenerations. These three species can be determined with a short analysis time (<12 min per assay) and excellent sensor-to-sensor/cycle-to-cycle reproducibility (RSD < 5%). When coupled with an autosampler, continuous assays can be performed in an unattended manner at a single chip for up to 6 days. Such a sensor capable of assaying serum samples containing the three species at different levels provides additional insights into the disease status and immunity of persons being tested, which should be helpful for containing the SARS-CoV-2 spread during the era of incessant viral mutations.


Assuntos
COVID-19 , SARS-CoV-2 , Ressonância de Plasmônio de Superfície , Humanos , Enzima de Conversão de Angiotensina 2 , Anticorpos Antivirais , COVID-19/diagnóstico , Reprodutibilidade dos Testes , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus , Vírion/isolamento & purificação
19.
Seizure ; 103: 108-114, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36399868

RESUMO

OBJECTIVE: To investigate the genotype and phenotype of epilepsy caused by ADGRV1 variants in Chinese children. METHODS: A total of 625 patients with epilepsy who had undergone whole-exon gene sequencing or epilepsy and related paroxysmal disease gene panel sequencing were recruited. Variants were evaluated for susceptibility pathogenicity based on their frequency in the Genome Aggregation Database (≤ 0.001). We used six algorithms (sorting intolerant from tolerant (SIFT), PolyPhen-2, Mutation Taster, CADD, REVEL and Splice AI) that predicted that the ADGRV1 variant would have a harmful impact on the function of genes and gene products. We retrospectively reviewed the clinical information of patients with susceptible pathogenic ADGRV1 variants. The relationship between the genotype and phenotype was also analyzed. RESULTS: Eighteen patients with epilepsy were found to have likely pathogenic variants in ADGRV1. The rate of ADGRV1 variants in patients with epilepsy in this cohort was 2.88%. A total of 19 ADGRV1 variants were found, of which 13 were novel and 6 had been previously reported. Eleven out of the 18 children (61.1%) had febrile and afebrile seizures (FS and AS), two children had only FS, one child had infantile spasms, and the other four children had only AS that occurred during sleep (Rolandic epilepsy or atypical Rolandic epilepsy). SIGNIFICANCE: Our study showed a statistically significant association between ADGRV1 variants and FS and AS (p < 0.05), supporting the hypothesis that ADGRV1 is a susceptibility gene for Rolandic epilepsy and infantile spasms. Most epilepsy cases caused by ADGRV1 variants have a good prognosis.


Assuntos
Epilepsia Rolândica , Convulsões Febris , Espasmos Infantis , Humanos , China , Febre , Genótipo , Mutação/genética , Fenótipo , Estudos Retrospectivos
20.
J Sci Food Agric ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377349

RESUMO

BACKGROUND: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. RESULTS: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. CONCLUSION: SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.

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