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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 603-609, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39223025

RESUMEN

Kupffer cells (KC),an important subset of immune cells in the liver,are essential for maintaining tissue homeostasis and responding quickly to liver damage.The complement receptor of the immunoglobulin superfamily (CRIg) is a receptor protein on the KC membrane.CRIg can not only capture pathogens in the blood flowing through the liver by complement binding but also mediate immune responses by regulating immune cells in the liver.Recent studies have confirmed the role of CRIg in regulating liver immunity.This article reviews the main modes of action of CRIg and the research progress of CRIg in regulating liver immunity.


Asunto(s)
Macrófagos del Hígado , Hígado , Receptores de Complemento , Humanos , Hígado/inmunología , Hígado/metabolismo , Macrófagos del Hígado/inmunología , Macrófagos del Hígado/metabolismo , Receptores de Complemento/inmunología , Receptores de Complemento/metabolismo , Animales
2.
Front Cell Infect Microbiol ; 14: 1442995, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39310786

RESUMEN

Chlamydia are Gram-negative, obligate intracellular bacterial pathogens that infect eukaryotic cells and reside within a host-derived vacuole known as the inclusion. To facilitate intracellular replication, these bacteria must engage in host-pathogen interactions to obtain nutrients and membranes required for the growth of the inclusion, thereby sustaining prolonged bacterial colonization. Autophagy is a highly conserved process that delivers cytoplasmic substrates to the lysosome for degradation. Pathogens have developed strategies to manipulate and/or exploit autophagy to promote their replication and persistence. This review delineates recent advances in elucidating the interplay between Chlamydia trachomatis infection and autophagy in recent years, emphasizing the intricate strategies employed by both the Chlamydia pathogens and host cells. Gaining a deeper understanding of these interactions could unveil novel strategies for the prevention and treatment of Chlamydia infection.


Asunto(s)
Autofagia , Infecciones por Chlamydia , Chlamydia trachomatis , Interacciones Huésped-Patógeno , Autofagia/fisiología , Chlamydia trachomatis/patogenicidad , Chlamydia trachomatis/fisiología , Humanos , Infecciones por Chlamydia/microbiología , Vacuolas/microbiología , Animales , Lisosomas/microbiología , Lisosomas/metabolismo
3.
Sensors (Basel) ; 24(16)2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39204867

RESUMEN

In order to solve the problem of difficult separation of audio signals collected in pig environments, this study proposes an underdetermined blind source separation (UBSS) method based on sparsification theory. The audio signals obtained by mixing the audio signals of pigs in different states with different coefficients are taken as observation signals, and the mixing matrix is first estimated from the observation signals using the improved AP clustering method based on the "two-step method" of sparse component analysis (SCA), and then the audio signals of pigs are reconstructed by L1-paradigm separation. Five different types of pig audio are selected for experiments to explore the effects of duration and mixing matrix on the blind source separation algorithm by controlling the audio duration and mixing matrix, respectively. With three source signals and two observed signals, the reconstructed signal metrics corresponding to different durations and different mixing matrices perform well. The similarity coefficient is above 0.8, the average recovered signal-to-noise ratio is above 8 dB, and the normalized mean square error is below 0.02. The experimental results show that different audio durations and different mixing matrices have certain effects on the UBSS algorithm, so the recording duration and the spatial location of the recording device need to be considered in practical applications. Compared with the classical UBSS algorithm, the proposed algorithm outperforms the classical blind source separation algorithm in estimating the mixing matrix and separating the mixed audio, which improves the reconstruction quality.

4.
Front Vet Sci ; 11: 1395718, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881785

RESUMEN

According to previous studies, the quality and fertilization rate of fresh sperm from boars of different ages were significantly different. However, the difference of freeze-thaw sperm quality and fertility in boars of different ages is unclear. In this study, boars of a Chinese native breed were assigned into two groups. Each group consisted of five boars aged aged either 2-3 years (young boars = YB) or 5-6 years (aging boars = AB) A total of 60 ejaculates for each group were collected and cryopreserved. Semen quality and in vitro fertility of post-thaw sperm was evaluated. The results showed that the concentration and motility of fresh sperm collected from AB were similar to YB, but their semen volume was higher than that in YB (p < 0.05). Frozen-thawed sperm of AB had lower viability than YB, and higher abnormal rate and reactive oxygen species (ROS) levels of YB (p < 0.05). There was no effect of the age on post-thaw sperm motility and time survival. Functional assessments indicated that increasing age markedly compromises the integrity of the sperm plasma membrane and acrosome, as well as mitochondrial functionality post-thaw, albeit without affecting DNA integrity. Furthermore, increasing age of boars reduces the ability of sperm to bind to the oocyte zona pellucida after thawing, delaying the time of the first embryo cleavage after fertilization. Finally, the early developmental efficiency of in vitro fertilized embryos progressing from 4-cell to blastocyst derived from post-thaw sperm in AB significantly decreased compared to those from YB (p < 0.05). Taken together, these results suggest that increasing age in boars impairs the quality and in vitro fertility of frozen thawed sperm.

5.
Front Public Health ; 12: 1385291, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887248

RESUMEN

Objective: The purpose of this study is to summarize the health system response to COVID-19 in four East Asian countries, analyze the effectiveness of their health system response, and provide lessons for other countries to control the epidemic and optimize their health system response. Methods: This study investigated and summarized COVID-19 data and health system response in four East Asian countries, China, Japan, Mongolia, and South Korea from national governments and ministries of health, WHO country offices, and official websites of international organizations, to assess the effectiveness of health system measures. Result: As of June 30, 2022, all four countries are in a declining portion of COVID-19. China has two waves, and new cases increased slowly, with the total cases per million remaining within 4, indicating a low level. Japan has experienced six waves, with case growth at an all-time high, total cases per million of 250.994. Mongolia started the epidemic later, but also experienced four waves, with total cases per million of 632.658, the highest of the four countries. South Korea has seen an increasing number of new cases per wave, with a total case per million of 473.759. Conclusion: In containment strategies adopted by China and Mongolia, and mitigation strategies adopted by Japan and South Korea, health systems have played important roles in COVID-19 prevention and control. While promoting vaccination, countries should pay attention to non-pharmaceutical health system measures, as evidenced by: focusing on public information campaigns to lead public minds; strengthening detection capabilities for early detection and identification; using technical ways to participate in contact tracing, and promoting precise judging isolation.


Asunto(s)
COVID-19 , Humanos , Asia Oriental/epidemiología , China/epidemiología , Control de Enfermedades Transmisibles , COVID-19/epidemiología , COVID-19/prevención & control , Atención a la Salud , Japón/epidemiología , Mongolia/epidemiología , República de Corea/epidemiología
6.
Virulence ; 15(1): 2350893, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38725096

RESUMEN

Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.


Asunto(s)
Proteínas Bacterianas , Coxiella burnetii , Lisosomas , Fosfatidilinositol 3-Quinasas , Fosfatos de Fosfatidilinositol , Canales de Potencial de Receptor Transitorio , Vacuolas , Animales , Humanos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Coxiella burnetii/metabolismo , Coxiella burnetii/crecimiento & desarrollo , Coxiella burnetii/genética , Células HeLa , Interacciones Huésped-Patógeno , Lisosomas/metabolismo , Lisosomas/microbiología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Fiebre Q/microbiología , Canales de Potencial de Receptor Transitorio/metabolismo , Canales de Potencial de Receptor Transitorio/genética , Vacuolas/microbiología , Vacuolas/metabolismo
7.
BMC Genomics ; 25(1): 447, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714941

RESUMEN

BACKGROUND: The health and size of the testes are crucial for boar fertility. Testicular development is tightly regulated by epigenetics. N6-methyladenosine (m6A) modification is a prevalent internal modification on mRNA and plays an important role in development. The mRNA m6A methylation in boar testicular development still needs to be investigated. RESULTS: Using the MeRIP-seq technique, we identify and profile m6A modification in boar testes between piglets and adults. The results showed 7783 distinct m6A peaks in piglets and 6590 distinct m6A peaks in adults, with 2,471 peaks shared between the two groups. Enrichment of GO and KEGG analysis reveal dynamic m6A methylation in various biological processes and signalling pathways. Meanwhile, we conjointly analyzed differentially methylated and expressed genes in boar testes before and after sexual maturity, and reproductive related genes (TLE4, TSSK3, TSSK6, C11ORF94, PATZ1, PHLPP1 and PAQR7) were identified. Functional enrichment analysis showed that differential genes are associated with important biological functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. CONCLUSION: The results demonstrate that m6A methylation, differential expression and the related signalling pathways are crucial for boar testicular development. These results suggest a role for m6A modification in boar testicular development and provided a resource for future studies on m6A function in boar testicular development.


Asunto(s)
Adenosina , Maduración Sexual , Testículo , Animales , Masculino , Testículo/metabolismo , Testículo/crecimiento & desarrollo , Adenosina/análogos & derivados , Adenosina/metabolismo , Porcinos/genética , Maduración Sexual/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Metilación , Regulación del Desarrollo de la Expresión Génica , Transducción de Señal , Perfilación de la Expresión Génica
8.
Ying Yong Sheng Tai Xue Bao ; 35(3): 577-586, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38646744

RESUMEN

The analytical equation based on Monin-Obukhov (M-O) similarity theory (i.e., wind profile equation) has been adopted since 1970s for using in the prediction of wind vertical profile over flat terrains, which is mature and accurate. However, its applicability over complex terrains remains unknown. This applicability signifies the accuracy of the estimations of aerodynamic parameters for the boundary layer of non-flat terrain, such as zero-displacement height (d) and aerodynamic roughness length (z0), which will determine the accuracy of frequency correction and source area analysis in calculating carbon, water, and trace gas fluxes based on vorticity covariance method. Therefore, the validation of wind profile model in non-flat terrain is the first step to test whether the flux model needs improvement. We measured three-dimensional wind speed data by using the Ker Towers (three towers in a watershed) at Qingyuan Forest CERN in the Mountainous Region of east Liaoning Province, and compared them with data from Panjin Agricultural Station in the Liaohe Plain, to evaluate the applicability of a generalized wind profile model based on the Monin-Obukhov similarity theory on non-flat terrain. The results showed that the generalized wind profile model could not predict wind speeds accurately of three flux towers separately located in different sites, indicating that wind profile model was not suitable for predicting wind speeds in complex terrains. In the leaf-off and leaf-on periods, the coefficient of determination (R2) between observed and predicted wind speeds ranged from 0.12 to 0.30. Compared to measured values, the standard error of the predicted wind speeds was high up to 2 m·s-1. The predicted wind speeds were high as twice as field-measured wind speed, indicating substantial overestimation. Nevertheless, this model correctly predicted wind speeds in flat agricultural landscape in Panjin Agricultural Station. The R2 between observed wind speeds and predicted wind speed ranged from 0.90 to 0.93. The standard error between observed and predicted values was only 0.5 m·s-1. Results of the F-test showed that the root-mean-square error of the observed and predicted wind speeds in each secondary forest complex terrain was much greater than that in flat agricultural landscape. Terrain was the primary factor affecting the applicability of wind profile model, followed by seasonality (leaf or leafless canopy). The wind profile model was not applicable to the boundary-layer flows over forest canopies in complex terrains, because the d was underestimated or both the d and z0 were underestimated, resulting in inaccurate estimation of aerodynamic height.


Asunto(s)
Bosques , Modelos Teóricos , Viento , China , Árboles/crecimiento & desarrollo , Monitoreo del Ambiente/métodos , Ecosistema , Altitud
9.
Front Public Health ; 12: 1358433, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510348

RESUMEN

Background: Cervical cancer is the fourth highest incidence of malignancy in the world and a common cause of cancer death in women. We assessed the trends of incidence and mortality and disability-adjusted life year (DALY) in China, England and India from 1990 to 2030. Method: Data were obtained from the Global Burden of Disease (GBD) database. We collected the number and rate of incidence, death and DALY from 1990 to 2019 and calculated the estimated annual percentage change (EAPC). Further analysis was carried out by ages and years. We also collected attributable risk factors to cervical cancer. Finally, we utilized the Bayesian Age-Period-Cohort (BAPC) model to forecast trends in the rate of age-standardized incidence (ASIR) and age-standardized death (ASDR) the for the next decade. Result: Globally, the incidence of cervical cancer cases increased from 335,641.56 in 1990 to 565,540.89 in 2019. In 2019, the ASIR and ASDR of cervical cancer were higher than those of India but lower than those of England. Furthermore, unsafe sex and smoking emerge as prominent risk factors for cervical cancer. Over the next decade, ASIR and ASDR are expected to decline in China and England, while India's ASIR is still on an upward trend and ASDR is on a downward trend. Conclusion: The epidemiological data of cervical cancer in these three countries reflects the influence of different stages of development and healthcare systems. Trends over the next decade suggest that China and India still face a huge burden of cervical cancer. When England has made significant progress, China and India need to take more measures to improve the prevention and control of cervical cancer.


Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/epidemiología , Carga Global de Enfermedades , Teorema de Bayes , Incidencia , China/epidemiología , Inglaterra/epidemiología , India/epidemiología
10.
Front Public Health ; 12: 1277457, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481850

RESUMEN

Objective: The purpose of this study is to provide experience and evidence support for countries to deal with similar public health emergencies such as COVID-19 by comparing and analyzing the measures taken by six countries in epidemic prevention and control. Methods: This study extracted public data on COVID-19 from the official website of various countries and used ecological comparative research methods to compare the specific situation of indicators such as daily tests per thousand people, stringency index, and total vaccinations per hundred people in countries. Results: The cumulative death toll in China, Germany and Australia was significantly lower than that in the United States, South Africa and Italy. Expanding the scale of testing has helped control the spread of the epidemic to some extent. When the epidemic situation is severe, the stringency index increases, and when the epidemic situation tends to ease, the stringency index decreases. Increased vaccination rates, while helping to build an immune barrier, still need to be used in conjunction with non-drug interventions. Conclusion: The implementation of non-drug interventions and vaccine measures greatly affected the epidemic prevention and control effect. In responding to public health emergencies such as the COVID-19 epidemic, countries should draw on international experience, closely align with their national conditions, follow the laws of epidemiology, actively take non-drug intervention measures, and vigorously promote vaccine research and development and vaccination.


Asunto(s)
COVID-19 , Epidemias , Vacunas , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Urgencias Médicas
11.
Microbiol Spectr ; 12(4): e0369523, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38358243

RESUMEN

Rickettsia rickettsii (R. rickettsii), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among Rickettsia spp. Previous studies have shown that tripartite motif-containing 56 (TRIM56) E3 ligase-induced ubiquitination of STING is important for cytosolic DNA sensing and type I interferon production to induce anti-DNA viral immunity, but whether it affects intracellular replication of R. rickettsii remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with R. rickettsii. We found that the expression of TRIM56 was upregulated in the R. rickettsii-infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while R. rickettsii replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-ß. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against R. rickettsii in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of R. rickettsii by regulating the cGAS-STING-mediated signaling pathway. This study gives new evidence for the role of TRIM56 in the innate immune response against intracellular bacterial infection and provides new therapeutic targets for RMSF. IMPORTANCE: Given that Rickettsia rickettsii (R. rickettsii) is the most pathogenic member within the Rickettsia genus and serves as the causative agent of Rocky Mountain spotted fever, there is a growing need to explore host targets. In this study, we examined the impact of host TRIM56 on R. rickettsii infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in R. rickettsii-infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-ß production. Notably, the mutation of the TRIM56's E3 ligase catalytic site did not impede R. rickettsii replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against R. rickettsii through the modulation of the cGAS-STING signaling pathway.


Asunto(s)
Interferón Tipo I , Fiebre Maculosa de las Montañas Rocosas , Humanos , Rickettsia rickettsii/metabolismo , Células HeLa , Ubiquitina-Proteína Ligasas/genética , Interferón beta/metabolismo , Nucleotidiltransferasas/metabolismo , Proteínas de Motivos Tripartitos/genética
12.
Sensors (Basel) ; 24(4)2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38400427

RESUMEN

In order to solve the problem of low recognition accuracy of traditional pig sound recognition methods, deep neural network (DNN) and Hidden Markov Model (HMM) theory were used as the basis of pig sound signal recognition in this study. In this study, the sounds made by 10 landrace pigs during eating, estrus, howling, humming and panting were collected and preprocessed by Kalman filtering and an improved endpoint detection algorithm based on empirical mode decomposition-Teiger energy operator (EMD-TEO) cepstral distance. The extracted 39-dimensional mel-frequency cepstral coefficients (MFCCs) were then used as a dataset for network learning and recognition to build a DNN- and HMM-based sound recognition model for pig states. The results show that in the pig sound dataset, the recognition accuracy of DNN-HMM reaches 83%, which is 22% and 17% higher than that of the baseline models HMM and GMM-HMM, and possesses a better recognition effect. In a sub-dataset of the publicly available dataset AudioSet, DNN-HMM achieves a recognition accuracy of 79%, which is 8% and 4% higher than the classical models SVM and ResNet18, respectively, with better robustness.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Femenino , Porcinos , Animales , Sonido , Cadenas de Markov
13.
Biosens Bioelectron ; 249: 116009, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38199082

RESUMEN

MicroRNA-21 (miRNA-21) is a significant biomarker for the development and progression of diverse cancers but is present in relatively low concentrations. Detecting such low-abundance molecules accurately can be challenging, especially in early-stage cancers where the concentration may be even lower. Herein, a self-calibration biosensing platform based on 3D novel MNPs-IL-rGO-AuNPs nanocomposites was successfully established for the ultrasensitive detection of miRNA-21. Duplex-specific nuclease (DSN) was introduced to recognize perfectly matched duplexes and trigger target recycling, enhancing the specificity and sensitivity of the biosensor. DSN-assisted target recycling, in conjunction with magnetic separation enrichment and high-performance MNPs-IL-rGO-AuNPs, collectively formed a multiple-signal amplification strategy. The obtained biosensor could output dual signals in both electrochemical and fluorescent modes, enabling self-correcting detection to enhance the accuracy. The obtained dual-mode biosensor prepared exhibited a wide detection range from 5 fM to 100 nM with a remarkably low LOD of 1.601 fM. It accomplished the sensitive evaluation of miRNA-21 in total RNA extracted from various human cancer cell lines and normal cell lines. Additionally, the greatly satisfactory outcomes in the analysis of human serum samples suggested that the proposed biosensor was a powerful screening candidate in early clinical diagnosis of cancer.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , MicroARNs , Humanos , MicroARNs/análisis , Oro/química , Nanopartículas del Metal/química , Calibración , Endonucleasas , Límite de Detección , Técnicas Electroquímicas
16.
Sensors (Basel) ; 23(21)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37960652

RESUMEN

The existing algorithms for identifying and tracking pigs in barns generally have a large number of parameters, relatively complex networks and a high demand for computational resources, which are not suitable for deployment in embedded-edge nodes on farms. A lightweight multi-objective identification and tracking algorithm based on improved YOLOv5s and DeepSort was developed for group-housed pigs in this study. The identification algorithm was optimized by: (i) using a dilated convolution in the YOLOv5s backbone network to reduce the number of model parameters and computational power requirements; (ii) adding a coordinate attention mechanism to improve the model precision; and (iii) pruning the BN layers to reduce the computational requirements. The optimized identification model was combined with DeepSort to form the final Tracking by Detecting algorithm and ported to a Jetson AGX Xavier edge computing node. The algorithm reduced the model size by 65.3% compared to the original YOLOv5s. The algorithm achieved a recognition precision of 96.6%; a tracking time of 46 ms; and a tracking frame rate of 21.7 FPS, and the precision of the tracking statistics was greater than 90%. The model size and performance met the requirements for stable real-time operation in embedded-edge computing nodes for monitoring group-housed pigs.


Asunto(s)
Algoritmos , Sus scrofa , Porcinos , Animales , Granjas , Postura , Reconocimiento en Psicología
17.
Curr Med Chem ; 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37916635

RESUMEN

BACKGROUND: Although immunotherapies have greatly improved diffuse large B-cell lymphoma (DLBCL) prognosis, a proportion of patients remain to be relapsed or refractory. Therefore, the identification of novel therapeutic targets and drugs is urgently required. Inhibition of the bromodomain and extra-terminal (BET) proteins has been a promising therapeutic strategy for various haematologic cancers. CPI-0610 is a potent and selective BET inhibitor. The effects of CPI-0610 in DLBCL cells have not been reported yet. AIMS: The aim of this study was to assess the effects of CPI-0610 in DLBCL and its underlying mechanisms. METHODS: DLBCL cells were treated with CPI-0610, followed by measuring cell viability, cell cycle, apoptosis, autophagy, and specific cell signaling pathways. Moreover, immunodeficient mice were engrafted with SUDHL2 cells and then treated with CPI-0610 for analysis of tumor burden. We also analyzed the synergistic effect of CPI-0610 with histone deacetylase inhibitor suberoylanilide hydroxamic acid. RESULTS: The present study demonstrated that CPI-0610 displayed cell cytotoxicity by arresting the G1 cell cycle and inducing endogenous and exogenous apoptotic pathways. Additionally, CPI-0610 decreased BRD4 and c-Myc expressions and affected MAPK, JAK/STAT, and AKT signalling pathways in human DLBCL cells. An in vivo experiment exhibited that CPI-0610 decreased the primary tumour growth of the DLBCL xenograft model. Furthermore, the use of CPI-0610 in combination with suberoylanilide hydroxamic acid exhibited a specific synergistic effect in inducing apoptosis through the regulation of STAT3 and p38. CONCLUSION: Targeting BET may be an effective therapeutic strategy and potentiated by a combination with histone deacetylase inhibition in DLBCL.

18.
mBio ; 14(5): e0038723, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37787515

RESUMEN

IMPORTANCE: Studying the co-evolution between viruses and humans is important for understanding why we are what we are now as well as for developing future antiviral drugs. Here we pinned down an evolutionary arms race between retroviruses and mammalian hosts at the molecular level by identifying the antagonism between a host antiviral restriction factor PSGL-1 and viral accessory proteins. We show that this antagonism is conserved from mouse to human and from mouse retrovirus to HIV. Further studying this antagonism might provide opportunities for developing new antiviral therapies.


Asunto(s)
Mamíferos , Retroviridae , Humanos , Ratones , Animales , Proteínas Reguladoras y Accesorias Virales , Antivirales/farmacología
19.
Virulence ; 14(1): 2250065, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37635408

RESUMEN

Clade 2.3.4.4 H5N6 avian influenza virus (AIV) has been predominant in poultry in China, and the circulating haemagglutinin (HA) gene has changed from clade 2.3.4.4h to clade 2.3.4.4b in recent years. In 2021, we isolated four H5N6 viruses from ducks during the routine surveillance of AIV in China. The whole-genome sequencing results demonstrated that the four isolates all belonged to the currently prevalent clade 2.3.4.4b but had different internal gene constellations, which could be divided into G1 and G2 genotypes. Specifically, G1 possessed H9-like PB2 and PB1 genes on the H5-like genetic backbone while G2 owned an H3-like PB1 gene and the H5-like remaining internal genes. By determining the characteristics of H5N6 viruses, including growth performance on different cells, plaque-formation ability, virus attachment ability, and pathogenicity and transmission in different animal models, we found that G1 strains were more conducive to replication in mammalian cells (MDCK and A549) and BALB/c mice than G2 strains. However, G2 strains were more advantageously replicated in avian cells (CEF and DF-1) and slightly more transmissible in waterfowls (mallards) than G1 strains. This study enriched the epidemiological data of H5 subtype AIV to further understand its dynamic evolution, and laid the foundation for further research on the mechanism of low pathogenic AIV internal genes in generating novel H5 subtype reassortants.


Asunto(s)
Patos , Virus de la Influenza A , Animales , Ratones , Virulencia/genética , China/epidemiología , Genotipo , Virus de la Influenza A/genética , Ratones Endogámicos BALB C , Mamíferos
20.
PeerJ ; 11: e15769, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37547719

RESUMEN

Objectives: The study aims to understand the impact of containment policy and mobility on COVID-19 cases in Chile, Singapore, South Korea and Israel. To provide experience in epidemic prevention and control. Methods: Structural equation modeling (SEM) of containment policies, mobility, and COVID-19 cases were used to test and analyze the proposed hypotheses. Results: Chile, Israel and Singapore adopted containment strategies, focusing on closure measures. South Korea adopted a mitigation strategy with fewer closure measures, focusing on vaccination and severe case management. There was a significant negative relationship among containment policies, mobility, and COVID-19 cases. Conclusion: To control the COVID-19 and slow down the increase of COVID-19 cases, countries can increase the stringency of containment policies when COVID-19 epidemic is more severe. Thus, countries can take measures from the following three aspects: strengthen the risk monitoring, and keep abreast of the COVID-19 risk; adjust closure measures in time and reduce mobility; and strengthen public education on COVID-19 prevention to motivate citizen to consciously adhere to preventive measures.


Asunto(s)
COVID-19 , Humanos , Chile/epidemiología , Israel/epidemiología , COVID-19/epidemiología , Singapur/epidemiología , República de Corea/epidemiología , Políticas
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