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1.
Int J Biol Sci ; 20(6): 2168-2186, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617532

RESUMEN

Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.


Asunto(s)
Acetatos , Ciclopropanos , FN-kappa B , Psoriasis , Quinolinas , Sulfuros , Humanos , Animales , Ratones , Interleucina-17 , Células Th17 , Psoriasis/tratamiento farmacológico , Diferenciación Celular , Citocinas
2.
Poult Sci ; 103(4): 103540, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417330

RESUMEN

CCAAT/enhancer binding protein zeta (C/EBPZ) was differentially expressed in abdominal adipose tissues of fat and lean broilers and regulated adipogenesis in chicken. The objective of this study was to elucidate the transcriptional regulation of C/EBPZ gene in chicken adipose tissue. A 2,031-base pair (bp) chicken C/EBPZ sequence (2,025 nucleotides upstream to 6 nucleotides downstream from the initiator codon, -2,025/+6) was studied. The sequence exhibited a significant promoter activity (P < 0.05) and had some cis-acting elements, notably, a core promoter was identified in nucleotides -94 to +6. Additionally, DNA pull-down assay showed that proteins interacted with chicken C/EBPZ promoter (-173/+6) in preadipocytes were implicated in transcription, post-transcriptional regulation and translation. In addition, KLF2 facilitated the activities of chicken C/EBPZ promoter (-2,025/+6, -1,409/+6, -793/+6, -485/+6, -173/+6, and -94/+6) in preadipocytes (P < 0.05). The expression levels of KLF2 and C/EBPZ in chicken abdominal adipose tissue were substantially associated (r = 0.5978278, P < 0.0001), and KLF2 increased C/EBPZ expression in vitro (P < 0.05). Additionally, chromatin immunoprecipitation (ChIP)-PCR analysis revealed that KLF2 has the ability to interact with the chicken C/EBPZ promoter regions at least at the positions -1,245/-1,048 and -571/-397. Mutation analysis showed that the CGCAGCGCCCG motif located in the chicken C/EBPZ promoter at positions -45 to -35 is involved in regulating transcription and facilitates trans activation by KLF2. These results provided some information of transcription control of C/EBPZ in chicken adipose tissue.


Asunto(s)
Proteína alfa Potenciadora de Unión a CCAAT , Pollos , Animales , Pollos/genética , Pollos/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Regulación de la Expresión Génica , Tejido Adiposo/metabolismo , Nucleótidos/metabolismo
3.
Nat Commun ; 15(1): 1669, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38396029

RESUMEN

The bacterial pathogen Neisseria gonorrhoeae is able to invade epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, the mechanistic details for interactions between gonococcal OMVs and epithelial cells and their impact on intracellular survival are currently not established. Here, we show that gonococcal OMVs induce epithelial cell mitophagy to reduce mitochondrial secretion of reactive oxygen species (ROS) and enhance intracellular survival. We demonstrate that OMVs deliver PorB to mitochondria to dissipate the mitochondrial membrane potential, resulting in mitophagy induction through a conventional PINK1 and OPTN/NDP52 mechanism. Furthermore, PorB directly recruits the E3 ubiquitin ligase RNF213, which decorates PorB lysine residue 171 with K63-linked polyubiquitin to induce mitophagy in a p62-dependent manner. These results demonstrate a mechanism in which polyubiquitination of a bacterial virulence factor that targets mitochondria directs mitophagy processes to this organelle to prevent its secretion of deleterious ROS.


Asunto(s)
Gonorrea , Mitofagia , Humanos , Especies Reactivas de Oxígeno/metabolismo , Mitocondrias/metabolismo , Gonorrea/microbiología , Células Epiteliales/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Adenosina Trifosfatasas/metabolismo
4.
J Infect Dis ; 228(12): 1776-1788, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-37926090

RESUMEN

Neisseria gonorrhoeae establishes tight interactions with mucosal epithelia through activity of its type IV pilus, while pilus retraction forces activate autophagic responses toward invading gonococci. Here we studied pilus-independent epithelial cell responses and showed that pilus-negative gonococci residing in early and late endosomes are detected and targeted by nucleotide-binding oligomerization domain 1 (NOD1). NOD1 subsequently forms a complex with immunity-related guanosine triphosphatase M (IRGM) and autophagy-related 16-like 1 (ATG16L1) to activate autophagy and recruit microtubule-associated protein light chain 3 (LC3) to the intracellular bacteria. IRGM furthermore directly recruits syntaxin 17 (STX17), which is able to form tethering complexes with the lysosome. Importantly, IRGM-STX17 interactions are enhanced by LC3 but were still observed at lower levels in an LC3 knockout cell line. These findings demonstrate key roles for NOD1 and IRGM in the sensing of intracellular N gonorrhoeae and subsequent directing of the bacterium to the lysosome for degradation.


Asunto(s)
Autofagia , Neisseria gonorrhoeae , Neisseria gonorrhoeae/metabolismo , Células Epiteliales/metabolismo , Lisosomas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Endosomas/metabolismo
5.
J Autoimmun ; 139: 103087, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37481835

RESUMEN

OBJECTIVES: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is a newly discovered immune checkpoint (IC) that exhibits immunosuppressive function in the regulation of immune system. Activation of TIGIT signaling has emerged as a promising approach for autoimmune disease immunotherapy, such as systemic lupus erythematosus (SLE). METHODS: We generated a chimeric protein, TIGIT-immunoglobulin (Ig), by fusing the extracellular domain of murine TIGIT to the Fc region of mouse IgG2a, which was used to investigated the effect of activating the TIGIT signaling in murine lupus models (MRL/lpr and chronic graft-versus-host disease mice). Treated mice were harvested, and samples of serum, kidney, and spleen were collected for outcome evaluation. In vitro treatment of TIGIT-Ig in B cells was used for exploring the roles of TIGIT in toll-like receptor 7 (TLR7)-mediated B cell differentiation and antibody production. RESULTS: TIGIT-Ig treatment delayed disease progression in both lupus models, accompanied by a decrease in the production of anti-double stranded DNA antibodies (anti-dsDNA), proteinuria, proteinuria/creatinine, and Ig kidney deposition. Additionally, the group treated with TIGIT-Ig displayed a decreased proportion of T helper cell (Th)1 cells, T follicular helper (Tfh) cells, and B-cell subsets, including germinal center B cells (GC B), plasmablasts, and plasma cells, compared to the group treated with control IgG. Interestingly, we also observed an increased proportion of Tregs in the spleen of the TIGIT-Ig group. We have discovered a new way in which activating the TIGIT pathway can regulate B-cell differentiation through the SPI-B-PAX5-XBP1 pathway, resulting in a reduction in autoantibodies. CONCLUSION: Together, TIGIT may be a promising IC target for SLE treatment.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Animales , Ratones , Nefritis Lúpica/terapia , Ratones Endogámicos MRL lpr , Autoanticuerpos , Receptores Inmunológicos/genética , Proteinuria , Diferenciación Celular , Modelos Animales de Enfermedad
6.
Int J Lab Hematol ; 45(6): 890-898, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37501513

RESUMEN

INTRODUCTION: Infectious mononucleosis (IM) is a common infectious disease in children mainly caused by Epstein-Barr virus (EBV) infection, followed by abnormal immune response, and resulting in serious complications. However, there are few clinical analyses of immune responses in children with IM at different stages. METHODS: This study combined EBV serological test and EBV DNA test to diagnose the infection status of children with IM, and the infection status was divided into primary acute IM infection (AIM), primary late IM infection (LIM) and reactivation IM infection (RIM). RESULTS: The results revealed that the absolute numbers of leukocytes and CD8+ T lymphocytes in primary IM infection were significantly higher than those in reactivation infection, while the frequencies of CD4+ T lymphocytes and B cells were significantly lower than those in reactivation infection. In addition, the activities of ALT, AST, α-HBDH and LDH in liver function indicators in primary infection were significantly increased compared with reactivation infection. Similarly, the EBV DNA levels of the primary infection were significantly higher than that of the reactivation infection. CONCLUSION: There are differences in immune response at different stages of infection, which can provide guidance for effective treatment in children with IM infection.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Mononucleosis Infecciosa , Infección Latente , Niño , Humanos , Mononucleosis Infecciosa/diagnóstico , Herpesvirus Humano 4 , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , ADN , Inmunidad
7.
Front Med ; 17(1): 43-57, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36811762

RESUMEN

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.


Asunto(s)
Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Psoriasis , Humanos , Enfermedades Autoinmunes/genética , Epigénesis Genética , Lupus Eritematoso Sistémico/genética , Metilación de ADN , Psoriasis/genética
8.
Virusdisease ; 33(4): 363-370, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36278030

RESUMEN

People who inject drugs (PWIDs) are primarily the high-risk population for HCV infection. This study aims to determine the optimal cut-off values for predicting HCV infection status based on the Signal-to-Cutoff (S/CO) ratio. In this study, a total of 719 PWIDs' samples were collected, and performed for screening test by ELISA assay, and followed by RIBA assay and NAT assay to detect HCV antibody and HCV RNA levels, respectively. The findings revealed that the prevalence of HCV infection among PWIDs was 54.66% (393/719), and the false-positive rate of HCV antibody detection by ELISA assay among PWIDs was only 3.85% (16/416). In addition, when the optimal cut-off value for S/CO ratio was 2.0, the sensitivity and specificity of HCV antibody were 100.00% and 93.55%, respectively. And when the optimal cut-off value for S/CO ratio was 21.36, the sensitivity and specificity of HCV RNA positive were 89.90% and 72.73%, respectively. In conclusion, the status of HCV infection can be predicted based on the S/CO ratios of the ELISA assay, which can improve diagnosis and facilitate timely treatment to effectively prevent the spread of HCV infection.

9.
Int J Obes (Lond) ; 46(3): 523-534, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34789850

RESUMEN

BACKGROUND/OBJECTIVES: This study investigated the functions of CCAAT/enhancer-binding protein zeta (C/EBPZ; Gene ID: 10153) in adipose tissue. SUBJECTS/METHODS: Bioinformatics analysis were used to study the expression pattern of C/EBPZ in human adipose tissue. The expression and function of C/EBPZ in adipose tissue were further studied using chicken as animal model in vivo and in vitro. RESULTS: The human C/EBPZ transcripts were greater and more stable in subcutaneous adipose tissue than in visceral adipose tissue (P < 0.01), and they were increased with age in adipose tissue (P < 0.05). In addition, the chicken C/EBPZ transcripts (C/EBPZ /ACTB) of visceral (abdominal) adipose tissue were significantly different between fat and lean broilers and decreased with age during development (P < 0.01). RNA-seq analysis showed that the C/EBPZ overexpression associated with adipose tissue development and DNA replication in chicken preadipocytes (P < 0.05). Additionally, overexpression of chicken C/EBPZ inhibited preadipocytes differentiation and promoted preadipoytes proliferation in vitro (P < 0.05). In addition, C/EBPZ overexpression suppressed the promoter activities of PPARγ, C/EBPα, FASN and LPL, and promoted the promoter activities of GATA2 and FABP4 in chicken preadipocytes (P < 0.05). CONCLUSIONS: C/EBPZ modulated the differentiation and proliferation of preadipocytes, and it might be a new negative regulator of adipogenesis.


Asunto(s)
Adipocitos , Pollos , Adipocitos/metabolismo , Adipogénesis/genética , Animales , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular , Proliferación Celular , Pollos/genética , Pollos/metabolismo , PPAR gamma/metabolismo
10.
World Neurosurg ; 154: e7-e18, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33992827

RESUMEN

BACKGROUND: Although previous studies have made significant contributions to establishing animal traumatic brain injury (TBI) models for simulation of human TBI, the accuracy, controllability, and modeling efficiency of animal TBI models need to be further improved. This study established a novel high-efficiency graded mouse TBI model induced by shock wave. METHODS: A total of 125 mice were randomly divided into sham, 0.7 mm, 0.6 mm, and 0.5 mm groups according to the depth of the cross groove of the aluminum sheets. The stability and repeatability of apparatus were evaluated, and the integrity of the blood-brain barrier, cerebral edema, neuropathologic immunohistochemistry, apoptosis-related protein, and behavioral tests of neurologic function were used to validate this new model. RESULTS: The results showed that 4 mice were injured simultaneously in 1 experiment. They received the same intensity of shock waves. Moreover, the mortality rates caused by 3 different aluminum sheets were consistent with the mortality rates of mild TBI, moderate TBI, and severe TBI. Compared with the sham group, mice in different injured groups significantly increased brain water content, blood-brain barrier permeability, and neuronal apoptosis. And the mice in all injured groups showed poor motor ability, balancing, spatial learning, and memory abilities. CONCLUSIONS: The novel TBI apparatus has advantages in its small size, simple operation, high repeatability, high efficiency, and graded severity. Our TBI apparatus provides a novel tool to investigate the neuropathologic changes and underlying mechanisms of TBI with various levels of severities.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Modelos Animales de Enfermedad , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Barrera Hematoencefálica/patología , Agua Corporal/metabolismo , Edema Encefálico/patología , Lesiones Traumáticas del Encéfalo/mortalidad , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/psicología , Inmunohistoquímica , Masculino , Aprendizaje por Laberinto , Ratones , Ratones Endogámicos ICR , Examen Neurológico , Neuronas/patología , Reproducibilidad de los Resultados
11.
Int J Nanomedicine ; 16: 1525-1551, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33658782

RESUMEN

Nanomedicines afford unique advantages in therapeutic intervention against tumors. However, conventional nanomedicines have failed to achieve the desired effect against cancers because of the presence of complicated physiological fluids and the tumor microenvironment. Stimuli-responsive drug-delivery systems have emerged as potential tools for advanced treatment of cancers. Versatile nano-carriers co-triggered by multiple stimuli in different levels of organisms (eg, extracorporeal, tumor tissue, cell, subcellular organelles) have aroused widespread interest because they can overcome sequential physiological and pathological barriers to deliver diverse therapeutic "payloads" to the desired targets. Furthermore, multiple stimuli-responsive drug-delivery systems (MSR-DDSs) offer a good platform for co-delivery of agents and reversing multidrug resistance. This review affords a comprehensive overview on the "landscape" of MSR-DDSs against tumors, highlights the design strategies of MSR-DDSs in recent years, discusses the putative advantage of oncotherapy or the obstacles that so far have hindered the clinical translation of MSR-DDSs.


Asunto(s)
Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Inmunoterapia , Nanomedicina Teranóstica , Microambiente Tumoral
12.
Acta Biochim Biophys Sin (Shanghai) ; 53(2): 149-159, 2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33330912

RESUMEN

Krüppel-like factor 7 (KLF7) has been reported to inhibit adipogenesis and regulate the development of the nervous system. However, transcription regulation of KLF7 remains poorly understood. In the current study, a 2196-bp-long 5'-flanking sequence of chicken KLF7 (-2286 bp to -91 bp, upstream of the translation start site) was studied for promoter activity, and there was a remarkable promoter activity in this sequence (P<0.05). The 5'-truncated mutation analysis showed that a minimal promoter was on the sequence from -241 bp to -91 bp. In addition, GATA2 overexpression facilitated the promoter activity of pGL3-KLF7(-2286/-91), pGL3-KLF7(-1215/-91), pGL3-KLF7(-521/-91), and pGL3-KLF7(-241/-91), and GATA3 overexpression inhibited the promoter activity of pGL3-KLF7(-1845/-91), pGL3-KLF7(-1215/-91), pGL3-KLF7(-521/-91), and pGL3-KLF7(-241/-91) in chicken preadipocytes (P<0.05). Knockdown of GATA2 expression inhibited the promoter activity of pGL3-KLF7(-1215/-91) and pGL3-KLF7(-241/-91), and knockdown of GATA3 expression facilitated the promoter activity of pGL3-KLF7(-521/-91) and pGL3-KLF7(-241/-91) (P<0.05). Additionally, overexpression and knockdown analyses showed that GATA3 inhibited KLF7 mRNA expression (P<0.05), and both overexpression and knockdown of GATA2 resulted in the downregulation of KLF7 mRNA expression in chicken preadipocytes (P<0.05). Western blot analysis in chicken preadipocytes showed that GATA2 facilitated KLF7 expression and GATA3 inhibited KLF7 expression. Mutation analysis showed that the motif of 'GGATCTATCA' (-107 bp/-98 bp) might be a cis-regulation element, which is involved in the KLF7 expression regulation by GATA3 in chicken preadipocytes. These results provided some details of KLF7 transcription regulation in chicken adipose tissue.


Asunto(s)
Adipocitos/metabolismo , Proteínas Aviares , Regulación de la Expresión Génica , Factores de Transcripción de Tipo Kruppel , Regiones Promotoras Genéticas , Transcripción Genética , Animales , Proteínas Aviares/biosíntesis , Proteínas Aviares/genética , Pollos , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo
13.
J Infect Dis ; 224(1): 141-150, 2021 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-33170275

RESUMEN

Neisseria gonorrhoeae is a bacterial pathogen that colonizes mucosal epithelia that are rich in antimicrobial molecules such as long-chain fatty acids. Here we studied the mechanisms involved in palmitic acid resistance and their impact on in vivo biological fitness in a murine genital tract infection model. A stable palmitic acid-resistant derivative was obtained by serial passage with incremental palmitic acid concentrations. This derivative outcompeted its parent strain for colonization and survival in the murine infection model. Subsequent whole-genome sequencing resulted in the identification of the 3 resistance-related SNPs ihfAC5T, fadDC772T, and farAG-52T (promoter) that were verified for resistance against palmitic acid. Subsequent characterization of the associated resistance determinants showed that ihfAC5T and farAG-52T induced gene expression of the FarAB efflux pump, whereas fadDC772T increased the maximum enzyme activity of the FadD long-chain fatty acid-coenzyme A ligase. Our results highlight the mechanisms involved in gonococcal adaptation to the murine host environment.


Asunto(s)
Proteínas Bacterianas/fisiología , Coenzima A Ligasas/genética , Gonorrea/etiología , Mutación , Ácido Palmítico/farmacología , Infecciones del Sistema Genital/etiología , Animales , Modelos Animales de Enfermedad , Femenino , Células HeLa , Humanos , Ratones , Ratones Endogámicos BALB C , Neisseria gonorrhoeae/efectos de los fármacos , Enfermedades Vaginales/etiología
14.
Artículo en Inglés | MEDLINE | ID: mdl-31540517

RESUMEN

China has established the universal medical insurance system and individual out of pocket costs have decreased, however, the average healthcare expenditure of the Chinese population and the expenses of the whole society have increased substantially. One major challenge which impedes the progress of attaining sustainable development of the social healthcare system in China is that the number of hospital admissions is disproportionate. Superior hospitals are overcrowded, whereas subordinate hospitals are experiencing low admissions. In this paper, we apply the game theory model to coordinate the healthcare supply chain network, which is composed of the government, medical insurance fund, superior hospitals, subordinate hospitals and patients. Especially by taking the reference price effect into account, this paper analyzes different medical insurance reimbursement strategies and their influence on patient choice and the healthcare supply chain network. The result shows that the reference price effect increases the leverage of medical insurance, guides patients' choice, optimizes the allocation of medical resources and reduces the medical expends. In comparison to a decentralized decision- making strategy, a centralized decision- making strategy can stimulate both superior hospital and subordinate hospital's cooperative intentions which benefits the social healthcare system.


Asunto(s)
Atención a la Salud/organización & administración , Agencias Gubernamentales/organización & administración , Administración Hospitalaria , Programas Nacionales de Salud/organización & administración , China/epidemiología , Atención a la Salud/economía , Teoría del Juego , Agencias Gubernamentales/economía , Humanos , Reembolso de Seguro de Salud , Programas Nacionales de Salud/economía , Prioridad del Paciente
15.
Cell Syst ; 9(2): 214-220.e5, 2019 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-31279504

RESUMEN

Mechanical factors play critical roles in mammalian development. Here, we report that colony-growing mouse embryonic stem cells (mESCs) generate significant tension on the colony surface through the contraction of a three-dimensional supracellular actomyosin cortex (3D-SAC). Disruption of the 3D-SAC, whose organization is dependent on the Rho/Rho-associated kinase (ROCK) signals and E-cadherin, results in mESC colony destruction. Reciprocally, compression force, which is generated by the 3D-SAC, promotes colony growth and expression of Nanog and Oct4 in mESCs and blastocyst development of mouse embryos. These findings suggest that autonomous cell forces regulate embryonic stem cells fate determination and provide insight regarding the biomechanical regulation of embryonic development.


Asunto(s)
Blastómeros/citología , Células Madre Embrionarias de Ratones/citología , Proteína Homeótica Nanog/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Actomiosina/metabolismo , Animales , Fenómenos Biomecánicos , Blastómeros/metabolismo , Cadherinas/metabolismo , Diferenciación Celular , Proliferación Celular/fisiología , Ratones , Células Madre Embrionarias de Ratones/metabolismo , Proteína Homeótica Nanog/genética , Factor 3 de Transcripción de Unión a Octámeros/genética , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Cultivo Primario de Células , Quinasas Asociadas a rho/metabolismo
16.
PLoS One ; 14(6): e0218782, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31220172

RESUMEN

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011-2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013-2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks.


Asunto(s)
Virus del Sarampión/genética , Sarampión/epidemiología , Sarampión/virología , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Brotes de Enfermedades , Enfermedades Endémicas , Femenino , Genotipo , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Sarampión/prevención & control , Virus del Sarampión/clasificación , Virus del Sarampión/inmunología , Tipificación Molecular , Filogenia , Análisis de Secuencia de ADN , Vacunación , Adulto Joven
17.
PLoS One ; 13(11): e0208161, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30500842

RESUMEN

In addition to high vaccination coverage, timely and accurate laboratory confirmation of measles cases is critical to interrupt measles transmission. To evaluate the role of real-time reverse transcription-polymerase chain reaction (RT-PCR) in the diagnosis of measles cases, 46,363 suspected measles cases with rash and 395 suspected measles cases without rash were analyzed in this study; the cases were obtained from the Chinese measles surveillance system (MSS) during 2014-2017 and simultaneously detected by measles-specific IgM enzyme-linked immunosorbent assay (ELISA) and real-time RT-PCR. However, some IgM-negative measles cases were identified by real-time RT-PCR. The proportion of these IgM-negative and viral nucleic acid-positive measles cases was high among measles cases with measles vaccination history, cases without rash symptoms, and cases within 3 days of specimen collection after onset. The proportion of IgM-negative and viral nucleic acid-positive measles cases in the 0-3 day group was up to 14.4% for measles cases with rash and 40% for measles cases without rash. Moreover, the proportions of IgM-negative and nucleic acid-positive measles cases gradually increased with the increase in the measles vaccination dose. Therefore, integrated with IgM ELISA, real-time RT-PCR would greatly improve the accurate diagnosis of measles cases and avoid missing the measles cases, especially for measles cases during the first few days after onset when the patients were highly contagious and for measles cases with secondary vaccine failure. In conclusion, our study reconfirmed that IgM ELISA is the gold-standard detection assay for measles cases confirmation. However, real-time RT-PCR should be introduced and used to supplement the laboratory diagnosis, especially in the setting of pre-elimination and/or elimination wherever appropriate.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática , Virus del Sarampión/aislamiento & purificación , Sarampión/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adolescente , Adulto , Anticuerpos Antivirales/análisis , Niño , Preescolar , China/epidemiología , Técnicas de Laboratorio Clínico , Humanos , Inmunoglobulina M/análisis , Lactante , Sarampión/epidemiología , Sarampión/prevención & control , Adulto Joven
18.
Int J Infect Dis ; 76: 38-44, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30170155

RESUMEN

BACKGROUND: Vaccinated individuals infected with measles can develop nodular pneumonia. These cases can be misdiagnosed due to the absence of specific IgM and typical symptoms. An effective diagnostic tool is needed. METHODS: During March 2016, adult inpatients in Yucheng People's Hospital were enrolled prospectively and included in the study. Patients were included if samples were obtained ≤14 days from the onset of fever. Measles virus was detected by RT-PCR of the oropharyngeal swab sample. Chest computed tomography scans and medical records were obtained. Oropharyngeal swabs and blood samples were collected for IgM and IgG testing, RT-PCR, and gene sequencing. RESULTS: Sixteen patients were enrolled. Ten were found to have nodular pneumonia and were defined as the nodular group. The remaining six patients were defined as the control group. Measles-specific IgG titers in the nodular group were high (3618.3-5000mIU/ml), while IgM titers were low (<25mIU/ml); IgG titers in the control group were low (241.4-2560.3mIU/ml), while IgM titers were high (137-5000mIU/ml). No obvious viral mutation was detected in the nodular group. CONCLUSIONS: Measles-associated nodular pneumonia was only evident in those patients with an IgG/IgM ratio >20. In measles outbreaks, the IgG/IgM ratio may be useful to identify nodular pneumonia.


Asunto(s)
Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Sarampión/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/inmunología , Adulto , Anticuerpos Antivirales/sangre , Antígenos Virales/sangre , Brotes de Enfermedades , Femenino , Humanos , Masculino , Sarampión/inmunología , Virus del Sarampión/aislamiento & purificación , Neumonía Viral/sangre , Tomografía Computarizada por Rayos X , Vacunación , Adulto Joven
19.
J Agric Food Chem ; 65(13): 2730-2736, 2017 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-28248099

RESUMEN

An endo-polygalacturonase gene (pga-zj5a) was cloned by reverse transcription from cDNAs synthesized from Aspergillus niger ZJ5 total RNA. The open reading frame of pga-zj5a was 1089 base pairs encoding 362 amino acids. Pga-zj5a lacking a signal peptide sequence was successfully amplified using A. niger ZJ5 cDNA as the template and was ligated into the pPIC9 vector. The resulting plasmid was transformed into competent cells of Pichia pastoris GS115 for heterologous expression. The polygalacturonase showed a maximum activity level of 10436 U/mL in the culture supernatant from a 3 L fermenter. Assays of enzymatic properties showed that the optimal pH and temperature of the recombinant PGA-ZJ5A were 4.5 and 40 °C, respectively. PGA-ZJ5A was effective in pear juice clarification, increased the volume of pear juice by 41.8%, and improved its light transmittance 3-fold.


Asunto(s)
Aspergillus niger/enzimología , Jugos de Frutas y Vegetales/análisis , Frutas/microbiología , Proteínas Fúngicas/química , Poligalacturonasa/química , Aspergillus niger/química , Aspergillus niger/genética , Biocatálisis , Clonación Molecular , Estabilidad de Enzimas , Fermentación , Frutas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Concentración de Iones de Hidrógeno , Pichia/genética , Pichia/metabolismo , Poligalacturonasa/genética , Poligalacturonasa/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Temperatura
20.
Shanghai Kou Qiang Yi Xue ; 20(3): 317-20, 2011 Jun.
Artículo en Chino | MEDLINE | ID: mdl-21779746

RESUMEN

PURPOSE: To investigate the condition of four kinds of noncarious hard tissue lesions of the teeth in teachers of one university in Shanghai municipality and provide guidance about oral health care. METHODS: The table and the standard on oral health survey authorized by WHO were adopted, condition of four kinds of noncarious hard tissue lesions of teeth in 776 teachers of East China University of Science was investigated and analyzed using SPSS16.0 software package. RESULTS: The average wedge-shaped defect teeth was 5.54±3.87, the incidence was 30.41%, caries incidence of the first bicuspid was the highest(29.52%). The incidence of tetracycline pigmentation teeth was 3.09%, the incidence of enamel hypoplasia was 2.06%, and the incidence of dental fluorosis was 1.55%. CONCLUSIONS: The average wedge-shaped defect teeth is higher than the data over the country, the incidence of dental textural anomaly is lower. The behaviors of oral health care of university teachers in Shanghai municipality remains to be further strengthened.


Asunto(s)
China , Caries Dental , Universidades , Diente Premolar , Docentes , Humanos
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