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BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.
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The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.
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Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.
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Polydnaviridae , Avispas , Animales , Spodoptera , Polydnaviridae/genética , Interacciones Huésped-Parásitos , LarvaRESUMEN
A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression.
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Vesículas Extracelulares , Polydnaviridae , Caspasa 3 , Fosfatidilinositol 3-Quinasas , Polydnaviridae/fisiología , Proteínas Proto-Oncogénicas c-aktRESUMEN
Background. Little is known about the induction of functional and brain structural reorganization in hemiplegic cerebral palsy (HCP) by constraint-induced movement therapy (CIMT). Objective. We aimed to explore the specific molecular mechanism of functional and structural plasticity related to CIMT in HCP. Methods. The mice were divided into a control group and HCP groups with different interventions (unconstraint-induced movement therapy [UNCIMT], CIMT or siRNA-Nogo-A [SN] treatment): the HCP, HCP+UNCIMT, HCP+CIMT, HCP+SN, and HCP+SN+CIMT groups. Rotarod and front-limb suspension tests, immunohistochemistry, Golgi-Cox staining, transmission electron microscopy, and Western blot analyses were applied to measure motor function, neurons and neurofilament density, dendrites/axon areas, myelin integrity, and Nogo-A/NgR/RhoA/ROCK expression in the motor cortex. Results. The mice in the HCP+CIMT group had better motor function, greater neurons and neurofilament density, dendrites/axon areas, myelin integrity, and lower Nogo-A/NgR/RhoA/ROCK expression in the motor cortex than the HCP and HCP+UNCIMT groups (P < .05). Moreover, the expression of Nogo-A/NgR/RhoA/ROCK, the improvement of neural remodeling and motor function of mice in the HCP+SN group were similar to those in the HCP+CIMT group (P > .05). The neural remodeling and motor function of the HCP+SN+CIMT group were significantly greater than those in the HCP+SN and HCP+CIMT groups (P < .05). Motor function were positively correlated with the density of neurons (r = 0.450 and 0.309, respectively; P < .05) and neurofilament (r = 0.717 and 0.567, respectively; P < .05). Conclusions. CIMT might promote the remodeling of neurons, neurofilament, dendrites/axon areas, and myelin in the motor cortex by partially inhibiting the Nogo-A/NgR/RhoA/ROCK pathway, thereby promoting the improvement of motor function in HCP mice.
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Parálisis Cerebral/rehabilitación , Terapia por Ejercicio , Hemiplejía/rehabilitación , Corteza Motora , Plasticidad Neuronal , Condicionamiento Físico Animal , Transducción de Señal , Animales , Conducta Animal/fisiología , Parálisis Cerebral/complicaciones , Modelos Animales de Enfermedad , Femenino , Hemiplejía/etiología , Ratones , Ratones Endogámicos C57BL , Corteza Motora/citología , Corteza Motora/fisiopatología , Plasticidad Neuronal/fisiología , Proteínas Nogo/metabolismo , Receptores Nogo/metabolismo , Condicionamiento Físico Animal/fisiología , Embarazo , ARN Interferente Pequeño/metabolismo , Transducción de Señal/fisiología , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
BACKGROUND: Previous studies have provided conflicting evidence about the increased overall survival (OS) in lung cancer patients with diabetes mellitus (DM) compared with those without DM. This study assessed progression-free survival (PFS)/OS in lung cancer patients with or without DM and tentatively analyzed the impact of blood glucose levels on PFS/OS in lung cancer patients. METHODS: Data were collected from lung cancer patients based upon admission records from January 2010 to January 2012 and follow-up records from January 2010 to January 2015 in the Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai. The data included patient sex, age, body mass index (BMI), smoking status, history of DM, level of blood glucose, pathological type, clinical stage of cancer, chemotherapy regimen, and history of anti-DM drugs. The Cox regression model and Kaplan-Meier method were used for the analysis of hazard factors and PFS/OS. For comparison of PFS/OS in lung cancer with or without DM, patients were divided into three groups: lung cancer with DM, lung cancer without DM but with elevated level of blood glucose, lung cancer without DM or elevated level of blood glucose. RESULTS: In total, the data from 200 lung cancer patients (138 males/62 females, aged 29.0 to 78.0 years, mean 60.0â±â8.6 years) were collected. For the comparison of PFS/OS in lung cancer patients with or without DM, patients were divided into three groups: lung cancer with DM (nâ=â31); lung cancer without DM but with elevated levels of blood glucose (nâ=â40); and lung cancer without both DM and elevated levels of blood glucose (nâ=â128), whereas 1 patient dropped out of the study. All the patients underwent complete chemotherapy and were followed up for 36.0 to 60.0 months. Kaplan-Meier survival analysis showed that lung cancer patients with DM had increased PFS and OS compared with those without DM (log-rank, Pâ<â0.05, Pâ<â0.01); the median PFS in lung cancer with DM was 12.0 months (95% confidence interval [CI], 4.0-16.0) vs. 6.0 months in those without DM (95% CI, 5.8-6.3); and the median OS in lung cancer patients with DM was 37.0 months (95% CI, 29.0-46.6) vs. 12.0 months in those without DM (95% CI, 10.9-13.1). For the other two groups of patients without DM, there was a trend toward a shorter PFS and OS in patients with elevated blood glucose compared with those without elevated blood glucose. Cox regression showed that PFS in lung cancer patients was favorably associated with the usage of anti-DM drugs, BMI, clinical stage of cancer, and chemotherapy regimen (all Pâ<â0.05) but was inversely associated with the level of blood glucose (Pâ<â0.05). CONCLUSIONS: Lung cancer patients with DM have prolonged PFS and OS compared with those without DM, and the level of blood glucose was inversely associated with PFS. The current results indicate that PFS may be a meaningful intermediate endpoint for OS and that the levels of blood glucose hopefully represent a prognostic factor in lung cancer patients.
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Diabetes Mellitus/sangre , Diabetes Mellitus/mortalidad , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Adulto , Anciano , Glucemia/metabolismo , China , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVE: Ulcerative colitis (UC), one of the most stubborn diseases, is mainly treated by aminosalicylic acid (ASA). However, the side effects of ASA include vomiting, nausea, rash, diarrhea, headache, etc, which seriously affect life-quality of UC patients. Probiotics such as bifid triple viable (BTV) could reduce drug-induced adverse reactions and has a good clinical effect on UC. Therefore, we aimed to evaluate the clinical efficacy and safety of BTV plus ASA in treating UC. METHODS: PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure, and Wanfang databases were searched from the inception dates to October 12, 2018. Randomized controlled trials (RCTs) were included by comparing BTV plus ASA programs with ASA alone in patients with UC. Methodological quality was assessed by 2 independent researchers according to the inclusion criteria and exclusion criteria. Meta-analysis was performed by using the Review Manager 5.3 Software. Risk ratios (RRs), 95% confidence interval (CI), and standardized mean difference were calculated. RESULTS: Sixty RCTs involving 4954 participants were selected for final review. Compared with ASA, BTV plus ASA significantly improved the clinical effect rate [RR = 1.23, 95% CI (1.20, 1.26), P < .00001]; reduced the relapse rate [RR = 0.34, 95% CI (0.18, 0.62), Pâ=â.0005]; and adverse effect rate [RRâ=â0.66, 95% CI (0.53, 0.82), Pâ=â.0002]. Compared with the controls, levels of tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, C-reactive protein (CRP), hypersensitive CRP, erythrocyte sedimentation rate, and malondialdehyde were reduced; levels of IL-10, CD3+, CD4+, and superoxide dismutase were increased in BTV plus ASA group. CONCLUSIONS: BTV plus ASA has positive therapeutic effects on UC, and it might be a safe way to treat UC. However, comprehensive clinical trials are needed to obtain high level of clinical evidence.
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Ácido Aminosalicílico/uso terapéutico , Colitis Ulcerosa/terapia , Probióticos/uso terapéutico , Ácido Aminosalicílico/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Terapia Combinada , Humanos , Probióticos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Higher concentrations of reactive oxygen species (ROS) have been associated with epithelial cell damage, cell shedding, and airway hyperresponsiveness. Previous studies have indicated that transforming growth factor-beta (TGF-ß) mediates ROS production and NADPH oxidase (NOX) activity. In our previous study, we also observed that TGF-ß3 increases mucus secretion in airway epithelial cells in an autophagy-dependent fashion. Although it is well known that the relationship between ROS and autophagy is cell context-dependent, the exact mechanism of action remains unclear. The following study examined whether ROS act as upstream of autophagy activation in response to TGF-ß3 induction. Using an allergic inflammation mouse model induced by house dust mite (HDM), we observed elevated lung amounts of TGF-ß3 accompanied by increased ROS levels. And we found that ROS levels were elevated and NOX4 expression was increased in TGF-ß3-induced epithelial cells, while the lack of NOX4 in the epithelial cells could reduce ROS generation and autophagy-dependent MUC5AC expression treated with TGF-ß3. Furthermore, our studies demonstrated that the Smad2/3 pathway was involved in TGF-ß3-induced ROS generation by promoting NOX4 expression. The inhibition of ROS generation by N-Acetyl-L-cysteine (NAC) resulted in a decrease in mucus expression and autophagy activity in vivo as well as in vitro. Finally, TGF-ß3-neutralizing antibody significantly reduced the ROS generation, mucus expression, and autophagy activity and also decreased the phosphorylation of Smad2 and Smad3. Taken together, the obtained results revealed that persistent TGF-ß3 activation increased ROS levels in a NOX4-dependent pathway and subsequently induced autophagy as well as MUC5AC expression in the epithelial cells.
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Autofagia/efectos de los fármacos , NADPH Oxidasa 4/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Crecimiento Transformador beta3/metabolismo , Acetilcisteína/farmacología , Animales , Western Blotting , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Mucina 5AC/metabolismo , NADPH Oxidasa 4/genética , NADPH Oxidasas/metabolismo , Pyroglyphidae/inmunología , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: To systematically evaluate the clinical efficacy and safety of Kangfuxin liquid (KFXL) combined with aminosalicylic acid (ASA) in treating ulcerative colitis (UC). METHODS: The PubMed, Cochrane Library, Embase, CBM, Wan fang, the Chinese Scientific Journal Database (VIP), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched for randomized controlled trials of KFXL combined with ASA for UC from the inception dates to March 3, 2017. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality according to the inclusion criteria. The meta-analysis was performed using Review Manager software (RevMan, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), and the risk of bias was assessed using the Cochrane Collaboration Tool. RESULTS: A total of 39 randomized controlled trials (RCTs) involving 3204 patients fulfilled the inclusion criteria. Compared with ASA alone, KFXL combined with ASA significantly improved the clinical effectiveness rate [RRâ=â1.19, 95% CI: (1.16, 1.23), Pâ<â.00001], reduced the relapse rate [RRâ=â0.26, 95% CI: (0.18, 0.38), Pâ<â.00001], reduced the inflammation factor levels of TNF-a, IL-1, IL-6, IL-8, and C-reactive protein, reduced the coagulation index of fibrinogen, increased the coagulation index of prothrombin time, and mean platelet volume, and reduced the clinical symptoms of abdominal pain, diarrhoea, pus and bloody stool, and tenesmus. However, KFXL combined with ASA did not increase the adverse event incidence [RRâ=â0.74, 95% CI (0.42, 1.32), Pâ=â.31], and no severe adverse events were reported. CONCLUSION: KFXL combined with ASA has good therapeutic effect for UC and might be a safe approach in managing UC. More high-quality, multicenter randomized, double-blind trials with a large sample size are required to generate a high level of clinical evidence.
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Ácido Aminosalicílico/uso terapéutico , Antituberculosos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Materia Medica/uso terapéutico , Ácido Aminosalicílico/efectos adversos , Antituberculosos/efectos adversos , Citocinas/sangre , Quimioterapia Combinada , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Materia Medica/efectos adversos , Inducción de Remisión , Resultado del TratamientoRESUMEN
The 2014-2015 Ebola epidemic was considered to be the largest and most complex outbreak, which caused 11,310 reported deaths. The epidemic disease can cause a mental health crisis, however, there is only a small amount of scientific literature available related to this health issue so far. We evaluated the psychological symptoms of 161 participants including Ebola survivors and healthcare workers in Sierra Leone, analyzed the impact of job classification, education level on psychological status. We found that the order of total general severity index (GSI) scores from high to low was EVD survivors, SL medical staff, SL logistic staff, SL medical students, and Chinese medical staff. There were 5 dimensions (obsession-compulsion, anxiety, hostility, phobic anxiety, and paranoid ideation) extremely high in EVD survivors. GSI were associated with university education negatively. We believed our information is necessary to develop the comprehensive emergency response plan for emerging infectious disease outbreak.
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Personal de Salud/psicología , Fiebre Hemorrágica Ebola/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/etiología , Sobrevivientes/psicología , Adolescente , Adulto , Niño , Estudios Transversales , Brotes de Enfermedades , Femenino , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Prevalencia , Sierra Leona , Adulto JovenRESUMEN
Recently, a meta-analysis including 5 large genome-wide association studies has identified rs12456492 variant of RIT2 gene as a novel risk locus for Parkinson's disease (PD) in Caucasian populations. However, the association between RIT2 polymorphism and PD risk has not been positively replicated in Asian population yet. We detected the genotypes of rs12456492 in 524 PD patients and 521 control subjects from a Han Chinese population. The allele and genotype distribution of rs12456492 variant were significantly different between PD patients and controls (allele p = 0.001, genotype p = 0.002). Logistic regression analysis showed that the G-carrying genotype (AG + GG) individuals exhibited a nearly 1.4-fold increased risk for PD compared with the AA genotype carriers (OR = 1.390; 95% confidence interval = 1.079-1.791; p = 0.011). Our data support that the carriage of G allele of rs12456492 variant of RIT2 gene significantly increases the risk for PD in Han Chinese population, suggesting a potential role of RIT2 in the etiology of PD.
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Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Proteínas de Unión al GTP Monoméricas/genética , Enfermedad de Parkinson/genética , Polimorfismo Genético/genética , Anciano , Alelos , Femenino , Genotipo , Heterocigoto , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
Recent studies have reported that a rare nonsynonymous variant rs75932628-T in the TREM2 gene is associated with increased risk of Alzheimer's disease and Parkinson's disease (PD) in European-descended populations. However, the association between rare TREM2 mutations and PD risk remains unknown in Chinese population. We directly sequenced exon2 of TREM2 in a cohort of 476 PD patients and 432 healthy controls from a Han Chinese population. Rs75932628-T (p.R47H) was found in 0.2% of PD cases (1/476) but in none of the controls (0/432, p = 1.000), with a minor allele frequency of 0.06% among the 908 subjects. Our findings suggest that variants in exon2 of TREM2 are extremely rare, and it is not a genetic risk factor for PD in the southern Han Chinese population.
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Glicoproteínas de Membrana/genética , Mutación/genética , Enfermedad de Parkinson/genética , Receptores Inmunológicos/genética , Pueblo Asiatico/genética , Estudios de Cohortes , Exones/genética , Femenino , Estudios de Asociación Genética , Humanos , Masculino , RiesgoRESUMEN
OBJECTIVE: To explore the effect of Changji'an Capsule (CA) on mRNA expressions of neuropeptide Y (NPY) in the hypothalamus and colon and serum levels of adreno-cortico-tropic hormone (ACTH) in rats of diarrhea predominant irritable bowel syndrome (IBS-D) model rats. METHODS: Totally 48 SD rats were randomly divided into six groups, i.e., the normal control group, the model group, the Pinaverium Bromide group (PB, 0.018 g/kg), the high dose CA group (2.812 g/kg), the medium dose CA group (1.406 g/kg), and the low dose CA group (0.703 g/kg), 8 in each group. The IBS-D rat model was established by using separation of breast milk + stimulation of acetic acid + constraint of four limbs. Normal saline was given to rats in the normal control group and the model group. All medication lasted for 14 successive days by gastrogavage. The serum content of ACTH was detected by enzyme linked immunosorbent assay (ELISA). The expressions of NPY mRNA in the colon and the hypothalamus were detected using real-time fluorescence quantitative PCR. RESULTS: Compared with the normal control group, the serum ACTH content significantly increased (P < 0.01), the NPY mRNA expression in the colon and the hypothalamus obviously decreased (P < 0.01) in the model control group. Compared with the model group, the serum ACTH obviously decreased in the high dose CA group, the medium dose CA group, and the PB group (P < 0.01, P < 0.05). The NPY mRNA expression in the colon and the hypothalamus were obviously up-regulated in the high dose CA group, the medium dose CA group, the low dose CA group, and the PB group (P < 0.05). CONCLUSIONS: CA could modulate the abnormity of brain-gut axis of IBS-D rats possibly by up-regulating NPY mRNA expressions in the hypothalamus and the colon and down-regulating the ACTH content in the hypothalamic-pituitary-adrenal axis.
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Medicamentos Herbarios Chinos/farmacología , Síndrome del Colon Irritable/metabolismo , Neuropéptido Y/metabolismo , Hormona Adrenocorticotrópica/sangre , Animales , Colon/metabolismo , Modelos Animales de Enfermedad , Femenino , Hipotálamo/metabolismo , Masculino , ARN Mensajero/genética , Ratas , Ratas Sprague-DawleyRESUMEN
LM23, a gene expressed specifically in the testis in a stage-specific manner, has a diverse range of functions that are important in both the life and death of spermatogenic cells. The aim of this study was to further investigate the expression of LM23 in the developing rat testis and the biological function of LM23 in proliferation and antiapoptosis in vitro. Semiquantitative reverse transcription (RT)-PCR and real-time PCR were used to examine the expression of LM23 in testis at different developmental stages. The results suggested that LM23 mRNA levels in the testis increased progressively after birth. The role of LM23 in proliferation was analyzed with cell counting kit-8 (CCK8), colony-forming efficiency (CFE) and flow cytometry assays. The results indicated that ectopic expression of LM23 in 293T cells significantly promoted cell proliferation by increasing cell numbers in S phase. Several methods were used, including CCK8, annexin V and propidium iodide staining and western blotting, to determine the role of LM23 in apoptosis. The results showed that LM23 played a protective role in H2O2-induced apoptosis of 293T cells, mediated at least in part through the Akt/PI3K signal pathway. Taken together, these results provide new insights into the role of LM23 in the development of the testes and spermatogenesis.
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Apoptosis/fisiología , Proteínas de Ciclo Celular/fisiología , Proliferación Celular , Testículo/crecimiento & desarrollo , Testículo/fisiología , Animales , Apoptosis/efectos de los fármacos , Proteínas de Ciclo Celular/genética , Regulación del Desarrollo de la Expresión Génica , Células HEK293 , Humanos , Peróxido de Hidrógeno/farmacología , Masculino , FN-kappa B/metabolismo , Oxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiología , Testículo/citologíaRESUMEN
AIM: To investigate the protective effect and mechanism of curcumin against ActD/TNF-α-induced synergistically apoptosis in PC12 cells. METHODS: MTT assay was used to evaluate the optimal concentration of drugs; Hoechst 33258 fluorescent staining to observe apoptosis of PC12 cells, JC-1 was used to detect the mitochondrial membrane potential (MMP), real-time PCR was used to detect the expression of two apoptotic genes: Bcl-1 and Bax. RESULTS: ActD/TNF-α can synergistically reduce viability of PC12 cells(P<0.05), increase the number of cells with pyknosis and karyorrhexis, increase apoptotic rate of cells (P<0.05), decrease MMP in cells, and downregulate expression of Bcl-2(P<0.05). After treating with curcumin(5 µmol/L), survival of PC12 cells was increased(P<0.05), the number of cells with pyknosis and karyorrhexis was reduced, MMP and expression of Bcl-2 were increased(P<0.05). CONCLUSION: Curcumin can resist the ActD/TNF-α-induced synergistically apoptosis in PC12 cells, the mechanisms of which may be related to an increase in MMP and Bcl-2 expression.
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Apoptosis/efectos de los fármacos , Curcumina/farmacología , Dactinomicina/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Animales , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Células PC12 , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Ratas , Proteína X Asociada a bcl-2/análisisRESUMEN
OBJECTIVE: To explore the clinical efficacy of electroacupuncture intervention on severe acute pancreatitis (SAP) at early stage complicated with intestinal paralysis. METHODS: Sixty-eight cases of SAP were randomly divided into observation group (48 cases) and control group (20 cases). In observation group, according to the course of sickness, the early-stage subgroup (30 cases, hospitalized in 3 d) and late-stage subgroup (18 cases, hospitalized in 3-7 d) were subdivided. In control group, the conventional treatment was applied. In observation group, based on the same treatment as control group, electroacupuncture was supplemented at Zhongwan (CV 12), Zusanli (ST 36), Neiguan (PC 6), Hegu (LI 4), etc. Acute physiology and chronic health evaluation (APACHE) II scores, the recovery time of intestinal paralysis and laboratory indices, complications, operation transfer rate, death rate and the admission time were compared among groups after treatment. RESULTS: The total effective rate was 83.3% (25/30) in early-stage subgroup, which was superior to 72.2% (13/18) in late-stage subgroup and 65.0% (13/20) in control group (P < 0.05, P < 0.01). In early-stage subgroup, the remission time of abdominal pain, the remission time of abdominal distention, the recovery time of borborygums, the recovery time of gas discharge, and the recovery time of defecation were all shorter significantly than those in late-stage subgroup and control group (P < 0.05, P < 0.01). In early-stage subgroup, APACHE II scores, the recovery time of WBC and blood/uric amylase, complications, operation transfer rate, death rate and admission time were all lower remarkably than those in late-stage subgroup and control group (P < 0.05, P < 0.01); but, there were no statistical significant differences in comparison between late-stage subgroup and control group (all P > 0.05). CONCLUSION: The clinical efficacy of electroacupuncture intervention on SAP complicated with intestinal paralysis is superior remarkably to that of conventional treatment, and the efficacy of electroacupuncture intervention at early stage is better than that at late stage.
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Electroacupuntura , Seudoobstrucción Intestinal/terapia , Pancreatitis/terapia , Enfermedad Aguda , Adulto , Anciano , Femenino , Humanos , Seudoobstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Pancreatitis/complicacionesRESUMEN
OBJECTIVE: To investigate the efficacy and safety of ademetionine for treatment of cholestatic or mixed-type drug-induced liver disease (DILD) in children. METHODS: The children with DILD were divided into the treated group and control group. Yinzhihuang Granule was orally administered and Compound Glycyrrhizin Injection intravenously given in patients of both groups. Those patients in the treated group were additionally treated with intravenous infusion of 250-1000 mg ademetionine for 28 d. The incidence of pruritus and adverse effects as well as biochemical parameters in all the patients and compared between the 2 groups. For statistical analysis, Chi2 test was used for between-group comparison and t test for processing the data. RESULTS: 1) Before treatment, severe pruritus was found in 17 and 16 children in the treated and control group, respectively. Two weeks after the treatment, the symptom was significantly relieved in 14 and 3 patients in the treated and control group, respectively (Chi2 = 4.52, P < 0.05). 2) As for comparisons between the 2 groups, a P value of 0.0014 for AST level was found 4 weeks, 0.045 and 0.007 for disappearance and recovery rate of jaundice, 0.0014 and 0.0006 for decrease in TBA level and 0.0003 for gammaGT level 2 and 4 weeks after the treatment. CONCLUSION: Intravenous administration of ademetionine is safe in children with DILD and it can effectively alleviate pruritus, promote the recovery of various biochemical parameters and fasten liver functional recovery in these children. Therefore, ademetionine can be widely used for treatment of intrahepatic cholestasis in children.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , S-Adenosilmetionina/efectos adversos , S-Adenosilmetionina/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: To study the relation of the mRNA and protein expression of Cyclin A and p21cip1 in different stages hypertrophic scar fibroblast (FB) with its cell cycle, so as to provide theoretical evidence for intervention therapy of cell cycle gene being used in hypertrophic scar. METHODS: The hypertrophic scar samples at different stages (the third month, the sixth month, the twelfth month, the twenty-fourth month) in 32 cases and the normal skin samples in 8 cases were used in this study. The expression of Cyclin A, p21cip1 mRNA and protein was detected by quantitative real-time PCR and Western Blot. And at the same time, the flow cytometer was used to detect the fibroblastic cell life cycle. RESULTS: 1) The expression of Cyclin A mRNA and protein in the third month group, the sixth month group, the twelfth month group, the twenty-fourth month group were 19.34 +/- 2.41, 0.99 +/- 0.11; 19.30 +/- 1.42, 0.96 +/- 0.09; 10.73 +/- 2.93, 0.66 +/- 0.58; 9.29 +/- 0.97, 0.65 +/- 0.14, respectively. And in corresponding stages, the expression of p21cip1 mRNA and protein were 2.80 +/- 0.69, 0.35 +/- 0.07; 4.95 +/- 1.82, 0.44 +/- 0.07; 9.98 +/- 1.19, 0.56 +/- 0.06; 10.25 +/- 1.46, 0.59 +/- 0.06, respectively. The expression intensity of Cyclin A mRNA and protein was no significantly different between the third month group and the sixth month group (P > 0. 05), but it was higher respectively than that in the twelfth month group, the twenty-fourth month group and normal group (P < 0.05). And the expression intensity was no different between the above three groups (P > 0.05). The expression intensity of P21cip1 mRNA and protein in the third month group was lower than that in the sixth month group, but that in the above two groups was lower respectively than that in the twelfth month group, the twenty-fourth month group and normal group (P < 0.05). And the expression intensity had no difference between the three later stage groups (P > 0.05). 2) Most FB were in S and G2/M stage (cycle) in 3rd month, 6th month group. And most FB were in G0/G1 stage (cycle) in 12th month, 24th month group and normal group. CONCLUSIONS: The expression of mRNA and protein of Cyclin A in hypertrophic scar changes from high level to low level as the hypertrophic scar develops, while the expression of P21cip1 changes from low level to high level. The mRNA and protein expression of Cyclin A and p21cip1 respectively are basically corresponded to different stages of hypertrophic scar. The distribution of cell life cycle of fibroblastic are also corresponded to the expression intensity of Cyclin A and p21cip1 in different stages hypertrophic scar. An early stage intervention to the two gene can be effective to prevent from the genesis and development of hypertrophic scar.
Asunto(s)
Cicatriz Hipertrófica/metabolismo , Ciclina A/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Fibroblastos/metabolismo , Adolescente , Adulto , Ciclo Celular , Células Cultivadas , Niño , Cicatriz Hipertrófica/patología , Femenino , Fibroblastos/patología , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To understand the occurrence and development of adolescent students' type 2 diabetes mellitus (T2DM) by researching the characteristics of the adolescent students' impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) effected by overweight or obesity. METHODS: From May to November 2007, 3856 middle school students aged 11 to 18 years old in Dongguan city were enrolled in the study. Overweight or obesity (b/Ob) depended on three indexes: the national unified school-age children and adolescent students' body mass index (BMI) and the temporary screening classification standard II established by the Working Group on Obesity in China, BP > or = 140/90 mm Hg (1mm Hg = 0.133 kPa) and fasting capillary whole glucose which was greater than or equal to 5.6 mmol/L. The fasting capillary whole glucose was screened by blood glucose meter from fingertips. Students who had any abnormal indexes were brought into this study. On basis of voluntary principle, blood lipid, fasting blood glucose (FPG) and 2-hour postprandial blood glucose (2 h PG), fasting insulin (FIns) of 368 male and 326 female students who conformed to these conditions were measured using their venous blood. By temporary BMI standard II, they were divided into overweight group (b) and obesity group (Ob). Data of different age groups (11 to 14; 15 to 18 years old) was analyzed. RESULTS: The BMI, low density lipoprotein cholesterol (LDL-C), insulin resistance index (IR), IFG and IGT of the same age stage in two groups were compared. The BMI value was (22.1 +/- 2.4) kg/m2, LDL-C was (2.38 +/- 0.65) mmol/L, IR was 1.15 +/- 0.58 and the detection rates of IFG and IGT were 3.5% and 1.4% respectively in female students aged 11 to 14 years old in b group. In Ob group, BMI value was (24.4 +/- 3.9) kg/m2, LDL-C was (2.70 +/- 0.73) mmol/L, IR was 1.36 +/- 0.67 and the detection rates of IFG and IGT were 14.6% and 6.3% respectively. t or chi2 values of two groups which were compared were 4.83, 2.45, 2.10, 7.41 and 7.99 (P < 0.01 or P < 0.05). BMI value was (25.8 +/- 3.1) kg/m2, LDL-C was (2.35 +/- 0.62) mmol/L, IR was 1.14 +/- 0.64 and the detection rates of IFG and IGT were 3.1% and 4.1% respectively in 15 to 18 years old in b group. In Ob group, BMI value was (28.0 +/- 4.3) kg/m2, LDL-C was (2.69 +/- 0.69) mmol/L, IR was 1.43 +/- 0.84 and the detection rates of IFG and IGT were 12.8% and 15.4% respectively. t or chi2 values of two groups which were compared were 3.33, 2.79, 1.87, 4.75 and 5.17 (P < 0.01 or P < 0.05). BMI value was (22.4 +/- 2.3) kg/m2, LDL-C was (2.36 +/- 0.67) mmol/L, IR was 1.19 +/- 0.65 and the detection rates of IFG and IGT were 3.6% and 1.8% respectively in male students of 11 to 14 years old in b group. In Ob group, BMI value was (24.6 +/- 4.2) kg/m2, LDL-C was (2.68 +/- 0.71) mmol/L, IR was 1.44 +/- 0.89 and the detection rates of IFG and IGT were 13.3% and 9.4% respectively. t or chi2 values of two groups which were compared were 4.85, 2.72, 2.19, 6.75 and 6.76 (P < 0.01 or P < 0.05). BMI value was (26.4 +/- 2.8) kg/m2, LDL-C was (2.35 +/- 0.70) mmol/L, IR was 1.24 +/- 0.68 and the detection rates of IFG and IGT were 4.7% and 5.6% respectively in 15 to 18 years old in b group. In Ob group, BMI value was (28.2 +/- 4.8) kg/m2, LDL-C was (2.71 +/- 0.73) mmol/L, IR was 1.50 +/- 0.95 and the detection rates of IFG and IGT were 17.9% and 17.9% respectively. t or chi2 values of two groups which were compared were 2.80, 2.69, 1.84, 6.68 and 6.27 (P < 0.01 or P < 0.05). The male students' FPG of 11 to 14 years old in b group was (4.88 +/- 0.76) mmol/L and FPG of Ob group was (5.09 +/- 0.80) mmol/L. Two groups were compared and t = 1.84 (P < 0.05). The statistical differences were all observed. We compared different age stages and found that the male students' 2-hour PG of 11 to 14 years old in Ob group was (5.13 +/- 1.18) mmol/L and the 2-hour PG of 15 to 18 years old was (5.36 +/- 1.24) mmol/L. Two groups were compared and t = 1.78 (P < 0.05) near the adults value. Male students' IGT of 11 to 14 years old (b/Ob) had 8 positive cases and the positive detection rate was 3.6%. IGT of 15 to 18 years old (b/Ob) had 13 positive cases and the positive detection rate was 8.9%. Two age stages were compared and chi2 = 6.86 (P < 0.01). Female students' IGT of 11 to 14 years old (b/Ob) had 5 positive cases and the positive detection rate was 2.6%. IGT of 15 to 18 years old (b/Ob) had 10 positive cases and the positive detection rate was 7.4%. Two age stages were compared and chi2 = 4.02 (P < 0.05). All had statistical significance. The high IGT incidence rate of b/Ob group's male and female students was in the stage of 15 - 18 years old. Male students were more obvious. CONCLUSION: T2DM prevention among adolescent students should start with body overweight control. Meanwhile, the adolescent students with high risk factors should be screened regularly and early measures should be taken to prevent the impaired glucose regulation (IFG, IGT) transforming into T2DM.