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BACKGROUND: Few studies have been conducted to explore medication non-adherence in persons with schizophrenia (PWS) and its influencing factors in rural China. This study aimed to investigate the medication non-adherence and its influencing factors among PWS in rural China. METHODS: A total of 269 PWS and their family caregivers in Xinjin district, Chengdu, China were investigated on medication adherence and related factors. Logistic regression was employed to identify the influencing factors. RESULTS: The results showed that 37.6% of PWS had medication non-adherence. PWS living with family caregivers had significantly lower rate of medication non-adherence (34.7%) than those not living with family caregivers (60.0%) (p < 0.01). Family caregivers' affiliate stigma of mental illness, knowledge of mental illness and self-esteem were significantly related to patients' medication non-adherence (p < 0.05). PWS' employment status, living with family caregiver, present mental status and social support were significantly related to medication adherence. CONCLUSION: This study shows medication non-adherence is severe among PWS in rural China. Both patient- and family-related factors affect patients' medication adherence seriously. Except improving patients' treatment and mental status, development of family caregiving, social support network and intervention on reducing stigma of mental illness should be crucial for enhancing PWS' medication adherence.
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BACKGROUND: Affiliate stigma of family caregivers may severely influence family caregiving, early treatment, and recovery of people with mental illness (PMI), and it may be impacted by the knowledge of mental illness and contact with PMI. However, little is known about the correlation between affiliate stigma of family caregivers of PMI and contact in Hong Kong. AIMS: This study aimed to investigate affiliate stigma and its influencing factors among family caregivers of PMI in Hong Kong. METHODS: A total of 106 family caregivers in Hong Kong participated in the study. The measurements included affiliate stigma, contacts (quantity, quality, and level), knowledge, prejudice, and discriminatory behaviors. Multiple regression analyses were employed. RESULTS: The mean score of affiliate stigma scale (ASS) in family caregivers was 2.17 (SD = 0.65). In regression analyses, the results showed that contact quantity and contact level were significantly associated with higher affiliate stigma and its cognitive domain, while contact quality (e.g. positive contact) were significantly associated with lower affiliate stigma and its all domains among family caregivers. The positive relationship between prejudicial attitudes and affiliate stigma was also found. CONCLUSIONS: Affiliate stigma is severe among family caregivers of PMI in Hong Kong. The results of this study indicate that contact, especially positive contact, contributes to reducing affiliate stigma among family caregivers of PMI. The results of this study are important for development of health policy on reducing stigma in family caregivers of PMI. The effectiveness of Enhancing Contact Model (ECM) should be examined in future anti-stigma interventions.
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Cuidadores , Trastornos Mentales , Humanos , Cuidadores/psicología , Hong Kong , Familia/psicología , Estigma Social , Trastornos Mentales/psicologíaRESUMEN
BACKGROUND: It remains unknown what the impacts of multiple dimensions of contact (e.g. level, quantity and quality) are on the stigma of mental illness. AIMS: To explore the relationship between the multiple dimensions of contact and stigma of mental illness among family members (FM), mental health workers (MHW) and community residents (CR) in Hong Kong. METHODS: The stigma, contact and knowledge were measured in FM, MHW and CR in Hong Kong. Multiple regression analyses were used. RESULTS: MHW (n = 141) had higher knowledge, more contact and lower stigma of mental illness than CR (n = 95) or FM (n = 62). Knowledge and contact quality were significantly associated with lower stigma of mental illness in the three groups. However, contact level and contact quantity were not significantly associated with most stigma components. The contact level was positively associated with stigma of mental illness among FM and CR. CONCLUSIONS: The results of this study highlight the differences in knowledge, contact and stigma of mental illness among different stakeholder groups. This study suggests that positive contact (e.g. equal, supportive, voluntary and pleasant contact) reduces stigma of mental illness, while negative contact (e.g. unfriendly, unsupportive, unpleasant contact) may increase stigma. The Enhancing Contact Model (ECM) should be tested in future anti-stigma interventions.
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Trastornos Mentales , Estigma Social , Hong Kong , HumanosRESUMEN
BACKGROUND: Although cultural factors play a crucial role in experience of stigma, there is scant review on the impact and importance of culture on stigma of mental illness across Pacific Rim Region. This study aims to investigate: 1) the cultural factors related to stigmatizing beliefs about mental illness in Pacific Rim region, and 2) culture-specific measures and interventions on stigma of mental illness. METHODS: A systematic search of papers was conducted in the MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus, Cochrane Library and Google scholar through January 2003 to April 2019. RESULTS: Forty-one studies in Pacific Rim region which met the inclusion criteria were included in the study. The rate of stigma of mental illness (e.g., public stigma: from 25.4 to 85.2%) was relatively high in Pacific Rim region. Culture factors (e.g., Collectivism, Confucianism, face concern and familism, religion and supernatural beliefs) contributed to people's stigmatizing behaviors and attitudes toward persons with mental illness, their relatives and mental health professionals. Certain measurements were developed and employed to assess different type of cultural factors related to stigma of mental illness. CONCLUSIONS: Cultural factors play an important role in influencing the rate and performance of stigma of mental illness. Further research on stigma of mental illness and culture-specific interventions to reduce the stigma should be conducted in the Pacific Rim region.
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Trastornos Mentales , Estigma Social , HumanosRESUMEN
BACKGROUND: Self-stigma exerts a range of adversities for persons with severe mental illness (SMI), however, little is known about the association between peer contact, social support and self-stigma. AIMS: This study aimed to explore the mediating role of social support on the relationship between peer contact and self-stigma among persons with SMI in Hong Kong. METHODS: A total of 159 persons with SMI (schizophrenia and mood disorder) in community service centres participated in the study through completing a survey on self-stigma, social functioning, social support, perception of peer contact and mass media. Logistic regression was utilised to explore the influencing factors of self-stigma among the participants. RESULTS: The results showed that 81.1% of participants reported moderate to severe levels of self-stigma. Self-stigma was significantly associated with diverse factors (e.g. social functioning). Importantly, positive peer contact was significantly associated with lower self-stigma of persons with SMI. Social support acted as a mediator between peer contact and self-stigma. CONCLUSION: The results of this study suggest that contact-based interventions, such as enhancing positive peer-to-peer contact, should be conducted for reducing self-stigma among persons with SMI.
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Trastornos Mentales , Estigma Social , Hong Kong , Humanos , Autoimagen , Apoyo SocialRESUMEN
BACKGROUND: Although knowledge is a crucial component in contact theory delineating how prejudice changes toward out-groups with stigmatized conditions, little is known about the mediating role of knowledge on contact, stigmatizing attitudes, and behaviors toward mental illness. AIM: This study aimed to examine the mechanism underlie contact and stigma change by knowledge. METHODS: A total of 366 participants including family members (FM), mental health providers (MHP), and community residents (CR) recruited across communities in Hong Kong and completed measures of contact level, contact quantity, contact quality, mental health related knowledge, prejudice, and discriminatory behaviors. Structural equation modeling was adopted to test the association among the key variables. RESULTS: Higher level of contact was significantly correlated with better knowledge, less prejudice, and less discriminatory behaviors. Knowledge was directly and negatively correlated with prejudicial attitudes but was not significantly related to discriminatory behaviors. Furthermore, lower levels of prejudice were associated with less discriminatory behaviors. CONCLUSION: Enhancement of contact may increase understanding toward people with mental illness (PMI) and diminish stigmatizing attitudes and behaviors. Although prejudicial attitudes may be reduced by broadening mental health knowledge, increasing knowledge only might not ameliorate discriminatory behaviors. Future research should test mediators on contact and stigma by using longitudinal data.
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Trastornos Mentales , Estigma Social , Hong Kong , Humanos , Salud Mental , PrejuicioRESUMEN
Landing is a crucial factor in gymnastics competitions, but the underlying biomechanical and neuromuscular strategies remains unclear. This study aimed to investigate the biomechanical characteristics and neuromuscular strategies of landing for backward somersault. A 19-segment human model was developed and bilateral lower-limb joint loadings were estimated using computer stimulation. Bilateral lower-limb joint angles, vertical ground reaction force (vGRF), impulse, joint reaction force, joint torque, power, work, stiffness and electromyogram (EMG) of the rectus femoris, biceps femoris, tibialis anterior, and lateral gastrocnemius were presented during initial (touchdown to peak vGRF) and terminal impact-phases of landing (peak vGRF to vGRF equaling to body weight). The hip, knee, and ankle joints were rapidly flexed (8º, 20º, and 18º, respectively) during initial impact-phase and maintained at around 90º, 120º, and 60º, respectively terminal impact-phase. Flexor and extensor torques were demonstrated for lower-limb joints during initial and terminal impact-phases, respectively. The stiffness of lower limb joints and the EMGs amplitude of all examined muscles during terminal impact-phase were several times larger than that during initial impact-phase. The absolute symmetry indexes were less than 10% for lower limb joint angles and larger than 10% for the kinetics and muscle activation. The findings demonstrated symmetrical motion for lower limb joints with flexing rapidly at initial impact-phase and maintaining unchanged at terminal impact-phase and asymmetry in joint loading and muscle activation during landing.
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Gimnasia/fisiología , Músculos Isquiosurales/fisiología , Articulaciones/fisiología , Músculo Cuádriceps/fisiología , Adolescente , Articulación del Tobillo , Antropometría , Fenómenos Biomecánicos , Simulación por Computador , Electromiografía , Humanos , Imagenología Tridimensional , Articulación de la Rodilla , Masculino , Modelos Anatómicos , Movimiento , Estrés Mecánico , Soporte de PesoRESUMEN
Two new aromatic glycosides, 2-methylphenyl O-ß-d-xylopyranosyl-(1â6)-O-ß-d-glucopyranoside (1) and 2-methylphenyl O-α-arabinofuranosyl-(1â6)-O-ß-glucopyranoside (2), together with eight known compounds were isolated from the roots of Ampelopsis delavayana. Their structures were elucidated on the basis of extensive spectroscopic analysis. Furthermore, the in vitro antibacterial activities of 1 and 2 were investigated using serial twofold dilution in three bacteria including Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.
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Ampelopsis/química , Antibacterianos/aislamiento & purificación , Glicósidos/aislamiento & purificación , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Glicósidos/química , Glicósidos/farmacología , Estructura Molecular , Raíces de Plantas/química , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Phytochemical investigation on the whole plant of Chloranthus japonicus (Chloranthaceae) led to the isolation and identification of three new lindenane-type sesquiterpenoid dimers, chlorajaponilides F-H (1-3), along with seven known ones (4-10). Their chemical structures were established by extensive spectral evidence. Compounds 1 and 2 are both dimeric sesquiterpenoids featuring a rare hydroperoxy group at C-5. All compounds were tested for their activities on wild type HIV-1 replication and compounds 1, 2, 5, and 9 were effective with EC50 values from 3.08 to 17.16µM. All these four compounds showed the same inhibitory effects on the two NNRTI-resistant HIV strains as on wild-type HIV-1 with EC50 change folds from 0.61 to 1.6µM. Furthermore, compounds 1, 5, and 9 exhibited inhibitory activities on HCV replication with the similar potency as their activities on HIV-1. Our finding may provide a clue to address the problem of HIV-1 and HCV co-infection.
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Antivirales/química , VIH-1/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Magnoliopsida/química , Sesquiterpenos/química , Replicación Viral/efectos de los fármacos , Antivirales/aislamiento & purificación , Células HEK293 , VIH-1/fisiología , Hepacivirus/fisiología , Humanos , Estructura Molecular , Sesquiterpenos/aislamiento & purificaciónRESUMEN
BACKGROUND The aim of this study was to compare the hemodynamic changes in 2 different cannulations in portal system (portal venous catheterization and splenic venous catheterization) during venovenous bypass (VVB) of swine orthotopic liver transplantation (OLT) MATERIAL AND METHODS Thirty pairs (a total of 60) of healthy Duroc pigs were selected for OLT. According to the difference of cannulation in portal venous system during VVB, these pigs were divided into 2 groups: the PVC group (pigs with portal venous catheterization, n=15) and the SVC group (pigs with splenic venous catheterization, n=15). Intraoperative hemodynamic parameters were monitored continuously. RESULTS Two recipients in the PVC group died: 1 died of unsmooth bypass during the operation and 1 died of disseminated intravascular coagulation (DIC). There was only 1 death in the SVC group, due to hemorrhagic shock. The duration of anhepatic phase (AP) in the SVC group was significantly shorter than in the PVC group (P<0.05). Moreover, hemodynamic parameters in phase III (5 min after start of portal vein suturing) and phase IV (5 min after graft reperfusion) were remarkably different between the SVC group and the PVC group (P<0.05). CONCLUSIONS Our results show that VVB via splenic venous catheterization in swine OLT: 1) shortens the AP time; 2) keeps the hemodynamics stable; and 3) reduces the occurrence of postoperative complications. Thus, SVC appears to be superior to PVC.
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Cateterismo Periférico/métodos , Trasplante de Hígado/métodos , Vena Porta/cirugía , Procedimientos Quirúrgicos Vasculares , Animales , Hemodinámica/fisiología , Porcinos , Vena Cava Inferior/cirugíaRESUMEN
OBJECTIVE: To investigate the effects of inhibiting TIM-4 function in Kupffer cells (KCs) on liver graft rejection in mice and explore the underlying mechanism. METHODS: Mouse models of orthotopic liver transplantation were treated with a control mAb group and TIM-4 mAb. The activated KCs were assayed with immunohistochemistry after operation. The expression of TIM-4 in KCs were assayed with Western blotting and RT-PCR and the levels of AST, ALT, TBIL, TNF-α, IFN-γ and CCL2 were assayed detected. The expression of TIM-4 in KCs was observed with laser confocal microscopy. HE staining was used to observe the microstructure of the liver tissues, and the number of CD25+Foxp3+T cells was determined using with flow cytometry; the proteins levels of p-P65and p-P38 were assayed with Western blotting. The donor mice were treated with clodronate liposomes to destroy the KCs in the liver before transplantation, and the liver grafts were examined for graft rejection. RESULTS: The number of activated KCs in the liver graft increased progressively over time. Compared with the sham-operated group, the liver graft showed significantly increased TIM-4 protein and mRNA levels at 1, 3, and 7 days after transplantation (P<0.05) and increased levels of AST, ALT, TBIL, TNF-α, IFN-γ and CCL2 at 7 days (P<0.05). The graft in TIM-4 mAb group showed mild pathological changes with a mean RAI score of 2.67∓0.75, which was significantly lower than that in control mAb group (P<0.05). The mean survival time of the recipient mice was 53.8∓6.4 days in TIM-4 mAb group, significantly longer than that in the control mAB group (14.5∓2.9 days, P<0.05). Donor treatment with clodronate liposomes resulted in comparable RAI scores in TIM-4 mAb and control mAb groups (8.01∓0.64 vs 7.93∓0.56, P>0.05). The protein levels of p-P65 and p-P38 in TIM-4 mAb group were significantly lower than those in control mAb group (P<0.05), and CD25+Foxp3+T cells in the liver graft increased significantly in TIM-4 mAb group. CONCLUSION: Inhibition of TIM-4 function in KCs reduces the production of inflammatory factors after liver transplantation possibly by inhibiting the NF-κB and MAPK signaling pathways and promoting the proliferation of Foxp3+Treg cells to induce allograft tolerance.
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Anticuerpos Monoclonales/farmacología , Rechazo de Injerto , Macrófagos del Hígado/metabolismo , Trasplante de Hígado , Proteínas de la Membrana/antagonistas & inhibidores , Animales , Inmunohistoquímica , Macrófagos del Hígado/efectos de los fármacos , Hígado/cirugía , Masculino , Ratones , FN-kappa B/metabolismo , Linfocitos T Reguladores/inmunologíaRESUMEN
Dendritic cells (DCs) are multifunctional cells that initiate adaptive immune responses. Patients with chronic hepatitis B virus (HBV) infection have reduced numbers of DCs which may be functionally impaired, a defect that may contribute to viral persistence. Autologous DC-based immunotherapy is considered to be a treatment option for chronic HBV infection (CHB). We evaluated the therapeutic efficacy of HBV-pulsed DCs in combination with the antiviral drug entecavir in patients with CHB. Eighty patients were divided into four groups: HBV-pulsed DCs only, HBV-pulsed DCs plus entecavir, entecavir only, and an untreated control group. Patients on combination therapy exhibited greater antiviral responses than patients on either monotherapy. The combination of HBV-pulsed DCs and entecavir resulted in the largest reduction in serum viral DNA levels and the highest percentage of virologic response. In addition, combination therapy resulted in viral e antigen (HBeAg) loss and seroconversion. These results suggest that the combination of HBV-pulsed autologous DCs and entecavir could be therapeutically advantageous for patients with CHB.
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Antivirales/uso terapéutico , Células Dendríticas , Guanina/análogos & derivados , Virus de la Hepatitis B , Hepatitis B Crónica/terapia , Adolescente , Adulto , Tratamiento Basado en Trasplante de Células y Tejidos , Terapia Combinada , ADN Viral/sangre , Células Dendríticas/inmunología , Células Dendríticas/virología , Quimioterapia Combinada , Femenino , Guanina/uso terapéutico , Antígenos e de la Hepatitis B , Hepatitis B Crónica/sangre , Hepatitis B Crónica/virología , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Seroconversión , Adulto JovenRESUMEN
The aim of this study was to investigate the effects of systematic rehabilitation programs on the quality of life (QOL) in patients undergoing lung resection of malignant lung lesions. In this prospective population-based cohort study, QOL in patients prior to, as well as 3 and 6 months after surgery, was investigated. Using a single-group design, 48 patients (7 females and 41 males) with suspected operable lung cancer were included in this study. The demographic characteristics and the clinical history of the patients were recorded. QOL [assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 3.0 (EORTC QLQ-C30)] was evaluated at baseline (immediately before), and 3 and 6 months after surgical resection. The systematic rehabilitation program, including breathing control, breathing exercises, relaxation training, upper and lower extremity exercises, mobilization and additional incorporating physiotherapy programs, was designed to meet each patient's individual needs. The χ2 and Fisher's tests showed no statistically significant difference in the two groups in terms of age, gender, behavior, clinical stage, adjuvant therapy and Karnofsky scores. QOL analysis of baseline was homogeneous between the experimental and control groups. Three months after the rehabilitation process, the experimental group demonstrated an increase in the general QOL functional scales and a decrease of symptom scales compared to the control group. These changes were statistically significant in the functional scales of global health (P<0.01), physical function (P<0.01), role function (P<0.01), emotional function (P<0.05), symptom scales of fatigue (P<0.01) and appetite loss (P=0.001). Six months after the intervention, the outcome was the same as 3 months after the intervention in functional scale domains. However, in the symptom scales, the symptoms in the experimental group were improved compared to the control group. The domains had been significant in the scales of fatigue (P<0.001), dyspnea (P<0.001), pain (P<0.001), insomnia (P<0.001), appetite loss (P<0.001) and constipation (P<0.001). Therefore, the two groups demonstrated a statistically significant difference in 10 domains. In addition, the experimental group demonstrated a significant recovery. In conclusion, systematic rehabilitation programs may be beneficial for lung cancer patients by reducing respiratory symptoms, pain, and improving health-related QOL. Consequently, the findings of this study suggest that systematic rehabilitation programs, prepared by taking into consideration the individual requirements of lung cancer patients, should be incorporated into lung cancer treatment.
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Magnetic fluid hyperthermia (MFH) induced by a magnetic field has become a new heating technology for the treatment of malignant tumors due to its ability to heat the tumor tissue precisely and properly, and due to its significant therapeutic effects. In this study, MFH induced by radiofrequency capacitive field (RCF) for the treatment of transplanted subcutaneous tumors in rats, was investigated. A total of 50 rats bearing subcutaneous tumors were randomly divided into five groups, including i) a pseudo-treatment (PT) control group, ii) magnetic fluid (MF) group, iii) pure hyperthermia (PH) group, iv) magnetic fluid hyperthermia 1 (MFH1) group, and v) magnetic fluid hyperthermia 2 (MFH2) group. Tumors were irradiated for 30 min in the MFH1 group 24 h following injection of MF. Tumors were irradiated for 30 min in the MFH2 group 24 h following injection of MF, and irradiation was repeated for 30 min 72 h following injection of MF. Tumor volumes, tumor volume inhibition ratios and survival times in the rat model were examined. Temperatures of tumor cores and rims both rapidly reached the desired temperature (â¼50°C) for tumor treatment within 5 to 10 min in the MFH1 and MFH2 groups, and we maintained this temperature level by manually adjusting the output power (70-130 W). Tumor volumes of the MFH1 and MFH2 groups were reduced compared to those of the PT, MF and PH groups. The inhibitory effect on tumor growth in the MFH2 group (91.57%) was higher compared to that in the MFH1 group (85.21%) and the other groups. The survival time of the MFH2 group (51.62±2.28 days) and MFH1 group (43.10±1.57 days) was increased compared to that of the PH, MF and PT groups. The results obtained show that MFH induced by RCF may serve as a potential and promising method for the treatment of tumors.
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BACKGROUND: Several experimental studies have observed better outcomes after glycine treatment in patients with endotoxin-induced liver injuries, but its molecular mechanism is not yet fully understood. The purpose of this study was to evaluate the hypothesis that glycine attenuates endotoxin-induced liver injury by affecting endotoxin signal transduction in liver macrophages. METHODS: An animal model of endotoxin-induced liver injury was established by intraperitoneally injecting mice with 10 mg/kg body weight endotoxin fed a pretreatment diet with or without 5% (w/w) glycine. Blood and liver samples were obtained for analysis of liver morphology and to determine concentrations of alanine aminotransferase, endotoxin receptor Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-10 at various time points after injection. To investigate the effect of glycine on liver macrophages, Kupffer cells (KCs) were isolated and challenged by LPS (100 ng/mL), with or without glycine (4 mmol/l) pretreatment, and the expressions of TLR4, IL-10, and TNF-alpha were assayed at mRNA and protein levels. DNA-binding activity of nuclear factor-kappa B (NF-kappaB) was also analyzed using enzyme-linked immunosorbent assay. RESULTS: Dietary glycine significantly improved the survival rate of endotoxemic mice (P < .05), whereas serum alanine aminotransferase and TNF-alpha levels were significantly decreased at different time points (P < .05); IL-10 levels were increased (P < .05). Concurrently, LPS-induced hepatic tissue injury was attenuated as indicated by morphologic analysis; secretion of IL-10 in liver tissue (P < .05) was enhanced; and expression of TLR4 and TNF-alpha in liver tissue was downregulated (P < .05). Consistent with these in vivo experiments, enhanced secretion of IL-10 and inhibited expression of TLR4 and TNF-alpha caused by glycine pretreatment were also observed in LPS-stimulated KCs. NF-kappaB DNA-binding activity was also significantly inhibited by glycine (P < .05, respectively). CONCLUSIONS: Dietary glycine improved survival rates and liver function in endotoxemic mice by regulating the production of proinflammatory or anti-inflammatory cytokines in liver. It attenuated liver injury by deactivating KCs through inhibiting TNF-alpha secretion and increasing IL-10 production. The downregulative effect of glycine on the endotoxin signaling pathway and TLR4/NF-kappaB/TNF-alpha may be a novel potential mechanism by which glycine inhibits KC activity.
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Antiinflamatorios/administración & dosificación , Glicina/administración & dosificación , Macrófagos del Hígado/metabolismo , Hepatopatías/prevención & control , Receptor Toll-Like 4/metabolismo , Administración Oral , Animales , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Lipopolisacáridos/efectos adversos , Hepatopatías/etiología , Hepatopatías/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Transducción de SeñalRESUMEN
BACKGROUND: Endotoxin tolerance (ET) is an important mechanism to maintain the homeostasis of Kupffer cells (KCs), because KCs are continually exposed to various pathogen-associated molecular patterns including lipopolysaccharide (LPS). ET involves multiple changes in cell signal transduction pathways; however, not all signaling pathways are down-regulated and some proteins are up-regulated. The latter proteins may be counter regulatory, including interleukin-1 receptor-associated kinase M (IRAK-M) expression. The aim of this study is to clarify weather or not IRAK-M is involved in the mechanisms of ET in KCs through dampening nuclear factor-kappa B (NF-kappaB) mediated pathway. MATERIALS AND METHODS: KCs isolated from male C57BL/6J mice were seeded in 24-well plates at 1 x 10(6) cells/well and cultured overnight prior to transfection, were randomly divided into two groups: the pIRAK-M-short hairpin RNA (shRNA) group (transfected with IRAK-M shRNA) and the control group (transfected with control vector); 24 h after transfection, the two groups were further randomly divided into two subgroups: non-endotoxin pretreatment group (incubation in Dulbecco's modified Eagle's medium [Invitrogen, Carlsbad, CA] with 10% fetal bovine serum) and endotoxin pretreatment group (incubation in the same medium containing 10 ng/mL LPS), named pIRAK-M-EP, pIRAK-M-NEP, pCV-EP, and pCV-NEP, respectively. Each subgroup contained 6 wells; 24 h later, fresh media containing LPS (100 ng/mL) was added to each subgroup and incubated for an additional 3 h. The expression of IRAK-M gene and protein level were determined by reverse transcription-polymerase chain reaction and Western blot, the activities of NF-kappaB were estimated by electrophoretic mobility shift assay and enzyme-linked immunosorbent assay, and the supernatant tumor necrosis factor-alpha levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: The recombinant plasmid of pIRAK-M-shRNA specifically inhibited IRAK-M expression after it was transfected into KCs. At 3 h after 100 ng/mL LPS was added to the medium, IRAK-M expression was significantly induced in pCV-EP than that in pCV-NEP; however, there was no difference between pIRAK-M-NEP and pIRAK-M-EP, accompanied with lowest level of NF-kappaB activation and tumor necrosis factor-alpha levels in pCV-EP, and a dramatic enhancement in the other three groups (P < 0.01). CONCLUSIONS: Although a primary low dose of LPS stimulation obviously attenuated KCs response to the second LPS stimulation, the inhibitive influences were partly refracted in pIRAK-M-EP than in pCV-EP, indicating that the absence of IRAK-M caused abnormal enhancement of inflammatory effects. IRAK-M negatively regulates toll-like receptors signaling and involves in the mechanisms of ET in KCs through dampening NF-kappaB mediated pathway; therefore it may be a key component of this important control system, and a new target for the clinical treatment of sepsis.
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Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Macrófagos del Hígado/metabolismo , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Receptores Toll-Like/metabolismo , Animales , Macrófagos del Hígado/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Interferencia de ARN , Transcripción Genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND & OBJECTIVE: Many nasopharyngeal carcinoma (NPC) patients could survive for a long time after radiotherapy. But the complications of radiotherapy, such as trismus, severely influence the quality of life of NPC patients. This study was to observe the effect of early rehabilitation training on radiation-induced trismus of NPC patients. METHODS: A total of 108 NPC patients received rehabilitation guidance by doctors at initial radiotherapy and subjected to early rehabilitation training regularly and intensively after radical radiotherapy between Dec. 2003 and Dec. 2004 at Xiangya Hospital of Central South University. They continued on rehabilitation training out of hospital as the same in hospital. According to the data of rehabilitation training obtained by questionnaire at 1 month after radiotherapy, the patients who completed the amount of rehabilitation training (>or=75%) were brought into rehabilitation training group, the others was brought into control group. The distance between two dens incivus medialis (DDIM) of the patients was measured at 1 month and 1 year after radiotherapy. RESULTS: The difference of rehabilitation training score was significantly higher in rehabilitation training group than in control group (9.80+/-3.02. vs.4.75+/-1.90 at 1 month after radiotherapy, P<0.05û 9.00+/-2.67 vs. 2.20+/-0.82 at 1 year after radiotherapy, P<0.05). The occurrence rates of trismus were 44.1% at 1 month and 51.5% at 1 year after radiotherapy in rehabilitation training group, and 60.0% and 85.0% in control group. The reduction of DDIM was significantly smaller in rehabilitation training group than in control group [(0.50+/-0.48) cm vs. (1.20+/-0.74) cm at 1 month after radiotherapy, P<0.05û (0.58+/-0.62) cm vs. (2.42+/-0.84) cm at 1 year after radiotherapy, P<0.01]. CONCLUSIONS: Early rehabilitation training is helpful to decrease the occurrence of trismus in NPC patients after radiotherapy and improve the quality of life of NPC patients.
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Terapia por Ejercicio , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Alta Energía , Trismo/rehabilitación , Adolescente , Adulto , Anciano , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Aceleradores de Partículas , Calidad de Vida , Radioterapia de Alta Energía/efectos adversos , Encuestas y Cuestionarios , Trismo/etiología , Trismo/prevención & control , Adulto JovenRESUMEN
OBJECTIVE: To explore the feasibility of interleukin 1 receptor associated kinase-4 (IRAK-4) as gene therapy target for liver ischemia/reperfusion injury (I/RI) and effective approach in vivo for short hairpin RNA (shRNA) interference used to gene therapy in liver graft hqappened. METHODS: Sprague-Dawley rats were randomly divided into three groups: the control group, the in vivo transfection group (IVT) and the cold ischemia transfection group (CIT). Experiments of orthotopic liver transplantation were performed by two-cuff method. CIT were perfused with IRAK-4-shRNA plasmid (pSIIRAK-4) during cold ischemia phase, IVT received the equivalent volumes (2 mL) of pSIIRAK-4 after portal vein inosculated, and the control group leaved without any treatment. At 0 min, 60 min and 180 min after reperfusion, the expression of IRAK-4 gene and protein level were determined by RT-PCR and Western blot. The serum TNF-alpha level was detected by ELISA. Liver histopathological changes and cell apoptosis were observed by electron microscope and TUNEL. RESULTS: After reperfusion, the expression of IRAK-4 were largely depressed in CIT than that of IVT and the control group (P < 0.01), and furthermore, the serum TNF-alpha level, proportion of hepatocyte apoptosis and severity of hepatocyte injury were also lower than the latter. CONCLUSION: These results indicate that depression IRAK-4 expression with IRAK-4-shRNA through portal vein perfusion during cold ischemia phase could effectively blunt graft hepatic I/RI.
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Quinasas Asociadas a Receptores de Interleucina-1/genética , Trasplante de Hígado/efectos adversos , Hígado/irrigación sanguínea , Daño por Reperfusión/genética , Daño por Reperfusión/prevención & control , Animales , Terapia Genética , Rechazo de Injerto , Quinasas Asociadas a Receptores de Interleucina-1/biosíntesis , Hígado/metabolismo , Masculino , Interferencia de ARN , Ratas , Ratas Sprague-Dawley , Transducción de Señal , TransfecciónRESUMEN
OBJECTIVE: To explore the protective mechanisms of glycine (Gly) on lipopolysaccharides (LPS) induced liver injury. METHODS: BABL/c mice were randomly divided into a LPS group, in which the animals were intraperitoneally injected with 10 mg/kg LPS, and a Gly group, in which the mice were pretreated with a 5% Gly-containing diet for 3 days before receiving the same dose of LPS. The livers of the mice were examined for histopathological changes. The TNF alpha and interleukin-10 (IL-10) levels in the blood plasma were measured using ELISA analysis. The mRNA expression of TNF alpha, IL-10 and Toll-like receptor 4 (TLR4) in hepatic tissues were detected using RT-PCR analysis. Protein expression of TLR4 in livers was detected using immunohistochemistry. RESULTS: The Gly group mice had an improved survival rate and attenuated LPS-induced pathological changes in the liver tissues in comparison with those of the LPS group animals. The TNF alpha levels [(1,852.80+/-126.64) pg/ml vs (708.83+/-51.29) pg/ml, P<0.05] in plasma, as well as the expression of TNF alpha (A 1.59+/-0.14 vs. 0.91+/-0.11, P<0.05) and TLR4 (A 0.97+/-0.12 vs. 0.53+/-0.11, P<0.05) mRNA in liver tissues were decreased. However, the levels of plasma interleukin-10 [(344.09+/-31.70) pg/ml vs (418.64+/-38.86) pg/ml, P<0.05] were significantly increased and the peaking time left, shifted. CONCLUSIONS: Gly pretreatment could attenuate LPS -induced liver injury in mice, which may be associated with its role in down-regulating TLR4 expression and up-regulating IL-10 production.
Asunto(s)
Glicina/farmacología , Hígado/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Regulación hacia Abajo , Femenino , Interleucina-10/sangre , Interleucina-10/metabolismo , Lipopolisacáridos/efectos adversos , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: To explore the possible mechanism and optimal treatment phase of glycine for inhibition lipopolysaccharide (LPS) induced Kupffer cells (KCs) activation. METHODS: The KCs were isolated from 40 BALB/c mice and divided into four groups: the endotoxin group, the prevention group, the early treatment group and the later treatment group (n = 10). The endotoxin group was treated with 10 mg/L LPS, and in the other three groups, glycine (1 mmol/L) was given 24 h before, or at 0 h or 4 h respectively after LPS stimulation. At 0 h, 1 h, 2 h, 6 h and 12 h after LPS stimulation, the mRNA levels and protein expression of interleukin-1 receptor associated kinase-4 (IRAK-4) were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot respectively, and nuclear factor-kappaB (NF-kappaB) activities as well as tumor necrosis factor alpha (TNF-alpha) levels were also detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The climax values of IRAK-4, NF-kappaB and TNF-alpha were significantly higher in the endotoxin group and the later treatment group than that in the other two groups (t = 3.17, 4.33, 2.47, 126.73, P < 0.01). CONCLUSION: The results indicated that prophylactic or simultaneous treatment with glycine could effectively inhibit LPS-induced KCs activation by inhibiting IRAK-4 expression.