RESUMO
Epstein-Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α-mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.
Assuntos
Infecções por Vírus Epstein-Barr , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Herpesvirus Humano 4/metabolismo , Infecções por Vírus Epstein-Barr/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Transdução de Sinais , Transporte ProteicoRESUMO
BACKGROUND: Phytobacter diazotrophicus (P. diazotrophicus) is an opportunistic pathogen that causes nosocomial outbreaks and sepsis. However, there are no reports of P. diazotrophicus isolated from human blood in China. CASE PRESENTATION: A 27-day-old female infant was admitted to our hospital with fever and high bilirubin levels. The clinical features included jaundice, abnormal coagulation, cholestasis, fever, convulsions, weak muscle tension, sucking weakness, ascites, abnormal tyrosine metabolism, cerebral oedema, abnormal liver function, clavicle fracture, and haemolytic anaemia. The strain isolated from the patient's blood was identified as P. diazotrophicus by whole-genome sequencing (WGS). Galactosemia type 1 (GALAC1) was diagnosed using whole-exome sequencing (WES). Based on drug sensitivity results, 10 days of anti-infective treatment with meropenem combined with lactose-free milk powder improved symptoms. CONCLUSION: P. diazotrophicus was successfully identified in a patient with neonatal sepsis combined with galactosemia. Galactosemia may be an important factor in neonatal sepsis. This case further expands our understanding of the clinical characteristics of GALAC1.
Assuntos
Galactosemias , Sepse , Humanos , Feminino , China , Galactosemias/complicações , Galactosemias/microbiologia , Sepse/microbiologia , Sepse/tratamento farmacológico , Sepse/complicações , Recém-Nascido , Antibacterianos/uso terapêutico , Meropeném/uso terapêutico , Sequenciamento Completo do Genoma , Gammaproteobacteria/genética , Gammaproteobacteria/isolamento & purificaçãoRESUMO
Depressed patients who medicate with selective serotonin reuptake inhibitors (SSRIs) often report ocular dryness. Epidemiological studies have found that serotonin and norepinephrine reuptake inhibitors (SNRIs) are not risk factors for dry eye in depressed patients. However, the effect of SNRIs on the ocular surface is unknown. A depression rat model was induced by chronic unpredictable mild stress (CUMS), and SNRIs or SSRIs were administered to the rats for 3 or 6 weeks. The levels of norepinephrine (NE) and serotonin in tear fluid were tested by ELISA. The corneal fluorescence and lissamine green staining were used to evaluate ocular surface damage. NE and/or serotonin were administered to human corneal epithelial cells in vitro. RNA sequencing (RNA-seq) analysis was performed to investigate the mRNA expression profiles. Tear NE levels were higher in the SNRIs group, and ocular surface inflammation and apoptosis were significantly reduced compared to the SSRIs group. RNA-Seq indicated that NE significantly activate MAPK signaling pathway. NE can inhibit serotonin-induced activation of the NF-κB signaling pathway through α-1 adrenergic receptors and promotes the proliferation of corneal epithelial cells through activation of the MAPK signaling pathway. SNRIs administration have less ocular surface damage than SSRIs. NE protects human corneal epithelial cells from damage, and reduce inflammation on the ocular surface via activating the MAPK signaling pathway. SNRIs might be used as an appropriate treatment for depression-related DED.
Assuntos
Inibidores Seletivos de Recaptação de Serotonina , Inibidores da Recaptação de Serotonina e Norepinefrina , Humanos , Ratos , Animais , Serotonina , Depressão/tratamento farmacológico , Norepinefrina/metabolismoRESUMO
Cholangiocarcinoma (CCA) is a serious health problem worldwide. The gut and bile microbiota have not been clearly characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA need to be established. The aim of this study was to investigate the characteristics of the gut and bile microbiota in CCA patients. Forty-two CCA patients and 16 healthy normal controls (HNCs) were enrolled. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. We found that there were significant differences in the species diversity, structure, and composition of the microbial communities between the CCA group and the HNC grouAt the phylum level, compared with that in the HNC group, the relative abundance of Firmicutes and Actinobacteriota was significantly decreased in the CCA group, whereas Proteobacteria and Bacteroidota were significantly enriched. The Firmicutes/Bacteroidota (F/B) ratio significantly decreased in the CCA group compared to the HNC grouThe relative abundance of Klebsiella in the CCA group was significantly higher than that in the HNC group, while the relative abundance of Bifidobacterium was significantly decreased. The Bifidobacterium/Klebsiella (B/K) ratio was established as a novel biomarker and was found to be significantly decreased in the CCA group compared with the HNC grouOur findings provide evidence supporting the use of Klebsiella and Bifidobacterium as noninvasive intestinal microbiomarkers for improving the diagnosis of CCA.
Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Bifidobacterium/genética , Klebsiella/genética , RNA Ribossômico 16S/genética , Bile , Firmicutes/genética , Bacteroidetes/genética , Fezes/microbiologiaRESUMO
Objectives: To investigate the effect of thermal pulsation treatment on meibomian gland function, ocular parameters and tear inflammatory cytokines compared with the warm compress group. Methods: Twenty-five participants with MGD underwent a 12-minute thermal pulsation treatment, while 25 participants with MGD underwent manual warm compress treatment. MGD related parameters, including meibomian gland function (MGE, MQ and lid margin), tear stability (NIKBUT, FBUT and LLT), tear secretion (SIT, and TMH), were examined and OSDI questionnaire was also obtained. Tear chemokines (MIG, IFN-γ, IL-8, IP-10 and MCP-1) were examined and analyzed the correlations with MGD related parameters and OSDI. Results: Compared with warm compress subjects, OSDI, lid margin and tear stability were found improved more in thermal pulsation treatment at 3 months (OSDI: *p = 0.014, lid margin: *p = 0.021, LLT: **p = 0.008, CFS: *p = 0.028). The level of IP-10 and MIG decreased more in thermal pulsation group than in warm compress group (IP-10: *p = 0.021, MIG: *p = 0.039). IP-10 was positively correlated with MQ (r = 0.522, *p = 0.037) and negatively correlated with tear stability (r = -0.613, **p = 0.002), and OSDI was only positively correlated with IL-8 (r = 0.679, ***p < 0.001). The decrease of MIG was positively correlated with less corneal epithelium injury (r = 0.557, **p = 0.006) and meibograde (r = 0.49, *p = 0.019). Conclusions: Thermal pulsation treatment obviously improved MGD probably by attenuating tear CXCL chemokines in ocular surface of MGD patients, which demonstrated an efficacy and well-tolerated therapy in clinical.
Assuntos
Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Humanos , Disfunção da Glândula Tarsal/terapia , Quimiocina CXCL10 , Interleucina-8 , Glândulas Tarsais , Citocinas , Síndromes do Olho Seco/terapiaRESUMO
PURPOSE: To evaluate the relations between nonmotor manifestations (dry eye, mood disorders, and sleep disturbance) and motor disorders in patients with benign essential blepharospasm (BEB), and to determine whether relieving motor disorders by botulinum neurotoxin can improve the nonmotor manifestations. METHODS: In this prospective case series study, 123 BEB patients were enrolled for evaluations. Among them, 28 patients underwent botulinum neurotoxin therapy and attended another two postoperative visits at 1 month and 3 months. Motor severity was measured with Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI). We assessed dry eye using OSDI questionnaire, Schirmer test, tear break-up time (TBUT), tear meniscus height, lipid layer thickness (LLT) and corneal fluorescence staining. Zung's Self-rating Anxiety and Depression Scale (SAS, SDS) and Pittsburgh Sleep Quality Index (PSQI) were for mood status and sleep quality evaluations. RESULTS: Patients with dry eye or mood disorders had higher JRS scores (5.78 ± 1.13, 5.97 ± 1.30) than those without (5.12 ± 1.40, 5.50 ± 1.16; P = 0.039, 0.019, respectively). BSDI values of patients with sleep disturbance (14.61 ± 4.71) was higher than those without (11.89 ± 5.44, P = 0.006). Correlations were found between JRS, BSDI and SAS, SDS, PSQI, OSDI, TBUT. Botulinum neurotoxin effectively relieved JRS, BSDI and improved PSQI, OSDI, TBUT, LLT (8.11 ± 5.81, 21.77 ± 15.76, 5.04 ± 2.15 s, 79.61 ± 24.11 nm) at the 1-month visit compared to baseline (9.75 ± 5.60, 33.58 ± 13.27, 4.14 ± 2.21 s, 62.33 ± 22.01 nm; P = 0.006, < 0.001, = 0.027, < 0.001, respectively). CONCLUSIONS: The BEB patients with dry eye, mood disorders, or sleep disturbance had more severe motor disorders. Motor severity was associated with the severity of the nonmotor manifestations. Relieving motor disorders by botulinum neurotoxin was effective in improving dry eye and sleep disturbance.
Assuntos
Blefarospasmo , Toxinas Botulínicas Tipo A , Síndromes do Olho Seco , Transtornos Motores , Humanos , Blefarospasmo/complicações , Blefarospasmo/diagnóstico , Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Transtornos Motores/complicações , Lágrimas , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/etiologiaRESUMO
In recent years, there has been a significant increase in age-related diseases due to the improvement in life expectancy worldwide. The pancreas undergoes various morphological and pathological changes with aging, such as pancreatic atrophy, fatty degeneration, fibrosis, inflammatory cell infiltration, and exocrine pancreatic metaplasia. Meanwhile, these may predispose the individuals to aging-related diseases, such as diabetes, dyspepsia, pancreatic ductal adenocarcinoma, and pancreatitis, as the endocrine and exocrine functions of the pancreas are significantly affected by aging. Pancreatic senescence is associated with various underlying factors including genetic damage, DNA methylation, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and inflammation. This paper reviews the alternations of morphologies and functions in the aging pancreas, especially ß-cells, closely related to insulin secretion. Finally, we summarize the mechanisms of pancreatic senescence to provide potential targets for treating pancreatic aging-related diseases.
Assuntos
Envelhecimento , Pâncreas Exócrino , Pancreatopatias , Humanos , Diabetes Mellitus/patologia , Pâncreas/patologia , Pâncreas Exócrino/patologia , Pancreatopatias/patologia , Hormônios Pancreáticos , Neoplasias Pancreáticas/patologia , Envelhecimento/patologiaRESUMO
The occurrence of high-level tigecycline resistance tet(X) variant genes represents a new transferable resistance crisis to food safety and human health. Here, we investigated the abundance of tet(X)-variant genes [tet(X), tet(X1) to tet(X6)] in 33 samples collected from layer manures, manured/un-manured soils, and corresponding lettuce from three provinces in China. The results showed the occurrence of tet(X)/(X2), tet(X3), and tet(X4) in 24 samples. The detection rate of tet(X)/(X2) (23/24) is higher than that of tet(X3) (7/24) and tet(X4) (2/24), and tet(X)/tet(X2) and tet(X3) were found to be enriched and more abundant in most manured soil and several lettuce samples from manured soils than that from manure samples. Twenty six tigecycline-resistant bacteria were isolated, and tet(X)-variant genes were found to be disseminated not only by bacterial clone spreading but also via multidrug resistance plasmids. The total concentrations of tet(X)-variant genes showed significantly positive correlations (R = 0.683, p < 0.001) with ISCR2. Two veterinary tetracyclines (tetracycline and oxytetracycline) and other classes of antimicrobials (enrofloxacin, azithromycin, thiamphenicol, and florfenicol) showed significant correlations with the total concentrations of tet(X)-variant genes (R = 0.35-0.516, p < 0.05). The findings indicate the transmission of tet(X)-variant genes from layer manures to their receiving environmental soils and lettuce and highlight the contribution of veterinary antimicrobials to the spread of tet(X)-variant genes.
Assuntos
Esterco , Solo , Antibacterianos/farmacologia , China , Fazendas , Genes Bacterianos , Lactuca/genética , Esterco/análise , Microbiologia do Solo , Resistência a TetraciclinaRESUMO
Corneal lymphangiogenesis plays a key role in diverse pathological conditions of the eye. Here, we demonstrate that a versatile extracellular matrix protein, transforming growth factor-ß induced protein (TGFBIp), promotes lymphatic sprouting in corneal lymphangiogenesis. TGFBIp is highly up-regulated in inflamed mouse corneas. Immunolocalization of TGFBIp is detected in infiltrating macrophages in inflamed mouse corneas. Subconjunctival injection of liposomal clodronate can significantly reduce macrophage infiltration in inflamed mouse cornea, and decrease the expression of TGFBIp and areas of corneal lymphangiogenesis and angiogenesis after corneal suture placement. In brief, these results indicate that the up-regulation of TGFBIp in sutured cornea correlates with macrophage infiltration. Although TGFBIp alone cannot significantly stimulate corneal lymph vessel ingrowth in vivo, it can enhance the effect of vascular endothelial growth factor-C in promoting corneal lymphangiogenesis. The in vitro results show that TGFBIp promotes migration, tube formation and adhesion of human lymphatic endothelial cells (HLECs), but it has no effect on HLECs' proliferation. We also find that the in vitro effect of TGFBIp is mediated by the integrin α5ß1-FAK pathway. Additionally, integrin α5ß1 blockade can significantly inhibit lymphatic sprouting induced by TGFBIp. Taken together, these findings reveal a new molecular mechanism of lymphangiogenesis in which the TGFBIp-integrin pathways plays a pivotal role in lymphatic sprouting.
Assuntos
Córnea/metabolismo , Proteínas da Matriz Extracelular/farmacologia , Linfangiogênese/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Animais , Córnea/efeitos dos fármacos , Córnea/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Integrina alfa5beta1/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Suturas , Regulação para Cima/efeitos dos fármacos , Fator C de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Osteoarthritis (OA) is characterized as the degeneration and destruction of articular cartilage. In recent decades, leonurine (LN), the main active component in medical and edible dual purpose plant Herba Leonuri, has been shown associated with potent anti-inflammatory effects in several diseases. In the current study, we examined the protective effects of LN in the inhibition of OA development as well as its underlying mechanism both in vitro and in vivo experiments. In vitro, interleukin-1 beta (IL-1ß) induced over-production of prostaglandin E2, nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor alpha were all inhibited significantly by the pretreatment of LN at a dose-dependent manner (5, 10, and 20 µM). Moreover, the expression of thrombospondin motifs 5 (ADAMTS5) and metalloproteinase 13 (MMP13) was downregulated by LN. All these changes led to the IL-1ß induced degradation of extracellular matrix. Mechanistically, the LN suppressed IL-1ß induced activation of the PI3K/Akt/NF-κB signaling pathway cascades. Meanwhile, it was also demonstrated in our molecular docking studies that LN had strong binding abilities to PI3K. In addition, LN was observed exerting protective effects in a surgical induced model of OA. To sum up, this study indicated LN could be applied as a promising therapeutic agent in the treatment of OA.
Assuntos
Ácido Gálico/análogos & derivados , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Regulação para Baixo/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Ácido Gálico/farmacologia , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular/métodos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/metabolismoRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as important regulators in the modulation of virus infection by targeting mRNA transcription. However, their roles in chronic hepatitis B (CHB) remain to be elucidated. OBJECTIVE: The study aimed to explore the lncRNAs and mRNA expression profiles in CHB and asymp-tomatic HBsAg carriers (ASC) and construct mRNA-lncRNA co-expression profile and ceRNA net-works to identify the potential targets of diagnosis and treatment in CHB. METHODS: We determined the expression profiles of lncRNAs and mRNAs in CHB and ASC using mi-croarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) path-way enrichment analyses were performed to explore their function. We also constructed co-expression, cis-regulatory, and competing endogenous RNA (ceRNA) networks with bioinformatics methods. RESULTS: We identified 1634 mRNAs and 5550 lncRNAs that were differentially expressed between CHB and ASC. Significantly enriched GO terms and pathways were identified, many of which were linked to immune processes and inflammatory responses. Co-expression analysis showed 1196 relation-ships between the top 20 up/downregulated lncRNAs and mRNA, especially 213 lncRNAs interacted with ZFP57. The ZFP57-specific ceRNA network covered 3 lncRNAs, 5 miRNAs, and 17 edges. Cis-correlation analysis showed that lncRNA T039096 was paired with the most differentially expressed gene, ZFP57. Moreover, by expending the clinical samples size, the qRT-PCR results showed that the expression of ZFP57 and T039096 increased in CHB compared to ASC. CONCLUSION: Our study provides insights into the roles of mRNA and lncRNA networks in CHB, high-lighting potential applications of lncRNA-T039096 and mRNA-ZFP57 for diagnosis and treatment.
RESUMO
PURPOSE: To evaluate the efficacy of corneal cross-linking (CXL) as adjuvant therapy for the treatment of fungal ulcerative keratitis. METHODS: Forty-one patients with fungal ulcerative keratitis were recruited and assigned into two randomized controlled groups. These groups were treated with CXL combined with antifungal medications (CXL-M) or antifungal medications alone (M). The ulcers were assessed by slit-lamp biomicroscopy, slit-lamp images, in vivo confocal microscopy (IVCM), and anterior segment optical coherence tomography (AS-OCT). The patients were followed up before surgery/first visit (FV), 1 day after surgery, 1 and 2 weeks, and 1, 2, 3, 4, 5, and 6 months after surgery/FV. RESULTS: In the cured patients, the area of corneal ulcers, the duration of ulcer healing, the time to non-observed fungal hyphae by IVCM, the number of antifungal medications, the frequency of administered medications, and the maximum ulcer depth decreased significantly after CXL (all P < 0.05) compared with the M group. There were no significant differences in either corneal thickness or epithelial thickness of ulcers after healing between 5 and 6 months after surgery in the CXL-M group, while these were increased significantly at 6 months compared with 5 months after FV in the M group (both P < 0.05). CONCLUSIONS: In our study, CXL accelerated healing of the fungal ulcers, shortened the treatment duration, and minimized the need for medications and surgery. It appears that CXL is an effective procedure and adjuvant therapy for managing fungal keratitis.
Assuntos
Antifúngicos/farmacologia , Córnea/patologia , Úlcera da Córnea/tratamento farmacológico , Reagentes de Ligações Cruzadas/farmacologia , Infecções Oculares Fúngicas/tratamento farmacológico , Fotoquimioterapia/métodos , Riboflavina/farmacologia , Córnea/microbiologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/microbiologia , Feminino , Seguimentos , Fungos/isolamento & purificação , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/farmacologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Raios UltravioletaRESUMO
BACKGROUND: Sjogren's syndrome dry eye (SSDE) mainly affects middle-aged women and can negatively affect women's psychological and social functioning. However, little is known about the correlation between vision-related quality of life (VR-QoL) and psychological status for women with SSDE. We therefore examined VR-QoL and psychological status in two groups of Chinese women: an SSDE group and a non-SSDE group. We also explored the associations between VR-QoL scores, sociodemographic measures, ophthalmologic parameters, and psychological status in women with SSDE. METHODS: The case-control study recruited 30 female outpatients with SSDE and 30 without SSDE from the Eye and Ear, Nose, and Throat (ENT) Hospital of Fudan University. Demographic and ophthalmologic data were collected from all participants. Ophthalmologic examinations included best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time (TBUT) and Schirmer test. Data collected using the National Eye Institute's Visual Function Questionnaire (NEI-VFQ) and Ocular Surface Disease Index (OSDI) survey instruments were analyzed to identify potential differences in VR-QoL between the SSDE group and the non-SSDE group. We also used the Zung Self-Rating Anxiety and Self-Rating Depression Scales (SAS and SDS) to determine psychological status in both groups. RESULTS: The SSDE group scored significantly lower than the non-SSDE group on the NEI-VFQ subscales of general health, general vision, and long-distance vision activities (all p < 0.05). The SSDE group achieved a significantly higher ocular symptoms score compared with the control group (p = 0.0256). The SAS and SDS scores of the SSDE group were significantly higher than the non-SSDE group (p = 0.0072 and 0.0162, respectively). The prevalence of anxiety and depression in the SSDE group was significantly higher than the non-SSDE group (p = 0.0240 and 0.0200, respectively). Nine of twelve NEI-VFQ subscales were negatively correlated with SAS/SDS scores (all p values were <0.05). The exceptions were social function, color vision and peripheral vision. The composite OSDI score and its three subscale scores for the women in the SSDE group were all positively correlated with overall SAS/SDS scores (all p values were <0.05). CONCLUSIONS: Both VR-QoL and psychological status were significantly worse in SSDE group than in the non-SSDE group. The VR-QoL of women with SSDE had a negative correlation with their anxiety and depression levels.
Assuntos
Efeitos Psicossociais da Doença , Qualidade de Vida/psicologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/psicologia , Adulto , Estudos de Casos e Controles , Queixo , Feminino , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Visão OcularRESUMO
The aim of the study was to observe the effect of different artificial tears on healing the drug-induced keratopathy. To this aim, 64 rabbits received topical administration of 0.01% benzalkonium chloride to establish models and were divided into four groups. The control group received ocular saline solution (Saline), while the others were treated with Refresh Plus® (RF), Hycosan® (H) and Systane® Ultra (SU). Surface abnormalities were examined daily using slit-lamp. Fluorescein staining, histopathological and transmission electron microscopic (TEM) examination were performed at day 0, 2 weeks, and 1 and 2 months. A significant difference was observed between RF and SU, but not between H and SU at 2 weeks. TEM examination revealed new microvilli close to the cavity surface, and the number of microvilli in SU was greater than in H at 2 weeks and 1 month. Based on the results, the effect in the SU group was the most significant. Eye drops with nontoxic preservative such as SU are an alternative to treat drug-induced keratopathy.
Assuntos
Compostos de Benzalcônio/toxicidade , Doenças da Córnea/tratamento farmacológico , Epitélio Corneano/efeitos dos fármacos , Lubrificantes Oftálmicos/uso terapêutico , Conservantes Farmacêuticos/toxicidade , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/patologia , Modelos Animais de Doenças , Epitélio Corneano/ultraestrutura , Masculino , CoelhosRESUMO
Melioidosis is an infectious disease of high mortality for humans and other animal species; it is prevalent in tropical regions worldwide. The pathogenesis of melioidosis depends on the ability of its causative agent, the Gram-negative bacterium Burkholderia pseudomallei, to enter and survive in host cells. B. pseudomallei can escape from the phagosome into the cytosol of phagocytic cells where it replicates and acquires actin-mediated motility, avoiding killing by the autophagy-dependent process, LC3 (microtubule-associated protein light chain 3)-associated phagocytosis (LAP). The type III secretion system cluster 3 (TTSS3) facilitates bacterial escape from phagosomes, although the mechanism has not been fully elucidated. Given the recent identification of small-molecule inhibitors of the TTSS ATPase, we sought to determine the potential of the predicted TTSS3 ATPase, encoded by bsaS, as a target for chemotherapeutic treatment of infection. A B. pseudomallei bsaS deletion mutant was generated and used as a control against which to assess the effect of inhibitor treatment. Infection of RAW 264.7 cells with wild-type bacteria and subsequent treatment with the ATPase inhibitor compound 939 resulted in reduced intracellular bacterial survival, reduced escape from phagosomes, and increased colocalization with both LC3 and the lysosomal marker LAMP1 (lysosome-associated membrane protein 1). These changes were similar to those observed for infection of RAW 264.7 cells with the bsaS deletion mutant. We propose that treatment with the ATPase inhibitor compound 939 decreased intracellular bacterial survival through a reduced ability of bacteria to escape from phagosomes and increased killing via LAP. Therefore, small-molecule inhibitors of the TTSS3 ATPase have potential as therapeutic treatments against melioidosis.
Assuntos
Adenosina Trifosfatases/antagonistas & inibidores , Sistemas de Secreção Bacterianos/imunologia , Burkholderia pseudomallei/efeitos dos fármacos , Burkholderia pseudomallei/enzimologia , Melioidose/tratamento farmacológico , Animais , Proteínas de Bactérias/genética , Burkholderia pseudomallei/genética , Linhagem Celular , Feminino , Evasão da Resposta Imune , Estimativa de Kaplan-Meier , Proteínas de Membrana Lisossomal/imunologia , Melioidose/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/imunologia , Fagocitose/imunologia , Fatores de Virulência/genéticaRESUMO
BACKGROUND: Previous findings have suggested that Helicobacter pylori induces autophagic processes and subsequently takes refuge in autophagosomes, thereby contributing to persistent infection. Recently, a noncanonical form of autophagy, LC3 (microtubule-associated protein 1 light chain 3)-associated phagocytosis (LAP), has been shown to be required for efficient clearance of some intracellular bacteria. Whether H. pylori infection induces LAP had not been examined previously. In this study, we determined the extent to which H. pylori infection induces canonical autophagy or LAP in macrophages, and the involvement of the H. pylori cag pathogenicity island (cagPAI) with these processes. METHODS: Immunofluorescence confocal microscopy was used to analyze the formation of GFP-LC3 puncta and their colocalization with H. pylori. Transmission electron microscopy was used to detect the ultrastructure of H. pylori-containing compartments. RESULTS: The majority of intracellular bacteria (85-95%) were found in phagosomes that were LC3-negative, with a small proportion (4-14%) appearing "free" in the cytosol. Only a very small percentage (0.5-6%) of intracellular H. pylori was sequestered in autophagosomes. Furthermore, no statistically significant difference in the relative distribution of H. pylori in the various compartments was observed between wild-type and cagPAI-mutant bacteria. CONCLUSIONS: In macrophages, H. pylori infection does not induce LAP, but can induce canonical autophagy, which entraps a very small fraction of intracellular bacteria. We propose that this subpopulation of intracellular H. pylori might have escaped from phagosomes into the cytosol before being sequestered by autophagosomes. The cagPAI of H. pylori has only minor influence, if any, on the extent of these processes.
Assuntos
Autofagia , Helicobacter pylori/imunologia , Interações Hospedeiro-Patógeno , Macrófagos/microbiologia , Macrófagos/fisiologia , Proteínas Associadas aos Microtúbulos/análise , Fagocitose , Animais , Células Cultivadas , Proteínas de Fluorescência Verde/análise , Humanos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Coloração e RotulagemRESUMO
PURPOSE: To compare the impact on corneal sensation after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (femto-LASIK) in patients with myopia. METHODS: In this prospective, nonrandomized comparative study, 71 subjects were enrolled. Thirty-eight eyes of 38 patients underwent SMILE and 33 eyes of 33 patients underwent femto-LASIK. Corneal sensation was tested with Cochet-Bonnet esthesiometry in five corneal areas preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Comparison of corneal sensation was performed for the SMILE and femto-LASIK groups. Additionally, the correlations were evaluated between the postoperative corneal sensation, preoperative spherical equivalent, and ablation depth. RESULTS: All tested areas within the cap or flap demonstrated corneal hypoesthesia immediately after both surgeries. SMILE-treated eyes showed less compromised corneal sensation than femto-LASIK-treated eyes at all postoperative visits in the central, inferior, nasal, and temporal areas at the 1-week and 1-month visits. In the SMILE group, the inferior, nasal, and temporal quadrants recovered faster than other areas. In the femto-LASIK group, the sensation over the flap did not recover to preoperative levels by postoperative 6 months. There was no correlation between postoperative corneal sensation, preoperative spherical equivalent, and ablation depth in both groups. CONCLUSIONS: The impairment of corneal sensation was less significant in the SMILE group than in the femto-LASIK group and was independent of preoperative spherical equivalent or ablation depth.
Assuntos
Córnea/fisiopatologia , Substância Própria/cirurgia , Hipestesia/fisiopatologia , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Sensação/fisiologia , Adulto , Córnea/inervação , Feminino , Humanos , Masculino , Miopia/fisiopatologia , Nervo Oftálmico/fisiopatologia , Estudos Prospectivos , Refração Ocular/fisiologia , Retalhos Cirúrgicos , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare diaphragmatic motion measured by M-mode ultrasonography of patients with CPFE, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary function, high-resolution computed tomography (HRCT), and diaphragmatic motion were examined in patients with CPFE (n = 25), IPF (n = 18), and COPD (n = 60), and in healthy controls (n = 21). Diaphragmatic motions were measured on M-mode ultrasonographic images during quiet breathing and deep breathing. RESULTS: There were no significant differences in right or left diaphragmatic motion during quiet breathing among the four groups, whereas differences were significant in right and left motion during deep breathing. Diaphragmatic motion in CPFE patients was the lowest among the four groups. COPD patients, especially those with severe COPD, showed significantly lower diaphragmatic motion than IPF patients or healthy controls. There were no differences in diaphragmatic motion between IPF patients and healthy controls. Right diaphragmatic motions during deep breathing were negatively correlated with emphysema scores (r = -0.606, p < 0.001), but were not correlated with fibrosis scores on HRCT. CONCLUSIONS: Diaphragmatic weakness was found in CPFE patients. Emphysema but not fibrosis may be one cause of limited diaphragmatic motion in patients with CPFE. M-mode ultrasonographic evaluation of diaphragmatic motion during deep breathing may be a useful tool in diagnosing CPFE and in discriminating CPFE patients from IPF or COPD patients.
Assuntos
Diafragma/diagnóstico por imagem , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diagnóstico Diferencial , Diafragma/fisiopatologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Debilidade Muscular/diagnóstico por imagem , Debilidade Muscular/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/fisiopatologia , Respiração , Testes de Função Respiratória , Tomografia Computadorizada Espiral , UltrassonografiaRESUMO
Researches of the correlation between sex hormones and dry eye have been concerned early.Ocular surface inflammation, epithelial apoptosis and abnormal expression of tear lipocalin and lipid may be important pathogenetic factors of various types of dry eye, and variedness of sex hormone level may have a certain correlation with these factors. The alteration of structure and function of tear film is the direct reason for dry eye. The change of sex hormone level likely gives influence to tear composition and pathological variation of related ocular surface tissues, then affects the structure and function of tear film, and finally lead to dry eye. Different sex hormones give certain different moderating effects to related ocular surface organization, so the recent correlational study of sex hormones and dry eye can be summarized in terms of androgen and estrogen, as these two sex hormones have certain impacts on tear composition and ocular surface organization respectively.