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1.
Arch Toxicol ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722348

RESUMEN

With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs). In addition, the most critical issue now is a COVID-19 vaccine that generates strong and durable immunity. A growing number of clinical studies confirm the potential of gut microbes to enhance the efficacy of COVID-19 vaccines. However, it is still unclear how gut bacteria interact with immune cells and what treatments are based on gut microbes. Here, we outline recent advances in the effects and mechanisms of the gut microbiota and its metabolites (tryptophan metabolites, bile acids, short-chain fatty acids, and inosine) on different immune cells (dendritic cells, CD4+T cells, and macrophages). It also highlights innovative intervention strategies and clinical trials of microbiota-based checkpoint blocking therapies for tumor immunity, and ongoing efforts to maintain the long-term immunogenicity of COVID-19 vaccines. Finally, the challenges to be overcome in this area are discussed. These provide an important basis for further research and clinical translation of gut microbiota.

2.
Arch Toxicol ; 98(5): 1297-1310, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38498160

RESUMEN

Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury.


Asunto(s)
Lesión Pulmonar , MicroARNs , Humanos , ARN Circular/genética , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/genética , Lesión Pulmonar/terapia , Pulmón/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores/metabolismo
3.
J Foot Ankle Surg ; 62(3): 413-416, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36335051

RESUMEN

The transfer of the posterior tibial tendon through the interosseous membrane is potentially an effective treatment to correct the deformity of the foot and ankle. Our study aimed to evaluate the anatomical feasibility of anterior transfer of the posterior tibial tendon through the interosseous membrane route using the musculotendinous junction (MTJ). Eighteen adult cadavers were used. The width and thickness of the tibial posterior MTJ, width of the interosseous membrane at the corresponding level, and the window size of the interosseous membrane were measured. Additionally, the distance between the distal end of the MTJ and the tip of the medial malleolus were recorded. The mean length of the posterior tibial tendon was 83.60 mm, the mean distance of the posterior tibial MTJ to medial malleolus tip was 45.48 mm and the mean length of MTJ was 31.74 mm. The mean width of distal end of MTJ was 7.76 mm, thickness of distal end of MTJ was 4.07 mm and the mean width of the interosseous membrane at the distal end of MTJ was 4.76 mm. We found the mean width of the proximal end of MTJ was 20.68 mm, the mean thickness of proximal end of MTJ was 5.52 mm, and mean width of interosseous membrane at the proximal end of MTJ was 8.76 mm. Our study has demonstrated that a 31 mm length incision made at approximately 45 mm from the proximal end of the medial malleolus can safely reach the MTJ. We recommend an opening length of the interosseous membrane of at least 20 mm.


Asunto(s)
Unión Miotendinosa , Transferencia Tendinosa , Adulto , Humanos , Estudios de Factibilidad , Membrana Interósea , Cadáver
4.
Med Sci Monit ; 26: e926224, 2020 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-32773731

RESUMEN

BACKGROUND We used fractional amplitude of low-frequency fluctuation (fALFF) technology to investigate spontaneous cerebral activity in patients with monocular blindness (MB) and in healthy controls (HCs). MATERIAL AND METHODS Thirty MB patient and 15 HCs were included in this study. All subjects were scanned by resting-state functional magnetic resonance imaging (rs-fMRI). The independent sample t test and chi-squared test were applied to analyze demographics of MB patients and HCs. The 2-sample t test and receiver operating characteristic (ROC) curves were applied to identify the difference in average fALFF values between MB patients and HCs. Pearson's correlation analysis was applied to explore the relationship between the average fALFF values of brain areas and clinical behavior in the MB group. RESULTS MB patients had lower fALFF values in the left anterior cingulate and higher fALFF values in the left precuneus and right and left inferior parietal lobes than in HCs. Moreover, the mean fALFF values of MB patients in the left anterior cingulate had negative correlations with the anxiety scale score (r=-0.825, P<0.001) and the depression scale score (r=-0.871, P<0.001). CONCLUSIONS Our study found that MB patients had abnormal spontaneous activities in the visual and vision-related regions. The finding of abnormal neuronal activity helps to reveal the underlying neuropathologic mechanisms of vision loss.


Asunto(s)
Ceguera/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Ceguera/fisiopatología , Mapeo Encefálico/métodos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
5.
Med Sci Monit ; 26: e925856, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33226973

RESUMEN

BACKGROUND The aim of this study was to explore potential changes in brain function network activity in patients with adult strabismus with amblyopia (SA) using the voxel-wise degree centrality (DC) method. MATERIAL AND METHODS We enrolled 15 patients with SA (6 males, 9 females) and 15 sex-matched healthy controls (HCs). All subjects completed resting functional magnetic resonance imaging scans. Independent-sample t tests and receiver operating characteristic (ROC) curves were used to assess DC value differences between groups, and Pearson correlation analysis was performed to evaluate correlations between DC-changed brain regions and clinical data of patients with SA. RESULTS Compared with the HC group, DC values that were lower in patients with SA included the left middle frontal gyrus and bilateral angular gyri. Increases were observed in the left fusiform gyrus, right lingual gyrus, right middle occipital gyrus, right postcentral gyrus, and left paracentral lobule. However, DC values were not correlated with clinical manifestations. ROC curve analysis showed high accuracy. CONCLUSIONS We found abnormal neural activity in specific brain regions in patients with SA. Specifically, we observed significant changes in DC values compared to HCs. These changes may be useful to identify the specific mechanisms involved in brain dysfunction in SA.


Asunto(s)
Ambliopía/diagnóstico por imagen , Ambliopía/fisiopatología , Encéfalo/fisiopatología , Imagen por Resonancia Magnética , Red Nerviosa/fisiopatología , Descanso , Estrabismo/diagnóstico por imagen , Estrabismo/fisiopatología , Adulto , Ambliopía/complicaciones , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Red Nerviosa/diagnóstico por imagen , Curva ROC , Estrabismo/complicaciones , Adulto Joven
6.
Yi Chuan ; 42(2): 161-171, 2020 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-32102773

RESUMEN

Congenital cataract (CC) is a rare disease with dysplasia of the lens, mainly characterized by partial or complete opacity of the lens. The molecular basis of the disease is complex, mutations in over 266 genes associated with congenital cataracts had been reported. In this study, a novel congenital cataract candidate gene TSR1 was identified by whole genome sequencing and Sanger sequencing in a Chinese congenital cataract family. The TSR1 c.202-1G>A substitution affected splicing of TSR1 mRNA was confirmed by a minigene assay. The expression of TSR1 in mouse lens, anterior lens capsule of age-related cataract patients and 24-week human fetal lens were determined by RT-PCR, Western blotting, and immunofluorescence assays. The expression of TSR1 in the embryonic and different developmental stages of the mouse lens was confirmed by analyzing the iSyTE database. The expression of TSR1 was down-regulated in the lens-specific CBP:p300 double knockout mouse, and a set of genes with the same expression pattern of Tsr1 in the CBP:p300 double knockout mouse lens were extracted for protein-protein interaction network analysis, and six proteins were screened for direct interaction with Tsr1. GO function analysis indicated that Tsr1 might play a role in the MAPK-Erk signaling pathway in addition to its involvement in ribosome assembly. This study provided valuable research clues to further clarify the function of Tsr1 in the lens.


Asunto(s)
Catarata/genética , Cristalino/patología , Proteínas Ribosómicas/genética , Animales , Pueblo Asiatico , Catarata/congénito , China , Humanos , Ratones , Ratones Noqueados , Mutación , Linaje , ARN Mensajero
7.
Biomed Pharmacother ; 175: 116687, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701568

RESUMEN

World Drug Report 2023 concluded that 296 million people abused drugs, 39.5 million became addiction and 494,000 died as a direct or indirect result of addiction. Addiction has become a growing problem that affects individuals, their families, societies, countries and even the world. However, treatment for addiction is only limited to some developed countries because of the high cost, difficult implementation, and time consuming. Therefore, there is an urgent need to develop a low-cost, effective drug for the development of addiction treatment in more countries, which is essential for the stability and sustainable development of the world. In this review, it provided an overview of the abuse of common addictive drugs, related disorders, and current therapeutic regimen worldwide, and summarized the mechanisms of drug addiction as reward circuits, neuroadaptation and plasticity, cognitive decision-making, genetics, and environment. According to their chemical structure, 43 natural products and 5 herbal combinations with potential to treat addiction were classified, and their sources, pharmacological effects and clinical trials were introduced. It was also found that mitragine, ibogine, L-tetrahydropalmatine and crocin had greater potential for anti-addiction.


Asunto(s)
Productos Biológicos , Trastornos Relacionados con Sustancias , Humanos , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Animales , Conducta Adictiva/tratamiento farmacológico
8.
Eur J Pharmacol ; 942: 175545, 2023 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-36708977

RESUMEN

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills (CDDPs). Previous study showed that IDHP exerted anti-inflammatory effects by abolishing the secretion of proinflammatory factors stimulated by lipopolysaccharide (LPS). However, the effects of IDHP on LPS-induced acute lung injury (ALI) are not fully understood. In the present study, we observed the effects of IDHP on mortality and lung injury in LPS-treated mice and on LPS-induced THP-1 macrophages. Pretreatment with high dose of IDHP was found to reduce the mortality of ALI mice, significantly improve LPS-induced pathological changes, and reduce protein leakage and inhibited myeloperoxidase (MPO) activity in lung tissue. IDHP also inhibited the release of inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissue. Meanwhile, IDHP treatment significantly reduced the expression of active-caspase1, Nlrp3, Asc speck formation, Gsdmd (part of the canonical pyroptosis pathway), caspase4 (part of the non-canonical pyroptosis pathway), therefore decreasing IL-1ß, IL-18, and ROS secretion in LPS-stimulated THP-1 macrophages. Moreover, after co-culturing endothelial/epithelial cells with conditioned medium (CM) from LPS-stimulated THP-1 macrophages, we found that the protein levels of occludin and Zonula occludens-1 (Zo-1) were increased in IDHP CM-treated endothelial cells compared to those that were LPS CM-treated. Lactic dehydrogenase (LDH) assay shows that IDHP also alleviated LPS-induced endothelial/epithelial cell injury. These findings indicate that the protective effect of IDHP on LPS-induced lung injury may be partly due to the inhibition of pyroptosis pathways.


Asunto(s)
Lesión Pulmonar Aguda , Lipopolisacáridos , Ratones , Animales , Lipopolisacáridos/farmacología , Piroptosis , Células Endoteliales , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/prevención & control , Pulmón
9.
Brain Behav ; 11(3): e02018, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33386699

RESUMEN

BACKGROUND: Neovascular glaucoma (NVG) can cause irreversible visual impairment and abnormal spontaneous changes in brain's visual system and other systems. There is little research on this aspect at present. However, amplitude of low-frequency fluctuations (ALFFs) can be used as an rs-fMRI analysis technique for testing changes in spontaneous brain activity patterns. PURPOSE: The aim of this study was to probe the local characteristics of spontaneous brain activity in NVG patients and analyze their correlation with clinical behaviors. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were obtained from eighteen patients with NVG (8 males, 10 females) and eighteen healthy controls (HCs; 8 males and 10 females) who were matched in age, gender, and education level. We evaluated spontaneous brain activity with the ALFF method. A receiver operating characteristic (ROC) curve was used to compare the average ALFF values for altered brain regions of NVG patients with those of HCs. RESULTS: Compared with HCs, NVG patients had lower ALFF values in the right cuneus, right middle occipital gyrus, left cingulate gyrus, right precuneus, and left medial frontal gyrus (p < 0.001). Higher ALFF values were observed in the right superior frontal gyrus and left middle frontal gyrus (p < 0.001). Analysis of the ROC curves of the brain regions showed that the specificity and accuracy of ALFF values between NVG and HCs in the area under the curve were acceptable (p < 0.001). CONCLUSION: The patients with NVG exhibited anomalous spontaneous activity in different brain regions; these finding should establish the foundation for a more comprehensive understanding of the pathological mechanisms of NVG. Furthermore, these abnormal variations in specific brain regions can be considered possible clinical indices of NVG.


Asunto(s)
Glaucoma Neovascular , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Curva ROC
10.
Neuropsychiatr Dis Treat ; 16: 1907-1917, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32821107

RESUMEN

OBJECTIVE: Previous studies demonstrated that myopia could result in alterations of brain activity in specific areas. However, whether the visual function could improve by Lasik surgery, with the brain activity alterations also change, is still unknown. Here, we intended to use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain activity changes in pre-Lasik (PRL) and post-Lasik (POL) patients. METHODS: A total of 15 patients with myopia (nine male and six female) were recruited in our study, who were matched according to age, weight, and height. These patients comprised both the PRL and POL groups, which is self-controlled. The patients all underwent resting-state functional magnetic resonance imaging (MRI), and the spontaneous brain activity changes were recorded by the ALFF technique. The data were recorded and arranged in the receiver operating characteristic (ROC) curve, which presented how intrinsic activities altered in different brain regions. Moreover, by Graphpad prism 8, we can analyze the linear correlation between HADS (Hospital Anxiety and Depression Scale) and ALFF values as well. RESULTS: Differences in ALFF values existed in brain regions between the same patient before and after the Lasik operation. The regions with increased ALFF values after Lasik surgery were the left parahippocampal gyrus, cerebellar vermis, and left posterior cingulate cortex. The regions with decreased ALFF values after Lasik surgery were the left supramarginal gyrus and right trigonometric inferior frontal gyrus. CONCLUSION: We demonstrated significant fluctuations of ALFF values in specific brain areas between the same patients before and after the Lasik surgery. The altered ALFF values reflected the hyperactivity or hypoactivity of the specific brain areas, which may help predict the recovery level of patients' vision after Lasik surgery. Furthermore, based on the experimental results that presented significant activity alterations in specific brian regions, patients could be speculated equipped with a better visual function.

11.
Mol Med Rep ; 22(3): 2263-2272, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32705251

RESUMEN

Psoriasis is a chronic inflammatory skin disease characterized by well­defined scaly papules and plaques. Interleukin (IL)­17 is involved in its pathogenesis and promotes the proliferation of epidermal keratinocytes through signal transducer and activator of transcription 3 (STAT3) activation. Shikonin, a natural naphthoquinone isolated from Lithospermum erythrorhizon, possesses anti­inflammatory and immunosuppressive properties and can suppress IL­17­induced vascular endothelial growth factor expression by inhibiting the JAK/STAT3 pathway. In the present study, MTS, iCELLigence and RT­qPCR were used to determine the optimal concentration and duration of IL­17 or shikonin acting on HaCaT cells. The changes in the expression levels of genes associated with the IL­6/STAT3 pathway in differentially treated cells were analyzed via RT2Profiler™ PCR Array. Small interfering RNA was used to silence the expression levels of the target gene CCAAT/enhancer­binding protein δ (CEBPD). Western blotting and immunohistochemistry were used to evaluate the effect of shikonin on imiquimod­induced psoriasis in mice and the expression levels of CEBPD. Shikonin reversed IL­17­mediated downregulation of the tumor suppressor CEBPD in HaCaT cells. Moreover, low levels of CEBPD in the imiquimod­induced mouse model of psoriasis were restored by shikonin treatment, which ameliorated excessive keratinocyte proliferation. Taken together, these findings suggest that CEBPD plays a key role in the pathogenesis of psoriasis and can be targeted by shikonin as a potential therapeutic strategy.


Asunto(s)
Proteína delta de Unión al Potenciador CCAAT/metabolismo , Imiquimod/efectos adversos , Interleucina-17/efectos adversos , Naftoquinonas/administración & dosificación , Psoriasis/tratamiento farmacológico , Animales , Proteína delta de Unión al Potenciador CCAAT/genética , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Células HaCaT , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Ratones , Naftoquinonas/farmacología , Psoriasis/inducido químicamente , Psoriasis/genética , Psoriasis/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos
12.
Medicine (Baltimore) ; 99(46): e22773, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33181649

RESUMEN

Nasopharyngeal carcinoma (NPC) has a distinctive geographical distribution in China, especially southern China. There are several risk factors for NPC, such as Epstein-Barr virus, genetics, and environmental exposures. Although the incidence of eye metastasis (EM) is lower than metastasis in other body parts, it often indicates poor prognosis.We assessed several serum biomarkers for their ability to predict EM in NPC. Patients with NPC were selected (n = 963), and were separated into two groups, EM and no eye metastasis. Ten factors were analyzed in both groups including triglyceride (TG), high-density lipoprotein, low-density lipoprotein, alkaline phosphatase, alpha fetoprotein, carbohydrate antigen-199, cancer antigen-153, apolipoproteins AI, apolipoprotein B, and cytokeratin fragment 19 (CYFRA21-1). Independent t tests, binary logistic regression, and receiver operating characteristic curves were used to assess the data.The EM group had significantly higher CYFRA21-1 and lower TG compared with the no eye metastasis group. Areas under the curve for CYFRA21-1, TG and CYFRA21-1/TG were 0.966, 0.771, and 0.976, respectively. The corresponding cut-off values were 12.12 ng/ml, 0.41 mmol/L, and 13.5. The sensitivity and specificity of CYFRA21-1/TG were 100% and 92.2%, respectively.The increased ratio of CYFRA21-1 to TG can be an accurate method to detect EM in patients with NPC.


Asunto(s)
Antígenos de Neoplasias/análisis , Neoplasias del Ojo/etiología , Queratina-19/análisis , Neoplasias Nasofaríngeas/genética , Metástasis de la Neoplasia/diagnóstico , Tiroglobulina/análisis , Adulto , Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/análisis , China/epidemiología , Neoplasias del Ojo/epidemiología , Neoplasias del Ojo/genética , Femenino , Humanos , Queratina-19/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/epidemiología , Metástasis de la Neoplasia/diagnóstico por imagen , Metástasis de la Neoplasia/fisiopatología , Factores de Riesgo , Sensibilidad y Especificidad , Tiroglobulina/sangre
13.
Dis Markers ; 2020: 8850873, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33376560

RESUMEN

PURPOSE: Liver metastasis is the final stage of cancer progression and is associated with poor prognosis. Although numerous indicators have been identified as having prognostic value for lung cancer and liver metastasis, liver metastases are still not diagnosed by imaging in many patients. To provide a more accurate method for clinical prediction of liver metastasis, we analyzed multiple factors to identify potential predictive factors for liver metastasis of lung cancer. METHODS: Patients first diagnosed with lung cancer between 2002 and 2016 (n = 1746) were divided into two groups, with and without liver metastasis. Serum concentrations of calcium, carcinoembryonic antigen (CEA), cancer antigen-125 (CA125), cancer antigen-153 (CA153), carbohydrate antigen-199 (CA199), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen (TPSA), and neuron-specific enolase (NSE) were analyzed in both patient groups. RESULTS: There was no significant difference in age or sex between the two groups. CA125 and NSE were significantly associated with liver metastasis. Compared with CA125, NSE was more specific, while it was less sensitive (P < 0.001). Further analysis of NSE concentrations was conducted in patients with non-small-cell lung cancer and indicated that NSE concentration differed significantly between those with and without liver metastasis (P = 0.023). We conducted analysis with NSE and CA125 combined, resulting in acceptable sensitivity (51.2%), specificity (72.6%), and area under the curve (0.64) values; sensitivity and area under the curve values were higher than those for individual factors, while specificity was higher than that for CA125. CONCLUSIONS: The combination of CA125 and NSE can assist prediction of liver metastasis of lung cancer, providing improved diagnostic accuracy.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno Ca-125/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/patología , Fosfopiruvato Hidratasa/sangre , Anciano , Antígenos de Neoplasias/sangre , Antígeno Carcinoembrionario/sangre , Femenino , Proteínas Ligadas a GPI/sangre , Humanos , Queratina-19/sangre , Masculino , Persona de Mediana Edad , Pronóstico
14.
Int Immunopharmacol ; 72: 511-521, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31075711

RESUMEN

Shikonin is an active compound of the oriental medicinal plant, Leptospermum erythrorhizon, which has been previously shown to inhibit psoriasis-like inflammation. However, the underlying mechanism is unclear. In the present study, the mechanisms of keratinocyte proliferation and apoptosis in psoriasis in response to shikonin were explored both in vitro and in vivo. Our results showed that shikonin significantly inhibits cell proliferation and induces apoptosis in both HaCaT and LV-STAT3 HaCaT cells by targeting CEBPD, while a decrease in cell survival, proliferation and viability were found through flow-cytometry and MTS assay. Furthermore, gavage with shikonin markedly alleviated psoriasis-like manifestations in IMQ-induced BALB/c mice clinically (PASI Score) and histopathologically. Immunohistochemistry revealed that shikonin potently suppresses the JAK/STAT3 signaling pathway in local skin lesions and increases CEBPD expression. These results imply that shikonin inhibits keratinocyte proliferation and induces apoptosis, which results in psoriasis treatment through the JAK/STAT3 dependent pathway. In addition, the activation of JAK/STAT3 downregulates CEBPD in HaCaT cells and IMQ-induced BALB/c mice. However, shikonin can reverse these effects, suggesting that CEBPD may be a potential therapeutic target for psoriasis.


Asunto(s)
Proteína delta de Unión al Potenciador CCAAT/metabolismo , Queratinocitos/efectos de los fármacos , Naftoquinonas/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteína delta de Unión al Potenciador CCAAT/genética , Línea Celular , Proliferación Celular/efectos de los fármacos , Humanos , Imiquimod , Quinasas Janus , Queratinocitos/fisiología , Masculino , Ratones Endogámicos BALB C , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Regulación hacia Arriba/efectos de los fármacos
15.
Int J Ophthalmol ; 9(8): 1112-20, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27588264

RESUMEN

AIM: To evaluate the effects of lentivirus-mediated pigment epithelium-derived factor (PEDF) gene transfer performed in treatment of rats with established choroidal neovascularization (CNV), and investigates the mechanism by which PEDF inhibits CNV in rats. METHODS: Brown Norway (BN) rats (n=204) were induced by exposure to a laser, and then randomly assigned to 3 groups: no treatment; treatments with intravitreal injection of lentivirus-PEDF-green fluorescent protein (GFP) or lentivirus-control GFP (free fluorescent protein). Following induction and treatment, the CNV tissue was assessed for form, size and vessel leakage by fluorescein fundus angiography (FFA), optical coherence tomography (OCT), histopathology, and examination of choroidal flat mounts. VEGF, Flk-1, and PEDF expression were evaluated by real-time polymerase chain reaction (PCR) and Western blot. RESULTS: A stable laser-induced rat model of CNV was successfully established, and used to demonstrate lentivirus-mediated PEDG gene transfer by intravitreal injection. Expression of green fluorescence labelled PEDF was observed in the retina up to 28d after injection. An intravitreal injection of lentivirus-PEDF-GFP at 7d led to a significant reduction in the size, thickness and area of CNV showed by FFA, OCT and choroidal flat mounts. PEDF was up-regulated while VEGF and Flk-1 were down-regulated in the lentivirus-PEDF-GFP group. The differences in VEGF and Flk-1 expression in the control and lentivirus-PEDF groups at 7, 14, 21 and 28d after laser induction were all statistically significant. CONCLUSION: Lentivirus-mediated PEDF gene transfer is effective for use in treatment of laser-induced CNV, and PEDF exerts its therapeutic effects by inhibiting expression of VEGF and Flk-1.

16.
J Ocul Pharmacol Ther ; 30(8): 657-64, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24963995

RESUMEN

PURPOSE: The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. In this study, we aim to evaluate the antioxidant effects of curcumin in BV-2 microglia oxidative damage and assess its neuroprotective effects in a chronic high IOP rat model. METHODS: BV-2 microglia cell line was used in an in vitro study and Wistar rats were used in an in vivo study. Cultured BV-2 microglia cells were pretreated with 10, 1, or 0.1 µM curcumin for 1 h, and sustained oxidative stress was induced by subjecting BV-2 microglia to 200 µM hydrogen peroxide (H2O2) for 24 h. MTT assay was used to determine cell viability. Changes of intracellular reactive oxygen species (ROS) and apoptosis were analyzed by flow cytometry. Three episcleral veins were cauterized to induce high IOP in Wistar rats and measured by Tonopen. After 6 weeks of treatment with curcumin (10 mg/kg/day) by intragastric administration, surviving of retinal ganglion cells was quantified. Activation of caspase 3, cytochrome c, BAX, and BCL2 was quantified by Western blotting both in BV-2 microglia and in animal model. Data were analyzed with the GraphPad Prism 5.0 software, and P<0.05 was considered to be statistically significant. RESULTS: The in vitro study showed that when BV-2 microglia was pretreated with curcumin, the cell viability increased and the intracellular ROS and apoptosis significantly decreased. In the in vivo study, chronic mild IOP elevation was induced for 4 weeks. In the curcumin-treated group, curcumin protected rat BV-2 microglia from death significantly. In both H2O2-treated BV-2 microglia and glaucoma models, caspase 3, cytochrome c, and BAX were downregulated and BCL2 was upregulated in the curcumin-treated group. CONCLUSIONS: Curcumin affords neuroprotective effects by inhibiting oxidative damage and could be a new or adjunctive treatment for glaucoma.


Asunto(s)
Curcumina/uso terapéutico , Presión Intraocular/efectos de los fármacos , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Hipertensión Ocular/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Curcumina/administración & dosificación , Curcumina/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Citometría de Flujo , Humanos , Microglía/metabolismo , Microglía/patología , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacología , Hipertensión Ocular/metabolismo , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo
18.
Int J Ophthalmol ; 5(5): 591-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23166870

RESUMEN

AIM: To investigate the efficacy of non-buckled vitrectomy with classical endotamponade agents in the treatment of primary retinal detachment (RD) complicated by inferior breaks and proliferative vitreoretinophathy (PVR). METHODS: A retrospective, consecutive and case series study of 40 patients with inferior break RD and PVR ≥C1 was conducted. All patients underwent a standard 3-port 20-gauge pars plana vitrectomy (PPV) with gas or silicone oil tamponade without supplementary scleral buckling. The vitreous and all proliferative membrane were completely removed, and retinectomy was performed when necessary. The mean follow-up was 12.5 months. The primary and final anatomic success rate, visual acuity and complications were recorded and analyzed. RESULTS: Primary anatomic success rate was achieved in 35 of 40 eyes (87.5%) and the final anatomic success rate was 100%. The most common cause of redetachment was recurrent PVR. The best-corrected visual acuity (BCVA) at final follow-up was improved in 34 eyes (85%), remained stable in 1 eye (2.5%), and worsened in 5 eyes (12.5%). The mean visual acuity at final follow-up was improved significantly (P=0.000). CONCLUSION: This retrospective study provides evidence that vitrectomy without scleral buckling seemed to be an effective treatment for inferior break RD with PVR. With complete removal of vitreous and proliferative membranes and timing of retinectomy, the inferior breaks which complicated with PVR could be closed successfully without additional scleral buckling.

19.
Chin Med J (Engl) ; 125(16): 2858-61, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22932080

RESUMEN

BACKGROUND: Copernicus optical coherence tomography (SOCT) is a new, ultra high-speed and high-resolution instrument available for clinical evaluation of optic nerve. The purpose of the study was to compare the agreements between SOCT and Heidelberg retinal tomography (HRT). METHODS: A total of 44 healthy normal volunteers were recruited in this study. One eye in each subject was selected randomly. Agreement between SOCT and HRT-3 in measuring optic disc area was assessed using Bland-Altman plots. Relationships between measurements of optic nerve head parameter obtained by SOCT and HRT-3 were assessed by Pearson correlation. RESULTS: There was no significant difference in the average cup area (0.306 vs. 0.355 mm, P = 0.766), cup volume (0.158 vs. 0.130 mm, P = 0.106) and cup/disc ration (0.394 vs. 0.349 mm, P = 0.576) measured by the two instruments. However, other optic disc parameters from SOCT were significantly lower compared with HRT-3. The Bland-Altman plot revealed good agreement of cup area and cup volume measured by SOCT and HRT-3. Bad agreement of disc area, rim area, rim volume and cup/disc ratio were found between SOCT and HRT-3. The highest correlations between the two instruments were observed for cup area (r(2) = 0.783, P = 0.000) and cup/disc ratio (r(2) = 0.669, P = 0.000), whereas the lowest correlation was observed for disc area (r(2) = 0.100, P = 0.037), rim area (r(2) = 0.275, P = 0.000), cup volume (r(2) = 0.005, P = 0.391) and rim volume (r(2) = 0.021, P = 0.346). CONCLUSIONS: There were poor agreements between SOCT and HRT-3 for measurement of optic nerve parameters except cup area and cup volume. Measurement results of the two instruments are not interchangeable.


Asunto(s)
Disco Óptico/patología , Retina/patología , Tomografía de Coherencia Óptica/métodos , Tomografía/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
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