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The tissue damage caused by transient ischemic injury is an essential component of the pathogenesis of retinal ischemia, which mainly hinges on the degree and duration of interruption of the blood supply and the subsequent damage caused by tissue reperfusion. Some research indicated that the retinal injury induced by ischemia-reperfusion (I/R) was related to reperfusion time.In this study, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model group and at different reperfusion time (24h, 72h, and 7d) with the aid of whole transcriptome sequencing technology, and the trend changes in time-varying mRNA, lncRNA, circRNA were obtained by chronological analysis. Then, candidate circRNAs, lncRNAs, and mRNAs were obtained as the intersection of differentially expression genes and trend change genes. Importance scores of the genes selected the key genes whose expression changed with the increase of reperfusion time. Also, the characteristic differentially expressed genes specific to the reperfusion time were analyzed, key genes specific to reperfusion time were selected to show the change in biological process with the increase of reperfusion time.As a result, 316 candidate mRNAs, 137 candidate lncRNAs, and 31 candidate circRNAs were obtained by the intersection of differentially expressed mRNAs, lncRNAs, and circRNAs with trend mRNAs, trend lncRNAs and trend circRNAs, 5 key genes (Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa) were selected by importance scores of the genes. The result of GSEA showed that key genes were found to play vital roles in antigen processing and presentation, regulation of the actin cytoskeleton, and the ribosome. A network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 34 miRNAs and 48 lncRNAs, and 81 regulatory relationship axes, and a network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 9 miRNAs and 3 circRNAs (circRNA_10572, circRNA_03219, circRNA_11359) and 12 regulatory relationship axes were constructed, the subcellular location, transcription factors, signaling network, targeted drugs and relationship to eye diseases of key genes were predicted. 1370 characteristic differentially expressed mRNAs (spec_24h mRNA), 558 characteristic differentially expressed mRNAs (spec_72h mRNA), and 92 characteristic differentially expressed mRNAs (spec_7d mRNA) were found, and their key genes and regulation networks were analyzed.In summary, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model groups and at different reperfusion time (24h, 72h, and 7d). 5 key genes, Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa, were selected. Key genes specific to reperfusion time were selected to show the change in biological process with the increased reperfusion time. These results provided theoretical support and a reference basis for the clinical treatment.
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MicroRNAs , RNA Longo não Codificante , Traumatismo por Reperfusão , Ratos , Animais , RNA Circular/genética , RNA Longo não Codificante/genética , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma , Traumatismo por Reperfusão/genética , Biologia Computacional/métodos , Isquemia , Redes Reguladoras de GenesRESUMO
BACKGROUND: Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear. METHODS: We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6flox/flox homozygous mice with UBC-creERT2+ transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration. RESULTS: Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1ß, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice. CONCLUSIONS: SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment.
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Camundongos Knockout , Sirtuínas , Cicatrização , Animais , Cicatrização/genética , Sirtuínas/genética , Sirtuínas/metabolismo , Sirtuínas/deficiência , Camundongos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Inflamação/genética , Inflamação/patologia , Inflamação/metabolismo , MasculinoRESUMO
Cyclic GMP-AMP synthase (cGAS) is a major cytosolic DNA sensor that plays a significant role in innate immunity. Upon binding to double stranded DNA (dsDNA), cGAS utilizes GTP and ATP to synthesize the second messenger cyclic GMP-AMP (cGAMP). The cGAMP then binds to the adapter protein stimulator of interferon genes (STING) in the endoplasmic reticulum, resulting in the activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent induction of type I interferon. An important question is how cGAS distinguishes between self and non-self DNA. While cGAS binds to the phosphate backbone of DNA without discrimination, its activation is influenced by physical features such as DNA length, inter-DNA distance, and mechanical flexibility. This suggests that the recognition of DNA by cGAS may depend on these physical features. In this article we summarize the recent progress in research on cGAS-STING pathway involved in antiviral defense, cellular senescence and anti-tumor response, and focus on DNA recognition mechanisms based on the physical features.
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OBJECTIVE: To evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI). METHODS: The medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC). RESULTS: The PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively. CONCLUSIONS: The results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.
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Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Humanos , Biomarcadores , Estudos Retrospectivos , Infecções Relacionadas à Prótese/cirurgia , Artroplastia de Quadril/efeitos adversos , Proteína C-Reativa/análise , Sensibilidade e Especificidade , Artrite Infecciosa/cirurgia , Sedimentação SanguíneaRESUMO
CD19 CAR-T (chimeric antigen receptor-T) cell immunotherapy achieves a remission rate of approximately 70% in recurrent and refractory lymphoma treatment. However, the loss or reduction of CD19 antigen on the surface of lymphoma cells results in the escape of tumor cells from the immune killing of CD19 CAR-T cells (CAR19-T). Therefore, novel therapeutic strategies are urgently required. In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment. When the CD19 antigen was lost or reduced, BV28-OKT3 redirected CAR19-T cells to CD79b+ CD19- lymphoma cells; therefore, BV28-OKT3 overcomes the escape of CD79b+ CD19- lymphoma cells by the killing action of CAR19-T cells in vitro and in vivo. Furthermore, BV28-OKT3 triggered the antitumor function of CAR- T cells in the infusion product and boosted the antitumor immune response of bystander T cells, markedly improving the cytotoxicity of CAR19-T cells to lymphoma cells in vitro and in vivo. In addition, BV28-OKT3 elicited the cytotoxicity of donor-derived T cells toward lymphoma cells in vitro, which depended on the presence of tumor cells. Therefore, our findings provide a new clinical treatment strategy for recurrent and refractory B-cell lymphoma by combining CD79b/CD3 BsAb with CAR19-T cells.
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Anticorpos Biespecíficos , Linfoma de Células B , Linfoma , Humanos , Linfócitos T , Antígenos CD19 , Muromonab-CD3 , Linfoma/tratamento farmacológico , Imunoterapia Adotiva/métodosRESUMO
OBJECTIVE: The presence of endoleak was associated with the failure of endovascular aortic aneurysm repair (EVAR) treatment. The key to eliminating type II endoleak has shifted from reintervention to prevention. This study aimed to evaluate the effectiveness and safety of applying fibrin sealant to prevent type II endoleak in conjunction with EVAR. METHODS: All patients with abdominal aortic aneurysm who underwent EVAR from June 2019 to July 2021 were reviewed. Patients were grouped as Group A: standard EVAR with preemptive embolization and Group B: standard EVAR alone. The primary endpoint was the incidence of type II endoleak. The secondary endpoints were aneurysm sac regression, the inferior mesenteric artery patency, the numbers of patent lumbar arteries, and all-cause mortality. RESULTS: A total of 104 patients were included in Group A, and 116 were included in Group B. Technical success rate was 100%. The overall incidence of type II endoleak in Group A was significantly lower than that in Group B (4.8% vs 19.0%). The mean time of freedom from type II endoleak was 22.71 months for Group A (95% confidence interval, 21.59-23.83 months) and 19.89 months for Group B (95% confidence interval, 18.08-21.70 months). The Kaplan-Meier estimate of freedom from type II endoleak showed a significantly longer duration of freedom from type II endoleak in Group A (81.0% vs 95.2%). Group A showed a continuous sac regression tendency. In Group B, the sac volume decreased within 12 months but increased by 3.07 cm3 at 24 months. No complications were noted in both groups. CONCLUSIONS: Nonselective preemptive embolization with porcine fibrin sealant during EVAR was safe and effective in preventing type II endoleak in the short and mid-term. Preemptive embolization can lead to a significantly higher sac regression rate. Larger patient populations and longer follow-ups with randomized control designed trials are expected to verify the long-term effectiveness and safety of preemptive embolization in preventing type II endoleak.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Embolização Terapêutica , Procedimentos Endovasculares , Animais , Suínos , Endoleak/etiologia , Adesivo Tecidual de Fibrina/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Fatores de Risco , Procedimentos Endovasculares/efeitos adversos , Aneurisma da Aorta Abdominal/cirurgia , Embolização Terapêutica/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the impact of prenatal and early childhood antimicrobial use on autism spectrum disorders (ASD). DATA SOURCES: We searched PubMed and Embase databases for relevant studies from inception to August 2022. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed, observational studies were all acceptable. Raw data were extracted into a predefined worksheet and quality analysis was performed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Nineteen studies were identified in the meta-analysis. Prenatal antimicrobial exposure was not associated with ASD (P = 0.06 > 0.05), whereas early childhood antimicrobial exposure was associated with an increased odds ratio of ASD (OR = 1.17, 95% CI = [1.08-1.27], P value < 0.001). The sibling-matched analysis, with a very limited sample size, suggested that neither prenatal (P = 0.47 > 0.05) nor early childhood (P = 0.13 > 0.05) antimicrobial exposure was associated with ASD. Medical professionals may need to take the possible association into consideration when prescribing an antimicrobial in children. CONCLUSIONS: Early childhood antimicrobial exposure could increase the incidence of ASD. In future studies, it would be necessary to control for confounding factors, such as genetic factors, parenteral age at birth, or low birthweight, to further validate the association.
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Anti-Infecciosos , Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Criança , Gravidez , Feminino , Recém-Nascido , Humanos , Pré-Escolar , Transtorno do Espectro Autista/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Anti-Infecciosos/efeitos adversos , Razão de Chances , VitaminasRESUMO
BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder involving multiple systems, with an incidence of about 1/10000-25000. Ovarian torsion (OT) is not commonly found in children. Ovarian cyst acts as one of the primary factors resulting in OT. While ovarian cyst torsion with Prader-Willi Syndrome has not been reported before. CASE PRESENTATION: A 12-years old female was admitted to Emergency Department of our hospital with the chief complaint of abdominal pain. The outcomes of physical examination revealed the height of 150 cm, weight of 103 kg, BMI of 45.77 kg/m2. The patient manifested the special facial features, an obese body, with the abdomen distended into a spherical shape. The fat accumulation in the abdomen significantly embarrassed the palpation. The abdominal CT scan indicated a huge cystic mass in the abdominal cavity, sized about 138 mm × 118 mm. According to medical history, the patient was born with low crying and hypotonia, who has developed the uncontrollable eating behavior since 3-years old. These abnormalities led to a speculation of PWS syndrome, so a genetic test was performed and finally confirmed it, concluding a torsion of ovarian cyst with PWS. With the multidisciplinary consultation, a careful treatment strategy containing the control of blood pressure and blood sugar, coenzyme Q10 was administrated to nourish the myocardium and the application of Growth Hormone was developed. All the above preoperative treatments have brought great benefits to patients. Thus promising the successful completion of operation. The postoperative follow-up till now indicated that the abdominal incision was well healed, without operative complications. CONCLUSIONS: This may be the first case report. In the treatment of ovarian cyst torsion, PWS syndrome requires fully consideration, as the latter can lead to multisystem abnormalities, especially the relation to perioperative management, and even fatalities. Genetic testing should be conducted early when PWS was suspected, accompanied with adequate preparation for the perioperative period, the follow-ups of patients should be maintained for a long time after surgery.
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Dor Abdominal , Cistos Ovarianos , Síndrome de Prader-Willi , Humanos , Feminino , Criança , Cistos Ovarianos/complicações , Cistos Ovarianos/cirurgia , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Hipotonia Muscular , Obesidade , Hormônio do Crescimento HumanoRESUMO
Objective: In the present study, we report a retrospective analysis of 23 cases of conjunctival congestion after laparoscopic operation in children and try to explore the causes and intervention measures. Methods and Results: This is a retrospective, single-centre and observational study, and all patients with conjunctival congestion after laparoscopic operation admitted to our institution between August 2021 and December 2021 were included in this study. Records of 23 patients including 16 male patients and 7 female patients were retrospectively analysed. These patients were in the age group of 2-12 years. Their primary symptom was different degrees of conjunctival congestion, and the symptom onset was between 2 and 7 days after laparoscopic operation, including laparoscopic inguinal hernia repair, laparoscopic appendectomies, laparoscopic Meckel's diverticulectomy, laparoscopic removal of foreign body ingestions and laparoscopic choledochal cystectomy, and the duration of operations varies from 20 min to 255 min. The symptom disappeared from 5 to 21 days after the operation, and the duration of the symptom ranged from 2 to 14 days. A total of 1718 operations were performed, of which 461 were laparoscopic and 1257 were general operations, the incidence of conjunctival congestion after laparoscopic surgery was 23/461, and compared with 0/1257 after ordinary surgery, there was a significant difference between them. Of these 23 patients, 5 patients received no treatment and the other 18 patients were intervened with steroid-containing eye drops. Although eye drops containing steroids can significantly relieve eye discomfort, the duration of conjunctival congestion between the two groups (i.e. steroid-containing eye drop treated vs. non-steroid-containing eye drop treated) did not differ significantly. All patients recovered well. In the follow-up till the end of February 2022, no serious complications had occurred. Conclusion: Conjunctival congestion after laparoscopic operation is extremely rare in children, and the underlying causes are still unclear. We speculate that the pressure of pneumoperitoneum may be the main cause of this phenomenon. Symptoms may be self-limiting, and steroid-containing eye drops can relieve effectively the discomfort.
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INTRODUCTION: The chemoresistance mechanism of diffuse large B-cell lymphoma (DLBCL) is still poorly understood, and patient prognosis remains unsatisfactory. This study aimed to investigate drug resistance mechanisms in non-germinal center B-cell-like (non-GCB) DLBCL. METHODS: Doxorubicin (DOX)-resistant OCI-Ly3 cells were generated through long-term incubation of cells in a medium with gradually increasing DOX concentrations. The expression levels of genes related to drug metabolism were determined using a functional gene grouping polymerase chain reaction (PCR) array. Drug-resistant proteins were identified using bioinformatics, and molecular association networks were subsequently generated. The association and mechanism of key genes were determined using a dual-luciferase reporter assay System and chromatin immunoprecipitation (ChIP). The expression of drug-resistant genes and target genes was then measured using Western blotting and immunohistochemistry. The correlation between gene expressions was analyzed using Spearman's rank correlation coefficient. RESULTS: Using the PCR array, MDR1 was identified as the key gene that regulates DOX resistance in OCI-Ly3/DOX-A100, a non-GCB DLBCL cell line. The dual-luciferase reporter assay system demonstrated that MDR1 transcription could be inhibited by PRDM1. ChIP results showed that PRDM1 had the ability to bind to the promoter region (-1,132 to -996) of MDR1. In OCI-Ly3/DOX cells, NF-κB activity and PRDM1 expression decreased with an increase in drug-resistant index, whereas MDR1 expression increased with enhanced drug resistance. Immunohistochemical analysis revealed that relative MDR1 expression was higher than that of PRDM1 in human DLBCL tissue samples. A negative correlation was observed between MDR1 and PRDM1. CONCLUSION: In non-GCB DLBCL cells, NF-κB downregulates PRDM1 and thereby promotes MDR1 transcription by terminating PRDM1-induced transcriptional inhibition of MDR1. Such a mechanism may explain the reason for disease recurrence in non-GCB DLBCL after R-CHOP or combined CHOP with bortezomib treatment. Our findings may provide a potential therapeutic strategy for reducing drug resistance in patients with DLBCL.
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Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Regulação da Expressão Gênica , Linfoma Difuso de Grandes Células B , Recidiva Local de Neoplasia , Fator 1 de Ligação ao Domínio I Regulador Positivo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Prognóstico , Rituximab/uso terapêuticoRESUMO
The protozoan Cryptocaryon irritans is one of the most important ectoparasites of marine fish, causing 'white spot disease' and mass mortality in aquaculture. To accurately predict disease outbreaks and develop prevention strategies, improved detection methods are required that are sensitive, convenient and rapid. In this study, a pair of specific primers based on the C. irritans 18S rRNA gene was developed and used in a real-time PCR (qPCR) assay. This assay was able to detect five theronts in 1 L of natural seawater. Furthermore, a linear model was established to analyse the log of Ct value and parasite abundance in seawater (y = -2.9623x + 24.2930), and the coefficient of determination (R2 ) value was 0.979. A lysis buffer was optimized for theront DNA extraction and used for storage sample. This method was superior to the commercial water DNA kit, and there was no significant degradation of DNA at room temperature for 24-96 hr. A dilution method was developed to manage qPCR inhibitors and used to investigate natural seawater samples in a net cage farm with diseased fish, and the findings were consistent with the actual situation. This study provides a valuable tool for assisting in the early monitoring and control of cryptocaryoniasis in aquaculture.
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Infecções por Cilióforos , Cilióforos , Doenças dos Peixes , Parasitos , Perciformes , Animais , Infecções por Cilióforos/diagnóstico , Infecções por Cilióforos/parasitologia , Infecções por Cilióforos/veterinária , Doenças dos Peixes/parasitologia , Perciformes/parasitologia , Água do Mar , Manejo de EspécimesRESUMO
OBJECTIVE: To investigate the effect of overexpression of miR-382-5p overexpression on malignant biological behavior of human glioma U251 cells. METHODS: U251 cells were transfected with miR-382-5pmimic. Then miR-382-5p and PTEN mRNA levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) after transfection. Used bioinformatics to predicted the presence of base binding sites between miR-382-5p and PTEN, and constructed PTEN pcDNA vector overexpression plasmid was constructed. Luciluciase reporting experiment was used to detect the targeting relationship between miR-382-5p and PTEN. Cells were randomly divided into four groups: control group, mimics group, pc-PTEN group and mimics+pc-PTEN group for follow-up experiments. RT-PCR was carried out to detect the level of PTEN mRNA in each group. Cell proliferation was detected by clone formation method. The mRNA levels of Ki67, Survivin and c-Myc were detected by RT-PCR. Transwell experiment was used to assayed cell invasion ability. The expression levels of E-cadherin, N-cadherin and Vimentin were determined by Western blot. RESULTS: Results showed that miR-382-5p directly targeted PTEN. Compared with the control group, miR-382-5p and c-Myc mRNA levels and E-cadherin protein level were increased (P<0.05),PTEN, Ki67 and Survivin mRNA levels were decreased (P<0.05), cell clonal formation rate and cell invasion number were decreased (P<0.05), N-cadherin and Vimentin protein levels were decreased (P<0.05) in the mimics group; In pc-PTEN group, miR-382-5p mRNA and c-Myc mRNA levels and E-cadherin protein level were decreased (P<0.05),PTEN, Ki67 and Survivin mRNA levels were increased (P<0.05), cell clonal formation rate and cell invasion number were increased (P<0.05), N-cadherin and Vimentin protein levels were increased (P<0.05). Compared with pc-PTEN group, PTEN, Ki67 and Survivin mRNA levels, the cell clone formation rate, the number of invasion cells and the N-cadherin and Vimentin levels of mimics+PC-PTEN group decreased significantly (P<0.05), while the c-Myc mRNA level and E-cadherin protein level increased significantly (P<0.05). CONCLUSION: Overexpression of miR-382-5p mediates the downregulation of PTEN expression, causing the inhibition of the proliferation, invasion, growth and EMT of U251 glioma cells.
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Produtos Biológicos , Glioma , MicroRNAs , PTEN Fosfo-Hidrolase , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Glioma/metabolismo , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/metabolismoRESUMO
Promotion of wound healing is one of the most important fields in clinical medical research. This study aimed to evaluate the potential use of a new surface-structured bacterial cellulose(S-BC) biomaterial with human urine-derived stem cells (hUSCs) for wound healing. In vitro, EA.hy926 were inoculated on structured/non-structured bacterial cellulose, and the growth of EA.hy926 on bacterial cellulose in medium with/without conditioned medium of the hUSCs were observed to explore the effect of bacterial cellulose's surface structure and hUSCs-CM on vascular endothelial cell growth. In vivo, we covered wound surface with various BC materials and/or injected the hUSCs into the wound site on group BC, group S-BC, group hUSCs, group BC + hUSCs, group S-BC + hUSCs to evaluate the effect of S-BC and hUSCs on wound healing in rat full-thickness skin defect model. In vitro study, surface structure of S-BC could promote the growth and survival of EA.hy926, and the hUSCs-CM could further promote the proliferation of EA.hy926 on S-BC. In vivo study, wound healing rate of the group BC, group S-BC, group hUSCs was significantly accelerated, accompanied by faster re-epithelialization, collagen production and neovascularization than control group. It is note worthy that the effect of S-BC on wound healing was better than BC, the effect of S-BC + hUSCs on wound healing was better than BC + hUSCs. Moreover, the effect of S-BC combined with hUSCs on wound is better than treated with S-BC or hUSCs alone. All the findings suggest that the combination of S-BC and hUSCs could facilitate skin wound healing by promoting angiogenesis. This combination of the role of stem cells and biomaterial surface structures may provide a new way to address clinical wound healing problems.
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Materiais Biocompatíveis/uso terapêutico , Celulose/uso terapêutico , Neovascularização Fisiológica , Transplante de Células-Tronco , Cicatrização , Animais , Materiais Biocompatíveis/química , Linhagem Celular , Células Cultivadas , Celulose/química , Células Endoteliais/citologia , Humanos , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/uso terapêutico , Ratos , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Propriedades de Superfície , Alicerces Teciduais/químicaRESUMO
BACKGROUND: Gastroparesis is a syndrome characterized by delayed gastric emptying with associated symptoms. It was reported that the symptoms of diabetic gastroparesis had been greatly improved by transpyloric stent placement. However, the use of stents in benign conditions is considered to be contraindicated because of the increasing risk of complications, such as stent migration, reflux, perforation, bleeding, and, most importantly, new strictures caused by stent-induced tissue hyperplasia. While temporary placement of a self-expanding metallic stent (SEMC) can drastically reduce the risk of complications, few reports are available on the treatment of refractory PSG by temporary transpyloric stent. Does it have a long-term clinical effect after the stent being retrieved? CASE PRESENTATION: After accepting partial resection of the lesser curvature in another hospital, a patient developed refractory gastroparesis. The symptoms hadn't been improved after long-term drug therapy and balloon dilation therapy. Four months after surgery, a fully covered SEMC was placed by endoscopy in our hospital. Gastroparesis had been greatly improved. Two weeks later, the transpyloric stent was retrieved and the patient didn't show recurrent symptoms. Follow-ups were arranged at 3 months, 6 months and 1 year respectively, and there was no evidence of recurrence was found. CONCLUSIONS: This case indicates that temporary transpyloric SEMC is a safe, effective and less invasive alternative for post-surgical gastroparesis patients.
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Gastrectomia/efeitos adversos , Gastroparesia/cirurgia , Implantação de Prótese , Piloro/cirurgia , Stents , Adulto , Coristoma/cirurgia , Constrição Patológica/cirurgia , Endoscopia , Feminino , Gastroparesia/diagnóstico por imagem , Gastroparesia/etiologia , Humanos , Masculino , Pâncreas/cirurgia , Piloro/diagnóstico por imagem , Gastropatias/diagnóstico por imagem , Gastropatias/cirurgia , Resultado do TratamentoRESUMO
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017. The pooled severe CRS proportion was 29.3% (95% confidence interval [CI] 12.3-49.1%) in B-ALL, 38.8% (95%CI 12.9-67.6%) in B-CLL, and 19.8% (95%CI 4.2-40.8%) in B-NHL. In the univariate meta regression analysis, the proliferation of CD19-CAR-T cell in vivo was correlated with the severe CRS. Specifically, total infusion cell dose contributed to the severe CRS occurring in B-ALL patients but not in B-CLL or B-NHL patients. Tumor burden was strongly associated with the severity of CRS in B-ALL. Besides, post-HSCT CD19 CAR-T cell infusion represented lower severe CRS incidence. Further investigations into the risk factors of CRS in B-CLL and B-NHL are needed.
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Antígenos CD19/imunologia , Imunoterapia Adotiva/métodos , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma de Células B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/imunologia , Ensaios Clínicos Fase I como Assunto , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Fatores de RiscoRESUMO
E-cadherin (E-cad) plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. This protein exists in two forms: a membrane-tethered form and a soluble form. Full-length E-cad is membrane tethered. As a type I transmembrane glycoprotein, E-cad mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. Soluble E-cad (sE-cad) is the extracellular fragment of the protein that is cleaved from the membrane after proteolysis of full-length E-cad. The production of sE-cad undermines adherens junctions, causing a reduction in cell aggregation capacity; furthermore, sE-cad can diffuse into the extracellular environment and the blood. As a paracrine/autocrine signaling molecule, sE-cad activates or inhibits multiple signaling pathways and participates in the progression of various types of cancer, such as breast cancer, ovarian cancer, and lung cancer, by promoting invasion and metastasis. This article briefly reviews the role of sE-cad in tumorigenesis and tumor progression and its significance in clinical therapeutics.
Assuntos
Caderinas/fisiologia , Neoplasias/metabolismo , Antígenos CD , Progressão da Doença , Receptores ErbB/metabolismo , Humanos , Neoplasias/patologia , Transdução de Sinais , SolubilidadeRESUMO
Dysfunction of learning and memory is widely found in many neurological diseases. Understanding how to preserve the normal function of learning and memory will be extremely beneficial for the treatment of these diseases. However, the possible protective effect of minocycline in memory impairment is unknown. We used the well-established D-galactose rat amnesia model and two behavioral tasks, the Morris water maze and the step-down task, for memory evaluation. Western blot and PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report that minocycline supplementation ameliorates both the spatial and fear memory deficits caused by D-galactose. We also found that Arc/Arg3.1, c-fos, and brain-derived neurotrophic factor levels are decreased in the D-galactose animal model, and that minocycline reverses the protein and mRNA levels of Arc in the hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline's neuroprotective mechanism. Our study strongly suggests that minocycline can be used as a novel treatment for memory impairment in neurological diseases.
Assuntos
Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Galactose/efeitos adversos , Transtornos da Memória/tratamento farmacológico , Minociclina/administração & dosagem , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Minociclina/farmacologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RatosRESUMO
Spontaneous isolated subclavian artery dissecting aneurysm is rare. This is to our knowledge the first case in the world's literature to report a patient with subclavian artery dissecting aneurysm. Although the endovascular approach of treating subclavian artery pathologies is not challenging, the choice of using a covered stent for this patient was a new attempt in treating subclavian artery dissections. This case report highlights the possibility and safety of using covered stent in treating patients with subclavian artery dissecting aneurysms after reassuring the patency of the cerebral circulation system.
Assuntos
Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Artéria Subclávia/cirurgia , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/fisiopatologia , Implante de Prótese Vascular/instrumentação , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/instrumentação , Humanos , Masculino , Fluxo Sanguíneo Regional , Stents , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/fisiopatologia , Resultado do TratamentoRESUMO
Long-chain acyl coenzyme A synthetase (ACSL) is a member of the synthetase family encoded by a multigene family; it plays an important role in the absorption and transport of fatty acid. Here we review the roles of ACSL in the regulating absorption and transport of fatty acid, as well as the connection between ACSL and some metabolic diseases.
Assuntos
Acil Coenzima A/metabolismo , Ácidos Graxos , Doenças MetabólicasRESUMO
Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline. Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases. In this paper, we review the advances in relations between cellular senescence and liver diseases.