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Epidermolysis bullosa (EB) is a rare disorder caused by autosomal genetic variation. Its main clinical features include skin and mucous membrane blisters, erosion, repeated ulcers and scar formation. The lesions mostly involve the skin, oral cavity, digestive system and urinary system. Epidermolysis bullosa complicated with esophageal stenosis is a common gastrointestinal manifestation of this disorder. Currently, there is no cure for EB, and thus symptomatic treatment is usually applied. Here we describe the case of a patient with recessive dystrophic EB complicated with severe esophageal stenosis. The narrow segment of esophagus was removed and the free part of jejunum was transplanted into the esophageal defect to reconstruct the esophagus and restore the patient's normal swallowing. For patients with EB complicated with severe esophageal stenosis, surgical resection of the diseased esophagus and jejunal transplantation can be used to repair the esophageal and restore normal swallowing pathway, providing an effective treatment for this condition.
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Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment. Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score. Clinical Trials Registration: NCT02654171.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Niño , Lactante , Humanos , Preescolar , Infecciones por Virus Sincitial Respiratorio/epidemiología , Sulfonas/farmacología , Sulfonas/uso terapéutico , Quinazolinas/farmacología , Quinazolinas/uso terapéuticoRESUMEN
Endothelial dysfunction is characterized by disturbances in nitric oxide (NO) bioavailability and increased circulating asymmetric dimethylarginine (ADMA) due to the enormous release of free radicals. Increased circulating ADMA may cause endothelial dysfunction and a variety of clinical disorders, such as liver and kidney disease. Young male Sprague-Dawley rats at postnatal day 17 ± 1 received continuous ADMA infusion via an intraperitoneal pump to induce endothelial dysfunction. Four groups of rats (n = 10 per group) were allocated: control, control and resveratrol, ADMA infusion, and ADMA infusion and resveratrol groups. Spatial memory, NLR family pyrin-domain-containing 3 (NLRP3) inflammasome, cytokine expression, tight junction proteins in the ileum and dorsal hippocampus, and microbiota composition were examined. We found cognitive deficits; increased NLRP3 inflammasome in the plasma, ileum, and dorsal hippocampus; decreased ileum and dorsal hippocampal cytokine activation and tight junction proteins; and microbiota composition alterations in the ADMA-infusion young male rats. Resveratrol had beneficial effects in this context. In conclusion, we observed NLRP3 inflammasome activation in peripheral and central dysbiosis in young male rats with increased circulating ADMA, and found that resveratrol had beneficial effects. Our work adds to the mounting evidence that inhibiting systemic inflammation is a promising therapeutic avenue for cognition impairment, probably via the gut-brain axis.
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A series of novel chiral thiourea fluorescent probes HL1-HL6 were designed and synthesized from (1R,2R)-1,2-diphenylethylenediamine, phenyl isothiocyanate, and different substituted salicylic aldehydes. All of the compounds were confirmed by 1H NMR, 13C NMR, and HRMS. They exhibit high selectivity and sensitivity to Zn2+ in the presence of nitrate ions with the detection limit of 2.3 × 10-8 M (HL5). Meanwhile, their zinc (II) complexes (L-ZnNO3) showed continuous response to H2PO4- in acetonitrile solution. The identification processes could further be verified by supramolecular chemistry data analysis, X-ray single-crystal diffraction analysis, and theoretical study. The research provides reliable evidence for an explanation of the mechanism of action of thiourea involved in coordination, which is important for the application of thiourea fluorescent probes. In short, the sensors HL1-HL6 based on chiral thiourea Schiff base will be promising detection devices for Zn2+ and H2PO4-.
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SLC2A3 is an important member of the glucose transporter superfamily. It has been recently suggested that upregulation of SLC2A3 is associated with poor survival and acts as a prognostic marker in a variety of tumors. Unfortunately, the prognostic role of SLC2A3 in head and neck squamous cell carcinoma (HNSC) is less known. In the present study, we analyzed SLC2A3 expression in HNSC and its correlation with prognosis using TCGA and GEO databases. The results showed that SLC2A3 mRNA expression was higher in HNSC compared with adjacent normal tissues, which was validated with our 9 pairs of HNSC specimens. Moreover, high SLC2A3 expression predicted poor prognosis in HNSC patients. Mechanistically, GSEA revealed that high expression of SLC2A3 was enriched in epithelial-mesenchymal transition (EMT) and NF-κB signaling. In HNSC cell lines, SLC2A3 knockdown inhibited cell proliferation and migration. In addition, NF-κB P65 and EMT-related gene expression was suppressed upon SLC2A3 knockdown, indicating that SLC2A3 may play a preeminent role in the progression of HNSC through the NF-κB/EMT axis. Meanwhile, the expression of SLC2A3 was negatively correlated with immune cells, suggesting that SLC2A3 may be involved in the immune response in HNSC. The correlation between SLC2A3 expression and drug sensitivity was further assessed. In conclusion, our study demonstrated that SLC2A3 could predict the prognosis of HNSC patients and mediate the progression of HNSC via the NF-κB/EMT axis and immune responses.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Pronóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Transición Epitelial-Mesenquimal , Neoplasias de Cabeza y Cuello/genética , Inmunidad , Transportador de Glucosa de Tipo 3RESUMEN
With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Melatonina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Ratas , Animales , Metotrexato/toxicidad , Melatonina/farmacología , Melatonina/uso terapéutico , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasas , Serina-Treonina Quinasas TOR , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & controlRESUMEN
BACKGROUND: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan. METHODS: This retrospective case-control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors. RESULTS: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p < 0.001) and mucoid (p = 0.005) stools, and lower AST levels (p = 0.020) in patients with campylobacteriosis. Lower parental educational attainment (p < 0.001), direct contact with acute gastroenteritis patients (p < 0.001), as well as diarrhea in the mutually cared children (p = 0.007) were linked to campylobacteriosis. Consumption of municipal water (p < 0.001), milk (OR 0.34, 95% CI 0.118-0.979), and soft beverages (OR 0.41, 95% CI 0.192-0.888) were identified as protective factors, while consuming takeout food (p = 0.032) and seafood (p = 0.019) increased risk of campylobacteriosis. CONCLUSIONS: Shorter vomiting duration, bloody and mucoid stool, and less elevated AST levels are manifestations suggestive of campylobacteriosis. Risk factors of campylobacteriosis were low parental educational attainment, direct contact with acute gastroenteritis patients, diarrhea in mutually cared children, takeout food and seafood intake. Potential protective factors include municipal water, milk, and soft beverage intake.
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Infecciones por Campylobacter , Campylobacter , Gastroenteritis , Niño , Humanos , Lactante , Preescolar , Infecciones por Campylobacter/diagnóstico , Infecciones por Campylobacter/epidemiología , Infecciones por Campylobacter/complicaciones , Estudios Retrospectivos , Estudios de Casos y Controles , Taiwán/epidemiología , Gastroenteritis/diagnóstico , Gastroenteritis/epidemiología , Gastroenteritis/etiología , Diarrea/complicaciones , Factores de Riesgo , Vómitos/complicacionesRESUMEN
BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) infection is increasing worldwide. However, its clinical significance is still uncertain. METHODS: The data of the Laboratory Medicine Department of Chang Gung Memorial Hospital in northern Taiwan was searched for children with molecular confirmed macrolide-susceptible Mycoplasma pneumoniae (MSMP) and MRMP infections between January 2011 and December 2018. The clinical features, laboratory data, and chest image presentations were compared between patients with MRMP and MSMP infections and between patients with good and poor macrolide response, respectively. RESULTS: Records from 158 patients were recovered. Of the enrolled patients 34 (22%) suffered MRMP infection, 27 (17%) had pleural effusions, and 47 (32%) had poor macrolide response. The macrolide resistance rate was 12% in 2011, 20% between 2015 and 2016, and 50% between 2017 and 2018, respectively. Other than a poor macrolide response, the MRMP and MSMP infections are clinically indistinguishable. The presence of pleural effusion and MRMP infections were found to be independently associated with a poor macrolide response, with odds ratios (95% confidence interval) of 14.3 (4.9-42.0) and 14.6 (5.4-40), respectively. The macrolide resistance rate of the patients with a poor macrolide response was 49% and 18% among all the patients enrolled and the patients with a pleural effusion, respectively. CONCLUSION: The macrolide resistance rate had possibly increased in recent years in Taiwan and should be continuously monitored. In addition, the macrolide response could be misleading in predicting a macrolide resistance especially for the patients with a pleural effusion.
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Derrame Pleural , Neumonía por Mycoplasma , Niño , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Neumonía por Mycoplasma/tratamiento farmacológico , Macrólidos/farmacología , Macrólidos/uso terapéutico , Estudios Retrospectivos , Relevancia Clínica , Farmacorresistencia Bacteriana , Mycoplasma pneumoniae/genética , Derrame Pleural/tratamiento farmacológicoRESUMEN
Three novel Ir(III) complexes, (ppy)2Ir(L-alanine) (Ir1) (ppy = 2-phenylpyridine), (F4ppy)2Ir(L-alanine) (Ir2) (F4ppy = 2-(4-fluorophenyl)pyridine), and (F2,4,5ppy)2Ir(L-alanine) (Ir3) (F2,4,5ppy = 2-(2,4,5-trifluorophenyl)pyridine), based on simple L-alanine as ancillary ligands were synthesized and investigated. Due to the introduction of fluorine substituents on the cyclometalated ligands, complexes Ir1-Ir3 exhibited yellow to sky-blue emissions (λem = 464-509 nm) in acetonitrile solution. The photoluminescence quantum yields (PLQYs) of Ir1-Ir3 ranged from 0.48-0.69, of which Ir3 with sky-blue luminescence had the highest PLQY of 0.69. The electrochemical study and density functional theory (DFT) calculations show that the highest occupied molecular orbital (HOMOs) energy of Ir1-Ir3 are stabilized by the introduction of fluorine substituents on the cyclometalated ligands, while L-alanine ancillary ligand has little contribution to HOMOs and lowest unoccupied molecular orbitals (LUMOs). Moreover, Ir1-Ir3 presented an excellent response to Cu2+ with a high selectivity, strong anti-interference ability, and short response time. Such a detection was based on significant phosphorescence quenching of their emissions, showing the potential application in chemosensors for Cu2+.
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Iridio , Compuestos Organometálicos , Iridio/química , Ligandos , Compuestos Organometálicos/química , Luminiscencia , Iones , Flúor , AlaninaRESUMEN
In addition to Pseudomonas aeruginosa, other organisms including Staphylococcus aureus have been reported to have associations with ecthyma gangrenosum (EG). There are very limited reports of Staphylococcus aureus EG causing systemic symptoms in an immunocompetent child. We present the case of an atopic child with transient neutropenia developing characteristic skin lesions of EG. Culture of the skin wounds yielded methicillin-susceptible Staphylococcus aureus (MSSA), and incisional biopsy of the skin lesions revealed aggregates of Gram-positive cocci at the subepidermal area and necrotic vasculitis but without perivascular bacterial invasion. In the literature review, seven cases of Staphylococcus aureus EG were reported, and only two were pediatric cases. From this case, we emphasize the importance of early culturing for microorganisms in cases presenting with EG. When toxin-mediated systemic symptoms accompany EG-like skin lesions, MSSA should be considered in an atopic child with transient neutropenia.
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Family with sequence similarity 107, member A(FAM107A) was supposed as a tumor suppressor for various types of tumors. However, no pan-cancer analysis of FAM107A is available. Therefore, we conducted a FAM107A-related pan-cancer analysis across thirty-three tumors based on TCGA database to explore the molecular characteristics of FAM107A. The FAM107A expression is reduced in most cancers, and its down-regulated expression was linked to poor overall survival and progression-free survival of tumor patients. Analysis of DNA methylation of the FAM107A gene showed a negative correlation between FAM107A expression and promoter methylation in numerous cancers. Furthermore, FAM107A expression was noted to be involved in myeloid-derived suppressor cell infiltration in multiple cancers. To explore the mechanism of FAM107A in cancers, KEGG, and GO enrichment analysis was performed and the result showed "cell adhesion" and "cAMP signaling pathway" terms as the potential impact of FAM107A on cancers. An experiment in vitro showed FAM107A knockdown promoted the proliferation, migration, and invasion of bladder cancer and renal cancer cells. Our study indicates that FAM107A may be a putative tumor suppressor in bladder cancer and other tumors.
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BACKGROUND: Human endogenous retrovirus-H long terminal repeat-associating protein 2 is a newly identified immune checkpoint molecule that was aberrantly expressed in many malignant tumors. However, its expression in medullary thyroid carcinoma is still unclear. This study aimed to investigate the human endogenous retrovirus-H long terminal repeat-associating protein 2 expression in medullary thyroid carcinoma tissues and to evaluate the relationships between its expression and clinicopathologic together with prognostic relevance. METHODS: Using 51 surgical specimens obtained from medullary thyroid carcinoma patients, the expression levels of the human endogenous retrovirus-H long terminal repeat-associating protein 2 protein in medullary thyroid carcinoma tumor tissues and adjacent noncancerous tissues were measured by immunohistochemistry, and its correlations with clinicopathologic and prognostic features were analyzed. Status of CD8+ tumor infiltrating lymphocytes was also investigated. RESULTS: The results showed that human endogenous retrovirus-H long terminal repeat-associating protein 2 was only detected in tumor tissues, and 31.4% of the medullary thyroid carcinoma patients had high expression of human endogenous retrovirus-H long terminal repeat-associating protein 2. High human endogenous retrovirus-H long terminal repeat-associating protein 2 expression was significantly associated with lymph node metastasis and advanced American Joint Committee on Cancer stages (P = 0.005). There existed an inverse trend between human endogenous retrovirus-H long terminal repeat-associating protein 2 expression and CD8+ tumor infiltrating lymphocytes infiltration in medullary thyroid carcinoma tumor samples (P = 0.042). The log-rank test showed a shorter disease-free survival in patients with high human endogenous retrovirus-H long terminal repeat-associating protein 2 expression (P = 0.002). The disease-free survival rates were also significantly low in cases of medullary thyroid carcinoma with lymph node metastasis, American Joint Committee on Cancer stages III-IV and multifocality. Multivariate Cox analysis confirmed that human endogenous retrovirus-H long terminal repeat-associating protein 2 acted as an independent predictive factor in the disease-free survival of medullary thyroid carcinoma patients (hazard ratio = 4.138, 95% confidence interval: 1.027-16.667, P = 0.046). CONCLUSIONS: Taken together, human endogenous retrovirus-H long terminal repeat-associating protein 2 is highly expressed in medullary thyroid carcinoma patients and is a poor prognostic biomarker of disease-free survival of medullary thyroid carcinoma patients.
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Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Carcinoma Neuroendocrino/cirugía , Humanos , Inmunoglobulinas/metabolismo , Metástasis Linfática , Pronóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugíaRESUMEN
PURPOSE: Identification of novel biomarkers could benefit the clinical therapy and management of papillary thyroid carcinoma (PTC). Human endogenous retrovirus long terminal repeat-associating protein 2 (HHLA2) has been reported to play roles in the development of various cancers. The clinical significance and biological function of HHLA2 in PTC were investigated. PATIENTS AND METHODS: The expression level of HHLA2 was evaluated in PTC tissues (from 107 PTC patients) and cell lines (TPC-1, IHH-4, CGTH-W3, and MDA-T32 cells) by RT-qPCR. The clinical significance of HHLA2 was estimated with a series of statistical analyses. The biological function of HHLA2 was assessed with the CCK8 assay and transwell assay. RESULTS: HHLA2 was upregulated in PTC compared with the normal samples and was associated with the positive lymph node metastasis and advanced TNM stage of PTC patients. HHLA2 was an independent prognostic factor associated with the poor survival of PTC patients. Additionally, HHLA2 functioned as a tumor promoter that enhanced the progression of PTC cells. CONCLUSION: HHLA2 could serve as a prognostic biomarker and tumor promoter in PTC, providing a novel therapeutic target of PTC.
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BACKGROUND: MiRNA is a small molecule RNA that plays an important role in a variety of physiological and pathological processes., and miR-34c-3p has been demonstrated to be closely related to the occurrence of tumors. Ferroptosis is a new form of cell death characterized by lipid-based reactive oxygen species accumulation. However, it is still unclear how miR-34c-3p influences the development of oral squamous cell carcinoma (OSCC) by regulating ferroptosis. Therefore, the main objective of this study was to explore the role and mechanism of miR-34c-3p in OSCC. MATERIALS AND METHODS: The expression of miR-34c-3p in OSCC and matched normal tissues was detected by quantitative real-time PCR (qRT-PCR). Subsequently, the effect of miR-34c-3p overexpression on cell proliferation and ferroptosis was evaluated using CCK8, colony formation assays, Live/Dead staining, Western blotting analysis, ROS, MDA, and GSH assay. RESULTS: The results showed lower expression of miR-34c-3p in OSSC compared with normal tissues. Overexpression of miR-34c-3p in SCC-25 cells suppressed cell proliferation. In addition, the overexpression of miR-34c-3p promoted ferroptosis by increasing ROS, MDA, and iron and decreasing GSH and GPX4 levels in SCC-25 cells. CONCLUSION: Our findings revealed a novel strategy to upregulate erastin-induced ferroptosis in OSCC through the miR-34c-3p/SLC7A11 axis, suggesting new insights into OSCC and a potentially useful therapeutic strategy for OSCC.
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Sistema de Transporte de Aminoácidos y+/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , MicroARNs/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Regulación hacia Arriba/genética , Anciano , Sistema de Transporte de Aminoácidos y+/farmacología , Femenino , Ferroptosis/efectos de los fármacos , Humanos , Masculino , MicroARNs/genética , MicroARNs/uso terapéutico , Persona de Mediana Edad , Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND/PURPOSE: Acute gastroenteritis (AGE) remains a significant health issue in children. The worldwide evolution of pediatric AGE pathogens had been recorded since the introduction of rotavirus vaccine. Ten years after the rotavirus vaccine was introduced to the private sectors in Taiwan, a nationwide study was conducted to elucidate the epidemiological changes among major AGE pathogens. METHODS: From January 2014 to December 2017, children younger than 5 years old, hospitalized with AGE at 10 hospitals across Taiwan were enrolled. Stool specimens were tested for Salmonella spp., Campylobacter spp., Clostridiodes difficile, norovirus, and rotavirus by polymerase chain reaction (PCR). The epidemiological and clinical information was collected. RESULTS: Enteric pathogen were detected in 1983 (42.2%) of 4700 subjects, with Salmonella spp. (12.5%) being the leading cause of AGE, followed by norovirus (11.2%), rotavirus (8.7%), C. difficile (4.2%), Campylobacter spp. (1.0%), and a mixture of at least 2 of 5 above-mentioned pathogens (4.6%). The case distributions varied across different regions. In eastern Taiwan, rotavirus (21/131, 16.0%) remained the most common pathogen detected. The rotavirus vaccine uptake rate is significantly lower in patients with rotavirus AGE. Besides, rotavirus AGE frequently occurred in children with foreign parent(s), Taiwanese indigenous people, and those with the household monthly income < NT$ 60,000. CONCLUSION: Salmonella spp. and norovirus were two major pathogens of pediatric AGE in Taiwan during 2014-17. Providing low-to middle-income households with free rotavirus vaccine nationwide and an industry-led act to reduce salmonellosis should be considered by the authorities.
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Clostridioides difficile , Gastroenteritis , Infecciones por Rotavirus , Rotavirus , Niño , Preescolar , Heces , Gastroenteritis/epidemiología , Humanos , Lactante , Infecciones por Rotavirus/epidemiología , Taiwán/epidemiologíaRESUMEN
Pseudopodium enriched atypical kinase 1(PEAK1) is a non-receptor tyrosine kinase, which is enriched in the pseudopodia of migrating cells and plays an important role in regulating cell migration and proliferation. In the study, we investigate the therapeutic effect of PEAK1 on melanoma cells in vitro and in vivo. We used a lentiviral vector to express short hairpin RNAs (Lv-PEAK1 shRNA) for inhibiting PEAK1 expression in the melanoma SKMEL28 cells. A full-length PEAK1 gene was cloned into the pcDNA 3.1 (+) plasmid and used to infect the melanoma SKMEL19 cells. P6 (also known as Pyridines 6, EMD Chemicals), the Pan-JAK inhibitor, was used to inhibit the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway. The cell counting kit-8 (CCK-8), colony formation assay and transwell assay were used to detect cell proliferation, growth and invasion in vitro. The effect of PEAK1 on melanoma progression in vivo was also evaluated. Protein expression of PEAK1, E-cadherin, vimentin and JAK/STAT3 was measured using western blot assay or immunohistochemistry. The results showed that enforced PEAK1 expression facilitated melanoma cell growth, invasion and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown inhibited melanoma cell growth, invasion and metastasis via inactivating JAK/STAT3 signals. Further work demonstrated that P6 (500 nM) treatment reversed PEAK1-induced effect in melanoma cells. PEAK1 promotes tumorigenesis and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown reduced tumorigenesis and metastasis in melanoma via inactivating JAK/STAT3 signals, providing a novel therapeutic strategy for melanoma treatment.
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Quinasas Janus/genética , Melanoma , Proteínas Tirosina Quinasas , Factor de Transcripción STAT3/genética , Animales , Línea Celular Tumoral , Femenino , Humanos , Quinasas Janus/metabolismo , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Ratones , Ratones Desnudos , Invasividad Neoplásica/genética , Metástasis de la Neoplasia/genética , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/genéticaAsunto(s)
Apnea Obstructiva del Sueño/etiología , Colgajos Quirúrgicos/efectos adversos , Insuficiencia Velofaríngea/cirugía , Adolescente , Adulto , Labio Leporino/complicaciones , Labio Leporino/cirugía , Fisura del Paladar/complicaciones , Fisura del Paladar/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Oxígeno/sangre , Faringe/cirugía , Polisomnografía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/fisiopatología , Insuficiencia Velofaríngea/etiología , Adulto JovenRESUMEN
BACKGROUND: As a new kind of noncoding RNAs, circular RNAs (circRNAs) have been substantiated to be involved in multiple biological processes. Accumulating studies indicate that circular RNAs (circRNAs) regulate the development of cancers by acting as miRNA sponges. However, the role of circRNAs in endometrial cancer (EC) is rarely reported. This study was aimed at investigating the functional roles of circSLC6A6 in EC. METHODS: The qRT-PCR assay was performed to detect the circSLC6A6 expression in EC tissues and cell lines. The luciferase reporter assay was performed to explore the connection between circSLC6A6 and miR-497-5p as well as the connection between miR-497-5p and PI4KB. The colony formation assay, EdU assay, wound healing assay, and transwell assay were performed to examine the proliferation, migration, and invasion of EC cells. The in vivo assay was performed to reveal the function of circSLC6A6 in tumorigenesis. RESULTS: We found that circSLC6A6 was highly expressed in both EC tissues and cells. And circSLC6A6 promoted the proliferation, migration, and invasion of EC cells in vitro. In vivo, circSLC6A6 promoted tumor growth. Besides, a mechanistic study demonstrated that circSLC6A6 could regulate tumor-associated signaling PI4KB/hedgehog pathway by sponging miR-497-5p. CONCLUSION: This study illustrates that circSLC6A6 plays a role in promoting EC progression via the miR-497-5p-mediated PI4KB/hedgehog pathway. Our study may provide a potential novel biomarker for EC diagnosis or treatment.
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Neoplasias Endometriales/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , ARN Circular/metabolismo , Animales , Línea Celular Tumoral , Neoplasias Endometriales/patología , Femenino , Proteínas Hedgehog/metabolismo , Humanos , Masculino , Ratones , Transducción de Señal/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective:To analyze the bacteriological distribution and drug resistance of nasopharynx in patients with adenoid hypertrophy complicated with secretory otitis media, and to clarify the distribution of pathogenic bacteria, so as to provide guidance and basis for antibiotic use in clinical treatment. Methods:A retrospective analysis was performed on 311 patients with adenoid hypertrophy and secretory otitis media who underwent surgical treatment in the department of otolaryngology head and neck surgery, Affiliated Hospital of Qingdao University from February 2013 to January 2020. They were divided into 3 groups by age: Group Aï¼0-5 years oldï¼, Group Bï¼6-10 years oldï¼, and Group Cï¼11-16 years oldï¼. The secretions from deep adenoid near the eustachian tube of the affected ear were collected during the surgery for bacterial culture and drug resistance analysis. Results:One hundred and forty-two strains of pathogenic bacteria were isolated and cultured, with a detection rate of 45.66%. Staphylococcus aureus ï¼63 strainsï¼, streptococcus pneumoniae ï¼15 strainsï¼ ,streptococcus pyogenes ï¼13 strainsï¼ and moraxella cachinellaï¼28 strainsï¼was the main strain.Staphylococcus aureus had high drug resistance rate to penicillin, erythromycin and clindamycin.Streptococcus pneumoniae and Streptococcus pyogenic had high resistance rates to erythromycin,clindamycin and tetracycline. The resistance rate of Moraxella catarrhalis to ampicillin and co-trimoxazole was higher. Conclusion:The main pathogens detected in patients with adenoid hypertrophy complicated with secretory otitis media are staphylococcus aureus, streptococcus pneumoniae, streptococcus pyogenes and moraxella catarrhalis. Drug resistance of different pathogens is quite different. So it is recommended to carry out extensive bacteriological detection, and select antibiotics according to the principle of rational drug use and the results of drug resistance test, so as to achieve good therapeutic effect.