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The patient was a male infant, born full-term, admitted to the hospital at 28 days of age due to jaundice for 20 days and abdominal distension for 15 days. The patient developed symptoms of jaundice, hepatosplenomegaly, massive ascites, and progressively worsening liver function leading to liver failure, severe coagulation disorders, and thrombocytopenia one week after birth. Various treatments were administered, including anti-infection therapy, fluid restriction, use of diuretics, use of hepatoprotective and choleretic agents, intermittent paracentesis, blood exchange, and intravenous immunoglobulin, albumin, and plasma transfusions. However, the patient's condition did not improve, and on the 24th day of hospitalization, the family decided to discontinue treatment and provide palliative care. Sequencing of the patient's liver tissue and parental blood samples using whole-exome sequencing did not identify any pathogenic variants that could explain the liver failure. However, postmortem liver tissue pathology suggested congenital hepatic fibrosis (CHF). Given the rarity of CHF causing neonatal liver failure, further studies on the prognosis and pathogenic genes of CHF cases are needed in the future. This article provides a comprehensive description of the differential diagnosis of neonatal liver failure and introduces a multidisciplinary diagnostic and therapeutic approach to neonatal liver failure.
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Enfermedades Genéticas Congénitas , Ictericia , Fallo Hepático , Lactante , Recién Nacido , Humanos , Masculino , Cirrosis Hepática , Fallo Hepático/etiologíaRESUMEN
A practical strategy for the synthesis of spiro[5.5]trienones-fused selenocyanates and spiro[4.5]trienones-fused selenocyanates through electrophilic selenocyanogen cyclization and dearomative spirocyclization is reported. This approach was conducted under mild conditions with broad substrate scope and good functional group tolerance. The utility of this procedure is exhibited in the late-stage functionalization of nature product and drug molecules.
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Compuestos de Espiro , Cianatos , Ciclización , Estructura Molecular , Compuestos de Selenio , Compuestos de Espiro/químicaRESUMEN
How cells drive the phospholipid signal response to heat stress (HS) to maintain cellular homeostasis is a fundamental issue in biology, but the regulatory mechanism of this fundamental process is unclear. Previous quantitative analyses of lipids showed that phosphatidylinositol (PI) accumulates after HS in Ganoderma lucidum, implying the inositol phospholipid signal may be associated with HS signal transduction. Here, we found that the PI-4-kinase and PI-4-phosphate-5-kinase activities are activated and that their lipid products PI-4-phosphate and PI-4,5-bisphosphate are increased under HS. Further experimental results showed that the cytosolic Ca2+ ([Ca2+ ]c ) and ganoderic acid (GA) contents induced by HS were decreased when cells were pretreated with Li+ , an inhibitor of inositol monophosphatase, and this decrease could be rescued by PI and PI-4-phosphate. Furthermore, inhibition of PI-4-kinases resulted in a decrease in the Ca2+ and GA contents under HS that could be rescued by PI-4-phosphate but not PI. However, the decrease in the Ca2+ and GA contents by silencing of PI-4-phosphate-5-kinase could not be rescued by PI-4-phosphate. Taken together, our study reveals the essential role of the step converting PI to PI-4-phosphate and then to PI-4,5-bisphosphate in [Ca2+ ]c signalling and GA biosynthesis under HS.
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Calcio/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Fosfatidilinositoles/metabolismo , Reishi/metabolismo , Citosol/metabolismo , Respuesta al Choque Térmico , Homeostasis , Transducción de Señal , Triterpenos/metabolismoRESUMEN
Ganoderma lucidum has become a potential model system for evaluating how environmental factors regulate the secondary metabolism of basidiomycetes. Heat stress (HS) is one of the most important environmental factors. It was previously reported that HS could induce the biosynthesis of ganoderic acids (GA). In this study, we found that HS increased GA biosynthesis and also significantly increased cell membrane fluidity. Furthermore, our results showed that addition of the membrane rigidifier dimethylsulfoxide (DMSO) could revert the increased GA biosynthesis elicited by HS. These results indicate that an increase in membrane fluidity is associated with HS-induced GA biosynthesis. Further evidence showed that the GA content was decreased in D9des-silenced strains and could be reverted to WT levels by addition of the membrane fluidizer benzyl alcohol (BA). In contrast, GA content was increased in D9des-overexpression strains and could be reverted to WT levels by the addition of DMSO. Furthermore, both membrane fluidity and GA biosynthesis induced by HS could be reverted by DMSO in WT and D9des-silenced strains. To the best of our knowledge, this is the first report demonstrating that membrane fluidity is involved in the regulation of heat stress induced secondary metabolism in filamentous fungi.
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Respuesta al Choque Térmico , Fluidez de la Membrana , Reishi/metabolismo , Calor , Metabolismo Secundario , TriterpenosRESUMEN
Phospholipid-mediated signal transduction plays a key role in responses to environmental changes, but little is known about the role of phospholipid signalling in microorganisms. Heat stress (HS) is one of the most important environmental factors. Our previous study found that HS could induce the biosynthesis of the secondary metabolites, ganoderic acids (GA). Here, we performed a comprehensive mass spectrometry-based analysis to investigate HS-induced lipid remodelling in Ganoderma lucidum. In particular, we observed a significant accumulation of phosphatidic acid (PA) on HS. Further genetic tests in which pld-silencing strains were constructed demonstrated that the accumulation of PA is dependent on HS-activated phospholipase D (PLD) hydrolysing phosphatidylethanolamine. Furthermore, we determined the role of PLD and PA in HS-induced secondary metabolism in G. lucidum. Exogenous 1-butanol, which decreased PLD-mediated formation of PA, reverses the increased GA biosynthesis that was elicited by HS. The pld-silenced strains partly blocked HS-induced GA biosynthesis, and this block can be reversed by adding PA. Taken together, our results suggest that PLD and PA are involved in the regulation of HS-induced secondary metabolism in G. lucidum. Our findings provide key insights into how microorganisms respond to heat stress and then consequently accumulate secondary metabolites by phospholipid remodelling.
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Respuesta al Choque Térmico/fisiología , Ácidos Fosfatidicos/metabolismo , Fosfolipasa D/metabolismo , Reishi/metabolismo , Triterpenos/metabolismo , 1-Butanol/farmacología , Activación Enzimática , Calor , Hidrólisis , Fosfatidiletanolaminas/metabolismo , Fosfolipasa D/genética , Interferencia de ARN , Reishi/genética , Metabolismo Secundario , Transducción de SeñalRESUMEN
Objective: To investigate the long-term protective effect of breviscapine on the bilateral testes of prepubertal rats after testicular torsion / detorsion. Methods: Thirty-two four-week-old healthy male SD rats were equally randomized into groups A(sham operation),B(normal saline),C(single-dose breviscapine, injected intraperitoneally at 2 mg per kg of the body weight at 30 min before testicular detorsion), and D( continuous-dosing breviscapine, injected intraperitoneally at 2 mg per kg of the body weight at 30 min before testicular detorsion qd for 7 days after surgery). At 6 weeks after establishment of the model of left testicular torsion /detorsion, the rats were sacrificed and the bilateral testes and epididymides harvested for detection of the total antioxidant capacity( TAOC),superoxide dismutase( SOD) level, nitric oxide synthase( NOS) activity, and malondialdehyde( MDA) content in the testis tissue, determination of sperm concentration, viability and motility, and observation of the pathological changes of the testis tissue. Results: Compared with group B, both groups C and D showed obvious increases in the levels of SOD,T-AOC and NOS and the concentration, survival rate and motility of sperm, but a remarkable decrease in the MDA content, with statistically significant differences(P < 0. 05) except in T-AOC, sperm concentration and motility in the contralateral testis of group C and in NOS activity in the bilateral testes of group D. In comparison with the ipsilateral testis of group C,group D exhibited markedly elevated levels of SOD,T-AOC and NOS, increased sperm concentration, viability and motility, and reduced content of MDA in the bilateral testes, with statistically significant differences( P < 0. 05) except in NOS activity in the contralateral testis. Bilateral seminiferous tubule degeneration and interstitial edema were observed in group B, more severe in the injured than in the contralateral testis. Obvious improvement was seen in the post-torsion / detorsion histological changes of the bilateral testis tissue in groups C and D. Conclusion: Breviscapine can obviously protect the bilateral testes of prepubertal rats after testicular torsion / detorsion by removal of oxygen free radicals and reduction of lipid peroxidation injury, and continuous dosing is even more effective than single-dose medication.
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Flavonoides/farmacología , Torsión del Cordón Espermático/tratamiento farmacológico , Testículo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Peroxidación de Lípido , Masculino , Malondialdehído/metabolismo , Óxido Nítrico Sintasa/metabolismo , Ratas , Ratas Sprague-Dawley , Túbulos Seminíferos , Recuento de Espermatozoides , Superóxido Dismutasa/metabolismoRESUMEN
miR-21, which is a putative tumor onco-miR and frequently overexpressed microRNA in various tumors, has been linked to tumor progression through targeting of tumor-suppressor genes. In this study, we sought to determine whether miR-21 has any role on tumor progression of salivary adenoid cystic carcinoma (SACC) and the possible mechanisms. We found that the level of miR-21 expression was significantly higher in SACC than that in normal salivary tissues, and it is also higher in tumors with metastasis than that without metastasis. Using an anti-miR-21 inhibitor in an in vitro model, downregulation of miR-21 significantly decreased the capacity of invasion and migration of SACC cells, whereas a pre-miR-21 increased the capacity of invasion and migration of SACC cells. To explore the potential mechanisms by which miR-21 regulate invasion and migration, we identified one direct miR-21 target gene, programmed cell death 4 (PDCD4), which has been implicated in invasion and metastasis. The suppression of miR-21 in metastatic SACC-LM cells significantly increased the report activity of PDCD4 promoter and the expression of PDCD4 protein. This subsequently resulted in downregulation of the p-STAT3 protein. The level of miR-21 expression positively related to the expression of PDCD4 protein and negatively related to the expression of p-STAT3 protein in SACC specimens, respectively, indicating the potential role of the STAT3-miR-21-PDCD4 pathway in these tumors. Dysregulation of miR-21 has an important role in tumor growth and invasion by targeting PDCD4. Therefore, suppression of miR-21 may provide a potential approach for the treatment of advanced SACC patients.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma Adenoide Quístico/metabolismo , MicroARNs/metabolismo , Proteínas de Unión al ARN/metabolismo , Factor de Transcripción STAT3/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , Carcinoma Adenoide Quístico/mortalidad , Estudios de Casos y Controles , Línea Celular Tumoral , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias de las Glándulas Salivales/mortalidadRESUMEN
BACKGROUND: Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced (ECE) delivery of lumen-apposing metal stent (LAMS) is gradually being recognized as a viable palliative technique for malignant biliary obstruction after endoscopic retrograde cholangiopancreatography (ERCP) failure. However, most of the studies that have assessed its efficacy and safety were small and heterogeneous. Prior meta-analyses of six or fewer studies that were published 2 years ago were therefore underpowered to yield convincing evidence. AIM: To update the efficacy and safety of ECE-LAMS for treatment of biliary obstruction after ERCP failure. METHODS: We searched PubMed, EMBASE, and Scopus databases from the inception of the ECE technique to May 13, 2022. Primary outcome measure was pooled technical success rate, and secondary outcomes were pooled rates of clinical success, reintervention, and adverse events. Meta-analysis was performed using a random-effects model following Freeman-Tukey double-arcsine transformation in R software (version 4.1.3). RESULTS: Fourteen eligible studies involving 620 participants were ultimately included. The pooled rate of technical success was 96.7%, and clinical success was 91.0%. Adverse events were reported in 17.5% of patients. Overall reintervention rate was 7.3%. Subgroup analyses showed results were generally consistent. CONCLUSION: ECE-LAMS has favorable success with acceptable adverse events in relieving biliary obstruction when ERCP is impossible. The consistency of results across most subgroups suggested that this is a generalizable approach.
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Objective: The objective of this study is to explore the utilization of next-generation sequencing (NGS) technology in evaluating the likelihood of identifying individuals with papillary thyroid microcarcinoma (PTMC ≤10 mm) who are at high or low risk. Design: NGS was used to analyze 393 formalin-fixed, paraffin-embedded tissues of PTC tumors, all of which were smaller than 15 mm. Results: The study found that bilateralism, multifocality, intrathyroidal spread, and extrathyroidal extension were present in 84 (21.4%), 153 (38.9%), 16 (4.1%), and 54 (13.7%) cases, respectively. Metastasis of cervical lymph nodes was identified in 226 (57.5%) cases and 96 (24.4%) cases with CLNM >5. Out of the total number of cases studied, 8 cases (2.3%) showed signs of tumor recurrence, all of which were localized and regional. Genetic alterations were detected in 342 cases (87.0%), with 336 cases revealing single mutations and 6 cases manifesting compound mutations. 332 cases (84.5%) had BRAFV600E mutation, 2 cases had KRASQ61K mutation, 2 cases had NRASQ61R mutation, 8 cases had RET/PTC1 rearrangement, 3 cases had RET/PTC3 rearrangement, and 1 case had TERT promoter mutation. Additionally, six individuals harbored concurrent mutations in two genes. These mutations were of various types and combinations: BRAFV600E and NRASQ61R (n = 2), BRAFV600E and RET/PTC3 (n = 2), BRAFV600E and RET/PTC1 (n = 1), and BRAFV600E and TERT promoter (n = 1). The subsequent analysis did not uncover a significant distinction in the incidence of gene mutation or fusion between the cN0 and cN1 patient cohorts. The presence of BRAFV600E mutation and CLNM incidence rates were found to be positively correlated with larger tumor size in PTMC. Our data showed that gene mutations did not appear to have much to do with high-risk papillary thyroid microcarcinoma (PTMC). However, when we looked at tumor size, we found that if the tumor was at least 5 millimeters in size, there was a higher chance of it being at high risk for PTM (P < 0.001, odds ratio (OR) = 2.55, 95% confidence interval (CI): 1.57-4.14). Identification of BRAFV600E mutation was not demonstrated to be significantly correlated with advanced clinicopathological characteristics, although it was strongly associated with a bigger tumor diameter (OR = 4.92, 95% CI: 2.40-10.07, P < 0.001). Conclusion: In clinical practice, BRAFV600E mutation does not consistently serve as an effective biomarker to distinguish high-risk PTMC or predict tumor progression. The size of the tumor has a significant correlation with its aggressive characteristics. PTMC with a diameter of ≤5 mm should be distinguished and targeted as a unique subset for specialized treatment.
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AIM: RegIV, a member of the Regenerating (REG) gene family, may be a marker for the prediction of resistance to 5-fluorouracil (5-FU)-based chemotherapy. However, the relationship between the intrinsic drug resistance of gastric cancer (GC) cells to 5-FU used alone (single FU) or in multidrug therapeutic regimens (5-FU combinations) and RegIV expression has not been investigated. METHODS: The patient cohort comprised 45 patients with primary GC. The chemoresistance of GC cells to therapeutic regimens consisting of single 5-FU or FU combinations was investigated using the ATP-tumor chemosensitivity assay. The level of RegIV mRNA transcripts was determined by real-time reverse transcriptase-PCR. RegIV expression was evaluated as a novel predictive biomarker for the intrinsic drug resistance of primary GC cells to single 5-FU or 5-FU combinations. RESULTS: Upregulation of RegIV mRNA transcripts was observed in 36 of the 45 tumor specimens and was positively correlated with the invasive depth of the tumor cells (p = 0.000), the clinical stages (p = 0.000) and the in vitro intrinsic drug resistance of primary GC cells to 5-FU (p = 0.000) or 5-FU combinations. CONCLUSION: RegIV mRNA transcript level was strongly associated with the intrinsic resistance of GC cells to single 5-FU or 5-FU combinations, suggesting that RegIV may play an important role in the intrinsic resistance of GC cells to 5-FU and that targeted therapy against the RegIV gene could be applied to overcome 5-FU resistance in the treatment of GC.
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Resistencia a Antineoplásicos/genética , Fluorouracilo/uso terapéutico , Lectinas Tipo C/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Pancreatitis , Valor Predictivo de las Pruebas , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias Gástricas/patología , Células Tumorales Cultivadas , Regulación hacia Arriba/genéticaRESUMEN
OBJECTIVE: To investigate the aberrant promoter methylation of hMLH1 gene promoter and its clinical significance in papillary thyroid cancer (PTC). METHODS: methylation of hMLH1 gene promoter in the cancer tissue and matched tumor-adjacent normal tissue of 152 PTC patients were detected by real-time methylation specific PCR (qMSP). The relationship between the methylation of hMLH1 gene promoter and clinicopathological features was analyzed. RESULTS: The methylation rate of hMLH1 gene promoter in cancer tissues was 37.5% (57/152), of which 33 cases were totally methylated and 24 cases were partially methylated. The methylation rate of adjacent normal tissues was 5.3% (8/152)(all were partially methylated). The methylation rate of PTC tissues was significantly higher than that in the tumor-adjacent normal tissue (P < 0.01). The promoter methylation of hMLH1 gene in PTC was significantly correlated with age, size and number of the primary lesion, local invasion, T stage and lymph node metastasis (P < 0.05) , but not correlated with gender and clinical stage (P > 0.05). CONCLUSION: Promoter methylation of hMLH1 gene is a common molecular event in PTC tissue, and it is significantly correlated with the progression of PTC.
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Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma , Metilación de ADN , Proteínas Nucleares/genética , Neoplasias de la Tiroides , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adolescente , Adulto , Factores de Edad , Anciano , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma Papilar , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Invasividad Neoplásica , Estadificación de Neoplasias , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas/genética , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Carga Tumoral , Adulto JovenRESUMEN
The aim of the present study was to explore the effects of Dapagliflozin on renal fibrosis in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats, and to determine the underlying mechanism of action. A total of 24 SPF male SD rats were randomly divided into 4 groups: A normal (Control) group, model group (STZ-induced T2DM rats), Dapagliflozin group (STZ-induced T2DM rats treated with 1 mg/kg Dapagliflozin), and a metformin group (STZ-induced T2DM rats treated with 200 mg/kg metformin), with 6 rats per a group. Peripheral blood and renal tissues were collected from these rats, and the renal indices of each group were examined. The fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), and serum creatinine (SCr) of rats were detected. After 24 h, the urine was collected and the urine protein levels were measured. Hematoxylin and eosin staining was used to detect histological changes in the rat kidney; Masson staining was used to observe the degree of fibrosis in rat renal tissues; and western blot was performed to determine the expression levels of α-smooth muscle actin (SMA), vimentin, E-cadherin, TGF-ß1, Smad7, and p-Smad3 in rat renal tissues. Dapagliflozin effectively inhibited the increase in FBG and HbA1c levels in diabetic mice, reduced renal tissue damage, reduced the renal index values, reduced collagen deposition in the glomerulus and interstitial area, and reduced the proliferation of glomerular mesangial cells. In addition, Dapagliflozin significantly lowered the levels of BUN, SCr, and 24-h urine protein, decreased the protein expression of α-SMA, vimentin, TGF-ß1, and p-Smad3, and increased the protein expression levels of E-cadherin and Smad7. Together, these results showed that Dapagliflozin alleviated renal fibrosis in STZ-induced T2DM rats, and its mechanism of action may be related to the inhibition of the TGF-ß1/Smad pathway.
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A new electrophilic trifluoromethylselenolation reagent, N-trifluoromethylselenophthalimide (Phth-SeCF3), was developed. A strategy for the synthesis of 4-trifluoromethylselenolated isoxazoles through electrophilic trifluoromethylselenolation cyclization has been established by using Phth-SeCF3 as an electrophilic reagent. Moreover, this protocol has the features of broad substrate scope, good functional group tolerance, and high yields.
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BACKGROUND: Helicobacter pylori has been recognized as a definite carcinogen for gastric cancer (GC); however, the pathogenesis of H. pylori infection remains unclear. Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene whose deficiency is causally related to GC. However, in H. pylori infection-associated GC, the role of RUNX3 has not been studied. METHODS: The authors used real-time methylation-specific polymerase chain reaction analysis to determine methylation status of the RUNX3 promoter in a spectrum of gastric lesions, including 220 samples of chronic atrophic gastritis, 196 samples of intestinal metaplasia, 134 samples of gastric adenoma, 102 samples of dysplasia, and 202 samples of GC with paired noncancerous mucosa tissues and corresponding blood specimens. The association of abnormal methylation with precancerous gastric lesions was evaluated along with the association between RUNX3 methylation and H. pylori infection, and the concordance of methylation levels was investigated between serum and tissues. RESULTS: The results indicated that increasing RUNX3 promoter methylation was correlated with distinct stages of GC progression. GC tissues had the highest methylation proportion (75.2%) compared with precancerous gastric lesions, including chronic atrophic gastritis (15.9%), intestinal metaplasia (36.7%), gastric adenoma (41.8%), and dysplasia (54.9%). H. pylori infection, a major risk factor for GC, contributed to the inactivation of RUNX3 in gastric epithelial cells through promoter hypermethylation. The levels of RUNX3 methylation in serum were in significant concordance with the methylation levels observed in GC tissues (P = .887). CONCLUSIONS: The current findings supported RUNX3 methylation as a risk factors for the carcinogenesis of chronic atrophic gastritis with H. pylori infection and indicated that circulating RUNX3 methylation is a valuable biomarker for the detection of early GC.
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Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Metilación de ADN , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiología , Adenoma/genética , Adulto , Anciano , Transformación Celular Neoplásica/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/sangre , Progresión de la Enfermedad , Femenino , Mucosa Gástrica , Gastritis Atrófica/genética , Infecciones por Helicobacter/patología , Humanos , Masculino , Metaplasia/genética , Persona de Mediana Edad , Regiones Promotoras Genéticas , Neoplasias Gástricas/patologíaRESUMEN
AIM: Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials, which fails to take into account the known heterogeneity of chemosensitivity between patients. This study was aimed to demonstrate the degree of heterogeneity of chemosensitivity in esophageal cancers. METHODS: A total of 42 esophageal cancer specimens were collected. The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). RESULTS: Thirty eight specimens produced evaluable results (90.5%). The most active single agent tested was nedaplatin, to which 28.9% of samples were sensitive. Combinations of chemotherapy agents exhibited much higher sensitivity: cisplatin + paclitaxel was sensitive in 16 of 38 (42.1%) of samples, while nedaplatin+paclitaxel was more effective, which was sensitive in 20 of 38 cases (52.6%). CONCLUSION: There was a marked heterogeneity of chemosensitivity in esophageal cancer. Chemosensitivity testing may provide a practical method for testing new regimens before clinical trials in esophageal cancer patients.
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Adenosina Trifosfato/metabolismo , Antineoplásicos/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Persona de Mediana EdadRESUMEN
Fungal keratitis (FK) is a refractory disease that poses a serious threat to vision, with common risk factors like eye trauma, contact lens wearing, topical corticosteroids and antibiotic abuse. Nowadays, topical and systemic anti-fungal drugs and ocular surgeries are still the main therapeutic modalities. However, the pathogenesis of FK, especially the immunologic mechanism within it, has not yet been deeply clarified. A better understanding of the pathogenesis of FK is imperative for more effective therapies and prognosis. Meanwhile, the immune protection strategies are also urgently required to manage FK. This review highlights recent advances in the immunologic mechanism in the pathogenesis of FK, in hope of providing valuable reference information for more effective anti-fungal treatment.
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BACKGROUND: As one of the main blinding ocular diseases, corneal blindness resulted from neovascularization that disrupts the angiogenic privilege of corneal avascularity. Following neovascularization, inflammatory cells are infiltrating into cornea to strengthen corneal injury. How to maintain corneal angiogenic privilege to treat corneal disease has been investigated for decades. METHODOLOGY: Local administration of viral and non-viral-mediated anti-angiogenic factors reduces angiogenic protein expression in situ with limited or free of off-target effects upon gene delivery. Recently, Mesenchymal Stem Cells (MSCs) have been studied to treat corneal diseases. Once MSCs are manipulated to express certain genes of interest, they could achieve superior therapeutic efficacy after transplantation. DISCUSSION: In the text, we first introduce the pathological development of corneal disease in the aspects of neovascularization and inflammation. We summarize how MSCs become an ideal candidate in cell therapy for treating injured cornea, focusing on cell biology, property and features. We provide an updated review of gene-based therapies in animals and preclinical studies in the aspects of controlling target gene expression, safety and efficacy. Gene transfer vectors are potent to induce candidate protein expression. Delivered by vectors, MSCs are equipped with certain characters by expressing a protein of interest, which facilitates better for MSC-mediated therapeutic intervention for the treatment of corneal disease. CONCLUSION: As the core of this review, we discuss how MSCs could be engineered to be vector system to achieve enhanced therapeutic efficiency after injection.
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Enfermedades de la Córnea/terapia , Terapia Genética , Vectores Genéticos/administración & dosificación , Animales , Enfermedades de la Córnea/genética , Técnicas de Transferencia de Gen , HumanosRESUMEN
Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg-1(d-1. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1ß in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.
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Medicamentos Herbarios Chinos/uso terapéutico , Houttuynia/química , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Polisacáridos/uso terapéutico , Animales , Citocinas/metabolismo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/fisiopatología , Extractos Vegetales/química , Polisacáridos/química , Polisacáridos/farmacología , Receptores Toll-Like/metabolismo , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
PURPOSE: This meta-analysis was performed to compare the risks and benefits of combined treatment with tiotropium plus formoterol versus tiotropium alone for stable moderate-to-severe COPD. METHODS: A comprehensive search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) that compared formoterol plus tiotropium to tiotropium alone in COPD patients with a duration of at least 4 weeks. The cut-off date for the search was July 1, 2015. The odds ratio (OR) or mean difference (MD) was used to pool the results with 95% confidence intervals (CI). RESULTS: Eight randomized controlled trials were eligible for this meta-analysis. A significant improvement was observed among patients treated with tiotropium plus formoterol compared with tiotropium alone in the following spirometric indices: mean change in trough FEV1 (P = .02), trough FVC (P = .007), peak FEV1 (P < .00001), and peak FVC (P < .00001). A similar result was noted for the transitional dyspnea index (TDI) (MD 1.46; 95% CI 1.07-1.85) and a clinically significant change in TDI between the tiotropium plus formoterol and tiotropium alone groups (P < .00001). Moreover, a trend toward fewer adverse events was seen in the combination treatment group compared with the tiotropium group (OR .88; 95% CI .70-1.11), although this difference was not statistically significant. CONCLUSIONS: Compared with tiotropium alone, tiotropium in combination with formoterol improved lung function and the symptoms of dyspnea in stable moderate-to-severe COPD patients. Moreover, the combined treatment group tended to have fewer adverse events compared with the tiotropium treatment alone group.