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Background: As a marker of the GABAergic system, the expression of glutamate decarboxylase 1 (GAD1) is mainly restricted to the central nervous system. Emerging studies have shown that aberrant expression of GAD1 in tumor tissues may promote tumor cell growth. The role of GAD1 in the development of osteosarcoma (OS) remains unclear, so this study sought to investigate the expression status of GAD1 and the effect of its specific inhibitor 3-mercaptopropionic acid (3-MPA) on OS. Methods: The R2 database was used to analyze the relationship between the expression of GAD1 and clinical prognosis in OS patients. Immunohistochemistry was used to compare the expression profile of GAD1 between OS and matched neighboring tissues. The potential antitumor effects of 3-MPA on cell viability, colony formation and the cell cycle were examined. Moreover, the in vivo effect of 3-MPA on tumor growth was investigated using tumor-bearing nude mice. Results: The expression level of GAD1 was aberrantly upregulated in OS tissues, but almost no expression of GAD1 was found in matched neighboring tissues. Western blotting analyses showed upregulation of GAD1 in OS cells compared to human osteoblast cells. In vitro and in vivo, 3-MPA significantly suppressed the growth of OS. Regarding the mechanism, 3-MPA inhibited ß-catenin and cyclin D1 in OS cells, thereby inactivating the Wnt/ß-catenin pathway. Conclusions: OS displays increased expression of the GABAergic neuronal marker GAD1, and 3-MPA significantly reduces OS growth by inhibiting the Wnt/ß-catenin pathway.
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BACKGROUND: According to practice guidelines, endoscopic band ligation (EBL) and endoscopic tissue adhesive injection (TAI) are recommended for treating bleeding from esophagogastric varices. However, EBL and TAI are known to cause serious complications, such as hemorrhage from dislodged ligature rings caused by EBL and hemorrhage from operation-related ulcers resulting from TAI. However, the optimal therapy for mild to moderate type 1 gastric variceal hemorrhage (GOV1) has not been determined. Therefore, the aim of this study was to discover an individualized treatment for mild to moderate GOV1. AIM: To compare the efficacy, safety and costs of EBL and TAI for the treatment of mild and moderate GOV1. METHODS: A clinical analysis of the data retrieved from patients with mild or moderate GOV1 gastric varices who were treated under endoscopy was also conducted. Patients were allocated to an EBL group or an endoscopic TAI group. The differences in the incidence of varicose relief, operative time, operation success rate, mortality rate within 6 wk, rebleeding rate, 6-wk operation-related ulcer healing rate, complication rate and average operation cost were compared between the two groups of patients. RESULTS: The total effective rate of the two treatments was similar, but the efficacy of EBL (66.7%) was markedly better than that of TAI (39.2%) (P < 0.05). The operation success rate in both groups was 100%, and the 6-wk mortality rate in both groups was 0%. The average operative time (26 min) in the EBL group was significantly shorter than that in the TAI group (46 min) (P < 0.01). The rate of delayed postoperative rebleeding in the EBL group was significantly lower than that in the TAI group (11.8% vs 45.1%) (P < 0.01). At 6 wk after the operation, the healing rate of operation-related ulcers in the EBL group was 80.4%, which was significantly greater than that in the TAI group (35.3%) (P < 0.01). The incidence of postoperative complications in the two groups was similar. The average cost and other related economic factors were greater for the EBL than for the TAI (P < 0.01). CONCLUSION: For mild to moderate GOV1, patients with EBL had a greater one-time varix eradication rate, a greater 6-wk operation-related ulcer healing rate, a lower delayed rebleeding rate and a lower cost than patients with TAI.
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Várices Esofágicas y Gástricas , Adhesivos Tisulares , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Úlcera/complicaciones , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Ligadura/efectos adversos , Ligadura/métodos , Endoscopía Gastrointestinal/efectos adversos , Endoscopía Gastrointestinal/métodos , Adhesivos Tisulares/efectos adversos , RecurrenciaRESUMEN
BACKGROUND: This research intended to predict the active ingredients and key target genes of Indigo Naturalis in treating human chronic myeloid leukemia (CML) using network pharmacology and conduct the invitro verification. METHODS: The active components of Indigo Naturalis and the corresponding targets and leukemia-associated genes were gathered through public databases. The core targets and pathways of Indigo Naturalis were predicted through protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, after intersecting with leukemia-related genes, the direct core target gene of Indigo Naturalis active components was identified. Subsequently, HL-60 cells were stimulated with indirubin (IND) and then examined for cell proliferation using CCK-8 assay and cell cycle, cell apoptosis, and mitochondrial membrane potential using flow cytometry. The content of apoptosis-associated proteins (Cleaved Caspase 9, Cleaved Caspase 7, Cleaved Caspase 3, and Cleaved parp) were detected using Western blot, HSP90AA1 protein, and PI3K/Akt signaling (PI3K, p-PI3K, Akt, and p-Akt) within HL-60 cells. RESULTS: A total of 9 active components of Indigo Naturalis were screened. The top 10 core target genes (TNF, PTGS2, RELA, MAPK14, IFNG, PPARG, NOS2, IKBKB, HSP90AA1, and NOS3) of Indigo Naturalis active components within the PPI network were identified. According to the KEGG enrichment analysis, these targets were associated with leukemia-related pathways (such as acute myeloid leukemia and CML). After intersecting with leukemia-related genes, it was found that IND participated in the most pairs of target information and was at the core of the target network; HSP90AA1 was the direct core gene of IND. Furthermore, the in-vitro cell experiments verified that IND could inhibit the proliferation, elicit G2/M-phase cell cycle arrest, enhance the apoptosis of HL-60 cells, reduce mitochondrial membrane potential, and promote apoptosis-related protein levels. Under IND treatment, HSP90AA1 overexpression notably promoted cell proliferation and inhibited apoptosis. Additionally, IND exerted tumor suppressor effects on leukemia cells by inhibiting HSP90AA1 expression. CONCLUSION: IND, an active component of Indigo Naturalis, could inhibit CML progression, which may be achieved via inhibiting HSP90AA1 and PI3K/Akt signaling expression levels.
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Antineoplásicos , Apoptosis , Proliferación Celular , Proteínas HSP90 de Choque Térmico , Indoles , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Humanos , Proliferación Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Indoles/farmacología , Indoles/química , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Estructura Molecular , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia/tratamiento farmacológico , Leucemia/patología , Leucemia/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Osteosarcoma (OS) is the most prevalent type of malignant bone tumor in adolescents. The overall survival of OS patients has reached a plateau recently. Thus, there is an urgent need to develop approaches to improve the sensitivity of OS to therapies. Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPα-PDT) is a new type of tumor therapy, and elucidating its mechanism is helpful to improve its anti-tumor efficacy. Here, we investigated how PERK signaling promotes the human OS (HOS) cell survival induced by MPPα-PDT, as overcoming this may enhance sensitivity to MPPα-PDT. We found that MPPα-PDT combined with PERK inhibitor GSK2656157 enhanced HOS cell apoptosis by suppressing autophagy and p21. Autophagy inhibition and p21 depletion enhanced cell death, indicating pro-survival effects in MPPα-PDT. Notably, p21 was found to be an effector of the PERK-Atf4 pathway, which could positively regulate autophagy mediated by MPPα-PDT. In conclusion, we found that the combination of MPPα-PDT and GSK2656157 enhanced apoptosis in HOS cells by inhibiting autophagy. Mechanistically, this autophagy is p21-dependent and can be suppressed by GSK2656157, thereby enhancing sensitivity to MPPα-PDT.
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Neoplasias Óseas , Osteosarcoma , Humanos , Adolescente , Línea Celular Tumoral , Apoptosis , Osteosarcoma/patología , Transducción de Señal , Neoplasias Óseas/patología , Autofagia , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismoRESUMEN
PURPOSE: This investigation aimed to compare the medical efficacy of the knotted and knotless suture-bridge procedures in rotator cuff repair. METHODS: The Pubmed, Embase, and Cochrane Library datasets were searched for all available publications comparing the medical results of arthroscopic rotator cuff repairs utilizing knotted or knotless suture-bridge procedures. Two researchers utilized Newcastle-Ottawa Scale and Cochrane risk-of-bias tool to evaluate the included studies. Employing Revman 5.3 software, meta-analysis was conducted following the PRISMA reporting guideline. RESULTS: Eleven investigations with 1083 patients were considered suitable for the final meta-analysis. 522 individuals were assigned to the knotted group, whereas 561 were assigned to the knotless group. No statistical difference was found between the knotted and knotless groups, regarding VAS score (WMD, 0.17; 95% CI, - 0.10 to 0.44; P = 0.21); Constant score (WMD, -1.50; 95% CI, - 3.52 to 0.52; P = 0.14); American Shoulder and Elbow Surgeons Shoulder (WMD, -2.02; 95% CI, - 4.53 to 0.49; P = 0.11); University of California Los Angeles score (WMD, -0.13; 95% CI, - 0.89 to 0.63; P = 0.73); ROM of flexion (WMD, 1.57; 95% CI, - 2.11 to 5.60; P = 0.37), abduction (WMD, 1.08; 95% CI, - 4.53 to 6.70; P = 0.71) and external rotation (WMD, 1.90; 95% CI, - 1.36 to 5.16; P = 0.25); re-tear rate (OR, 0.74; 95% CI, 0.50 to 1.08; P = 0.12), and medical complications (OR, 0.90; 95% CI, 0.37 to 2.20; P = 0.82). CONCLUSION: For arthroscopic rotator cuff repairs, there were no statistical differences in medical results among knotted and knotless suture-bridge procedures. Overall, both techniques showed excellent clinical outcomes and could be safely utilized to treat rotator cuff injuries.
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Articulación del Codo , Laceraciones , Humanos , Manguito de los Rotadores/cirugía , Procedimientos Neuroquirúrgicos , SuturasRESUMEN
BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an intestinally produced hormone released by the L-cells to stimulate glucose-dependent insulin release. Vine tea, a traditional Chinese medicine made from the delicate stem and leaves of Ampelopsis grossedentata, has been reported to exert antidiabetic effects; however, the role and mechanism of dihydromyricetin, the main active ingredient of vine tea, remain unclear. METHODS AND RESULTS: MTT assay was applied to detect cell viability. GLP-1 levels in the culture medium using a mouse GLP-1 ELISA kit. The level of GLP-1 in cells was examined using IF staining. NBDG assay was performed to evaluate the glucose uptake by STC-1 cells. The in vivo roles of dihydromyricetin in the diabetes mellitus mouse model were investigated. In this study, 25 µM dihydromyricetin, was found to cause no significant suppression of STC-1 cell viability. Dihydromyricetin markedly elevated GLP-1 secretion and glucose uptake by STC-1 cells. Although metformin increased GLP-1 release and glucose uptake by STC-1 cells more, dihydromyricetin further enhanced the effects of metformin. Moreover, dihydromyricetin or metformin alone significantly promoted the phosphorylation of AMPK, increased GLUT4 levels, inhibited ERK1/2 and IRS-1 phosphorylation, and decreased NF-κB levels, and dihydromyricetin also enhanced the effects of metformin on these factors. The in vivo results further confirmed the antidiabetic function of dihydromyricetin. CONCLUSION: Dihydromyricetin promotes GLP-1 release and glucose uptake by STC-1 cells and enhances the effects of metformin upon STC-1 cells and diabetic mice, which might ameliorate diabetes through improving L cell functions. The Erk1/2 and AMPK signaling pathways might be involved.
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Diabetes Mellitus Experimental , Metformina , Animales , Metformina/farmacología , Péptido 1 Similar al Glucagón/metabolismo , Proteínas Quinasas Activadas por AMP , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Glucosa , Té , Insulina/metabolismoRESUMEN
Background: Peritoneal metastasis (PM) is an advanced stage of intra-abdominal malignancy with a very poor prognosis. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has been utilized as an active treatment in the prevention and treatment of PM, with encouraging results. However, compared with CRS alone, the results of the CRS plus HIPEC strategy in the treatment of patients with intra-abdominal malignancies are still controversial. This study sought to determine the impact of HIPEC + CRS on patient survival and adverse events (AEs) by reviewing randomized controlled trials (RCTs) for all types of intra-abdominal malignancies. Methods: A PubMed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov search extracted all RCTs until 12 October 2022, examining the CRS + HIPEC vs. CRS alone strategies in the treatment of various types of intra-abdominal malignancies. The outcomes included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and AEs. The dichotomous data were pooled and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The survival outcome data were pooled using hazard ratios (HRs) and corresponding 95% CIs. The Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias in the included studies. Results: A total of 12 RCTs were included in this meta-analysis, including 873 patients in the CRS + HIPEC group and 878 patients in the CRS alone group. The studies included 3 (617 patients) on colorectal cancer, 4 (416 patients) on gastric cancer, and 5 (718 patients) on ovarian cancer. Our analysis showed no difference in OS between the CRS + HIPEC and CRS alone groups (HR: 0.79, 95% CI 0.62-1.01). Subgroup analysis showed that CRS + HIPEC improved the OS of gastric cancer patients (HR: 0.49, 95% CI 0.32-0.76) compared with CRS alone. However, CRS + HIPEC did not significantly improve the OS of colorectal cancer (HR: 1.06, 95% CI 0.81-1.38) and ovarian cancer (HR: 0.82, 95% CI 0.62-1.07) patients. In addition, there was no significant difference in DFS/RFS (HR: 0.78, 95% CI 0.57-1.07) or PFS (HR: 1.03, 95% CI 0.77-1.38) between the two groups. Compared with CRS alone, CRS with HIPEC had greater nephrotoxicity (OR: 0.45, 95% CI 0.21-0.98), while other AEs did not differ significantly between the two groups. Conclusion: Our results suggest that CRS + HIPEC may improve OS in gastric cancer patients compared with CRS alone, but we did not observe a benefit for DFS/RFS. For patients with ovarian and colorectal cancers, our results suggest that HIPEC + CRS does not appear to improve survival outcomes. In addition, CRS + HIPEC has higher nephrotoxicity than CRS alone. More evidence from RCTs is needed to evaluate whether the use of CRS + HIPEC is an appropriate option.
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OBJECTIVE: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. BACKGROUND: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries. METHODS: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3-week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee. RESULTS: As of January 29, 2021, 31 patients were enrolled. The median follow-up was 5.1 months (range, 1.5-9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3-68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4-100). The median time to response was 1.4 months (95% CI, 1.3-1.4), the median duration of response was not reached, and the median progression-free survival was 6.3 months (95% CI, 4.9-not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment-emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostly Asunto(s)
Antineoplásicos
, Neoplasias de los Conductos Biliares
, Colangiocarcinoma
, Adulto
, Humanos
, Antineoplásicos/efectos adversos
, Antineoplásicos/uso terapéutico
, Neoplasias de los Conductos Biliares/tratamiento farmacológico
, Neoplasias de los Conductos Biliares/genética
, Conductos Biliares Intrahepáticos/patología
, Colangiocarcinoma/tratamiento farmacológico
, Colangiocarcinoma/genética
, Pueblos del Este de Asia
, Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética
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INTRODUCTION: The objective was to investigate the risk factors for poor pain control in patients with herpes zoster (HZ)-associated neuropathic pain treated with drugs combined with nerve block therapy. Neuropathic pain commonly follows HZ. Nerve block therapy is the most commonly used clinical treatment for such pain, combining anti-inflammation and analgesia to prevent peripheral sensitization of nerve. METHODS: Using clinical practice data from a cohort study at our research center, we established a multivariate logistic regression model to investigate potential risk factors for poor control of zoster-associated pain (ZAP) treated with drugs plus nerve block therapy, including demographic characteristics, complications, laboratory tests, and characteristics of HZ attacks. RESULTS: Of the 429 patients with ZAP who received drugs plus nerve block therapy, 95 (22.14%) had poor pain control after treatment. The risk of poor pain control was closely related to presence of cancer (odds ratio (OR) 4.173, 95% confidence interval (CI) 1.342-12.970), numerical rating scale score on admission (OR 1.929, 95% CI 1.528-2.434), and red blood cell count (OR 0.560, 95% CI 0.328-0.954). Area under the receiver operator characteristic curve was 0.730. Goodness of fit (Hosmer-Lemeshow) was 0.874. CONCLUSIONS: The risk of poor pain control in patients with ZAP increased as a result of certain patient characteristics and complications, especially severe pain before treatment and cancer.
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Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.
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Alginatos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Insuficiencia Cardíaca , Hipertensión , Oligosacáridos/farmacología , Animales , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/microbiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/prevención & control , Hipertensión/sangre , Hipertensión/microbiología , Hipertensión/fisiopatología , Hipertensión/prevención & control , Masculino , Ratas , Ratas Endogámicas SHRRESUMEN
The success of immunotherapy was overshadowed by its low response rate, and the hot or cold tumor microenvironment was reported to be responsible for it. However, due to the lack of an appropriate method, it is still a huge challenge for researchers to understand the molecular differences between hot and cold tumor microenvironments. Further research is needed to gain deeper insight into the molecular characteristics of the hot/cold tumor microenvironment. A large-scale clinical cohort and single-cell RNA-seq technology were used to identify the molecular characteristics of inflamed or noninflamed tumors. With single-cell RNA sequencing technology, we provided a novel method to dissect the tumor microenvironment into a hot/cold tumor microenvironment to help us understand the molecular differences between hot and cold tumor microenvironments. Compared with cold tumors, hot tumors highly expressed B cell-related genes, such as MS4A1 and CXCR5, neurogenesis-related miRNA such as MIR650, and immune molecule-related lncRNA such as MIR155HG and LINC00426. In cold tumors, the expression of genes related to multiple biological processes, such as the neural system, was significantly upregulated, and methylome analysis indicated that the promoter methylation level of genes related to neurogenesis was significantly reduced. Finally, we investigated the pan-cancer prognostic value of the cold/hot microenvironment and performed pharmacogenomic analysis to predict potential drugs that may have the potential to convert the cold microenvironment into a hot microenvironment. Our study reveals the multiomics characteristics of cold/hot microenvironments. These molecular characteristics may contribute to the understanding of immune exclusion and the development of microenvironment-targeted therapy.
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This study was the first report for the complete chloroplast genome of Passiflora serrulata Jacq. (Passifloraceae). The cp genome was 149,683 bp in length contained two inverted repeats (IRs) of 25,470 bp, which were separated by large single-copy (LSC) and small single-copy (SSC) of 86,252 bp and 13,491 bp, respectively. A total of 110 functional genes were encoded, comprised 76 protein-coding genes, 30 tRNA genes, and four rRNA genes. The GC content was 37.0%. The maximum likelihood phylogenetic tree indicated that P. serrulata was recovered as the member of subg. Passiflora and most closely related to the clade formed by P. serratodigitata and P. ligularis.
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Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/secundario , Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Quimioembolización Terapéutica , Resultado Fatal , Hepatectomía , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidoresRESUMEN
In order to explore the pollution levels and characteristics of perfluorinated alkyl substances (PFASs), seawater, sediment, and Ruditapes philippinarum samples were collected near the Jiaozhou Bay coast in April 2018. All samples were analyzed by using the high performance liquid chromatography-mass spectrometry method to determine the content of 35 types of PFASs. The results showed that 12 different PFASs were tested in the seawater with ∑PFASs concentrations of 21.1-38.0 ng·L-1; 10 types of PFASs were detected in sediments, with ∑PFASs content (dry weight) ranging from 0.459 to 1.20 µg·kg-1; 19 types of PFASs were measured in Ruditapes philippinarum, with ∑PFASs content (dry weight) of 15.5-27.5 µg·kg-1. Compared with other areas reported in the literature, the total pollution of Jiaozhou Bay was at medium or high levels. In addition, perfluorooctanoic acid (PFOA) was the dominant PFAS in the seawater, sediments, and Ruditapes philippinarum with a detection rate of 100%. 6:2 fluorotelomer phosphate diester (6:2 diPAP) was observed for the first time in seawater and sediments from Jiaozhou Bay and had the highest detection frequency and concentration of the precursor. Perfluorooctanesulfonamide (PFOSA) was the main precursor in Ruditapes philippinarum, of which the detection rate was 93.8%. Moreover, the organic carbon normalized sediment-water distribution coefficient (lg KOC) values were 5.24-6.37 and increased with an increase in carbon chain length. The bioaccumulation factors (lg BAF) and field-based biota-sediment accumulation factors (lg BSAF) were 2.53-4.32 and 1.30-2.50, respectively. The lg BAF values positively correlated with the carbon chain length, whereas the lg BSAF values decreased with an increase in the carbon chain length (C8-C13).
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Fluorocarburos , Contaminantes Químicos del Agua , Animales , Bahías , China , Monitoreo del Ambiente , Sedimentos Geológicos , Agua de MarRESUMEN
Alginate lyase degrades alginate by the ß-elimination mechanism to produce oligosaccharides with special bioactivities. The low thermal stability of alginate lyase limits its industrial application. In this study, introducing the disulfide bonds while using the rational design methodology enhanced the thermal stability of alginate lyase cAlyM from Microbulbifer sp. Q7. Enzyme catalytic sites, secondary structure, spatial configuration, and molecular dynamic simulation were comprehensively analyzed. When compared with cAlyM, the mutants D102C-A300C and G103C-T113C showed an increase by 2.25 and 1.16 h, respectively, in half-life time at 45 °C, in addition to increases by 1.7 °C and 0.4 °C in the melting temperature, respectively. The enzyme-specific activity and kcat/Km values of D102C-A300C were 1.8- and 1.5-times higher than those of cAlyM, respectively. The rational design strategy that was used in this study provides a valuable method for improving the thermal stability of the alginate lyase.
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Alginatos/química , Alteromonadaceae/química , Proteínas Bacterianas/química , Polisacárido Liasas/química , Dominio Catalítico , Estabilidad de Enzimas/efectos de los fármacos , Oligosacáridos/química , Especificidad por Sustrato , TemperaturaRESUMEN
Alginate oligosaccharides (AlgO), agarose oligosaccharides (AO), and κ-carrageenan oligosaccharides (KCO) were obtained by specific enzymatic hydrolysis method. The molecular weight distributions of the three oligosaccharides were 1.0â»5.0 kDa, 0.4â»1.4 kDa, and 1.0â»7.0 kDa, respectively. The culture medium was supplemented with the three oligosaccharides and fermented by pig fecal microbiota in vitro, for 24 h. Each oligosaccharide was capable of increasing the concentration of short-chain fatty acids (SCFAs), especially butyric acid, and altering the microbiota composition. Linear discriminant analysis effect size (LEfSe) analysis results showed that the opportunistic pathogenic bacteria Escherichia, Shigella, and Peptoniphilus, were significantly decreased in AlgO supplemented medium. AO could improve the gut microbiota composition by enriching the abundance of Ruminococcaceae, Coprococcus, Roseburia, and Faecalibacterium. Besides, KCO could increase the abundance of SCFA microbial producers and opportunistic pathogenic flora. Therefore, these results indicate that AlgO and AO can be used as gut microbial regulators and can potentially improve animal/human gastrointestinal health and prevent gut disease, whereas the physiological function of KCO needs further evaluation.
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Organismos Acuáticos/química , Bacterias/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Oligosacáridos/administración & dosificación , Prebióticos/administración & dosificación , Alginatos/administración & dosificación , Alginatos/química , Alginatos/aislamiento & purificación , Animales , Bacterias/aislamiento & purificación , Carragenina/administración & dosificación , Carragenina/química , Carragenina/aislamiento & purificación , Heces/microbiología , Hidrólisis , Oligosacáridos/química , Oligosacáridos/aislamiento & purificación , Phaeophyceae/química , Rhodophyta/química , Algas Marinas/química , Sefarosa/administración & dosificación , Sefarosa/química , Sefarosa/aislamiento & purificación , PorcinosRESUMEN
A top-down method was developed to synthesize hierarchical composites consisting of NiCo2O4 nanocubes and graphene nanosheets through the electrostatic interaction of negatively charged graphene oxide nanosheets and positively charged NiCo2O4 spheres. Employed as anode materials for lithium-ion batteries, the hierarchical composites exhibit remarkably high electrochemical performance, including large reversible capacity, superior rate capability, and excellent cycling performance. Large reversible capacities of 1024 and 648 mA h g-1 are maintained at a current density of 500 and 3000 mA g-1, respectively, for over 200 cycles. The excellent electrochemical performance of the composite is attributed to the synergistic effect of the hierarchical structure, the well dispersed NiCo2O4 nanocubes and the uniform graphene coating. This work provides an effective and promising strategy for the rational structural design of the metal oxide electrode material.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Receptor ErbB-2/genética , Trastuzumab/uso terapéutico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/genética , China , Colangiocarcinoma/genética , Femenino , Humanos , Lapatinib/uso terapéutico , Masculino , Retratamiento , Insuficiencia del TratamientoRESUMEN
Enantiopure ligands, namely (R,R)- and (S,S)-2,2'-(1,4-phenylene) bis(4,5-dihydrothiazole-4-carboxylic acid) (H2LRR, and H2LSS) were synthesized, and homochiral metallocyclic rings {Ni6LRR6(H2O)12} (1RR) and {Ni6LSS6(H2O)12} (1SS) were obtained and their structures were determined. The complexes exhibit excellent activity for the photocatalytic degradation of organic dyes.
RESUMEN
Schwertmannite is usually naturally found in acidic mining wastewater and frequently used in the adsorption of heavy metal anions from water and wastewater. Schwertmannite was synthesized through a facile chemical method and utilized to remove Cr(â ¥) from contaminated groundwater. The kinetics, thermodynamics and isotherms, as well as the effects of environmental factors on the Schwertmannite adsorption processes were investigated. The experimental results showed that the synthesized Schwertmannite had a strong adsorption capability of Cr(â ¥) from aqueous solution. At the pre-set initial concentrations of Cr(â ¥), the Schwertmannite adsorption of Cr(â ¥) achieved equilibrium within 24 h, and the Lagergren's second-order model fitted the adsorption process better compared to Lagergren's first-order model and intraparticle diffusion model. Langmiur equation fitted the adsorption isotherms better than Freundlich equation. The Cr(â ¥) adsorption on Schwertmannite mainly involved ion exchange reaction between Cr(â ¥) and anions such as OH- and SO42- and surface complexation reactions. The ΔHθ and ΔGθ were 6.368 kJ·mol-1 and -1.215 kJ·mol-1, respectively, therefore the adsorption of Cr(â ¥) was a spontaneous and endothermic process. The removal of Cr(â ¥) from aqueous solution increased with increasing Schwertmannite dosage at pH=4.5. Acidic pH in the range of 4.5-6 favored Cr(â ¥) removal with Schwertmannite compared to that under basic conditions. Under the conditions of 5 mg·L-1of initial Cr(â ¥) concentration, 0.5 g·L-1 of Schwertmannite dosage, pH=6, maximum Cr(â ¥) removal of 93.1% was achieved and the adsorption capacity of Cr(â ¥) with Schwertmannite reached up to 40.4 mg·g-1. Batch tests showed that the presence of HCO3- and SO42- inhibited the adsorption of Cr(â ¥) while Cl- had no significant impact. Cations and natural organic matter had a pH-dependent impact on Cr(â ¥) removal:at pH=8 natural organic matter and cations would significantly inhibit the Cr(â ¥) sorption, while the impact could be neglected at weak acidic conditions (pH=6).