RESUMO
STUDY OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has caused a severe burden on medical professionals, as the rapid disposition of patients is important. Therefore, we aimed to develop a new clinical assessment tool based on the shock index (SI) and age-shock index (ASI). We proposed the hypoxia-age-shock index (HASI) and determined the usability of triage for COVID-19 infected patients in the first scene. METHODS: The predictive power for three indexes on mortality, intensive care unit (ICU) admission, and endotracheal intubation rate was evaluated using the receiver operating curve (ROC). We used DeLong's method for comparing the ROCs. RESULTS: The area under the curve (AUC) for ROC on mortality for SI, ASI, and HASI were 0.546, 0.771, and 0.773, respectively. The AUC on ICU admission mortality for SI, ASI, and HASI were 0.581, 0.700, and 0.743, respectively. The AUC for intubation for SI, ASI, and HASI were 0.592, 0.708, and 0.757, respectively. The AUC differences between HASI and SI showed statistically significant (P = 0.001) results on mortality, ICU admission, and intubation. Additionally, statistically significant results were found for the AUC difference between the HASI and ASI on ICU admission and intubation (P = 0.001 and P = 0.004, respectively). CONCLUSION: HASI can provide a better prediction compared to ASI on ICU admission and endotracheal intubation. HASI was more sensitive in mortality, ICU admission, and intubation prediction than the ASI.
Assuntos
COVID-19 , Humanos , Triagem , Unidades de Terapia Intensiva , Hospitalização , Estudos Retrospectivos , Curva ROCRESUMO
BACKGROUND: Sp1, an important transcription factor, is involved in the progression of various cancers. Our previous studies have indicated that Sp1 levels are increased in the early stage of lung cancer progression but decrease during the late stage, leading to poor prognosis. In addition, estrogen has been shown to be involved in lung cancer progression. According to previous studies, Sp1 can interact with the estrogen receptor (ER) to coregulate gene expression. The role of interaction between Sp1 and ER in lung cancer progression is still unknown and will be clarified in this study. METHODS: The clinical relevance between Sp1 levels and survival rates in young women with lung cancer was studied by immunohistochemistry. We validated the sex dependence of lung cancer progression in EGFRL858R-induced lung cancer mice. Wound healing assays, chamber assays and sphere formation assays in A549 cells, Taxol-induced drug-resistant A549 (A549-T24) and estradiol (E2)-treated A549 (E2-A549) cells were performed to investigate the roles of Taxol and E2 in lung cancer progression. Luciferase reporter assays, immunoblot and q-PCR were performed to evaluate the interaction between Sp1, microRNAs and CD44. Tail vein-injected xenograft experiments were performed to study lung metastasis. Samples obtained from lung cancer patients were used to study the mRNA level of CD44 by q-PCR and the protein levels of Sp1 and CD44 by immunoblot and immunohistochemistry. RESULTS: In this study, we found that Sp1 expression was decreased in premenopausal women with late-stage lung cancer, resulting in a poor prognosis. Tumor formation was more substantial in female EGFRL858R mice than in male mice and ovariectomized female mice, indicating that E2 might be involved in the poor prognosis of lung cancer. We herein report that Sp1 negatively regulates metastasis and cancer stemness in E2-A549 and A549-T24 cells. Furthermore, E2 increases the mRNA and protein levels of RING finger protein 4 (RNF4), which is the E3-ligase of Sp1, and thereby decreases Sp1 levels by promoting Sp1 degradation. Sp1 can be recruited to the promoter of miR-3194-5p, and positively regulate its expression. Furthermore, there was a strong inverse correlation between Sp1 and CD44 levels in clinical lung cancer specimens. Sp1 inhibited CD44 expression by increasing the expression of miR-3194-5p, miR-218-5p, miR-193-5p, miR-182-5p and miR-135-5p, ultimately resulting in lung cancer malignancy. CONCLUSION: Premenopausal women with lung cancer and decreased Sp1 levels have a poor prognosis. E2 increases RNF4 expression to repress Sp1 levels in premenopausal women with lung cancer, thus decreasing the expression of several miRNAs that can target CD44 and ultimately leading to cancer malignancy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Estradiol/farmacologia , Feminino , Humanos , Receptores de Hialuronatos/genética , Neoplasias Pulmonares/genética , Masculino , Camundongos , MicroRNAs/genética , Proteínas Nucleares , Fator de Transcrição Sp1/genética , Fatores de TranscriçãoRESUMO
BACKGROUND: Psoriasis, a chronic inflammatory skin disease, poses an elevated risk of developing diabetes mellitus. PURPOSE: To investigate the effects of antidiabetic medications on psoriasis. DATA SOURCES, STUDY SELECTION AND DATA EXTRACTION: We conducted a systemic review and meta-analysis and searched MEDLINE, EMBASE and CENTRAL for relevant randomized controlled trials. Our outcomes included 75% improvement in the psoriasis area and severity index from baseline (PASI 75), change in the psoriasis area and severity index (PASI) score, or change in the Dermatology Life Quality Index score under antidiabetic agents. Cochrane Collaboration's tool was used to evaluate the risk of bias of included studies. Subgroup analysis of different dosages of the antidiabetic agents was also performed. DATA SYNTHESIS: We included 10 randomized controlled studies examining the effect of antidiabetic agents. Eight studies were rated high risk of bias. Pioglitazone demonstrated significant increase in PASI 75 (risk difference = 0.42; 95% CI: 0.18-0.65) and decrease in mean PASI (mean difference = -3.82; 95% CI: -6.05-1.ã59). In subgroup analysis, 30 mg pioglitazone group demonstrated a significantly higher portion of PASI 75 than 15 mg pioglitazone group (P = .003). LIMITATIONS: Some biases are reported high risk in involved articles. The main limitation of the study is in the inclusion of only glitazones. The lack of effect was seen for rosiglitazone and metformin. In the case of metformin, there was only one study available, which is also an important issue. CONCLUSIONS: The current evidence demonstrates therapeutic efficacy of pioglitazone, which may be a treatment option in patients with psoriasis and diabetes mellitus.
Assuntos
Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pioglitazona/uso terapêutico , Psoríase/tratamento farmacológico , Humanos , Liraglutida/uso terapêutico , Rosiglitazona/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: There are limited studies that compare the cost and outcome of robotic-assisted surgery to open and laparoscopic surgery for colon cancer treatment. We aimed to compare the three surgical modalities for colon cancer treatment. METHODS: We performed a cohort study using the population-based Nationwide Inpatient Sample database. Patients with a primary diagnosis of colon cancer who underwent robotic, laparoscopic, or open surgeries between 2008 and 2014 were eligible for enrollment. We compared in-hospital mortality, complications, length of hospital stay, and cost for patients undergoing one of these three procedures using a multivariate adjusted logistic regression analysis and propensity score matching. RESULTS: Of the 531,536 patients undergoing surgical treatment for colon cancer during the study period, 348,645 (65.6%) patients underwent open surgeries, 174,748 (32.9%) underwent laparoscopic surgeries, and 8143 (1.5%) underwent robotic surgeries. In-hospital mortality, length of hospital stay, wound complications, general medical complications, general surgical complications, and costs of the three surgical treatment modalities. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had a higher mortality rate (OR 2.98, 95% CI 2.61-3.40), more general medical complications (OR 1.77, 95% CI 1.67-1.87), a longer length of hospital stay (6.60 vs. 4.36 days), and higher total cost ($18,541 vs. $14,487) in the propensity score matched cohort. Mortality rate and general medical complications were equivalent in the laparoscopic and robotic surgery groups, but the median cost was lower in the laparoscopic group ($14641 vs. $16,628 USD). CONCLUSIONS: Laparoscopic colon cancer surgery was associated with a favourable short-term outcome and lower cost compared with open surgery. Robot-assisted surgery had comparable outcomes but higher cost as compared to laparoscopic surgery.
Assuntos
Neoplasias do Colo/economia , Neoplasias do Colo/cirurgia , Laparoscopia/economia , Procedimentos Cirúrgicos Robóticos/economia , Adulto , Idoso , Estudos de Coortes , Custos e Análise de Custo , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Registros Hospitalares , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Pontuação de Propensão , Estudos Retrospectivos , TaiwanRESUMO
BACKGROUND: Aquatic animals have great economic and ecological importance. Among them, non-model organisms have been studied regarding eco-toxicity, stress biology, and environmental adaptation. Due to recent advances in next-generation sequencing techniques, large amounts of RNA-seq data for aquatic animals are publicly available. However, currently there is no comprehensive resource exist for the analysis, unification, and integration of these datasets. This study utilizes computational approaches to build a new resource of transcriptomic maps for aquatic animals. This aquatic animal transcriptome map database dbATM provides de novo assembly of transcriptome, gene annotation and comparative analysis of more than twenty aquatic organisms without draft genome. RESULTS: To improve the assembly quality, three computational tools (Trinity, Oases and SOAPdenovo-Trans) were employed to enhance individual transcriptome assembly, and CAP3 and CD-HIT-EST software were then used to merge these three assembled transcriptomes. In addition, functional annotation analysis provides valuable clues to gene characteristics, including full-length transcript coding regions, conserved domains, gene ontology and KEGG pathways. Furthermore, all aquatic animal genes are essential for comparative genomics tasks such as constructing homologous gene groups and blast databases and phylogenetic analysis. CONCLUSION: In conclusion, we establish a resource for non model organism aquatic animals, which is great economic and ecological importance and provide transcriptomic information including functional annotation and comparative transcriptome analysis. The database is now publically accessible through the URL http://dbATM.mbc.nctu.edu.tw/ .
Assuntos
Organismos Aquáticos/genética , Perfilação da Expressão Gênica/métodos , Genômica/métodos , Animais , Bases de Dados Genéticas , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Anotação de Sequência Molecular , Filogenia , Análise de Sequência de RNA/métodos , SoftwareAssuntos
Antipsicóticos , Clozapina , Diabetes Mellitus Tipo 2 , Hiperlipidemias , Hipertrigliceridemia , Esquizofrenia , Humanos , Clozapina/efeitos adversos , Cloridrato de Lurasidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Antipsicóticos/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/tratamento farmacológicoRESUMO
BACKGROUND: This study aims to examine the effects of green tea extract (GTE) supplement on overweight and obese women with high levels of low density lipoprotein-cholesterol (LDL-C). METHODS: The randomized, double-blind, crossover and placebo-controlled clinical trial was conducted from August 2012 to December 2013. Seventy-three out of 90 subjects aged between 18 and 65 years, with body mass index (BMI) ≥ 27 kg/m2 and LDL-C ≥ 130 mg/dl were included in the analysis. The subjects were randomly divided into Groups A and B. Group A received GTE supplement treatment for the first 6 weeks, while Group B received placebo daily. After 6 weeks of treatment and 14 days of washout period, Group A switched to placebo and Group B switched to GTE treatment for 6 weeks. The reduction of LDL-C level between treatments was assessed as the outcome. Additionally, anthropometric measurements, plasma lipoproteins and hormone peptides of both groups were measure at the beginning of weeks 6, 8, and 14 after treatment. RESULTS: Subjects treated with GTE (n = 73) for 6 weeks showed significant differences, with 4.8% (p = 0.048) reduction in LDL-C and 25.7% (p = 0.046) increase in leptin. However, there was no statistical difference in the levels of total cholesterol, triglyceride and high density lipoprotein between the GTE and placebo groups after treatments. CONCLUSIONS: This study shows that green tea extract effectively increases leptin and reduces LDL in overweight and obese women after 6 weeks of treatment even though there were no significant changes in other biochemical markers related to overweight. TRIAL REGISTRATION: This clinical trial is registered with ClinicalTrials.gov: NCT02116517 on 17 April 2014. Retrospectively registered. The first patient enrolled in October 2012 and the study was completed December 2013.
Assuntos
Camellia sinensis , LDL-Colesterol/sangue , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Antropometria , Catequina/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , PlacebosRESUMO
BACKGROUND AND OBJECTIVE: Local anesthetic cream (LAC) has been used for analgesia in various procedures. However, the analgesic effect of LAC in cryotherapy for warts is unclear. We aimed to evaluate the effects of LAC in cryotherapy for warts. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) on the effects of LAC in cryotherapy for warts. We searched MEDLINE, CENTRAL, and EMBASE on 31 March 2017 for relevant RCTs. Two authors independently selected trials, assessed risk of bias, and extracted data. Disagreement was resolved by discussion with a third author. RESULTS: We included three RCTs with 228 participants. Two included RCTs had a high risk of reporting bias, with one having a high risk of other bias as well. Use of LAC decreased the pain associated with cryotherapy for warts on the hardened skin of children (visual analogue scale, mean difference -20.80, 95 % confidence interval -40.71 to -0.89), but not in adults or on the nonhardened skin of either adults or children. CONCLUSIONS: The available evidence does not support the routine use of LAC applied for ≤ 60 min in cryotherapy for warts.
Assuntos
Anestésicos Locais/administração & dosagem , Crioterapia , Combinação Lidocaína e Prilocaína/administração & dosagem , Verrugas/terapia , Adulto , Criança , Humanos , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
HINTERGRUND UND ZIEL: Lokalanästhetische Creme (LAC) wird zur Analgesie bei verschiedenen Verfahren angewendet. Ihre analgetische Wirkung bei der Kryotherapie von Warzen ist jedoch unklar. Wir untersuchten die Wirkung von LAC bei der Kryotherapie von Warzen. MATERIAL UND METHODEN: Wir erstellten eine systematische Übersicht und Meta-analyse randomisierter kontrollierter Studien (RCTs) zu Wirkungen von LAC bei der Kryotherapie von Warzen. Dazu haben wir MEDLINE, CENTRAL und EMBASE am 31. März 2017 nach relevanten RCTs durchsucht. Zwei Autoren wählten unabhängig voneinander die Studien aus, schätzten das Verzerrungsrisiko ab und extrahierten Daten. Meinungsdifferenzen wurden durch Diskussion mit einem dritten Autor gelöst. ERGEBNISSE: Wir schlossen drei RCTs mit 228 Teilnehmern ein. Zwei dieser RCTs bergen ein hohes Risiko einer selektiven Berichterstattung (reporting bias), wobei bei einer der beiden Studien auch das Risiko anderer Bias hoch ist. Lokalanästhetische Creme senkte bei Kindern den Schmerz bei der Kryotherapie von Warzen auf verhornter Haut (visuelle Analogskala, mittlere Differenz -20,80; 95 % - Konfidenzintervall -40,71 bis -0,89), jedoch nicht bei Erwachsenen oder auf nicht verhornter Haut von Erwachsenen oder Kindern. SCHUSSFOLGERUNGEN: Die routinemäßige Verwendung von LAC ≤ 60 min bei der Kryotherapie von Warzen wird nicht durch Literaturbelege gestützt.
RESUMO
The healing of a corneal epithelial defect is essential for preventing infectious corneal ulcers and subsequent blindness. We previously demonstrated that mesenchymal stem cells (MSCs) in the corneal stroma, through a paracrine mechanism, yield a more favorable therapeutic benefit for corneal wound re-epithelialization than do MSCs in the corneal epithelium. In this study, MSCs were grown on a matrix with the rigidity of the physiological human vitreous (1 kPa), corneal epithelium (8 kPa), or corneal stroma (25 kPa) for investigating the role of corneal tissue rigidity in MSC functions regarding re-epithelialization promotion. MSC growth on a 25-kPa dish significantly promoted the wound healing of human corneal epithelial (HCE-T) cells. Among growth factors contributing to corneal epithelial wound healing, corneal stromal rigidity selectively enhanced transforming growth factor-beta (TGF-ß) secretion from MSCs. Inhibitors of TGF-ß pan receptor, TGF-ß receptor 1, and Smad2 dose dependently abrogated MSC-mediated HCE-T wound healing. Furthermore, MSCs growth on a matrix with corneal stromal rigidity enhanced the ability of themselves to promote corneal re-epithelialization by activating matrix metalloproteinase (MMP) expression and integrin ß1 production in HCE-T cells through TGF-ß signaling pathway activation. Smad2 activation resulted in the upregulation of MMP-2 and -13 expression in HCE-T cells, whereas integrin ß1 production favored a Smad2-independent TGF-ß pathway. Altogether, we conclude that corneal stromal rigidity is a critical factor for MSC-induced promotion of corneal re-epithelialization. The activation of the TGF-ß signaling pathway, which maintains the balance between integrin and MMP expression, in HCE-T cells is the major pathway responsible for MSC-mediated wound healing. Stem Cells 2016;34:2525-2535.
Assuntos
Lesões da Córnea/patologia , Lesões da Córnea/terapia , Substância Própria/patologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Cicatrização , Linhagem Celular , Proliferação de Células , Humanos , Integrina beta1/metabolismo , Metaloproteinases da Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , Reepitelização , Proteína Smad2/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Anguilla japonica (Japanese eel) is currently one of the most important research subjects in eastern Asia aquaculture. Enigmatic life cycle of the organism makes study of artificial reproduction extremely limited. Henceforth genomic and transcriptomic resources of eels are urgently needed to help solving the problems surrounding this organism across multiple fields. We hereby provide a reconstructed transcriptome from deep sequencing of juvenile (glass eels) whole body samples. The provided expressed sequence tags were used to annotate the currently available draft genome sequence. Homologous information derived from the annotation result was applied to improve the group of scaffolds into available linkage groups. RESULTS: With the transcriptome sequence data combined with publicly available expressed sequence tags evidences, 18,121 genes were structurally and functionally annotated on the draft genome. Among them, 3,921 genes were located in the 19 linkage groups. 137 scaffolds covering 13 million bases were grouped into the linkage groups in additional to the original partial linkage groups, increasing the linkage group coverage from 13 to 14%. CONCLUSIONS: This annotation provide information of the coding regions of the genes supported by transcriptome based evidence. The derived homologous evidences pave the way for phylogenetic analysis of important genetic traits and the improvement of the genome assembly.
Assuntos
Anguilla/genética , Genoma , Animais , Mapeamento Cromossômico , Peixes/genética , Ligação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Polimorfismo de Nucleotídeo Único , Receptores Citoplasmáticos e Nucleares/classificação , Receptores Citoplasmáticos e Nucleares/genética , Análise de Sequência de RNA , Fatores de Transcrição/classificação , Fatores de Transcrição/genéticaRESUMO
Polydopamine (pDA) coatings afford tremendous versatility due to their capabilities to provide substrate-independent functionalization with a wide range of amine- and thiol-containing molecules. In this work, we developed a new and facile conjugation approach to the formation of ß-amino carbonyl linkages between pDA and acrylate/acrylamide molecules via the aza-Michael reaction. Sulfobetaine acrylamide (SBAA), sulfobetaine methacrylate (SBMA), and poly(ethylene glycol) methacrylate (PEGMA) were employed to graft onto pDA films, giving rise to formation of antifouling coatings. Because of the universal adhesive property of pDA, the coating strategy was applied to different substrates, including TiO2, gold, SiO2, Nitinol alloy, polystyrene, and poly(dimethylsiloxane). The variation of surface chemistry and surface wettability upon pDA modification and subsequent conjugation was monitored with X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. Antifouling properties of coatings were challenged by three common Gram-negative and Gram-positive bacteria. Cytocompatibility of the coatings with NIH-3T3 fibroblasts was accessed using MTT assay. The results showed that pDA coatings grafted with SBAA exhibited superhydrophilicity and excellent fouling resistance likely due to the high chemical reactivity of acrylamide, leading to high grafting density. In addition, dual functional coatings containing passive and active antibacterial components were constructed through the in situ deposition of antimicrobial agent, silver nanoparticles, in pDA, followed by the grafting of SBAA for bacterial repellence. The composite coatings allowed reducing adsorption of E. coli by >95%, while killing attached bacteria by up to 98% upon the releasing of Ag(+) ions as measured by inductively coupled plasma mass spectrometry. Consequently, this work paves a new avenue to the grafting strategy to engineer pDA and to the functional bioinspired antifouling interfaces in a substrate-independent fashion.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Indóis/química , Indóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Animais , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Incrustação Biológica/prevenção & controle , Indóis/toxicidade , Camundongos , Células NIH 3T3 , Polímeros/toxicidadeRESUMO
BACKGROUND: To characterize the utilization of Traditional Chinese Medicine (TCM) among patients with hepatitis C (HC). METHODS: This study examined datasets from the National Health Insurance Research Database in Taiwan. One cohort, including one million patients randomly sampled from the beneficiaries of the National Health Insurance Programme from January 1 to December 31 in 2010, was chosen for this analysis. People who had at least three outpatient or inpatient records and had been diagnosed with hepatitis C virus infection from 2000 to 2010 were defined as patients with HC. Patients with HC who had at least one TCM outpatient clinical record from 2000 to 2010 were defined as TCM users (N = 5,691), whereas patients with no TCM outpatient records were defined as non-TCM users (N = 2,876). The demographic data, treatment modalities and disease distributions of TCM users were analysed. RESULTS: Overall, 66.4 % of the patients with HC had used TCM from 2000 to 2010. Of the TCM users, 54.1 % were female. The utilization rate of TCM increased with age and peaked in the age group of those 40 - 64 years old. Herbal remedies (52.4 %) were the most commonly used agents, followed by combination therapy (46.4 %) and acupuncture alone (1.2 %). Patients who had more extrahepatic diseases and were taking more antiviral agents tended to visit TCM clinics. Jia-Wei-Xiao-Yao-San and Dan-Shen (Salvia miltiorrhiza) were the most commonly used formula and single herb, with 88,124 person-days and 59,252 person-days, respectively. CONCLUSIONS: Our nationwide population-based study revealed a high prevalence and specific usage patterns of TCM in patients with HC in Taiwan.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite C/epidemiologia , Hepatite C/terapia , Medicina Tradicional Chinesa/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Taiwan/epidemiologia , Adulto JovemRESUMO
Preclinical Research This study was conducted to investigate the analgesic activities and mechanism of anti-inflammatory activities of a 50% ethanol extract of Taxillus tsaii (ETT) in vivo using the acetic acid induced writhing test and formalin induced paw licking in mice. The anti-inflammatory effect of ETT was evaluated using a mouse model of λ-carrageenan (Carr)-induced paw edema. ETT reduced the writhing in the acetic acid assay test at a dose 1.0 g/kg po and reduced the licking time in the late phase of the formalin test at doses of 0.5 and 1.0 g/kg po). Carr-induced paw edema was reduced when ETT (0.5 and 1.0 g/kg po) was administered 3-5 h after Carr injection. ETT (1.0 g/kg po) reduced the level of malondialdehyde in the edemic paw by increasing the activity of antioxidant enzymes, e.g., superoxide dismutase and glutathione reductase, in the liver and reducing TNF-α, IL-1ß, and IL-6 activity in the edemic paw. This study demonstrates the analgesic and anti-inflammatory effects of ETT, thus verifying its application in traditional Chinese medicine.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Loranthaceae , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Ácido Acético , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Carragenina , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Etanol/química , Formaldeído , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Medicina Tradicional Chinesa , Camundongos Endogâmicos ICR , Dor/induzido quimicamente , Dor/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Solventes/química , Superóxido Dismutase/metabolismoRESUMO
PURPOSE: To investigate the relationship between health-related quality of life (HRQoL) and different cutoff value of low level of high-density lipoprotein cholesterol (HDL-C) in Taiwanese women with different definition of obesity. METHODS: Prospective observational study in women with central obesity was conducted in Taipei City Hospital. A total of 572 women were screened at our clinic, and 227 of them with a body mass index â§27 kg/m2 defined by the Department of Health in Taiwan and weight circumference â§80 cm were eligible for the study. We defined two groups as group A-low HDL (HDL-C < 40 mg/dL) and group B-high HDL (HDL-C < 50 mg/dL) according to different definition of hypoalphalipoproteinemia in obese women. RESULTS: Significantly reduced HRQoL score was noted in group A-low HDL compared to group A-high HDL (HDL-C ⧠40 mg/dL), but not between group B-low HDL and group B-high HDL (HDL-C ⧠50 mg/dL). Positively correlation was noted between HDL-C level and physical domain of HRQoL score. HDL-C contributes independently to physical domain of HRQoL score after controlling for other factors. Decreased leptin and adiponectin level were noted in hypoalphalipoproteinemia groups. CONCLUSION: Taiwanese obese women with hypoalphalipoproteinemia have adverse impact on HRQoL, especially when the HDL-C level is lower than 40 mg/dL. Both hypoalphalipoproteinemia and hypertension accounted for a great variance to lower scores of physical domain of HRQoL with positively correlation with HDL-C level observed. Decreased leptin and adiponectin were also observed in hypoalphalipoproteinemia group, which implied increased cardiovascular risk. HDL-C level may deem as another indicator for HRQoL in women with central obesity.
Assuntos
Indicadores Básicos de Saúde , Hipoalfalipoproteinemias/sangue , Obesidade Abdominal/psicologia , Qualidade de Vida , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Hipoalfalipoproteinemias/diagnóstico , Hipoalfalipoproteinemias/epidemiologia , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/complicações , Estudos Prospectivos , Fatores de Risco , TaiwanRESUMO
Drug resistance in cancer therapy is the major reason for poor prognosis. Addressing this clinically unmet issue is important and urgent. In this study, we found that targeting USP24 by the specific USP24 inhibitors, USP24-i and its analogues, dramatically activated autophagy in the interphase and mitotic periods of lung cancer cells by inhibiting E2F4 and TRAF6, respectively. USP24 functional knockout, USP24C1695A, or targeting USP24 by USP24-i-101 inhibited drug resistance and activated autophagy in gefitinib-induced drug-resistant mice with doxycycline-induced EGFRL858R lung cancer, but this effect was abolished after inhibition of autophagy, indicating that targeting USP24-mediated induction of autophagy is required for inhibition of drug resistance. Genomic instability and PD-L1 levels were increased in drug resistant lung cancer cells and were inhibited by USP24-i-101 treatment or knockdown of USP24. In addition, inhibition of autophagy by bafilomycin-A1 significantly abolished the effect of USP24-i-101 on maintaining genomic integrity, decreasing PD-L1 and inhibiting drug resistance acquired in chemotherapy or targeted therapy. In summary, an increase in the expression of USP24 in cancer cells is beneficial for the induction of drug resistance and targeting USP24 by USP24-i-101 optimized from USP24-i inhibits drug resistance acquired during cancer therapy by increasing PD-L1 protein degradation and genomic stability in an autophagy induction-dependent manner.
Assuntos
Autofagia , Resistencia a Medicamentos Antineoplásicos , Ubiquitina Tiolesterase , Animais , Humanos , Camundongos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/antagonistas & inibidoresRESUMO
Objective: We aimed to determine the reliability of using the Fibrosis-4 (FIB-4) index in COVID-19 patients without underlying liver illness. Method: We employed multivariate logistic regression to identify variables that exhibited statistically significant influence on the ultimate outcome. Multilayer perceptron analysis was employed to develop a prediction model for the FIB-4 index concerning ICU admission and intubation rates. However, the scarcity of cases rendered the assessment of the mortality rate unfeasible. We plotted ROC curves to analyze the predictive strength of the FIB-4 index across various age groups. Result: In univariate logistic regression, only the FIB-4 index and respiratory rate demonstrated statistical significance on all poor outcomes. The FIB-4 index for mortality prediction had an ROC and AUC of 0.863 (95% CI: 0.781-0.9444). It demonstrates predictive power across age groups, particularly for age ≥65 (AUC: 0.812, 95% CI: 0.6571-0.9673) and age <65 (AUC: 0.878, 95% CI: 0.8012-0.9558). Its sensitivity for intubation and ICU admission prediction is suboptimal. Conclusion: FIB-4 index had promising power in prediction of mortality rate in all age groups.
RESUMO
BACKGROUND: The present study was undertaken to evaluate the anti-depressive activity of turmerone after one-week administration by using a mouse forced swimming test (FST) and tail suspension test (TST). METHODS: Animals were divided into four groups (n = 10 /group): control (0.9% saline), the three doses of turmerone (1.25, 2.5, 5.0 mg/kg) for one-week treatment. To assess the effect of turmerone on locomotor activity, mice were evaluated in the open-field paradigm. Forced swimming test (FST) and Tail suspension test (TST) were used to take as a measure of antidepressant activity. The probable mechanisms of action of the anti-depressive effect of turmerone was also investigated by measuring the activity of monoamine oxidase-A and corticosterone levels in the blood and the levels of monoamines in the cortex, striatum, hippocampus and hypothalamus of the mice. RESULTS: Turmerone (2.5, 5.0 mg/kg, p.o.) significantly reduced the immobility time of mice in both the FST and TST, but it did not significantly affect the ambulatory and total movements of mice. However, hyperactivity might explain the results. In addition, turmerone decreased the corticosterone level in the blood while it increased the levels of 5-HT in cortex, striatum, hippocampus, and hypothalamus, the level of NE in striatum and hippocampus, the levels of MHPG and DOPAC in hypothalamus, the level of 5-HIAA in striatum, and the level of DA in striatum, hippocampus, and hypothalamus. Turmerone (2.5, 5.0 mg/kg) decreased the activity of MAO-A in the frontal cortex and hippocampus of mouse brain. CONCLUSIONS: After one-week administration, turmerone produced antidepressant-like effects. The mechanisms of action of anti-depressive effect of turmerone seemed to involve an increase of the monoamines level decreasing the MAO-A activity and the stress of mice.
Assuntos
Antidepressivos/administração & dosagem , Curcuma/química , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Corticosterona/metabolismo , Depressão/psicologia , Elevação dos Membros Posteriores , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Serotonina/metabolismo , NataçãoRESUMO
We have previously isolated several IgG rheumatoid factors (RFs) from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren's syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6 × 10â»8 M. This effect resulted from longer complementarity-determining region (CDR) combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren's syndrome and may play an important role in the pathogenesis of this autoimmune disease.
Assuntos
Hepatite C/complicações , Fator Reumatoide/química , Fator Reumatoide/imunologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/imunologia , Sequência de Aminoácidos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Especificidade de Anticorpos/imunologia , Sequência de Bases , Proteínas de Transporte/metabolismo , Técnicas de Visualização da Superfície Celular , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/imunologia , Regiões Determinantes de Complementaridade/metabolismo , Sequência Conservada , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/metabolismo , Imunoglobulina G/química , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Biblioteca de Peptídeos , Ligação Proteica/imunologia , Conformação Proteica , Mapeamento de Interação de Proteínas , Fator Reumatoide/metabolismo , Alinhamento de Sequência , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismo , Síndrome de Sjogren/metabolismoRESUMO
Objective: This study aimed to identify the predictors of quality of life (QoL) related to lower limb lymphedema among women who had undergone gynecological cancer surgery. Additionally, the association between fatigue and the QoL was examined. Methods: A cross-sectional design with a convenience sample was adopted. Participants included 200 women with lymphadenectomy following gynecological cancer surgery. Demographic data, QoL related to lower limb lymphedema, and fatigue symptoms were collected. Results: Of the 200 participants, 60 percent (n â= â120) reported a mild to severe impact on QoL related to lower limb lymphedema, with the main impact on the function of mobility and physical symptoms. Age less than 55 years (ß â= â0.706, OR â= â2.027, P â= â0.017), a diagnosis of ovarian cancer (ß â= â0.804, OR â= â2.235, P â= â0.048), undergoing chemotherapy (ß â= â0.616, OR â= â1.854, P â= â0.046), time after surgery (ß â= â-0.833, OR â= â0.435, P â= â0.05), and fatigue (ß â= â0.055, OR â= â1.06, P â< â0.001) were independently associated with QoL related to lower limb lymphedema. Hierarchical multiple regression demonstrated that fatigue was significantly associated with QoL related to lower limb lymphedema after controlling for age, types of cancer, time after surgery, and chemotherapy. Fatigue explained 11% of the variance in the QoL. Conclusions: More than half of the women with gynecological cancer requiring lymphadenectomy experienced an impact on QoL related to lower limb lymphedema. Effective interventions are warranted to improve the QoL related to lower limb lymphedema among women with gynecological cancer, particularly those who present with fatigue.