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Severe asthma is a syndromic label assigned to patients based on clinical parameters, yet there are diverse underlying molecular endotypes in severe asthma pathobiology. Immunophenotyping of asthma biospecimens commonly includes a mixture of granulocytes and lymphocytes. Recently, a subset of severe asthma patients was defined as non-type 2 with neutrophil-enriched inflammation associated with increased Th17 CD4+ T cells and IL-17 levels. Here, we used an allergen-driven mouse model of increased IL-17 and mixed granulocyte lung inflammation to determine the impact of upstream regulation by an Anticalin protein that specifically binds IL-23. Airway administration of the IL-23 binding Anticalin protein (AcIL-23) decreased lung neutrophils, eosinophils, macrophages, and lymphocytes, IL-17+ CD4 T cells, mucous cell metaplasia and methacholine-induced airway hyperresponsiveness. Selective targeting of IL-23 with a monoclonal antibody (IL-23p19) (αIL-23) also decreased macrophages, IL-17+ CD4 T cells and airway hyperresponsiveness. In contrast, a monoclonal antibody against IL-17A (αIL-17A) had no significant effect on airway hyperresponsiveness, but did decrease lung neutrophils, macrophages, and IL-17+ CD4 T cells. Targeting the IL-23 pathway did not significantly change IL-5+ or IL-13+ CD4 T cells. Together, these data indicate that airway AcIL-23 mirrored the activity of systemic anti-IL-23 antibody to decrease airway hyperresponsiveness in addition to mixed granulocytic inflammation, and that these protective actions were broader than blocking only IL-17A or IL-5, which selectively decreased airway neutrophils and eosinophils, respectively.
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BACKGROUND: The population of elderly patients with gastric cancer is increasing, which is a major public health issue in China. Malnutrition is one of the greatest risk factors for adverse clinical outcomes in elderly patients with gastric cancer. AIM: To investigate the preoperative nutritional status and its association with delayed discharge of elderly gastric cancer patients following radical gastrectomy. METHODS: A total of 783 patients aged 65 years and older harboring gastric adenocarcinoma and following radical gastrectomy were retrospectively analyzed from the prospectively collected database of Zhongshan Hospital of Fudan University between January 2018 and May 2020. RESULTS: The overall rate of malnutrition was 31.8%. The incidence of postoperative complications was significantly higher in the malnourished group compared to the well-nourished group (P < 0.001). Nutritional characteristics in the malnourished group, including body mass index, prognostic nutritional index (PNI), albumin, prealbumin, and hemoglobin, were all significantly lower than those in the well-nourished group. The percentage of patients who received postoperative total nutrient admixture was lower in the malnourished group compared to the well-nourished group (22.1% vs 33.5%, P = 0.001). Age ≥ 70 years (HR = 1.216, 95%CI: 1.048-1.411), PNI < 44.5 (HR = 1.792, 95%CI: 1.058-3.032), operation time ≥ 160 minutes (HR = 1.431, 95%CI: 1.237-1.656), and postoperative complications grade III or higher (HR = 2.191, 95%CI: 1.604-2.991) were all recognized as independent risk factors associated with delayed discharge. CONCLUSION: Malnutrition is relatively common in elderly patients undergoing gastrectomy. Low PNI is an independent risk factor associated with delay discharge. More strategies are needed to improve the clinical outcome of these patients.
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Specialized proresolving mediators (SPMs) promote local macrophage efferocytosis but excess leukocytes early in inflammation require additional leukocyte clearance mechanism for resolution. Here, neutrophil clearance mechanisms from localized acute inflammation were investigated in mouse dorsal air pouches. 15-HEPE (15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid) levels were increased in the exudates. Activated human neutrophils converted 15-HEPE to lipoxin A5 (5S,6R,15S-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), 15-epi-lipoxin A5 (5S,6R,15R-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), and resolvin E4 (RvE4; 5S,15S-dihydroxy-6E,8Z,11Z,13E,17Z-eicosapentaenoic acid). Exogenous 15-epi-lipoxin A5, 15-epi-lipoxin A4 and a structural lipoxin mimetic significantly decreased exudate neutrophils and increased local tissue macrophage efferocytosis, with comparison to naproxen. 15-epi-lipoxin A5 also cleared exudate neutrophils faster than the apparent local capacity for stimulated macrophage efferocytosis, so the fate of exudate neutrophils was tracked with CD45.1 variant neutrophils. 15-epi-lipoxin A5 augmented the exit of adoptively transferred neutrophils from the pouch exudate to the spleen, and significantly increased splenic SIRPa+ and MARCO+ macrophage efferocytosis. Together, these findings demonstrate new systemic resolution mechanisms for 15-epi-lipoxin A5 and RvE4 in localized tissue inflammation, which distally engage the spleen to activate macrophage efferocytosis for the clearance of tissue exudate neutrophils.
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Lipoxinas , Macrófagos , Neutrófilos , Baço , Animais , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Humanos , Lipoxinas/metabolismo , Lipoxinas/farmacologia , Baço/metabolismo , Baço/citologia , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Camundongos Endogâmicos C57BL , Fagocitose , Masculino , Inflamação/metabolismo , Ácidos HeptanoicosRESUMO
PURPOSE: This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes. METHODS: This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested. RESULTS: Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years. CONCLUSION: AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.
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OBJECTIVES: To evaluate the learning gain and students' perceptions towards Jigsaw collaborative learning in comparison with lectures in learning about pharmacokinetic changes in special populations. METHODS: Undergraduates learn about A-D-M-E of specific populations via Jigsaw collaborative learning and didactic lectures. Pre- and post-lesson quizzes were conducted to evaluate the effectiveness of the teaching method in terms of knowledge gain. Surveys comprising Likert scale statements and open-ended questions were conducted to elucidate students' perception towards the teaching methods. RESULTS: From a class of 192 students, 118 (62%) and 110 (57%) students completed the pre- and post-lecture quizzes, respectively, while 176 (92%) and 168 (88%) students completed the pre- and post-Home Group discussion of Jigsaw quizzes, respectively. There was an improvement of 22.2% and 14.3% in median percentage quiz scores for the lecture and Jigsaw method respectively. Most students agreed that they have learned (54-60%) and collaborated (78-89%) through the Jigsaw method and rated Jigsaw as useful for their learning (54%). Open-ended survey responses offered a mixed conclusion where the didactic lecture was perceived to be as, or more effective than the Jigsaw method. CONCLUSION: Learning gains were observed through the Jigsaw collaborative learning method which relied solely on peer-teaching, despite students perceiving it to be not as effective as lecture. The method provided opportunities for active and peer-learning. Further studies are needed to evaluate the long-term effects of this teaching method.
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This study aims to assess the quality of evidence for the treatment of diabetic retinopathy with traditional Chinese medicine based on the systematic reviews/Meta-analyses of relevant studies. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for the systematic reviews/Meta-analyses of traditional Chinese medicine interventions in diabetic retinopathy published from the inception to November 2023. A Measurement Tool to Assess Systematic Reviews 2(AMSTAR2) scale was used to assess the methodological quality of the included studies. An evidence map was built to present the information on intervention measures, the number of studies included in the systematic reviews/Meta-analyses, research conclusions, and methodological quality assessment results. A total of 51 studies were included. Traditional Chinese medicine interventions accounted for a large proportion of the intervention measures, followed by Chinese patent medicines. The treatment methods mainly included tonifying deficiency, activating blood, and resolving stasis. According to the AMSTAR2 scale assessment results, the descriptions of funding information for included studies, lists of excluded articles, and preliminary research protocols were particularly lacking. The evidence map showed that 48, 2, and 1 studies concluded with beneficial effects, possible beneficial effects, and unclear effects, respectively. On the whole, traditional Chinese medicine demonstrated definite efficacy in the treatment of diabetic retinopathy, while the evidence pre-sents moderate to low quality. It is suggested that higher-quality studies remain to be carried out to provide more evidence.
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Retinopatia Diabética , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/terapia , Humanos , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.
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Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Mutação Puntual , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Receptores de Superfície Celular , Animais , Suínos , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Animais Geneticamente Modificados/genética , Linhagem CelularRESUMO
Soil salinity is a significant challenge in agriculture, particularly in arid and semi-arid regions such as Pakistan, leading to soil degradation and reduced crop yields. The present study assessed the impact of different salinity levels (0, 25, and 50 mmol NaCl) and biochar treatments (control, wheat-straw biochar, rice-husk biochar, and sawdust biochar applied @ 1% w/w) on the germination and growth performance of wheat. Two experiments: a germination study and a pot experiment (grown up to maturity), were performed. The results showed that NaCl-stress negatively impacted the germination parameters, grain, and straw yield, and agronomic and soil parameters. Biochar treatments restored these parameters compared to control (no biochar), but the effects were inconsistent across NaCl levels. Among the different biochars, wheat-straw biochar performed better than rice-husk and sawdust-derived biochar regarding germination and agronomic parameters. Biochar application notably increased soil pHs and electrical conductivity (ECe). Imposing NaCl stress reduced K concentrations in the wheat shoot and grains with concomitant higher Na concentrations in both parts. Parameters like foliar chlorophyll content (a, b, and total), stomatal and sub-stomatal conductance, and transpiration rate were also positively influenced by biochar addition. The study confirmed that biochar, particularly wheat-straw biochar, effectively mitigated the adverse effects of soil salinity, enhancing both soil quality and wheat growth. The study highlighted that biochar application can minimize the negative effects of salinity stress on wheat. Specifically, the types and dosages of biochar have to be optimized for different salinity levels under field conditions.
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Carvão Vegetal , Clorofila , Germinação , Potássio , Estresse Salino , Sódio , Triticum , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Triticum/efeitos dos fármacos , Triticum/fisiologia , Germinação/efeitos dos fármacos , Carvão Vegetal/farmacologia , Clorofila/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Sementes/metabolismo , Solo/química , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/efeitos dos fármacos , Grão Comestível/metabolismo , Paquistão , SalinidadeRESUMO
Biochar (BC) is an organic compound formed by the pyrolysis of organic wastes. Application of BCs as soil amendments has many benefits including carbon sequestration, enhanced soil fertility and sustainable agriculture production. In the present study, we acidified the different BCs prepared from rice straw, rice husk, wheat straw, cotton stalk, poultry manure, sugarcane press mud and vegetable waste; following which, we applied them in a series of pot experiments. Comparisons were made between acidified and non- acidified BCs for their effects on seed germination, soil properties (EC, pH) nutrient contents (P, K, Na) and organic matter. The treatments comprised of a control, and all above-described BCs (acidified as well as non-acidified) applied to soil at the rate of 1% (w/w). The maize crop was selected as a test crop. The results showed that acidified poultry manure BC significantly improved germination percentage, shoot length, and biomass of maize seedlings as compared to other BCs and their respective control plants. However, acidified BCs caused a significant decrease in nutrient contents (P, K, Na) of soil,maize seedlings, and the soil organic matter contents as compared to non- acidified BCs. But when compared with control treatments, all BCs treatments (acidified and non-acidified) delivered higher levels of nutrients and organic matter contents. It was concluded that none of the BCs (acidified and non-acidified) had caused negative effect on soil conditions and growth of maize. In addition, the acidification of BC prior to its application to alkaline soils might had altered soil chemistry and delivered better maize growth. Moving forward, more research is needed to understand the long-term effects of modified BCs on nutrient dynamics in different soils. In addition, the possible effects of BC application timings, application rates, particle size, and crop species have to be evaluated systemtically.
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Carvão Vegetal , Germinação , Solo , Zea mays , Zea mays/crescimento & desenvolvimento , Zea mays/efeitos dos fármacos , Zea mays/metabolismo , Carvão Vegetal/química , Carvão Vegetal/farmacologia , Solo/química , Germinação/efeitos dos fármacos , Nutrientes/metabolismo , Esterco , Agricultura/métodos , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacosRESUMO
Since obstructive sleep apnea (OSA) affects various parts of the body, there has been little interest about the effect of OSA on voice. The objective of this study was to evaluate the risk of benign vocal fold lesions (BVFL) in OSA patients. This study used data from the National Health Insurance Service (NHIS) database. The study group was defined as the group diagnosed with OSA between 2008 and 2011. Non-OSA groups were selected based on propensity score (PS) matching. Incidence of BVFL among participants during the follow-up was analyzed. Cox proportional hazard regression analyses were performed to evaluate the association between OSA and incident BVFL. The HR value of the OSA group calculated by considering 8 variables indicates that the risk of developing BVFL is 79% higher than that of the control group. Further, among OSA patients, patients with a history of OP had a 35% lower risk of developing BVFL. The relationships between BVFL and 7 individual variables considered were as follows: For age, HR for the 40 to 59 years group was 1.20 (95%CI, 1.09-1.32). For sex, the HR in the female group was 1.22 (95%CI, 1.10-1.35). For residential areas, the HR values for "Seoul" 1.39 (95%CI, 1.23-1.59). In the high economic status group, the HR was 1.10 (95%CI, 1.01-1.21). This observational study indicated that OSA is associated with an increased incidence of BVFL. The incidence of BVFL increased with older age, female sex, and high SES.
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Apneia Obstrutiva do Sono , Prega Vocal , Humanos , Masculino , Feminino , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/complicações , Pessoa de Meia-Idade , Adulto , Seguimentos , Prega Vocal/fisiopatologia , Incidência , Fatores de Risco , República da Coreia/epidemiologia , Idoso , Modelos de Riscos Proporcionais , Doenças da Laringe/epidemiologia , Doenças da Laringe/etiologia , Pontuação de Propensão , Fatores Sexuais , Fatores EtáriosRESUMO
OBJECTIVE: The purpose of this article was to investigate the value of combined MRI, enhanced CT and 18F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer. METHODS: Ninety-five ovarian cancer patients were selected as the study subjects, all of them underwent surgical treatment, and MRI, enhanced CT and 18F-FDG PET/CT were performed on all of them in the postoperative follow-up, and the pathological results after the second operation were used as the diagnostic "gold standard". The diagnostic value (sensitivity, specificity, accuracy, negative predictive value and positive predictive value) of the three examination methods alone or in combination for the diagnosis of postoperative recurrence and metastasis of ovarian cancer was compared, and the detection rate was calculated when the lesion was the unit of study, so as to compare the efficacy of the three methods in the diagnosis of postoperative recurrent metastatic lesions of ovarian cancer. RESULTS: The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the combined group were higher than those of MRI and enhanced CT for recurrence and metastasis of ovarian cancer after surgery, and the specificity, accuracy and positive predictive value of the combined group were higher than those of the 18F-FDG PET/CT group, and those of the 18F-FDG PET/CT group were higher than those of the enhanced CT group (all P < 0.05). When the postoperative recurrent metastatic lesions of ovarian cancer were used as the study unit, the detection rate of lesions in the combined group was higher than that of the three examinations detected individually, and the detection rate of lesions in 18F-FDG PET/CT was higher than that of enhanced CT and MRI (P < 0.05). CONCLUSION: The combination of MRI, enhanced CT and 18F-FDG PET/CT can accurately diagnose recurrence and metastasis of ovarian cancer after surgery, detect recurrent metastatic lesions as early as possible, and improve patients' prognosis.
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Antibiotic residue stands as a significant ongoing environmental issue, with aquaculture being a major source of annual antibiotic discharge into the ocean. Nevertheless, there is still an incomplete evaluation of antibiotic residues in the Beibu Gulf, an area encompassed by two prominent aquaculture nations, China and Vietnam. The present systematic review and meta-analysis was conducted to examine the presence antibiotic residues in the Beibu Gulf based on published studies. Data were obtained through eight databases up to December 19th, 2023, and were updated on April 15th, 2024. The pooled concentration of antibiotic residues in seawater was 5.90 (ng/L), ranging from 5.73 to 6.06 (ng/L), and was 8.03 (ng/g), ranging from 7.77 to 8.28 (ng/g) in sediments. Fluoroquinolones, tetracyclines, and macrolides were identified as the main antibiotics found in both seawater and sediment samples. The Beibu Gulf showed higher antibiotic levels in its western and northeastern areas. Additionally, the nearshore mangrove areas displayed the highest prevalence of antibiotic residues. It is strongly advised to conduct regular long-term monitoring of antibiotic residues in the Beibu Gulf. Collaborative surveys covering the entire Beibu Gulf involving China and Vietnam are recommended.
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Antibacterianos , Monitoramento Ambiental , Água do Mar , Poluentes Químicos da Água , Antibacterianos/análise , Água do Mar/química , Poluentes Químicos da Água/análise , China , Vietnã , AquiculturaRESUMO
BACKGROUND: The randomized, open-label, phase III LYNK-003 study assessed the efficacy of first-line maintenance olaparib, alone or in combination with bevacizumab, versus bevacizumab plus a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer (mCRC). We present results of the prespecified interim futility analysis. METHODS: Eligible participants were ≥18 years of age with unresectable or mCRC that had not progressed after induction with first-line bevacizumab plus 5-fluorouracil plus oxaliplatin plus leucovorin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Participants were randomly assigned 1:1:1 to olaparib plus bevacizumab, olaparib alone, or bevacizumab plus a fluoropyrimidine (5-fluorouracil or capecitabine). The primary end point was progression-free survival (PFS) per RECIST v1.1 by central review. RESULTS: Between August 2020 and May 2022, 309 participants were assigned to olaparib plus bevacizumab (n = 104), olaparib (n = 107), or bevacizumab plus fluoropyrimidine (n = 98). At interim analysis, with a median follow-up of 7.6 months (range 0.1-19.7 months), the median PFS was 3.7 months (95% CI 2.8-5.3) with olaparib plus bevacizumab (HR 1.52; 95% CI 1.02-2.27; P = 0.982) and 3.5 months (95% CI 2.0-3.7) with olaparib (HR 2.11; 95% CI 1.39-3.18; P = 0.999) versus 5.6 months (95% CI 3.8-5.9) with bevacizumab plus fluoropyrimidine. Treatment-related adverse events occurred in 64 (62%), 52 (50%), and 57 (59%) participants, respectively. There were no treatment-related deaths. CONCLUSION: The LYNK-003 study was stopped prematurely as criteria for futility were met. Maintenance olaparib with or without bevacizumab did not demonstrate clinical efficacy compared with bevacizumab plus a fluoropyrimidine. GOV REGISTRATION: NCT04456699.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Fluoruracila , Ftalazinas , Piperazinas , Humanos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Ftalazinas/administração & dosagem , Ftalazinas/efeitos adversos , Ftalazinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Adulto , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Quimioterapia de Manutenção/métodos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Idoso de 80 Anos ou mais , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/efeitos adversos , Intervalo Livre de ProgressãoRESUMO
To investigate the effect of retinoids, such as retinol (ROL), retinal (RAL), and retinyl palmitate (RP), on epidermal integrity, skin deposition, and bioconversion to retinoic acid (RA). 3-D human skin equivalent model (EpiDermFT™) was used. Epidermal cellular integrity measured by TEER values was significantly higher for a topical treatment of ROL and RAL than RP (p < 0.05). The skin deposition (µM) of ROL and RAL was approximately 269.54 ± 73.94 and 211.35 ± 20.96, respectively, greater than that of RP (63.70 ± 37.97) over 2 h incubation. Spectral changes were revealed that the CO maximum absorbance occurred between 1600â¼1800 cm-1 and was greater from ROL than that from RAL and RP, indicating conjugation of R-OH to R-CHO or R-COOH could strongly occur after ROL treatment. Subsequently, a metabolite from the bioconversion of ROL and RAL was identified as RA, which has a product ion of m/z 283.06, by using liquid a chromatography-mass spectrometry (LC-MS) - total ion chromatogram (TIC). The amount of bioconversion from ROL and RAL to RA in artificial skin was 0.68 ± 0.13 and 0.70 ± 0.10 µM at 2 h and 0.60 ± 0.04 and 0.57 ± 0.06 µM at 24 h, respectively. RA was not detected in the skin and the receiver compartment after RP treatment. ROL could be a useful dermatological ingredient to maintain epidermal integrity more effectively, more stably deposit on the skin, and more steadily metabolize to RA than other retinoids such as RAL and RP.
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Retinaldeído , Retinoides , Pele , Tretinoína , Humanos , Tretinoína/metabolismo , Pele/metabolismo , Retinoides/metabolismo , Retinaldeído/metabolismo , Cinética , Ésteres de Retinil/metabolismo , Vitamina A/análogos & derivados , Vitamina A/metabolismo , Diterpenos/química , Diterpenos/farmacocinética , Espectrometria de Massas , Modelos Biológicos , Epiderme/metabolismo , Absorção CutâneaRESUMO
Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.
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Asma , Pneumonia , Deficiência de Vitamina D , Camundongos , Animais , Humanos , Vitamina D/farmacologia , Interleucina-2 , Inflamação , Células Th2 , Deficiência de Vitamina D/metabolismo , VitaminasRESUMO
INTRODUCTION: Among youth with type 1 diabetes (T1D), longitudinal poor glycemic control is associated with adverse socioeconomic conditions at the neighborhood level. Child Opportunity Index (COI), which encompasses measures of education, health, environment, social, and economic factors, is associated with obesity in youth but has not been evaluated in youth with new-onset T1D or type 2 diabetes (T2D). We hypothesized that lower COI would be associated with adverse clinical outcomes at diabetes diagnosis, and due to differing risk factors and pathophysiology, that youth with new-onset T2D would have lower COI than youth with T1D. RESEARCH DESIGN AND METHODS: Retrospective cohort of youth with new-onset diabetes admitted to a large academic pediatric hospital. COI was compared by diabetes type using t-tests and Χ2 tests. Multivariable linear and logistic regression analyses were used to evaluate associations between COI and clinical characteristics, stratified by diabetes type and adjusted for age and sex. RESULTS: The cohort (n=484) differed in race and age by diabetes type (T1D: n=389; 10.0% black, 81.2% white; age 9.6±0.2 years; T2D: n=95; 44.2% black, 48.4% white; age 14.8±0.3 years). Youth with T2D had lower COI (p<0.001). Low COI was associated with diabetic ketoacidosis in T1D and T2D. Black youth with low COI had the highest hemoglobin A1c among youth with T2D and the highest obesity prevalence among youth with T1D. CONCLUSIONS: COI is associated with differing characteristics at diagnosis in youth-onset T1D and T2D but is worse among youth with T2D overall. These findings underscore the need to address socioeconomic adversity when designing interventions to reduce T2D risk and to improve outcomes at diabetes diagnosis in youth.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Criança , Humanos , Adolescente , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Obesidade/complicaçõesRESUMO
Prior studies have explored the links between congenital anomalies and assisted reproduction techniques, among other factors. However, it remains unclear whether a particular technique harbors an inherent risk of major congenital anomalies, either cumulatively or in an organ-specific manner. A meta-analysis was conducted using relevant studies from inception to February 2023 using six databases and two appropriate registers. Sources of heterogeneity were explored using sub-group analysis, using study weight, risk of bias and geographical location of original studies. Neonates conceived through assisted reproduction appear to have a higher risk of major congenital anomalies compared to naturally conceived neonates, OR 0.67 [95% CI 0.59, 0.76], I2 = 97%, p < 0.00001, with neonates conceived through intracytoplasmic sperm injection (ICSI) at a 9% higher chance of being affected in comparison to neonates conceived through in vitro fertilization (IVF). The increase in cardiac, gastrointestinal (GI), and neurological congenital anomalies appears to be independent of the assisted reproduction technique, while urogenital and musculoskeletal (MSK) anomalies were found to be increased in ICSI compared with IVF, OR 0.83 [95% CI 0.69, 0.98]; p = 0.03, I2 = 0%, and OR 0.65 [95% CI 0.49, 0.85]; p = 0.002, I2 = 80%, respectively. Neonates conceived using assisted reproduction techniques appear to be at higher risk of major congenital anomalies, with a higher risk attributable to conception using ICSI. The increase in cardiac, neurological, and GI congenital anomalies does not appear to be technique-specific, while the opposite held true for urogenital and MSK anomalies.
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Anormalidades Congênitas , Técnicas de Reprodução Assistida , Humanos , Anormalidades Congênitas/epidemiologia , Técnicas de Reprodução Assistida/efeitos adversos , Recém-Nascido , Feminino , Gravidez , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Injeções de Esperma Intracitoplásmicas/métodos , Fertilização in vitro/métodosRESUMO
BACKGROUND: Recent developments in addressing dental aesthetic concerns, encompassing issues like teeth discoloration and halitosis, underscore the demand for safer alternative solutions. PURPOSE: This study aims to confirm the effects of lactic acid bacteria (LAB) from kimchi on artificial teeth bleaching and their potential impact in terms of preventing halitosis-related bacteria. MATERIALS AND METHODS: To evaluate the antimicrobial effects against oral pathogens, disc diffusion tests and broth microdilution methods were used. Additionally, crystal violet analysis was performed to confirm the biofilm inhibition effect. The bleaching effects on stained artificial teeth were analyzed using the CIEDE2000 colorimetric method. Statistical analyses were performed using GraphPad Prism 9 with one-way and two-way ANOVA, with the significance level set at α < 0.05. RESULTS: The strain THK-30, isolated from kimchi, exhibited antibacterial activity against Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum, and was identified as Pediococcus inopinatus. Moreover, THK-30 showed a synergistic antibacterial effect against Gram-negative oral pathogens with 8% sodium hexametaphosphate (SHMP). In the stained artificial teeth bleaching test and artificial teeth biofilm inhibition test, the cell-free supernatant of THK-30 displayed significant teeth bleaching effects and caused the inhibition of biofilm formation, both independently and in combination with SHMP 8%. CONCLUSIONS: This study has demonstrated the potential applicability of LAB in teeth discoloration and halitosis. These findings are poised to provide a foundation for the development of research pertaining to the control of oral bacteria.