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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is classified under fibrotic interstitial pneumonia, characterized by a chronic and progressive course. The predominant clinical features of IPF include dyspnea and pulmonary dysfunction. AIM: To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients. METHODS: A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023. These patients were divided into two groups: control group (n = 53) and observation group (n = 60). In the control group, patients received routine therapy in combination with methylprednisolone tablets, while those in the observation group received routine therapy together with pirfenidone. After applying these distinct treatment approaches to the two groups, we assessed several parameters, including the overall effectiveness of clinical therapy, the occurrence of adverse reactions (e.g., nausea, vomiting, and anorexia), symptom severity scores, pulmonary function index levels, inflammatory marker levels, and the 6-min walk distance before and after treatment in both groups. RESULTS: The observation group exhibited significantly higher rates than the control group after therapy, with a clear distinction (P < 0.05). After treatment, the observation group experienced significantly fewer adverse reactions than the control group, with a noticeable difference (P < 0.05). When analyzing the symptom severity scores between the two groups of patients after treatment, the observation group had significantly lower scores than the control group, with a distinct difference (P < 0.05). When comparing the pulmonary function index levels between the two groups of patients after therapy, the observation group displayed significantly higher levels than the control group, with a noticeable difference (P < 0.05). Evaluating the inflammatory marker data (C-reactive protein, interleukin-2 [IL-2], and IL-8) between the two groups of patients after therapy, the observation group exhibited significantly lower levels than the control group, with significant disparities (P < 0.05). Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group, with a marked difference (P < 0.05). CONCLUSION: Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function, elevate inflammatory factor levels, and increase the distance covered in the 6-min walk test. This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.
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BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.
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Criopreservação , Transferência Embrionária , Placenta , Criopreservação/métodos , Feminino , Gravidez , Animais , Camundongos , Transferência Embrionária/métodos , Placenta/metabolismo , Embrião de Mamíferos , Implantação do Embrião/genética , Desenvolvimento Fetal/genética , Blastocisto/metabolismoRESUMO
BACKGROUND: Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. METHODS: Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. RESULTS: Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. CONCLUSIONS: Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Diabetes Gestacional , Hiperglicemia , Músculo Esquelético , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais , Animais , Feminino , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Gravidez , Camundongos , Masculino , Músculo Esquelético/metabolismo , Diabetes Gestacional/metabolismo , Hiperglicemia/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Mitocôndrias/metabolismo , Glicemia/metabolismoRESUMO
We isolated a polypeptide PNP2 from Corn Cervi Pantotrichum and investigated its effect and mechanism on cognitive impairment in Alzheimer's disease (AD) mice. Morris water maze was used to assess the degree of cognitive impairment in mice. Histopathological changes were detected by H&E staining; the expressions of inflammatory cytokines were assayed by ELISA. Western blotting was employed to detect the protein expressions. PNP2 could improve cognitive impairment, central inflammatory response, and NLRP3 signaling in AD mice. In vitro experiments revealed that PNP2 could suppress the inflammatory response of microglial cells and reduce the activation of NLRP3 in microglial cells, while MCC950 could antagonize the effects of PNP2. Polypeptide component PNP2 in Corn Cervi Pantotrichum can ameliorate central nervous inflammation and cognitive impairment in AD mice by suppressing NLRP3 signaling.
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OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.
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Adenoma , Colonoscopia , Neoplasias Colorretais , Imagem de Banda Estreita , Humanos , Masculino , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico , Feminino , Pessoa de Meia-Idade , Adenoma/diagnóstico por imagem , Adenoma/diagnóstico , Imagem de Banda Estreita/métodos , Colonoscopia/métodos , Idoso , Método Simples-Cego , Luz , AdultoRESUMO
Development of high-performance cutting tool materials is one of the critical parameters enhancing the surface finishing of high-speed machined products. Ti(C,N)-based cermets reinforced with and without different contents of silicon nitride were designed and evaluated to satisfy the requirements. In fact, the effect of silicon nitride addition to Ti(C,N)-based cermet remains unclear. The purpose of this study is to investigate the influence of Si3N4 additive on microstructure, mechanical properties, and thermal stability of Ti(C,N)-based cermet cutting tools. In the present work, α-Si3N4 "grade SN-E10" was utilized with various fractions up to 6 wt.% in the designed cermets. A two-step reactive sintering process under vacuum was carried out for the green compact of Ti(C,N)-based cermet samples. The samples with 4 wt.% Si3N4 have an apparent solid density of about 6.75 g/cm3 (relative density of about 98 %); however, the cermet samples with 2 wt.% Si3N4 exhibit a superior fracture toughness of 10.82 MPa.m1/2 and a traverse rupture strength of 1425.8 MPa. With an increase in the contents of Si3N4, the Vickers hardness and fracture toughness of Ti(C,N)-based cermets have an inverse behavior trend. The influence of Si3N4 addition on thermal stability is clarified to better understand the relationship between thermal stability and mechanical properties of Ti(C,N)-based cermets.
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Cholangiocarcinoma (CCA), a rare yet notably aggressive cancer, has experienced a surge in incidence in recent years. Presently, surgical resection remains the most effective curative strategy for CCA. Nevertheless, a majority of patients with CCA are ineligible for surgical removal at the time of diagnosis. For advanced stages of CCA, the combination of gemcitabine and cisplatin is established as the standard chemotherapy regimen. Despite this, treatment efficacy is often hindered by the development of resistance. In recent times, immune checkpoint inhibitors, particularly those that block programmed death 1 and its ligand (PD1/PD-L1), have emerged as promising strategies against a variety of cancers and are being increasingly integrated into the therapeutic landscape of CCA. A growing body of research supports that the use of PD1/PD-L1 monoclonal antibodies in conjunction with chemotherapy may significantly improve patient outcomes. This article seeks to meticulously review the latest studies on PD1/PD-L1 involvement in CCA, delving into their expression profiles, prognostic significance, contribution to oncogenic processes, and their potential clinical utility.
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Antígeno B7-H1 , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Inibidores de Checkpoint Imunológico , Imunoterapia , Receptor de Morte Celular Programada 1 , Colangiocarcinoma/terapia , Colangiocarcinoma/imunologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Humanos , Antígeno B7-H1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , AnimaisRESUMO
BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.
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This study aimed to evaluate the safety and efficiency of hybrid endoscopic submucosal dissection (H-ESD) using a newly developed ALL IN ONE (AIO) snare. This was a matched control study in a porcine model. Five paired simulated stomach lesions 2-2.5 cm in size were removed by H-ESD using an AIO snare or conventional ESD (C-ESD) using an endoscopic knife. The outcomes of the two procedures were compared, including en-bloc resection rates, procedure times, intraprocedural bleeding volumes, muscular injuries, perforations, thicknesses of the submucosal layer in resected specimens, and stomach defects. All simulated lesions were resected en-bloc. Specimens resected by H-ESD and C-ESD were similar in size (7.68 ± 2.92 vs. 8.42 ± 2.42 cm2; P = 0.676). H-ESD required a significantly shorter procedure time (13.39 ± 3.78 vs. 25.99 ± 4.52 min; P = 0.031) and submucosal dissection time (3.99 ± 1.73 vs. 13.1 ± 4.58 min; P = 0.003) versus C-ESD; H-ESD also yielded a faster dissection speed (241.37 ± 156.84 vs. 68.56 ± 28.53 mm2/min; P = 0.042) and caused fewer intraprocedural bleeding events (0.40 ± 0.55 vs. 3.40 ± 1.95 times/per lesion; P = 0.016) than C-ESD. The thicknesses of the submucosal layer of the resected specimen (1190.98 ± 134.07 vs. 1055.90 ± 151.76 µm; P = 0.174) and the residual submucosal layer of the stomach defect (1607.94 ± 1026.74 vs. 985.98 ± 445.58 µm; P = 0.249) were similar with both procedures. The AIO snare is a safe and effective device for H-ESD and improves the treatment outcomes of gastric lesions by shortening the procedure time.
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Ressecção Endoscópica de Mucosa , Mucosa Gástrica , Animais , Ressecção Endoscópica de Mucosa/métodos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/instrumentação , Suínos , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Duração da Cirurgia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estômago/cirurgia , Modelos AnimaisRESUMO
One patient with rifampin-resistant tuberculosis underwent emergency left pneumonectomy and thoracic gauze packing for hemoptysis due to recurrent hemoptysis after transcatheter arterial embolization. Vital signs were maintained by mechanical ventilation and medication. Tracheotomy and anti-tuberculosis treatment were performed. After half a year of follow-up, the patient's condition was stable.
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AIM: Through network pharmacology, molecular docking, molecular dynamics in combination with experimentation, we explored the mechanism whereby 1-ethoxycarbonyl-beta-carboline (EBC) regulates the M2 polarization of tumor-associated macrophages. METHODS: Network pharmacology was adopted for analyzing the targets and signaling pathways related to the M2 polarization of EBC-macrophages, small molecular-protein docking was employed to analyze the possibility of EBC bonding to related protein, and molecular dynamics was introduced to analyze the binding energy between EBC and HDAC2. The M2 polarization of RAW264.7 macrophages was triggered in vitro by IL-4. After EBC intervention, the expressions of M1/M2 polarization-related cytokines were detected, and the mechanism of EBC action was explored in HDAC2-knockout RAW264.7 macrophages. A tumor-bearing mouse model was established in vitro to find the impact of EBC on tumor-associated M2 macrophages. RESULTS: As revealed by the network pharmacology, molecular docking and molecular dynamics analyses, EBC was associated with 51 proteins, including HDAC2, NF-κB and HDAC4. Molecular docking and dynamics analyses suggested that HDAC2 was the main target of EBC. In vitro experiments discovered that EBC could hinder the M2 polarization of RAW264.7 macrophages, which exerted insignificant effect on the M1-associated cytokines, but could lower the levels of M2-associated cytokines. After knocking out HDAC2, EBC could not further inhibit the M2 polarization of macrophages. At the mouse level, EBC could hinder the tumor growth and the tissue levels of M2 macrophages, whose effect was associated with HDAC2. CONCLUSION: Our study combining multiple methods finds that EBC inhibits the HDAC2-mediated M2 polarization of macrophages, thereby playing an anti-tumor role.
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Farmacologia em Rede , Macrófagos Associados a Tumor , Animais , Camundongos , Simulação de Acoplamento Molecular , Macrófagos Associados a Tumor/metabolismo , Citocinas/metabolismo , Carbolinas/farmacologia , Carbolinas/uso terapêuticoRESUMO
Background: Assisted reproductive technology (ART) has been reported to have negative effects on maternal and neonatal health. Ovulation induction (OI) was reported to be associated with alteration of epigenetic modification of mice embryos, and extinguishing the influence of ovulation induction and in vitro operations on maternal and neonatal health will bring benefits for reducing side effects. The present study aimed to determine whether ovulation induction alone and ART are associated with adverse pregnancy outcomes and whether ART could induce a higher risk than ovulation induction alone. Methods: A total of 51,172 cases with singleton live birth between Jan 2016 and May 2019 at the International Peace Maternal and Child Health Hospital were included in this study. Conception modes documented during registration were classified into natural conception (NC), OI, and ART. Pregnancy outcomes of the three groups with balanced baseline characteristics by propensity score matching were compared. The relative risks of maternal and neonatal outcomes were calculated by logistic regression analysis. Results: Compared with natural conception, infertility treatments are associated with gestational diabetes (OI: OR 1.72, 95% CI 1.31-2.27; ART: OR 1.67, 95% CI 1.26-2.20), preeclampsia/eclampsia (OI: OR 1.86, 95% CI 1.03-3.36; ART: OR 2.23, 95% CI 1.26-3.92). Even if gestational diabetes, gestational hypertension, and placental problems were adjusted, infertility treatments are associated with birth before 37 weeks (OI: OR 1.99, 95% CI 1.28-3.12; ART: OR 1.70, 95% CI 1.08-2.69), low birth weight (OI: OR 2.19, 95% CI 1.23-3.91; ART: OR 1.90, 95% CI 1.05-3.45), and SGA (OI: OR 2.42, 95% CI 1.20-4.87; ART: OR 2.56, 95% CI 1.28-5.11). ART but not OI is associated with a higher risk of birth before 34 weeks (OR:3.12, 95% CI 1.21-8.05). By comparing the OI group with the ART group, we only found that ART could induce a higher ratio of placental problems (5.0%, 26/518 vs 2.1%, 11/519, p<0.05). Conclusion: Both OI and ART are associated with adverse pregnancy outcomes. ART induced comparable negative effects with OI on gestational complications, birth weight, and premature birth (<37 weeks). However, ART resulted in a higher risk of placental problems than group NC and OI. The incidence of birth before 34 weeks of gestation in the ART group tends to be higher than in the OI group, but not statistically significant. The side effects of ART may originate from OI.
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Diabetes Gestacional , Infertilidade , Complicações na Gravidez , Humanos , Criança , Gravidez , Feminino , Animais , Camundongos , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Pontuação de Propensão , Placenta , Complicações na Gravidez/epidemiologia , Infertilidade/terapiaRESUMO
Heat stress (HS) causes oxidative damage and abnormal metabolism of muscle, thus impairing the meat quality in broilers. Selenium is an indispensable element for enhancing antioxidant systems. In our previous study, we synthesized a novel type of biogenic selenium nanoparticles synthesized with alginate oligosaccharides (SeNPs-AOS), and found that the particle size of Se is 80 nm and the Se content is 8% in the SeNPs-AOS; and dietary 5 mg/kg SeNPs-AOS has been shown to be effective against HS in broilers. However, whether SeNPs-AOS can mitigate HS-induced the impairment of thigh muscle quality in broilers is still unclear. Therefore, the purpose of this study was to investigate the protective effects of dietary SeNPs-AOS on meat quality, antioxidant capacity, and metabolomics of thigh muscle in broilers under HS. A total of 192 twenty-one-day-old Arbor Acres broilers were randomly divided into 4 groups with 6 replicates per group (8 broilers per replicate) according to a 2 × 2 experimental design: thermoneutral group (TN, broilers raised under 23±1.5°C); TN+SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (broilers raised under 33 ± 2°C for 10 h/d); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). The results showed that HS increased the freezing loss, cooking loss, and malondialdehyde (MDA) content of thigh muscle, whereas decreased the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, as well as downregulated the mRNA expression of SOD2, CAT, GPX3, nuclear factor erythroid 2-related factor 2 (Nrf2), selenoprotein S (SELENOS), solute carrier family 7 member 11 (SLC7A11), GPX4, and ferroportin 1 (Fpn1) of thigh muscle (P < 0.05). Dietary SeNPS-AOS reduced the b* value, elevated the pH0min value and the activities of T-SOD, GSH-Px, glutathione S-transferase (GST) and the mRNA expression levels of GSTT1, GSTA3, GPX1, GPX3, ferritin heavy polypeptide-1 (FTH1), and Fpn1 of thigh muscle in broilers under HS (P < 0.05). Nontargeted metabolomics analysis identified a total of 79 metabolites with significant differences among the four groups, and the differential metabolites were mainly enriched in 8 metabolic pathways including glutathione metabolism and ferroptosis (P < 0.05). In summary, dietary 5 mg/kg SeNPs-AOS (Se content of 8%) could alleviate HS-induced impairment of meat quality by improving the oxidative damage, metabolic disorders and ferroptosis of thigh muscle in broilers challenged with HS. Suggesting that the SeNPs-AOS may be used as a novel nano-modifier for meat quality in broilers raised in thermal environment.
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Ferroptose , Selênio , Animais , Antioxidantes/metabolismo , Selênio/metabolismo , Galinhas/fisiologia , Coxa da Perna , Suplementos Nutricionais/análise , Músculo Esquelético , Resposta ao Choque Térmico , Superóxido Dismutase/metabolismo , Carne/análise , RNA Mensageiro/metabolismo , Ração Animal/análiseRESUMO
AIM: We focused on investigating the role and mechanism of ganodermanontriol (GAN) in regulating the M2 polarization of tumor-associated macrophages in the gastric cancer microenvironment. METHODS: M2 polarization of RAW264.7 macrophages was induced by IL-4 or co-culture with MFC, and the expression levels of M1 macrophage markers (TNF-α, IFN-γ, IL-1ß) and M2 macrophage markers (IL-10, TGF-ß, Arg-1) were detected by enzyme-linked immunosorbed assay (ELISA). The protein expression was assayed by Western-Blotting. For in vitro experiments, a tumor-bearing mouse model was established, with which the CD206 level was detected by histochemistry, and the binding mode between GAN and STAT6 was simulated through molecular dynamics. RESULTS: Both IL-4 and MFC could induce the M2 polarization of macrophages. GAN could inhibit such polarization, which produced unobvious effects on M1 markers, but could suppress the levels of M2 markers. GAN could inhibit the phosphorylated expression of STAT6, and M2 macrophages treated by it had a weakened ability to promote malignant behavior of MFC. According to the results of in vitro experiments, GAN could inhibit tumor growth, suppress the tissue infiltration of CD206 cells, and inhibit the phosphorylated expression of STAT6. CONCLUSION: Our results show that GAN can inhibit the M2 macrophage polarization in gastric cancer microenvironment, whose mechanism of action is associated with the regulation of STAT6 phosphorylation.
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Lanosterol/análogos & derivados , Neoplasias Gástricas , Macrófagos Associados a Tumor , Camundongos , Animais , Neoplasias Gástricas/patologia , Interleucina-4/metabolismo , Macrófagos/metabolismo , Microambiente TumoralRESUMO
INTRODUCTION AND IMPORTANCE: The ectopic thyroid gland is a rare disease in which abnormal migration of the embryonic thyroid germ is thought to be the basis for the formation of the ectopic thyroid gland. CASE PRESENTATION: A 37 year old female sought medical attention due to feeling a sensation of swallowing foreign objects, without any other positive symptoms such as pain or difficulty breathing. Preoperative examination revealed a nodule in the left lobe of the thyroid gland and a nodule behind the left lobe. The patient ultimately underwent non-inflatable endoscopic surgery under the axilla to completely remove the tumor located in the suprasternal fossa. Postoperative pathological examination confirmed ectopic thyroid adenoma. The patient's postoperative thyroid function was normal. CLINICAL DISCUSSION: The diagnosis of ectopic thyroid is difficult due to its highly non-specific histological characteristics and positional changes. However, clinical diagnosis and treatment should not overlook the possibility of ectopic thyroid. On the basis of completely removing the lesion, the transaxillary non-inflatable endoscopic surgery also meets the patient's minimally invasive and aesthetic needs. CONCLUSION: The diagnosis of ectopic thyroid is difficult, and through transaxillary non-inflatable endoscopic surgery, the tumor can be completely removed and the patient's aesthetic needs can be met.
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Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet ß-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.
Assuntos
Hormônio Foliculoestimulante , Ilhotas Pancreáticas , Camundongos , Animais , Humanos , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/metabolismo , Secreção de Insulina , Glucose/farmacologia , Glucose/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Ilhotas Pancreáticas/metabolismo , Transdução de Sinais , Insulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Mamíferos/metabolismoRESUMO
Selenium (Se) is an essential trace element for maintaining health due to its ideal antioxidant properties. We previously prepared a new type of biogenic selenium nanoparticles based on alginate oligosaccharides (SeNPs-AOS), and this study aimed to investigate the protective effects of SeNPs-AOS (Se particle size = 80 nm, Se content = 8%) on organ health in broilers challenged with HS. A total of 192 21-day-old Arbor Acres broilers were randomly divided into four groups according to a 2 × 2 experimental design, including a thermoneutral zone group (TN, raised under 23 ± 1.5 °C); TN + SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (HS, raised under 33 ± 2 °C for 10 h/day); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). There were six replicates in each group (eight broilers per replicate). The results showed that SeNPs-AOS improved the splenic histomorphology, enhanced the activity of catalase (CAT) and glutathione peroxidase (GSH-Px) of the spleen, as well as upregulating the splenic mRNA expression of antioxidant-related genes in broilers under HS. In addition, SeNPs-AOS reversed the pathological changes in bursa caused by HS increased the activity of GST, GSH-Px, and CAT and upregulated the mRNA expression of Nrf2 and antioxidant-related genes in the bursa of heat-stressed broilers. In addition, dietary SeNPs-AOS improved the hepatic damage, increased the activity of GSH-Px in the liver, and upregulated the mRNA expression of antioxidant-related genes while downregulating the Keap1 gene expression of the liver in broilers during HS. Moreover, dietary SeNPs-AOS upregulated the anti-ferroptosis-related genes expression of liver in broilers under HS. In conclusion, dietary SeNPs-AOS could relieve HS-induced oxidative damage to the spleen, bursa of Fabricius and liver in broilers by upregulating the Nrf2-mediated antioxidant gene expression and SeNPs-AOS could also upregulate the expression of hepatic Nrf2-related anti-ferroptosis genes in heat-stressed broilers. These findings are beneficial for the development of new nano-antioxidants in broilers.
RESUMO
COPD causes significant morbidity and mortality worldwide. Epithelial damage is fundamental to disease pathogenesis, although the mechanisms driving disease remain undefined. Published evidence from a COPD cohort (SPIROMICS) and confirmed in a second cohort (COPDgene) demonstrate a polymorphism in Fucosyltransferese-2 (FUT2) is a trans-pQTL for E-cadherin, which is critical in COPD pathogenesis. We found by MALDI-TOF analysis that FUT2 increased terminal fucosylation of E-cadherin. Using atomic force microscopy, we found that FUT2-dependent fucosylation enhanced E-cadherin-E-cadherin bond strength, mediating the improvement in monolayer integrity. Tracheal epithelial cells from Fut2-/- mice have reduced epithelial integrity, which is recovered with reconstitution of Fut2. Overexpression of FUT2 in COPD derived epithelia rescues barrier function. Fut2-/- mice show increased susceptibility in an elastase model of disease developing both emphysema and fibrosis. We propose this is due to the role of FUT2 in proliferation and cell differentiation. Overexpression of FUT2 significantly increased proliferation. Loss of Fut2 results in accumulation of Spc+ cells suggesting a failure of alveolar type 2 cells to undergo transdifferentiation to alveolar type 1. Using a combination of population data, genetically manipulated mouse models, and patient-derived cells, we present a novel mechanism by which post-translational modifications modulate tissue pathology and serve as a proof of concept for the development of a disease-modifying target in COPD.
RESUMO
Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.