RESUMO
Objectives: Sleep is an indispensable part of human health, which can help us to restore physical strength, enhance immunity and maintain nervous system stability. The relationship between sleep quality and cognitive dysfunction is unclear, especially at the community population level. This study aims to explore the association between sleep quality and cognitive dysfunction. Methods: A total of 5,224 community residents were enrolled in this cross-sectional study. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Sleep quality was assessed by the multidimensional sleep questionnaire. Multivariate logistic regression was used to analyze the association between sleep quality and cognitive dysfunction. The adjusted models took into account relevant demographic, clinical, and sleep variables. Results: A total of 3,106 participants were enrolled in this study, of whom 463 (15%) had cognitive dysfunction. Total sleep duration, staying up, sleep latency, number of awakenings, and history of sleep medications were associated with cognitive dysfunction in unadjusted models, and these effects were consistent after adjustment. First, those who slept 6-7.9 h per day (OR = 0.57, 95% CI 0.40 to 0.80, p = 0.001) had a lower risk for cognitive dysfunction compared to those who slept less than 6 h per day. Second, participants who stayed up more than 10 times over the 3 months (OR = 1.90, 95% CI 1.20 to 3.00, p = 0.006) were more likely to suffer cognitive dysfunction than those who never stayed up. Third, we also found that participants with sleep latencies of 16-30 min were less likely to experience cognitive dysfunction than those with sleep latencies of less than 16 min after adjusting confounders (OR = 0.33, 95% CI 0.23 to 0.47, p < 0.001). Fourth, participants who woke up once (OR = 1.65, 95% CI 1.19 to 2.30, p = 0.003) and three or more times (OR = 2.34, 95% CI 1.25 to 4.36, p = 0.008) after falling asleep had a higher risk than those who did not wake up at night. Last, participants taking sleep medication (OR = 2.97, 95% CI 1.19 to 7.45, p = 0.020) were more vulnerable to cognitive dysfunction, relative to participants without taking any medications. Conclusion: Our results suggest that after adjustment for potential confounding variables, poor sleep quality is associated with cognitive dysfunction.
RESUMO
BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are exposed to a higher risk of developing neuroendocrine tumors (NETs). Periampullary neuroendocrine neoplasms (NENs) in NF1 patients primarily affect the duodenum and periampullary region. CASE SUMMARY: A 50-year-old male patient was admitted to our hospital due to progressive skin and scleral yellowing for over 6 months. An abdominal contrast-enhanced computed tomography scan revealed a tumor in the periampullary region, which measured 1.2 cm × 1.4 cm in size and showed a progressive enhancement. Magnetic resonance cholangiopancreatography indicated the dilation of intrahepatic and extrahepatic bile ducts. The patient was diagnosed with an ampullary tumor with the possibility of malignancy. A Whipple procedure was performed. Microscopically, the duodenum tumor was found to invade the mucosa, sphincter, and muscular layer of the duodenal papilla. Histologic hematoxylin and eosin staining confirmed the presence of duodenal G1 NET. Subsequently, a bibliometric analysis was performed to evaluate the state of NEN research. Publications about periampullary NENs showed an annual increase, with most of them focusing on the treatment and diagnosis of NENs. CONCLUSION: This article reported a case of periampullary duodenal NET in a patient with NF1, and a bibliometric analysis was conducted.
RESUMO
INTRODUCTION: Triple-negative breast cancer (TNBC) is the primary cause of breast cancer-induced death in women. Literature has confirmed the benefits of Salidroside (Sal) in treating TNBC. However, the study about potential therapeutic targets and mechanisms of Sal-anchored TNBC remains limited. OBJECTIVE: This study was designed to explore the main targets and potential mechanisms of Sal against TNBC. METHODS: Network pharmacology, bioinformatics, and machine learning algorithm strategies were integrated to examine the role, potential targets, and mechanisms of the Sal act in TNBC. MDA-MB-231 cells and tumor-bearing nude mice were chosen for in vitro and in vivo experimentation. Cell viability and cytotoxicity were determined using CCK-8, LDH test, and Calcein-AM/PI staining. Antioxidant defense, lipid peroxidation, and iron metabolism were explored using glutathione, glutathione peroxidase, malondialdehyde (MDA), C11-BODIPY 581/591 probe, and FerroOrange dye. Glutathione peroxidase 4 (GPX4) or stearoyl-CoA desaturase 1 (SCD1) overexpression or nuclear receptor co-activator 4 (NCOA4) deficiency was performed to demonstrate the mechanism of Sal on TNBC. RESULTS: The prediction results confirmed that 22 ferroptosis-related genes were identified in Sal and TNBC, revealing that the potential mechanism of the Sal act on TNBC was linked with ferroptosis. Besides, these genes were mainly involved in the mTOR, PI3K/AKT, and autophagy signaling pathway by functional enrichment analysis. The in vitro validation results confirmed that Sal inhibited TNBC cell proliferation by modulating ferroptosis via elevation of intracellular Fe2+ and lipid peroxidation. Mechanistically, Sal sensitized TNBC cells to ferroptosis by inhibiting the PI3K/AKT/mTOR axis, thereby suppressing SCD1-mediated lipogenesis of monounsaturated fatty acids to induce lipid peroxidation, additionally facilitating NCOA4-mediated ferritinophagy to increase intracellular Fe2+ content. The GPX4 or SCD1 overexpression or NCOA4 deficiency results further supported our mechanistic studies. In vivo experimentation confirmed that Sal is vital for slowing down tumor growth by inducing ferroptosis. CONCLUSIONS: Overall, this study elucidates TNBC pathogenesis closely linked to ferroptosis and identifies potential biomarkers in TNBC. Meanwhile, the study elucidates that Sal sensitizes TNBC to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy, regulated by PI3K/AKT/mTOR signaling pathways. Our findings provide a theoretical basis for applying Sal to treat TNBC.
RESUMO
BACKGROUND: Secondary reduction mammaplasty poses challenges. OBJECTIVES: This article delves into the reasons and complaints regarding secondary repair following double-ring method and outlines the principle and logic of utilizing vertical incision for repair. METHODS: A retrospective analysis of patients who underwent secondary reduction mammaplasty in our hospital was conducted. The analysis included baseline demographic data, reasons for consultation, surgical records, and postoperative outcomes. RESULTS: Thirty-five patients (70 breasts) underwent secondary reduction mammaplasty. The mean time between the primary reduction mammaplasty and second procedure was 2.99 years (range, 0.5-15years). The mean weights were 210.49g (range, 42-558g) and 207.91g (range, 6-560g) for left and right mastectomies, respectively. Reasons for secondary reduction mammaplasty include poor shape (flat breasts and pseudoptosis), widened incision scar, persistent macromastia, and bilateral asymmetry. CONCLUSIONS: The superior and superomedial vertical techniques are safe, effective, and satisfactory in secondary reduction mammaplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
RESUMO
Background: Recent studies have shown that the triglyceride glucose index (TyG) and cystatin C (CysC) are closely related to cardiovascular disease, but there is limited research on the prognosis of patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). The aim of this study was to explore the predictive value of the combination of the TyG index and CysC in predicting major adverse cardiovascular events (MACEs) in ACS patients who underwent PCI. Methods: This retrospective study included 319 ACS patients who underwent PCI. The clinical endpoint was the occurrence of MACEs, including all-cause mortality, heart failure, non-fatal myocardial infarction, target vessel revascularization, and angina requiring hospitalization. Patients were classified into MACEs (65 cases) and non-MACEs (254 cases) groups. Univariate factor and multivariate analysis were used to identify predictors of MACEs. The receiver operating curve (ROC) of the prediction model of MACEs was determined. Additionally, the net reclassification improvement and integrated discrimination improvement indexes were calculated to further assess the additional predictive value of the risk factors for MACEs. Subgroup and interaction analysis between the TyG index combined with CysC and MACEs were conducted in various subgroups. Patients were stratified according to the optimal cutoff point value of the TyG index and the CysC determined by ROC curve analysis. The Kaplan-Meier analysis method was used to construct a survival curve 1 year after PCI. Results: During a median follow-up period of 14 months, 65 (20.38%) patients had experienced at least one primary endpoint event. Multivariate logistic regression analysis indicated that the TyG index and CysC were independently associated with an increased risk of MACEs after PCI (OR, 2.513, 95% CI 1.451-4.351, P= 0.001; and OR, 4.741, 95% CI 1.344-16.731, P=0.016, respectively). The addition of the TyG index and CysC to the baseline risk model had the strongest incremental effect for predicting MACEs in terms of the C-statistic from 0.789 (95% CI 0.723-0.855, P<0.001) to 0.799 (95% CI 0.733-0.865, P<0.001). Furthermore, Kaplan-Meier analysis demonstrated that a TyG index greater than 9.325 and a CysC value greater than 1.065 mg/ml were significantly associated with an increased risk of MACEs (log-rank, all P < 0.01). Conclusion: The TyG index predicts MACEs after PCI in patients with ASC independent of known cardiovascular risk factors. Adjustment of the CysC by the TyG index further improves the predictive ability for MACEs in patients with ACS undergoing PCI. Thus, both of them are expected to become new prognostic indicators for MACEs in patients with ACS after PCI.
Assuntos
Síndrome Coronariana Aguda , Glicemia , Cistatina C , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Triglicerídeos , Humanos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Feminino , Masculino , Cistatina C/sangue , Estudos Retrospectivos , Prognóstico , Pessoa de Meia-Idade , Triglicerídeos/sangue , Idoso , Glicemia/análise , Glicemia/metabolismo , Biomarcadores/sangue , Fatores de RiscoRESUMO
Objective: To investigate the effects of inhibiting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome on neuronal damage and chronic pro-inflammatory responses during epileptogenesis in a mouse model of pilocarpine-induced status epilepticus (SE). Methods: Mice were randomly allocated into three groups: control, SE, and SE + MCC 950. The expression patterns of M1 and M2 microglial biomarkers in the hippocampus were quantified using Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. Additionally, seizure susceptibility, video-electroencephalography recording, Morris water maze test, and brain immunofluorescence staining were performed to evaluate the epileptic brain 4 weeks post-SE. Results: Within 72 hours post-SE, hippocampal microglia demonstrated a preferential polarization towards the M1 phenotype, a trend that was mitigated by NLRP3 inflammasome inhibition. During epileptogenesis, SE mice treated with NLRP3 inflammasome inhibition exhibited reduced neuronal damage, improved cognitive function, decreased seizure susceptibility, and attenuated chronic pro-inflammatory responses. Conclusion: Inhibition of NLRP3 inflammasome post-SE effectively ameliorates neuronal loss, seizure susceptibility, and cognitive dysfunction during epileptogenesis. This neuroprotective effect may be mediated through the mitigation of chronic pro-inflammatory responses within the epileptic brain.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ovarian cancer ranks the first in the mortality of gynecological tumors. Because there are no obvious symptoms in the early stage of ovarian cancer, most patients are in the advanced stage of the disease at the time of diagnosis. The incidence of ovarian cancer is increasing year by year, and the incidence of ovarian cancer has a trend of younger age. In recent years. Traditional Chinese medicine (TCM) has a significant impact on improving the quality of life of cancer patients, reducing drug toxicity, preventing metastasis and recurrence, enhancing the efficacy of radiotherapy and chemotherapy, and prolonging survival time, so patients have benefited a lot. AIM OF THE STUDY: This review summarizes the mechanisms and molecular pathways through which active ingredients of TCM act in ovarian cancer. It explores the advantages of TCM in treating ovarian cancer. This review provides theoretical support for the use of TCM in the treatment of ovarian cancer, offering new perspectives for its clinical prevention and treatment. MATERIALS AND METHODS: This review conducted a literature search on PubMed, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) for relevant studies on TCM active ingredients in preventing ovarian cancer. The search terms included "ovarian cancer" combined with "Chinese herbal medicine," "Herbal medicine," "Traditional Chinese medicine," and "Active ingredients of Chinese medicine". Based on existing experimental and clinical research, the paper systematically summarized and analyzed the mechanisms of TCM in treating ovarian cancer. RESULTS: Active ingredients of TCM inhibit the occurrence and development of ovarian cancer through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, suppressing tumor cell migration and invasion, inducing tumor cell autophagy, promoting epithelial-mesenchymal transition, and enhancing the efficacy of radiotherapy and chemotherapy drugs. Chinese medicine provides a comprehensive treatment option for ovarian cancer patients, synergizing with radiotherapy and chemotherapy drugs to enhance treatment effectiveness and introduce new hope and possibilities in clinical therapy. CONCLUSIONS: Active ingredients of TCM can inhibit the occurrence and development of ovarian cancer, but further clinical research is needed to support their application.
RESUMO
Polysaccharides with various molecular structures and morphology may influence the aggregation kinetics of nanoplastics. This study used various characterization methods to elucidate the heteroaggregation mechanism of polystyrene nanoplastics (PSNPs) in the presence of polysaccharides (ionic strength (IS) 1-800 mM NaCl and 0.01-60 mM CaCl2). The results showed that under high IS, cellulose (CL) accelerated the heteroaggregation of PSNPs, and the aggregation rate of PSNPs increased by approximately 62.05 %, while amylose (AM) had little effect (10.38 %). Compared with AM (43.2 nm), the morphology of the CL (78.4 nm) gully had improved surface roughness, leading to its decisive role in the heteroaggregation of PSNPs. Quantum chemistry calculations indicated that van der Waals forces of PSNPs-CL systems (-217.28 kJ mol-1) were stronger than those of PSNPs-AM systems (-184.62 kJ mol-1) based on the subtle molecular conformation differences between CL and AM (opposite and same sides of OH groups in CL and AM, respectively). The morphology and molecular conformation of polysaccharides collaboratively controlled the heteroaggregation of PSNPs. Because the morphology of polysaccharides was based on their molecular conformation, the latter is the most critical factor. These findings provide new insights into the effects of PSNPs stability in the environment.
RESUMO
This study aims to explore the potential mechanism of action of Trichosanthis Pericarpium(TP) in improving coronary heart disease(CHD) based on a CHD rat model and metabolomics. The rat model of CHD was built by subcutaneous injection of high-fat diet combined with isoprenaline hydrochloride(ISO). To compare the expression level of lactate dehydrogenase, cardiac troponin â (cTnâ ), creatine kinase-MB(CK-MB), creatine kinase(CK), tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß),interleukin-6(IL-16), hypersensitive C-reactive protein(hs-CRP) in serum and cardiac pathological changes of model animals after administration of TP, LTQ-Orbitrap-MS analysis was combined with principal component analysis. The effect of TP on endogenous metabolites in the feces of CHD rats was studied. In addition, biomarkers were identified using the HMDB database and metabolic pathway enrichment analysis was performed using the MetaboAnalyst online pathway enrichment tool. The content of bile acid was further determined in the feces and serum of different groups of rats. Compared with blank group, the myocardial injury markers(CK,LDH, cTnâ , CK-MB) and inflammatory factors(TNF-α, IL-1ß, IL-6, hs-CRP) in serum of CHD rats were significantly increased.Myocardial injury and inflammatory infiltration in CHD rats were significantly improved by TP extract. The primary bile acid biosynthetic metabolism pathway was enriched by non-targeted metabolome analysis. The levels of total bile acid, primary bile acid,secondary bile acid, and unconjugated bile acids in the feces of CHD rats were significantly lower than those of control rats. Fecal excretion of total bile acid, primary bile acid, and unconjugated bile acid was significantly improved by TP extract. The levels of total bile acid, primary bile acid, secondary bile acid, and unconjugated bile acids in the serum of CHD rats were significantly higher than those of control rats. Circulating blood levels of total bile acids, primary bile acids, secondary bile acids, and unconjugated bile acids were significantly reduced by TP extract. Increasing fecal excretion of bile acid and decreasing the level of bile acid in blood circulation can improve CHD, and maintaining proper bile acid metabolism is one of the mechanisms of TP to improve CHD.
Assuntos
Ácidos e Sais Biliares , Doença das Coronárias , Modelos Animais de Doenças , Ratos Sprague-Dawley , Animais , Ratos , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/metabolismo , Ácidos e Sais Biliares/metabolismo , Masculino , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Interleucina-6/metabolismo , Interleucina-6/genéticaRESUMO
This study investigated the impacts of sulfamethazine (SMZ) and oxytetracycline (OTC) antibiotics on the marine microalgae Nitzschia closterium and its release of volatile halocarbons (VHCs), which contribute to ozone depletion and climate change. High concentrations of SMZ and OTC suppressed cell density, reduced chlorophyll a content, and hindered Fv/Fm elevation in N. closterium, indicating its growth was inhibited. The exposure of N. closterium to antibiotics led to increased reactive oxygen species (ROS), reduced soluble protein content, and heightened catalase (CAT) activity, indicative of increased oxidative stress. This stress increased the release of three VHCs (CHBrCl2, CHBr2Cl, and CHBr3). Ship-borne experiments showed that high phytoplankton biomass was linked to high VHC release. Notably, the production and release of VHCs were significantly higher in the high-concentration antibiotic group (100 µg/L) than the low-concentration group (0.1 µg/L). These findings suggested that antibiotics induce excess ROS in algal cells, stimulating VHC production and release.
RESUMO
Pesticide application can result in residue drift deposition in off-field areas, which can be harmful to non-target organisms inhabiting adjacent off-field environments. In order to comprehend the impact of pesticide drift deposition on off-field non-target organisms, an integrated modeling approach was incorporated into the life cycle analysis perspective for the assessment of their exposure to pesticide residues and the characterization of their human toxicity and ecotoxicity potentials. The modeling assumption comprises four modeling scenarios: children & cattle & sensitive crops (tomatoes) based on exposure assessment, and the continent-scale human health toxicity & ecotoxicity under a life cycle analysis perspective. The simulation results for the nearby off-field exposure scenario revealed that pesticide dissipation kinetics in environments and drift deposition type were two important factors influencing non-target organisms' exposure to pesticide residues deposited in off-field environments. The continental scenario simulated via USEtox revealed that considering off-field drift deposition resulted in lower simulated human toxicity potentials of pesticides when compared to simulation results that did not consider drift deposition, given that pesticide residues remaining within the treated field contributed the most to overall human exposure. Taking drift deposition into account, on the other hand, could result in higher or lower simulated ecotoxicity potentials of pesticides than not taking drift deposition in off-field areas into account, depending on the physicochemical properties of pesticides. The proposed modeling approach, which is adaptable to drift deposition types and chemical species, can aid in investigating the off-field impacts of pesticide residues. Future research will incorporate spatiotemporal factors to characterize region-specific drift deposition functions and pesticide fate in off-field environments to conduct site-specific impact assessments.
RESUMO
BACKGROUND: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. OBJECTIVES: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. METHODS: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. RESULTS: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. CONCLUSIONS: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.
Assuntos
Tecido Adiposo , Camundongos Nus , Mitocôndrias , Animais , Camundongos , Mitocôndrias/metabolismo , Humanos , Tecido Adiposo/metabolismo , Sobrevivência de Enxerto/fisiologia , FemininoRESUMO
This Mendelian randomization (MR) study aims to explore the relationship between gut microbiota and the occurrence of cholelithiasis, as well as the impact of cholecystectomy on the gut microbiota. This study leverages data on exposures and outcomes from the GWAS database, employing the inverse variance weighting (IVW) method to obtain primary causal estimates. Heterogeneity is assessed using Cochran Q and Rücker Q tests through both IVW and MR-Egger methods. Pleiotropy is evaluated using the Egger-intercept method, while sensitivity analyses are conducted via leave-one-out tests. Additionally, the F-statistic is calculated to assess the presence of weak instrument bias. Finally, the MR-PRESSO method is utilized to validate the findings concerning the relationship between gut microbiota and the incidence of cholelithiasis, as well as the impact of cholecystectomy on gut microbiota composition. The genera Butyricicoccus (ID: 2055), Solibacillus (ID: 11348), Anaerotruncus (ID: 2054), Allisonella (ID: 2174), and Howardella (ID: 2000) have been found to decrease the genetically predicted probability of cholelithiasis. Reverse MR analysis indicates that the occurrence of cholelithiasis reduces the levels of gut microbiota such as Blautia (ID: 1992), Anaerofilum (ID: 2053), Howardella (ID: 2000), Butyricicoccus (ID: 2055), Solibacillus (ID: 11348), Allisonella (ID: 2174), Anaerotruncus (ID: 2054), and Firmicutes (ID: 1672). Additionally, the genera Odoribacter (ID: 952), and Holdemanella (ID: 2157) increase the genetically predicted risk of cholecystectomy. Reverse MR results show that post-cholecystectomy reduces the levels of gut microbiota such as Blautia (ID: 1992), Butyricicoccus (ID: 2055), Alistipes (ID: 11296), Oxalobacteraceae (ID: 2966), and Ruminococcaceae UCG010 (ID: 11367). Conversely, post-cholecystectomy increases the levels of gut microbiota such as Odoribacter (ID: 952), an unknown family (ID: 1000001214), an unknown genus (ID: 1000001215), Aeromonadales (ID: 1591), Holdemanella (ID: 2157), Phascolarctobacteria (ID: 1589), and Eggerthella (ID: 819). All study results show no horizontal pleiotropy, and the MR-PRESSO validation results are consistent with the MR analysis findings. This study elucidates the relationship between gut microbiota and the occurrence of cholelithiasis, as well as the impact of cholecystectomy on the gut microbiota. These findings have clinical significance for diagnosing disease onset and understanding digestive function changes following gallbladder removal, providing theoretical support for further investigation into the molecular mechanisms underlying cholelithiasis.
Assuntos
Colecistectomia , Colelitíase , Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Microbioma Gastrointestinal/genética , Humanos , Colelitíase/microbiologia , Colelitíase/genética , Variação Genética , Estudo de Associação Genômica AmplaRESUMO
The focus of current studies was to fabricate dose flexible printlets of dapsone (DDS) for pediatric patients by selective laser sintering (SLS) 3D printing method, and evaluate its physicochemical, patient in-use stability, and pharmacokinetic attributes. Eight formulations were fabricated using Kollicoat® IR, Eudragit® L-100-55 and StarCap®as excipients and evaluated for hardness, disintegration, dissolution, amorphous phase by differential scanning calorimetry and X-ray powder diffraction, in-use stability at 30 oC/75% RH for a month, and pharmacokinetic study in Sprague Dawley rats. The hardness, and disintegration of the printlets varied from 2.6±1.0 (F4) to 7.7±0.9 (F3) N and 2.0±0.4 (F2) to 7.6±0.6 (F3) sec, respectively. The drug was partially present as an amorphous form in the printlets. The drug was completely (>85%) dissolved in 20 min. No change in drug form or dissolution extent was observed after storage at in use condition. Pharmacokinetic profiles of both formulations (tablets and printlets) were almost superimposable with no statistical difference in pharmacokinetic parameters (Tmax, Cmax, and AUC0-¥)between formulations (p>0.05). Values of EC50 (half maximal effective concentration) and EC90 (maximal concentration inducing 90% maximal response) were 0.50±0.15 and 1.32±0.26 mM, 0.41±0.06 and 1.11±0.21, and 0.42±0.13 and 1.36±0.19 mM for DDS, printlet and tablet formulations, respectively, and differences were statistically insignificant (p>0.05). In conclusion, tablet and printlet formulations are expected to be clinical similar, thus clinically interchangeable.
Assuntos
Antimaláricos , Dapsona , Impressão Tridimensional , Ratos Sprague-Dawley , Antimaláricos/farmacocinética , Antimaláricos/administração & dosagem , Animais , Ratos , Dapsona/farmacocinética , Dapsona/administração & dosagem , Dapsona/química , Química Farmacêutica/métodos , Solubilidade , Masculino , Excipientes/química , Humanos , Comprimidos/farmacocinética , Estabilidade de Medicamentos , Criança , Varredura Diferencial de Calorimetria/métodos , Composição de Medicamentos/métodos , Difração de Raios X/métodosRESUMO
6:2 Chlorinated polyfluorinated ether sulfonate, commonly known as F-53B, is widely used as a mist suppressant in various industries and is frequently detected in the environment. Despite its prevalent presence, the adverse effects of F-53B are not well understood and require future investigation. This study utilized zebrafish embryos and adults to examine the toxic effects of F-53B. Our findings revealed that F-53B impaired gill structure and increased erythrocyte numbers in adult zebrafish. Notably, F-53B demonstrated a higher sensitivity for inducing mortality (LC50 at 96 h) in adult zebrafish compared to embryos. Additionally, F-53B disrupted the expression of critical steroidogenic genes and hindered sex hormone production, which negatively affecting egg production. In conclusion, this study underscores the detrimental impact of F-53B on gill structure and reproductive toxicity in zebrafish, providing valuable insights into its overall toxicity.
Assuntos
Embrião não Mamífero , Brânquias , Reprodução , Poluentes Químicos da Água , Peixe-Zebra , Animais , Brânquias/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Reprodução/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Feminino , Masculino , Dose Letal MedianaRESUMO
This study investigated the toxicological effects and mechanisms of cadmium (Cd) (5 and 50 µg/L) and selenium (Se) (3 and 30 µg/L) at environmentally relevant concentrations on the gills and digestive glands of clams Ruditapes philippinarum. Results indicated that Cd and Se could tissue-specifically impact osmoregulation, energy metabolism, and synaptic transmission in the gills and digestive glands of clams. After exposure to 50 µg/L Cd, the digestive glands of clams up-regulated the expression of methionine-gamma-lyase and metallothionein for detoxification. Clam digestive glands exposed to 3 µg/L Se up-regulated the expression of catalase and glutathione peroxidase to alleviate oxidative stress, and down-regulated the expression of selenide-water dikinase to reduce the conversion of inorganic Se. Additionally, the interaction mode between Cd and Se largely depended on their molar ratio, with a ratio of 11.71 (50 µg/L Cd + 3 µg/L Se) demonstrated to be particularly harmful, as manifested by significantly more lesions, oxidative stress, and detoxification demand in clams than those exposed to Cd or Se alone. Collectively, this study revealed the complex interaction patterns and mechanisms of Cd and Se on clams, providing a reference for exploring their single and combined toxicity.
Assuntos
Bivalves , Cádmio , Estresse Oxidativo , Selênio , Poluentes Químicos da Água , Animais , Cádmio/toxicidade , Bivalves/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Selênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Inativação Metabólica , Estresse Fisiológico/efeitos dos fármacosRESUMO
Ruminal microbes catabolise feed carbohydrates mainly into SCFA, methane (CH4), and carbon dioxide (CO2), with predictable relationships between fermentation end products and net microbial increase. We used a closed in vitro batch culture system, incubating grass and maize silages, and measured total gas production at 8 and 24 h, as well as the truly degraded substrate, the net production of SCFA, CH4, and microbial biomass at 24 h, and investigated the impact of silage type and inoculum microbial mass on fermentation direction. Net microbial yield was negatively correlated with total gas at 8 h (P < 0â¢001), but not at 24 h (P = 0â¢052), and negatively correlated with CH4 production (P < 0â¢001). Higher initial inoculum microbial mass was related to a lower net microbial yield (P < 0â¢001) but a higher CH4 production (P < 0â¢001). A significant difference between grass silage and maize silage was detected within the context of these relationships (P < 0â¢050). The metabolic hydrogen (2H) recovery was 102.8 ± 12.3 % for grass silages and 118.8 ± 13.3% for maize silages. Overall, grass silages favoured more substrate conversion to microbial biomass and less to fermentation end products than maize silage. Lower inoculum microbial mass facilitated more microbial growth and, because of the 2H sink by microbial synthesis, decreased CH4 production.
Assuntos
Biomassa , Fermentação , Metano , Poaceae , Silagem , Zea mays , Metano/metabolismo , Silagem/microbiologia , Zea mays/microbiologia , Animais , Rúmen/microbiologia , Rúmen/metabolismo , Dióxido de Carbono/metabolismo , Ácidos Graxos Voláteis/metabolismo , Hidrogênio/metabolismoRESUMO
The testis evolves a highly organized testicular microenvironment to support spermatogenesis. However, the knowledge about it is limited in crustacean. In this study, we identified a member of immunoglobulin superfamily (IgSF) from Macrobrachium nipponense testis and explored its roles as a potential pattern recognition receptor (PRR) involved in reproductive immunity. Based on the domains it contains and homology analysis result, we designate it as leucine-rich repeats and immunoglobulin-like domains protein-1 (MnLrig-1). The Mnlrig-1 comprises a 3288 bp open reading frame (ORF) encoding a 1095 amino acid protein. MnLrig-1 is consisted of one signaling peptide; one LRR_NT domain; eight LRR domains; five LRR_TYP domains; one LRR_CT domain; three IGc2 regions; one transmembrane region, and C-terminal cytoplasmic tail, sharing similar domains with orthologs in other crustacean species. MnLrig-1 is widely expressed in various tissues of M. nipponense. Mnlrig-1 is significantly induced by LPS, PGN, Aeromonas hydrophila, and Vibrio alginolyticus challenge in the testis at 3 h and maintained a high level from 3 h to 24 h. Additionally, two recombinant immunoglobulin domains of MnLrig-1 are obtained, while only one domain shows direct binding affinity towards LPS, PGN, Escherichia coli, A. hydrophila, Staphylococcus aureus, and Bacillus subtilis in vitro. Moreover, silencing Mnlrig-1 results in a significant upregulation of three anti-lipopolysaccharide factors (ALFs) in the testis. These results reveal the potential role of MnLrig-1 as a PRR involved in the testis reproductive immunity in M. nipponense. The insights gained from this study will expand our understanding of immune system in crustacean and may have implications for aquaculture and disease management in crustaceans.
RESUMO
The spatial co-presence of aberrant long non-coding RNAs (lncRNAs) and abnormal coding genes contributes to malignancy development in various tumors. However, precise coordinated mechanisms underlying this phenomenon in tumorigenesis remains incompletely understood. Here, we show that Prohibitin 2 (PHB2) orchestrates the transcription of an oncogenic CASC15-New-Isoform 2 (CANT2) lncRNA and the coding tumor-suppressor gene CCBE1, thereby accelerating melanoma tumorigenesis. In melanoma cells, PHB2 initially accesses the open chromatin sites at the CANT2 promoter, recruiting MLL2 to augment H3K4 trimethylation and activate CANT2 transcription. Intriguingly, PHB2 further binds the activated CANT2 transcript, targeting the promoter of the tumor-suppressor gene CCBE1. This interaction recruits histone deacetylase HDAC1 to decrease H3K27 acetylation at the CCBE1 promoter and inhibit its transcription, significantly promoting tumor cell growth and metastasis both in vitro and in vivo. Our study elucidates a PHB2-mediated mechanism that orchestrates the aberrant transcription of lncRNAs and coding genes, providing an intriguing epigenetic regulatory model in tumorigenesis.