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Introduction: Obesity, mainly caused by excessive accumulation of visceral fat, excessive fat metabolism will cause hormone secretion imbalance and inflammation and other diseases. is extremely detrimental to human health. Although many treatments are available for obesity, most treatments fail to exert a radical effect or are associated with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipid content and inflammation is considered effective. Based on previous studies, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were selected to prepare an innovative herbal formula. Methods: TCM was characterized by UHPLC-Q-Orbitrap-MS. The anti-inflammatory and lipid-lowering effects of the TCM formula prepared were evaluated in a high-fat diet-fed obese mouse model. The effects of the TCM formula on the intestinal flora were also investigated. Results: Weights and insulin resistance, as well as inflammation, decreased in the mice after treatment. At the same time, lipid metabolism increased after the mice were gavaged with the TCM formula for 2 weeks. The intestinal motility of the drug administration group was enhanced, with partial restoration of the intestinal flora. Conclusion: In summary, our innovative Chinese herbal formula significantly reduced weight, reduced intestinal inflammation, improved intestinal motility, and improved lipid metabolism in obese mice. Furthermore, the innovative formula effectively prevented relevant obesity-induced metastatic diseases in the mice.
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PURPOSE: Lipid parameters have been shown to have significant predictive value for cardiovascular disease, but few studies have evaluated their correlation with erectile dysfunction (ED) in young men. METHODS: The case-control study encompassed 186 young ED patients (ages 20-40) and 186 healthy controls. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL ratio, TG/HDL ratio, and LDL-C/HDL-C ratio, were assessed in all participants. The International Index of Erectile Function (IIEF-5) scores were collected for all participants to evaluate erectile status. Multivariate logistic regression analysis was utilized to appraise the association of lipid-related parameters with ED. Single-nucleotide polymorphisms (SNPs) significantly correlated with lipid parameters (TC, TG, LDL-C, HDL-C) were selected from genome-wide association studies (GWAS) as instrumental variables (IV) (P < 5.0 × 10-8). Summary data for ED was gathered from a GWAS with a sample size of (n = 17,353 cases/28,210 controls). The inverse variance weighted (IVW) method was employed as the primary mendelian randomization (MR) analysis method to assess causal effects. Causal estimates were represented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Results from the case-control study revealed that, when compared with the control group, levels of LDL-C, TG, UA, LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C in the ED group were significantly elevated (P < 0.01), while HDL-C was significantly decreased (P < 0.01) in the ED group. Multivariate logistic regression analysis indicated LDL-C/HDL-C as a risk factor for both the incidence and severity of ED (P < 0.001). Two-sample MR analysis demonstrated no significant causal correlation between lipid parameters-LDL-C (OR, 0.98, 95% CI, 0.88-1.08, P = 0.616), HDL-C (OR, 1.07, 95% CI: 0.96-1.19, P = 0.249), TC (OR, 1.07, 95% CI, 0.96-1.18, P = 0.208), TG (OR, 0.98, 95% CI, 0.80-1.13, P = 0.579) -and an increased risk of ED (all P > 0.05). CONCLUSIONS: The case-control analysis ascertained a significant association between LDL-C, HDL-C, LDL-C/HDL-C, and ED and its severity. However, results from the MR study do not support a causal role of lipid parameters in ED.
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Disfunção Erétil , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Triglicerídeos , Humanos , Masculino , Estudos de Casos e Controles , Disfunção Erétil/sangue , Disfunção Erétil/genética , Disfunção Erétil/epidemiologia , Adulto , Adulto Jovem , Triglicerídeos/sangue , Lipídeos/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudo de Associação Genômica AmplaRESUMO
Background: The use of an artificial intelligence (AI)-based diagnostic system can significantly aid in analyzing the histogram of pulmonary nodules. The aim of our study was to evaluate the value of computed tomography (CT) histogram indicators analyzed by AI in predicting the tumor invasiveness of ground-glass nodules (GGNs) and to determine the added value of contrast-enhanced CT (CECT) compared with nonenhanced CT (NECT) in this prediction. Methods: This study enrolled patients with persistent GGNs who underwent preoperative NECT and CECT scanning. AI-based histogram analysis was performed for pathologically confirmed GGNs, which was followed by screening invasiveness-related factors via univariable analysis. Multivariable logistic models were developed based on candidate CT histogram indicators measured on either NECT or CECT. Receiver operating characteristic (ROC) curve and precision-recall (PR) curve were used to evaluate the models' performance. Results: A total of 116 patients comprising 121 GGNs were included and divided into the precancerous lesion and adenocarcinoma groups based on invasiveness. In the AI-based histogram analysis, the mean CT value [NECT: odds ratio (OR) =1.009; 95% confidence interval (CI): 1.004-1.013; P<0.001] and solid component volume (NECT: OR =1.005; 95% CI: 1.000-1.010; P=0.032) were associated with the adenocarcinoma and used for multivariable logistic modeling. The area under ROC curve (AUC) and PR curve (AUPR) were not significantly different between the NECT model (AUC =0.765, 95% CI: 0.679-0.837; AUPR =0.907, 95% CI: 0.825-0.953) and the optimal CECT model (delayed phase: AUC =0.772, 95% CI: 0.687-0.843; AUPR =0.895, 95% CI: 0.812-0.944). No significantly different metrics were observed between the NECT and CECT models (precision: 0.707 vs. 0.742; P=0.616). Conclusions: The AI diagnostic system can help in the diagnosis of GGNs. The system displayed decent performance in GGN detection and alert to malignancy. Mean CT value and solid component volume were independent predictors of tumor invasiveness. CECT provided no additional improvement in diagnostic performance as compared with NECT.
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Parent's nutrition knowledge, attitudes, and dietary practices (KAP) play imperative roles in preventing malnutrition for themselves and their children. Our study aimed to determine the status and contributing factors of nutrition KAP among parents of children and adolescents. A total of 1746 parents (mean age 39.67 ± 5.38 years, females accounting for 69.82%) of primary and junior high school students in Weifang, China, completed a self-reported KAP questionnaire in August 2021. An analysis of Pearson product-moment correlation was conducted to determine the relationship between knowledge, attitudes, and practices. Chi-square test, followed by a multivariable robust Poisson regression analysis, was performed to identify the contributing factors to parents' KAP. A 65.94% awareness rate of nutritional knowledge was observed. The correlations between nutrition knowledge and attitudes (r = 0.03, P = 0.23), knowledge and practices (r = 0.02, P = 0.34), and attitudes and practices (r = 0.16, P < 0.01) were relatively weak. After adjusting for other contributing factors, females [prevalence ratio (PR) = 1.28, 95% confidence interval (CI) = 1.13-1.45], participants with secondary education (PR = 4.64, 95% CI = 1.60-13.50), junior college education (PR = 5.87, 95% CI = 2.01-17.13) and college degree or above education (PR = 6.58, 95% CI = 2.25-19.23) acquired higher nutrition knowledge scores. Moreover, healthy diet behaviors were more commonly implemented by females than males (PR = 1.42, 95% CI = 1.14-1.76), and which needed to be improved in those with abnormal body mass indexes (BMIs) [overweight (PR = 0.86, 95% CI = 0.74-0.99) and obese (PR = 0.76, 95% CI = 0.56-0.99)]. It was necessary for nutrition KAP promotion to be emphasized in nutritional knowledge and dietary practices, as well as health behavior guidance, especially for parents with low education and elevated BMIs.
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Lumefantrine (LMN) is one of the first-line drugs in the treatment of malaria due to its long circulation half-life, which results in enhanced effectiveness against drug-resistant strains of malaria. However, LMN's therapeutic efficacy is diminished due to its low bioavailability when dosed as a crystalline solid. The goal of this work was to produce low-cost, highly bioavailable, stable LMN powders for oral delivery that would be suitable for global health applications. We report the development of a LMN nanoparticle formulation and the translation of that formulation from laboratory to industrial scale. We applied Flash NanoPrecipitation (FNP) to develop nanoparticles with 90% LMN loading and sizes of 200-260 nm. The integrated process involves nanoparticle formation, concentration by tangential flow ultrafiltration, and then spray drying to obtain a dry powder. The final powders are readily redispersible and stable over accelerated aging conditions (50°C, 75% RH, open vial) for at least 4 weeks and give equivalent and fast drug release kinetics in both simulated fed and fasted state intestinal fluids, making them suitable for pediatric administration. The nanoparticle-based formulations increase the bioavailability of LMN 4.8-fold in vivo when compared to the control crystalline LMN. We describe the translation of the laboratory-scale process at Princeton University to the clinical manufacturing scale at WuXi AppTec.
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Malária , Nanopartículas , Humanos , Criança , Lumefantrina/uso terapêutico , Química Farmacêutica/métodos , Pós , Malária/tratamento farmacológico , Tamanho da Partícula , Nanopartículas/química , SolubilidadeRESUMO
Background: Bacterial vaginosis (BV) is the most common microbiological syndrome in women of childbearing age, causing numerous adverse health issues in pregnant women. Several observational studies have discussed the association between vitamin D deficiency and the risk of BV during pregnancy, but the results were inconclusive. Therefore, this meta-analysis aimed to explore the association between vitamin D deficiency and BV risk in pregnant women. Materials and methods: We searched four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2022. Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated using random effects models. Additionally, we conducted subgroup analyses to identify the potential sources of between-study heterogeneity. Sensitivity analysis was performed using the method of exclusion, one study at a time. Publication bias was examined using Egger's test and funnel plot. Results: A total of 14 studies from 13 articles including 4,793 participants were eligible for this meta-analysis. The outcome showed that vitamin D deficiency may increase the risk of BV during pregnancy by 54% (OR, 1.54; 95% CI, 1.25-1.91; P < 0.001). In subgroup analyses, positive associations were also found in studies that were: conducted in black women (OR, 1.56; 95% CI, 0.98-2.48; P = 0.060), focused on the first trimester of pregnancy (OR, 2.22; 95% CI, 1.35-3.64; P = 0.002), of high quality (OR, 3.05; 95% CI, 1.26-7.41; P = 0.014), and adjusted for confounders (OR, 1.28; 95% CI, 1.06-1.55; P = 0.012). Sensitivity analysis reported that BV risk during pregnancy resulting from vitamin D deficiency increased by 157% (OR, 2.57; 95% CI, 1.50-4.42; P = 0.001) when removing the first two high-weight studies. Publication bias was observed using Egger's test (t = 3.43, P = 0.005) and a visual funnel plot. Conclusion: This meta-analysis showed that vitamin D deficiency is positively associated with the risk of BV during pregnancy. Further high-quality prospective cohort studies are needed to determine whether vitamin D intake reduces the prevalence of BV in pregnant women.
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Psoriasis is a systemic disease that is associated with metabolic disorders, which may contribute to abnormal adipokine levels. However, the underlying mechanism is largely unknown. Here, we investigated the role of the adipokine CTRP3 in the pathogenesis of psoriasis and comorbidities. The circulating CTRP3 level in patients with psoriasis was significantly lower than that in healthy controls and negatively correlated with metabolic risk factors. Rescuing CTRP3 levels with the GLP-1 receptor agonist exendin-4 in diet-induced obese mice could alleviate its more severe psoriatic symptoms in an imiquimod-induced mouse model. Topical application of CTRP3 also exerted a protective effect on imiquimod-induced normal diet mice. Moreover, CTRP3 could directly inhibit the inflammatory responses of psoriatic keratinocytes by blocking phosphorylation of signal transducer and activator of transcription 3 via LAMP1 in vitro. We identified the critical psoriatic cytokines, including IL-17A and TNF-α, that impaired adipocyte differentiation and sufficient CTRP3 secretion. In sum, our study reveals that adipocyte dysfunction and low level of CTRP3 caused by IL-17A exacerbates psoriasis progression and related metabolic syndrome, implying a mechanism underlying the vicious cycle between psoriasis and metabolic disorders. Pharmacological agents that improve CTRP3 level in obese patients with psoriasis may be considered as a potential strategy for psoriasis treatment.
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Adipocinas/metabolismo , Interleucina-17 , Psoríase , Adipócitos/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Humanos , Imiquimode/farmacologia , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Camundongos , Psoríase/patologia , Fator de Transcrição STAT3/metabolismoRESUMO
PURPOSE: To evaluate ocular surface status and corneal higher-order aberrations after a new ocular nebulization therapy combined with meibomian gland massage for the treatment of meibomian gland dysfunction (MGD). PATIENTS AND METHODS: This prospective randomized study involved 38 patients diagnosed with MGD. Subjects were classified into two groups: the nebulization and meibomian gland massage group (or NB group, 14 patients, 28 eyes) and the eye drop group (or ED group, 24 patients, 48 eyes). Azithromycin solution and esculin and digitalis glycoside eye drops were tested in the therapy. Best-corrected visual acuity (BCVA) testing; noncontact tonometry; fundoscopy; the Ocular Surface Disease Index (OSDI) questionnaire; tear film assessment encompassing tear meniscus height (TMH) and non-invasive keratograph breakup time (NIKBUT); corneal fluorescein staining; the Schirmer I test (SIT); and anterior, posterior and total corneal aberrations were evaluated at 1 and 3 months after treatment. RESULTS: At 3 months, the NB group showed significantly better improvement than the ED group in terms of TMH (0.23 ± 0.04 versus 0.19 ± 0.05, p = 0.002) and first breakup time (f-BUT; 7.42 ± 2.49 versus 5.53 ± 2.12, p = 0.001). The average breakup time (Av-BUT) of the NB group was significantly longer than that of the ED group at 1 month (9.52 ± 2.70 versus 8.02 ± 2.33, p = 0.013) and 3 months (5.53 ± 2.12 versus 8.35 ± 2.38, p = 0.018). Both groups achieved improvement in corneal fluorescein staining (CFS) and SIT results at 1 and 3 months (p < 0.05). At the 3-month follow-up, anterior corneal trefoil aberrations decreased significantly in the NB group (p = 0.008), and improvements in anterior corneal coma aberrations and posterior corneal higher-order aberrations (HOAs) were observed in the ED group (p < 0.05) over the 4 mm pupil zone. Over a 6 mm zone at 3 months, anterior, posterior and total trefoil aberrations as well as total HOAs were significantly decreased in the NB group (p < 0.05), while posterior HOAs and trefoil aberrations were found to be decreased in the ED group (p < 0.05). For individual Zernike terms, anterior and total corneal Z(3, -3) showed decreases over the 4 and 6 mm zones, while no improvement was detected in the NB group at 3 months. CONCLUSION: In terms of comfort and visual quality, nebulization therapy combined with meibomian gland massage to deliver azithromycin solution and esculin and digitalis glycoside eye drops appears to be more effective in treating clinical symptoms and signs of MGD than simply applying esculin and digitalis glycoside eye drops.
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Síndromes do Olho Seco , Doenças Palpebrais , Disfunção da Glândula Tarsal , Azitromicina , Glicosídeos Digitálicos , Síndromes do Olho Seco/diagnóstico , Esculina , Doenças Palpebrais/diagnóstico , Fluoresceína , Humanos , Massagem , Glândulas Tarsais , Soluções Oftálmicas , Estudos Prospectivos , LágrimasRESUMO
Understanding the molecular level changes of oocyte cryopreservation and the subsequent warming process is essential for improving the oocyte cryopreservation technologies. Here, we collected the mature metaphase II (MII) oocytes from mice and vitrified. After thawing, single-cell whole-genome bisulphite sequencing (scWGBS) and single-cell RNA sequencing (scRNA-seq) were used to investigate the molecular attributes of this process. Compared to the fresh oocytes, the vitrified oocytes had lower global methylation and gene expression levels, and 1426 genes up-regulated and 3321 genes down-regulated. The 1426 up-regulated differentially expressed genes (DEGs) in the vitrified oocytes were mainly associated with the histone ubiquitination, while the 3321 down-regulated genes were mainly enriched in the mitochondrion organisation and ATP metabolism processes. The differentially methylated regions (DMRs) were mainly located in promoter, intron and exon region of genes, and the length of DMRs in the vitrified oocytes were also significantly lower than that of the fresh oocytes. Notably, there were no significant difference in the expression levels of DNA demethylases (Tet1, Tet2 and Tet3) and methyltransferases (Dnmt3a and Dnmt3b) between two treatments of oocytes. However, Dnmt1 and kcnq1ot1, which are responsible for maintaining DNA methylation, were significantly down regulated in the vitrified oocytes. Gene regulatory network (GRN) analysis showed the Dnmt1 and kcnq1ot1 play a core role in regulating methylation and expression levels of downstream genes. Moreover, some genes associated with oocyte quality were significantly down-regulated in the vitrified oocytes. The present data provides a new perspective for understanding the impact of vitrification on oocytes.
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Oócitos , Vitrificação , Animais , Criopreservação/veterinária , Metilação de DNA , Expressão Gênica , Camundongos , Oócitos/metabolismo , RNA-Seq/veterináriaRESUMO
OBJECTIVE: To explore the pathogenesis of two siblings (including a fetus) from a pedigree affected with Joubert syndrome. METHODS: Peripheral blood samples of the proband and his parents as well as amniotic fluid and abortion tissues of the fetus were collected. Part of the samples were used for the extraction of DNA, and whole exome sequencing (WES) was carried out to screen potential variants in the proband and his parents. Suspected variants were subjected to bioinformatics analysis with consideration of the clinical phenotype, and were verified by Sanger sequencing of the proband, fetus and their parents.The remainders were used for the extraction of RNA, and the mechanism of splicing variant was validated by reverse transcription-PCR (RT-PCR). RESULTS: WES showed that both patients have carried c.175C>T (p.R59X) and c.553+1G>A compound heterozygous variants of the TMEM237 gene. Among these, c.175C>T was a nonsense mutation inherited from the asymptomatic mother, while c.553+1G>A was an alternative splicing mutation inherited from the asymptomatic father. RT-PCR showed that this variant has resulted in aberrant splicing by exon skipping. CONCLUSION: The compound heterozygous variants of the TMEM237 gene probably underlay the etiology of Joubert syndrome in this pedigree. Above finding has enriched the phenotype and variant spectrum of the TMEM237 gene, and facilitated genetic counseling and prenatal diagnosis for the family.
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Anormalidades Múltiplas , Anormalidades do Olho , Doenças Renais Císticas , Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Feminino , Genótipo , Humanos , Mutação , Linhagem , Fenótipo , Gravidez , Retina/anormalidadesRESUMO
Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.
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INTRODUCTION: Irisin is a unique myokine with striking effects on regulating insulin sensitivity and energy metabolism. This study aimed to investigate the changes in serum irisin in patients with newly diagnosed type 2 diabetes mellitus (T2DM) following sitagliptin treatment. METHODS: Thirty-two patients with T2DM were treated with 100 mg/day sitagliptin for 16 weeks. Twenty age-, sex- and body mass index (BMI)-matched healthy subjects were enrolled as the control group. Irisin and metabolic parameters were measured at baseline and after treatment. RESULTS: Patients with T2DM had lower irisin levels than the controls (10.03 ± 2.06 vs. 13.06 ± 3.10 ng/ml, P < 0.01). Sitagliptin treatment significantly increased serum irisin levels in T2DM patients compared to baseline (11.18 ± 1.91 vs. 10.03 ± 2.06 ng/ml, P < 0.01). Increased irisin levels were associated with decreased fasting blood glucose (FBG) (ß = - 0.24, P < 0.05) and glycosylated hemoglobin (HbA1c) (ß = - 0.15, P < 0.05). CONCLUSIONS: Sitagliptin treatment significantly increased serum irisin levels in patients with T2DM, and the increase of the irisin level was associated with decreases of FBG and HbA1c levels. These results suggest that irisin might be involved in the antidiabetic mechanisms of sitagliptin. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04495881.
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Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1) is a member of the C2 H2 zinc finger protein family. However, the exact effect of ZNF667-AS1 in uveal melanoma (UM) progression has not been elucidated. The biological roles of ZNF667-AS1 and MEGF10 were assessed using cell counting kit-8 and flow cytometry. Quantitative reverse-transcription polymerase chain reaction and Western blot analyses were conducted to measure the expression of subjects. ZNF667-AS1 expression was significantly decreased in metastasized UM tissues and its low expression was related to poorer prognosis of UM patients. MEGF10 expression was positively associated with ZNF667-AS1 expression. The inhibitory effect of ZNF667-AS1 overexpression on UM cellular malignant behaviors could be reversed by MEGF10 knockdown, which was re-ascertained by the detection of corresponding protein levels (p53, cyclin D1, Bcl-2, and Bax). In conclusion, ZNF667-AS1 might play an inhibitory role in the development of UM by regulating cellular aggressiveness, which was partially realized by positively regulating MEGF10.
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Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , Proteínas de Membrana/biossíntese , Proteínas de Neoplasias/biossíntese , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Neoplasias Uveais/metabolismo , Linhagem Celular Tumoral , Humanos , Melanoma/genética , Melanoma/patologia , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Neoplasias Uveais/genética , Neoplasias Uveais/patologiaRESUMO
Obacunone, a limonin triterpenoid extracted from Phellodendronchinense Schneid or Dictamnus dasycarpusb Turcz plant, elicits a variety of pharmacological effects such as anti-inflammatory, anti-neoplastic, anti-oxidation, and anti-lung-fibrosis ones. However, the anti-fibrotic effect of obacunone and the detailed underlying mechanism in liver fibrosis remain unclear. Liver fibrosis is a debilitating disease threatening human health. Transforming growth factor (TGF)-ß/P-Smad is a major pathway of fibrosis featured with epithelia mesenchymal transformations (EMT) and collagen depositions, accompanying with excessive oxygen-free radicals. Nrf-2 acts as a key anti-oxidative regulator driving the expressions of various antioxidant-related genes. Glutathionperoxidase-4 (GPx-4) is a member of the glutathione peroxidase family that directly inhibits phospholipid oxidation to alleviate oxidative stress. In the present study, we aimed to explore the role of obacunone in mouse liver fibrosis model induced by carbon tetrachloride (CCl4) and in hepatic stellate cells (LX2 cell line) challenging with TGF-ß. Obacunone demonstrated potent ameliorative effects on liver fibrosis both in activated LX2 and in mice liver tissues with reduced levels of α-SMA, collagen1, and vimentin. Obacunone also remarkably suppressed the TGF-ß/P-Smad signals and EMT process. Meanwhile, obacunone exerted a potent anti-oxidation effect by reducing the levels of reactive oxygen species (ROS) in both models. The antioxidant effect of obacunone was attributed to the activation of GPx-4 and Nrf-2. In addition, the therapeutic effect of obacunone on LX2 cells was significantly removed in vitro plus with GPx-4 antagonist RSL3, in parallel with the re-elevated levels of ROS. Thus, we demonstrate that obacunone is able to attenuate liver fibrosis via enhancing GPx-4 signal and inhibition of the TGF-ß/P-Smad pathway and EMT process.
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Antioxidantes/farmacologia , Benzoxepinas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Limoninas/farmacologia , Cirrose Hepática/tratamento farmacológico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , Animais , Antioxidantes/química , Benzoxepinas/química , Células Cultivadas , Humanos , Limoninas/química , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE: To explore the application value of primary trauma treatment (PTC) teaching mode in special professional cardiopulmonary resuscitation (CPR) guide training. METHODS: Cluster sampling method was adopted, and the residents' committee selected special occupation population from every town/sub-district office in the southern mountainous area of Ningxia Hui Autonomous Region for CPR training. A monthly session was held from January to December 2019, with personnel trained by traditional operation teaching and individual practice method from January to June 2019 as the control group and personnel trained by PTC teaching mode from July to December 2019 as the observation group. The two groups of trainers, training objectives and assessment standards were consistent. Questionnaire survey was conducted at the beginning and end of each training period, including the degree of mastery of first-aid knowledge and skills and the level of self-efficacy, etc., to evaluate the training effect. RESULTS: There were 503 trainees in each group, and there was no significant difference in gender, age, education and occupation distribution between the two groups. There was no significant difference in the first aid principles, CPR skill level and self-efficacy between the two groups before the training. The first aid principle, CPR skills level and self-efficacy of the two groups after training were all improved, and the principle of first aid and CPR skills level in the observation group was obviously higher than that in the control group (first aid related concepts: 4.39±0.76 vs. 3.87±0.89, gold life-saving time: 5.71±0.49 vs. 4.53±0.62, the meaning of the first witnesses: 5.33±0.82 vs. 4.18±0.78, cardiac, respiratory cardiac arrest in the judgment: 5.12±0.73 vs. 4.07±0.73, CPR skills: 5.29±0.64 vs. 4.15±0.71, all P < 0.05). The self-efficacy score of the observation group was significantly higher than that of the control group (emergency attitude: 18.17±1.24 vs. 17.35±1.25, self-efficacy: 13.56±1.54 vs. 11.35±1.26, behavioral intention: 9.56±0.84 vs. 8.92±0.95, all P < 0.05). CONCLUSIONS: The application of PTC teaching mode in the training of CPR guidelines for special professions has significant effects, which can effectively help special professions to master CPR knowledge and skills, and has promotion value.
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Reanimação Cardiopulmonar , Parada Cardíaca , Cidades , Primeiros Socorros , Humanos , OcupaçõesRESUMO
Hexyl aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinic acid (5-ALA) and can induce more protoporphyrin IX (PpIX) formation and stronger fluorescence intensity (FI) than 5-ALA, which will greatly facilitate photodynamic diagnosis and therapy. The main drawback of HAL is its low solubility in neutral aqueous media. In this study, surfactants were used to increase HAL solubility in the cell culture medium and serum, followed by in vitro fluorescence formation measurement in human pancreatic cancer cells (SW1990) and in vivo fluorescence detection in tumor-bearing mice. The results showed that Tween 80 (TW80) and Kolliphor® HS 15 (HS15) increased the solubility of HAL in the selected media. Although TW80 and HS15 exhibited in vitro cytotoxicity at high concentrations (5 mg mL-1 ), they facilitated fluorescent signal formation at the early stage of cell incubation. When surfactants were used, the FI should be determined without the routine washing process because surfactant-containing culture medium caused the loss of synthesized PpIX during the washing process. When HAL dissolved in TW80 solution was injected intraperitoneally into pancreatic cancer-bearing mice at a dose of 50 mg kg-1 , the tumors exhibited red fluorescence, which indicated that systemic administration of surfactant-solubilized HAL might be applicable for tumor fluorescence detection in vivo.
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Ácido Aminolevulínico/química , Neoplasias/diagnóstico , Tensoativos/química , Animais , Linhagem Celular Tumoral , Estudos de Viabilidade , Fluorescência , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Imagem Óptica , SolubilidadeRESUMO
The complete chloroplast genome sequence of Senna tora was characterized from Illumina pair-end sequencing. The chloroplast genome of S. tora was 161,050 bp in length, containing a large single-copy region (LSC) of 90,411 bp, a small single-copy region (SSC) of 18,537 bp, and two inverted repeat (IR) regions of 26,050 bp. The overall GC content is 36.20%, while the correponding values of the LSC, SSC, and IR regions are 64.5%, 69.4%, and 60.2%, respectively. The genome contains 129 complete genes, including 8 rRNAs, 37 tRNAs and 84 protein coding genes. The Neighbour-joining phylogenetic analysis showed that S. tora and S. bicapsularis clustered together as sisters to other Senna species.
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There is a strong need to develop MRI contrast agents (CAs) with lower in-vivo retention, stronger signal enhancement, and more specific imaging. Here, we report a novel dextran (DEX)-based nanomicelle system as an MRI CA with superior tumor imaging and relatively short intravascular persistence. Gadolinium (Gd)-chelate (DTPA-Gd) was conjugated directly to DEX hydroxyl via a degradable ester bond. DEX-DTPA-Gd was then modified with dodecylsuccinic anhydride to obtain the amphiphilic derivative, 2-dodecylsuccinic acid (DSA)-grafted DEX-DTPA-Gd. Nanomicelles were prepared by dissolving DSA-DEX-DTPA-Gd in water using ultrasonication. The physicochemical properties, cytotoxicity, and MRI efficiency of the synthesized CA were evaluated. The synthesized DSA-DEX-DTPA-Gd self-assembled into nanomicelles with an average diameter of 67.80 ± 5.21 nm. Within the given Gd concentration range, DSA-DEX-DTPA-Gd and Magnevist® exhibited similar cytotoxicity. DEX-based CAs resulted in a greater contrast enhancement of T1-weighted signal intensity in the tumor region than Magnevist®, and the tumors were clearly defined for at least 3 h. Simultaneously, the ester bond in DSA-DEX-DTPA-Gd facilitated the elimination of Gd chelates, compared with the relatively more stable amide linker. The DEX-based nanomicelle system with directly ester-bound DTPA-Gd may serve as an MRI CA with superior tumor imaging and relatively rapid elimination.
RESUMO
PURPOSE: Theranostic nanoplatforms are promising approaches for diagnosis and treatment. Here, we report a drug-loaded nanomicelle system with biocleavable gadolinium (Gd) chelates as a multifunctional biodegradable agent for simultaneous magnetic resonance imaging (MRI) and drug delivery. METHODS: Self-assembled nanomicelles based on stearic acid-grafted chitooligosaccharide were utilized as vehicles. Gd chelates, DTPA-Gds, were linked to the nanomicelles via redox-responsive disulfide bonds, and hydrophobic drugs were encapsulated in the micelle cores. MRI and cargo delivery were investigated in orthotopic pancreatic tumor-bearing mice. RESULTS: In vivo MRI demonstrated that the biodegradable agent was cleaved by endogenous thiols after intravenous injection, and the released DTPA-Gds were eliminated rapidly. At the same time, the agent resulted in a greater contrast enhancement of T1-weighted MR signal intensity at the tumor region than Magnevist®, and the tumor boundaries were clearly defined for at least 2 h. In addition, the agent possessed high drug-loading and tumor-targeting capacities. Loading content and encapsulation efficiency of docetaxel were 3.2% and 99.4%, respectively. Compared with Taxotere®, the commercially available docetaxel injection, the docetaxel-loaded agent significantly increased the drug concentration in tumor tissue in vivo. CONCLUSION: The fabricated multifunctional agent may serve as a biodegradable nanoscale MRI contrast agent and as a drug delivery system for tumor diagnosis and treatment.
Assuntos
Quitina/análogos & derivados , Portadores de Fármacos , Nanopartículas , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Ácidos Esteáricos/química , Animais , Quelantes , Quitina/química , Quitosana , Sistemas de Liberação de Medicamentos , Feminino , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Camundongos Endogâmicos ICR , Micelas , OligossacarídeosRESUMO
Developing effective and low-cost adsorbents is of great significance for controlling water contamination. To eliminate anionic water contaminants, four modified/non-modified aluminum (AlHMD, AlOSSD) and silica (SiHMD, SiOSSD) aerogels have been successfully employed. The four as-prepared aerogels were applied as adsorbents for removal of an anionic dye (acid orange 7, AO) from aqueous solution. Compared to silica aerogels, aluminum aerogels showed efficient adsorption performance for anionic water contaminants. The AO maximum adsorption capacity of Al2O3 aerogel is twice as high as that of SiO2 aerogel. The maximum adsorption capacity of aerogels was in the following order: AlHMD > AlOSSD > SiHMD > SiOSSD. Adsorption kinetics and isotherms of AO dye on the four as-prepared aerogels have also been studied. The kinetic data fitted well with the pseudo first-order kinetics model and the adsorption isotherm could be described by the Langmuir model. Adsorption rate of AO dye was mainly governed by film diffusion and intra-particle diffusion. Based on the adsorption mechanism, this work provides an idea for the design of superior adsorbents for anionic water contaminants.