Genetic or pharmacologic blockade of mPGES-2 attenuates renal lipotoxicity and diabetic kidney disease by targeting Rev-Erbα/FABP5 signaling.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and no specific drugs are clinically available. We have previously demonstrated that inhibiting microsomal prostaglandin E synthase-2 (mPGES-2) alleviated type 2 diabetes by enhancing ß cell function and promoting insulin production. However, the involvement of mPGES-2 in DKD remains unclear. Here, we aimed to analyze the association of enhanced mPGES-2 expression with impaired metabolic homeostasis of renal lipids and subsequent renal damage. Notably, global knockout or pharmacological blockage of mPGES-2 attenuated diabetic podocyte injury and tubulointerstitial fibrosis, thereby ameliorating lipid accumulation and lipotoxicity. These findings were further confirmed in podocyte- or tubule-specific mPGES-2-deficient mice. Mechanistically, mPGES-2 and Rev-Erbα competed for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney. Our findings suggest a potential strategy for treating DKD via mPGES-2 inhibition.

Targeting mPGES-2 to protect against acute kidney injury via inhibition of ferroptosis dependent on p53.

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality but no specific therapy. Microsomal prostaglandin E synthase-2 (mPGES-2) is a PGE2 synthase but can metabolize PGH2 to malondialdehyde by forming a complex with heme. However, the role and mechanism of action of mPGES-2 in AKI remain unclear. To examine the role of mPGES-2, both global and tubule-specific mPGES-2-deficient mice were treated with cisplatin to induce AKI. mPGES-2 knockdown or overexpressing HK-2 cells were exposed to cisplatin to cause acute renal tubular cell injury. The mPGES-2 inhibitor SZ0232 was used to test the translational potential of targeting mPGES-2 in treating AKI. Additionally, mice were subjected to unilateral renal ischemia/reperfusion to further validate the effect of mPGES-2 on AKI. Interestingly, both genetic and pharmacological blockage of mPGES-2 led to decreased renal dysfunction and morphological damage induced by cisplatin and unilateral renal ischemia/reperfusion. Mechanistic exploration indicated that mPGES-2 deficiency inhibited ferroptosis via the heme-dependent regulation of the p53/SLC7A11/GPX4 axis. The present study indicates that mPGES-2 blockage may be a promising therapeutic strategy for AKI.

Viscoelasticity in trapezius myofascial pain syndrome: quantitative assessment using Real-Time Shear-Wave Elastography.

OBJECTIVE: To investigate the differences in the viscoelastic properties between normal trapezius muscles and those in patients with trapezius myofascial pain syndrome (MPS) using real-time shear-wave elastography (SWE). MATERIALS AND METHODS: This study included 31 patients with trapezius MPS and 31 volunteers. Sixty-one trapezius muscles (41 and 20 on the affected and non-affected side, respectively) of patients with MPS and 62 normal trapezius muscles in volunteers were assessed. Conventional ultrasonic parameters, including skeletal muscle thickness, resistance index (RI), and mean shear wave velocity (SWVmean) of trapezius muscles, were obtained in the seated position with the shoulders and neck relaxed. The daily neck leaning time (unit:hours) of all participants was obtained using a questionnaire. RESULTS: Ultrasound showed no statistically significant differences in thickness or RI of the trapezius muscles of the affected and non-affected sides in MPS patients versus normal trapezius muscles (p = 0.976 and 0.106, respectively). In contrast, the SWVmean of trapezius muscles in patients with MPS was significantly higher than that of normal trapezius muscles in both the affected and non-affected sides (4.41 ± 1.02 m/s vs. 3.35 ± 0.79 m/s, p < 0.001; 4.05 ± 0.63 m/s vs. 3.35 ± 0.79 m/s, p = 0.002). There was no significant difference between the SWVmean of the trapezius muscles on the affected and non-affected sides in patients with MPS (4.41 ± 1.02 m/s vs. 4.05 ± 0.63 m/s, p = 0.225). Correlation analysis showed that daily neck forward time was positively correlated with the SWVmean of the trapezius muscles on the affected and non-affected sides in patients with MPS (r = 0.635, p < 0.001; r = 0.576, p = 0.008). CONCLUSION: SWE can quantitatively evaluate stiffness of trapezius muscles in patients with trapezius MPS. The stiffness of both affected and non-affected trapezius muscles increased in patients with trapezius MPS, and the degree of increase positively correlated with the time of cervical forward leaning.

Upper trapezius muscle elasticity in cervical myofascial pain syndrome measured using real-time ultrasound shear-wave elastography.

Background: Myofascial pain syndrome (MPS) is a common cause of neck pain, which is a global public health problem. Because MPS does not present morphological changes within lesioned muscles, there are no imaging diagnostic criteria for this condition. In this study, we evaluate elasticity changes in upper trapezius muscles most frequently involved in cervical MPS using real-time ultrasound shear-wave elastography, and we examine their potential diagnostic value. Methods: We consecutively enrolled 109 right posterior neck pain patients for this prospective study. Of these, 51 were diagnosed with MPS and 58 with non-MPS in the right side of their neck. Among MPS patients, 19 fell into the 1-3 range (mild pain) for pain scores on the visual analog scale (VAS), 25 fell into the 4-6 range (moderate pain), and 7 into the 7-10 range (severe pain). MPS was diagnosed by two independent clinicians using the diagnostic criteria proposed by Simons et al. Using real-time ultrasound shear-wave elastography, we measured right trapezius mean shear-wave velocity (SWVmean). The midpoint of the line between the foramen magnum and the end of the right acromion served as measuring point. Regions of interest were scaled to span 0-8.0 m/s. Results: Trapezius SWVmean was significantly higher in MPS patients compared with non-MPS patients (P<0.001). Stratified analysis of MPS patients according to pain severity revealed similar trapezius SWVmean between mild pain and non-MPS patients (P=0.324), however SWVmean was higher in moderate and severe pain MPS patients compared with non-MPS patients (P<0.001). The area under the curve (AUC) value for upper trapezius SWVmean in MPS patients was 0.791 (95% CI: 0.703-0.863). Corresponding sensitivity and specificity values were 86.27% (95% CI: 73.7-94.3%) and 62.07% (95% CI: 48.4-74.5%). Stratified analysis of MPS patients by pain severity produced the following AUC values for trapezius SWVmean in MPS patients with mild, moderate, and severe pain: 0.578 (95% CI: 0.460-0.690), 0.899 (95% CI: 0.814-0.955), and 0.983 (95% CI: 0.914-0.999), respectively. Conclusions: Elasticity changes and increased stiffness in the trapezius occur in cervical MPS patients with moderate and severe pain. The SWVmean parameter reflecting trapezius muscle elasticity may be valuable for successful screening of cervical MPS, especially in patients with moderate and severe pain.

Comparison of the efficacy and safety of total laparoscopic hysterectomy without and with uterine manipulator combined with pelvic lymphadenectomy for early cervical cancer.

OBJECTIVE: Some studies have reported that the prognosis of total laparoscopic hysterectomy (TLH) for early-stage cervical cancer (CC) is worse than that of open surgery. And this was associated with the use of uterine manipulator or not. Therefore, this study retrospectively analyzes the efficacy and safety of TLH without uterine manipulator combined with pelvic lymphadenectomy for early-stage CC. METHODS: Fifty-eight patients with CC (stage IB1-IIA1) who received radical hysterectomy from September 2019 to January 2020 were divided into no uterine manipulator (n = 26) and uterine manipulator group (n = 32). Then, clinical characteristics were collected and intraoperative/postoperative related indicators were compared. RESULTS: Patients in the no uterine manipulator group had significantly higher operation time and blood loss than in the uterine manipulator group. Notably, there was no significant difference in hemoglobin change, blood transfusion rate, number of pelvic nodules, anal exhaust time, complications and recurrence rate between the two groups. Additionally, patients in the uterine manipulator group were prone to urinary retention (15.6%) and lymphocyst (12.5%), while the no uterine manipulator group exhibited high probability of bladder dysfunction (23.1%) and urinary retention (15.4%). Furthermore, the 1-year disease-free survival rate and the 1-year overall survival rate were not significantly different between the two groups. CONCLUSION: There was no significant difference in the efficacy and safety of TLH with or without uterine manipulator combined with pelvic lymphadenectomy in the treatment of patients with early-stage CC. However, the latter requires consideration of the negative effects of high operation time and blood loss.

Observation of robust edge mode and in-gap corner mode in Kagome surface-wave photonic crystals.

Recent theory has demonstrated that Kagome photonic crystals (PCs) support first-order and second-order topological phenomena. Here, we extend the topological physics of the Kagome lattice to surface electromagnetic waves and experimentally show a Kagome surface-wave PC. Under the protection of first-order and second-order topologies, both robust edge modes and in-gap corner modes are observed. The robust transport of edge modes is demonstrated by high transmission through the waveguide with a sharp bend. The localized corner mode is found at the corner with one isolated rod when a triangle-shaped sample is constructed. Our work not only shows a platform to mimic the topological physics in classical wave systems, but also offers a potential application in designing high-performance photonic devices.

Dietary fatty acids differentially affect secretion of pro-inflammatory cytokines in human THP-1 monocytes.

Monocytes are a major population of circulating immune cells that play a crucial role in producing pro-inflammatory cytokines in the body. The actions of monocytes are known to be influenced by the combinations and concentrations of certain fatty acids (FAs) in blood and dietary fats. However, systemic comparisons of the effects of FAs on cytokine secretion by monocytes have not be performed. In this study, we compared how six saturated FAs (SFAs), two monounsaturated FAs (MUFAs), and seven polyunsaturated FAs (PUFAs) modulate human THP-1 monocyte secretion of TNF, IL-1ß, and IL-6 in the absence or presence of lipopolysaccharide. SFAs generally stimulated resting THP-1 cells to secrete pro-inflammatory cytokines, with stearic acid being the most potent species. In contrast, MUFAs and PUFAs inhibited lipopolysaccharide-induced secretion of pro-inflammatory cytokines. Interestingly, the inhibitory potentials of MUFAs and PUFAs followed U-shaped (TNF and IL-1ß) or inverted U-shaped (IL-6) dose-response curves. Among the MUFAs and PUFAs that were analyzed, docosahexaenoic acid (C22:6 n-3) exhibited the largest number of double bonds and was found to be the most potent anti-inflammatory compound. Together, our findings reveal that the chemical compositions and concentrations of dietary FAs are key factors in the intricate regulation of monocyte-mediated inflammation.

A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes.

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA1c level 8.1% [0.6%]) completed the trial. At week 20, HbA1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.

Delivery of mitochondria confers cardioprotection through mitochondria replenishment and metabolic compliance.

Mitochondrial dysfunction is a hallmark of heart failure. Mitochondrial transplantation has been demonstrated to be able to restore heart function, but its mechanism of action remains unresolved. Using an in-house optimized mitochondrial isolation method, we tested efficacy of mitochondria transplantation in two different heart failure models. First, using a doxorubicin-induced heart failure model, we demonstrate that mitochondrial transplantation before doxorubicin challenge protects cardiac function in vivo and prevents myocardial apoptosis, but contraction improvement relies on the metabolic compatibility between transplanted mitochondria and treated cardiomyocytes. Second, using a mutation-driven dilated cardiomyopathic human induced pluripotent stem cell-derived cardiomyocyte model, we demonstrate that mitochondrial transplantation preferentially boosts contraction in the ventricular myocytes. Last, using single-cell RNA-seq, we show that mitochondria transplantation boosts contractility in dystrophic cardiomyocytes with few transcriptomic alterations. Together, we provide evidence that mitochondria transplantation confers myocardial protection and may serve as a potential therapeutic option for heart failure.

Growth differentiation factor-15 is independently associated with metabolic syndrome and hyperglycemia in non-elderly subjects.

Metabolic syndrome (MetS) is a major health issue worldwide accompanied by cardiovascular comorbidities. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine expressed in cardiomyocytes, adipocytes, macrophages, and endothelial cells. Previous research in elderly subjects revealed that GDF-15 levels were associated with the MetS. However, the association between GDF-15 levels and MetS or its components in the non-elderly subjects remains unclear. In this study, a total of 279 subjects younger than 65-year-old with (n = 84) or without (n = 195) MetS were recruited. MetS was defined according to modified NCEP/ATP III criteria. The GDF-15 levels were measured by an enzyme-linked immunosorbent assay. A multiple linear regression analysis was conducted to identify factors independently associated with GDF-15 levels. Subjects with MetS had higher GDF-15 levels than those without MetS (median (interquartile range), 1.72 ng/mL (1.38, 2.26) vs. 1.63 ng/mL (1.27, 2.07), P = 0.037). With the number of MetS components increased, the GDF-15 levels increased significantly (P for trend = 0.005). Multiple linear regression analysis revealed that the presence of MetS was positively associated with the GDF-15 levels (ß = 0.132, P = 0.037). When substituting MetS with its components, only the presence of hyperglycemia was positively associated with the GDF-15 levels after adjustment for covariates (ß = 0.193, P = 0.003). Taken together, the presence of the MetS in non-elderly was associated with higher GDF-15 levels. Among the MetS components, only hyperglycemia was significantly associated with the GDF-15 levels. Future longitudinal studies will be needed to explore whether GDF-15 has the potential to be a biomarker of gluco-metabolic dysfunction in non-elderly subjects.

Real-World Comparative Evaluation of Add-On Glucagon-like Peptide 1 Receptor Agonist in Type 2 Diabetes Treated with or without Insulin.

Glucagon-like peptide 1 receptor agonist (GLP-1 RA) is a potent antidiabetic agent with cardiorenal and weight-losing benefits in patients with type 2 diabetes (T2D). The combination of GLP-1 RA with basal insulin has been suggested in several clinical studies as a useful treatment for intensifying insulin therapy in T2D. However, there has been no real-world evidence study comparing the glycemic effects of GLP-1 RAs add-on to background treatment with and without insulin. A retrospective study was performed in 358 patients with T2D who initiated liraglutide or dulaglutide. Among them, 147 patients were prior and concurrent insulin users, and 211 patients were non-insulin users. After 12 months of GLP-1 RA treatment, the changes in hemoglobin A1c (HbA1C) and body weight were evaluated. The effectiveness of GLP-1 RAs on HbA1C reduction was greater in insulin users than non-insulin users at 12 months (−1.17% vs. −0.76%; p = 0.018). There was no significant difference in body weight change between insulin users and non-insulin users at 12 months (−1.42 kg vs. −1.87 kg; p = 0.287). The proportion of responders (decrease of HbA1C > 1%) in insulin users was much higher than that in non-insulin users (48% vs. 37 %; p = 0.04). In insulin users, those who had increased insulin dosage at 12 months had significantly less HbA1C reduction than that of non-increased patients (−0.62% vs. −1.57%; p = 0.001). GLP-1 RAs provide superior glucose-lowering effects in insulin-treated patients compared with non-insulin-treated patients with T2D without significant differences in body weight decrease.

Work-Related Stress and Occurrence of Cardiovascular Disease: A 13-Year Prospective Study.

OBJECTIVE: The aim of the study is to investigate the influence of work-related psychological and physical stresses on risk of cardiovascular disease (CVD). METHODS: A total of 5651 CVD-free participants older than 50 years from the Survey of Health, Ageing and Retirement in Europe were followed up for 13 years to detect incident CVD. Work-related stress was assessed using job strain and job reward questionnaire. Cox regression model was used to estimate the association. RESULTS: High physical demands (hazard ratio [HR], 1.30) and low reward (HR, 1.19) compared with their counterparts, as well as active physical jobs (HR, 1.41) and high physical strain (HR, 1.45) in comparison with low physical strain were associated with higher risk of incident CVD after adjusting for confounders. However, combining physically stressful jobs with low reward did not further increase the CVD risk. CONCLUSIONS: Avoiding physically stressful jobs or providing appropriate reward may reduce the occurrence of CVD.

Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Type II Cell Proliferation and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia.

Although it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide- (LPS-) induced BPD rat model and to clarify the underlying mechanism. We demonstrate that antenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature, which restored by hUCMSCs and MVs treatment. Furthermore, MVs were large vesicles with a diameter of 100-900 nanometers and mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, PTEN/AKT and MAPK pathways were associated with the protection of MVs. Taken together, this study suggests MVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuating lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.

Erratum: Comparative study of nanostructured carriers of calcium phosphate and magnesium phosphate loaded with SRT1720 for the protection of H2O2-induced senescent endothelium.

[This corrects the article on p. 2068 in vol. 10, PMID: 30093944.].

High glucose enhances lipopolysaccharide-induced inflammation in cultured BV2 microglial cell line.

INTRODUCTION: Diabetes mellitus emerges as a global health crisis and is related to the development of neurodegenerative diseases. Microglia, a population of macrophages-like cells, govern immune defense in the central nervous system. Activated microglia are known to play active roles in the pathogenesis of neurodegenerative diseases. METHODS: This study aimed to investigate the effects of high glucose on low-dose lipopolysaccharide (LPS)-induced activations of inflammation-related signaling molecules in cultured BV2 microglial cells. RESULTS: Compared to cells cultured in the normal glucose medium (NGM, 5.5 mM), the LPS-induced activation of NF-κB lasted longer in cells cultured in high glucose medium (HGM, 25 mM). HGM also enhanced the expression of inducible nitric oxide synthase (iNOS). Among the mitogen-activated protein kinases, HGM enhanced the LPS-induced phosphorylation of p38 without affecting the phosphorylation of Erk1/2 or JNK. BV2 cells cultured in HGM expressed higher levels of TLR4 than those cells cultured in NGM. CONCLUSION: High glucose aggravated LPS-induced inflammatory responses of microglia via enhancing the TLR4/p38 pathway and prolonging the activation of NF-κB/iNOS signaling. Controlling blood glucose levels is advised to manage neuroinflammation and related neurodegenerative diseases.

Hypoxic preconditioning improves the survival and pro-angiogenic capacity of transplanted human umbilical cord mesenchymal stem cells via HIF-1α signaling in a rat model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious chronic respiratory disease that predominates in the neonatal period. Currently, efficacious and effective specific treatments are lacking. Mesenchymal stem cells (MSCs) transplantation has emerged as a promising option for treating BPD. However, the lower cell survival rate limits its therapeutic efficacy. Hypoxic preconditioning is a direct and effective strategy for promoting MSCs survival, proliferation, and paracrine secretion in the recipient after transplantation, which is greatly important to tissue engineering. We investigated whether hypoxia-pretreated MSCs (HPMSCs) confer superior benefit in an experimental BPD rat model. Neonatal Sprague-Dawley rats were exposed to 80-85% O2 for 14 days. Before tracheal transplantation, the MSCs were pretreated for 48 h with deferoxamine, a chemical hypoxia-mimicking agent. In vitro, the HPMSCs reduced the apoptosis rare, caspase-3 expression, and reactive oxygen species (ROS) generation and promoted proliferation, hypoxia inducible factor-1α (HIF-1α) expression, VEGF secretion, and human umbilical vein endothelial cell tube formation (p < 0.05). In vivo, the HPMSCs restored alveolar structure and lung function, ameliorated pulmonary hypertension, increased vessel density in the BPD rat model (p < 0.05). This work demonstrates for the first time that HPMSCs could have a markedly improved therapeutic effect in BPD, presenting a new potential strategy for the clinical implementation of stem cell biotechnology.

Research progress of the correlation between genotype and phenotype in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease characterized by left ventricular hypertrophy with prevalence of 1/500-1/200. Up to now, 1500 mutations in more than 30 genes have been found to be related to the disease. Pathogenic gene mutations together with polymorphisms of modifying genes and environmental factors play various roles in the disease processes, resulting in phenotypic heterogeneity of the disease, ranging from no symptoms to sudden cardiac death. The pathological phenotypes of HCM mainly include cardiomyocyte hypertrophy, disordered array, fibrosis, myocardial ischemia, and others. In recent years, many research efforts have been devoted to exploring the influence of HCM genotype on phenotype, and development of treatment methods based on genetics. This article focuses on the correction between HCM genotype and phenotype and summarizes the research progresses on HCM in terms of pathogenic genes, pathogenesis, associated modification factors and treatment methods, thereby providing insights on the future research and development on the genetics of HCM.

Associations between GDF15 levels and pre-diabetes in non-obese subjects.

Growth differentiation factor 15 (GDF15) is a stress-response cytokine which belongs to the transforming growth factor ß superfamily. Although GDF15 was initially found to have a role in metabolic diseases, the association between GDF15 and dysglycemic status remains inconclusive. Thus, the aim of this study was to examine the relationships between GDF15 and different glycemic statuses in non-obese subjects. We enrolled 502 non-obese subjects, among individuals who had normal glucose tolerance (NGT; n=125), isolated impaired fasting glucose (IFG; n=116), isolated impaired glucose tolerance (IGT; n=106), IFG plus IGT (n=27), and newly diagnosed diabetes (NDD; n=128). A multivariate linear regression analysis of GDF15 levels was used to find independent predictors. The median (IQR) GDF15 levels were 1641.0 (1187.0-1985.5) pg/mL, 1656.1 (1226.8-2379.7) pg/mL, 1487.8 (1145.9-1987.2) pg/mL, 1722.2 (1172.9-1939.0) pg/mL, and 2204.5 (1767.4-2919.1) pg/mL in NGT, IFG, IGT, IFG plus IGT, and NDD groups, respectively. The NDD group had significantly higher GDF15 levels than those with NGT, IFG, IGT, and IFG plus IGT. The IFG group had a significantly higher GDF15 value than the NGT group. In multivariate linear regression analysis, IFG (beta=0.145, 95% CI 192.487 to 740.937, p=0.001), NDD (beta=0.227, 95% CI 390.459 to 888.145, p<0.001), and high-sensitivity C reactive protein (beta=0.105, 95% CI 3.276 to 27.768, p=0.013) were independently associated with GDF15 levels. Non-obese subjects with isolated IFG and NDD had significantly higher GDF15 levels than those with NGT. In addition, A1C was independently associated with GDF15 levels. IFG and NDD, but not isolated IGT or IFG plus IGT, were positively associated with GDF15 levels.

High-fat diet-induced increases in glucocorticoids contribute to the development of non-alcoholic fatty liver disease in mice.

This study aimed to investigate the causal relationship between chronic ingestion of a high-fat diet (HFD)-induced secretion of glucocorticoids (GCs) and the development of non-alcoholic fatty liver disease (NAFLD). We have produced a strain of transgenic mice (termed L/L mice) that have normal levels of circulating corticosterone (CORT), the major type of GCs in rodents, but unlike wild-type (WT) mice, their circulating CORT was not affected by HFD. Compared to WT mice, 12-week HFD-induced fatty liver was less pronounced with higher plasma levels of triglycerides in L/L mice. These changes were reversed by CORT supplement to L/L mice. By analyzing a sort of lipid metabolism-related proteins, we found that expressions of the hepatic cluster of differentiation 36 (CD36) were upregulated by HFD-induced CORT and involved in CORT-mediated fatty liver. Dexamethasone, an agonist of the glucocorticoid receptor (GR), upregulated expressions of CD36 in HepG2 hepatocytes and facilitated lipid accumulation in the cells. In conclusion, the fat ingestion-induced release of CORT contributes to NAFLD. This study highlights the pathogenic role of CORT-mediated upregulation of hepatic CD 36 in diet-induced NAFLD.

Characterization of butaselen-2,6-dimethyl-β-cyclodextrin inclusion complexes and preparation of injectable solutions / 药学学报

In this study, butaselen-2,‍6-dimethyl-‍β‍-cyclodextrin inclusion complexes were prepared by saturated aqueous solution method to improve the solubility of butaselen, so as to obtain its injection solutions. The content of butaselen in the inclusions was determined by high performance liquid chromatography (HPLC), and then the preparation process was optimized by orthogonal design using the inclusion ratio as an indicator. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) were used to verify the structure of the inclusions. The effects of the inclusions on the solubility and stability of butaselen were also investigated. The results showed that the optimized preparation process with a mass ratio of 1∶340, an encapsulation time of 3 h and an encapsulation temperature of 70 ℃ resulted in an encapsulation ratio of (91.24 ± 0.42) %, and the results of XRD, FTIR and SEM demonstrated the formation of inclusion complexes. The developed HPLC method is rapid, simple, accurate, applicable, specific and reproducible for the determination of butaselen content in butaselen cyclodextrin inclusion complexes, which can lay the foundation for the development of new butaselen dosage forms and clinical applications and provide technical support.