Dietary supplements: clinical cholesterol-lowering efficacy and potential mechanisms of action.

This review aims to analyse the efficacy of dietary supplements in reducing plasma cholesterol levels. Focusing on evidence from meta-analyses of randomised controlled clinical trials, with an emphasis on potential mechanisms of action as supported by human, animal, and cell studies. Certain dietary supplements including phytosterols, berberine, viscous soluble dietary fibres, garlic supplements, soy protein, specific probiotic strains, and certain polyphenol extracts could significantly reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 3-25% in hypercholesterolemic patients depending on the type of supplement. They tended to be more effective in reducing plasma LDL cholesterol level in hypercholesterolemic individuals than in normocholesterolemic individuals. These supplements worked by various mechanisms, such as enhancing the excretion of bile acids, inhibiting the absorption of cholesterol in the intestines, increasing the expression of hepatic LDL receptors, suppressing the activity of enzymes involved in cholesterol synthesis, and activating the adenosine monophosphate-activated protein kinase signalling pathway.

The role of toll-like receptors (TLRs) and their therapeutic applications in glomerulonephritis.

One of the most important features of innate immunity is the presence of a special group of pattern recognition receptors (PRRs) called toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), resulting in a quick and effective immune response to them. Glomerulonephritis (GN) is one of the most important categories of renal disorders characterized by destructive responses of the immune system to the glomerulus. To date, the association of TLRs as important innate immune system members with GN has been one of the topics that attracted the attention of researchers in this field. However, the exact role of these receptors in the immunopathogenesis of GN has not yet been fully discussed. Therefore, this study aims to overview the role of TLRs in GN and the possibility of using them as a potential therapeutic target.

Therapeutic effect of sodium­glucose cotransporter 2 inhibitor and benazepril on diabetic nephropathic rats.

The present study aimed to compare the therapeutic effect of sodium/glucose cotransporter 2 (SGLT2) inhibitor and benazepril on diabetic nephropathy (DN) rats and provide a potential novel agent for the clinical treatment of DN. The DN model was established on rats. Animals were dosed orally with SGLT2 and benazepril daily for 4 weeks. The pathological state of renal tissues were evaluated using hematoxylin and eosin, Masson and periodic acid-Schiff staining. The change in the morphology of renal tissues was observed through transmission electron microscopy. Western blotting was utilized to determine the expression level of TGF-ß, N-terminal fragment of the B-type natriuretic peptide precursor (NT-proBNP) and matrix metalloproteinase-9 (MMP-9). The expression level of endothelin 1 (ET-1), von Willebrand factor (vWF), collagen (col)-I and α smooth muscle actin (α-SMA) in renal tissues was visualized using immunohistochemical assay. Significant pathological changes in the glomerular basement membrane, mesangial membrane, renal tubules, lumen, renal interstitial region and renal tubular epithelial cells were observed in DN rats, accompanied by increased collagen fibers. SGLT2 inhibitor treatment demonstrated more alleviatory effects on the pathological changes of renal tissues compared with benazepril. Compared with control, TGF-ß and NT-proBNP were upregulated in DN rats, accompanied by the downregulation of MMP-9, ET-1, vWF, col-I and α-SMA, which were markedly reversed by treatment with SGLT2 inhibitor and benazepril. Compared with benazepril, the effects of SGLT2 inhibitor on the expression level of TGF-ß, NT-proBNP, MMP-9, ET-1, vWF, col-I and α-SMA were more significant. Overall, SGLT2 inhibitor demonstrated an increased therapeutic effect against DN rats compared with benazepril by regulating cytokines, renal fibrosis and extracellular matrix degradation.

Carney complex presenting as subclinical Cushing syndrome in a child due to a novel Phosphodiesterase 11A mutation.

Background: Several disease-causing genes have been implicated in Carney complex (CNC), including PRKAR1A, PDE8B(Phosphodiesterase 8B),and PDE11A (Phosphodiesterase 11A). The purpose of this study was to describe the clinical features of CNC in a Chinese patient and identify potential pathogenic mutations. Methods: Genomic DNA was extracted from the peripheral venous blood obtained from one Chinese CNC family from Shandong province. Subsequently, targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate likely pathogenic mutations. Results: Genetic analyses revealed a novel PDE11A variant that was predicted to lead to CNC. The patient's mother presented with the same genetic mutation. Conclusion: This study identifies new genetic mutation in CNC（PDE11A: NM_016953: exon11: c1921A>G (p./p.Lys641Glu). CNC patients presenting with subclinical Cushing's syndrome should be treated.

Multi-parameter influenced acquisition model with an in-orbit jitter for inter-satellite laser communication of the LCES system.

With the development of large low earth orbit (LEO) communication constellations, the efficiency of laser inter-satellite link (ISL) establishing become the bottleneck for subsequent large-scale launch and rapid networking applications of LEO communication constellations. Hence, we establish the pointing jitter error structure of LEO communication experiment satellites (LCES) system. The error structure can be used to trace the source of errors and evaluate the in-orbit jitter. And we derive an analytical expression of the acquisition probability density function (PDF) which comprehensively considering the influence of the scanning region, the pointing jitter error, the overlap factor and the in-orbit jitter error. The multi-parameter influenced acquisition model is validated by Monte Carlo (MC) simulations and semi-physical tests. The results reveals that the multi-parameter influenced acquisition model can be used to guide the in-orbit ISL establishing.

Exploring the Impact of Individual and Social Antecedents on Teachers' Teaching Innovation: Perspective of Goal-Oriented Behavior and Social Identity.

Many scholars have investigated education management. Scholars in the education field have made significant achievements in contributing to multiple educational reform policies, while other scholars discuss teacher-related issues from the perspective of organizational behavior. The teaching innovation of high school teachers plays a critical role in students' learning attitude and motivation, especially in the context of the COVID-19 pandemic. Teachers need to utilize more diversified teaching methods to enable students to carry out effective learning. In order to examine teachers' teaching innovation, this study explores teaching innovation intentions and performance from the perspective of individual and social factors in combination with goal-oriented behavior and social identity theory. This study conducts questionnaires with a sample of Chinese coastal high school teachers, and obtains a total of 475 responses. The research results show that innovation attitude, positive anticipated emotion, group norms and social identity positively affect teachers' teaching innovation intention; furthermore, teachers' teaching innovation intention also positively affects their teaching innovation performance. Based on the comprehensive research findings, this research proposes corresponding theoretical and practical implications.

How Determinants of Employee Innovation Behavior Matter During the COVID-19 Pandemic: Investigating Cross-Regional Role via Multi-Group Partial Least Squares Structural Equation Modeling Analysis.

The COVID-19 pandemic cropping up at the end of 2019 started to pose a threat to millions of people's health and life after a few weeks. Nevertheless, the COVID-19 pandemic gave rise to social and economic problems that have changed the progress steps of individuals and the whole nation. In this study, the work conditions for employees from Taiwan, Malaysia, and the Chinese mainland are explored and compared, and the relationship between support mechanisms and innovation behaviors (IB) is evaluated with a view of the social cognitive career theory. This study adopts the cross-sectional survey and purposive sampling to collect questionnaires. A total of 623 copies of a questionnaire from Taiwanese, 440 copies from Malaysians, and 513 copies from mainlanders were collected in this study to compare the three groups in developing employees' IBs. Smart-partial least squares for partial least squares structural equation modeling was applied in the structural model to conduct a verification of the hypotheses and comparative analysis in this study. According to the findings, compared with employees from the Chinese mainland, the Taiwanese and Malaysian samples show more significant paths regarding employee employability, IB, prior knowledge, perceived organizational support, self-efficacy, and job performance. Our results will offer more insights and advice concerning theories of human resource.

Characterization of the complete chloroplast genome of Tulipa iliensis (Liliaceae).

The chloroplast genome and evolutionary relationship analysis of Tulipa gesneriana L. could provide fundamental genetic reference for its molecular breeding and biological research. The complete chloroplast genome of Tulipa iliensis was sequenced and reported here. Its chloroplast genome was 151,744 bp in length, containing a pair of inverted repeated regions (26,354 bp) which were separated by a large single copy region of 81,794 bp, and a small single copy region of 17,242 bp. Moreover, a total of 133 functional genes were annotated, including 87 mRNA, 38 tRNA genes, and 8 rRNA genes.The phylogenetic relationships of 16 species indicated that T. iliensis was closely related to T. altaica.

Long non-coding RNA MALAT1 promotes cardiac remodeling in hypertensive rats by inhibiting the transcription of MyoD.

Hypertension is the leading preventable cause of premature deaths worldwide. Although long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has been identified to play important roles in the development of cardiovascular diseases, the regulatory function of lncRNA MALAT1 in hypertension remains poorly understood. This study aimed to explore the role of lncRNA MALAT1 in spontaneously hypertensive rats (SHRs). LncRNA MALAT1 was determined to be elevated and MyoD to be reduced in myocardial tissues and thoracic aortic vascular tissues of SHRs. Over-expression of lncRNA MALAT1 caused severe myocardial fibrosis in SHRs. In addition, lncRNA MALAT1 over-expression in vitro enhanced arterial smooth muscle cells (ASMCs) activity and fibrosis of SHRs, which, was rescued by over-expressed MyoD. Furthermore, lncRNA MALAT1 transcripts were found to be highly enriched in the nucleus, and lncRNA MALAT1 suppressed the transactivation of MyoD. Moreover, lncRNA MALAT1 was found to recruit Suv39h1 to MyoD-binding loci, leading to H3K9me3 trimethylation and down-regulation of the target gene. Taken conjointly, this study revealed an important role of lncRNA MALAT1 in promoting cardiac remodeling in hypertensive rats by inhibiting the transcription of MyoD. These results highlight the value of lncRNA MALAT1 as a therapeutic target for the management of hypertension.

Protective effect of umbilical cord mesenchymal stem cells combined with resveratrol against renal podocyte damage in NOD mice.

BACKGROUND: The role of chronic inflammation initiated by persistent hyperglycemia in podocyte injury has attracted increasing attention. The advanced glycation end products (RAGE) receptor- nuclear factor-kappa B (NF-кB) signaling pathway is involved in the occurrence of inflammation. We speculate that treatment with human umbilical cord mesenchymal stem cells (hUCMSCs) combined with resveratrol can block this signaling pathway and protect podocyte function. METHODS: Non obesity diabetes(NOD) mice were randomly divided into 5 groups: NOD-T1DM, Res, hUCMSCs, hUCMSCs + Res and insulin (INS)groups. Mice without diabetes were classified as NOD control group(NOD group). Blood glucose(BG), blood urea nitrogen(BUN), serum creatinine(SCr), 24-h urine albumin excretion rate (UAER) were measured. The expression of nephrin, WT1 and RAGE, MCP-1 in renal tissues were detected by Western blot, expression of NF-кB protein(P65) was determined by immunohistochemistry. RESULTS: The combined treatment of hUCMSCs and Resveratrol can reduce BG, BUN, SCr, 24-h UAER, and the expression of the inflammatory factors MCP-1, RAGE and NF-кB; increase the number of podocytes and the expression of the podocyte-related proteins nephrin and WT1 in type 1 diabetes mellitus, and improve renal pathological structure. CONCLUSIONS: Combining of hUCMSCs and resveratrol can better protect renal podocyte function, and the effects on the reduction of blood glucose and renal injury are better than those obtained by insulin treatment. This indicated that the combination of Res and hUCMSCs may be a novel therapeutic method for the treatment of DN.

Bisphenol S Triggers the Migration and Invasion of Pheochromocytoma PC12 Cells via Estrogen-Related Receptor α.

Pheochromocytoma (PCC) is a tumor of the adrenal medulla for which surgical resection is the only therapy approach. Risk factors responsible for the tumorigenesis and progression of PCC are not well illustrated. Our present study revealed that an industrial chemical, bisphenol S (BPS), can promote the migration and invasion of PCC PC12 cells, which was evidenced by the upregulation of fibronectin (FN) and matrix metalloproteinases (MMP-2 and MMP-9). The inhibitor of estrogen-related receptor α (ERRα), while not estrogen receptor α/ß (ERα/ß) or G protein-coupled estrogen receptor (GPER), can attenuate BPS-induced cell migration. Mechanically, BPS can increase the binding between ERRα and promoter of FN1 and then induce the expression of FN in PC12 cells. Further, BPS can induce the expression of miR-10b in PC12 cells via ERRα. The upregulated miR-10b inhibited the expression of KLF4, which can suppress the migration and invasion of cancer cells. BPS can trigger the mRNA and protein expression of ERRα in PC12 cells via a time-dependent manner. Collectively, our study revealed that nanomolar BPS can trigger the migration and invasion of PC12 cells via activation and upregulation of ERRα.

miR-146a down-regulation alleviates H2O2-induced cytotoxicity of PC12 cells by regulating MCL1/JAK/STAT pathway : miR-146a down-regulation relieves H2O2-induced PC12 cells cytotoxicity by MCL1/JAK/STAT.

Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in H2O2-induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 µM of H2O2 to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in H2O2-induced PC12 cells. Functional analysis showed that down-regulation of miR-146a alleviated H2O2-induced cytotoxicity in PC12 cells. Dual-luciferase reporter and western blot assay verified that MCL1 was a direct target gene of miR-146a. Moreover, anti-miR-146a-mediated suppression on cell cytotoxicity was abated following MCL1 knockdown in H2O2-induced PC12 cells. Furthermore, MCL1 activated JAK/STAT signaling pathway and MCL1 overexpression attenuated H2O2-induced cytotoxicity in PC12 cells by JAK/STAT signaling pathway. In conclusion, this study suggested that suppression of miR-146a abated H2O2-induced cytotoxicity in PC12 cells via regulating MCL1/JAK/STAT pathway.

Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.

Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature-dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake. In high-fat diet-fed mice, low temperature exposure improved browning of visceral fat, global metabolism via nonshivering thermogenesis, insulin sensitivity, and hepatic steatosis. Genome-wide expression profiling showed upregulation of WAT browning-related genes including Cidea and Dio2. Conversely, Prdm16 was unchanged in healthy mice or was downregulated in obese mice. Surgical removal of visceral fat and genetic knockdown of UCP1 in epididymal fat largely ablated low temperature-increased global thermogenesis and resulted in the death of most mice. Thus, browning of visceral fat may be a compensatory heating mechanism that could provide a novel therapeutic strategy for treating visceral fat-associated obesity and diabetes.

Nursing Care of Lower Respiratory Tract Infection After Abdominal Surgery.

The harm, the causes, and nursing care methods of lower respiratory tract infection after abdominal operation were described in this article.

Upregulation of ICAM-1 in diabetic rats after transient forebrain ischemia and reperfusion injury.

BACKGROUND: Hyperglycemia exacerbates brain damage caused by cerebral ischemia. Neuroinflammation may play a role in mediating such enhanced damage. The objectives of this study were to examine the mRNA and protein levels and cell type distribution of ICAM-1 after cerebral ischemia in normo-and diabetic hyperglycemic rats. RESULTS: Compared to normoglycemic ischemia animals, diabetes aggravated neuronal death, decreased Nissl body staining, and increased ICAM-1 mRNA and protein levels in the frontal cortex. The increased ICAM-1 was located not only in vascular endothelial cells but also in cortical neurons. CONCLUSIONS: Our results suggest that exacerbated neuro-inflammation in the brain may mediate the detrimental effects of diabetes on the ischemic brain.

Comparison of a multiple daily insulin injection regimen (glargine or detemir once daily plus prandial insulin aspart) and continuous subcutaneous insulin infusion (aspart) in short-term intensive insulin therapy for poorly controlled type 2 diabetes patients.

Aims. To examine the potential differences between multiple daily injection (MDI) regimens based on new long-acting insulin analogues (glargine or detemir) plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII) in patients with poorly controlled type 2 diabetes. Methods. Patients (n = 119) with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes.

Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes.

AIM: To evaluate the correlation between nonalcoholic fatty liver disease (NAFLD) and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS: Data were obtained from 1217 inpatients with T2DM (757 females, 460 males; aged 63.39 ± 12.28 years). NAFLD was diagnosed by hepatic ultrasonography. Diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR) were diagnosed according to their respective criteria. The prevalence of NAFLD and the independent correlations of clinical characteristics with NAFLD were determined by cross-tabulation and logistic regression, respectively. RESULTS: Approximately 61% of inpatients with T2DM in Qingdao, China had NAFLD, which decreased significantly with increase in age and prolonged course of diabetes. The prevalence of NAFLD in patients presenting with DN, DPN and DR was 49.4%, 57.2% and 54.9%, respectively. These rates were significantly lower than those of patients without DN, DPN and DR (65.9%, 65.6% and 66.1%, respectively, P < 0.05). Participants with NAFLD had greater body weight, waist circumference (WC), body mass index (BMI), fasting blood glucose (FBG), hemoglobin A1c, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, blood pressure, as well as triglyceride (TG) levels and lower high-density lipoprotein (HDL) concentration than those without NAFLD (P < 0.05). NAFLD was positively correlated with BMI, WC, TG, FBG, diastolic blood pressure, and systolic blood pressure but negatively correlated with the duration of diabetes, DR, DPN, DN, and HDL. CONCLUSION: Despite the benign nature of NAFLD, efforts should be directed toward early diagnosis, intensive blood glucose and blood pressure control, and effective dyslipidemia correction.

The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats.

Metformin appears to be involved in altering energy expenditure and thermogenesis, and could affect hypothalamic feeding circuits. However, it is not clear whether metformin is able to cross the blood-brain barrier (BBB) to reach the hypothalamus and exert a direct effect on the central nervous system. Here we show the presence of metformin in cerebrospinal fluid (CSF) of diabetic rats administered orally with metformin which was confirmed by detecting the concentration of metformin with liquid chromatography-tandem mass spectrometry. Food intake of diabetic rats treated with metformin was reduced, and glucose homeostasis was gained. Expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased in the hypothalamus of metformin-treated diabetic rats, though anorexigenic peptides pro-opiomelanocortin (POMC) did not change significantly. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) was increased but phosphorylated AMP-activated kinase (AMPK) was similar in the hypothalamus of metformin-treated diabetic rats. Our findings suggest that metformin may cross BBB and play a central mechanism on regulation of food intake in the hypothalamus. The anorexic effect of metformin may be mediated by inhibition of NPY and AgRP gene expression through the STAT3 signaling pathway.

Increased expression of CYP17 and CYP11B1 in subclinical Cushing's syndrome due to adrenal adenomas.

OBJECTIVES: To determine whether steroidogenic enzyme expression is associated with the steroid secretory pattern of subclinical Cushing's syndrome (SCS) by investigating the mRNA and protein expression of CYP17 and CYP11B1 in SCS adenomas, normal adrenal cortices (NA), non-functional adrenal adenomas (NFA) and cortisol-producing adenomas (CPA). METHODS: Total RNA and protein were extracted from 20 CPA, six SCS, 15 NFA, and eight NA. Real-time quantitative polymerase chain reaction (PCR) and western blotting analysis were performed to determine the mRNA and protein expression of CYP17 and CYP11B1 in different tissues. The expression of CYP17 and CYP11B1 in the adrenocortical tumors was compared expression in NA. RESULTS: Expression of both CYP11B1 and CYP17 mRNA and protein was detected in all samples tested. The expression of CYP11B1 mRNA and protein was significantly higher in the CPA group than in the other groups and was slightly higher in SCS samples compared with NA and NFA samples (all P < 0.05). There was no significant difference in CYP11B1 mRNA and protein expression between NA and NFA samples (P > 0.05). The expression of CYP17 mRNA and protein in different tissues was similar to that of CYP11B1. Neither CYP11B1 nor CYP17 mRNA and protein expression was correlated with plasma cortisol or adrenocorticotrophin levels (all P > 0.05). CONCLUSIONS: In conclusion, CYP11B1 and CYP17 are overexpressed in subclinical CPA and their overexpression accounts for the increased production of cortisol that is characteristic of CPA.