Relationship Between Thyroid Hormone and Liver Steatosis Analysis Parameter in Obese Participants: A Case-Control Study.

Objective: The thyroid hormone has been demonstrated to be associated with nonalcoholic fatty liver disease (NAFLD) in different populations. However, the relationship between thyroid hormone and the degree of liver steatosis in overweight/obese subjects is still unclear. Liver ultra-sound attenuation (LiSA) is a newly developed ultrasound attenuation parameter for the analysis of hepatic steatosis. The study aimed to characterize the relationship between thyroid hormone and LiSA in overweight/obese participants. Methods: This case-control study was performed in Ningbo First Hospital, China. A total of 24 lean, 66 overweight and 49 obese participants were consecutively recruited from January 2021 to May 2021. Thyroid hormone and other clinical features were measured. LiSA was acquired by using a Hepatus ultrasound machine. Multiple linear regression analyses were performed to examine associations of LiSA and clinic indices. Results: Obese subjects had higher LiSA, fT3 and TSH levels than lean participants of similar age and sex (P < 0.05). LiSA was positively associated with the fT3 level. The multiple linear regression analyses showed that fT3 (ß = 0.353, P < 0.001) was independently associated with LiSA in overweight/obese participants. Conclusion: The fT3 level was independently associated with the degree of liver steatosis among the overweight/obese participants.

IGF-1 contributes to liver cancer development in diabetes patients by promoting autophagy.

INTRODUCTION AND OBJECTIVES: Type 2 diabetes mellitus (T2DM) increases the occurrence and mortality of liver cancer. Insulin growth factor (IGF) plays a crucial role in the development of diabetes and liver cancer, and specifically, IGF-1 may be involved in the development of liver cancer with preexisting T2DM. Autophagy contributes to cancer cell survival and apoptosis. However, the relationship between IGF-1 and autophagy has rarely been evaluated. The purpose of this study was to investigate whether IGF-1 promotes the development of liver cancer in T2DM patients by promoting autophagy. MATERIALS AND METHODS: Thirty-three hepatocellular carcinoma (HCC) patients with T2DM and 33 age-matched patients with HCC without T2DM were included in this study. We analyzed the expression of IGF-1 and autophagy-related LC3 and p62 mRNA and the prognosis of two groups. In vitro, we stimulated HepG2 cells with IGF-1 and then detected changes in autophagy and cell proliferation, apoptosis, and migration in the presence/absence of wortmannin, an autophagy inhibitor. RESULTS: IGF-1 promoted autophagy, resulting in inhibition of apoptosis and induction of growth and migration of HepG2 cells. Inhibition of autophagy by wortmannin impaired IGF-1 function. Higher expression of IGF-1 was detected in HCC patients with T2DM. IGF-1 expression was higher in liver cancer tissue compared to paracancerous tissue. Elevated IGF-1 was associated with a poor prognosis in patients with HCC. CONCLUSIONS: IGF-1 participates in the development of liver cancer by inducing autophagy. Elevated IGF-1 was a prognostic factor for patients with HCC, especially when accompanied by T2DM.

Cross talk between exosomes and pancreatic ß-cells in diabetes.

Exosomes are a class of extracellular vesicles with a diameter of 50-100 nm secreted by various cells. They are generated through complex intracellular production mechanisms before being secreted to the extracellular environment. Due to their inclusion of proteins, lipids, and nucleic acids, exosomes play an important role in intercellular communication. Pancreatic ß-cells play an irreplaceable role in the body's glucose metabolism. Their dysfunction is one of the causes of diabetes. Exosomes of various cells regulate the function of ß-cells by regulating autoimmunity, delivering non-coding RNAs, or directly regulating intracellular signal pathways. This communication between ß-cells and other cells plays an important role in the pathogenesis and development of diabetes, and has potential for clinical application. This paper reviews the biological sources and functions of exosomes, as well as intercellular crosstalk between ß-cells and other cells that is involved in ß-cell failure and regeneration.

Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines.

Colorectal cancer is a common malignant tumor of the gastrointestinal tract. Currently, the main treatment is surgical resection, which can be combined with other treatments. However, treatment efficacy is poor, and colorectal cancer is prone to relapse and metastasis; thus, identifying an effective anti-cancer drug is an urgent requirement. The present study examined the antagonistic effect of penicillin on cultured colorectal cancer cells and the related mechanism. A MTT assay was used to assess the growth of the colorectal cancer cells treated with penicillin and to determine the optimal drug concentration. The wound healing and Transwell invasion assays were performed to investigate the effect of penicillin on the migration and invasion of the colorectal cancer cells. Live cell mitochondrial energy metabolism analysis was performed to detect changes in mitochondrial energy metabolism of the colorectal cancer cells, while western blot analysis was used to measure the expression of cytochrome c and autophagy-related protein, LC3. RFP-GFP-LC3 lentivirus was used to detect autophagic flux, and autophagosomes were observed using a transmission electron microscope, while flow cytometry was used to analyze the effect of penicillin on cell cycle progression and apoptosis of the colorectal cancer cells. After penicillin treatment, the growth, migration and invasion ability of the colorectal cancer cells were inhibited. The mitochondrial energy metabolism of the cell was impaired, and the basic respiratory capacity, maximum respiratory capacity, respiratory potential, and ATP production were all reduced. The protein expression levels of the autophagy-related proteins, LC3-II/LC3-I increased in a dose- and time-dependent manner. In addition, autophagy flux and the number of autophagosomes increased, and mitochondrial structural damage was observed. The cell cycle was arrested at the G1 phase, the number of early apoptotic cells increased and the protein expression level of cleaved caspase-3 increased, while penicillin-induced apoptosis was blocked by the autophagy inhibitor 3-MA. In conclusion, penicillin disrupted mitochondrial function and energy metabolism in the colorectal cancer cells, which resulted in the induction of autophagic apoptosis and ultimately the inhibition of cancer cell growth and metastasis.

Differential expression of long non-coding RNAs SRA, HCG22 and MHRT in children with Kawasaki disease.

Kawasaki disease (KD) is an acute, self-limited inflammatory illness during childhood that may lead to thrombosis in the coronary arteries (CA). The major aims of the present study were to estimate the serum levels of long non-coding RNAs (lncRNAs) and the metabolic profiles of patients with KD. A total of 40 specimens were obtained from pediatric patients (40 specimens before and 40 specimens after treatment) who were diagnosed with KD (n=40). The controls comprised healthy children without KD (n=40). The serum levels of lncRNAs steroid receptor RNA activator (SRA), human leukocyte antigen complex group 22 (HCG22) and myosin heavy chain-associated RNA transcript (MHRT) were determined using reverse transcription-quantitative PCR. Subsequently, the correlation between the expression levels of lncRNAs and biochemical parameters of patients was assessed. Receiver operating characteristic curves were constructed to determine the diagnostic value of the lncRNAs. The results indicated that the serum levels of lncRNAs SRA and HCG22 were higher in patients with acute KD compared with those in healthy controls. B-type natriuretic peptide (BNP) and C-reactive protein were positively correlated with HCG22 in patients with acute KD, while total cholesterol and low-density lipoprotein were negatively correlated with HCG22 in patients with acute KD. The lncRNA MHRT was significantly upregulated in convalescent KD compared with acute KD following intravenous immunoglobulin therapy. In patients with convalescent KD, creatine kinase was positively correlated with MHRT, while BNP and adenosine deaminase were negatively correlated with MHRT. In conclusion, to the best of our knowledge, the present study was the first to identify that the serum levels of lncRNAs SRA and HCG22 in patients with acute KD were higher compared with those in control subjects. MHRT levels in patients with convalescent KD were higher than those in the acute phase. LncRNAs SRA and HCG22 may have crucial roles in KD and are potential novel diagnostic biomarkers for KD. LncRNA MHRT may be considered a novel biomarker for predicting the clinical prognosis of patients with KD.

Hsa_circ_0054633 association of C peptide is related to IL-17 and TNF-α in patients with diabetes mellitus receiving insulin treatment.

BACKGROUND: Chronic inflammation damaged the islet and resulted in dysfunction of T2D. Circular RNA is stable and better for biomarker in many diseases. Here, we aimed to identify potential circular RNA hsa_circ_0054633 that can be a biomarkers for the effects of insulin therapy in T2D. METHODS: In this retrospective case-control study, patients were from Li Huili Hospital, Ningbo, China, from February 10, 2019, to August 15, 2019. We included 47 healthy adults, 46 new-onset T2D with insulin resistance, and 51 patients with insulin therapy. Serum inflammation factors were tested by ELISA assays. We selected hsa_circ_0054633 as a candidate biomarker and measured its concentration in serum by qRT-PCR. The Pearson correlation test was used to evaluate the correlation between this circRNA and clinical variables. RESULTS: Clinical data indicated that serum C peptide was increased in T2D treatment with insulin. Serum hsa_circ_0054633 was decreased in insulin treatment group. Hsa_circ_0054633 was negative correlated with C peptide (r = -0.2841, p = 0.0433,). IL-1 and IL-6, IL-17, and TNF-α were higher in T2D patients and decreased after insulin treatment, only IL-17 and TNF-α showed a positive correlation to hsa_circ_0054633 (r = 0.4825, p < 0.0001, and r = 0.6190, p < 0.0001). The area under ROC curve was 0.7432, 0.5839, and 0.7573 for Hsa_circ_0054633, C peptide, and their combination. CONCLUSION: Hsa_circ_0054633 level was lower in T2D with insulin treatment than untreated and was a negative correlation with C peptide, and positively correlated with IL-17 and TNF-α, suggesting that hsa_circ_0054633 may be a potential early indicator of insulin treatment effect to improve inflammation condition.

Lower expression of Hsa_circRNA_102682 in diabetic hyperhomocysteinemia negatively related to creatinemia is associated with TGF-ß and CTGF.

BACKGROUND: Diabetic nephropathy is a kidney disease caused by long-term hyperglycemia. Hsa_circRNA_102682 is related to the pathogenesis of preeclampsia. Preeclampsia is related to hypertension and proteinuria, and diabetic nephropathy is mainly manifested by hypertension and proteinuria. The main pathological change in diabetic nephropathy is glomerular fibrosis. METHODS: This study used serum samples of patients treated at Li Huili Eastern Hospital, Ningbo, China, from July 10, 2018 to February 15, 2019. We included 73 patients with diabetes and divided them into a normal-homocysteine group and a high-homocysteine group. We selected used quantitative reverse transcriptase-polymerase chain reaction to measure Hsa_circRNA_102682 concentration in the serum. Serum transforming growth factor-beta and connective tissue growth factor levels were tested using ELISA. The Pearson correlation test was used to assess the correlations between Hsa_circRNA_102682, transforming growth factor-beta, connective tissue growth factor, homocysteine, and creatinine. RESULT: Hsa_circRNA_102682 was significantly lower in diabetic patients with high levels of homocysteine than in those with normal levels of homocysteine, whereas transforming growth factor-beta and connective tissue growth factor levels were higher in diabetic patients with hyperhomocysteinemia. Hsa_circRNA_102682 was negatively correlated with the levels of transforming growth factor-beta, connective tissue growth factor, homocysteine, and creatinine. Transforming growth factor-beta and connective tissue growth factor were both positively correlated with homocysteine and creatinine. CONCLUSION: Low Hsa_circRNA_102682 was associated with high levels of transforming growth factor-beta and connective tissue growth factor as well as homocysteine and creatinine. These results suggest that Hsa_circRNA_102682 might be related to the pathogenesis of hyperhomocysteinemia in diabetic nephropathy.

Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus.

Ferroptosis is a novel form of nonapoptotic regulated cell death (RCD). It features iron-dependent lipid peroxide accumulation accompanied by inadequate redox enzymes, especially glutathione peroxidase 4 (GPX4). RAS-selective lethal 3 (RSL3), erastin, and ferroptosis inducing 56 (FIN56) induce ferroptosis via different manners targeting GPX4 function. Acyl-CoA synthetase long-chain family 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and lipoxygenases (LOXs) participate in the production of lipid peroxides. Heat shock protein family B member 1 (HSPB1) and nuclear receptor coactivator 4 (NCOA4) regulate iron homeostasis preventing ferroptosis caused by the high concentration of intracellular iron. Ferroptosis is ubiquitous in our body as it exists in both physiologic and pathogenic processes. It is involved in glucose-stimulated insulin secretion (GSIS) impairment and arsenic-induced pancreatic damage in the pathogenesis of diabetes. Moreover, iron and the iron-sulfur (Fe-S) cluster influence each other, causing mitochondrial iron accumulation, more reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, failure in biosynthesis of insulin, and ferroptosis in ß-cells. In addition, ferroptosis also engages in the pathogenesis of diabetic complications such as myocardial ischemia and diabetic cardiomyopathy (DCM). In this review, we summarize the mechanism of ferroptosis and especially its association with type 2 diabetes mellitus (T2DM).

Circulating miRNAs miR-574-5p and miR-3135b are potential metabolic regulators for serum lipids and blood glucose in gestational diabetes mellitus.

OBJECTIVES: MicroRNAs (miRNAs) are potentially involved in the regulation of glucose and lipid metabolism. The aim of this study was to investigate potential miRNA regulators for serum lipids and blood glucose in gestational diabetes mellitus. METHODS: Plasma samples were obtained from 53 women with GDM and 46 normal pregnant women. Fasting blood glucose and a blood lipid profile were measured. Plasma miRNA expression profiles were analyzed using microarray. To verify the microarray data, the expression of miRNAs was evaluated by real-time PCR. Gene ontology (GO) and genes and genomics (KEGG) pathway enrichment of the predicted target genes of miRNAs were analyzed. RESULTS: The miRNA expression profiles of plasma samples from healthy and GDM women are distinct. We identified 93 differently expressed miRNAs. Compared with healthy pregnant women, 48 miRNAs including miR-574-5p and miR-3135b exhibited significantly lower expression in plasma samples from GDM patients. The expression of miR-574-5p was significantly correlated with levels of blood glucose and LDL-C; miR-3135b was significantly correlated with HDL-C. Some predicted common target genes of these two miRNAs are associated with the metabolism of glucose and lipids as well as the insulin signaling pathway. CONCLUSIONS: miR-574-5p and miR-3135b may serve as metabolic regulators of glucose and lipids for GDM.

Expression of long non-coding RNA H19 in colorectal cancer patients with type 2 diabetes.

The aim of this study was to explore the lncRNAs expression in colorectal cancer (CRC) patients with type 2 diabetes (T2DM) and evaluate the diagnostic value of lncRNAs expression in CRC patients with T2DM. The present study was conducted on two cohorts with CRC patients. The tissues levels of lncRNAs were measured by real-time PCR analysis. The results showed that H19 and MALAT1 expression were higher in CRC tissues than in normal colorectal mucosa (p = 1.59 × 10-6 and p = 6.95 × 10-9, respectively), whereas lincRNA-p21 showed lower expression in CRC tissues (p = 1.10 × 10-4). Logistic regression analysis results indicated that the expression of H19 was significantly lower in CRC patients with T2DM compared with CRC patients without T2DM (p = .032). H19 expression in CRC group without T2DM was significantly associated with hypertension (p = .040). Additionally, the area under the receiver operating characteristic curve of H19 was 0.672 of the group CRC with T2DM, which suggests that H19 could be a useful biomarker and predictive targets for diagnosis of T2DM in CRC patients.

Acellular Collagen Scaffold With Basic Fibroblast Growth Factor for Repair of Traumatic Tympanic Membrane Perforation in a Rat Model.

OBJECTIVE: To evaluate the efficacy of acellular collagen scaffold (ACS) in combination with basic fibroblast growth factor (bFGF) for the repair of traumatic tympanic membrane (TM) perforation in a rat model. STUDY DESIGN: A prospective controlled animal study in a rat model of traumatic TM perforation. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Sprague-Dawley rats (N = 84) with unilateral traumatic perforation of the right TMs were randomized to receive ACS, bFGF, ACS in combination with bFGF (ACS/bFGF), or nothing (spontaneous healing without any interventions as a control group). The healing outcomes were evaluated by otoscopy, optical coherence tomography, histology, and transmission electron microscopy at 1, 2, and 4 weeks postoperatively. The hearing outcomes were assessed with auditory brainstem response testing. RESULTS: ACS/bFGF resulted in higher perforation closure rates at an earlier stage than spontaneous healing, ACS, and bFGF. Based on histology, optical coherence tomography, and transmission electron microscopy, a trilaminar structure and uniform thickness with mature, densely packed collagen fibers were seen in the ACS/bFGF group. Auditory brainstem response evaluation also showed that ACS/bFGF treatment promoted faster functional hearing recovery as compared with the control group. CONCLUSIONS: ACS is an effective TM scaffold and a carrier for bFGF. ACS/bFGF improves the TM closure rate, results in better-reconstructed TMs, and improves hearing. ACS/bFGF serves as a potential substitute for TM perforations in clinical settings.

Mitochondrial dysfunction and pancreatic islet ß-cell failure (Review).

Pancreatic ß-cells are the only source of insulin in humans. Mitochondria uses pyruvate to produce ATP as an intermediate link between glucose intake and insulin secretion in ß-cells, in a process known as glucose-stimulated insulin secretion (GSIS). Previous studies have demonstrated that GSIS is negatively regulated by various factors in the mitochondria, including tRNALeu mutations, high p58 expression, reduced nicotinamide nucleotide transhydrogenase activity, abnormal levels of uncoupling proteins and reduced expression levels of transcription factors A, B1 and B2. Additionally, oxidative stress damages mitochondria and impairs antioxidant defense mechanisms, leading to the increased production of reactive oxygen species, which induces ß-cell dysfunction. Inflammation in islets can also damage ß-cell physiology. Inflammatory cytokines trigger the release of cytochrome c from the mitochondria via the NF-κB pathway. The present review examined the potential factors underlying mitochondrial dysfunction and their association with islet ß-cell failure, which may offer novel insights regarding future strategies for the preservation of mitochondrial function and enhancement of antioxidant activity for individuals with diabetes mellitus.

Long-term supplementation of dehydroepiandrosterone improved depressive-like behaviors by increasing BDNF expression in the hippocampus in ovariectomized rats.

OBJECTIVE: Dehydroepiandrosterone (DHEA), a precursor of estrogen, partially exhibits its biological effect after conversion to estrogen. Its biological significance in perimenopausal depressive disorder or postpartum depression remains unknown. Here, we observed the effects of long-term supplementation of DHEA on depression-like behaviors in ovariectomized rats. METHODS: We established the model as one of sex hormone deficiency in female rats by bilateral ovariectomy. We observed the effects of 13.3 mg/kg DHEA or 0.27 mg/kg estradiol were given daily by gavage for 12 weeks on lipid metabolism, glucose tolerance, and depression-like behaviors in ovariectomized rats. Furthermore, the expression of brain-derived neurotrophic factor (BDNF) and its signaling molecule in the hippocampus was analyzed. RESULTS: The 12-week supplementation of DHEA or estradiol significantly alleviated weight gain and improved the glucose tolerance in the ovariectomized rats. Moreover, Long-term supplement of DHEA or estradiol significantly increased sucrose preference and locomotion activities, and reduced immobility duration of the ovariectomized rats in the water. Both DHEA and estradiol treatments increased the expression of BDNF, phosphorylation of ERK and CREB, and ERß, but not that of ERα in the hippocampus of the ovariectomized rats. CONCLUSIONS: Overall, chronic treatment with DHEA improved depression-like behaviors in ovariectomized rats, suggesting that it may be useful for the treatment of sex hormone deficiency such as perimenopausal depressive disorder or postpartum depression.

Aspirin restores endothelial function by mitigating 17ß-estradiol-induced α-SMA accumulation and autophagy inhibition via Vps15 scaffold regulation of Beclin-1 phosphorylation.

AIMS: Previous studies have shown that the widespread use of estrogen preparations can cause adverse outcomes such as thrombosis and cardiovascular disease. Autophagy is a biochemical process necessary to maintain cell homeostasis. The present study investigated whether E-2 mediates autophagy-induced endothelial cell dysfunction. The role of aspirin in this process was then studied. MAIN METHODS: Western blot, fluorescence microscopy, electron transmission microscopy, plasma construction and transfection, vasoreactivity study in wire myograph are all used in this study. KEY FINDINGS: We found that E-2 activated the PI3K/mTOR signaling pathway and inhibited the formation of the Atg14L-Beclin1-Vps34-Vps15 complex, thereby inhibiting autophagy. Aspirin promoted Beclin1 phosphorylation in autophagy initiation complexes and enhanced autophagy. Furthermore, E-2 treatment of HAECs resulted in endothelial dysfunction by inhibiting autophagy and leading to accumulation of α-smooth muscle actin (α-SMA). E-2 inhibited the activation of eNOS and reduced the expression of eNOS protein. In the mouse aortic vascular function test, E-2 disrupted endothelium-dependent vasodilation. An α-SMA-shRNA lentivirus eliminated the disruption to endothelium-dependent vasodilation by E-2. Aspirin inhibited α-SMA accumulation by enhancing autophagy, reversed endothelial functional impairment caused by E-2, and promoted endothelium-dependent vasodilation. SIGNIFICANCE: This study provides new evidence that E-2 inhibits autophagy and induces abnormal accumulation of α-SMA, resulting in endothelial cell dysfunction and affecting vasodilation. Aspirin can effectively restore the endothelial cell function disrupted E-2.

Noncoding RNAs in Diabetic Nephropathy: Pathogenesis, Biomarkers, and Therapy.

The correlation between diabetes and systematic well-being on human life has long established. As a common complication of diabetes, the prevalence of diabetic nephropathy (DN) has been increasing globally. DN is known to be a major cause of end-stage kidney disease (ESKD). Till now, the molecular mechanisms for DN have not been fully explored and the effective therapies are still lacking. Noncoding RNAs are a class of RNAs produced by genome transcription that cannot be translated into proteins. It has been documented that ncRNAs participate in the pathogenesis of DN by regulating inflammation, apoptosis, autophagy, cell proliferation, and other pathological processes. In this review, the pathological roles and diagnostic and therapeutic potential of three types of ncRNAs (microRNA, long noncoding RNA, and circular RNA) in the progression of DN are summarized and illustrated.

LncRNAs GACAT3 and LINC00152 regulate each other through miR-103 and are associated with clinicopathological characteristics in colorectal cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) perform pivotal regulatory roles in tumor development. Our previous work revealed that the lncRNA gastric cancer-associated transcript 3 (GACAT3) was significantly overexpressed and associated with tumor size and metastasis in gastric cancer. METHODS: Total RNAs were extracted from colorectal cancer (CRC) and reverse transcribed, and then quantitative real-time PCR (qRT-PCR) was conducted. Cell counting was performed to assess the effect of GACAT3 on CRC cell line proliferation. Bioinformatics prediction, dual luciferase assay, miRNA mimics, siRNAs, and transfection experiments were applied to determine whether GACAT3 and LINC00152 are reciprocally regulated by miR-103. The relationship between their expression levels and clinicopathological factors of patients was explored. A receiver operating characteristic (ROC) curve was used to assess the potential diagnostic value of GACAT3 and LINC00152. RESULTS: GACAT3 was identified to be highly expressed in CRC tissues and associated with cell proliferation. Furthermore, we demonstrated that GACAT3 acted as a competing endogenous RNA of LINC00152 and they were both regulated by miR-103. Moreover, analysis of clinicopathological characteristics revealed that GACAT3 and LINC00152 were positively correlated with the depth of invasion, TNM stage, lymph node metastasis, and CA19-9 level. Importantly, a combination of GACAT3 and LINC00152 showed a superior diagnostic capacity compared with the use of the two molecules alone. CONCLUSION: Our work shows that GACAT3 and LINC00152 are both overexpressed in CRC and they act as a ceRNA network. Therefore, our data suggest that GACAT3 and LINC00152 may be a promising potential diagnostic biomarker for CRC.

Pancreatic islet dysfunction in type 2 diabetes mellitus.

Islet dysfunction is a hallmark of type 2 diabetes mellitus (T2DM). Compelling evidence suggests that accumulation of islet amyloid in the islets of Langerhans significantly contribute to ß-cell dysfunction and diabetes. Emerging evidence implicates a role for cystic fibrosis transmembrane-conductance regulator in the regulation of insulin secretion from pancreatic islets. Impaired first-phase insulin responses and glucose homeostasis have also been reported in cystic fibrosis patients. The transforming growth factor-ß protein superfamily is central regulators of pancreatic cell function, and has a key role in pancreas development and pancreatic disease, including diabetes and islet dysfunction. It is also becoming clear that islet inflammation plays a key role in the development of islet dysfunction. Inflammatory changes, including accumulation of macrophages, have been documented in type 2 diabetic islets. Islet dysfunction leads to hyperglycemia and ultimately the development of diabetes. In this review, we describe these risk factors and their associations with islet dysfunction.

NK cells induce hepatic ER stress to promote insulin resistance in obesity through osteopontin production.

High-fat diet (HFD) induced hepatic endoplasmic reticulum (ER) stress drives insulin resistance (IR) and steatosis. NK cells in adipose tissue play an important role in the pathogenesis of IR in obesity. Whether NK cells in the liver can induce hepatic ER stress and thus promote IR in obesity is still unknown. We demonstrate that HFD-fed mice display elevated production of proinflammatory cytokine osteopontin (OPN) in hepatic NK cells, especially in CD49a+ DX5- tissue-resident NK (trNK) cells. Obesity-induced ER stress, IR, and steatosis in the liver are ameliorated by ablating NK cells with neutralizing antibody in HFD-fed mice. OPN treatment enhances the expression of ER stress markers, including p-PERK, p-eIF2, ATF4, and CHOP in both murine liver tissues and HL-7702, a human liver cell line. Pretreatment of HL-7702 cells with OPN promotes hyperactivation of JNK and subsequent decrease of tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), resulting in impaired insulin signaling, which can be reversed by inhibiting ER stress. Collectively, we demonstrate that hepatic NK cells induce obesity-induced hepatic ER stress, and IR through OPN production.

Diagnosis of coronary artery disease in patients with atrial fibrillation using low tube voltage coronary CT angiography with isotonic low-concentration contrast agent.

This prospective study evaluated the image quality and accuracy of coronary computed tomography angiography (CCTA) for diagnosing coronary artery disease (CAD) in patients with atrial fibrillation (AF), in which CCTA used adaptive iterative dose reduction (AIDR) with a low tube voltage and low concentration of isotonic contrast agent. Sixty-eight consecutive patients with AF and suspected CAD were equally and randomly apportioned to two groups and underwent CCTA. In the experimental group, the contrast agent was iodixanol (270 mg I/mL), patients were scanned with 100 kV, and reconstruction was by AIDR. In the conventional scanning (control) group, the contrast agent was iopromide (370 mg I/mL), patients were scanned with 120 kV, and reconstruction was by filtered back projection. The image quality, effective radiation dose (E), and total iodine intake of the groups were compared. Thirty-nine patients with coronary artery stenosis later were given invasive coronary angiography (ICA). The groups were similar with regard to mean CT value, noise, and signal-to-noise and contrast-to-noise ratios. The figure of merit of the experimental group was significantly higher than that of the control group, while the E and total iodine were significantly lower. Using ICA as the diagnostic reference, the groups shared similar sensitivity, specificity, and false positive and false negative rates for diagnosing coronary artery stenosis. For determining CAD in patients with AF, CCTA with isotonic low-concentration contrast agent and low-voltage scanning is a feasible alternative that improves accuracy and reduces radiation dose and iodine intake.

Aberrant expression of serum circANRIL and hsa_circ_0123996 in children with Kawasaki disease.

BACKGROUND: Kawasaki disease is a childhood systemic vasculitis that causes coronary artery abnormalities. The etiology remains unknown and there are no specific diagnostic tests. Circular non-coding RNAs are a special class of endogenous RNAs that display some characteristics of an ideal biomarker. However, few studies have examined the expression of circRNAs in the serum of Kawasaki disease (KD) patients. The aim of this study was to identify circRNAs in the serum that can serve as potential biomarkers for KD diagnosis. METHODS: The cases were children diagnosed with KD (n = 56). The controls comprised healthy children (n = 56). Blood was collected from the patients before and after intravenous immunoglobulin therapy, and from the healthy controls. Levels of circANRIL and hsa_circ_0123996 in the serum were measured by quantitative reverse transcription PCR. Then, the potential relationship between serum circRNA levels and patients' biochemical parameter levels was investigated. Receiver operating characteristic curves were constructed for evaluating the diagnostic value of these circRNAs. RESULTS: The serum levels of circANRIL were lower in patients with KD before therapy than in the controls, but became higher in the patients after therapy than before therapy. The serum levels of hsa_circ_0123996 were higher in patients with KD before therapy than in healthy controls. CONCLUSION: Our study indicated that the circANRIL and hsa_circ_0123996 levels in the serum of patients with KD were significantly different from those in healthy individuals. circANRIL and hsa_circ_0123996 may become potential biomarkers for early KD diagnosis.