Changes in miroRNA-103 expression in wound margin tissue are related to wound healing of diabetes foot ulcers.

To investigate the relationship between small noncoding microRNA-103 (miR-103) and wound healing of diabetic foot ulcers (DFU) and the underlying molecular mechanism, forty type 2 diabetes mellitus with DFU (DFU group), and 20 patients with a chronic skin ulcer of lower limbs and normal glucose tolerance (SUC group) were included. Quantitative real-time PCR method was used to determine miR-103 expression levels in the wound margin tissue of subjects, and to analyse the relationship between the expression of miR-103 and DFU wound healing. In vitro experiments were also performed to understand the effect of miR-103 on the high glucose-induced injury of normal human dermal fibroblasts (NHDFs) cells. The results showed that the miR-103 expression level in the DFU group was significantly higher than that in the SUC group [5.81 (2.25-9.36) vs 2.08 (1.15-5.72)] (P < 0.05). The expression level of miR-103 in the wound margin tissue of DFU was negatively correlated with the healing rate of foot ulcers after four weeks (P = 0.037). In vitro experiments revealed that miR-103 could inhibit the proliferation and migration of NHDF cells and promote the apoptosis of NHDF cells by targeted regulation of regulator of calcineurin 1 (RCAN1) gene expression in a high glucose environment. Down-regulation of miR-103 could alleviate high glucose-induced NHDF cell injury by promoting RCAN1 expression. Therefore, the increased expression of miR-103 is involved in the functional damage of NHDF cells induced by high-glucose conditions, which is related to poor wound healing of DFU. These research findings will provide potential targets for the diagnosis and treatment of chronic skin wounds in diabetes.

Decreased expression of miR-204-3p in peripheral blood and wound margin tissue associated with the onset and poor wound healing of diabetic foot ulcers.

To investigate the relationship between small non-coding RNA-204-3p (miR-204-3p) and the onset and wound healing of diabetic foot ulcers (DFU) and the underlying molecular mechanism, sixty four newly diagnosed patients with T2DM without DFU (T2DM group), 82 T2DM patients with DFU (DFU group), and 60 controls with normal glucose tolerance (NC group) were included. Quantitative real-time PCR (qRT-PCR) method was used to determine miR-204-3p expression levels in peripheral blood and wound margin tissue of subjects, and to analyse the relationship between the expression of miR-204-3p and wound healing. In vitro experiments were also performed to understand the effect of miR-204-3p on high glucose induced injury of HaCaT cells (human keratinocytes). The results showed that miR-204-3p expression level of peripheral blood in the T2DM group was marked lower than that in the NC group [2.38 (1.31-5.04) vs 3.27 (1.51-6.98)] (P < .05). Similarly, the miR-204-3p expression level of peripheral blood in the DFU group was significantly lower than the T2DM group [1.15 (0.78-2.89) vs 2.38 (1.31-5.04)] (P < .01). The expression level of miR-204-3p in peripheral blood and wound margin tissues of DFU patients was positively correlated with the healing rate of foot ulcers after 8 weeks (P < .05). Multifactorial logistic regression analysis showed that decreased expression of miR-204-3p in peripheral blood was an independent risk factor for DFU (OR = 2.95, P < .05). The results of in vitro experiments showed that miR-204-3p could improve the proliferation and migration of HKC cells and reduce the proportion of apoptosis of HKC cells by targeted regulation of zinc finger protein Kruppel like factor 6 (KLF6) in high glucose environment. Therefore, the decreased expression of miR-204-3p in peripheral blood and wound tissue of T2DM patients is closely related to the occurrence and poor wound healing of DFU. The down-regulated expression of miR-204-3p can reduce its ability to antagonise the functional damage of keratinocytes induced by high-glucose conditions. These results will provide potential targets for the treatment of DFU.

Effects of dulaglutide on endothelial progenitor cells and arterial elasticity in patients with type 2 diabetes mellitus.

BACKGROUND: Randomised controlled trial showed that dulaglutide can reduce the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2DM), but the underlying mechanisms remain unclear. This study aimed to investigate the effect of dulaglutide on the number and function of endothelial progenitor cells (EPCs) in the peripheral blood of patients with T2DM and its role in improving arterial elasticity, so as to determine potential mechanisms of preventive effect of dulaglutide on ASCVD. METHODS: Sixty patients with T2DM were treated with 1000 mg/day of metformin and randomly divided into two groups for 12 weeks: metformin monotherapy group (MET group, n = 30), and metformin combined with dulaglutide group (MET-DUL group, n = 30). Before and after treatment, the number of CD34+CD133+KDR+ EPCs and the brachial-ankle pulse wave velocity (baPWV) of the participants were measured, and EPC proliferation, adhesion, migration, and tubule formation were assessed in vitro. RESULTS: There were no significant differences in the number and function of EPCs and baPWV changes in MET group (P > 0.05). In MET-DUL group, nitric oxide (NO) levels and the number of EPCs increased after treatment (P < 0.05), while the levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), advanced glycation end products (AGEs), and baPWV decreased (P < 0.05). EPC proliferation, adhesion, migration, and tubule formation abilities were significantly enhanced (P < 0.05). Correlation analysis showed that in MET-DUL group, the changes in CRP, IL-6, TNF-α, and AGEs were negatively correlated with the number of EPCs and their proliferation and migration abilities (P < 0.05). Body weight, NO, CRP, and IL-6 levels were independent factors affecting the number of EPCs (P < 0.05). The changes in number of EPCs, proliferation and migration abilities of EPCs, and NO and IL-6 levels were independent influencing factors of baPWV changes (P < 0.05). CONCLUSION: Dulaglutide can increase the number and function of EPCs in peripheral blood and improve arterial elasticity in patients with T2DM; it is accompanied by weight loss, inflammation reduction, and high NO levels. Dulaglutide regulation of EPCs may be a mechanism of cardiovascular protection.

Krüppel-like factors in glycolipid metabolic diseases.

Krüppel-like factors (KLFs) are a family of transcription factors characterised by zinc-finger structures at the C-terminal. They play the key roles in cell proliferation, differentiation, and migration, as well as in embryonic development. They have been widely expressed in multiple systems in vivo, and their dysregulation is closely associated with a variety of human diseases. Glycolipid metabolism is a complex physiological process which can be regulated at the transcriptional level. Glycolipid metabolic diseases, such as obesity, non-alcoholic fatty liver disease, diabetes, and their complications, are a serious threat to human health. Recently, increasing studies have shown that KLFs are closely related to glycolipid metabolism and energy balance of the liver, adipose tissue, heart, skeletal muscle, lung, pancreas, and nervous system. In this review, we focused on the correlation between the subtypes of the KLF family and glycolipid metabolic diseases to describe new directions and trends in endocrine and glycolipid metabolic disease treatments.

Effect of omentin-1 on cancer stem cell surface markers and tumour-suppressive miRNA expression in a high-glucose environment associated with colorectal cancer.

Objective: To investigate how omentin-1 impacts colorectal cancer stem cell surface markers and the expression levels of tumour-suppressive micro ribonucleic acid in a colorectal cancer-associated high-glucose environment. METHODS: The study was conducted in the First Affiliated Hospital of Anhui Medical University，Anhui, China，from April 2018 to January 2019 and comprised cluster of differentiation133 and colorectal cancer stem cells from the SW480 cell line（the human colon adenocarcinoma cell line） obtained through immunomagnetic beads-based cell isolation. The colon cancer stem cells were divided into 6 groups: Z0 (control), Z1 (1ug/mL omentin-1), Z2 (2ug/mL omentin-1), G0 (5.0g/mL glucose), G1 (1ug/mL omentin-1 and 5.0g/mL glucose), and G2 (2ug/mL omentin-1 and 5.0 g/mL glucose). After 24 hours of intervention, quantitative polymerase chain reaction and western blot test were used for the detection of messenger ribonucleic acid and protein levels of stem cell surface markers. The colorectal cancer stem cells were divided into three groups: the control group, omentin group 1 (1ug/mL omentin-1) and omentin group 2 (2ug/mL omentin-1). After 24 hours of intervention, the expression of tumour suppressor micro ribonucleic acid was measured using quantitative polymerase chain reaction. Data was analysed using SPSS 23. RESULTS: Compared to the Z0 group, cluster of differentiation133 messenger ribonucleic acid expression reduced sharply in Z1 group (p<0.05), while Z2 group saw a marked increase in the expression (p<0.05). With respect to tumour-suppressive micro ribonucleic acid expression, micro ribonucleic acid 126, 145, 34a and 342-5P in omentin group 2 exhibited an expression level significantly higher than those in the control group and the omentin group 1 (p<0.05). Conclusion: High glucose levels were found to upregulate the expression of colorectal cancer stem cell surface markers cluster of differentiation133 messenger ribonucleic acid and protein. Also, omentin-1 was found to be associated with the downregulation of cluster of differentiation133 messenger ribonucleic acid and protein expression and the upregulation of cluster of differentiation 44 messenger ribonucleic acid expression in a high-glucose environment. Finally, omentin-1 was found to have the ability to promote the expression of relevant tumour-suppressive micro ribonucleic acids 126, 14, 34a and 342-5P.

Application of convolutional neural network on early human embryo segmentation during in vitro fertilization.

Selection of the best quality embryo is the key for a faithful implantation in in vitro fertilization (IVF) practice. However, the process of evaluating numerous images captured by time-lapse imaging (TLI) system is time-consuming and some important features cannot be recognized by naked eyes. Convolutional neural network (CNN) is used in medical imaging yet in IVF. The study aims to apply CNN on day-one human embryo TLI. We first presented CNN algorithm for day-one human embryo segmentation on three distinct features: zona pellucida (ZP), cytoplasm and pronucleus (PN). We tested the CNN performance compared side-by-side with manual labelling by clinical embryologist, then measured the segmented day-one human embryo parameters and compared them with literature reported values. The precisions of segmentation were that cytoplasm over 97%, PN over 84% and ZP around 80%. For the morphometrics data of cytoplasm, ZP and PN, the results were comparable with those reported in literatures, which showed high reproducibility and consistency. The CNN system provides fast and stable analytical outcome to improve work efficiency in IVF setting. To conclude, our CNN system is potential to be applied in practice for day-one human embryo segmentation as a robust tool with high precision, reproducibility and speed.

Regioselective Synthesis of Tetrasubstituted Benzenes via Co-Catalyzed Cycloaddition of Alkynyl Ketones and 2-Acetylpyridines.

A Co(II)-catalyzed cycloaddition reaction of alkynyl ketones and 2-acetylpyridines using 2,2'-bipyridine as the ligand has been developed. These reactions have been realized through Co-catalyzed reductive coupling of two molecules of 2-acetylpyridine followed by regioselective insertion of the alkynone. It is the first example of regioselective cyclotrimerization of one molecule of alkyne and two molecules of monoketone to polysubstituted benzene derivatives in good to excellent yields. A mechanism involving the formation of a cobaltacyclopentane via homocoupling of 2-acetylpyridines is proposed, and it is supported by the DFT calculations.

Antithyroid arthritis syndrome: A case report and review of the literature.

A 29-year-old woman was diagnosed with Graves' disease because of her symptoms of thyrotoxicosis. After a 15-day treatment with methimazole, she began to suffer from a repeated fever, rash, and polyarticular migratory arthralgias. The clinical examination on admission showed that her white blood cell count, neutrophil count, and erythrocyte sedimentation rate (ESR) were within normal limits, while the concentration of C-creative protein (CRP) was 26.14 mg/L (ref. 0 - 10) and anti-nuclear immune body (ANA) and anti-neutrophil cytoplasmic antibody (ANCA) were both negative. Upon stopping the drug treatment, the patient's symptoms promptly disappeared. Antithyroid arthritis syndrome is poorly characterized, and the findings from our literature review indicate that this syndrome exhibits serological features that are distinct from those of antithyroid agent-induced vasculitis syndrome. Furthermore, physician's awareness of this syndrome is essential for its diagnosis in clinical practice.

Expression of miR-210 in the peripheral blood of patients with newly diagnosed type 2 diabetes mellitus and its effect on the number and function of endothelial progenitor cells.

OBJECTIVE: This study aims to investigate the correlation between the expression of miR-210 in peripheral blood and the number of peripheral endothelial progenitor cells (EPCs) in patients with type 2 diabetes mellitus (T2DM). We also determined the effect of miR-210 on EPC proliferation, adhesion, migration, tube formation, and apoptosis. METHODS: A total of 32 patients with newly diagnosed T2DM (T2DM group) and 32 control subjects with normal glucose tolerance (NC group) were included. Peripheral blood samples were collected from each subject. The miR-210 level was determined by quantitative real-time polymerase chain reaction (qRT-PCR), and the number of positive EPCs indicated by CD34, CD133, and KDR expressions was detected by flow cytometry. After isolation, culture, and identification by fluorescent staining, EPCs were divided into four groups: NC group, untransfected type 2 diabetic group, miR-210 inhibitor NC group, and miR-210 inhibitor group. The expression of miR-120 in each group was detected by qRT-PCR, and the changes in the proliferation, adhesion, migration, tube formation, and apoptosis of EPCs after transfection with a miR-210 inhibitor were observed. RESULTS: The expression level of miR-210 in the T2DM group (5.83 ± 1.26) was significantly higher than that in the NC group (1.18 ± 0.54) (t = 17.26, P < 0.001). The number of EPCs was significantly lower in the T2DM group (39.3 ± 12.6)/106 cells than that in the NC group (76.2 ± 10.7)/106 cells (t = 10.49, P < 0.001). Spearman's correlation analysis showed that the expression of miR-210 in the peripheral blood of patients with T2DM was negatively correlated with the number of EPCs (r = -0.558, P = 0.001). Multiple linear stepwise regression analysis showed that the peripheral blood level of miR-210 was an independent correlation factor that affected the number of EPCs (P < 0.001). After transfection with the miR-210 inhibitor, the proliferation, adhesion, tube formation, and migration levels of EPCs in miR-210 inhibitor group were higher than those in untransfected type 2 diabetic group and miR-210 inhibitor NC group, whereas the apoptosis rate was lower than that in these groups, and these results were statistically significant (P < 0.05). CONCLUSION: The increased expression of miR-210 in patients with T2DM may be related to the decreased number and function of EPCs in peripheral blood.

Synthesis of indoline-fused eight-membered azaheterocycles through Zn-catalyzed dearomatization of indoles and subsequent base-promoted C-C activation.

A cascade reaction involving the Zn-catalyzed dearomatization of indoles, base-promoted ring-expansion and intramolecular SNAr reaction has been developed. This process realized a novel, atom economical and efficient synthesis of indoline-fused eight-membered azaheterocycles in a one pot manner.

Acute effects of sitagliptin on progenitor cells and soluble mediators in newly diagnosed type 2 diabetes.

OBJECTIVE: Studies have confirmed that endothelial progenitor cells (EPCs) are involved in diabetic complications. The present study assessed the action of the dipeptidyl peptidase-4 inhibitor sitagliptin on EPCs in newly diagnosed type 2 diabetes patients. MATERIALS AND METHODS: 60 newly-diagnosed type 2 diabetes patients were randomly divided into three treatment groups: sitagliptin (n = 20), metformin (n = 20), and combination sitagliptin and metformin (n = 20). Patients were treated once daily for 3 days. Before and after each treatment, the number of EPCs and concentration of soluble mediators (glucagon-like peptide 1 (GLP-1), nitric oxide (NO), endothelin-1 (ET-1), and stromal cell-derived factor-1α (SDF-1α)) were determined. RESULTS: The number of CD34+KDR+ and CD34+CD133+KDR+ EPCs and concentration of GLP-1, NO, and SDF-1α in sitagliptin and combination groups were both increased (both p < 0.05) but to a greater extent in the combination group (p < 0.05). Pearson correlation analysis and multiple linear regression analyses showed that the change in EPC numbers correlated with changes in peripheral GLP-1, NO, and SDF-1α levels (p < 0.05). CONCLUSION: Sitagliptin is able to directly increase the number of peripheral blood EPCs. This direct effect is to be important for lowering vascular risk in early diabetes before macrovascular complications appear.

Controllable synthesis of pyrido[2,3-b]indol-4-ones or indolo[3,2-b]quinolines via formal intramolecular C(sp2)-H functionalization.

A novel Fe-catalyzed protocol for the controllable synthesis of pyrido[2,3-b]indol-4-ones or indolo[3,2-b]quinolines has been developed by using indole-2-carboxylic derivatives as starting materials. Indole-2-carboxenamines were transformed into pyrido[2,3-b]indol-4-ones through intramolecular N-H/C-H coupling, in which a carbonyl 1,2-migration was involved. Whereas, when indole-2-carboxarylamines were employed, indolo[3,2-b]quinolones were produced through direct N-H/C-H coupling. The desired products were obtained under mild reaction conditions in moderate to good yields with wide substrate scope. The natural product quindolinone was conveniently prepared by this reaction.

Transition-metal-free C-C σ-bond activation of α-aryl ketones and subsequent Zn-catalyzed intramolecular cyclization: synthesis of tetrasubstituted furans.

A highly atom-economical protocol for the synthesis of tetrasubstituted furans has been developed. This process is realized through the tandem reactions of Cs2CO3 promoted C-C σ-bond activation of α-aryl ketones followed by Zn-catalyzed intramolecular cyclization. This represents the first example for the preparation of tetrasubstituted furans through rearrangement of molecular skeletons and subsequent transformations. Mild reaction conditions and readily accessible starting materials make the protocol attractive in organic synthesis.

Cobalt-catalyzed regioselective syntheses of indeno[2,1-c]pyridines from nitriles and diynes bearing propargyl fragments.

A highly efficient CoI2/o-phenanthroline catalyzed cycloaddition reaction of diynes bearing TBS protected propargylic alcohol fragments with nitriles has been developed. This methodology offers regioselective access, with good functional group tolerance, to various indeno[2,1-c]pyridine derivatives in moderate to excellent yields. It was found that o-phenanthroline as a bidentate nitrogen ligand showed high efficacy in this cycloaddition reaction.

PBr3-Mediated Cyclization of 1,7-Diyn-3,6-bis(propargyl carbonate)s: Synthesis of 5-Bromotetracenes.

A new and straightforward method for the synthesis of 5-bromotetracenes through PBr3-mediated cyclization of 1,7-diyn-3,6-bis(propargyl carbonate)s has been developed. This method offers several advantages such as easily accessible starting materials, high efficiency, and wide functional group compatibility. In addition, chloro- and iodo-substituted tetracenes were also synthesized using appropriate halogenating reagents. The utility of the 5-bromotetracene products has been illustrated by their efficient transformations through various palladium-catalyzed cross-coupling reactions.

Selective synthesis of pyrrolo[1,2-a]azepines or 4,6-dicarbonyl indoles via tandem reactions of alkynones with pyrrole derivatives.

Novel methodologies for the selective synthesis of pyrrolo[1,2-a]azepines or 4,6-dicarbonyl indoles starting from pyrrole derivatives and alkynones are described. When reactions were carried out with 1,2,4-trisubstituted N-propargyl pyrroles using a ZnI2 catalyst, pyrrolo[1,2-a]azepines were obtained. Whereas 4,6-dicarbonyl indoles were produced selectively with 1,2-disubstituted pyrroles in the presence of silica gel. The reaction outcomes depend on the substituent pattern of the substrates and the nature of the catalysts chosen. Control reactions suggested that the formation of a conjugated enamine intermediate was crucial for both the processes. With easily accessible starting materials, inexpensive catalysts and an easy-to-handle procedure, this reaction has the potential to become a general protocol for the synthesis of pyrrolo[1,2-a]azepines or indoles.

Base-mediated insertion reaction of alkynes into carbon-carbon σ-bonds of ethanones: synthesis of hydroxydienone and chromone derivatives.

Transition-metal free insertions of alkynes into carbon-carbon σ-bonds of ethanones have been reported. These tandem reactions offer an efficient synthesis of hydroxydienones and multi-substituted chromones. This is the first example of base-promoted insertion reactions of isolated carbon-carbon triple bonds into carbon-carbon σ-bonds with active methylene compounds bearing only one electron-withdrawing group.

Greatly Accelerated Condensation of d-Mannose Diacetonide with Aqueous Formaldehyde (Formalin).

Condensation of d-mannose diacetate with aqueous formaldehyde, a long known quaternary center-generating transformation, was reinvestigated to solve the hidden problem of incomplete conversion, a lasting challenge since 1979 despite many previous efforts. The mysterious cause for the retarded transformation was found to be generation of formic acid by a Cannizzaro reaction. By using additional amounts of base, the reaction time was shortened from 48 h to 100 min and the product was readily isolated in 81% yield.

Role of Decreased Expression of miR-155 and miR-146a in Peripheral Blood of Type 2 Diabetes Mellitus Patients with Diabetic Peripheral Neuropathy.

Objective: To Study the Correlations of microRNA-155 (miR-155) and microRNA-146a (miR-146a) Expression in Peripheral Blood of Type 2 Diabetes Mellitus (T2DM) Patients with Diabetic Peripheral Neuropathy (DPN), and Explore the Clinical Value of miR-155 and miR-146a in the Diagnosis and Treatment Outcomes of DPN. Methods: The study included 51 T2DM patients without DPN (T2DM group), 49 T2DM patients with DPN (DPN group), and 50 normal controls (NC group). Quantitative real-time PCR was utilized to determine the expression levels of miR-155 and miR-146a. Clinical features and risk factors for DPN were assessed. Multivariate stepwise logistic regression analysis was conducted to confirm whether the expressions of miR-155 and miR-146a could independently predict the risk of DPN. ROC curve analysis evaluated their diagnostic value. Results: The T2DM group exhibited significantly lower expression levels of miR-155 and miR-146a compared to the NC group (P < 0.05). Moreover, the DPN group exhibited a significantly decreased expression level of miR-155 and miR-146a compared to the T2DM group (P < 0.01). Multivariate logistic regression analysis indicated that higher levels of miR-155 and miR-146a might serve as protective factors against DPN development. ROC curve analysis revealed that miR-155 (sensitivity 91.8%, specificity 37.3%, AUC 0.641,) and miR-146a (sensitivity 57.1%, specificity 84.3%, AUC 0.722) possess a strong ability to discriminate between T2DM and DPN. Their combined use further enhanced the diagnostic potential of DPN (sensitivity 83.7%, specificity 60.8%, AUC 0.775). A multi-index combination can improve DPN diagnostic efficiency. Conclusion: The decreased expression of miR-155 and miR-146a in the peripheral blood of T2DM patients is closely related to the occurrence of DPN, highlighting their potential as valuable biomarkers for diagnosing and prognosticating DPN.

Application of oral inorganic iodine in the treatment of Graves' disease.

Iodine is a crucial trace element for the human body and the basic raw material for the synthesis of thyroid hormones. Oral inorganic iodine includes dietary iodine and therapeutic iodine, both of which are closely associated with thyroid immunity and metabolism. Graves' disease (GD), also known as diffuse toxic goiter, is characterized by hyperthyroidism and high iodine metabolism. Clinically, patients diagnosed with GD are often asked to limit iodine intake or even avoid iodine in their diet. The latest research has demonstrated that the interference of dietary iodine with antithyroid drugs (ATDs) treatment may be overestimated. In addition, as a medication for GD treatment, the administration of inorganic iodine has shown positive results in patients with mild hyperthyroidism, a low thyroid autoantibody concentration, a small thyroid volume, a high iodine diet and so on. Inorganic iodine may also be used as an alternative when patients experience side effects with traditional ATDs and for those who still prefer conservative treatment. Due to its low teratogenicity, blood toxicity and bone marrow toxicity, inorganic iodine plays a unique role in special populations, such as pregnant or lactating patients and patients receiving tumor radiotherapy or chemotherapy. In this review, the research progress, biological function, doses and effects, applicable populations and specific applications of dietary iodine and therapeutic iodine are summarized to provide references for the diagnosis and treatment of GD, thus improving the quality of life of GD patients.