Nanomaterials for diabetic wound healing: Visualization and bibliometric analysis from 2011 to 2021.

Background: Nanomaterials have recently been shown to have a considerable advantage in promoting wound healing in diabetic patients or animal models. However, no bibliometric analysis has been conducted to evaluate global scientific production. Herein, this study aimed to summarize the current characteristics, explore research trends, and clarify the direction of nanomaterials and diabetic wound healing in the future. Methods: Relevant publications from 2011 to 2021 were collected from the Web of Science Core Collection on October 3, 2022. VOSviewer, CiteSpace, bibliometrix-R package, Origin 2021, and Microsoft Excel 2019 were used for bibliometric and visualization analyses. Results: We identified 409 publications relating to nanomaterials and diabetic wound healing. The number of annual productions remarkably increased from 2011 to 2021, with China and Shanghai Jiao Tong University being the most productive. The most prolific authors were Hasan Anwarul. The leading journal was the International Journal of Biological Macromolecules, with 22 publications. The most popular keywords were "nanoparticles," "delivery," "in vitro," "electrospinning," "angiogenesis," and "antibacterial." Keyword burst analysis showed "cerium oxide," "matrix metalloproteinase 9," "composite nanofiber," "hif 1 alpha," and "oxide nanoparticle" were emerging research hotspots. Conclusion: We found there has been a great progress in the application of nanomaterials in diabetic wound healing from 2011 to 2021. Although many researchers and institutions from different countries or regions contributed contributed to publications, it will be helpful or the development of this field if the degree of international cooperation can be enhanced. In the future, nanomaterials with powerful antioxidant and antibacterial qualities and promoting angiogenesis are the research hotspots.

Distribution of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8 in type 1 diabetes and latent autoimmune diabetes: A nationwide, multicentre, cross-sectional study.

AIMS: This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes. MATERIALS AND METHODS: This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency. RESULTS: IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD. CONCLUSIONS: IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.

circCYP24A1 facilitates esophageal squamous cell carcinoma progression through binding PKM2 to regulate NF-κB-induced CCL5 secretion.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor, while the molecular mechanisms have not been fully elucidated. Multiple circular RNAs have been reported to involve in the onset and progression of malignant tumors through various molecular mechanisms. However, the clinical significance and functional mechanism of most circRNAs involved in the progression of ESCC remains obscure. METHODS: RNA-Seq was used to explore potential circRNAs in participated in 5 pairs of ESCC and their corresponding normal esophageal tissues. The up-regulated circCYP24A1 was selected. Fluorescence in situ hybridization was cunducted to verificated the expression and intracellular localization of circCYP24A1 by using the tissue microarray. The Kaplan-Meier method and Cox proportional hazards model was used to examine the potential prognostic value of circCYP24A1 on overall survival of ESCC patients. The biological function were confirmed by gain- and loss-of-function approaches in vivo. mRNA expression profile microarray was proformed to investigate the downstream signaling pathways involved in circCYP24A1. RNA pull-down assay and mass spectrometry were performed to identify the proteins associated with circCYP24A1. Rescue experiments were carried out to identified hypothetical regulatory role of circCYP24A1 on ESCC progression in vivo and in virto. RESULTS: In this study, we identified circCYP24A1 in ESCC tissues by RNA sequencing, which is up-regulated in 114 cases of ESCC tissues and acts as a novel prognosis-related factor. Moreover, circCYP24A1 promoted the ability of proliferation, migration, invasion and clone formation in vitro, as well as tumor growth in vivo. Mechanistically, chemokine (C-Cmotif) ligand 5 (CCL5) is functional downstream mediator for circCYP24A1, which is screened by mRNA microarray. Moreover, circCYP24A1 physically interacts with M2 isoform of pyruvate kinase (PKM2). Rescue experiments showed that PKM2 knockdown partly reverses the promotional effects of circCYP24A1. It was revealed that circCYP24A1 increases secretion of CCL5 through the mechanism mainly by interacting with PKM2, an activator of NF-κB pathway, and thereby accelerate malignant progression of ESCC. CONCLUSIONS: Up-regulated circCYP24A1 could activate NF-κB pathway by binding PKM2, which promotes the secretion of CCL5 and accelerate malignant progression of ESCC. Our fndings recommended a novel function for circCYP24A1 as a potential effective biomarker for judging prognosis and a therapeutic target in ESCC.

Thyroid autoantibody distribution in patients with latent autoimmune diabetes in youth: a multicenter, national survey.

Background: A high seropositive rate of thyroid autoantibodies is often reported in patients with type 1 diabetes mellitus (T1DM), latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM). However, the positive rate of thyroid autoantibodies in latent autoimmune diabetes in youth (LADY) patients has not been reported in China. Thus, the purpose of the current study was to clarify the thyroid autoantibody distribution in patients with LADY to provide evidence for the clinical screening of autoimmune thyroid diseases (AITD). Methods: This nationwide, multicenter and cross-sectional study included 1,723 younger patients (<30 years old) and 2,000 older patients (≥30 years old) aged 15 to 79 years. The patients were grouped into younger T1DM (n=281), LADY (n=130), younger T2DM (n=200), older T1DM (n=287), LADA (n=129), and older T2DM (n=200) groups. Autoantibodies against thyroid peroxidase (TPOA) and thyroglobulin (TGA) prevalence were analyzed in each group. Results: The prevalence of TGA or TPOA in LADY patients was similar to that in younger T1DM patients. The seropositive rate of TPOA in LADY patients was higher than that in LADA patients (36.2% vs. 23.3%, respectively; P=0.023); the risk of TPOA was higher in LADY patients than in LADA patients, even after adjusting for sex, glutamic acid decarboxylase (GADA)- and insulinoma-associated-2 (IA-2A)-positivity (OR =1.94, P=0.023). LADY patients with high GADA titers exhibited a higher frequency of thyroid autoantibodies than patients with low GADA titers did (TPOA, P=0.005; TGA, P=0.023; TPOA or TGA, P=0.004). Further analysis showed that only male patients showed a strong association between high GADA titers and thyroid autoantibodies positivity, and the association remained significant after adjustment for age (OR =11.14, P=0.025 for TGA; OR =4.99, P=0.011 for TPOA; OR =5.52, P=0.007 for TPOA or TGA). Conclusions: Routine screening for thyroid autoantibodies is recommended in LADY patients, and special clinical attention should be paid to the thyroid autoantibodies status of male patients of LADY with high GADA titers to identify patients at high risk of developing AITD.

The circRNA circADAMTS6 promotes progression of ESCC and correlates with prognosis.

Circular RNAs (circRNAs) are a type of noncoding RNA, which play a vital role in the occurrence and development of esophageal squamous cell carcinoma (ESCC). While the role of novel circADAMTS6 in ESCC remains unknown. We assessed circADAMTS6 expression in ESCC tissues and cells, and the relationship between circADAMTS6 expression and overall survival of ESCC patients. Functional experiments in vitro and xenograft in vivo assay were applied to explore the functions and mechanisms of circADAMTS6 in ESCC. Results found that up-regulation of circADAMTS6 was associated with poor overall survival and may acted as an independent risk factor for ESCC prognosis. Knockdown of circADAMTS6 significantly inhibited the proliferation, migration and invasion of ESCC cells and growth of xenograft tumors in vivo. Induced AGR2 expression was able to rescue the loss of function induced by si-circADAMTS6 in KYSE150 cell. CircADAMTS6 may acts as oncogene by activating AGR2 and the Hippo signaling pathway coactivator YAP in ESCC.

Circular RNA circCCDC85A inhibits breast cancer progression via acting as a miR-550a-5p sponge to enhance MOB1A expression.

BACKGROUND: A growing body of evidence indicates that abnormal expression of circular RNAs (circRNAs) plays a crucial role by acting as molecular sponges of microRNAs (miRNAs) in various diseases, including cancer. In this study, we explored whether circCCDC85A could function as a miR-550a-5p sponge and influence breast cancer progression. METHODS: We detected the expression of circCCDC85A in breast cancer tissues and cells using fluorescence in situ hybridization (FISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). CCK-8 and colony formation assay were used to detect the proliferative ability of breast cancer cells. Wound healing assay and transwell migration and invasion assays were used to detect the migrative and invasive abilities of breast cancer cells. We also examined the interactions between circCCDC85A and miR-550a-5p using FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Moreover, we performed luciferase reporter assay, qRT-PCR, and Western blot to confirm the direct targeting of miR-550a-5p to MOB1A. RESULTS: The expression of circCCDC85A in breast cancer tissues was obviously lower than that in normal breast tissues. Over-expression of circCCDC85A substantially inhibited the proliferative, migrative, and invasive ability of breast cancer cells, while knocking down of circCCDC85A enhanced the aforementioned properties of breast cancer cells. Moreover, enforced expression of circCCDC85A inhibits the oncogenic activity of miR-550a-5p and increases the expression of MOB1A targeted by miR-550a-5p. Further molecular mechanism research showed that circCCDC85A may act as a molecular sponge for miR-550a-5p, thus restoring miR-550a-5p-mediated targeting repression of tumor suppressor MOB1A in breast cancer cells. CONCLUSION: Our findings provide novel evidence that circCCDC85A inhibits the progression of breast cancer by functioning as a molecular sponge of miR-550a-5p to enhance MOB1A expression.

Screening Strategy for Islet Autoantibodies in Diabetes Patients of Different Ages.

Background: The detection of islet autoantibodies is essential for the accurate classification and diagnosis of diabetes mellitus (DM). The islet autoantibody distribution varies by age. However, screening strategies for DM patients with different onset ages remain lacking. Materials and Methods: This cross-sectional study included 17,536 DM patients from 46 medical centers across China. The seroprevalence of glutamic acid decarboxylase autoantibody (GADA), insulinoma-associated-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), and insulin autoantibody (IAA) was determined in younger and older patients with type 1 DM (T1DM) (n = 287 and 285, respectively), younger and older patients with latent autoimmune diabetes (LAD) (n = 140 and 121, respectively), and younger and older patients with type 2 DM (n = 200 in each group). Results: The cutoff age between younger and older patients was 35 years using restricted cubic spline method (n = 17,536, adjusted R2 = 0.97, residual standard error = 1.32; P < 0.001). The seroprevalence rates of four islet autoantibodies were higher in patients aged 15-35 years than in those ≥35 years (GADA: 17% vs. 5.6%, IA-2A: 8.5% vs. 1.3%, ZnT8A: 6.3% vs. 2.3%, IAA: 2.2% vs. 1.0%). The prevalence of ZnT8A was higher in LAD patients than in T1DM patients, especially in older LAD patients. The results indicated that ZnT8A detection can increase the detection rate of older LAD patients from 70.2% (based on GADA detection alone) to 91.7%. Conclusions: In patients stratified according to the cutoff age of 35 years, the optimal detection sequence should be GADA, IA-2A, and ZnT8A in younger patients and GADA, ZnT8A, and IA-2A in older patients, so as to reduce the screening cost while improving the detection rate. Particularly, the ZnT8A test is recommended in older patients to avoid a missed LAD diagnosis.