Endoscopic Approach With an Innovative Mini-Trocar for Forehead Osteoma Excision.

Traditionally forehead bony lesion is approached directly through the forehead skin or invasive coronal incision resulting prominent scar. An endoscopic approach through mini hairline incisions may provide a unique way to achieve the best esthetic results, but often time the authors encounter potential soft tissue injury from the high-speed burr. The authors present a case with multiple frontal bone osteoma lesions which were successfully removed through 2 small hairline incisions with the help of an otorhinolaryngological system and an innovative mini-trocar. Significant improvement in forehead shape with minimal scars was observed at an 18-month follow-up. This innovative and easily manipulating technique may help surgeons achieve better outcomes when treating frontal bone osteoma endoscopically.

Gene Profiling of Circular RNAs in Keloid-prone Individuals and ceRNA Network Construction During Wound Healing.

Epigenetic alterations of non-coding RNA (ncRNA) are pivotal in the continuous activation and differentiation of fibroblasts in keloid. However, the epigenetic mechanism of circRNA in keloid is still not clear yet. In this study, we aimed to investigate the interplay among differentially expressed circRNAs, miRNAs, and mRNAs during wound healing in keloid-prone individuals, construct a competing endogenous RNA (ceRNA) network, and gain an in-depth insight into the pathophysiological mechanisms underlying keloid development. Utilizing bioinformatic methods, we analyzed the expression profiles from the GSE113621 database. We identified 29 differentially expressed circRNAs (DEcircRNAs) in keloid-prone individuals during wound healing, from which we constructed 14 ceRNA networks. Subsequently, we validated the expression of predicted DEcircRNAs in keloid tissues and elucidated the ceRNA network involving circ_064002 and fibronectin-1 (FN1) through competing miR-30a/b-5p. Knocking down circ_064002 led to down-regulation of FN1 expression and various cellular functions in keloid-derived fibroblasts (KFs), including cell viability, migration, invasion, and repair capacity. Our study introduces a novel approach to explore the presence of DEcircRNAs and the ceRNA regulatory network during wound healing in keloid-prone individuals through in-depth mining of GEO data and also proves the epigenetic regulatory mechanism of circ_064002 in KFs. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Study on the Expression of Messenger RNAs and Long Noncoding RNA in Keloid Fibroblasts Based on Gene Expression Omnibus Microarray Data Mining.

OBJECTIVE: The purpose of this study was to find the coding RNA [messenger RNA (mRNA)] and long noncoding RNA (lncRNA) expressed in keloid through the analysis of Gene Expression Omnibus microarray chip of keloid fibroblasts. MATERIALS AND METHODS: Gene Expression Omnibus database GSE7890 database was downloaded with selection of keloids and normal scar group data. The data were analyzed by R language combined with online database. The log2FC>1, P value <0.01 was chosen as screening criteria, and the differentially expressed mRNAs were screened for GO and KEGG function analysis. RESULTS: One hundred fifty-five mRNA expression in the keloid group was significantly different from that in the normal group, including 31 groups with upregulated mRNA expression and 124 groups with down-regulated mRNA expression. Meanwhile, 8 lncRNAs were changed in the keloid group, including 3 upregulated (Rp11-420a23.1, Rp11-522b15.3, and Rp11-706j10.1) and 5 down-regulated (LINC00511, LINC00327, Hoxb-as3, Rp11-385n17.1, and Rp3-428l16.2). Quantitative polymerase chain reaction analysis of DElncRNAs in keloid fibroblasts showed that the expression of all DElncRNAs except for RP11-385N17.1 was increased in the keloid group compared with the control group. Moreover, the differences in LINC00511 and RP11-706J10.1 were statistically significant. CONCLUSION: The noncoding RNA information of Gene Expression Omnibus chip data can be deeply mined through bioinformatics, and the potential epigenomic mechanism affecting keloid formation can be found from the existing database.

Competing Endogenous RNA Network in Non-Keloid-Prone Individuals During Wound Healing.

ABSTRACT: To study the interaction between differentially expressed long non-coding RNAs (lncRNAs), microRNAs, and messenger RNAs during wound healing in normal individuals. The GSE113621 dataset was downloaded from gene expression matrix, specimens regarding non-keloid-prone individuals were selected, including items before and 6 weeks after injury. A Pearson correlation coefficient of > 0.95 was selected as the index to screen targeting relationships among different RNAs. Cytoscape was used to construct a network diagram. The expression of 2547 lncRNAs was changed during the wound healing process-1479 were upregulated and 1068 were downregulated. After analyzing competitive endogenous RNA network, 4 upregulated (MEG8, MEG3, MIR181A1HG, MIR4435-2HG) lncRNAs were found expressed during wound healing. MEG8/MEG3 may regulate fibroblast proliferation, differentiation, and apoptosis through hsa-miR-296-3p/miR-6763-5p. In-depth mining of gene expression matrix data indicated that lncRNAs and a competitive endogenous RNA regulatory network participate in the wound healing process, possibly providing novel intervention targets and treatment options for delayed wound healing.

Effect of Induction Time on the Proliferation and Differentiation of Induced Schwann-Like Cells from Adipose-Derived Stem Cells.

To compare how different induction time takes effect on the proliferation and secretion ability of adipose-derived stem cell (ADSC)-induced Schwann-like cells (iSCs), ADSCs were isolated from healthy adult female rats. Flow cytometry (FCM) was performed to detect the ADSC-positive markers CD29, CD44, and CD90 and the negative marker CD45. iSC induction medium was used to culture the ADSCs. S-100, GFAP, MBP, and P75 were detected by immunofluorescence staining to identify iSC differentiation. Cell morphological changes were observed by an inverted microscope after induction. An MTS assay was used to evaluate the cell proliferation ability. Western blot analyses of caspase-3/cleaved caspase-3 and FCM were applied to assess cell apoptosis. Co-culture system of PC12 and ADSCs or iSCs was established to analyse the biological function of iSCs. Among the examined proteins, S-100, GFAP, MBP, and P75 were expressed in iSCs. After day 7, the cell proliferation rate was significantly lower than that before induction, and on day 19, the proliferation rate of iSCs was lower than 50% of the proliferation rate before induction (OD value = 0.016 ± 0.003 vs. 0.400 ± 0.004, p < 0.01). Starting from day 19, P21, P53, Apoj, S100, Gdnf, and Mbp all consistently showed a trend toward increased expression. Secretion of NGF, MBP, and BDNF was more enhanced at 19 days than that at 7 days. In co-culture system, the induction effect of iSCs was more pronounced at 19 days than that at 7 days, and the difference was statistically significant (55.40 ± 4.50 µm vs 37.15 ± 3.75 µm, p < 0.01). In conclusion, the proliferation ability of ADSC-derived iSCs was negatively correlated with the induction time, while the expression of SC marker proteins was positively correlated. Therefore, iSCs are suitable for use at 19 days after induction.

The relationship between total cholesterol and postpartum impaired glucose tolerance in women with gestational diabetes mellitus.

BACKGROUND: History of gestational diabetes mellitus (GDM) and serum lipid abnormalities were associated with postpartum impaired glucose tolerance. To investigate the association between concentration of total cholesterol (TC), at the time of GDM diagnosis, and risk of postpartum glucose intolerance. METHODS: Women who were diagnosed GDM with a live singleton delivery between January 1, 2013 and December 31, 2017 were included. Women were grouped based on the TC quartiles at the time of GDM diagnosis and had an OGTT at 6-12 weeks after delivery. The relationship between TC and the risk of postpartum glucose intolerance was assessed by COX regression. RESULTS: A total of 845 women were in the final analysis. Higher TC quartile at diagnosis of GDM was associated with a decreased risk of postpartum glucose intolerance. Women in the highest TC quartile (>7.0 mmol L- 1) had approximately only half-risk of any postpartum glucose intolerance, compared with women in the lowest TC quartile (<5.5 mmol L- 1). CONCLUSIONS: The decreased concentration of TC, at the time of GDM diagnosis, was related to an increased risk of postpartum abnormal glucose regulation in GDM women. Therefore, because both excessively increased and decreased TC were associated with pregnancy and postpartum complications, the optimal concentration of maternal TC throughout pregnancy remained to be further researched.

Secondary analysis of existing microarray data reveals potential gene drivers of cutaneous squamous cell carcinoma.

Cutaneous squamous-cell carcinoma (cSCC) is the second most common skin cancer, with an increasing incidence in recent years. To define the molecular basis that drive cSCC development and progression, this study aimed at identifying potential novel molecular targets for the diagnosis and therapy of patients with cSCC. Two data sets with the accession number GSE45164 and GSE66359 were downloaded from Gene Expression Omnibus (GEO) database. After the identification of differentially expressed genes (DEGs) from these two data sets, respectively, between cSCC samples and controls, a combination of DEGs from these two data sets were subjected to the following analyses, including functional annotation, protein-protein interaction (PPI) network and module construction, transcription factor (TF)-target regulation prediction, and drug-gene interaction predictive analysis. A total of 204 upregulated genes and 213 downregulated genes were found in two data sets which were used for the follow-up analysis. Upregulated and downregulated genes were mainly involved in the functions such as cell division, mitotic nuclear division, cell cycle, and p53 signaling pathway. Interferon induced protein family members and proteasome subunit members were involved in the TF-target regulatory network, such as PSMB8, CXCL10, and IFIT3. Eight upregulated genes ( TOP2A, CXCL8, RRM2, PSMB8, PSMB9, PBK, CXCL10, and ISG15) that were hub genes in the PPI network and significant modules were identified in the predicted drug-gene interaction. In conclusion, TOP2A, CXCL8, RRM2, PSMB8, PSMB9, PBK, CXCL10, and ISG15 may be potential targets for the diagnosis and therapy of patients with cSCC.

Early usage of Bakri postpartum balloon in the management of postpartum hemorrhage: a large prospective, observational multicenter clinical study in South China.

AIM: To evaluate the success rate and protocol of the Bakri balloon for postpartum hemorrhage (PPH) in the course of a prospective observational multicenter cohort study in South China. METHODS: At 20 hospitals in South China, women with postpartum bleeding who failed to respond to the first-line conservative management and received the Bakri balloon were recruited for the study. Maternal characteristics, PPH characteristics, PPH management and outcomes in regard to the Bakri balloon use were recorded. RESULTS: A total of 472 women had a Bakri balloon tamponade and 407 (86.23%) women were enrolled (67 after vaginal delivery and 340 either during or after cesarean delivery). The success rate of the Bakri balloon in this study was 91.65% (373/407 women). During vaginal deliveries, the group with a hemorrhage >2000 mL before balloon insertion had significantly more blood loss (551.67±635.17 mL vs. 242.06±313.69 mL, P=0.039) and lower maternal hemoglobin (73±21.77 g/L vs. 92.06±19.60 g/L, P=0.029) after using Bakri balloon than the group with a hemorrhage <1000 mL. Similar data were found during cesarean deliveries. The blood loss before and after balloon insertion were significantly higher in the Bakri balloon failure group (1700±1429.88 mL before and 1209.58±1139.72 mL after using the balloon) than those in the success group [918±493.92 mL before (P=0.002) and 266.57±361.60 mL after using the balloon (P=0.001)]. CONCLUSION: Rapid diagnosis or prognosis of PPH, in combination with early usage of the Bakri postpartum balloon is more effective for the management of PPH.

The associations between triglyceride to high-density lipoprotein cholesterol ratios and the risks of gestational diabetes mellitus and large-for-gestational-age infant.

OBJECTIVE: To evaluate the associations between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratios and the risks of gestational diabetes mellitus (GDM) and delivering large-for-gestational-age (LGA) infant. DESIGN: This was a single-centre prospective observational study. PATIENTS: Six hundred and thirty-six women with a singleton pregnancy were recruited. MEASUREMENTS: Lipids profile, HbA1c and glucose were measured at the time of oral glucose tolerance test (OGTT) during 24-28 gestational weeks. TG/HDL-C ratios were calculated and clinical data including perinatal parameters were analysed. RESULTS: The prevalence of GDM was 17·30% (n = 110) and LGA was 3·93% (n = 25) in this study. TG/HDL-C ratios were found to be significantly higher in GDM group (P < 0·01) and LGA group (P = 0·045) compared with those in non-GDM group and non-LGA group, respectively. TG/HDL-C ratios were independently associated with the risks of GDM (OR = 1·64, P = 0·02) and LGA (OR = 2·87, P < 0·01). The area under the combined ROC curve of TG/HDL-C ratio and HbA1c to detect GDM was 0·705 (95% CI, 0·637-0·772). Furthermore, the area under the ROC curve of TG/HDL-C ratio combined with HbA1c and prepregnancy BMI to detect LGA was 0·806 (95% CI, 0·719-0·893). CONCLUSIONS: TG/HDL-C ratios in combination with HbA1c and prepregnancy BMI can be good markers to predict the risks of GDM and delivering LGA infant.

Derazantinib Inhibits the Bioactivity of Keloid Fibroblasts via FGFR Signaling.

Keloids are common benign cutaneous pathological fibrous proliferation diseases, which are difficult to cure and easily recur. Studies have shown that fibroblast growth factor receptor-1 (FGFR1) was enhanced in pathological fibrous proliferation diseases, such as cirrhosis and idiopathic pulmonary fibrosis (IPF), suggesting the FGFR1 pathway has potential for keloid treatment. Derazantinib is a selective FGFR inhibitor with antiproliferative activity in in vitro and in vivo models. The present study determined the effects of derazantinib on human keloid fibroblasts (KFs). Cell viability assay, migration assay, invasion assay, immunofluorescence staining, quantitative polymerase chain reaction, Western blot analysis, HE staining, Masson staining, and immunohistochemical analysis were used to analyze the KFs and keloid xenografts. In this study, we found that derazantinib inhibited the proliferation, migration, invasion, and collagen production of KFs in vitro. The transcription and expression of plasminogen activator inhibitor-1 (PAI-1), which is closely related to collagen deposition and tissue fibrosis, was significantly inhibited. Also, derazantinib inhibited the expression of FGFR1 and PAI-1 and reduced the weight of the implanted keloid from the xenograft mice model. These findings suggest that derazantinib may be a potent therapy for keloids via FGFR signaling.

Long non-coding RNAs influence aging process of sciatic nerves in SD rats.

OBJECTIVES: To investigate the long non-coding RNAs (lncRNAs) changes in the sciatic nerve (SN) in Sprague Dawley (SD) rats during aging. METHODS: Eighteen healthy SD rats were selected at the age of 1 month (1M) and 24 months (24M) and SNs were collected. High-throughput transcriptome sequencing and bioinformatics analysis were performed. Protein-protein interaction (PPI) networks and competing endogenous RNA (ceRNA) networks were established according to differentially expressed genes (DEGs). RESULT: As the length of lncRNAs increased, its proportion to the total number of lncRNAs decreased. A total of 4079 DElncRNAs were identified in Con vs. 24M. GO analysis was primarily clustered in nerve and lipid metabolism, extracellular matrix, and vascularization-related fields. There were 17 nodes in the PPI network of the target genes of up-regulating genes including Itgb2, Lox, Col11a1, Wnt5a, Kras, etc. Using quantitative RT-PCR, microarray sequencing accuracy was validated. There were 169 nodes constructing the PPI network of down-regulated target genes, mainly including Col1a1, Hmgcs1, Hmgcr. CeRNA interaction networks were constructed CONCLUSION: Lipid metabolism, angiogenesis, and ECM fields might play an important role in the senescence process in SNs. Col3a1, Serpinh1, Hmgcr, and Fdps could be candidates for nerve aging research.

IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation.

Keloids are considered the manifestation of a fibroproliferative disease characterized by chronic inflammation that is induced following skin injury. Deciphering the underlying mechanism of keloid formation is essential for improving treatment outcomes. Here, we found that more macrophages were activated toward the M2 subtype in keloid dermis when compared with normal dermis. Western blotting revealed that the level of phosphorylated STAT6 (p-STAT6), a known inducer of M2 polarization, was higher in keloid fibroblasts as opposed to fibroblasts from normal dermis. Moreover, keloid fibrosis was shown to be positively correlated with the level of p-STAT6. Further, we identified downregulation of IL-13RA2, a decoy receptor for IL-13, in keloid fibroblasts compared with fibroblasts from normal dermis. Ectopic expression of IL-13RA2 in keloid fibroblasts resulted in inhibition of STAT6 phosphorylation, cell proliferation, migration, invasion, extracellular matrix secretion, and myofibroblast marker expression, as well as an increase in apoptosis. Consistently, knockdown of IL-13RA2 in normal fibroblasts induced a keloidal status. Furthermore, both in vitro application and intratumoral injection of p-STAT6 inhibitor AS1517499 in a patient-derived xenograft keloid-implantation mouse model resulted in proliferation inhibition and tissue necrosis, apoptosis, and myofibroblast marker reduction. Collectively, this study elucidates the key role of IL-13RA2 in keloid pathology and inspires further translational research of keloid treatment concerning JAK/STAT6 inhibition.

The Downregulated Lipo-Related Gene Expression Pattern in Keloid Indicates Fat Graft Is a Potential Clinical Option for Keloid.

Background: Keloids are a common complication of wounds, often manifesting with continuous hyperplasia and aggressive growth. Keloids also have a high recurrence rate and are largely resistant to treatment, making them clinically incurable, highlighting the need to translate basic research into clinical practice. Materials and Methods: We used GSE158395 and GSE92566 as discovery datasets to identify specific enriched hub genes and lncRNAs associated with keloid development and progression. This data was then used to identify the competing endogenous RNAs (ceRNAs) in these pathways by using a bidirectional selection method. Then, all hub genes and lncRNAs in ceRNAs were validated using GSE90051, GSE178562, and GSE175866, which describe the transcriptional profiles of keloid tissues, fibroblasts from pathological scars, and keloid fibroblast subpopulations, respectively. The keloid tissues were measured with qPCR. Results: Both fat-associated biological processes and fat cell differentiation were enriched in the downregulated gene set. Further evaluation revealed that all 11 hub genes were lipo-related, and most of these were differentially expressed in all three validation datasets. We then identified a clear ceRNA network within the data comprising six hub genes and four lncRNAs. Evaluations of the validation datasets confirmed that all six of these hub genes and two of the four lncRNAs were downregulated in keloid tissues; two hub genes and one lncRNA were downregulated in fibroblasts from pathological scars; and five hub genes and one lncRNA were significantly downregulated in mesenchymal subpopulation. Three genes had statistical difference and eight genes showed downregulated trend through qPCR of the keloid tissue. Conclusion: Our results suggest that keloid development relies on the downregulation of lipo-related genes and pre-adipocytes in diseased tissues and may be one of the key mechanisms underlying fat grafting-mediated treatment of pathological scarring.

Comprehensive Analysis of Age-related Changes in Lipid Metabolism and Myelin Sheath Formation in Sciatic Nerves.

To investigate the molecular changes related to myelin formation and lipid metabolism in the sciatic nerve in Sprague Dawley (SD) rats during aging. Thirty-six healthy male SD rats were divided into five groups according to age: 1 week, 1 month, 6 months, 12 months, and 24 months. Sciatic nerves were collected from 1-month-old and 24-month-old SD rats (n = 3) to perform next-generation sequencing (NGS) and bioinformatics analysis. Specimens from each group were harvested and analyzed by qPCR, Western blotting, and transmission electron microscopy (TEM). Protein-protein interaction (PPI) networks of differentially expressed mRNAs (DEmRNAs) related to myelin and lipid metabolism were constructed. DEmRNAs in subnetworks were verified using qPCR. A total of 4580 DEmRNAs were found during aging. The top enriched GO biological processes were primarily clustered in cholesterol and lipid metabolism, including the cholesterol biosynthetic process (RF = 3.16), sterol biosynthetic process (RF = 3.03), cholesterol metabolic process (RF = 2.15), sterol metabolic process (RF = 2.11), fatty acid biosynthetic process (RF = 2.09), and lipid biosynthetic process (RF = 1.79). The mRNA levels of MBP, PMP22, and MPZ were downregulated during aging, while the protein expression of MBP showed an increasing trend. The TEM results showed thin myelin sheaths and an increased number of unmyelinated axons in the 1-week-old rats, and the sheaths became thickened with degenerated axons appearing in older animals. Forty PPI subnetworks related to lipid metabolism were constructed, including one primary subnetwork and two smaller subnetworks. The hub genes were mTOR in sub-network 1, Akt1 in sub-network 2, and SIRT1 in sub-network 3. No gene expression was found consistent with the sequencing results, while in the downregulated genes, AKT1, CEBPA, LIPE, LRP5, PHB, and Rara were significantly downregulated in 24-month-old rats. Lipid metabolism might play an important role in maintaining the structure and physiological function in sciatic nerves during aging and could be candidates for nerve aging research.

Integrated analysis of long noncoding RNAs and mRNA expression profiles reveals the potential role of lncRNAs in early stage of post-peripheral nerve injury in Sprague-Dawley rats.

The regulatory role of lncRNAs in the early stage post peripheral nerve injury (PNI) is not yet clear. In this study, next-generation sequencing was used to perform deep sequencing on normal sciatic nerves (control) and lesional tissues derived on the 4th (D4) and 7th days (D7) after sciatic nerve injury in rats. Time-point unique differentially expressed lncRNAs (DElncRNAs) were analyzed for functional enrichment. The results showed that 776 DElncRNAs were unique to D4, and their functions were mainly enriched in wound healing, phosphatase binding and MAPK signaling pathways; 317 DElncRNAs were unique to D7, and their functions were mainly enriched in ion transmembrane transporter channel activity; 579 DElncRNAs were shared by these two days, and their functions were mainly enriched in axongenesis, the PI3K-Akt signaling pathway and cell cycle. Furthermore, lncRNA-mRNA interaction networks were constructed in functions or pathways with a high enrichment rate. Finally, 3 mRNAs and 4 lncRNAs in the axongenesis interaction network were selected, and their expression levels were verified by RT-qPCR. This study preliminarily revealed the regulatory role of lncRNAs at different time points in the early stage post PNI, which provides potential targets for basic research and clinical treatment of PNI.

Interactions Among Nerve Regeneration, Angiogenesis, and the Immune Response Immediately After Sciatic Nerve Crush Injury in Sprague-Dawley Rats.

To preliminarily explore the primary changes in the expression of genes involved in peripheral nerve processes, namely, regeneration, angiogenesis, and the immune response, and to identify important molecular therapeutic targets, 45 Sprague-Dawley (SD) rats were randomly divided into a control group and an injury group. In the injury group, tissue samples were collected at 4 and 7 days after the injury for next-generation sequencing (NGS) analysis combined with gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Venn diagram construction to identify the differentially expressed mRNAs (DEmRNAs) associated with regeneration, angiogenesis, and the immune response of the nerve. The expression of genes in the distal and proximal ends of the injured nerve after injury was analyzed by qRT-PCR. NGS revealed that compared with the control group, the injury group had 4020 DEmRNAs 4 days after injury and 3278 DEmRNAs 7 days after injury. A bioinformatics analysis showed that C-C chemokine receptor type 5 (CCR5), Thy1 cell surface antigen (Thy1), Notch homolog 1 (Notch1), and semaphorin 4A (Sema4A) were all associated with regeneration, angiogenesis, and the immune response of the nerve at both 4 and 7 days after injury, but qPCR revealed no significant difference in the expression of Thy1 (P = 0.29) or Sema4A (P = 0.82) in the proximal end, whereas a significant difference was observed in CCR5 and Notch1 (P < 0.05). The trend in the Notch1 change was basically consistent with the RNA-seq result after injury, which implied its indispensable role during endothelial cell proliferation and migration, macrophage recruitment, and neurotrophic factor secretion.

FGF15/FGF19 alleviates insulin resistance and upregulates placental IRS1/GLUT expression in pregnant mice fed a high-fat diet.

INTRODUCTION: This study aimed to evaluate whether FGF19 can alleviate insulin resistance and change the expression of placental IRS1/GLUTs. METHODS: Mice transgenic for Fgf15 (the murine homologue of human FGF19) were constructed, and human recombinant FGF19 was administered to pregnant high-fat diet mice. Then, glycolipid metabolism parameters and the weight of foetus and placenta were observed. The expression levels of key molecules of the insulin signalling pathway and glucose transporters in placentae were detected by qRT-PCR and western blotting. Primary trophoblasts and JAR cells were cultured in high-glucose medium, and FGF19 was added to observe its regulatory effects on IRS1/GLUTs. RESULTS: Overexpressing FGF15 or exogenously administering FGF19 reduced the levels of fasting blood glucose, HOMA-IR, triglycerides, and free fatty acids in pregnant high-fat diet mice compared to control mice (P < 0.05). FGF15/FGF19 did not significantly affect placental weight, foetal weight or litter size (P > 0.05). In addition, FGF15/FGF19 upregulated the expression of p-IRS1 and GLUT4 in the placentae of high-fat diet mice and upregulated GLUT1 levels in the placentae of normal diet-fed mice (P < 0.05), while it did not significantly alter total IRS1 and GLUT3 levels (P > 0.05). Consistent with the results of the animal experiments, FGF19 increased the expression of p-IRS1 and GLUT4 in trophoblast cells cultured in high-glucose medium (P < 0.05). DISCUSSION: Overexpressing FGF15 or administering FGF19 to pregnant high-fat diet mice can improve glycolipid metabolism and alleviate systemic and local insulin resistance. The possible underlying mechanism may involve upregulation of placental expression of p-IRS1 and GLUT4.

Long-wave Ultraviolet Ray Promotes Inflammation in Keloid-derived Fibroblasts by Activating P38-NFκB1 Signaling Pathway.

One of the main mechanisms of keloid formation is the persistent chronic inflammation, which initiates the activation of keloid-derived fibroblasts (KFs) and boosts the production of extracellular matrix. Meanwhile, 95% of the ultraviolet rays that reach the earth are long-wave ultraviolet (UVA). However, the effect of UVA on keloids is currently unclear. The objective of our research is to investigate UVA's impact on keloids. Cell viability assay, migration assay, and cell cycle analysis were conducted. UVA's impacts on gene expressions were detected by real-time quantitative polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence. Our results indicated that UVA inhibited the proliferation and migration of KFs. In addition, after UVA irradiation, the expressions of matrix metallopeptidase 1 and matrix metallopeptidase 2 markedly increased in KFs. Moreover, the expression of α-smooth muscle actin and collagen I decreased. Furthermore, KFs with UVA irradiation secreted more interleukin-6 and interleukin-8 in the culture medium. And it was confirmed that the protein expressions of inflammation-related factors, including P38, CK2A, NFκB1, and P65, increased observably in KFs with UVA irradiation. The protein expression of IKBα, also known as NFκB inhibitor α, decreased. All these observations suggested that UVA irradiation could inhibit cellular activity and collagen production in KFs while promoting inflammation by activating P38-NFκB1 signal pathway.

Secondary data mining of GEO database for long non-coding RNA and Competing endogenous RNA network in keloid-prone individuals.

This study aimed to identify long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) differentially expressed (DE) during keloid formation, predict DElncRNA-DEmiRNA-DEmRNA interactions, and construct a competing endogenous RNA (ceRNA) network through secondary data mining of keloid-related sequencing and microarray data in the open-source Gene Expression Omnibus (GEO) database. The GSE113621 dataset was downloaded from the GEO database, |log2FC|>1 and p<0.05 were set as screening criteria, genes expressed only in keloid-prone individuals were selected as research objects, and DEmRNAs, DElncRNAs, and DEmiRNAs before injury and 6 weeks after injury were screened. A Pearson correlation coefficient (PCC) of > 0.95 was selected as the index to predict the targeting relationships among lncRNAs, miRNAs, and mRNAs; and a network diagram was constructed using Cytoscape. The expression of 2356 lncRNAs was changed in the keloid-prone group-1306 were upregulated and 1050 were downregulated. Six lncRNAs, namely, 2 upregulated (DLEU2 and AP000317.2) and 4 downregulated (ADIRF-AS1, AC006333.2, AL137127.1 and LINC01725) lncRNAs, were expressed only in the keloid-prone group and were used to construct a ceRNA network. DLEU2 may regulate fibroblast proliferation, differentiation, and apoptosis through hsa-miR-30a-5p/hsa-miR-30b-5p. In-depth mining of GEO data indicated that lncRNAs and a ceRNA regulatory network participate in the wound healing process in keloid-prone individuals, possibly providing novel intervention targets and treatment options for keloid scars.