In vivo pilot study into superficial microcirculatory characteristics of colorectal adenomas using novel high-resolution magnifying endoscopy with blue laser imaging.

BACKGROUND: No studies have yet been conducted on changes in microcirculatory hemodynamics of colorectal adenomas in vivo under endoscopy. The microcirculation of the colorectal adenoma could be observed in vivo by a novel high-resolution magnification endoscopy with blue laser imaging (BLI), thus providing a new insight into the microcirculation of early colon tumors. AIM: To observe the superficial microcirculation of colorectal adenomas using the novel magnifying colonoscope with BLI and quantitatively analyzed the changes in hemodynamic parameters. METHODS: From October 2019 to January 2020, 11 patients were screened for colon adenomas with the novel high-resolution magnification endoscope with BLI. Video images were recorded and processed with Adobe Premiere, Adobe Photoshop and Image-pro Plus software. Four microcirculation parameters: Microcirculation vessel density (MVD), mean vessel width (MVW) with width standard deviation (WSD), and blood flow velocity (BFV), were calculated for adenomas and the surrounding normal mucosa. RESULTS: A total of 16 adenomas were identified. Compared with the normal surrounding mucosa, the superficial vessel density in the adenomas was decreased (MVD: 0.95 ± 0.18 vs 1.17 ± 0.28 µm/µm2, P < 0.05). MVW (5.11 ± 1.19 vs 4.16 ± 0.76 µm, P < 0.05) and WSD (11.94 ± 3.44 vs 9.04 ± 3.74, P < 0.05) were both increased. BFV slowed in the adenomas (709.74 ± 213.28 vs 1256.51 ± 383.31 µm/s, P < 0.05). CONCLUSION: The novel high-resolution magnification endoscope with BLI can be used for in vivo study of adenoma superficial microcirculation. Superficial vessel density was decreased, more irregular, with slower blood flow.

Usefulness of analyzing endoscopic features in identifying the colorectal serrated sessile lesions with and without dysplasia.

BACKGROUND: Sessile serrated lesions (SSLs) are often missed on colonoscopy, and studies have shown this to be an essential cause of interstitial colorectal cancer. The SSLs with dysplasia (SSL-D+), in particular, have a faster rate of carcinogenesis than conventional tubular adenomas. Therefore, there is a clinical need for some endoscopic features with independent diagnostic value for SSL-D+s to assist endoscopists in making immediate diagnoses, thus improving the quality of endoscopic examination and treatment. AIM: To compare the characteristics of SSLs, including those with and without dysplasia (SSL-D+ and SSL-D-), based on white light and image-enhanced endoscopy, to achieve an immediate differential diagnosis for endoscopists. METHODS: From January 2017 to February 2023, cases of colorectal SSLs confirmed by colonoscopy and histopathology at the Gastrointestinal Endoscopy Center of Beijing Tsinghua Changgung Hospital were collected. The general, endoscopic, and histopathological data were reviewed and analyzed to determine the diagnostic utility. Univariate analysis was used to find potential diagnostic factors, and then multivariate regression analysis was performed to derive endoscopic features with independent diagnostic values for the SSL-D+. RESULTS: A total of 228 patients with 253 lesions were collected as a result. There were 225 cases of colorectal SSL-D-s and 28 cases of SSL-D+s. Compared to the colorectal SSL-D-, the SSL-D+ was more common in the right colon (P = 0.027) with complex patterns of depression, nodule, and elevation based on cloud-like surfaces (P = 0.003), reddish (P < 0.001), microvascular varicose (P < 0.001), and mixed type (Pit II, II-O, IIIL, IV) of crypt opening based on Pit II-O (P < 0.001). Multifactorial logistic regression analysis indicated that lesions had a reddish color [odds ratio (OR) = 18.705, 95% confidence interval (CI): 3.684-94.974], microvascular varicose (OR = 6.768, 95%CI: 1.717-26.677), and mixed pattern of crypt opening (OR = 20.704, 95%CI: 2.955-145.086) as the independent predictors for SSL-D+s. CONCLUSION: The endoscopic feature that has independent diagnostic value for SSL-D+ is a reddish color, microvascular varicose, and mixed pattern of crypt openings.

Development of curcumin-loaded galactosylated chitosan-coated nanoparticles for targeted delivery of hepatocellular carcinoma.

Curcumin (CUR) has good antitumor effects, but its poor aqueous solubility severely limits its clinical application and the systemic nonspecific distribution of the free drug in tumor patients is a key therapeutic challenge. In order to overcome the limitations of free drugs and improve the therapeutic efficacy, we developed novel galactosylated chitosan (GC)-modified nanoparticles (GC@NPs) based on poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PEG-PLGA), which can target asialoglycoprotein receptor (ASGPR) expressed on hepatocellular carcinoma cells and have excellent biocompatibility. The results showed that the drug loading (DL) of CUR was approximately 4.56 %. A favorable biosafety profile was maintained up to concentrations of 500 µg/mL. Furthermore, in vitro cellular assays showed that GC@NPs could be efficiently internalized by HepG2 cells via ASGPR-mediated endocytosis and successfully released CUR for chemotherapy. More importantly, in vivo anti-tumor experiments revealed that GC@NPs were able to accumulate effectively within tumor sites through EPR effect and ASGPR-mediated endocytosis, leading to superior inhibition of tumor growth compared to free CUR. Overall, GC@NPs are a promising CUR nanocarrier for enhanced tumor therapy with a good biosafety profile.

Targeted Drug Delivery Systems for Curcumin in Breast Cancer Therapy.

Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR's therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.

Inferring cancer common and specific gene networks via multi-layer joint graphical model.

Cancer is a complex disease caused primarily by genetic variants. Reconstructing gene networks within tumors is essential for understanding the functional regulatory mechanisms of carcinogenesis. Advances in high-throughput sequencing technologies have provided tremendous opportunities for inferring gene networks via computational approaches. However, due to the heterogeneity of the same cancer type and the similarities between different cancer types, it remains a challenge to systematically investigate the commonalities and specificities between gene networks of different cancer types, which is a crucial step towards precision cancer diagnosis and treatment. In this study, we propose a new sparse regularized multi-layer decomposition graphical model to jointly estimate the gene networks of multiple cancer types. Our model can handle various types of gene expression data and decomposes each cancer-type-specific network into three components, i.e., globally shared, partially shared and cancer-type-unique components. By identifying the globally and partially shared gene network components, our model can explore the heterogeneous similarities between different cancer types, and our identified cancer-type-unique components can help to reveal the regulatory mechanisms unique to each cancer type. Extensive experiments on synthetic data illustrate the effectiveness of our model in joint estimation of multiple gene networks. We also apply our model to two real data sets to infer the gene networks of multiple cancer subtypes or cell lines. By analyzing our estimated globally shared, partially shared, and cancer-type-unique components, we identified a number of important genes associated with common and specific regulatory mechanisms across different cancer types.

Plasma metabolomic characterization of premature ovarian insufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) patients are predisposed to metabolic disturbances, including in lipid metabolism and glucose metabolism, and metabolic disorders appear to be a prerequisite of the typical long-term complications of POI, such as cardiovascular diseases or osteoporosis. However, the metabolic changes underlying the development of POI and its subsequent complications are incompletely understood, and there are few studies characterizing the disturbed metabolome in POI patients. The aim of this study was to characterize the plasma metabolome in POI by using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) metabolomics and to evaluate whether these disturbances identified in the plasma metabolome relate to ovarian reserve and have diagnostic value in POI. METHODS: This observational study recruited 30 POI patients and 30 age- and body mass index (BMI)-matched controls in the Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, from January 2018 to October 2020. Fasting venous blood was collected at 9:00 am on days 2-4 of the menstrual cycle and centrifuged for analysis. An untargeted quantitative metabolomic analysis was performed using UHPLC-MS/MS. RESULTS: Our study identified 48 upregulated and 21 downregulated positive metabolites, and 13 upregulated and 48 downregulated negative metabolites in the plasma of POI patients. The differentially regulated metabolites were involved in pathways such as caffeine metabolism and ubiquinone and other terpenoid-quinone biosynthesis. Six metabolites with an AUC value > 0.8, including arachidonoyl amide, 3-hydroxy-3-methylbutanoic acid, dihexyl nonanedioate, 18-HETE, cystine, and PG (16:0/18:1), were correlated with ovarian reserve and thus have the potential to be diagnostic biomarkers of POI. CONCLUSION: This UHPLC-MS/MS untargeted metabolomics study revealed differentially expressed metabolites in the plasma of patients with POI. The differential metabolites may not only be involved in the aetiology of POI but also contribute to its major complications. These findings offer a panoramic view of the plasma metabolite changes caused by POI, which may provide useful diagnostic and therapeutic clues for POI disease.

Mining Potential Drug Targets for Osteoporosis Based on CeRNA Network.

OBJECTIVE: To identify key pathological hub genes, micro RNAs (miRNAs), and circular RNAs (circRNAs) of osteoporosis (OP) and construct their ceRNA network in an effort to explore the potential biomarkers and drug targets for OP therapy. METHODS: GSE7158, GSE201543, and GSE161361 microarray datasets were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by comparing OP patients with healthy controls and hub genes were screened by machine learning algorithms. Target miRNAs and circRNAs were predicted by FunRich and circbank, then ceRNA network were constructed by Cytoscape. Pathways affecting OP were identified by functional enrichment analysis. The hub genes were verified by receiver operating characteristic (ROC) curve and real time quantitative PCR (RT-qPCR). Potential drug molecules related to OP were predicted by DSigDB database and molecular docking was analyzed by autodock vina software. RESULTS: A total of 179 DEGs were identified. By combining three machine learning algorithms, BAG2, MME, SLC14A1, and TRIM44 were identified as hub genes. Three OP-associated target miRNAs and 362 target circRNAs were predicted to establish ceRNA network. The ROC curves showed that these four hub genes had good diagnostic performance and their differential expression was statistically significant in OP animal model. Benzo[a]pyrene was predicted which could successfully bind to protein receptors related to the hub genes and it was served as the potential drug molecules. CONCLUSION: An mRNA-miRNA-circRNA network is reported, which provides new ideas for exploring the pathogenesis of OP. Benzo[a]pyrene, as potential drug molecules for OP, may provide guidance for the clinical treatment.

Clinical value of the Toronto inflammatory bowel disease global endoscopic reporting score in ulcerative colitis.

BACKGROUND: Endoscopic evaluation in diagnosing and managing ulcerative colitis (UC) is becoming increasingly important. Several endoscopic scoring systems have been established, including the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score and Mayo Endoscopic Subscore (MES). Furthermore, the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting (TIGER) score for UC has recently been proposed; however, its clinical value remains unclear. AIM: To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES. METHODS: This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University (Qingdao, China). We retrospectively analysed endoscopic scores, laboratory and clinical data, treatment, and readmissions within 1 year. Spearman's rank correlation coefficient, receiver operating characteristic curve, and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, United States) and GraphPad Prism version 9.0.0 for Windows (GraphPad Software, Boston, Massachusetts, United States). RESULTS: The TIGER score significantly correlated with the UCEIS score and MES (r = 0.721, 0.626, both P < 0.001), showed good differentiating values for clinical severity among mild, moderate, and severe UC [8 (4-112.75) vs 210 (109-219) vs 328 (219-426), all P < 0.001], and exhibited predictive value in diagnosing patients with severe UC [area under the curve (AUC) = 0.897, P < 0.001]. Additionally, the TIGER (r = 0.639, 0,551, 0.488, 0.376, all P < 0.001) and UCEIS scores (r = 0.622, 0,540, 0.494, and 0.375, all P < 0.001) showed stronger correlations with laboratory and clinical parameters, including C-reactive protein, erythrocyte sedimentation rate, length of hospitalisation, and hospitalisation costs, than MES (r = 0.509, 0,351, 0.339, and 0.270, all P < 0.001). The TIGER score showed the best predictability for patients' recent advanced treatment, including systemic corticosteroids, biologics, or immunomodulators (AUC = 0.848, P < 0.001) and 1-year readmission (AUC = 0.700, P < 0.001) compared with the UCEIS score (AUC = 0.762, P < 0.001; 0.627, P < 0.05) and MES (AUC = 0.684, P < 0.001; 0.578, P = 0.132). Furthermore, a TIGER score of ≥ 317 was identified as an independent risk factor for advanced UC treatment (P = 0.011). CONCLUSION: The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment, guiding therapeutic decision-making, and predicting short-term prognosis.

Principle and progress of radical treatment for locally advanced esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is one of the most common malignant tumors in the digestive system in China and the world. Most patients are diagnosed as locally advanced or advanced stage. Concurrent chemoradiotherapy is the standard treatment for locally advanced esophageal squamous cell carcinoma. This study intends to summarize the evidence-based medical evidence of the treatment principle of locally advanced esophageal squamous cell carcinoma, the selection of radiotherapy dose, the outline of radiotherapy target and the selection of chemotherapy scheme. As a result, the effect of radiotherapy and chemotherapy is equivalent to that of surgery for the radical treatment of esophageal squamous cell carcinoma. In the era of immunization, it is recommended to use involved field irradiation. Fluorouracil plus cisplatin regimen is the standard chemotherapy regimen. FOLFOX regimen and paclitaxel plus fluorouracil regimen are optional concurrent chemotherapy regimens. The toxic and side effects of different chemotherapy regimens are different, which can be selected according to the actual situation of patients.

Review targeted drug delivery systems for norcantharidin in cancer therapy.

Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects.

Stereotactic body radiotherapy plus transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma patients with portal vein tumour thrombus: A meta-analysis.

BACKGROUND: The efficacy and safety of stereotactic body radiotherapy (SBRT) plus transcatheter arterial chemoembolization (TACE) versus SBRT or TACE alone(monotherapy) for hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) remains controversial. This meta-analysis was performed to provide more powerful evidence for clinical strategies in inoperable HCC with PVTT. METHODS: We searched the PubMed, EMBASE, Web of Science, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), VIP Journal Integration Platform (VIP), and WanFang databases for eligible studies. We pooled the results of 1- and 2-year overall survival rates (OSRs), objective response rates (ORRs), and adverse events (AEs) between the two groups and performed a subgroup meta-analysis for study type, control group, treatment order, and the interval between SBRT and TACE. RESULTS: Nine studies with 10 cohorts involving 938 patients were included in our meta-analysis. SBRT plus TACE yielded significantly higher 1-year OSR (RR, 1.52[95% CI, 1.33-1.74]), 2-year OSR (RR, 2.00 [95% CI: 1.48-2.70]), ORR (RR = 1.22 [95% CI, 1.08-1.37]), and a lower progression disease (PD) rate (RR = 0.45 [95% CI:0.26-0.79]) than monotherapy. No significant differences were detected in CR, PR, SD, or AEs between the two groups. Subgroup analysis regarding study type, control group, and treatment order indicated that compared with monotherapy, the combination of SBRT with TACE was associated with an increase in 1- and 2-year OSRs but not in ORR. In regard to the interval between SBRT and TACE, subgroup analysis found that the combination therapy for patients with an SBRT-TACE interval <28 days was preferable to monotherapy in the 1- and 2-year OSRs, and ORR. However, for patients with an SBRT-TACE interval ≥28 days, no obvious distinctions were observed in the 1-year OSR, 2-year OSR, or ORR between the two groups. CONCLUSION: The combination of SBRT with TACE appears to be better than monotherapy in treating HCC with PVTT and should be recommended for inoperable HCC patients with PVTT.

Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.

Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.

Sphingobacterium faecale sp. nov., a 1-aminocyclopropane-1-carboxylate deaminase producing bacterium isolated from camel faeces.

An investigation of the diversity of 1-aminocyclopropane-1-carboxylate deaminase producing bacteria associated with camel faeces revealed the presence of a novel bacterial strain designated C459-1T. It was Gram-stain-negative, short-rod-shaped and non-motile. Strain C459-1T was observed to grow optimally at 35 °C, at pH 7.0 and in the presence of 0 % NaCl on Luria-Bertani agar medium. The cells were found to be positive for catalase and oxidase activities. The major fatty acids (>10 %) were identified as iso-C15 : 0, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) and iso-C17 : 0 3-OH. The predominant menaquinone was MK-7. The major polar lipids consisted of phosphatidylethanolamine, one sphingophospholipid, two unknown aminophospholipids, three unknown glycolipids and five unknown lipids. The genomic DNA G+C content was 40.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain C459-1T was affiliated with the genus Sphingobacterium and had the highest sequence similarity to Sphingobacterium tabacisoli h337T (97.0 %) and Sphingobacterium paucimobilis HER1398T (95.6 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain C459-1T and S. tabacisoli h337T were 83.8 and 33.8 %, respectively. Phenotypic characteristics including enzyme activities and carbon source utilization differentiated strain C459-1T from other Sphingobacterium species. Based on its phenotypic, chemotaxonomic and phylogenetic properties, strain C459-1T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium faecale sp. nov. is proposed, with strain is C459-1T (CGMCC 1.18716T=KCTC 82381T) as the type strain.

Identifying Gene Network Rewiring Based on Partial Correlation.

It is an important task to learn how gene regulatory networks change under different conditions. Several Gaussian graphical model-based methods have been proposed to deal with this task by inferring differential networks from gene expression data. However, most existing methods define the differential networks as the difference of precision matrices, which may include false differential edges caused by the change of conditional variances. In addition, prior information about the condition-specific networks and the differential networks can be obtained from other domains. It is useful to incorporate prior information into differential network analysis. In this study, we propose a new differential network analysis method to address the above challenges. Instead of using the precision matrices, we define the differential networks as the difference of partial correlations, which can exclude the spurious differential edges due to the variants of conditional variances. Furthermore, prior information from multiple hypothesis testing is incorporated using a weighted fused penalty. Simulation studies show that our method outperforms the competing methods. We also apply our method to identify the differential network between luminal A and basal-like subtypes of breast cancers and the differential network between acute myeloid leukemia tumors and normal samples. The hub genes in the differential networks identified by our method carry out important biological functions.

[Clinical observation of acupoint application of Chinese herbal medicine in preventing postoperative nausea and vomiting after orthopaedic surgery under general anesthesia].

OBJECTIVE: To explore clinical effect of acupoint application of Chinese herbal medicine in preventing postoperative nausea and vomiting after orthopaedic surgery under general anesthesia. METHODS: From January 2018 to December 2019, 168 patients who met inclusion criteria and were underwent selective spine surgery, were double-blind divided into two groups according to central random system, 84 patients in each group. In control group, there were 39 males and 45 females aged from 30 to 65 years old with an average of (53.83±9.17) years old, 37 patients were classified to typeⅠand 47 patients were typeⅡ according to American Society of Anesthesiologists (ASA) grading. In experiment group, there were 39 males and 45 females aged from 30 to 65 years old with an average of (54.08±9.00) years old; 32 patients were classified to typeⅠand 52 patients were typeⅡ according to ASA grading. Both of two groups were obtained acupoint application before anesthesia induction, and acupoint application were put on Zhongwan (CV 12) and bilateral Neiguan (PC 6) for 6 h, changed after 24 h, last for 2 d. The drug prescription of plasters in experimental group was consist of Rhizome Pinelliae Preparata, Ginger and Clove. The plasters in control group was consistent with drug plasters in experimental group in appearance and smell to the greatest extent. The ingredients were flour and excipients with 10% of experimental drug concentration. Incidence of nausea vomiting, visual analogue scale (VAS) of narusea degree at 24 h and 24 to 48 h after operation between two groups were compared, SF- 12 simple quality of life score before operation, 24 and 48 h after operation were also compared by using R3.6.1 Rstudio software by the third-party. RESULTS: There were no statistical differences in incidence of nausea vomiting, VAS of narusea degree at 24 h after operation (P>0.05), while there were no differences in incidence of nausea vomiting, VAS of narusea degree at 24 to 48 h after operation (P>0.05) . There were no statistical differences in SF-12 before operation, 24 and 48 h after opertaion (P>0.05). CONCLUSION: The curative effect of acupoint application of traditional Chinese medicine on the prevention and treatment of postoperative nausea and vomiting is not obvious.

Hypoxic ucMSC-secreted exosomal miR-125b promotes endothelial cell survival and migration during wound healing by targeting TP53INP1.

A hypoxic microenvironment is a common feature of skin wounds. Our previous study demonstrated that three-dimensional coculture of umbilical cord-derived mesenchymal stem cells (ucMSCs) and endothelial cells facilitates cell communication and host integration in skin tissue engineering. Here, we aimed to identify the mechanism by which ucMSCs affect endothelial cells under hypoxic conditions after skin injury. We demonstrate that hypoxia enhances the exosome-mediated paracrine function of ucMSCs, which increases endothelial cell proliferation and migration. In a mouse full-thickness skin injury model, ucMSC-derived exosomes can be taken up by endothelial cells and accelerate wound healing. Hypoxic exosomes lead to a better outcome than normoxic exosomes by promoting proliferation and inhibiting apoptosis. Mechanistically, microRNA-125b (miR-125b) transcription is induced by hypoxia in ucMSCs. After being packaged into hypoxic exosomes and transported to endothelial cells, miR-125b targets and suppresses the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1) and alleviates hypoxia-induced cell apoptosis. Inhibition of miR-125b-TP53INP1 interaction attenuates the protective effect of hypoxic exosomes. Moreover, artificial agomiR-125b can accelerate wound healing in vivo. Our findings reveal communication between ucMSCs and endothelial cells via exosomal miR-125b/TP53INP1 signaling in the hypoxic microenvironment and present hypoxic exosomes as a promising therapeutic strategy to enhance cutaneous repair.

[Exploration of emulsifying material basis of Angelicae Sinensis Radix volatile oil based on partial least squares and hydrophile-lipophile balance value].

This study explores the emulsifying material basis of Angelicae Sinensis Radix volatile oil (ASRVO) based on partial least squares (PLS) method and hydrophile-lipophile balance (HLB) value.The turbidity of ASRVO emulsion samples from Gansu,Yunnan,and Qinghai was determined and the chemical components in the emulsion were analyzed by GC-MS.The PLS model was established with the chemical components as the independent variable and the turbidity as the dependent variable and evaluated with indexes R~2X and R~2Y.The chemical components which were in positive correlation with the turbidity were selected and the HLB values were calculated to determine the emulsification material basis of ASRVO.The PLS models for the 81 emulsion samples had high R~2X and R~2Y values,which showed good fitting ability.Seven chemical components,2-methoxy-4-vinylphenol,trans-ligustilide,3-butylidene-1(3H)-isobenzofuranone,dodecane,1-methyl-4-(1-methylethylidene)-cyclohexene,trans-beta-ocimene,and decane,had positive correlation with turbidity.Particularly,the HLB value of 2-methoxy-4-vinylphenol was 4.4,which was the HLB range of surfactants to be emulsifiers and 2-methoxy-4-vinylphenol was positively correlated with turbidity of the ASRVO emulsion samples from the main producing area.Therefore,2-methoxy-4-vinylphenol was the emulsifying material basis of ASRVO.The selected emulsifying substances can lay a foundation for exploring the emulsification mechanism and demulsification solution of ASRVO.

Differential network analysis by simultaneously considering changes in gene interactions and gene expression.

MOTIVATION: Differential network analysis is an important tool to investigate the rewiring of gene interactions under different conditions. Several computational methods have been developed to estimate differential networks from gene expression data, but most of them do not consider that gene network rewiring may be driven by the differential expression of individual genes. New differential network analysis methods that simultaneously take account of the changes in gene interactions and changes in expression levels are needed. RESULTS: : In this article, we propose a differential network analysis method that considers the differential expression of individual genes when identifying differential edges. First, two hypothesis test statistics are used to quantify changes in partial correlations between gene pairs and changes in expression levels for individual genes. Then, an optimization framework is proposed to combine the two test statistics so that the resulting differential network has a hierarchical property, where a differential edge can be considered only if at least one of the two involved genes is differentially expressed. Simulation results indicate that our method outperforms current state-of-the-art methods. We apply our method to identify the differential networks between the luminal A and basal-like subtypes of breast cancer and those between acute myeloid leukemia and normal samples. Hub nodes in the differential networks estimated by our method, including both differentially and nondifferentially expressed genes, have important biological functions. AVAILABILITY AND IMPLEMENTATION: All the datasets underlying this article are publicly available. Processed data and source code can be accessed through the Github repository at https://github.com/Zhangxf-ccnu/chNet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Let-7e modulates the proliferation and the autophagy of human granulosa cells by suppressing p21 signaling pathway in polycystic ovary syndrome without hyperandrogenism.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in reproductive-aged women, and its pathogenesis is still under debate. Recent studies suggest crucial roles for microRNAs (miRNAs) in PCOS development. The let-7 family miRNAs constitute the most abundant miRNAs in human granulosa cells (GCs), and plays an important role in follicular development. However, research on the let-7e implications of the non-hyperandrogenic (non-HA) phenotype remains unclear. This study aimed at determining the role of let-7e in the progression of PCOS. We performed quantitative real-time PCR to examine the levels of let-7e in fifty-two non-HA PCOS patients and fifty-two controls. A receiver operating characteristic (ROC) curve were used to reveal the diagnostic value of let-7e in non-HA PCOS. Using an immortalized human granulosa cell line, KGN, we investigated the influence of let-7e on cell proliferation and autophagy. Our data substantiated the expression of let-7e was significantly increased in non-HA PCOS group, and associated with an increased antral follicle count. The ROC curve indicated a major separation between non-HA PCOS group and the control group. Let-7e knockdown suppressed cell proliferation and enhanced cell autophagy by activating p21 pathway. Conversely, let-7e overexpression promoted cell proliferation and inhibited cell autophagy by suppressing p21 pathway. Our results indicate that increased let-7e levels in non-HA PCOS GCs may contribute to excessive follicular activation and growth, thereby involving in the pathogenesis of PCOS. Let-7e may thus be a potential therapeutic target in non-HA PCOS.

M5C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in lung adenocarcinoma.

BACKGROUND: In recent years, immunotherapy has made great progress, and the regulatory role of epigenetics has been verified. However, the role of 5-methylcytosine (m5C) in the tumor microenvironment (TME) and immunotherapy response remains unclear. METHODS: Based on 11 m5C regulators, we evaluated the m5C modification patterns of 572 lung adenocarcinoma (LUAD) patients. The m5C score was constructed by principal component analysis (PCA) algorithms in order to quantify the m5C modification pattern of individual LUAD patients. RESULTS: Two m5C methylation modification patterns were identified according to 11 m5C regulators. The two patterns had a remarkably distinct TME immune cell infiltration characterization. Next, 226 differentially expressed genes (DEGs) related to the m5C phenotype were screened. Patients were divided into three different gene cluster subtypes based on these genes, which had different TME immune cell infiltration and prognosis characteristics. The m5C score was constructed to quantify the m5C modification pattern of individual LUAD patients. We found that the high m5C score group had a better prognosis. The role of the m5C score in predicting prognosis was also verified in the dataset GSE31210. CONCLUSIONS: Our study revealed that m5C modification played a significant role in TME regulation of LUAD. Investigation of the m5C regulation mode may have some implications for tumor immunotherapy in the future.