Search

Guo-Hong Zhao,1 Jin-Da Wang,1 Mei-Rui Liu,2,3 Li-Jun Zhang,4 Yan Sun,5 Kai Cao6 1Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pulmonary Rehabilitation, Emergency General Hospital, Beijing, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, Hebei, People’s Republic of China; 4Department of Obstetrics and Gynecology, Linyi Hospital of Traditional Chinese Medicine, Linyi, Shandong, People’s Republic of China; 5Department of Ophthalmology, Linyi Hospital of Traditional Chinese Medicine, Linyi, Shandong, People’s Republic of China; 6Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Kai Cao, Email crcteam@163.comObjective: To explore the distribution and influence factors of non-invasive tear film break-up time (NIBUT) in children.Methods: This is a hospital-based cross-sectional study. Spherical equivalent error (SER) was measured with cycloplegia. NIBUT was measured by an ocular surface integrated analyzer.Results: A total of 1269 children (1269 eyes) were included in this study. Participants’ median age was 11 (range 6– 18) years. 47.1% (598/1269) of participants were boys. The median NIBUT of myopic children and non-myopic children were 9.9 seconds (s) (Inter-quartile range, IQR: 6.4 to 16.1) and 10.9 s (IQR: 8.8 to 17.9), respectively, which was statistically significant (p = 0.004). In myopic children, 49.9% (573/1148) were able to achieve NIBUT of 10 s or more, compared to 67.8% (82/121) in non-myopic children, which was statistically significant (p < 0.001). There were 41 (3.57%) children in the myopic group and none (0%) in the non-myopic group with dry eye disease (p = 0.028). There was a positive correlation between NIBUT and age: NIBUT = 9.256 + 0.352&ast;Age. 71.8% (824/1148) of myopic children used electronic products almost every day, compared to 37.2% (45/121) of non-myopic children, which was statistically significant (p < 0.001).Conclusion: The NIBUT of myopic children was significantly shorter than that of non-myopic children. Children with myopia are more likely to have dry eyes. NIBUT increases with age. High frequency of electronic product use may be an important cause to NIBUT shortening in children.Keywords: Tear film break-up time, dry eye, Myopia, ocular surface, children

Kun Cao,1,2,&ast; Zehui Wang,1,3,5,6,&ast; Xiaojiao Sun,3– 6,&ast; Di Yan,1– 3 Yanwen Liu,3 Ting Ma,3 Xiaojuan Sun1,2 1Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3School of Stomatology, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 4Animal Experiment Center of Ningxia Medical University, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 5Stem Cell Institute, General Hospital, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 6Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zehui Wang, Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email wangzehui364@163.com Xiaojuan Sun, Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email ms_sunxiaojuan@126.comIntroduction: Nano-mesoporous bioactive glass and RGD peptide-coated collagen membranes have great potential in wound healing. However, the application of their compound has not been further studied. Our purpose is to prepare a novel bioactive collagen scaffold containing both NMBG stent and adhesion peptides (BM), which then proves its promising prospect the assessment of physical properties, biocompatibility, GSK-3β/β-catenin signaling axis and toxicological effects.Methods: The structural and morphological changes of BM were analyzed using scanning electron microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). In vivo, wound healing of BM was assessed in SD rats through dynamic monitoring and calculation of wound healing rate. Immunohistofluorescence (IHF), H&E, and Masson staining were utilized; in vitro, primary cell culture, and a variety of assays including CCK-8, Transwell, Scratch, Immunocytofluorescence (ICF), and Western blot (WB) were performed, both for morphology and molecular analysis.Results and Discussion: Preparation of BM involved attaching NMBG to RGD-exposed collagen while avoiding the use of toxic chemical reagents. BM exhibited a distinctive superficial morphology with increased Si content, indicating successful NMBG attachment. In vivo studies on SD rats demonstrated the superior wound healing capability of BM, as evidenced by accelerated wound closure, thicker epithelial layers, and enhanced collagen deposition compared to the NC group. Additionally, BM promoted skin fibroblast migration and proliferation, possibly through activation of the GSK-3β/β-catenin signaling axis, which was crucial for tissue regeneration. This study underscored the potential of BM as an effective wound-healing dressing.Conclusion: A new method for synthesizing ECM-like membranes has been developed using nano-mesoporous bioactive glass and collagen-derived peptides. This approach enhances the bioactivity of biomaterials through surface functionalization and growth factor-free therapy.Keywords: NMBG, proliferation, RGD, migration, wound healing, GSK-3β/β-catenin signaling axis

Lian Gong,1 Ming Zhong,2 Kai Gong,3 Zhanwang Wang,1 Yong Zhong,4 Yi Jin,1 Haotian Chen,1 Panpan Tai,1 Xinyu Chen,1 Aiyan Chen,1 Ke Cao1 1Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China; 2Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Clinical Medicine, Xiangnan University, Chenzhou, People’s Republic of China; 4Department of Clinical Medicine, Hubei Enshi College, Enshi, People’s Republic of ChinaCorrespondence: Ke Cao, Email csucaoke@163.comBackground: Chaperonin-containing TCP1 subunit 8 (CCT8) has been proved to be involved in the occurrence and development of some cancers. However, no study has reported the potential role of CCT8 in a pan-cancer manner.Methods: TIMER2.0, GEPIA2, UALCAN and Sangerbox were used to explore the expression, prognosis and methylation of CCT8. We used cBioPortal, TISIDB, SangerBox, TIMER2.0 and TISMO to investigate the genetic alteration of CCT8 and the relationship of CCT8 with molecular subtype, immune subtype, immune infiltration and immunotherapy response. CCT8-related genes were screened out through GEPIA and STRING for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. CCK-8, the colony formation assay, the wound healing assay and the Transwell assay were performed to explore the influence of CCT8 on proliferation and migration.Results: CCT8 was highly expressed in most cancers with a poor prognosis. The expression level of CCT8, which was affected by the promoter region methylation and genetic alteration, was related to the molecular and immune subtype of cancers. Interestingly, CCT8 was positively associated with the activated CD4 T cells and type 2 T-helper cells. CCT8 played a vital role in the cell cycle and RNA transport of cancers, and it significantly inhibited the proliferation and migration of lung adenocarcinoma cells when it was knocked down.Conclusion: CCT8 plays an indispensable role in promoting the proliferation and migration of many cancers. CCT8 might be a biomarker of T-helper type 2 (Th2) cell infiltration and a promising therapeutic target for T-helper type 1(Th1)/Th2 imbalance.Keywords: CCT8, survival, immune infiltration, biomarker, pan-cancer

Uet Yu,1 Ke Cao,2 Chunlan Yang,1 Chunjing Wang,1 Yue Li,1 Xiaohui Zhou,1 Qian Zhang,1 Yuanxiang Wang,3 Feiqiu Wen,1 Sixi Liu,1 Xiaodong Wang1 1Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Laboratory Medicine, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 3Department of Cardiothoracic Surgery, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xiaodong Wang; Sixi Liu, Email donlevin@live.cn; tiger647@126.comAbstract: Invasive fungal infections (IFIs) are among the most severe complications in recipients of hematopoietic stem cell transplantation (HSCT) recipients and in patients with hematological malignancies. An increasing number of uncommon fungal infections have been reported in this era of antifungal prophylaxis. Coprinopsis cinerea is a rare pathogen that causes opportunistic infections in the immunocompromised patients, including HSCT recipients and is associated with very high mortality rates. Herein, we present a successfully treated pediatric HSCT patient with breakthrough pulmonary IFI caused by Coprinopsis cinerea despite posaconazole, prophylaxis using multidisciplinary approaches.Keywords: Coprinopsis cinerea, Hormographiella aspergillata, invasive fungal infection, hematopoietic stem cell transplantation, leukemia, case report

Ling Tang,&ast; Hui Wang,&ast; Kangli Cao,&ast; Yajuan Li, Tingting Li, Ying Huang, Yuanhong Xu Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Xu, Email xyhong1964@163.comPurpose: Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative bacterium that is predominantly associated with liver abscesses in global diabetic patients. High levels of glucose in the surrounding of K. pneumonia increase its pathogenicity including capsular polysaccharide (CPS) and fimbriae. Other important virulent factors include outer membrane protein A (ompA) and regulator mucoid phenotype A (rmpA). The objective of this investigation was to elucidate the effects of high glucose on rmpA and ompA gene expression and serum resistance of K. pneumoniae causing liver abscess.Patients and Methods: The clinical history of 57 patients suffering from K. pneumoniae-caused liver abscesses (KLA) was acquired and their clinical and laboratory manifestations in the presence or absence of diabetes were analyzed. The antimicrobial susceptibility, serotypes, and virulence genes were tested. Clinical isolates of 3 serotype-K1 hypervirulent K. pneumoniae (hvKP) were used to detect the effect of exogenous high glucose on rmpA, ompA, and clbB genes expression, and bacterial serum resistance.Results: KLA patients with diabetes showed higher C-reactive protein (CRP) compared to non-diabetic KLA patients. Furthermore, the diabetic group showed increased incidences of sepsis and invasive infections, and their length of hospital stay was also prolonged. Pre-incubation of K. pneumoniae in high glucose (0.5%) concentration up-regulated rmpA, ompA, and clbB genes expression. However, cAMP supplementation, which was inhibited by environmental glucose, reversed the increase of rmpA and ompA in a cAMP-dependent manner. Moreover, hvKP strains incubated in high glucose also exhibited enhanced protection from serum killing.Conclusion: High glucose levels reflected by poor glycemic control has increased gene expression of rmpA and ompA in hvKP by the cAMP signaling pathway and enhanced its resistance to serum killing, thus providing a new and reasonable explanation for the high incidences of sepsis and invasive infections in KLA patients with diabetes.Keywords: Klebsiella pneumoniae, liver abscess, diabetes, rmpA, ompA, serum resistance

Ziqi Jiang,&ast; Shanglin Jin,&ast; Xiaoyao Fan, Ke Cao, Ye Liu, Xuan Wang, Ying Ma, Leihong Xiang Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leihong Xiang; Ying Ma, Department of Dermatology, Huashan Hospital, Fudan University, No. 12 Wulumuqizhong Road, Shanghai, 200040, People’s Republic of China, Tel: +86 21 52889999, Fax: +86 21 62489191, Email flora_xiang@vip.163.com; alle_ma@163.comBackground: Acne is a common inflammatory skin disease, while cannabidiol (CBD) is a representative non-psychoactive phytocannabinoid which has been proved to exert universal anti-inflammatory properties. This study aimed to explore the effect of CBD on acne inflammation induced by Cutibacterium acnes-derived extracellular vesicles (CEVs) in keratinocytes and reveal the underlying mechanisms.Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated by CEVs in the presence of CBD or vehicle. Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels were examined by RT-PCR and ELISA. The expression of cannabinoid type-2 (CB2) receptor and transient receptor potential vanilloid type-1 (TRPV1) was detected by Western blotting. TNF-α levels in the presence of CB2 receptor antagonist (AM630) or TRPV1 antagonist (Capsazepine) were detected by RT-PCR. The activation of MAPK and NF-κB signaling pathways and the nuclear translocation of NF-κB p65 upon CBD treatment were analyzed by Western blotting and immunofluorescence assay, respectively.Results: The expression of inflammatory cytokines (IL-6, IL-8 and TNF-α) in CEVs-stimulated NHEKs was suppressed by CBD. CB2 receptor expression was upregulated by CBD, whereas CEVs-promoted TRPV1 expression was downregulated by CBD. AM630 reversed TNF-α levels inhibited by CBD. Capsazepine exerted an inhibitory effect on CEVs-induced inflammation and had synergistic effect with CBD. The phosphorylation of ERK1/2 and NF-κB p65 and nuclear translocation of NF-κB p65 were induced by CEVs but reduced by CBD.Conclusion: The results indicated that CBD could inhibit inflammation induced by CEVs in NHEKs, which was mediated by activation of CB2 receptor and enhanced by the TRPV1 antagonist, through inactivation of the MAPK and NF-κB signaling pathways. CBD might be a potential novel strategy for acne treatment in the future.Keywords: cannabidiol, acne, inflammation, Cutibacterium acnes, keratinocytes

Songwei Lv,1,&ast; Ran Jing,2,&ast; Xiaowu Liu,3,4 Honglei Shi,3,4 Yunfeng Shi,3,4 Xugang Wang,3,4 Xiubo Zhao,1,5 Kai Cao,3,4 Zhong Lv3,4 1School of Pharmacy, Changzhou University, Changzhou, 213164, People’s Republic of China; 2Division of Nephrology, The Affiliated Changzhou NO. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213164, People’s Republic of China; 3Department of Urology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213164, People’s Republic of China; 4Department of Urology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, 213164, People’s Republic of China; 5Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S1 3JD, UK&ast;These authors contributed equally to this workCorrespondence: Kai Cao; Zhong Lv Email caokai9001@126.com; lzabc0105@163.comIntroduction: Cancer of the bladder is one of the most common and life-threatening. Compared with traditional delivery methods, intravesical administration reduces the amount of drugs required, increases the amount of drugs reaching the lesion site, and minimizes systemic exposure to therapeutic agents. To overcome the limitations of urinary voiding, low urothelium permeability, and intermittent catheterization for large dilution and irrigation of drugs in the bladder, magnetic and photothermal-responsive folate receptor-targeted thermal liposomes (FA-TMLs) were designed for the targeted delivery of doxorubicin (DOX) to bladder cancer cells.Methods: Through a microfluidic mixer chip, the magnetic nanoparticles (MNPs), gold nanorods (GNRs) and DOX were encapsulated in folate-modified thermosensitive liposomes to form FA-TMLs@MNPs-GNRs-DOX. DLS, TEM, DSC, and magnetic hysteresis loop were used to characterize the construction of FA-TMLs@MNPs-GNRs-DOX.Results: FA-TMLs@MNPs-GNRs-DOX had a size of about 230 nm and exhibited superparamagnetic properties with the saturation magnetization of 20 emu/g. The DOX loading capacity was as high as 0.57 mg/mL. Additionally, drug release of the FA-TMLs@MNPs-GNRs-DOX could be controlled by temperature change through the photothermal effect. A 980 nm laser beam was selectively irradiated on the FA-TMLs@MNPs-GNRs-DOX to trigger the structural changes of the FA-TMLs, and an average of 95% of the drug was released after 3 hours. The results of cell uptake experiments reveal indicated that FA-TMLs@MNPs-GNRs-DOX were able to specifically bind folate-receptor-positive cells and exhibited toxicity to bladder tumor cells.Conclusion: The present results suggest FA-TMLs@MNPs-GNRs-DOX have a promising multifunctional response and can act as an ideal multifunctional drug delivery system (DDS) for the treatment of bladder tumors.Keywords: bladder cancer, drug delivery, magnetic response, thermo-sensitive liposomes, folate-targeted, photothermal effect

Dongli Xie,1,&ast; Jianchen Hu,1,&ast; Tong Wu,2 Kangli Cao,3 Xiaogang Luo1 1College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, People’s Republic of China; 2Shanghai LEVSON Nanotechnology Co., Ltd, Shanghai, 200444, People’s Republic of China; 3Shanghai Institute of Spacecraft Equipment, Shanghai, 200240, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Luo Tel +86 512-67162531Email xgluo@suda.edu.cnBackground: Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM.Methods: Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein–protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers.Results: WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥ 4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of > 0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1).Conclusion: These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.Keywords: carbon nanotubes, malignant transformation, malignant pleural mesothelioma, tumor-infiltrating immune cells, prognosis, diagnosis

Cao K, Fang Y, Wang H, Jiang Z, Guo L, Hu Y. Cancer Manag Res. 2019;11:4505–4518. The authors have advised due to an error at the time of figure assembly, Figure 3B on page 4512 is incorrect. The correct Figure 3 is shown in Download Article. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Hui Jiang1,2 *,* Kefeng Cao3 *,* Chang Fan,1,2 Xiaoya Cui,1,2 Yanzhen Ma,1,2 Jian Liu1 1Experimental Center of Clinical Research, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Departments of Laboratory Medicine, Traditional Chinese Medical Hospital of Taihe County, Fuyang, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian LiuFirst Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Hefei, Anhui, People’s Republic of ChinaTel +86 181 5607 8363Email liujian_arthritis@126.comIntroduction: N6-methyladenosine (m6A) is the most frequent internal modification in eukaryotic mRNAs and is closely related to the occurrence and development of many diseases, especially tumors. However, the relationship between m6A methylation and rheumatoid arthritis (RA) is still a mystery.Methods: Two high-throughput sequencing methods, namely, m6A modified RNA immunoprecipitation sequence (m6A-seq) and RNA sequence (RNA-seq) were performed to identify the differentially expressed m6A methylation in human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A after stimulation with TNF-α. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to obtain enriched GO terms and significant KEGG pathways. Then, four candidate genes, Wilms tumor 1-associating protein (WTAP), receptor-interacting serine/threonine protein kinase 2 (RIPK2), Janus kinase 3 (JAK3) and tumor necrosis factor receptor SF10A (TNFRSF10A) were selected to further validate the m6A methylation, mRNA and protein expression levels in MH7A cells and synovial tissues of adjuvant arthritis (AA) rats by RT-qPCR and Western blot.Results: Using m6A-seq, we identified a total of 206 genes with differentially expressed m6A methylation, of which 118 were significantly upregulated and 88 genes were significantly downregulated. Likewise, 1207 differentially mRNA expressed mRNAs were obtained by RNA-seq, of which 793 were upregulated and 414 downregulated. Further joint analysis showed that the m6A methylation and mRNA expression levels of 88 genes changed significantly, of which 30 genes displayed increased m6A methylation and decreased mRNA expression, 57 genes displayed decreased m6A methylation and increased mRNA expression increased, and 1 gene displayed increased m6A methylation and increased mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in inflammation-related pathways, cell proliferation and apoptosis. In addition, the validations of WTAP, RIPK2, JAK3 and TNFRSF10A were in accordance with the m6A and RNA sequencing results.Conclusion: This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and RA related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent.Keywords: m6A methylation, m6A-seq, RNA-seq, rheumatoid arthritis, MH7A cells

Loss of heterozygosity (LOH) has been shown to be associated with leukemia relapse after haploidentical transplantation. Whether such changes are an important cause of relapse after HLA-matched transplantation remains unclear. We retrospectively HLA-typed leukemic blasts for 71 patients with AML/myelodysplastic syndrome obtained from stored samples, and the results were compared with those obtained at diagnosis and/or before the transplant. No LOH or any other changes in HLA Ag were found in any of the samples tested post transplant as compared with pretransplant specimens. One patient had LOH in HLA class I Ag (HLA-A,-B and -C); however, these changes were present in the pretransplant sample indicating that they occurred before the transplant. We concluded that, in contrast with haploidentical transplantation, HLA loss does not have a major role as a mechanism of relapse after allogeneic transplantation with a closely HLA-matched donor.