Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion.

The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache1,2. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system, affecting more than 2.5 million people a year3-5. How pain and neuroimmune interactions impact meningeal antibacterial host defences are unclear. Here we show that Nav1.8+ nociceptors signal to immune cells in the meninges through the neuropeptide calcitonin gene-related peptide (CGRP) during infection. This neuroimmune axis inhibits host defences and exacerbates bacterial meningitis. Nociceptor neuron ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors through its pore-forming toxin pneumolysin to release CGRP from nerve terminals. CGRP acted through receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, suppressing macrophage chemokine expression, neutrophil recruitment and dural antimicrobial defences. Macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses and bacterial clearance in the meninges and brain. Therefore, bacteria hijack CGRP-RAMP1 signalling in meningeal macrophages to facilitate brain invasion. Targeting this neuroimmune axis in the meninges can enhance host defences and potentially produce treatments for bacterial meningitis.

Facial Rejuvenation with Open Technique After Previous Filler Injection.

The complications associated with polyacrylamide hydrogel injection including tissue infection, nodular formation, and migration along tissue planes have been well-documented. Complete removal of injected material is seldom possible. Patients who underwent removal of injected material were significantly more likely to express interest in facelift. We provide an open surgical technique with facelift incision to deal with the removal of polyacrylamide hydrogel and complication due to volume deflation and tissue descent.

Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems.

Gene therapy offers great promise in addressing neuropathologies associated with the central and peripheral nervous systems (CNS and PNS). However, genetic access remains difficult, reflecting the critical need for the development of effective and non-invasive gene delivery vectors across species. To that end, we evolved adeno-associated virus serotype 9 (AAV9) capsid in mice and validated two capsids, AAV-MaCPNS1 and AAV-MaCPNS2, across rodent species (mice and rats) and non-human primate (NHP) species (marmosets and rhesus macaques). Intravenous administration of either AAV efficiently transduced the PNS in rodents and both the PNS and CNS in NHPs. Furthermore, we used AAV-MaCPNS1 in mice to systemically deliver the following: (1) the neuronal sensor jGCaMP8s to record calcium signal dynamics in nodose ganglia and (2) the neuronal actuator DREADD to dorsal root ganglia to mediate pain. This conclusively demonstrates the translatability of these two systemic AAVs across four species and their functional utility through proof-of-concept studies in mice.

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma.

BACKGROUND: The role of HOXA family genes in the occurrence and progression of a variety of human cancers has been scatteredly reported. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD. METHODS: In-house immunohistochemistry (IHC), multi-center microarrays, RT-qPCR and RNA-seq data were incorporated for comprehensively evaluating the expression and prognostic value of HOXA4 and HOXA5 in LUAD. The mechanism of HOXA4 and HOXA5 in the formation and development of LUAD was analyzed from multiple aspects of immune correlations, upstream transcriptional regulation, functional states of single cells and co-expressed gene network. The functional roles of HOXA4 and HOXA5 in LUAD were validated by in vitro experiments. RESULTS: As a result, in 3201 LUAD samples and 2494 non-cancer lung samples, HOXA4 and HOXA5 were significantly downexpressed (P < 0.05). The aberrant expression of HOXA5 was significantly correlated with the clinical progression of LUAD (P < 0.05). HOXA5 showed remarkable prognostic value for LUAD patients (P < 0.05). The expression of HOXA4 and HOXA5 in LUAD were negatively correlated with tumor purity and positively correlated with the infiltration of various immune cells such as B cells, T cells and macrophages. HOXA4 and HOXA5 overexpression had notable inhibitory effect on the proliferation, migration and invasion of LUAD cells. CONCLUSIONS: In conclusion, the identified downexpressed HOXA4 and HOXA5 had significant distinguishing ability for LUAD samples and affected the cellular functions of LUAD cells. The low expression of HOXA5 indicated worse overall survival of LUAD patients. Therefore, the two HOXA family genes especially HOXA5 may serve as potential biomarkers for LUAD.

Downregulation of miR-125b-5p and Its Prospective Molecular Mechanism in Lung Squamous Cell Carcinoma.

Background: To explore the clinical significance of miR-125b-5p and its potential mechanisms in lung squamous cell carcinoma (LUSC). Materials and Methods: An integrated analysis of data from in-house quantitative real-time polymerase chain reaction (qRT-PCR), microRNA-sequencing, and microarray assays to appraise the expression level of miR-125b-5p in LUSC tissues compared to adjacent noncancerous controls. The authors identified the candidate targets of miR-125b-5p and conducted functional analysis using computational biology strategies from gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, disease ontology (DO), and protein-protein interaction (PPI) network analyses to investigate the prospective mechanisms. Results: According to qRT-PCR results, the expression level of miR-125b-5p was markedly decreased in LUSC tissues compared to noncancerous control tissues. Receiver operating characteristic and summary receiver operating characteristic analyses showed that miR-125b-5p had good specificity and sensitivity for distinguishing LUSC tissue from noncancerous lung tissue. The standard mean difference revealed that men and women with lower expression levels of miR-125b-5p may have a higher risk for LUSC. KEGG analysis and DO analysis intimated that target genes were evidently enriched in pyrimidine metabolism and pancreatic carcinoma. The PPI network of the top assembled KEGG pathway indicated that RRM2, UMPS, UCK2, and CTPS1 were regarded as crucial target genes for miR-125b-5p, and RRM2 was eventually deemed a key target. Conclusions: The authors' findings implicate a low expression level of miR-125b-5p in LUSC. A tumor-suppressive role of miR-125b-5p is proposed, based on its effects on LUSC tumor growth, clinical stage progression, and lymph node metastasis.

Special Considerations in Chinese Face-Lift Procedure: Insights From a 15-Year Experience of 1026 Cases.

BACKGROUND: There is extensive literature on different face-lift techniques; however, few articles published in the English language address the particularities of the face-lift for Chinese patients. Because of differences in facial anatomy, facial aging, and patient expectations, facial rejuvenation procedures for Chinese patients can be quite different from those of White patients. METHODS: The study includes 1026 consecutive primary face-lift cases performed by the senior author (D.Y.) from 2006 to 2019. Of these, 1010 patients were female and 16 were male. The average age of the patient at the time of primary face-lift was 40.5 years. The face-lift procedures included midface lift in 108 cases, midface and lower-face lift in 882 cases, and midface and lower-face lift with brow lift in 36 cases. All patients received superficial musculoaponeurotic system (SMAS) treatment, in the form of lateral SMASectomy in 607 cases, high-SMAS technique in 84 cases, modified high-SMAS short-scar technique in 108 cases, minimal access cranial suspension technique in 38 cases, and modified minimal access cranial suspension technique in 189 cases. Photographs of patients were analyzed to assess persistent features of facial aging. Complications such as hematoma, skin slough, infection, and nerve injury were also reviewed. RESULTS: Most patients obtained consistently good results with minimal risk and complications. All surgical techniques discussed were safe and reproducible, providing various options for surgeons. CONCLUSIONS: Special attention should be taken when planning a facial rejuvenation procedure for Chinese patients. Anatomic variations dictate a greater emphasis on the management of tissue ptosis, particularly regarding lateral brow descent and malar fat pad descent. In our practice, various face-lift techniques can produce excellent results. Surgeons must adopt a technique that serves patients well and is, ideally, safe, consistent, easily reproducible, and applicable to various anatomic problems. In addition, every surgery is customized to the patient's anatomy and concerns. Therefore, the surgeon must adopt individualized technique according to the needs and desires of each patient.

Clinical significance of transcription factor RUNX2 in lung adenocarcinoma and its latent transcriptional regulating mechanism.

RUNX family transcription factor 2 (RUNX2) overexpression has been found in various human malignancies. However, the expression levels of RUNX2 mRNA and protein in lung adenocarcinoma (LUAD) were not investigated. This study aims to thoroughly analysis the expression level and potential mechanisms of RUNX2 mRNA in LUAD. We applied in-house immunohistochemistry, high-throughput RNA-sequencing, and gene microarrays to comprehensively investigate the expression level of RUNX2 in LUAD. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to assess the integrated expression value of RUNX2 in LUAD. The hazard ratios (HRs) were integrated to evaluate the overall prognostic effect of RUNX2 on the LUAD patients. The differentially expressed genes (DEGs) of LUAD, the potential target genes of RUNX2, and its co-expressed genes were overlapped to obtain a set of specific genes for GO and KEGG enrichment analyses. RUNX2 overexpression in LUAD was validated using a large number of cases (2 418 LUAD and 1 574 non-tumor lung samples). The pooled SMD was 0.85 (95 % CI: 0.64-1.05) and the area under the curve (AUC) of the SROC was 0.86 (95 %CI: 0.83-0.89). The integrated HR was 1.20 [1.04-1.38], indicating that increased expression of RUNX2 was an independent risk factor for the poor survival of the LUAD patients. RUNX2 and its transcriptionally regulates potential target genes may promote cell proliferation and drug resistance of LUAD by modulating the cell cycle and MAPK signaling pathways. RUNX2 can provide new research directions for targeted drug therapy and drug resistance for LUAD treatment.

Integrated expression analysis revealed RUNX2 upregulation in lung squamous cell carcinoma tissues.

This study aimed to investigate the clinicopathological significance and prospective molecular mechanism of RUNX family transcription factor 2 (RUNX2) in lung squamous cell carcinoma (LUSC). The authors used immunohistochemistry (IHC), RNA-seq, and microarray data from multi-platforms to conduct a comprehensive analysis of the clinicopathological significance and molecular mechanism of RUNX2 in the occurrence and development of LUSC. RUNX2 expression was significantly higher in 16 LUSC tissues than in paired non-cancerous tissues detected by IHC (P < 0.05). RNA-seq data from the combination of TCGA and genotype-tissue expression (GTEx) revealed significantly higher expression of RUNX2 in 502 LUSC samples than in 476 non-cancer samples. The expression of RUNX2 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples (P = 0.031). The pooled standardised mean difference (SMD) for RUNX2 was 0.87 (95% CI, 0.58-1.16), including 29 microarrays from GEO and one from ArrayExpress. The co-expression network of RUNX2 revealed complicated connections between RUNX2 and 45 co-expressed genes, which were significantly clustered in pathways including ECM-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection and PI3K-Akt signalling pathway. Overexpression of RUNX2 plays an essential role in the clinical progression of LUSC.

Downregulation of miRNA-126-3p is associated with progression of and poor prognosis for lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is the main pathological type of pulmonary malignant tumors; at present, less than 10% of patients with advanced metastatic LUSC live for more than 5 years. We previously reported that low expression of miRNA-126-3p is associated with the occurrence and progression of lung adenocarcinoma (LUAD). Here, we examined expression of miRNA-126-3p in 23 samples from patients with LUSCs and 23 normal control specimens by quantitative real-time PCR (RT-qPCR). Associations between miRNA-126-3p expression and clinical features were studied from materials derived from Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) database. Twelve online platforms were used to identify candidate target genes of miRNA-126-3p. Further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) network were performed on the target genes. GEO microarray analysis, TCGA data mining, RT-qPCR, and integration analysis consistently reported low expression of miRNA-126-3p in LUSC. A total of 42 genes were identified as potential target genes of miRNA-126-3p from online platforms, GEO microarrays, and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in several biological processes that promote the progression of LUSC. SOX2, E2F2, and E2F3 were selected as hub genes from the PPI network for further analysis. In summary, our results suggest that the low expression of miRNA-126-3p may play a role in promoting the development of LUSC and miRNA-126-3p may be a biomarker for LUSC early diagnosis and prognosis.

ADSCs inhibit photoaging- and photocarcinogenesis-related inflammatory responses and extracellular matrix degradation.

BACKGROUND: Skin is a dynamic organ that maintains homeostasis and provides protection against environmental stimuli and pathogens. However, constant solar ultraviolet (UV) radiation can induce photoaging and photocarcinogenesis, thus reducing skin barrier function by altering skin at the cellular and structural levels. Adipose-derived stem cells (ADSCs) ameliorate signs of skin photoaging, but their antiphotoaging mechanism remains elusive. In this study, we explored the mechanism by which ADSCs improve skin photoaging. METHODS: Female C57BL/6J mice were used as experimental subjects and were randomly divided into three groups. We used Western blot analysis, Real time-polymerase chain reaction, and immunofluorescence to analyze the expression of photoaging- and photocarcinogenesis-related inflammasomes, extracellular matrix components, and related factors. RESULTS: The results showed that ADSCs reduced the UVB irradiation-mediated increase in MMP2, MMP13, phospho-NF-κB p65, Nlrp3, and VCAM-1 mRNA expression. The TGF-ß2 expression trend was opposite that of the above genes. ADSCs ameliorated the downregulation of α6 integrin, CD34, and collagen I by UVB irradiation. Simultaneously, ADSCs reduced the overexpression of COX2 and TNF-α induced by UVB irradiation. CONCLUSION: These results demonstrated that ADSCs could restore skin barrier function at the cellular and structural levels, enhance hair follicle stem cell (HFSCs) activity by regulating TGF-ß2 and inhibit photoaging- and photocarcinogenesis-related inflammatory responses and extracellular matrix degradation.

Lateral Superficial Muscular Aponeurotic System Stacking/Superficial Muscular Aponeurotic Systemectomy With Orbicularis-Malar Fat Repositioning: A Procedure Tailored for Female Asian Patients.

BACKGROUND: Important differences in facial anatomy and how faces age must be considered when performing facelifts in Asian populations. Few facelift methods are specifically designed for Asian patients. OBJECTIVE: This study evaluated the efficacy of lateral superficial muscular aponeurotic system (SMAS)-stacking/SMAS-ectomy with orbicularis-malar fat repositioning. MATERIALS AND METHODS: Between February 2013 and December 2016, 62 women underwent the evaluated technique and completed the follow-up (15 months, ranging from 3 to 38.5 months). Three blinded, independent observers graded wrinkles, laxity, nasolabial fold depth, malar prominence, and tear trough deformity using quantitative comprehensive grading scales. FACE-Q scale items were assessed, and complications were recorded. RESULTS: The mean postoperative scores for wrinkles, laxity, nasolabial fold depth, malar prominence, and tear trough deformity decreased from 2.64, 2.62, 2.01, 2.06, and 2.40 to 1.48, 1.34, 0.93, 1.21, and 1.27, respectively. The preoperative and postoperative scores differed significantly for all parameters (p < .05). The FACE-Q results showed that the patients were highly satisfied with their appearance, quality of life, adverse effects, and care. CONCLUSION: The authors' technique allows midfacial and periorbital rejuvenation and offers dual benefits by correcting individual facial asymmetries and reshaping the jowls and neck contour in Asian patients.

Facial Resurfacing With Prefabricated Induced Expanded Skin Flap.

Massive facial damages extremely affect the facial appearance and function. In existing publications, the surgical flap transfer was still prior to other methods in repairing the facial injury. Among them, the prefabricated induced expanded skin flap seems more effective based on the facial specific features and damage range. In this study, a literature research was carried out in the database of PubMed. A total of 85 patients were included and all of them underwent the method of prefabricated expanded flap to reconstruct the massive facial defects. The prefabricated induced expanded skin flaps harvested from the neck and chest area have prominent advantage in resetting massive facial deformities. All the flaps survived demonstrated an excellent texture and color match with the facial defects areas. However, the unsolved problems are still existed in these flaps and further research is necessary to obtain a satisfactory outcome for both patients and surgeons.

Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles.

Idiopathic pulmonary fibrosis (IPF) is a severe form of lung fibrosis with a high mortality rate. However, the etiology of IPF remains unknown. Here, we report that alterations in lung microbiota critically promote pulmonary fibrosis pathogenesis. We found that lung microbiota was dysregulated, and the dysregulated microbiota in turn induced production of interleukin-17B (IL-17B) during bleomycin-induced mouse lung fibrosis. Either lung-microbiota depletion or IL-17B deficiency ameliorated the disease progression. IL-17B cooperated with tumor necrosis factor-α to induce expression of neutrophil-recruiting genes and T helper 17 (Th17)-cell-promoting genes. Three pulmonary commensal microbes, which belong to the genera Bacteroides and Prevotella, were identified to promote fibrotic pathogenesis through IL-17R signaling. We further defined that the outer membrane vesicles (OMVs) that were derived from the identified commensal microbes induced IL-17B production through Toll-like receptor-Myd88 adaptor signaling. Together our data demonstrate that specific pulmonary symbiotic commensals can promote lung fibrosis by regulating a profibrotic inflammatory cytokine network.

Protective Mechanism of Adipose-Derived Stem Cells in Remodelling of the Skin Stem Cell Niche During Photoaging.

BACKGROUND/AIMS: Skin photoaging is primarily caused by the functional attrition of skin stem cells. The skin stem cell niche plays an important role in maintaining stem cell survival and behaviour. In our study, we hypothesized that UVB irradiation induces skin photoaging by changing skin stem cell niches and that transferred adipose-derived stem cells (ADSCs) can remodel the niches by affecting the BMP signalling pathway and transdifferentiating into skin stem cells. METHODS: Sixty-four C57BL/6J mice were divided into the following groups: a control group, the UVB group and the UVB+ADSCs group. Western blot assays, immunofluorescence analysis and real-time PCR were used to measure differences in the expression of niche components among the three groups. Furthermore, we tested whether transplanted ADSCs express skin stem cell markers, such as p63, α6-integrin and CD34. RESULTS: The expression levels of Bmp4, its downstream factors Smad1 and MAPK1 and a regulatory factor of the niche, i.e., NFATc1, were lower in the UVB group than were those in the control group (P< 0.05) but higher in the UVB+ADSCs group than were those in the UVB group (P< 0.05). Compared with Bmp4, Nanog (a downstream factor of Bmp4), and MMP13 (a regulatory factor of the niche), ICAM-1 (a proinflammatory gene), p63 (a basal transcription factor), ß1-integrin, Mtnr1a and Tyr (melanogenesis-related factors) showed the opposite expression trends (P< 0.05). Bmp2 and Collagen IV levels did not significantly change among the three groups (P> 0.05). Skin stem cell markers, such as p63, α6-integrin and CD34, were coexpressed in the ADSCs, which suggested the ADSCs may transdifferentiate into skin stem cells. CONCLUSION: We found that UVB irradiation results in typical photoaging signs by altering skin stem cell niches and that Bmp4 was a key factor in BMP signalling in hair follicles. ADSCs reversed these typical photoaging signs by remodelling skin stem cell niches through BMP4 pathway modulation and transdifferentiation into skin stem cells.

The Individualized Facelift Technique in Improving Facial Asymmetry for Asian Patients.

PURPOSE: Among multiple influential factors affecting facial symmetry, the role of soft tissue is often overlooked. Skin and skeletal differences between Asian and Caucasian people also require the adaptation of current techniques for Asian patients. This article aimed to explore the ability of individual facelift techniques to improve facial symmetry and reset youthful eye in Asian people, while a new method, called the grid method, was tried to evaluate the improvement in facial symmetry. METHODS: The authors conducted a review of 58 consecutive facelifts, which were all performed by a single surgeon between April 2009 and December 2016 following institutional review board approval. Among them, 21 patients underwent lower eyelid blepharoplasty. The original frontal photograph of each patient was evaluated by the grid method. Five independent plastic surgeons reviewed the facial asymmetry of the images before and after the operations using a visual analog scale to analyze the facial asymmetry of the patients. RESULTS: In the preoperative group evaluated by the grid, the mean facial asymmetry score was 4.11, while in the postoperative group, the mean score was 1.07, which was significantly lower than the mean score before the operation (p < 0.001). The change in mean scores illustrated that the technique was effective in improving facial symmetry in Asian people. A total of 8 patients experienced hematomas and recovered well without obvious sequelae. CONCLUSIONS: The individual facelift technique was effective for improving facial symmetry and reshaping youthful eye in Asian people.

Quantitative proteomics analysis of the role of tetraspanin-8 in the drug resistance of gastric cancer.

Gastric cancer, due to its high incidence rate, is the second leading cause of cancer-related mortality worldwide. Chemotherapy is an important component of the multimodal treatment for gastric cancer; however, a significant impediment to successful treatment is multidrug resistance (MDR) in patients with gastric cancer. In the present study, the protein profiles of the MDR cell line, SGC7901/DDP, and its parental cell line, SGC7901, were comparatively analyzed through an iTRAQ-based quantitative proteomics technique. The protein tetraspanin-8 (TSPAN8) was found to be highly expressed in the SGC7901/DDP cells. To examine the role of TSPAN8 in the MDR of SGC7901/DDP cells, we increased cell sensitivity to drugs by increasing apoptosis. Additionally, the silencing of TSPAN8 downregulated Wnt pathway activity, ß-catenin expression and ß-catenin transfer to the nucleus. TSPAN8 was found to bind to NOTCH2, facilitating its mediation of the Wnt/ß-catenin pathway by regulating ß-catenin expression. Overall, the suppression of TSPAN8 expression may prove to be a promising strategy which may aid in the development of novel gastric cancer therapeutic drugs.

miR-135a-5p affects adipogenic differentiation of human adipose-derived mesenchymal stem cellsby promoting the Hippo signaling pathway.

MicroRNAs (miRNAs) have been extensively studied and play a regulatory role during adipogenesis. Specifically, many miRNAs participate in regulation of mesenchymal stem cell (MSC) differentiation into adipogenic and osteogenic lineages. However, the regulatory mechanisms of miR-135a-5p in the Hippo signaling pathway during adipogenesis need to be explored. In this study, we observed that miR-135a-5p promotes adipogenesis of human adipose-derived MSCs (hADMSCs). miR-135a-5p was overexpressed in adipocytes compared to hADMSCs and further upregulation of miR-135a-5p promoted proliferation and adipogenesis of hADMSCs. In contrast, miR-135a-5p reduction inhibited these processes. Luciferase activity detection and Western blotting confirmed that overexpressed miR-135a-5p had the ability to upregulate the HIPPO signaling pathway. Subsequently, we observed that miR-135a-5p is targeted to key negative regulators in the HIPPO signaling pathway, including MOB kinase activator 1B (MOB1B) and large tumor suppressor 1 (LATS1). Moreover, suppression of LATS1 and MOB1B upregulated the activity of TEAD. In conclusion, we have verified that miR-135a-5p plays an active role in adipogenesis by targeting LATS1 and MOB1B expression, thereby enhancing the HIPPO signaling pathway.

Cytoprotective effects of glycyrrhetinic acid liposome against cyclophosphamide-induced cystitis through inhibiting inflammatory stress.

This study was designed to investigate the pharmacological efficacy of glycyrrhetinic acid liposome (GAL) against female mice with nonbacterial cystitis induced by cyclophosphamide (CPS). Mice in different groups were subjected to tests for lactate dehydrogenase (LD), cytokine contents (IL-6, TNF-α) in serum, and histological changes in bladder tissue and to immunoassays. As a result, cyclophosphamide-induced cystitis in mice showed an increased LD level in serum, and the contents of cytokines (IL-6, TNF-α) were elevated. Interestingly, GAL-treated mice showed decreased LD and inflammatory cytokines of IL-6 and TNF-α in blood. Inflammatory infiltration and cell death in bladder tissue were reduced by GAL treatments. In addition, intravesical mRNAs of NF-κB and TNF-α were lowered dose-dependently in GAL-treated mice. As shown in cytohistological staining, the number of intravesical caspase-3, PARP-positive cells decreased in GAL-treated mice. Furthermore, a GAL-treated bladder showed down-regulated NF-κB and TNF-α expressions in a dose-dependent manner. In conclusion, our current findings may be the first to provide scientific evidence demonstrating that glycyrrhetinic acid liposomes provide benefits against cyclophosphamide-induced cystitis, which possibly occurs through underlying mechanisms that inhibit cell death and inflammatory stress.

Identification of the key miRNAs associated with survival time in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is one of the leading causes of cancer morbidity and mortality worldwide. The present study aimed to identify the microRNAs associated with STAD survival time. The clinical information and microarray miRNA and mRNA expression profiles of STAD patients were downloaded from The Cancer Genome Atlas. Differential expression (DE) analysis was performed to identify DEmiRNAs and DEmRNAs in STAD. The DEmiRNAs associated with the survival time of patients with STAD were identified through DE analysis, negative correlation pair analysis, miRNA target gene prediction, univariate Cox regression analysis and Kaplan-Meier analysis. The functions of the target genes of the DEmiRNAs were predicted with Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 355 DEmiRNAs and 1,722 DEmRNAs were identified between STAD and normal tissues. A total of 5 DEmiRNAs were identified to be associated with STAD survival, including 4 risk-associated DEmiRNAs (miR-30a, -143, -145 and -133b) and 1 protective DEmiRNA (miR-135b). The target DEmRNAs were significantly enriched for DNA metabolic process in the biological process GO category, and in KEGG cell cycle signaling pathways. Kaplan-Meier curves indicated that the overall survival time in the miR-30a, -143, -145 and -133b high expression groups was significantly shorter than that in the low expression groups, whereas the survival time was prolonged in the miR-135b high expression group compared with that in the low expression group. Therefore, miR-30a, -143, -145, -133b and -135b may be involved in the tumorigenesis and development of STAD, and may be potential biomarkers for its early diagnosis and prognosis.

Development and in vivo validation of tissue-engineered, small-diameter vascular grafts from decellularized aortae of fetal pigs and canine vascular endothelial cells.

BACKGROUND: Tissue engineering has emerged as a promising alternative for small-diameter vascular grafts. The aim of this study was to determine the feasibility of using decellularized aortae of fetal pigs (DAFPs) to construct tissue-engineered, small-diameter vascular grafts and to test the performance and application of DAFPs as vascular tissue-engineered scaffolds in the canine arterial system. METHODS: DAFPs were prepared by continuous enzymatic digestion. Canine vascular endothelial cells (ECs) were seeded onto DAFPs in vitro and then the vascular grafts were cultured in a custom-designed vascular bioreactor system for 7 days of dynamic culture following 3 days of static culture. The grafts were then transplanted into the common carotid artery of the same seven dogs from which ECs had been derived (two grafts were prepared for each dog with one as a backup; therefore, a total of 14 tissue-engineered blood vessels were prepared). At 1, 3, and 6 months post-transplantation, ultrasonography and contrast-enhanced computed tomography (CT) were used to check the patency of the grafts. Additionally, vascular grafts were sampled for histological and electron microscopic examination. RESULTS: Tissue-engineered, small-diameter vascular grafts can be successfully constructed using DAFPs and canine vascular ECs. Ultrasonographic and CT test results confirmed that implanted vascular grafts displayed good patency with no obvious thrombi. Six months after implantation, the grafts had been remodeled and exhibited a similar structure to normal arteries. Immunohistochemical staining showed that cells had evenly infiltrated the tunica media and were identified as muscular fibroblasts. Scanning electron microscopy showed that the graft possessed a complete cell layer, and the internal cells of the graft were confirmed to be ECs by transmission electron microscopy. CONCLUSIONS: Tissue-engineered, small-diameter vascular grafts constructed using DAFPs and canine vascular ECs can be successfully transplanted to replace the canine common carotid artery. This investigation potentially paves the way for solving a problem of considerable clinical need, i.e., the requirement for small-diameter vascular grafts.