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1.
Asian J Androl ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119686

RESUMO

ABSTRACT: Testicular descent occurs in two consecutive stages: the transabdominal stage and the inguinoscrotal stage. Androgens play a crucial role in the second stage by influencing the development of the gubernaculum, a structure that pulls the testis into the scrotum. However, the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated. To identify the androgen-regulated genes, we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout (Lhcgr KO) mice, an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency. We found that the expression of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (Smoc1) was the most severely suppressed at both the transcript and protein levels, while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice. The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist, flutamide. In addition, in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells. In the cultures of myogenic differentiation medium, both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7 (Pax7) and myogenic factor 5 (Myf5). After short-interfering RNA-mediated knocking down of Smoc1, the expression of Pax7 and Myf5 diminished, and testosterone alone did not recover, but additional SMOC1 did. These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.

2.
Front Oncol ; 14: 1352865, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933440

RESUMO

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

3.
Adv Clin Exp Med ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353506

RESUMO

BACKGROUND: Oral chronic graft-versus-host disease (cGVHD) impacts quality of life of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its precise pathogenesis remains unknown, with potential associations with differential microRNA (miRNA) expression and the TGF-â/Smad signaling pathway. OBJECTIVES: This study aims to explore miRNA expression profiles in the peripheral blood of oral cGVHD patients, focusing on miRNA-769-5p and its relationship with Smad2. MATERIAL AND METHODS: Peripheral venous blood samples were collected for RNA extraction from 8 patients with oral cGVHD, 8 patients without cGVHD and 8 participants from the healthy control group. The miRNA library was constructed using the Illumina Hiseq 2500 platform. We focused on identifying miRNAs associated with the TGF-â/Smad signaling pathway and subsequently conducted validation experiments. The oral cGVHD and without cGVHD groups were each expanded to include 15 individuals. Peripheral blood samples were subjected to polymerase chain reaction (PCR) analysis to assess miRNA levels and to evaluate Smad2 mRNA levels in peripheral blood mononuclear cells (PBMC). Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to determine the Smad2 protein levels in peripheral blood. RESULTS: The most significantly differentially expressed miRNAs among the 3 groups were miRNA-505-5p and miRNA-769-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated an enrichment of the target genes of miRNA-769-5p in the TGF-â signaling pathway. It was observed that miRNA-769-5p expression was higher in patients without oral cGVHD in comparison to those with oral cGVHD. Receiver operating characteristic (ROC) analysis demonstrated that miRNA-769-5p holds diagnostic value for oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA exhibited a negative correlation with it. Moreover, both Smad2 mRNA and protein levels were higher in patients with oral cGVHD as opposed to those without cGVHD. CONCLUSIONS: Differential expression of miRNAs, particularly the downregulation of miRNA-769-5p, may influence the development of oral cGVHD by diminishing its inhibitory effect on the TGF-â/Smad signaling pathway through its interaction with Smad2.

4.
Microbes Infect ; 26(1-2): 105244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37914020

RESUMO

OBJECTIVE: This study aimed to investigate the impact of Corydalis Saxicola Bunting Total Alkaloid (CSBTA) on Porphyromonas gingivalis internalization within macrophages and explore the potential role of Toll-Like Receptor 2 (TLR2) in this process. METHODS: We established a P. gingivalis internalization model in macrophages by treating P. gingivalis-infected macrophages (MOI=100:1) with 200 µg/mL metronidazole and 300 µg/mL gentamicin for 1 h. Subsequently, the model was exposed to CSBTA at concentrations of 0.02 g/L or 1 µg/mL Pam3CSK4. After a 6 h treatment, cell lysis was performed with sterile water to quantify bacterial colonies. The mRNA expressions of TLR2 and interleukin-8 (IL-8) in macrophages were analyzed using RT-qPCR, while their protein levels were assessed via Western blot and ELISA respectively. RESULTS: P. gingivalis could internalize into macrophages and enhance the expression of TLR2 and IL-8. Activation of TLR2 by Pam3CSK4 contributed to P. gingivalis survival within macrophages and increased TLR2 and IL-8 expression. Conversely, 0.02 g/L CSBTA effectively cleared intracellular P. gingivalis, achieving a 90 % clearance rate after 6 h. Moreover, it downregulated the expression of TLR2 and IL-8 induced by P. gingivalis. However, the inhibitory effect of CSBTA on the internalized P. gingivalis model was attenuated by Pam3CSK4. CONCLUSION: CSBTA exhibited the ability to reduce the presence of live intracellular P. gingivalis and lower IL-8 expression in macrophages, possibly by modulating TLR2 activity.


Assuntos
Alcaloides , Corydalis , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Porphyromonas gingivalis/metabolismo , Corydalis/metabolismo , Alcaloides/metabolismo , Alcaloides/farmacologia , Macrófagos/microbiologia
5.
J Cosmet Dermatol ; 23(2): 630-638, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37846506

RESUMO

BACKGROUND: The application of nasolabial perforator flap for nasal reconstruction has been reported previously with satisfactory outcomes, but the outcomes and risk factors of postoperative adverse events have been unclear to plastic surgeons. AIMS: To statistically analyze the effectiveness of the nasolabial perforator flap in nasal reconstruction and the risk factor of postoperative complications and re-operation. PATIENTS/METHODS: This retrospective study evaluated 58 Chinese patients who underwent nasal reconstruction with the nasolabial perforator flap from 2009 to 2021. The esthetic and blood supply outcomes were measured by plastic surgeons on a 5-point Likert scale. Binary logistic regression was used to determine the risk factors associated with postoperative complications and re-operation. RESULTS: The mean age of the cohort was 66.4 ± 2.0 years. The defect size ranged from 6.5 × 5.5 mm2 to 40 × 70 mm2 , and 48.3% of defects covered more than one nasal subunit. Venous congestion occurred in 4.9% of flaps, and the immediate overall postoperative score was 7.72/10. More than one nasal subunit of involvement was the risk factor associated with re-operation (p = 0.004), but no risk factor was associated with complications. CONCLUSIONS: The nasolabial perforator flap is reliable for nasal reconstruction with good esthetic outcomes and fewer complications. However, a large number of involved subunits may lead to multiple surgeries for flap trimming in easterners.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Pessoa de Meia-Idade , Idoso , Retalho Perfurante/efeitos adversos , Retalho Perfurante/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Nariz/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
6.
Aesthetic Plast Surg ; 48(6): 1084-1093, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37932507

RESUMO

BACKGROUND: Correction of the crooked nose, especially the perpendicular plate of the ethmoid bone, has the potential to cause skull base injury. At present, the safe and effective method for perpendicular plate resection has not been clearly defined through biomechanics. METHOD: CT scan data of 48 patients with crooked nose and deviated nasal septum were divided into C-type, angular deformity-type, and S-type based on the morphology of the 3D model. Different types of finite element models of the nasal bony septum and skull base were established. The osteotomy depth, angle, and force mode of the PPE resection were simulated by assembling different working conditions for the models. The von Mises stress of the anterior cranial fossa was observed. RESULTS: When the osteotomy line length was 0.5 cm, the angle was at 30° to the Frankfurt plane, and 50 N·mm torque was applied, the von Mises stress of the skull base was minimal in the four models, showing 0.049 MPa (C-type), 0.082 MPa (S-type), 0.128 MPa (angular deformity-type), and 0.021 MPa (control model). The maximum von Mises stress values were found at the skull base when the osteotomy line was 1.5 cm, the angle was 50°, and the force was 10 N along the X-axis, showing 0.349 MPa (C-type), 0.698 MPa (S-type), 0.451 MPa (angular deformity-type), and 0.149 MPa (control model). CONCLUSION: The use of smaller resection angle with the Frankfurt plane, conservative resection depth, and torsion force can better reduce the stress value at the skull base and reduce the risk of basicranial fracture. It is a safe and effective technique for perpendicular plate resection of the ethmoid bone in the correction of crooked nose. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Nariz , Rinoplastia , Humanos , Nariz/cirurgia , Rinoplastia/métodos , Análise de Elementos Finitos , Osso Etmoide/diagnóstico por imagem , Osso Etmoide/cirurgia , Septo Nasal/diagnóstico por imagem , Septo Nasal/cirurgia , Tomografia Computadorizada por Raios X
7.
J Craniofac Surg ; 34(8): 2417-2421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37682000

RESUMO

BACKGROUND: A crooked nose is an external nose deformity predominantly caused by congenital aplasia or acquired secondary to trauma or surgery, often accompanied by a deviated nasal septum. Patients with crooked nose have dual needs to improve both esthetic and functional problems. METHODS: The clinical and photographic information of 48 patients diagnosed with a crooked nose and nasal septum deviation treated from January 2018 to January 2022 was acquired. The morphology and functional effects were investigated by evaluating the general condition of the operation, measuring the esthetic indexes of the nose, and subjectively scoring. RESULTS: For both morphology and function, endoscopy-assisted one-stage correction showed positive results in this study. The external nose deviation distance postoperatively measured 1.28 (0.85, 1.97) mm, which significantly decreased from the preoperative value of 3.96 (3.31, 5.29) mm. The scores of doctors and irrelevant medical students on nose morphology increased significantly from 4.75±1.88 and 3.84±0.76 to 6.48±1.21 and 7.21±0.67, respectively. The rhinoplasty outcome evaluation score and the "nasal obstruction symptom evaluation "score of patients were both significantly improved ( t = -7.508 and t =6.310, respectively, P < 0.001). CONCLUSION: Endoscope-assisted one-stage correction of the crooked nose can restore nasal morphology, improve the symptoms of nasal obstruction, and achieve patient satisfaction. It is a minimally invasive, safe, effective, and fast recovery approach for patients who need to solve both esthetic and functional problems.


Assuntos
Obstrução Nasal , Deformidades Adquiridas Nasais , Rinoplastia , Humanos , Septo Nasal/cirurgia , Septo Nasal/anormalidades , Obstrução Nasal/cirurgia , Deformidades Adquiridas Nasais/cirurgia , Deformidades Adquiridas Nasais/complicações , Estética Dentária , Nariz/cirurgia , Nariz/anormalidades , Rinoplastia/métodos , Resultado do Tratamento
8.
Front Neurol ; 14: 1184246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37377855

RESUMO

The nerve trunk healing process of a transected peripheral nerve trunk is composed of angiogenesis, nerve fiber regeneration, and scarring. Nerve trunk healing and neuroma formation probably share identical molecular mediators and similar regulations. At the nerve transection site, angiogenesis is sufficient and necessary for nerve fiber regeneration. Angiogenesis and nerve fiber regeneration reveal a positive correlation in the early time. Scarring and nerve fiber regeneration show a negative correlation in the late phase. We hypothesize that anti-angiogenesis suppresses neuromas. Subsequently, we provide potential protocols to test our hypothesis. Finally, we recommend employing anti-angiogenic small-molecule protein kinase inhibitors to investigate nerve transection injuries.

9.
BMC Oral Health ; 22(1): 511, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397049

RESUMO

BACKGROUND: Changes in alveolar bone dimension after tooth extraction may affect placement of the subsequent implant, resulting in ridge deficiency that can adversely impact long-term implant stability or aesthetics. Alveolar ridge preservation (ARP) was effective in reducing the amount of ridge resorption following tooth extraction. There is sparse evidence regarding the benefit of ARP at periodontally compromised molar extraction sockets. This study will be a randomized trial to assess the soft tissue contour, radiographical, and histological changes of ARP at molar extraction sites in order to compare severe periodontitis cases with natural healing results and determine the most beneficial and least traumatic clinical treatment for such patients. METHODS: This research is designed as a two-group parallel randomized controlled trial. The total number of tooth extraction sites will be 70 after calculation with power analysis. Teeth will be randomly assigned to two groups with the test group conducting ridge preservation and the control group healing naturally. Periodontal examination, cone beam-computed tomography (CBCT) data, and stereolithographic (STL) files obtained by intraoral scanning will be collected through the follow-up period, and bone biopsy samples would be obtained during implant surgery. The primary outcomes are the vertical and horizontal change of alveolar ridge measured on CBCT images, soft tissue contour changes evaluated by superimposing the digital impressions, alterations of mucosa thickness (as measured by superimposing the CBCT data and STL files), histological features of implant sites and periodontal parameter changes. The secondary outcomes are patient-reported post-operative reaction and conditions of simultaneous bone graft or sinus lifting procedures during implantation. DISCUSSION: This study will provide information about hard and soft tissue dimension changes and histomorphology evaluation following ARP and natural healing in periodontally compromised molar sites, which may contribute to complement the missing information of ARP at periodontally compromised molar extraction sockets. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on February 4, 2022, Version 1.0.


Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Periodontite , Extração Dentária , Humanos , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/patologia , Aumento do Rebordo Alveolar/métodos , Dente Molar/cirurgia , Periodontite/cirurgia , Periodontite/patologia , Alvéolo Dental/diagnóstico por imagem , Alvéolo Dental/cirurgia
10.
Front Pediatr ; 10: 973016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263151

RESUMO

Background: Investigations regarding the association between maternal smoking and specific urogenital teratogenesis exist. However, an integrated systematic review and meta-analysis studying the relationship by encompassing the whole urogenital system is essential. Objective: Even though many studies about inborn urogenital malformations have been conducted, its etiologic factors and exact pathogenesis are still unclear. Our aim is to assess the risk of congenital urogenital malformations in offspring of smoking pregnant women. Results: The meta-analysis, covering 41 case-control and 11 cohort studies, suggested that maternal smoking was associated with an increased risk of urogenital teratogenesis (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.04-1.23, p = 0.005), cryptorchidism (OR = 1.18, 95%CI: 1.12-1.24, p = 0.0001), hypospadias (OR = 1.16, 95%CI: 1.01-1.33, p = 0.039), and kidney malformations (OR = 1.30, 95%CI: 1.14-1.48, p = 0.0001). Moreover, paternal smoking during the mother's pregnancy was also significantly associated (OR = 1.26, 95%CI: 1.03-1.55, p = 0.028). The association between smoking > 10 cigarettes/day was evident but was not significant (OR = 1.24, 95%CI:0.81-1.88, p = 0.323). Conclusion: Our results showed that maternal smoking during pregnancy increased the risk of congenital urogenital malformations. In numerous epidemiological studies, maternal smoking during pregnancy has a significant role in fetal development. Therefore, quitting tobacco use may be an effective method for reducing the risk of congenital urogenital malformation in pregnant women.

11.
PeerJ ; 10: e13421, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669955

RESUMO

Background: Information regarding using a pig cadaver model for teaching purposes in dentistry is limited, especially for periodontal surgery procedures. The aim of this study was to assess the feasibility and efficacy of teaching crown lengthening surgical procedures using a prepared pig cadaver model. Methods: Mandibles of slaughtered pigs with subgingival crown fracture defects on two premolars and two molars on each side were prepared as periodontal surgery teaching cases. A resident group (n = 20) and an instructor group (n = 18) participated in assessing the efficacy of the model by completing questionnaires before and after training sessions. Data was either assessed descriptively or analyzed statistically with Wilcoxon signed-rank test with the significance level at α = 0.05. Results: Results revealed that all the knowledge points showed statistically significant improvements (p < 0.05) except for the procedure to determine the quantity of bone removal during osteotomy procedures. Most residents rated the efficacy of the model obtained with 9.0 out of 10 scale. The data of effectiveness of the pig cadaver model from the instructor group ranged from 7.4 ± 1.4 to 9.0 ± 1.0. Conclusion: Results of this study support feasibility in using prepared pig cadaver models to teach crown lengthening surgical procedures to postgraduates.


Assuntos
Aumento da Coroa Clínica , Coroas , Suínos , Animais , Aumento da Coroa Clínica/métodos , Cadáver
12.
BMC Oral Health ; 22(1): 99, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35354462

RESUMO

BACKGROUND: Whether to preserve a structurally compromised tooth or remove it is a dilemma often encountered by clinicians. The aim of this study was to assess the long-term success rate of fractured teeth preserved by modified crown lengthening surgery and restorations. METHODS: Thirty-nine patients with a total of 45 fractured teeth who had received modified crown lengthening surgery were recruited and examined. Numbers of teeth lost were recorded, and the criteria for successful teeth were defined. Kaplan-Meier estimator was used to determine the success rate. Possible risk factors were compared between successful and unsuccessful groups by a Cox regression analysis to explore the potential predictors of failure with a significant level at α = 0.05. RESULTS: The mean ± SD of success time without considering variants was 6.2 ± 0.6 years (95% CI 5.1-7.7). The mean survival rates ± SD at 1.0-, 2.0-, 3.0-, 5.0-, 7.0-, and 9.0-year intervals was 97.8 ± 2.2%, 92.2 ± 4.4%, 72.8 ± 7.9%, 68.2 ± 8.6%, 60.7 ± 10.5%, and 40.4 ± 13.6%, respectively. Failure cases in teeth with poor plaque control and step-shaped fracture margin were significantly more than those with good plaque control and knife-shaped fracture margin (HR = 7.237, p = 0.011; HR = 15.399, p = 0.006; respectively). CONCLUSIONS: Fractured teeth treated with modified crown lengthening surgery are anticipated to have a high clinical success rate for 6.2 ± 0.6 years. Plaque control and fracture morphology appeared to be significantly associated with the success of the multidisciplinary treatment approach.


Assuntos
Aumento da Coroa Clínica , Fraturas dos Dentes , Aumento da Coroa Clínica/efeitos adversos , Coroas , Humanos , Coroa do Dente/cirurgia , Fraturas dos Dentes/etiologia , Fraturas dos Dentes/cirurgia
13.
FEBS Open Bio ; 11(11): 2988-3004, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34449964

RESUMO

Clear-cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy. The pathogenesis of the disease is currently poorly understood, and the prognosis is poor. Therefore, in this study, we focused on exploring and identifying genes and signal transduction pathways that are closely related to ccRCC. Differentially expressed genes (DEGs) were analyzed using the renal cell oncogene expression profiles GSE100666 and GSE68417. DAVID evaluation of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses was used. We constructed a protein-protein interaction (PPI) network of DEGS using Cytoscape software and analyzed the submodules with the CytoHubba plugin. Finally, we performed western blot, immunohistochemistry, and PCR validation by collecting tissues, and also utilized cells for in vitro functional analysis of ceruloplasmin (CP). In total, 202 DEGs (52 upregulated and 150 downregulated genes) were identified. Upregulated DEGs are significantly rich in angiogenesis, cell adhesion, and response to hypoxia, whereas downregulated DEGs are involved in intracellular pH regulation, excretion, coagulation, and chloride transmembrane transport. We selected the interactions of the top 20 hub genes provided by the PPI network, all of which are involved in important physiological pathways in vivo, such as complement and coagulation cascades. Tissue protein assays demonstrated that renal cancer highly expressed CP, while in vitro experiments showed that CP could promote the invasion of renal cancer cells. Our study suggests that ALB, C3, LOX, HRG, CXCR4, GPC3, SLC12A3, CP, and CASR may be involved in the development of ccRCC, and is expected to provide theoretical support for future studies on the diagnosis and targeted therapy of ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Ceruloplasmina/genética , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Ceruloplasmina/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Redes Reguladoras de Genes/genética , Glipicanas , Humanos , Neoplasias Renais/genética , Oncogenes , Prognóstico , Mapas de Interação de Proteínas/genética , Receptores CXCR4 , Membro 3 da Família 12 de Carreador de Soluto , Taxa de Sobrevida
14.
World J Gastrointest Oncol ; 12(8): 857-876, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32879664

RESUMO

BACKGROUND: Gastric cancer (GC) is the most commonly diagnosed malignancy worldwide. Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC. AIM: To construct an immune-related gene (IRG) signature for accurately predicting the prognosis of patients with GC. METHODS: Differentially expressed genes (DEGs) between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas (TCGA) GDC data portal. Then, differentially expressed IRGs from the ImmPort database were identified for GC. Cox univariate survival analysis was used to screen survival-related IRGs. Differentially expressed survival-related IRGs were considered as hub IRGs. Genetic mutations of hub IRGs were analyzed. Then, hub IRGs were selected to conduct a prognostic signature. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of the signature. The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed. RESULTS: Among all DEGs, 70 hub IRGs were obtained for GC. The deletions and amplifications were the two most common types of genetic mutations of hub IRGs. A prognostic signature was identified, consisting of ten hub IRGs (including S100A12, DEFB126, KAL1, APOH, CGB5, GRP, GLP2R, LGR6, PTGER3, and CTLA4). This prognostic signature could accurately distinguish patients into high- and low- risk groups, and overall survival analysis showed that high risk patients had shortened survival time than low risk patients (P < 0.0001). The area under curve of the ROC of the signature was 0.761, suggesting that the prognostic signature had a high sensitivity and accuracy. Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features. Furthermore, we found that the prognostic signature was significantly correlated with macrophage infiltration. CONCLUSION: Our study proposed an immune-related prognostic signature for GC, which could help develop treatment strategies for patients with GC in the future.

15.
Aging (Albany NY) ; 12(14): 14885-14896, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32717723

RESUMO

Mounting evidence indicates that circular RNAs modulate the initiation of clear cell renal cell carcinoma (ccRCC). However, their specific roles in the malignancy of ccRCC is understudied. Here, we present a novel circular RNA, circDHX33, that is up-regulated in ccRCC cell lines and tissues. Upregulated circDHX33 in ccRCC patients significantly correlates with advanced TNM stage and metastasis. Suppressing circDHX33 expression inhibits the proliferation and invasion of cultured cells, and suppresses tumor growth in vivo. Mechanistically, we show that circDHX33 promotes ccRCC progression by sponging miR-489-3p and modulating MEK1 expression. In conclusion, our findings suggest that circDHX33 plays a role in promoting ccRCC via the miR-489-3p/MEK1 axis and may serve as a novel therapeutic target for the treatment of ccRCC patients.


Assuntos
Carcinoma de Células Renais , RNA Helicases DEAD-box/metabolismo , MAP Quinase Quinase 1/metabolismo , MicroRNAs/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Estadiamento de Neoplasias , RNA Circular/genética , Transdução de Sinais , Células Tumorais Cultivadas , Regulação para Cima
16.
Int Wound J ; 17(2): 317-325, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31850679

RESUMO

Human skin fibroblast (HSF) cells were irradiated with different energy lasers to detect cell proliferation, apoptosis, and expression of microRNA-206 and protein, and to further summarise the therapeutic effect of laser on scar cells. Human scar cell line HSF cells were cultured in three groups. The control group was not irradiated by laser, the low-energy group was irradiated by 10 J/cm2 laser, and the high-energy group was irradiated by 20 J/cm2 laser. After irradiation, HSF cells were cultured for 20 hours. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were detected by flow cytometry. Transwell migration assay was used to detect cell migratory ability. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect miR-206 and mTOR gene levels. The levels of MMP-9, Bax, Bcl-2, cyclin D1, and mTOR signalling pathway proteins were detected by Western blotting assays. The results showed that after laser irradiation, the proliferation of cells decreased, and the difference between the control group and the experimental group was significant (P < .05). The higher the energy was, the greater the upregulation of apoptosis was. Apoptosis and cell migration increased (P < .05). The expressions of microRNA-206, MMP-9, and Bax were upregulated, while the expressions of mTOR, Bcl-2, and cyclin D1 were downregulated. To sum up, laser irradiation can significantly inhibit the proliferation of HSF cells, affect cell cycle, and increase cell apoptosis and migratory ability.


Assuntos
Apoptose/efeitos da radiação , Cicatriz/radioterapia , Fibroblastos/patologia , Regulação da Expressão Gênica , Terapia com Luz de Baixa Intensidade/métodos , MicroRNAs/genética , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células Cultivadas , Cicatriz/genética , Cicatriz/patologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , MicroRNAs/biossíntese , Transdução de Sinais
17.
Semin Thromb Hemost ; 46(5): 637-652, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31404934

RESUMO

Nanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.


Assuntos
Bioensaio/métodos , Teste de Materiais/métodos , Nanopartículas/normas , United States Food and Drug Administration/normas , Humanos , Estados Unidos
18.
Biochem Biophys Res Commun ; 500(2): 229-235, 2018 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-29634928

RESUMO

Forkhead box R2 (FOXR2), a new member of the FOX family, is an important player in a wide range of cellular processes such as proliferation, migration, differentiation and apoptosis. Recently, FOXR2 has been reported to be implicated in cancer development. However, the biological functions of FOXR2 in non-small cell lung cancer (NSCLC) remain unclear. In this study, we investigated the specific role of FOXR2 in NSCLC. The results showed that down-regulation of FOXR2 significantly inhibited NSCLC cell proliferation and invasion in vitro and suppressed NSCLC cell growth and metastasis in vivo. In addition, the decrease in FOXR2 expression markedly reduced the protein levels of ß-catenin, cyclinD1 and c-Myc and hence inactivated the Wnt/ß-catenin pathway in NSCLC cells. Taken together, we concluded that FOXR2 might be considered as a promising therapeutic target for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação para Baixo , Fatores de Transcrição Forkhead/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt , Animais , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo/genética , Feminino , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Regulação para Cima/genética
19.
RSC Adv ; 8(6): 3348-3356, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35541180

RESUMO

The production cost of microbial oil was reduced by improving the exopolysaccharide (EPS) production to share the production cost using Sporidiobolus pararoseus JD-2. Batch fermentation demonstrated that S. pararoseus JD-2 has the potential to co-produce oil and EPS with 120 g L-1 glucose, 20 g L-1 corn steep liquor and 10 g L-1 yeast extract as carbon and nitrogen sources. Using fed-batch fermentation for 72 h resulted in oil and EPS production of 41.6 ± 2.5 g L-1 and 13.1 ± 0.6 g L-1 with the productivity of 0.58 g L-1 h-1 and 0.182 g L-1 h-1, respectively. The fat soluble nutrients in the oil were studied, indicating that it was constituted of 79.19% unsaturated fatty acids and contained 505 mg per kg-oil of carotenoids. Moreover, the EPS contained only one type of polysaccharide; the main monosaccharide compositions were galactose, glucose and mannose in a proportion of 16 : 8 : 1. These results implied that EPS produced by S. pararoseus JD-2 was a new type of EPS.

20.
Sci Rep ; 7(1): 12707, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28983091

RESUMO

Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly self-renewable with multi-potent differentiation capability. In this study, keratinocyte-like cells with self-regeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSG-EpiPCs). hMSG-EpiPCs were easily obtained via minor intraoral incision; they expressed epithelial progenitor/stem cell and other tissue stem cell markers such as CD29, CD49f, cytokeratins, ABCG2, PLET-1, salivary epithelial cell markers CD44 and CD166, and the Wnt target related gene LGR5 and LGR6. The cells were induced into functional hepatocytes in vitro which expressed liver-associated markers ALB, CYP3A4, AAT, and CK18. Upon transplantation in vivo, they ameliorated severe acute liver damage in SCID mice caused by carbon tetrachloride (CCl4) injection. In a two-thirds partial hepatectomy mouse model, the transplanted cells survived at least 4 weeks and exhibited hepatic potential. These findings demonstrate that hMSG-EpiPCs have potential as a cellular therapy basis for hepatic diseases, physiological and toxicology studies and regenerative medicine.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Terapia Baseada em Transplante de Células e Tecidos , Regeneração Hepática/genética , Transplante de Células-Tronco Mesenquimais , Glândulas Salivares Menores/transplante , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Tetracloreto de Carbono/toxicidade , Diferenciação Celular/genética , Autorrenovação Celular/genética , Células Epiteliais/transplante , Regulação da Expressão Gênica no Desenvolvimento , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , Glândulas Salivares Menores/citologia , Células-Tronco/citologia
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