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1.
Phys Chem Chem Phys ; 26(36): 23998-24007, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39246281

RESUMEN

Janus TiPX (X = F, Cl, and Br) monolayers were systematically investigated through first-principles calculations. The Janus TiPX monolayers exhibit mechanical and dynamic stability. Two monolayers are indirect bandgap semiconductors, except the TiPBr monolayer, which has the features of a quasi-direct bandgap semiconductor. Biaxial strain can modify the band gap of single layers. The Janus TiPX monolayers have remarkable flexibility and piezoelectric properties. In particular, the TiPF monolayer shows high horizontal (44.18 pm V-1) and vertical piezoelectric coefficients (-3.59 pm V-1). These values exceed those of conventional bulk materials, like GaN (3.1 pm V-1) and α-quartz (2.3 pm V-1). All of the monolayers have absorption coefficients of 105 cm-1 for visible and ultraviolet (UV) light, which are one order of magnitude greater than that of MoSSe. Furthermore, TiPX monolayers have high carrier mobility. Janus TiPX monolayers represent a class of two-dimensional (2D) materials with exceptional properties and multifunctionality, holding significant promise for various applications in piezoelectric sensors, solar cells, and nano-electronic devices.

2.
Ecotoxicol Environ Saf ; 281: 116662, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38944008

RESUMEN

OBJECTIVE: This study aimed to investigate the mechanism that Lactobacillus murinus (L. murinus) alleviated lung inflammation induced by polycyclic aromatic hydrocarbons (PAHs) exposure based on metabolomics. METHODS: Female mice were administrated with PAHs mix, L. murinus and indoleacrylic acid (IA) or indolealdehyde (IAId). Microbial diversity in feces was detected by 16 S rRNA gene sequencing. Non-targeted metabolomics analysis in urine samples and targeted analysis of tryptophan metabolites in serum by UPLC-Orbitrap-MS and short-chain fatty acids (SCFA) in feces by GC-MS were performed, respectively. Flow cytometry was used to determine T helper immune cell differentiation in gut and lung tissues. The levels of IgE, IL-4 and IL-17A in the bronchoalveolar lavage fluid (BALF) or serum were detected by ELISA. The expressions of aryl hydrocarbon receptor (Ahr), cytochrome P450 1A1 (Cyp1a1) and forkheadbox protein 3 (Foxp3) genes and the histone deacetylation activity were detected by qPCR and by ELISA in lung tissues, respectively. RESULTS: PAHs exposure induced lung inflammation and microbial composition shifts and tryptophan metabolism disturbance in mice. L. murinus alleviated PAHs-induced lung inflammation and inhibited T helper cell 17 (Th17) cell differentiation and promoted regulatory T cells (Treg) cell differentiation. L. murinus increased the levels of IA and IAId in the serum and regulated Th17/Treg imbalance by activating AhR. Additionally, L. murinus restored PAHs-induced decrease of butyric acid and valeric acid which can reduce the histone deacetylase (HDAC) level in the lung tissues, enhancing the expression of the Foxp3 gene and promoting Treg cell differentiation. CONCLUSION: our study illustrated that L. murinus alleviated PAHs-induced lung inflammation and regulated Th17/Treg cell differentiation by regulating host tryptophan metabolism and SCFA levels. The study provided new insights into the reciprocal influence between gut microbiota, host metabolism and the immune system, suggesting that L. murinus might have the potential as a novel therapeutic strategy for lung diseases caused by environmental pollution in the future.


Asunto(s)
Lactobacillus , Neumonía , Hidrocarburos Policíclicos Aromáticos , Animales , Ratones , Femenino , Hidrocarburos Policíclicos Aromáticos/toxicidad , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Receptores de Hidrocarburo de Aril/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/inmunología , Triptófano , Células Th17/efectos de los fármacos , Células Th17/inmunología , Probióticos/farmacología , Probióticos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/química , Metabolómica , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética
3.
Front Microbiol ; 15: 1400079, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863747

RESUMEN

Background and objectives: The oral and gut microbiota play significant roles in childhood asthma pathogenesis. However, the communication dynamics and pathogenic mechanisms by which oral microbiota influence gut microbiota and disease development remain incompletely understood. This study investigated potential mechanisms by which oral-originated gut microbiota, specifically Prevotella genus, may contribute to childhood asthma etiology. Methods: Oral swab and fecal samples from 30 asthmatic children and 30 healthy controls were collected. Microbiome composition was characterized using 16S rRNA gene sequencing and metagenomics. Genetic distances identified potential oral-originated bacteria in asthmatic children. Functional validation assessed pro-inflammatory properties of in silico predicted microbial mimicry peptides from enriched asthma-associated species. Fecal metabolome profiling combined with metagenomic correlations explored links between gut microbiota and metabolism. HBE cells treated with Prevotella bivia culture supernatant were analyzed for lipid pathway impacts using UPLC-MS/MS. Results: Children with asthma exhibited distinct oral and gut microbiota structures. Prevotella bivia, P. disiens, P. oris and Bacteroides fragilis were enriched orally and intestinally in asthmatics, while Streptococcus thermophilus decreased. P. bivia, P. disiens and P. oris in asthmatic gut likely originated orally. Microbial peptides induced inflammatory cytokines from immune cells. Aberrant lipid pathways characterized asthmatic children. P. bivia increased pro-inflammatory and decreased anti-inflammatory lipid metabolites in HBE cells. Conclusion: This study provides evidence of Prevotella transfer from oral to gut microbiota in childhood asthma. Prevotella's microbial mimicry peptides and effects on lipid metabolism contribute to disease pathogenesis by eliciting immune responses. Findings offer mechanistic insights into oral-gut connections in childhood asthma etiology.

4.
Aesthetic Plast Surg ; 48(17): 1-8, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38587672

RESUMEN

BACKGROUND: Botulinum toxin alone is unable to sufficiently reduce the muscle in cases of severe static glabellar lines due to the folded skin and dermal breakdown that frequently accompany these conditions. Augmentation of the soft tissue and removal of folded skin at the same time is the final solution. To simultaneously resolve interbrow skin laxity and replenish tissue volume, we present for the first time the method of glabellar lines excision combined with FDFG. METHODS: This retrospective study involved 23 patients with moderate-to-severe static glabellar lines underwent resection and/or free dermal fat grafting (FDFG) from June 2022 to June 2023. Fifteen of them underwent glabellar lines excision combined with FDFG, and seven were filled only. These patients were followed up at least 6 months to evaluate the effect. We utilized FACE-Q and WSRS for assessment in order to investigate the clinical results. RESULTS: There is no complication such as discoloration, hematoma, infection and palpability in all cases. After 6-15 months of follow-up, all the patients' dynamic and static lines were improved to a certain degree, and the patients were satisfied with the results with the WSRS score decreased from 3.5 ± 0.47 to 1.8 ± 0.62, and FACE-Q assessments in "Line between the eyebrows" decreased from 87 ± 7.39 to 43 ± 10.3. CONCLUSIONS: Resection in conjunction with FDFG is a brief, innovative and effective technique to correct static and dynamic severe glabellar wrinkles and maintain an acceptable outcome over an extended period of time which worthy clinical promotion. 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 .


Asunto(s)
Tejido Adiposo , Estética , Frente , Envejecimiento de la Piel , Humanos , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Tejido Adiposo/trasplante , Frente/cirugía , Resultado del Tratamiento , Estudios de Cohortes , Ritidoplastia/métodos , Estudios de Seguimiento
5.
Int Wound J ; 21(3): e14506, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38010070

RESUMEN

The incidence of squamous cell carcinoma (SCC) is on the rise, making it a significant global health concern. Environmental risk factors are crucial to the development of SCC. This study sought to examine comprehensively the impact of these factors on the onset of SCC. We conducted a cross-sectional study involving 480 participants at Beijing tertiary care hospital. Utilizing structured questionnaires, data on demographics, environmental exposures, medical history and clinical characteristics were collected. The cohort was composed of 272 men (56.67%) and 208 women (43.33%). The majority (44.38%) were between ages of 41 and 60, and Type III skin predominated (34.79%). Most of the participants belonged to the middle socioeconomic class (60.83%). 'Vegetarian' dietary habits (46.67%) were prevalent, as was the 'Sedentary' lifestyle (49.79%). Regarding environmental exposures, moderate sun exposure of 3 to 5 h per day (54.58%) and UV protective eyewear (30.83%) were prevalent. The majority (69.58%) of respondents indicated 'Never' exposure to carcinogens. A variety of wound characteristics were observed, with 'non-smokers' (64.17%) dominating. Most SCC lesions were located on the extremities (40.21%), lasted less than 6 months (44.38%) and measured 1-3 cm (39.79%). The majority (54.58%) did not have a history of cutaneous injuries. Our research uncovered substantial relationships between SCC and numerous environmental variables, gender, Fitzpatrick skin type, occupation, duration of sun exposure, exposure to carcinogens, dietary practices, history of skin wounds, wound location, duration, size and depth were significantly associated with the onset of SCC. These results highlighted the complexity of SCC aetiology and need for individualized prevention and treatment strategies.

6.
Biotechnol Biofuels Bioprod ; 16(1): 129, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37592325

RESUMEN

BACKGROUND: Genomic three-dimensional (3D) spatial organization plays a key role in shaping gene expression and associated chromatin modification, and it is highly sensitive to environmental stress conditions. In microalgae, exposure to nitrogen stress can drive lipid accumulation, yet the associated functional alterations in the spatial organization of the microalgal genome have yet to be effectively characterized. RESULTS: Accordingly, the present study employed RNA-seq, Hi-C, and ChIP-seq approaches to explore the relationship between 3D chromosomal architecture and gene expression during lipid accumulation in the marine microalga Nannochloropsis oceanica in response to nitrogen deprivation (ND). These analyses revealed that ND resulted in various changes in chromosomal organization, including A/B compartment transitions, topologically associating domain (TAD) shifts, and the disruption of short-range interactions. Significantly higher levels of gene expression were evident in A compartments and TAD boundary regions relative to B compartments and TAD interior regions, consistent with observed histone modification enrichment in these areas. ND-induced differentially expressed genes (DEGs) were notably enriched in altered TAD-associated regions and regions exhibiting differential genomic contact. These DEGs were subjected to Gene Ontology (GO) term analyses that indicated they were enriched in the 'fatty acid metabolism', 'response to stress', 'carbon fixation' and 'photosynthesis' functional categories, in line with the ND treatment conditions used to conduct this study. These data indicate that Nannochloropsis cells exhibit a clear association between chromatin organization and transcriptional activity under nitrogen stress conditions. Pronounced and extensive histone modifications were evident in response to ND. Observed changes in chromatin architecture were linked to shifts in histone modifications and gene expression. CONCLUSIONS: Overall, the reprogramming of many lipid metabolism-associated genes was evident under nitrogen stress conditions with respect to both histone modifications and chromosomal organization. Together these results revealed that higher-order chromatin architecture represents a new layer that can guide efforts to understand the transcriptional regulation of lipid metabolism in nitrogen-deprived microalgae.

7.
Oral Dis ; 2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37246926

RESUMEN

OBJECTIVES: The aim of this study was to explore the potential role of zinc-finger homeodomain transcription factor (TCF8) in osteoclastogenesis and inflammation during periodontitis. MATERIALS AND METHODS: Rats with periodontitis were induced via Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) injection. The recombinant lentivirus delivering short hairpin RNA (shRNA) against TCF8 was used to downregulate TCF8 in vivo. Alveolar bone loss in rats was determined by micro-computed tomography (Micro-CT). Typical pathological changes, periodontal tissue inflammation, and osteoclastogenesis were evaluated via histological analyses. The RAW264.7-derived osteoclasts were induced by RANKL stimulation. TCF8 downregulation in vitro was achieved by lentivirus infection. The osteoclast differentiation and inflammatory signaling in RANKL-induced cells were measured via immunofluorescence methods and molecular biology approaches. RESULTS: Porphyromonas gingivalis-lipopolysaccharide induced rats exhibited overexpressed TCF8 in their periodontal tissues, while TCF8 knockdown attenuated the bone loss, tissue inflammation, and osteoclastogenesis in LPS-induced rats. Besides, TCF8 silencing inhibited RANKL-induced osteoclast differentiation in RAW264.7 cells, as evidenced by the reduced numbers of TRAP-positive osteoclasts, less formation of F-actin rings, and downregulated expressions of osteoclast-specific markers. It also exerted an inhibitory effect on the NF-κB signaling in RANKL-induced cells via blocking NF-κB p65 phosphorylation and nuclear translocation. CONCLUSIONS: TCF8 silencing inhibited alveolar bone loss, osteoclast differentiation, and inflammation in periodontitis.

8.
J Pers Med ; 13(3)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36983611

RESUMEN

Recently, many clinical trials have applied platelet-rich plasma (PRP) dressings to treat wounds that have stopped healing, which are also called chronic wounds. However, the clinical efficiency of PRP dressings in treating chronic wounds is still controversial. Therefore, we conducted this study to compare PRP dressings with normal saline dressings in treating chronic wounds. Relevant randomized controlled trials focusing on utilizing PRP dressings in treating chronic wounds were extracted from bibliographic databases. Finally, 330 patients with chronic wounds, reported in eight randomized controlled trials, were included in this study. In total, 169 out of 330 (51.21%) were treated with PRP dressings, and 161 out of 330 (48.79%) were treated with normal saline dressings. The pooled results showed that the complete healing rate of the PRP group was significantly higher than that of saline group at 8 weeks and 12 weeks, respectively. In addition, there were no significant differences in wound infection and adverse events. Compared with normal saline dressing, the PRP dressing could effectively enhance the prognosis of chronic wounds. Furthermore, the PRP did not increase wound infection rate or occurrence of adverse events as an available treatment for chronic wounds.

9.
J Pers Med ; 13(3)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36983613

RESUMEN

In recent years, various clinical trials have focused on treating knee osteoarthritis (KOA) with multiple injections of platelet-rich plasma (PRP). However, compared with the multiple hyaluronic acid (m-HA) injections, the clinical efficacy of multiple PRP (m-PRP) injections for KOA still remains controversial among these studies. Therefore, we aimed to compare the clinical effectiveness of m-PRP injections with m-HA injections in the treatment of KOA in this systematic review. Relevant clinical trials were searched via bibliographic databases, including Medline, PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, to compare the m-PRP and m-HA injections in the treatment of KOA. Finally, fourteen randomized controlled trials, including 1512 patients, showed the postoperative VAS, WOMAC, IKDC, or EQ-VAS scores and were enrolled in this systematic review. Compared with the group of intra-articular m-HA injections, the group of intra-articular m-PRP injections was lower in the VAS scores at 3-month (WMD = -0.25; 95%CI, -0.40 to -0.10, p = 0.0009) and 12-month (WMD = -0.64; 95%CI, -0.79 to -0.49, p < 0.00001) follow-ups. In addition, the group of intra-articular m-PRP injections was also lower in the WOMAC scores at 1-month (WMD = -1.23; 95%CI, -2.17 to -0.29, p = 0.01), 3-month (WMD = -5.34; 95%CI, -10.41 to -0.27, p = 0.04), 6-month (WMD = -11.02; 95%CI, -18.09 to -3.95, p = 0.002), and 12-month (WMD = -7.69; 95%CI, -12.86 to -2.52, p = 0.004) follow-ups. Furthermore, compared with the group of intra-articular m-HA injections, the group of intra-articular m-PRP injections was higher in the IKDC scores at 3-month (WMD = 7.45; 95%CI, 2.50 to 12.40, p = 0.003) and 6-month (WMD = 5.06; 95%CI, 1.94 to 8.18, p = 0.001) follow-ups. However, the long-term adverse side of m-PRP injections for KOA still needs more large-scale trials and long-term follow-ups.

10.
J Appl Toxicol ; 43(7): 1026-1038, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36727205

RESUMEN

In recent years, chromium (Cr) has been found to induce neurotoxicity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of chromium exposure on the metabolome and microbiome that may contribute to neurotoxicity in juvenile zebrafish. Zebrafish embryos were exposed to 1 mg/L Cr (III) and 1 mg/L Cr (VI) for 7 days, respectively. Swimming distance and locomotor behavior was decreased, and acetylcholinesterase activity was reduced in Cr-exposed groups. Total cholesterol levels were decreased in Cr-exposed groups. The differential-expressed metabolites due to Cr exposure were mainly enriched in primary bile acid biosynthesis, which indicated that Cr exposure may promote cholesterol conversion. The abundance of Bacteroidetes decreased and the abundance of Actinomycetes increased in Cr-exposed groups, as compared with that in the control group. At the genus level, the abundance of Acinetobacter, Acidophorax, Mycobacterium, Aeromonas, Hydrophagophaga, and Brevundimonas increased, whereas Chryseobacterium, Pseudomonas, Delftia, and Ancylobacter decreased in the Cr-exposed groups. Analysis of the correlation between gut microbiota and bile acid metabolites showed that changes of gut microbial community due to Cr exposure may be related to secondary bile acid metabolism. Collectively, chromium exposure may disturb cholesterol metabolism, including primary bile acid and microbiota-related secondary bile acid metabolism. This study provides potential mechanism of the effects of chromium on neurotoxicity based on modulation of metabolome and gut microbiota diversity, which needs further verification.


Asunto(s)
Microbioma Gastrointestinal , Pez Cebra , Animales , Cromo/toxicidad , Acetilcolinesterasa , Metaboloma , Ácidos y Sales Biliares
11.
Environ Sci Pollut Res Int ; 30(5): 13739-13754, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36136199

RESUMEN

Epidemiological studies have shown that PAHs may exert adverse effects on childhood asthma. However, the underlying molecular mechanism remains to be fully elucidated. This study aimed to investigate this process in view of metabolic pathways, especially one-carbon metabolism and tryptophan metabolism. Fifty asthmatic children and 50 control subjects were recruited for this study. Serum IgE and IL-17A levels were detected by ELISA. Serum PAH concentrations were measured by GC-MS. One-carbon-related metabolites and tryptophan metabolites were determined by UPLC-Orbitrap-MS. DNA methylation was analyzed by bisulfite sequencing PCR. ChIP assays were used to examine H3K4me3 enrichment on IL-17A gene. Multivariable linear regression was performed to evaluate the association between PAHs and childhood asthma mediated by intermediators. HE staining in lung tissue, IgE and IL-17A in BALF, metabolic profiles in urine, and Ahr, Il-17a, and Cyp1a1 gene expression were determined in PAH-exposed mice. Serum Fla level was associated with childhood asthma (OR = 1.380, 95% CI: 1.063-1.792), and had a great effect on one-carbon metabolites, especially SAH, SAM, and Ser, which exerted significant mediation effects on the relationship between the Fla concentration and asthma. Moreover, we did find significant mediation effects between serum Fla and asthma by LINE-1 DNA methylation and H3K4me3 levels in the IL-17A promoter region. The differential Trp metabolites, such as Trp, tryptamine, IA, IAA, indole, IAld, and IAAld, indicated that asthmatic children had increased indole-AhR pathway. Mediation analysis failed to show a mediator effect of Trp metabolites in the association between PAHs and childhood asthma. An animal study confirmed that PAH exposure increased methylation levels, and altered Trp metabolite-AhR-IL-17A axis, which may be influenced by gender. PAHs disturbed one-carbon metabolism to influence the methyl group refilling DNA methylation and histone methylation, and disturbed tryptophan metabolism to regulate Th17-cell differentiation, which may elevate serum IL-17A concentration in asthmatic children.


Asunto(s)
Asma , Interleucina-17 , Animales , Ratones , Triptófano , Inflamación , Inmunoglobulina E
12.
Front Cell Infect Microbiol ; 13: 1325103, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38173793

RESUMEN

Polymethyl methacrylate (PMMA) frequently features in dental restorative materials due to its favorable properties. However, its surface exhibits a propensity for bacterial colonization, and the material can fracture under masticatory pressure. This study incorporated commercially available RHA-1F-II nano-silver loaded zirconium phosphate (Ag-ZrP) into room-temperature cured PMMA at varying mass fractions. Various methods were employed to characterize Ag-ZrP. Subsequently, an examination of the effects of Ag-ZrP on the antimicrobial properties, biosafety, and mechanical properties of PMMA materials was conducted. The results indicated that the antibacterial rate against Streptococcus mutans was enhanced at Ag-ZrP additions of 0%wt, 0.5%wt, 1.0%wt, 1.5%wt, 2.0%wt, 2.5%wt, and 3.0%wt, achieving respective rates of 53.53%, 67.08%, 83.23%, 93.38%, 95.85%, and 98.00%. Similarly, the antibacterial rate against Escherichia coli registered at 31.62%, 50.14%, 64.00%, 75.09%, 86.30%, 92.98%. When Ag-ZrP was introduced at amounts ranging from 1.0% to 1.5%, PMMA materials exhibited peak mechanical properties. However, mechanical strength diminished beyond additions of 2.5%wt to 3.0%wt, relative to the 0%wt group, while PMMA demonstrated no notable cytotoxicity below a 3.0%wt dosage. Thus, it is inferred that optimal antimicrobial and mechanical properties of PMMA materials are achieved with nano-Ag-ZrP (RHA-1F-II) additions of 1.5%wt to 2.0%wt, without eliciting cytotoxicity.


Asunto(s)
Antiinfecciosos , Polimetil Metacrilato , Polimetil Metacrilato/farmacología , Contención de Riesgos Biológicos , Temperatura , Antibacterianos/farmacología
13.
Artículo en Inglés | MEDLINE | ID: mdl-35731761

RESUMEN

Machine life cycle performance assessment is of great significance to use a health index to inform the time of incipient fault initiation in a normal stage and realize fault identification and fault trending in a performance degradation stage. However, most existing works consider using unexplainable model parameters and historical data to build models and infer their off-line parameters for machine life cycle performance assessment. To overcome these limitations, an online piecewise convex-optimization interpretable weight learning framework without needing any historical abnormal and faulty data is proposed in this article to generate a piecewise health index to practically implement machine life cycle performance assessment. Firstly, based on a separation criterion, the first submodel in the proposed framework is built to detect the time of incipient fault initiation. Here, the piecewise health index generated by the first submodel is continuously updated by on-line monitoring data to timely detect the occurrence of any abnormal health conditions. Secondly, once the time of incipient fault initiation is informed, online updated model weights are highly correlated with fault characteristic frequencies and informative frequency bands for immediate fault identification. Simultaneously, the second submodel integrated with monotonicity and fitness properties in the proposed framework is triggered to generate the piecewise health index to realize overall monotonic fault trending. The significance of this article is that only online monitoring data are used to continuously update interpretable model weights as fault frequencies and informative frequency bands to generate the proposed piecewise health index so as to practically realize machine life cycle performance assessment. Two run-to-failure cases are studied to show the effectiveness and superiority of the proposed framework.

14.
Cell Biol Int ; 44(4): 998-1008, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31889370

RESUMEN

Oral squamous cell carcinoma (OSCC) is a common cancer with poor prognosis and high mortality. The role of CCN5 has attracted a great focus on the regulation of cancer progression. However, the biological function and mechanism of CCN5 in OSCC are still not well elucidated. The current study was designed to determine the effects of CCN5 on OSCC cell proliferation and apoptosis using two OSCC cell lines. Further, LY294002, a PI3K/AKT antagonist, was employed to explore the mechanism underlying the effects of CCN5 in the regulation of OSCC. The results showed that overexpression of CCN5 in TSCCa cells significantly reduced viable cell number, arrested cell cycle, and suppressed cell-cycle regulators (cyclin D1, cyclin E, and CDK2). CCN5 overexpression increased the apoptotic ratio and Hoechst-positive cell number, and altered the apoptotic-related proteins (caspase-3/9, Bax, and Bcl-2). However, CCN5 silencing induced opposite effects on cell proliferation and apoptosis in Tca-8113 cells. In addition, we observed that CCN5 knockdown increased the expression levels of PI3K (p85α and p110α) and phosphorylated AKT at serine 473 (p-AKT Ser473) in Tca-8113 cells. Inhibiting PI3K/AKT signaling with LY294002 rescued the apoptotic process in CCN5-silenced OSCC cells. Finally, xenograft analysis showed that CCN5 represses tumorigenesis of OSCC cells. These findings together suggest that CCN5 functions as a tumor suppressor for OSCC cell development through inactivation of PI3K/AKT signaling pathway, providing a potential candidate for OSCC therapy.


Asunto(s)
Apoptosis , Proteínas CCN de Señalización Intercelular/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Proteínas Represoras/metabolismo , Animales , Carcinoma de Células Escamosas/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias de la Boca/metabolismo , Trasplante de Neoplasias , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo
15.
Ann Plast Surg ; 77(3): e46-9, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25144422

RESUMEN

BACKGROUND: Scar contracture (SC) is one of the most common complications resulting from major burn injuries. Numerous treatments are currently available but they do not always yield excellent therapeutic results. Recent reports suggest that botulinum toxin type A (BTXA) is effective at reducing SC clinically, but the molecular mechanism for this action is unknown. α-Smooth muscle actin (α-SMA) and myosin II are the main components of stress fibers, which are the contractile structures of fibroblasts. The effects of BTXA on α-SMA and myosin II in SC are still unknown. This study aimed to explore the effect of BTXA on α-SMA and myosin II expression in fibroblasts derived from SC and to elucidate its actual mechanism further. METHODS: Fibroblasts were isolated from tissue specimens of SC. Fibroblasts were cultured in Dulbecco modified Eagle medium with different concentrations of BTXA and their proliferation was analyzed through the tetrazolium-based colorimetric method at 1, 4, and 7 days. Proteins of α-SMA and myosin II were checked using Western blot in fibroblasts treated with different concentrations of BTXA at 1, 4, and 7 days. RESULTS: Fibroblasts without BTXA treatment had a higher proliferation than that in other groups, which indicated that the proliferation of fibroblasts was significantly inhibited by BTXA (P < 0.05). Proteins of α-SMA and myosin II between fibroblasts with BTXA and fibroblasts without BTXA are statistically significant (P < 0.05). CONCLUSIONS: These results suggest that BTXA effectively inhibited the growth of fibroblasts derived from SC and reduced the expression of α-SMA and myosin II, which provided theoretical support for the application of BTXA to control SC.


Asunto(s)
Actinas/antagonistas & inhibidores , Toxinas Botulínicas Tipo A/farmacología , Cicatriz/tratamiento farmacológico , Contractura/tratamiento farmacológico , Fármacos Dermatológicos/farmacología , Fibroblastos/efectos de los fármacos , Miosina Tipo II/antagonistas & inhibidores , Biomarcadores/metabolismo , Toxinas Botulínicas Tipo A/uso terapéutico , Quemaduras/complicaciones , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cicatriz/etiología , Cicatriz/metabolismo , Contractura/etiología , Contractura/metabolismo , Fármacos Dermatológicos/uso terapéutico , Fibroblastos/metabolismo , Humanos
16.
Ann Plast Surg ; 74(1): 26-9, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25305228

RESUMEN

BACKGROUND: Hypertrophic scars (HSs) and keloids (KDs) are commonly seen as 2 different diseases. We aimed to find potential genes associated with KD and HS formation. METHODS: We selected 4 single-nucleotide polymorphisms (SNPs) (based on the whole genome resequencing we have done) for replication in 71 KDs and 50 HSs using the Sequenom Massarray system. RESULTS: We found evidence of significant association at rs181924090, P = 0.0075; rs183178644, P = 0.0151; and rs151091483, P = 0.0073. However, at rs141156594, there was no significant association between KD and HS (P = 0.7893). CONCLUSIONS: rs181924090 (11p15.5, SIRT3), rs151091483 (17p13.1, MYH8), and rs183178644 (6p25.3, HUS1B) are new potential SNPs associated with KD formation, especially closely related to tumor behaviors as KD is, whereas rs141156594 (18q22.2, RTTN) is a new SNP involved in the extracellular matrix formation in wound healing.


Asunto(s)
Cicatriz Hipertrófica/genética , Queloide/genética , Polimorfismo de Nucleótido Simple , Cicatrización de Heridas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Proteínas Portadoras/genética , Proteínas de Ciclo Celular/genética , Niño , Preescolar , China , Cicatriz Hipertrófica/etnología , Femenino , Marcadores Genéticos , Humanos , Queloide/etnología , Masculino , Persona de Mediana Edad , Cadenas Pesadas de Miosina/genética , Receptores Acoplados a Proteínas G/genética , Sirtuina 3/genética , Adulto Joven
17.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 30(4): 279-82, 2014 Jul.
Artículo en Chino | MEDLINE | ID: mdl-25322576

RESUMEN

OBJECTIVE: To investigate the genome structure variation (SV) related with keloid using the whole-gene resequencing technology. METHODS: We studied a keloid pedigree containing 4 generation of 27 people. 5 people (4 cases of keloid patients, and 1 case of normal) were selected to extract the genomic DNA. Then the whole-gene resequencing technique was used to check the variations. RESULTS: Through database comparison and variation annotation analysis, we obtained 2 SVs associated with keloid formation. We used DAVID software to do the gene ontology and pathway analysis. We found a 168 bp inversion in gene tetraspanin 8 (TSPAN8) in all keloid patients, which contained the forth exon of TSPAN8. CONCLUSIONS: There was no report about SVs related to keloid. In this study, we found 2 SVs associated with keloid, especially TSPAN8. The tumor cells express the TSPAN8 can up-regulate the vascular endothelial growth factor and its receptors, promote the adjacent fibroblasts secrete matrix metalloproteinases and uridylyl phosphate adenosine. So we hypothesis that the inversion of the forth exon in TSPAN8 may lead to the signal transduction disorder in the keloid patients. This study was a preliminary research. It needs a further study containing large sample to confirm.


Asunto(s)
Queloide/genética , Análisis de Secuencia/métodos , Tetraspaninas/genética , Secuencia de Bases , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Linaje
18.
Zhonghua Wai Ke Za Zhi ; 52(6): 446-9, 2014 Jun.
Artículo en Chino | MEDLINE | ID: mdl-25219561

RESUMEN

OBJECTIVE: To investigate the genome copy number variation (CNV) related with keloid using the whole-gene resequencing technology. METHODS: A keloid pedigree containing 4 generation of 27 people was studied. Five people (4 cases of keloid patients, and 1 case of normal) were selected to extract the genomic DNA. Then the whole-gene resequencing technique was used to check the variations based on the Illumina Hiseq 2000. RESULTS: Through database comparison and variation annotation analysis, 15 CNVs associated with scar hyperplasia were obtained. DAVID software was used to do the Gene Ontology and pathway analysis. Five CNVs were closely related to the keloid formation. They were growth factor receptor-bound 7 (Grb7), mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), mitogen-activated protein kinase kinase kinase 15 (MAP3K15), kruppel-like factors 7 (KLF7) and NK2 homeobox 2 (NKX2-2). These CNVs were involved in the process of epidermal cells formation and differentiation, cell exocrine and cell adhesion. CONCLUSIONS: There are 5 CNVs associated with scar hyperplasia. Especially MAP3K15 and MAP4K4 deserve more research to find their function in keloid formation.


Asunto(s)
Cicatriz/genética , Variaciones en el Número de Copia de ADN , Femenino , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodominio , Humanos , Masculino , Proteínas Nucleares , Linaje , Factores de Transcripción
19.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 30(2): 118-21, 2014 Mar.
Artículo en Chino | MEDLINE | ID: mdl-24941763

RESUMEN

OBJECTIVE: To investigate the effects of botulinum toxin type A (BTXA) on the expression of alpha smooth muscle actin(alpha-SMA) and myosin-II of fibroblasts in scars. Methods Fibroblasts were isolated from tissue specimens of scars contracture. Cells from passages 3-5 were randomly divided into 3 groups (control group, low BTXA group (1 U/10(6) Cells), and high BTXA group (2.5 U/ 10(6)Cells)). Growth condition of fibroblasts was observed at 1 , 4, 7 day after BTXA treated. Changes of alpha-SMA and myosin-II in fibroblasts were detected by Western blot. RESULTS: Fibroblasts grew well in control group. The proliferation was decreased 4 days later in BTXA groups. Lots of apoptotic cells were seen in high BTXA group at 7th day. Proteins of alpha-SMA and myosin-II in fibroblasts were statistically different between BTXA group and control groups at 4th day (P < 0.05). The expression of alpha-SMA and myosin-II in low BTXA group was higher than that in high BTXA group at 7th day (P < 0.05). CONCLUSIONS: BTXA could induce the apoptosis of fibroblasts and decrease the expression of alpha-SMA and myosin-II in fibroblasts. The inhibitory effect was strengthened with BTXA concentration increase within a certain range.


Asunto(s)
Actinas/metabolismo , Toxinas Botulínicas Tipo A/farmacología , Fibroblastos/efectos de los fármacos , Músculo Liso/metabolismo , Miosina Tipo II/metabolismo , Cicatriz , Fibroblastos/metabolismo , Humanos , Distribución Aleatoria
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