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1.
J Biol Chem ; : 107733, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233228

RESUMO

Transient receptor potential vanilloid 3 channel (TRPV3) is closely associated with skin inflammation, but there is a lack of effective and specific inhibitors for clinical use. In this study, we identified antimalarial HCQ as a selective TRPV3 inhibitor following the prediction by network pharmacology data analysis. In whole-cell patch-clamp recordings, HCQ inhibited the current of the TRPV3 channel, with an IC50 of 51.69 ± 4.78 µM. At the single-channel level, HCQ reduced the open probability of TRPV3 and decreased single-channel conductance. Molecular docking and site-directed mutagenesis confirmed that residues in the pore domain were critical for the activity of HCQ. In vivo, HCQ effectively reduced carvacrol-induced epidermal thickening, erythema, and desquamation. Additionally, the serum IgE and inflammatory factors such as TNF-α and IL-6 were markedly decreased in the dorsal skin tissues in the HCQ treatment group, as compared to the model group. Our results suggested the antimalarial HCQ may represent a potential alleviator for treating skin inflammation by inhibiting TRPV3 channels.

2.
Skin Res Technol ; 30(6): e13777, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899718

RESUMO

BACKGROUND: Ultraviolet (UV)-induced fluorescence technology is widely used in dermatology to identify microbial infections. Our clinical observations under an ultraviolet-induced fluorescent dermatoscope (UVFD) showed red fluorescence on the scalps of androgenetic alopecia (AGA) patients. In this study, based on the hypothesis that microbes are induced to emit red fluorescence under UV light, we aimed to explore the microbial disparities between the AGA fluorescent area (AF group) and AGA non-fluorescent area (ANF group). METHODS: Scalp swab samples were collected from 36 AGA patients, including both fluorescent and non-fluorescent areas. The bacterial communities on the scalp were analyzed by 16S rRNA gene sequencing and bioinformatics analysis, as well as through microbial culture methods. RESULTS: Significant variations were observed in microbial evenness, abundance composition, and functional predictions between fluorescent and non-fluorescent areas. Sequencing results highlighted significant differences in Cutibacterium abundance between these areas (34.06% and 21.36%, respectively; p < 0.05). Furthermore, cultured red fluorescent colonies primarily consisted of Cutibacterium spp., Cutibacterium acnes, Staphylococcus epidermidis, and Micrococcus spp. CONCLUSIONS: This is the first study to investigate scalp red fluorescence, highlighting microbial composition variability across different scalp regions. These findings may provide novel insights into the microbiological mechanisms of AGA.


Assuntos
Alopecia , Raios Ultravioleta , Humanos , Alopecia/microbiologia , Masculino , Adulto , Pessoa de Meia-Idade , Couro Cabeludo/microbiologia , Feminino , Dermoscopia/métodos , Fluorescência , Microbiota , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/isolamento & purificação
3.
Artigo em Inglês | MEDLINE | ID: mdl-39193652

RESUMO

OBJECTIVE: To investigate the effect of spectacle correction on refractive progression in children with unilateral myopic anisometropia (UMA). METHODS: In this retrospective study, 153 children with UMA (aged 8-12 years) were recruited and classified into an uncorrected (UC) group (n = 47) and a spectacle (SP) group (n = 106). The spherical equivalent refraction (SER) of the myopic eyes ranged from -0.75 to -4.00 D; the SER of the emmetropic eyes ranged from +1.00 to -0.25 D; anisometropia was ≥1.00 D and the follow-up duration was 1 year. Nineteen subjects from the SP group with follow-up records spanning at least 6 months before and after wearing spectacles were selected as a subgroup. Changes in the SER and axial length (AL), the degree of anisometropia and interocular AL differences of the two groups and the subgroup were analysed. RESULTS: During the 1-year follow-up period, AL and SER changes in myopic eyes were significantly greater than those in emmetropic eyes in the UC group (p < 0.001). For the UC group, the degree of anisometropia and AL change increased (all p < 0.001). For the SP group, there were no significant differences in the degree of anisometropia or AL change (all p > 0.05). When comparing the groups, AL elongation of the myopic eyes in the UC group occurred significantly faster than in the SP group (p = 0.02), and AL elongation for the emmetropic eyes in the UC group occurred significantly slower than in the SP group (p = 0.04). For the subgroup, the AL and SER changes in the myopic eyes 6 months before wearing spectacles occurred significantly faster than those after correction (p < 0.001). CONCLUSIONS: Spectacle correction could prevent increased anisometropia in uncorrected children with UMA by slowing myopia progression in the myopic eyes and accelerating the myopic shift in the contralateral eye.

4.
Biochem Genet ; 62(1): 485-503, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37382751

RESUMO

Pancreatic adenocarcinoma (PAAD) is one of the most hazardous cancers in digestive system, and the prognosis is notoriously bad. Increasing evidences indicate that Laminin Subunit Gamma 2 (LAMC2) is critical for the initiation and the growth of various sorts of human cancers. However, the involved molecular pathways of LAMC2 in PAAD are still poorly understood. In this study, prediction programs and databases were employed to conduct pan-cancer analysis. Multiple variations of human malignancies showed increased LAMC2 expression, which was positively correlated to a poor prognosis in PAAD. Moreover, LAMC2 was positively correlated with the biomarkers of immune cells including CD19, CD163, and NOS2 in PAAD. The lncRNA C5orf66 /PTPRG-AS1- miR-128-3p -LAMC2 axis was identified to be a potential upstream regulatory pathway of LAMC2 in PAAD. Furthermore, LAMC2 upregulation in PAAD was associated with PD-L1 expression, indicating promoting carcinoma immune cell infiltration. Our study elucidated prognostic and immunological values of LAMC2 in PAAD, providing a promise target for PAAD treatment.


Assuntos
Adenocarcinoma , Carcinoma , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , Adenocarcinoma/genética , Prognóstico , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Laminina
5.
Ultrason Imaging ; 46(4-5): 211-219, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38881032

RESUMO

Skeletal muscle is a vital organ that promotes human movement and maintains posture. Accurate assessment of muscle strength is helpful to provide valuable insights for athletes' rehabilitation and strength training. However, traditional techniques rely heavily on the operator's expertise, which may affect the accuracy of the results. In this study, we propose an automated method to evaluate muscle strength using ultrasound and deep learning techniques. B-mode ultrasound data of biceps brachii of multiple athletes at different strength levels were collected and then used to train our deep learning model. To evaluate the effectiveness of this method, this study tested the contraction of the biceps brachii under different force levels. The classification accuracy of this method for grade 4 and grade 6 muscle strength reached 98% and 96%, respectively, and the overall average accuracy was 93% and 87%, respectively. The experimental results confirm that the innovative methods in this paper can accurately and effectively evaluate and classify muscle strength.


Assuntos
Aprendizado Profundo , Força Muscular , Músculo Esquelético , Ultrassonografia , Humanos , Força Muscular/fisiologia , Ultrassonografia/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Masculino , Adulto Jovem , Adulto , Feminino
6.
Anal Chem ; 95(10): 4786-4794, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36854667

RESUMO

Precise characterization of miRNA expression patterns is critical to exploit the complexity of miRNA regulation in biology. Herein, we developed a Pumilio/FBF (PUF) protein-based engineering luciferase reporter system, PUF/miR, to quantitatively and non-invasively sense miRNA activity in living cells and animal models. We verified the feasibility of this reporter by monitoring the expression of several types of miRNAs (miRNA-9, 124a, 1, and 133a) in neural and muscle differentiated cells as well as subcutaneous or tibial anterior muscles in mice. The quantitative RT-PCR also validated the reliability and quantitative consistency of bioluminescence imaging in detecting miRNA expression. We further effectively employed this reporter system to visualize the expression of miRNA-1 and miRNA-133a in mouse models of skeletal muscle injury. As a non-invasive and convenient innovative approach, our results have realized the positive bioluminescence imaging of endogenous miRNAs in vitro and in vivo using the PUF/miR system. We believe that this approach would provide a potential means for noninvasive monitoring of disease-related miRNAs and could facilitate a deeper understanding of miRNA biology.


Assuntos
MicroRNAs , Camundongos , Animais , Reprodutibilidade dos Testes , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular , Luciferases/genética , Diagnóstico por Imagem
7.
Electrophoresis ; 44(15-16): 1187-1196, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37183951

RESUMO

DNA-based ancestry inference has long been a research hot spot in forensic science. The differentiation of Han Chinese population, such as the northern-to-southern substructure, would benefit forensic practice. In the present study, we enrolled participants from northern and southern China, each participant was genotyped at ∼400 K single-nucleotide polymorphisms (SNPs) and data of CHB and CHS from 1000 Genomes Project were used to perform genome-wide association analyses. Meanwhile, a new method combining genome-wide association study (GWAS) analyses with k-fold cross-validation in a small sample size was introduced. As a result, one SNP rs17822931 emerged with a p-value of 7.51E - 6. We also simulated a huge dataset to verify whether k-fold cross-validation could reduce the false-negative rate of GWAS. The identified ABCC11 rs17822931 has been reported to have allele frequencies varied with the geographical gradient distribution in humans. We also found a great difference in the allele frequency distributions of rs17822931 among five different cohorts of the Chinese population. In conclusion, our study demonstrated that even small-scale GWAS can also have potential to identify effective loci with implemented k-fold cross-validation method and shed light on the potential maker of rs17822931 in differentiating the north-to-south substructure of the Han Chinese population.


Assuntos
População do Leste Asiático , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , China , População do Leste Asiático/genética , Frequência do Gene , Genótipo , Polimorfismo de Nucleotídeo Único
8.
Environ Sci Technol ; 57(19): 7599-7611, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37140343

RESUMO

Spent lithium-ion batteries (LIBs) and benzene-containing polymers (BCPs) are two major pollutants that cause serious environmental burdens. Herein, spent LIBs and BCPs are copyrolyzed in a sealed reactor to generate Li2CO3, metals, and/or metal oxides without emitting toxic benzene-based gases. The use of a closed reactor allows the sufficient reduction reaction between the BCP-derived polycyclic aromatic hydrocarbon (PAH) gases and lithium transition metal oxides, achieving the Li recovery efficiencies of 98.3, 99.9, and 97.5% for LiCoO2, LiMn2O4, and LiNi0.6Co0.2Mn0.2O2, respectively. More importantly, the thermal decomposition of PAHs (e.g., phenol and benzene) is further catalyzed by the in situ generated Co, Ni, and MnO2 particles, which forms metal/carbon composites and thus prevent the emissions of toxic gases. Overall, the copyrolysis in a closed system paves a green way to synergistically recycle spent LIBs and handle waste BCPs.


Assuntos
Benzeno , Lítio , Plásticos , Compostos de Manganês , Óxidos , Metais , Fontes de Energia Elétrica , Reciclagem , Polímeros
9.
J Infect Chemother ; 29(1): 48-54, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36130707

RESUMO

BACKGROUND: Klebsiella pneumoniae is a major pathogen of bacterial liver abscess in Asia. Particularly, patients with community-acquired Klebsiella pneumoniae liver abscess (CA-KPLA) tend to have a higher risk of invasive infection and pulmonary is a common invasive infectious site, making it a global clinical crisis. Therefore, considerable attention should be focused on the early prediction and active treatment strategies of such patients. METHODS: The clinical data of 127 CA-KPLA cases hospitalized from January 2017 to February 2022 were collected from a single center. Risk factors were analyzed by the use of univariable and multivariable analysis. Furthermore, independent risk factors of pulmonary affection were utilized to construct a predictive nomogram. RESULTS: The incidence of pulmonary affection in KPLA patients was 57.5% (73/127) and the majority manifested as nodular lesions with cavities and pleural effusion in chest CT images. Based on the predictive nomogram, the SOFA score (>2) was defined as the most dominant independent risk factor for the occurrence of pulmonary affection, followed by the maximum diameter of liver abscess (>3 cm), multiple liver abscesses, bacteremia, and badly-controlled diabetes sequentially. The validation of this nomogram also demonstrated good discriminative ability and satisfactory consistency. Finally, early drainage of liver abscess, initial combinational antibiotics, and early Carbapenem-including antibiotic usage were established as favorable factors for therapy in pulmonary affected CA-KPLA patients. CONCLUSION: This study provided an effective model for the early prediction of pulmonary affection in patients with CA-KPLA and some rational strategies for their early therapeutic remission.


Assuntos
Infecções Comunitárias Adquiridas , Infecções por Klebsiella , Abscesso Hepático Piogênico , Pneumonia , Humanos , Klebsiella pneumoniae , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella , Abscesso Hepático Piogênico/epidemiologia , Abscesso Hepático Piogênico/tratamento farmacológico , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia/tratamento farmacológico
10.
Anal Chem ; 94(44): 15525-15533, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36310422

RESUMO

As a strategy that induces gene silencing by the delivery of small interfering RNA (siRNA) targeting a specific gene locus into cells or tissues, RNA interference (RNAi) technology holds the potential to be a powerful tool in a range of intractable disorder therapeutics. However, reliable noninvasive probes for visualizing the siRNA delivery and silencing efficiency have become a major obstacle in siRNA-based treatment. Here, we describe the development of an RNA-binding protein Pumilio/FBF (PUF)-based reporter probe for the monitoring of siRNA delivery efficiency and functional screening of effective siRNA target sites in vivo. This reporter consisted of a Firefly luciferase (Fluc) gene whose expression is regulated by the unique interaction architecture of the PUF protein with its Nanos response element (NRE) target RNA. We showed that a robust and rapid increase in the luminescence signal was detected by the successful delivery of siRNA against the enhanced green fluorescent protein (EGFP) or p53 genes into mammalian cells or the livers of mice. The delivery efficiencies of various commercial transfection vehicles were quantitatively evaluated with this reporter. In addition, we also employed in vivo bioluminescence imaging to screen and identify the most potent siRNA targeting p53. Our study indicates that the positive-readout reporter represents a promising indicator for siRNA optimization and visualization, advancing the development of siRNA therapeutic products.


Assuntos
Inativação Gênica , Mamíferos , Camundongos , Animais , Interferência de RNA , RNA Interferente Pequeno/genética , Genes Reporter/genética , Transfecção
11.
Clin Exp Hypertens ; 44(7): 589-594, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-35766216

RESUMO

OBJECTIVES: We aimed to investigate the differences in clinical features between pulmonary embolism (PE) patients concomitant with lung cancer and without lung cancer (LC) and gain further understanding of the impact of lung cancer on pulmonary embolism. METHODS: This retrospective study sampled 114 patients diagnosed with pulmonary embolism from January 2017 to April 2021 in the First Affiliated Hospital of Soochow University. The patients were categorized into the LC group (n = 22) or non-LC group (n = 92). Myocardial injury, coagulation and blood cell parameters, along with imaging findings, were analyzed for the two groups. The primary outcome measure was the 90-day mortality. RESULTS: Of the 114 patients with pulmonary embolism in the present study, the 90 intermediate-risk patients were enrolled for further investigations. Compared to the non-LC group, patients in the LC group had milder myocardial injury, more severe coagulation function disorder, a higher incidence of central PE and a smaller change in diameter of the main pulmonary artery. We found that the occurrence of pericardial effusion created the risk of lung cancer in patients with pulmonary embolism, but there was no increase in the 90-day mortality for non-LC group versus LC group. CONCLUSION: Intermediate risk PE patients concomitant with lung cancer seem to be more likely to present specific clinical features, accordingly, clinicians must pay great attention to PE patients concomitant with lung cancer and implement effective treatments to simultaneously manage the two conditions.


Assuntos
Neoplasias Pulmonares , Embolia Pulmonar , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco
12.
Ultrason Imaging ; 44(5-6): 204-212, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950552

RESUMO

Photoacoustic (PA) imaging technology is of some value in medical diagnoses such as breast cancer detection, vasculature imaging, and surgery navigating. While as most imaging objects are bounded, the received RF signals consist of the direct-arrived signals (DAS) from the PA sources and the boundary-reflected signals (BRS). The undesired BRS will severely impair the quality during the image reconstruction. They will bring in many artifacts and confuse the actual shape and location of the PA sources. We improved the reconstruction procedure by removing the BRS before the regular reconstruction process to suppress those artifacts. To verify our proposed method, we compared the results of the conventional and optimized procedures experimentally. In terms of qualitative observation, the reconstructed images by the optimized procedure illustrate fewer artifacts and more accurate shapes of the PA sources. To quantitatively evaluate the traditional and the optimized imaging procedure, we calculated the Distribution Relative Error (DRE) between each experiment result and its standard drawing of the phantoms. For both phantoms and the ex-vivo sample, the DREs of reconstruction result by the optimized reconstruction procedure decrease significantly. The results suggest that the optimized reconstruction process can effectively suppress the reflection artifacts and improve the shape accuracy of the PA sources.


Assuntos
Artefatos , Técnicas Fotoacústicas , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Técnicas Fotoacústicas/métodos
13.
Cancer Cell Int ; 21(1): 157, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685462

RESUMO

BACKGROUND: Uterine leiomyosarcoma (ULMS) is a malignant tumor found in the smooth muscle lining the walls of the uterus. Cancer stem cells (CSCs) are responsible for metastasis, drug resistance, and relapse of cancer, resulting in treatment failure. However, little is known about CSCs and their associated-markers in ULMS. We aimed to characterize and identify a subpopulation of CD133+ cancer stem-like cells derived from SK-UT-1 cell line. METHODS: SK-UT-1 cells were sphere-forming cultured in vitro. We also sorted the CD133+ cells derived from SK-UT-1 cell line by immunomagnetic beads. CD133+ subpopulation and apoptotic cells were detected by flow cytometry. Self-renewal and anchorage-independent growth capabilities were examined using sphere and colony formation assays. The tumorigenicity of the fourth-passage spheres and parental SK-UT-1 cells was used by mouse xenograft model in vivo. Cell proliferation ability and sensitivity to doxorubicin (DXR) were assessed by CCK-8 assay. Cell migration and invasion were tested by wound healing assay or Transwell migration and invasion assays. Expressions of CSC-related marker were analyzed by Western blotting. RESULTS: The fourth-passage spheres were defined as a CD133+ cell population, which was accompanied by increase of sphere and colony forming rate, migration and invasion abilities, as well as drug-resistant properties in vitro. Moreover, the fourth-passage spheres showed a stronger tumorigenic potential in vivo. CD133+ cell population sorted from SK-UT-1 line showed an increased ability in sphere and colony formation, proliferation, migration, invasion, resistance to apoptosis after treatment with doxorubicin (DXR) compared with CD133- cell population. The expression levels of CSCs-related markers (e.g., CD44, ALDH1,BMI1, and Nanog), were significantly elevated in CD133+ cells compared with those in CD133- cells. CONCLUSIONS: Collectively, our findings indicated that CD133 may be a significant marker for cancer stem-like cells, and it may be a potential therapeutic target for human ULMS.

14.
World J Surg Oncol ; 19(1): 182, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154596

RESUMO

BACKGROUND: The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC. METHODS: We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS). RESULTS: We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67-0.86, p<0.001) but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than monochemotherapy (HR 0.59, 95% Cl 0.52-0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR 0.76, 95% Cl 0.61-0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR 0.91, 95% Cl 0.82-1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea. CONCLUSION: These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Prognóstico
15.
Environ Res ; 181: 108803, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31761334

RESUMO

A reducing agent can reduce Co3+ to Co2+ in LiCoO2, thus increasing the leaching efficiency and extraction rate of Co-based cathode materials from spent lithium-ion batteries (LIBs). Herein, ethanol was employed as the reducing agent to leach LiCoO2 obtained from LIBs in a sulfuric acid solution. The effects of operating temperatures (50-90 °C), dosage of ethanol (0-20 vol%), concentration of sulfuric acid (2-6 mol/L), and solid/liquid ratio (10-40  g/L) on the leaching efficiency of LiCoO2 were investigated. By adding 5 vol% ethanol in a 6 mol/L sulfuric acid solution at 90 °C, the extraction efficiency of Co and Li are both over 99%, meaning that ethanol can reduce Co3+ to Co2+ while the ethanol was oxidized to acetic acid. The dissolution of LiCoO2 obeys the residue layer diffusion control model. Although ethanol is a promising reducing agent, future efforts should pay to the management of the secondary wastewater. Overall, the ethanol can be used as a reducing agent to assist the leaching of cathode materials from spent LIBs.


Assuntos
Cobalto , Fontes de Energia Elétrica , Lítio , Reciclagem/métodos , Eletrodos , Etanol
16.
Mol Ther ; 25(9): 2129-2139, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28571917

RESUMO

A major challenge for cancer chemotherapy is the development of safe and clinically effective chemotherapeutic agents. With its low toxicity profile, sophocarpine (SC), a naturally occurring tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L, has shown promising therapeutic properties, including anti-inflammatory, anti-nociceptive, and antivirus activities. However, the antitumor efficacy of SC and its underlying mechanisms have not been completely delineated. In the present study, the inhibitory effect of SC on head and neck squamous cell carcinoma (HNSCC) progression and possible mechanisms for this effect involving microRNA-21 (miR-21) regulation were investigated. By cell viability, Transwell, and wound healing assays, we show that SC effectively inhibited proliferation, invasion, and migration of HNSCC cells. Moreover, SC exerted its growth-inhibitory effect via the downregulation of miR-21 expression by blocking Dicer-mediated miR-21 maturation. Furthermore, SC treatment led to the increased expression of PTEN and p38MAPK phosphorylation as well as the reversal of epithelial-mesenchymal transition (EMT), which was rescued by ectopic expression of miR-21 in cells. Notably, SC dramatically repressed tumor growth without observable tissue cytotoxicity in a mouse xenograft model of HNSCC. Our findings offer a preclinical proof of concept for SC as a leading natural agent for HNSCC cancer therapy.


Assuntos
Alcaloides/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , MicroRNAs/genética , Alcaloides/química , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Camundongos , MicroRNAs/química , Mutação , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Biochem Biophys Res Commun ; 493(4): 1464-1470, 2017 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-28988111

RESUMO

AIM: This study intented to clarify the intracellular effect of PAI-1 on Non-small cell lung cancer (NSCLC) metastasis and the precise mechanism involved. METHODS: The metastatic properties of NSCLC cells were determined by transwell assays and wound-healing assay in vitro. The mRNA and protein expressions of genes were analyzed by Real-time qPCR and western blot, respectively. Pulmonary metastasis model of NSCLC cells was established to evaluate the pro-metastasis effect of PAI-1 and anti-metastatic effect of miR-34a in vivo. The gene targets of miR-34a were confirmed by luciferase reporter assays. Chromatin immunoprecipitation assay was employed to detect the transcriptional regulation of miR-34a. Co-immunoprecipitation assay was performed to observe the interaction of proteins. RESULTS: PAI-1, which was elevated in NSCLC patients with recurrence and metastasis, augmented NSCLC metastasis and was negatively related to the prognosis of NSCLC. miR-34a, which was decreased in NSCLC patients with metastasis, attenuated NSCLC metastasis and was positively correlated with the prognosis of NSCLC. Moreover, PAI-1 was identified as the target gene of miR-34a and activated the Stat3 signaling pathway to promote epithelial-mesenchymal transition (EMT) in NSCLC cells. PAI-1 interacted with PIAS3 to regulate Stat3-dependent gene expression and miR-34a was transcriptionally suppressed by Stat3 to form a positive regulatory loop through Stat3 signaling. CONCLUSION: Our findings suggest that PAI-1 and miR-34a, which can be clinically utilized as biomarkers for the clinical prognosis or diagnosis of NSCLC, are potential targets for the treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Chaperonas Moleculares/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteínas Inibidoras de STAT Ativados/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Retroalimentação Fisiológica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Chaperonas Moleculares/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Prognóstico , Proteínas Inibidoras de STAT Ativados/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais
18.
Acta Biochim Biophys Sin (Shanghai) ; 48(6): 554-62, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27151296

RESUMO

High mobility group box1 (HMGB1), as a damage-associated inflammatory factor, contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, we explored the role of HMGB1 in CDI (Clostridium difficile infection) by in vivo and in vitro experiments. Our results showed that HMGB1 might play an important role in the acute inflammatory responses to C. difficile toxin A (TcdA), affect early inflammatory factors, and induce inflammation via the HMGB1-TLR4 pathway. Our study provides the essential information for better understanding the molecular mechanisms of CDI and the potential new therapeutic strategies for the treatment of this infection.


Assuntos
Toxinas Bacterianas/toxicidade , Enterocolite Pseudomembranosa/etiologia , Enterotoxinas/toxicidade , Proteína HMGB1/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Enterocolite Pseudomembranosa/metabolismo , Enterocolite Pseudomembranosa/patologia , Feminino , Ácido Glicirrízico/farmacologia , Proteína HMGB1/antagonistas & inibidores , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Camundongos , Células RAW 264.7 , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/metabolismo
19.
Pak J Pharm Sci ; 29(5 Suppl): 1869-1876, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28476716

RESUMO

Amino glycosides, one of the important broad-spectrum antibacterials, treat clinically against various bacterial infections. In the last decade, amino glycoside micro arrays have become one of main technologies for analyzing interactions between antibiotics and therapeutic targets in a high-throughput manner. A series of methods have been developed to immobilize amino glycosides on the functional group-coated glass slides in a micro array format. The amino glycoside micro arrays technology has been widely used for rapid determination of interactions of the amino glycosides with ribosome RNAs (rRNA) and proteins. Several clinically used amino glycosides are mainly exerted by binding to bacterial rRNA, which leads to mistranslation of protein. However, amino glycosides are losing efficacy due to the increased resistance mostly caused by enzymes modification. The micro array-based technology is mainly used in developing novel antibiotics, discovering new RNA targets, and identifying inhibitors of resistance-causing enzymes. This review will focus on the construction of amino glycoside micro arrays, their recent status and applications in biological and biomedical research and some challenges in further research.


Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Aminoglicosídeos/química , Antibacterianos/química , Sequência de Carboidratos
20.
World J Surg ; 39(4): 890-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25472890

RESUMO

BACKGROUND: Human factors research has suggested benefits of consistent teams yet no surgical team consistency measures have been established for teamwork improvement initiatives. METHODS: Retrospective analysis was conducted of teams performing consecutive elective procedures of unilateral primary total knee and hip replacement between June 2008 and May 2010 at a large tertiary medical center. Surgeons who performed fewer than 50 cases of the procedures during the study period were excluded. A team was defined as consistent when its nurse and surgical technologist members were both among the three most frequent working with the surgeon during the study period. Odds ratios for prolonged operative time (in the longest quartile), prolonged hospital stay (longer than median), and 30-day all-cause readmissions were adjusted for patient characteristics (sex, age, comorbidity, American Society of Anesthesiology status), surgery characteristics (procedures, time of day), and surgeons. RESULTS: Inconsistent teams performed 61% of the 1,923 cases with eight surgeons, each of which worked with a median of 43.5 (range, 28-58) nurses and 29 (range, 13-47) technologists. Inconsistent teams were associated with higher likelihood of prolonged operative time [odds ratio 1.52, 95% confidence interval (CI) 1.20-1.91], higher likelihood of prolonged hospital stay (odds ratio 1.51, 95% CI 1.23-1.86), and more readmissions (adjusted odds ratio 1.42, 95% CI 1.07-1.89). CONCLUSIONS: Team consistency was an independent predictor of prolonged operative time, prolonged hospital stay, and 30-day hospital readmission in elective, primary, unilateral total knee, and hip replacement procedures, after adjusting for patient and surgery characteristics and surgeons.


Assuntos
Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Tempo de Internação , Duração da Cirurgia , Equipe de Assistência ao Paciente/organização & administração , Readmissão do Paciente , Idoso , Artroplastia de Quadril/estatística & dados numéricos , Artroplastia do Joelho/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Tempo
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