Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 314
Filtrar
1.
Artigo em Chinês | MEDLINE | ID: mdl-34628818

RESUMO

Objective:To observe the effect of nasal mucosa flap in the repair of nasopharyngeal skull base bone exposure after radiotherapy for nasopharyngeal carcinoma, and to provide a basis for the repair with nasal mucosa flap in skull base bone exposure after radiotherapy. Methods:The clinical data of 8 patients who underwent nasal endoscopic surgery were analyzed retrospectively. The survival of mucosal flap, the mucosal epithelialization of bone defect or exposed site, the improvement of main clinical symptoms and complications were followed up after operation. Results:Severe mucosal flap necrosis and bone exposure occurred in 1 case after operation, in the other 7 cases, the mucosal flap survived and the mucosal epithelium of nasopharynx recovered well. After operation, most of the patients' clinical symptoms such as headache and nasal odor were improved compared with those before operation. Conclusion:Nasal mucosal flap is a safe and minimally invasive autogenous material with good biocompatibility. It has a good application prospect in repairing bone defect or exposure of nasopharyngeal skull base after radiotherapy and is worth popularizing in clinic.


Assuntos
Neoplasias Nasofaríngeas , Procedimentos Cirúrgicos Reconstrutivos , Humanos , Mucosa Nasal , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Nasofaringe , Estudos Retrospectivos , Base do Crânio/cirurgia
3.
J Biomed Nanotechnol ; 17(8): 1535-1544, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544531

RESUMO

This study aimed to detect miR-455-5p and S1PR1 proteins using nanoparticle-assisted polymerase chain reaction (nano-PCR) to determine their correlation with cervical carcinoma prognosis. To achieve this study's goals, we selected 48 cervical carcinoma patients between January 2014 to January 2016 and subjected them to the miR-455-5p test by nano-PCR. The collected samples were then divided into two groups based on miR-455-5p levels. We had four HeLa cell groups, one group as the control, and one group overexpressed the miR-455-5p protein. A third group was miR-455-5p silent, and a separate group overexpressed both the miR-455-5p and S1PR1 proteins. Results also proved that the nano-PCR had a higher sensitivity than RT-PCR, and patients with poor prognosis had lesser miR-455-5p levels. Similarly, high levels of miR-455-5 contributed to cancer cell apoptosis and migration inhibition by targeting S1PR1 expression negatively. These two biomarkers are therefore significantly related to the prognosis of cervical carcinoma patients.


Assuntos
Carcinoma , Nanopartículas Metálicas , MicroRNAs , Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Ouro , Células HeLa , Humanos , Fosfatos , Reação em Cadeia da Polimerase , Esfingosina , Neoplasias do Colo do Útero/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-34524634

RESUMO

Dispersin B (DspB) is a member of glycoside hydrolase family 20 (GH20) and catalyzes degradation of biofilms forming by pathogenic bacteria such as Staphylococcus aureus. Magnetoreceptor (MagR) is a magnetic protein that can be used as a fusion partner for functionally immobilizing proteins on magnetic surfaces. In the present study, a recombinant protein DspB-MagR was constructed by fusing MagR to the C-terminus of DspB and expressed in Escherichia coli. Magnetic immobilization of purified DspB-MagR on magnetic core-shell structured Fe3O4@SiO2 nanoparticles was achieved and characterized by means of various techniques including SDS-PAGE, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential measurement, and scanning electron microscopy. It was evaluated the influence of temperature, pH, and storage time on the performance of immobilized DspB-MagR on Fe3O4@SiO2 nanoparticles. Removal of biofilms forming by Staphylococcus aureus and other medical sourced bacterial species was achieved by using Fe3O4@SiO2 nanoparticles loading with DspB-MagR. This work promoted potential applications of DspB and similar enzymes for medical purposes.

5.
Microb Physiol ; : 1-12, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34535588

RESUMO

Postnatal colonization and development of the gut microbiota is linked to health and growth. A comprehensive understanding of the postnatal compositional changes and development of the microbial community is helpful to understand the gut health and improve the survival rate of South China tiger cubs (Panthera tigris amoyensis). Fecal samples from three tiger cubs were collected on the day of birth in 2018 (June 17-21 [G0], July 18 [G1], July 31 [G2], and August 7 [G3]). The 16S rRNA genes of the fecal microflora were sequenced. Results showed that 38 phyla, 58 classes, 134 orders, 272 families, and 636 genera of bacteria from 3,059 operational taxonomic units were identified from 12 fecal samples. The diversity and abundance of species of group G0 were significantly higher (p < 0.05 or 0.01) than those of groups G2 and G3. The predominant phylum was Proteobacteria in groups G0 and G1 (38.85% and 48%, respectively) and Firmicutes in groups G2 and G3 (71.42% and 75.29%, respectively). At the phylum level, the abundance of Deinococcus-Thermus was significantly decreased in groups G1, G2, and G3 as compared to group G0 (p < 0.05), while that of Firmicutes was significantly increased in groups G2 and G3 (p < 0.05). At the genus level, the abundance of Faecalibacterium, Ralstonia, and unidentified Rickettsiales was significantly decreased in groups G1, G2, and G3 as compared with group G0 (p < 0.05), while that of Pseudomonas was significantly decreased in groups G2 and G3 (p < 0.05). The composition and structure of fecal microbiota of South China tiger cubs changed after birth.

6.
Lung Cancer ; 160: 84-91, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34479175

RESUMO

OBJECTIVES: CD66b positive tumor-infiltrating neutrophils (TINs) are key immunity cells in the tumor microenvironment (TME). However, their relationship with clinicopathological features, immune checkpoints (ICs), and prognostic value remains undetermined in lung adenocarcinoma (LUAD). In this study, we aimed to characterize the infiltration by TINs and the prognostic significance in patients with surgically resected LUAD. MATERIALS AND METHODS: Expression of CD66b and ICs, including PD-L1, PD-1, CTLA4, LAG3, TIM3, TIGIT, VISTA, and BTLA, in both cancer cell and tumor-infiltrating lymphocytes (TILs) were estimated by immunohistochemistry in resected LUAD. The associations between CD66b expression and clinicopathological characteristics in patient prognoses were analyzed. We also verified results in another cohort from 85 patients with untreated LUAD and further analyzed the correlation between CD66b expression and EGFR and KRAS mutation status in addition to the rearrangement of the anaplastic lymphoma receptor tyrosine kinase gene (ALK). RESULTS: A total of 240 patients were included in this study. CD66b expression was observed in 87 (36.2%) samples. ICs including PD-L1, PD-1, CTLA4, LAG3, TIM3, TIGIT, VISTA, and BTLA were observed in percentages that ranged from 23.8% to 59.4%. Positive CD66b expression significantly correlated with smoking history (p = 0.029), pathological stage (p = 0.040), and the positive expression of LAG-3 (p < 0.001), PD-1 (p = 0.008), CTLA-4 (p = 0.013), TIM-3 (p = 0.025), TIGIT (p = 0.002), PD-L1 in TILs (p = 0.015), and PD-L1 in tumor cells (p = 0.010). CD66b positivity was significantly associated with worse recurrence-free survival (RFS) (hazard ratio, HR, 1.687; 95% confidence interval, CI, 1.058-2.690, p = 0.028) and overall survival (OS) (HR, 1.667; 95% CI, 1.097-2.534, p = 0.017). Subgroup analysis revealed that the CD66b+/LAG-3 + group had the worst RFS (5-year rate: 39.5%,) and OS (5-year rate: 53.7%,), while the CD66b-/LAG-3 - group had the best RFS (5-year rate: 65.6%) and OS (5-year rate: 78.8%). The p value in analysis of RFS and OS was 0.005 and 0.008, respectively. In the verification set, high expression of CD66b was also significantly correlated with the positive expression of LAG-3 (p < 0.001), PD-1 (p = 0.002), CTLA-4 (p = 0.034), TIM-3 (p = 0.049), PD-L1 in TILs (p = 0.003), and PD-L1 in tumor cells (p = 0.045). There was no correlation between CD66b expression and positive TIGIT expression (p = 0.077), EGFR mutation (p = 0.223), KRAS mutation (p = 0.151), and ALK fusion (p = 0.310). CONCLUSION: CD66b had a relatively high positive expression rate and special clinicopathological features in patients with LUAD. CD66b + TINs were related to the expression of ICs and associated with poor prognoses in LUAD. A combination of CD66b and ICs, especially LAG-3 could further stratify patients into different groups with distinct prognoses.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Procedimentos Cirúrgicos Pulmonares , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Prognóstico , Microambiente Tumoral
7.
Bioengineered ; 12(1): 5971-5984, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34488536

RESUMO

Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive disease that leads to an increased disability rate. This study aimed to ascertain biomarkers, infiltrating immune cells, and therapeutic drugs for SONFH. The gene expression profile of the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the NetworkAnalyst platform. Functional enrichment, protein-protein interaction network (PPI), and module analyses were performed using Metascape tools. An immune cell abundance identifier was used to explore immune cell infiltration. Furthermore, hub genes were identified based on maximal clique centrality (MCC) evaluation using cytoHubba application and confirmed by qRT-PCR using clinical samples. Finally, the L1000 platform was used to determine potential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effects of aspirin. In total, 429 DEGs were identified in SONFH samples. Functional enrichment analysis showed that these DEGs were enriched in myeloid leukocyte activation and osteoclast differentiation processes. A set of nine immune cell types was confirmed to be markedly different between the SONFH and control samples. All 10 hub genes were significantly highly expressed in the serum of SONFH patients, as shown by qRT-PCR. Finally, the therapeutic effect of aspirin on SONFH was examined in animal experiments. Taken together, our data revealed the hub genes and infiltrating immune cells in SONFH, and we also screened potential drugs for use in SONFH treatment.

8.
Medicine (Baltimore) ; 100(33): e26760, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414932

RESUMO

ABSTRACT: The present study reported early clinical outcomes and perioperative precautions for medical staffs during joint arthroplasty procedures in SARS-CoV-2-infected patients.The medical records of 8 patients with SARS-CoV-2 infection who underwent joint arthroplasty from January 19 to September 24, 2020 were retrospectively reviewed and analyzed. Perioperative precautions and follow-up (time length varies from 6 month to 13 months, 11 months in average) for SARS-CoV-2 infection of medical staffs were reported.All patients recovered well from both the primary disease and SARS-CoV-2 infection. Significant improved Visual analogue scale was observed with no major complications or recurrence of the COVID-19 at discharge. There was no evidence indicating SARS-CoV-2 infection in any health providers.Elective joint arthroplasties for patients in recovery period of SARS-CoV-2 infection could be continued under comprehensive preoperative evaluation and appropriate medical protection. For patients with currently confirmed or highly suspected COVID-19, the operation should be carried out only if it was essential.


Assuntos
Artroplastia de Quadril , COVID-19/transmissão , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Corpo Clínico Hospitalar , Assistência Perioperatória/métodos , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Protocolos Clínicos , Feminino , Quadril/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Equipamento de Proteção Individual , Cuidados Pós-Operatórios , Complicações Pós-Operatórias , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento , Fluxo de Trabalho
9.
Angew Chem Int Ed Engl ; 60(38): 20695-20699, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34288332

RESUMO

Due to the high risk of heart disease caused by the intake of trans fatty acids, a method to eliminate trans fatty acids from foods has become a critical issue. Herein, we engineered fatty acid photo-decarboxylase from Chlorella variabilis (CvFAP) to selectively catalyze the decarboxylation of trans fatty acids to yield readily-removed hydrocarbons and carbon dioxide, while cis fatty acids remained unchanged. An efficient protein engineering based on FRISM strategy was implemented to intensify the electronic interaction between the residues and the double bond of the substrate that stabilized the binding of elaidic acid in the channel. For the model compounds, oleic acid and elaidic acid, the best mutant, V453E, showed a one-thousand-fold improvement in the trans-over-cis (ToC) selectivity compared with wild type (WT). As the first report of the direct biocatalytic decarboxylation resolution of trans/cis fatty acids, this work offers a safe, facile, and eco-friendly process to eliminate trans fatty acids from edible oils.

10.
Nat Ecol Evol ; 5(9): 1309-1316, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34312523

RESUMO

In addition to habitat loss and fragmentation, demographic processes-the vagaries of births, deaths and sex ratio fluctuations-pose substantial threats to wild giant panda populations. Additionally, climate change and plans for the Giant Panda National Park may influence (in opposing directions) the extinction risk for wild giant pandas. The Fourth National Giant Panda Census showed pandas living in 33 isolated populations. An estimated 259 animals live in 25 of these groups, ~14% of the total population. We used individual-based models to simulate time series of these small populations for 100 years. We analysed the spatial pattern of their risk of extinction under current conditions and multiple climate change models. Furthermore, we consider the impact of the proposed Giant Panda National Park. Results showed that 15 populations face a risk >90%, and for 3 other populations the risk is >50%. Of the 15 most at-risk populations, national parks can protect only 3. Under the Representative Concentration Pathway 8.5 climate change scenario, the 33 populations will probably further divide into 56 populations. Some 41 of them will face a risk >50% and 35 face a risk >90%. Although national parks will probably connect some fragmented habitats, 26 populations will be outside national park planning. Our study gives practical advice for conservation policies and management and has implications for the conservation of other species in the world that live in isolated, fragmented habitats.


Assuntos
Ursidae , Animais , Mudança Climática , Conservação dos Recursos Naturais , Ecossistema , Parques Recreativos
11.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(7): 829-835, 2021 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-34308589

RESUMO

Objective: To compare the early effectiveness of arthroscopic suture bridge technique and conventional double tunnel suture technique in the treatment of avulsion fracture of posterior cruciate ligament (PCL) insertion. Methods: Between June 2013 and December 2018, 62 patients with tibial avulsion fracture of PCL insertion that met the criteria were selected and randomly divided into trial group (using arthroscopic suture bridge technique) and control group (using conventional double tunnel suture technique), 31 cases in each group. There was no significant difference in gender, age, injured side, cause of injury, time from injury to operation, Meyers & McKeever classification, Kellgren-Lawrence classification, and preoperative knee range of motion, difference of posterior relaxation of bilateral knee joints, International Knee Documentation Committee (IKDC) score, and Lysholm score between the two groups ( P>0.05). The operation time and IKDC score, Lysholm score, knee range of motion, the difference of posterior relaxation of bilateral knee joints (measured by KT-2000 under knee flexion of 90° and 30 lbs) were recorded and compared between the two groups before operation and at 3 and 12 months after operation. Results: Both groups successfully completed the operation, and the operation time of the trial group and the control group were (61.81±6.83) minutes and (80.42±4.22) minutes respectively, showing significant difference between the two groups ( t=12.911, P=0.000). All the incisions healed by first intention, and there was no wound infection and other early postoperative related complications. All patients were followed up 13-18 months (mean, 14.6 months). The fractures in both groups healed at 3 months after operation. No knee pain, limited movement, or other complications occurred. At 3 and 12 months after operation, the IKDC score, Lysholm score, knee range of motion, and the difference of posterior relaxation of bilateral knee joints in both groups were significantly improved when compared with preoperative ones, and further improved at 12 months after operation when compared with at 3 months after operation ( P<0.05). At each time point after operation, the above indexes and the grade of the difference of posterior relaxation of bilateral knee joints in the trial group were significantly better than those in the control group ( P<0.05). Conclusion: Arthroscopic suture bridge technique in the treatment avulsion fracture of PCL insertion is simple and reliable, which can significantly improve the function and stability of the knee joint and obtain satisfactory early effectiveness.


Assuntos
Fratura Avulsão , Ligamento Cruzado Posterior , Fraturas da Tíbia , Artroscopia , Humanos , Articulação do Joelho/cirurgia , Ligamento Cruzado Posterior/cirurgia , Técnicas de Sutura , Suturas , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
12.
Huan Jing Ke Xue ; 42(8): 3837-3846, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309270

RESUMO

The adsorption of heavy metals by suspended sediment particles is a key process in the migration of heavy metals in lakes and is affected by various environmental conditions. To reveal the effects and mechanisms of dissolved organic matter (DOM) on the adsorption of copper ions by suspended sediment particles, a Cu(Ⅱ) adsorption test was conducted through a laboratory simulation test. The results showed that DOM promoted the adsorption of Cu(Ⅱ) onto the suspended particles. Under the respective influences of fulvic acid and DOM extracted from the sediment of the Xiangjiang River, the adsorption percentage of Cu(Ⅱ) increased from 71.51% to 75.31% and 85.69%. Scanning electron microscope-energy spectroscopy results showed that under the influence of DOM, Cu(Ⅱ) existed inside the sediment particles after being adsorbed. The results of UV-visible (UV-Vis) spectroscopy showed that Cu(Ⅱ) and DOM were first complexed and then dissociated during the adsorption reaction. The results of fluorescent excitation-emission matrix spectroscopy combined with parallel factor analysis and synchronous fluorescence spectroscopy combined with two-dimensional correlation analysis indicate that protein-like components promoted the adsorption of Cu(Ⅱ) onto the sediment suspended particles. In particular, tyrosine-like components played a critical role in promoting adsorption. However, humic-like components hardly promote this adsorption. This study has improved the theory of heavy metal migration in lakes and can be used as a basis for the prevention and control of heavy metal pollution in sediments.


Assuntos
Cobre , Substâncias Húmicas , Adsorção , Sedimentos Geológicos , Substâncias Húmicas/análise , Espectrometria de Fluorescência
13.
Hum Immunol ; 82(10): 775-781, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34294459

RESUMO

Th9 is a subset of CD4+ T cells that mainly secrete IL-9. Th9/IL-9 participates in immune response during Staphylococcus aureus and methicillin-resistant Staphylococcus aureus pneumonia (MRSA) infection. Here, we collected bronchoalveolar lavage fluid (BALF) from 30 children with MRSA pneumonia (MRSA group) and 10 children with bronchial foreign bodies (Control group). RT-PCR, ELISA and flow cytometry were used to detect the expression of miR-155 and IL-9 in BALF and the number of Th9 cells. CD4+ T cells isolated from BALF of MRSA and Control group were transfected with miR-155 mimic or inhibitor, and then induced Th9 cell differentiation. The results showed that the expression of miR-155 and IL-9 were significantly increased in BALF and Th9 cell of MRSA group, as well as the number of Th9 cells. miR-155 mimic upregulated IL-9 mRNA expression, IL-9 secretion and increased number of Th9 cells. On the contrary, miR-155 inhibitor inhibited IL-9 mRNA expression, IL-9 secretion and decreased number of Th9 cells. The dual luciferase assays demonstrated miR-155 can target binding to SIRT1 3'UTR. Moreover, overexpression of SIRT1 could reverse the effect of miR-155 mimic on IL-9 expression level, Th9 cell number and transcription factors PU.1 and IRF4 expression. In conclusion, miR-155 regulates Th9 differentiation in children with MRSA by targeting SIRT1.

14.
Sci Rep ; 11(1): 13247, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168166

RESUMO

Probiotics when applied in complex evolving (micro-)ecosystems, might be selectively beneficial or detrimental to pathogens when their prophylactic efficacies are prone to ambient interactions. Here, we document a counter-intuitive phenomenon that probiotic-treated zebrafish (Danio rerio) were respectively healthy at higher but succumbed at lower level of challenge with a pathogenic Vibrio isolate. This was confirmed by prominent dissimilarities in fish survival and histology. Based upon the profiling of the zebrafish microbiome, and the probiotic and the pathogen shared gene orthogroups (genetic niche overlaps in genomes), this consequently might have modified the probiotic metabolome as well as the virulence of the pathogen. Although it did not reshuffle the architecture of the commensal microbiome of the vertebrate host, it might have altered the probiotic-pathogen inter-genus and intra-species communications. Such in-depth analyses are needed to avoid counteractive phenomena of probiotics and to optimise their efficacies to magnify human and animal well-being. Moreover, such studies will be valuable to improve the relevant guidelines published by organisations such as FAO, OIE and WHO.

15.
Nat Commun ; 12(1): 3983, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172745

RESUMO

Despite the well-established chemical processes for C-D bond formation, the toolbox of enzymatic methodologies for deuterium incorporation has remained underdeveloped. Here we describe a photodecarboxylase from Chlorella variabilis NC64A (CvFAP)-catalyzed approach for the decarboxylative deuteration of various carboxylic acids by employing D2O as a cheap and readily available deuterium source. Divergent protein engineering of WT-CvFAP is implemented using Focused Rational Iterative Site-specific Mutagenesis (FRISM) as a strategy for expanding the substrate scope. Using specific mutants, several series of substrates including different chain length acids, racemic substrates as well as bulky cyclic acids are successfully converted into the deuterated products (>40 examples). In many cases WT-CvFAP fails completely. This approach also enables the enantiocomplementary kinetic resolution of racemic acids to afford chiral deuterated products, which can hardly be accomplished by existing methods. MD simulations explain the results of improved catalytic activity and stereoselectivity of WT CvFAP and mutants.


Assuntos
Carboxiliases/química , Carboxiliases/metabolismo , Chlorella/enzimologia , Deutério/química , Carboxiliases/genética , Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Catálise , Descarboxilação , Óxido de Deutério/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Engenharia de Proteínas/métodos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
16.
Front Oncol ; 11: 669518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178653

RESUMO

In non-small-cell lung carcinoma (NSCLC), aberrant activation of mammalian target of rapamycin (mTOR) contributes to tumorigenesis and cancer progression. PQR620 is a novel and highly-potent mTOR kinase inhibitor. We here tested its potential activity in NSCLC cells. In primary human NSCLC cells and established cell lines (A549 and NCI-H1944), PQR620 inhibited cell growth, proliferation, and cell cycle progression, as well as cell migration and invasion, while inducing significant apoptosis activation. PQR620 disrupted assembles of mTOR complex 1 (mTOR-Raptor) and mTOR complex 2 (mTOR-Rictor-Sin1), and blocked Akt, S6K1, and S6 phosphorylations in NSCLC cells. Restoring Akt-mTOR activation by a constitutively-active Akt1 (S473D) only partially inhibited PQR620-induced cytotoxicity in NSCLC cells. PQR620 was yet cytotoxic in Akt1/2-silenced NSCLC cells, supporting the existence of Akt-mTOR-independent mechanisms. Indeed, PQR620 induced sphingosine kinase 1 (SphK1) inhibition, ceramide production and oxidative stress in primary NSCLC cells. In vivo studies demonstrated that daily oral administration of a single dose of PQR620 potently inhibited primary NSCLC xenograft growth in severe combined immune deficient mice. In PQR620-treated xenograft tissues, Akt-mTOR inactivation, apoptosis induction, SphK1 inhibition and oxidative stress were detected. In conclusion, PQR620 exerted potent anti-NSCLC cell activity via mTOR-dependent and -independent mechanisms.

17.
World J Surg Oncol ; 19(1): 158, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039365

RESUMO

BACKGROUND: Bronchopleural fistula (BPF) refers to an abnormal channel between the pleural space and the bronchial tree. It is a potentially fatal postoperative complication after pulmonary resection and a complex challenge for thoracic surgeons because many patients with BPF ultimately develop refractory empyema, which is difficult to manage and has a major impact on quality of life and survival. Therefore, an operative intervention combined with conservative and endoscopic therapies may be required to control infection completely, to occlude BPF, and to obliterate the empyema cavity during treatment periods. CASE PRESENTATION: Two patients who suffered from BPF complicated with chronic empyema after lobectomy were treated in other hospitals for a long time and did not recover. In our department, we performed staged surgery and creatively combined an Amplatzer Septal Occluder (ASO) device (AGA Medical Corp, Golden Valley, MN, USA) with pedicled muscle flap transposition. First, open-window thoracostomy (OWT), or effective drainage, was performed according to the degree of contamination in the empyema cavity after the local infection was controlled. Second, Amplatzer device implantation and pedicled muscle flap transposition was performed at the same time, which achieved the purpose of obliterating the infection, closing the fistula, and tamponading the residual cavity. The patients recovered without complications and were discharged with short hospitalization stays. CONCLUSIONS: We believe that the union of the Amplatzer device and pedicle muscle flap transposition seems to be a safe and effective treatment for BPF with chronic empyema and can shorten the length of the related hospital stay.


Assuntos
Fístula Brônquica , Empiema Pleural , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Empiema Pleural/etiologia , Empiema Pleural/cirurgia , Humanos , Músculos , Pneumonectomia/efeitos adversos , Prognóstico , Qualidade de Vida
18.
Ann Palliat Med ; 10(5): 5046-5054, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34044552

RESUMO

BACKGROUND: Postoperative chronic empyema (PPE) remains a complex challenge for thoracic surgeons. We retrospectively investigated patients with PPE who were treated with free vastus lateralis muscle flap transplantation, and report our results. METHODS: Eight patients with PPE and persistent bronchopleural fistula (BPF) treated in our hospital from January 2015 to June 2019 were retrospectively analyzed, the time since onset of empyema ranged from 5 to 72 months. The operation was performed in two stages, stage I surgery included empyema debridement, rib resection drainage or open-window thoracostomy (OWT), meanwhile, BPF was treated under bronchoscope. Stage II surgery included obliteration of the pleural space by free muscle flap transplantation. The keys to the operation are thorough debridement, closure of the BPF, and complete obliteration of the residual pleural space. The challenge lies in the anastomosis of the lateral femoral circumflex artery and vein that supply the vastus lateralis muscle flap to the thoracodorsal vessels. RESULTS: The free muscle flaps survived in all eight patients. The abscess cavity was completely obliterated with the muscle flap. Good efficacy was achieved with primary wound healing. No serious perioperative complications were reported. No empyema recurrence, atrophy, infection, or necrosis of the muscle flap was seen during the 18- to 72-month follow-up. CONCLUSIONS: The vastus lateralis muscle flap has a large volume with good blood supply and strong antibacterial ability. It can be used for effective obliteration of a large residual cavity caused by empyema and maintains a good thoracic shape. It is an ideal choice for the treatment of postoperative chronic refractory empyema.


Assuntos
Fístula Brônquica , Empiema Pleural , Doenças Pleurais , Fístula Brônquica/cirurgia , Empiema Pleural/cirurgia , Humanos , Músculo Quadríceps/cirurgia , Estudos Retrospectivos
19.
Clinics (Sao Paulo) ; 76: e2604, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34008772

RESUMO

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.


Assuntos
COVID-19 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Projetos Piloto , SARS-CoV-2 , Cordão Umbilical
20.
Pathol Res Pract ; 223: 153463, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33971545

RESUMO

The presence and clinical significance of IL-17 and IL-17-expressing cells have been studied for several cancers, although their correlation with tumor development remains controversial. Peripheral blood was collected from healthy donors and glioma patients to isolate peripheral blood mononuclear cells (PBMCs). The percentage of IL-17-expressing cells and the production of inflammatory cytokines in PBMCs and tissues were measured. Human IL­17 cDNA was then inserted into the pEGFP­N1 plasmid and transfected into the glioma U87MG cell line, and tumstatin was used to block the effect of the IL-17 overexpression. Stem cell transcription factors were evaluated in each group using qRT-PCR and western blotting, and proliferation and migration were detected using colony formation and wound-healing assays. The cells were then subcutaneously inoculated into nude mice to evaluate the growth of glioma. Compared with healthy donors, the PBMCs from glioma patients showed a significant accumulation of IL-17-expressing T cells. Th17 cell differentiation-related cytokines (IL-23, TGF-ß and IL-6) were increased in the tumor microenvironment. IL­17 transfection increased the mRNA and protein expression of stem cell transcription factors in U87MG cells in vitro. The proliferation and migration of U87MG cells were also increased. Moreover, the pEGFP­N1­IL­17­U87MG cells grew more rapidly than other cells. However, tumstatin-treated U87MG cells showed significantly inhibited the effects of IL-17 overexpression. Tumstatin effectively suppressed IL-17-derived U87MG cell growth by downregulating stem cell maintenance factors and inducing proliferation and migration. These findings indicated that IL-17 represents a potential prognostic marker for glioma, while tumstatin has potential in the treatment for glioma.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...