Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 306
Filtrar
1.
Drug Deliv ; 28(1): 2548-2561, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34854786

RESUMO

Effective and accurate delivery of drugs to tissue with spinal cord injury (SCI) is the key to rehabilitating neurological deficits. Sustained-release microspheres (MS) have excellent degradability and can aid in the long-term release of drugs. However, the burst release phenomenon can cause unexpected side effects. Herein, we developed and optimized an injectable poly(lactic-co-glycolic acid) (PLGA) MS loaded with melatonin(Mel), which were mixed further with Laponite hydrogels (Lap/MS@Mel, a micro-gel compound) in order to reduce the burst release of MS. Thus, these MS were able to achieve stable and prolonged Mel release, as well as synergistic Lap hydrogel in order to repair neural function in SCI by in situ injection. In clinical practice, patients with SCI have complicated conditions and significant inter-individual differences, which means that a single route of administration does not meet actual clinical needs. Thus, the nanospheres are synthesized and subsequently coated with platelet membrane (PM) in order to form PM/MS@Mel (nano-PM compound) for sustained and precision-targeted delivery of Mel intravenously in the SCI. Notably, optimized microsphere delivery systems have improved Mel regulation polarization of spinal microglial/macrophages, which can reduce loss of biomaterials due to macrophage-induced immune response during implantation of spinal cord tissue. These two new delivery systems that are based on MS provide references for the clinical treatment of SCI, according to different requirements.

2.
Front Psychiatry ; 12: 783091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916978

RESUMO

Objective: Depression is a common disorder with a high recurrence rate. Since the effect of sleep deprivation on depression in existing studies were inconsistent, the present study aimed to reassess the effects of SD on patients by performing a meta-analysis of updated research. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles before January 20th, 2021. Data on participant characteristics, SD characteristics, adjunctive method and tests for depression were extracted. A comprehensive analysis was conducted to assess the effect of SD on depression and subgroup analysis was used to determine the sources of heterogeneity. Results: In total, 8 articles were included. An SD time of <7 days slightly worsened depression levels [0.24 (-0.21, 0.69); I 2 = 0%; P = 0.43], a time of 7-14 days had antidepressant effects [-1.52 (-2.07, -0.97); I 2 = 19.6%; P = 0.288], and a time of more than 14 days also worsened depression [0.76 (0.12, 1.40); I 2 = 43.7%; P = 0.169]. Conclusion: SD may serve as an effective antidepressant measure in humans when the time was 7-14 days, while a time of <7 days and more than 14 days worsened depression.

3.
Front Psychiatry ; 12: 793804, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966313

RESUMO

Objective: The aim of this study was to perform a quantitative analysis to evaluate the efficacy of cognitive behavioral therapy (CBT) on mood disorders, sleep, fatigue, and its impact on quality of life (QOL) in Parkinson's Disease (PD). Methods: We searched for randomized controlled trials in three electronic databases. Fourteen studies, including 507 patients with PD, met the inclusion criteria. We determined the pooled efficacy by standard mean differences and 95% confidence intervals, using I 2 to reveal heterogeneity. Results: The result showed CBT had a significant effect on depression [-0.93 (95%CI, -1.19 to -0.67, P < 0.001)] and anxiety [-0.76 (95%CI, -0.97 to -0.55, P < 0.001)]. Moderate effect sizes were noted with sleep disorders [-0.45 (95% CI, -0.70 to -0.20, P = 0.0004)]. There was no evident impact of CBT on fatigue or QOL. We found an intervention period >8 weeks was advantageous compared with <8 weeks, and CBT implemented in non-group was more effective than in group. Between the delivery methods, no significant difference was found. Conclusion: We found that CBT in patients with PD was an efficacious therapy for some non-motor symptoms in PD, but not efficacious for fatigue and QOL. These results suggest that CBT results in significant improvement in PD and should be used as a conventional clinical intervention.

4.
Genes (Basel) ; 12(11)2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34828292

RESUMO

This study aims to investigate the differentiation trajectory of osteosarcoma cells and to construct molecular subtypes with their respective characteristics and generate a multi-gene signature for predicting prognosis. Integrated single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data and microarray data from osteosarcoma samples were used for analysis. Via scRNA-seq data, time-related as well as differentiation-related genes were recognized as osteosarcoma tumor stem cell-related genes (OSCGs). In Gene Expression Omnibus (GEO) cohort, osteosarcoma patients were classified into two subtypes based on prognostic OSCGs and it was found that molecular typing successfully predicted overall survival, tumor microenvironment and immune infiltration status. Further, available drugs for influencing osteosarcoma via prognostic OSCGs were revealed. A 3-OSCG-based prognostic risk score signature was generated and by combining other clinic-pathological independent prognostic factor, stage at diagnosis, a nomogram was established to predict individual survival probability. In external independent TARGET cohort, the molecular types, the 3-gene signature as well as nomogram were validated. In conclusion, osteosarcoma cell differentiation occupies a crucial position in many facets, such as tumor prognosis and microenvironment, suggesting promising therapeutic targets for this disease.

5.
Head Neck ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837286

RESUMO

BACKGROUND: Compared to conventional intensity-modulated photon radiation therapy (IMRT), intensity-modulated proton radiation therapy (IMPT) has potential to reduce irradiation-induced late toxicities while maintaining excellent tumor control in patients with nasopharyngeal carcinoma (NPC). However, the relevant cost-effectiveness remains controversial. METHODS: A Markov decision tree analysis was performed under the assumption that IMPT offered normal tissue complication probability reduction (NTCP reduction) in long-term dysphagia, xerostomia, and hearing loss, compared to IMRT. Base-case evaluation was performed on T2N2M0 NPC of median age (43 years old). A Chinese societal willingness-to-pay threshold (33558 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. RESULTS: For patients at median age and having NTCP reduction of 10%, 20%, 30%, 40%, 50%, and 60%, their incremental cost-effectiveness ratios were $102684.0/QALY, $43161.2/QALY, $24134.7/QALY, $13991.6/QALY, $8259.8/QALY, and $4436.1/QALY, respectively; IMPT should provide an NTCP reduction of ≥24% to be considered cost-effective. CONCLUSIONS: IMPT has potential to be cost-effective for average Chinese NPC patients and should be validated clinically.

6.
Gland Surg ; 10(10): 2978-2996, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804885

RESUMO

Background: Breast-conserving surgery followed by radiotherapy is recommended in most women with early-stage unilateral breast cancer. However, its role in contralateral breast cancer (CBC) patients remains unclear. This retrospective study aimed to evaluate the breast cancer-specific survival (BCSS) outcomes after breast-conserving surgery plus radiotherapy compared with mastectomy in women with early-stage (T1-2N0-1M0) CBC. Methods: Data were extracted from the Surveillance, Epidemiology, and End Results database. BCSS was analyzed using the log-rank method, competing risks regression model, and propensity score matching method. Results: A total of 9,336 early-stage CBC patients were included. After multivariable adjustment, no significant difference in BCSS was found between early-stage CBC patients undergoing breast-conserving surgery plus radiotherapy and those undergoing mastectomy [hazard ratio (HR) 1.11, 95% confidence interval (CI): 0.90-1.37, P=0.329]. BCSS was similar in both treatment groups and in the subgroups stratified by age at first primary breast cancer or CBC diagnosis (≤50, 51-60, and >60 years), time interval between cancers (<0.25, 0.25-4, 5-9, and ≤10 years), stage of first primary breast cancer, T classification of CBC, histology and hormone receptors status of both cancers (all P>0.05). Among patients with N1 disease at CBC diagnosis, breast-conserving surgery plus radiotherapy was associated with a boundary significantly improved BCSS (HR 1.45, 95% CI: 1.00-2.12, P=0.050). Among patients who underwent breast-conserving surgery for first primary cancer, bilateral mastectomy for contralateral cancer did not improve BCSS compared with breast-conserving surgery plus radiotherapy (P>0.05). There was no significant difference in BCSS between breast-conserving surgery plus radiotherapy and mastectomy plus radiotherapy (P>0.05). Stable results were obtained after propensity score matching. Conclusions: Breast-conserving surgery plus radiotherapy did not significantly influence BCSS outcomes of patients with early-stage CBC. Bilateral mastectomy and mastectomy plus radiotherapy did not confer a survival advantage over breast-conserving surgery plus radiotherapy in these patients. Future prospective studies are necessary to expand on these results.

7.
Cell Death Discov ; 7(1): 306, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686673

RESUMO

Breast cancer is the most common cancer worldwide. JWA is a microtubule-associated protein that has been identified as a tumor suppressor, and its downregulation in tumors is an independent adverse prognostic factor. The objective of this study was to explore the expression, regulation, and mechanism of JWA in trastuzumab-resistant breast cancers. In this study, we found that JWA expression was lower in trastuzumab-resistant breast cancers than that in trastuzumab-sensitive breast cancers. Furthermore, it was confirmed that overexpression of JWA inhibited proliferation and promoted apoptosis in trastuzumab-resistant breast cancers both in vitro and in vivo. In addition, the low expression of JWA in trastuzumab-resistant breast cancers is associated with a poor prognosis. Combining RNA-sequence datasets and next-generation sequencing, it was found that JWA negatively regulated CDK12, and was involved in the G1-to-S transition of the cell cycle. It has been reported that CDK12 drives breast cancer initiation and induces trastuzumab resistance. Taken together, high expression of JWA could inhibit the growth of trastuzumab-resistant breast cancer, and JWA is a potential predictive marker for trastuzumab resistance. In addition, targeted therapy with JWA may be a novel therapeutic strategy to improve the survival rate of trastuzumab-resistant breast cancer.

8.
Aging (Albany NY) ; 13(17): 21758-21777, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520390

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that commonly occurs worldwide. Usually, Asia, especially China, has a high incidence of esophageal cancer. ESCC often has a poor outcome because of a late diagnosis and lack of effective treatments. To build foundations for the early diagnosis and treatment of ESCC, we used the gene expression datasets GSE20347 and GSE17351 from the GEO database and a private dataset to uncover differentially expressed genes (DEGs) and key genes in ESCC. Notably, we found that replication factor C subunit 4 (RFC4) and guanine monophosphate synthase (GMPS) were upregulated but have been rarely studied in ESCC. In particular, to the best of our knowledge, our study is the first to explore GMPS and ESCC. Furthermore, we found that high levels of RFC4 and GMPS expression may result from an increase in DNA copy number alterations. Furthermore, RFC4 and GMPS were both upregulated in the early stage and early nodal metastases of esophageal carcinoma. The expression of RFC4 was strongly correlated with GMPS. In addition, we explored the relationship between RFC4 and GMPS expression and tumor-infiltrating immune cells (TILs) in esophageal carcinoma. The results showed that the levels of RFC4 and GMPS increased with a decrease in some tumor-infiltrating cells. Upregulated RFC4 and GMPS with high TILs indicate a worse prognosis. In summary, our study shows that RFC4 and GMPS have potential as biomarkers for the early diagnosis of ESCC and may played a crucial role in the process of tumor immunity in ESCC.

9.
Clin Cancer Res ; 27(22): 6265-6278, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526362

RESUMO

PURPOSE: Bladder cancer treatment remains a major clinical challenge due to therapy resistance and a high recurrence rate. Profiling intratumor heterogeneity can reveal the molecular mechanism of bladder cancer recurrence. EXPERIMENTAL DESIGN: Here, we performed single-cell RNA sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on tumors from 13 patients with low recurrence risk, high recurrence risk, and recurrent bladder cancer. RESULTS: Our study generated a comprehensive cancer-cell atlas consisting of 54,971 single cells and identified distinct cell subpopulations. We found that the cancer stem-cell subpopulation is enriched during bladder cancer recurrence with elevated expression of EZH2. We further defined a subpopulation-specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of the NCAM1 gene, thereby inactivating the cell invasive and stemness transcriptional program. Furthermore, taking advantage of this large single-cell dataset, we elucidated the spectrum of epithelial-mesenchymal transition (EMT) in clinical samples and revealed distinct EMT features associated with bladder cancer subtypes. We identified that TCF7 promotes EMT in corroboration with single-cell ATAC with high-throughput sequencing (scATAC-seq) analysis. Additionally, we constructed regulatory networks specific to recurrent bladder cancer. CONCLUSIONS: Our study and analytic approaches herein provide a rich resource for the further study of cancer stem cells and EMT in the bladder cancer research field.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34516378

RESUMO

Stroke is a world-leading disease for causing disability. Brain-computer interaction (BCI) training has been proved to be a promising method in facilitating motor recovery. However, due to differences in each patient's neural-clinical profile, the potential of recovery for different patients can vary significantly by conducting BCI training, which remains a major problem in clinical rehabilitation practice. To address this issue, the objective of this study is to prognosticate the outcome of BCI training using motor state electroencephalographic (EEG) collected during the first session of BCI tasks, with the aim of prescribing BCI training accordingly. A Convolution Neural Network (CNN) based prognosis model was developed to predict the outcome of 11 stroke patients' recovery following a 2-week rehabilitation training with BCI. In our study, functional connectivity and power spectrum have been evaluated and applied as the inputs of CNN to regress patients' recovery rate. A saliency map was used to identify the correlation between EEG channels with the recovery outcome. The performance of our model was assessed using the leave-one-out cross-validation. Overall, the proposed model predicted patients' recovery with R2 0.98 and MSE 0.89. According to the saliency map, the highest functional connectivity occurred in Fp2/Fpz-AF8, Fp2/F4/F8-P3, P1/PO7-PO5 and AF3-AF4. Our results demonstrated that deep learning method has the potential to predict the recovery rate of BCI training, which contributes to guiding individualized prescription in the early stage of clinical rehabilitation.


Assuntos
Interfaces Cérebro-Computador , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Eletroencefalografia , Humanos , Redes Neurais de Computação
11.
Medicine (Baltimore) ; 100(30): e26748, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397716

RESUMO

ABSTRACT: The aim of this study was to retrospectively analyze the clinical data of COVID-19 patients with different severity during February 2020 in Wuxi, China.The present retrospective study included a total of 60 cases who were diagnosed as COVID-19 patients and hospitalized in the Wuxi Fifth People's Hospital during February 2020 to March 2020. Among all patients 14 cases were asymptomatic, 25 cases were with mild stage, 13 cases were with moderate stage, and 8 cases were with severe stage. Basic clinical data as well as clinical characteristics, including temperature, respiratory rate, heart rate, blood gas analysis data, whole blood test data, and the prognosis condition, were collected and analyzed. Statistical analysis was conducted in different severity stage patients.Among the patients, the median temperature gradually increased from the asymptomatic to the severe patients and the median age increased from the mild to the severe patients with statistical difference. The hospitalization duration was the highest in severe patients. Higher heart rate, as well as lower oxygen partial pressure and oxygenation index were observed in severe patients than the other groups. Besides, higher CRP and globulin levels after admission were found in severe patients, and were gradually increased from the asymptomatic patients to the severe patients. On the contrary, the lymphocyte ratio and count was significant lower in severe patients. We also observed higher D-Dimer levels in the severe patients and the difference was statistical. Among all patients, 2 cases (3.33%) died and other patients were all cured after treatment.Statistical difference was mainly found mainly in age, hospitalization duration, temperature, CRP levels, O2 partial pressure and oxygenation index, globulin, lymphocyte ratio, and D-Dimer in patients with different severity. The higher CRP levels, lower O2 partial pressure and oxygenation index, higher globulin, lower lymphocyte ratio, and higher D-Dimer might be associated with the patients' severity.


Assuntos
COVID-19/patologia , Adolescente , Adulto , Idoso , Infecções Assintomáticas/epidemiologia , COVID-19/epidemiologia , COVID-19/terapia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
12.
Front Oncol ; 11: 722916, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386431

RESUMO

Tumor microenvironment (TME) formation is a major cause of immunosuppression. The TME consists of a considerable number of macrophages and stromal cells that have been identified in multiple tumor types. CCL2 is the strongest chemoattractant involved in macrophage recruitment and a powerful initiator of inflammation. Evidence indicates that CCL2 can attract other host cells in the TME and direct their differentiation in cooperation with other cytokines. Overall, CCL2 has an unfavorable effect on prognosis in tumor patients because of the accumulation of immunosuppressive cell subtypes. However, there is also evidence demonstrating that CCL2 enhances the anti-tumor capability of specific cell types such as inflammatory monocytes and neutrophils. The inflammation state of the tumor seems to have a bi-lateral role in tumor progression. Here, we review works focusing on the interactions between cancer cells and host cells, and on the biological role of CCL2 in these processes.

13.
BMC Cancer ; 21(1): 944, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419008

RESUMO

BACKGROUND: Proton beam therapy (PBT) is a new-emerging cancer treatment in China but its treatment costs are high and not yet covered by Chinese public medical insurance. The advanced form of PBT, intensity-modulated proton radiation therapy (IMPT), has been confirmed to reduce normal tissue complication probability (NTCP) as compared to conventional intensity-modulated photon-radiation therapy (IMRT) in patients with oropharyngeal cancer (OPC). Herein, we evaluated the cost-effectiveness and applicability of IMPT versus IMRT for OPC patients in China, aiming at guiding the proper use of PBT. METHODS: A 7-state Markov model was designed for analysis. Base-case evaluation was performed on a 56-year-old (median age of OPC in China) patient under the assumption that IMPT could provide a 25% NTCP-reduction in long-term symptomatic dysphagia and xerostomia. Model robustness was examined using probabilistic sensitivity analysis, cohort analysis, and tornado diagram. One-way sensitivity analyses were conducted to identify the cost-effective scenarios. IMPT was considered as cost-effective if the incremental cost-effectiveness ratio (ICER) was below the societal willingness-to-pay (WTP) threshold. RESULTS: Compared with IMRT, IMPT provided an extra 0.205 quality-adjusted life-year (QALY) at an additional cost of 34,926.6 US dollars ($), and had an ICER of $170,082.4/ QALY for the base case. At the current WTP of China ($33,558 / QALY) and a current IMPT treatment costs of $50,000, IMPT should provide a minimum NTCP-reduction of 47.5, 50.8, 55.6, 63.3 and 77.2% to be considered cost-effective for patient age levels of 10, 20, 30, 40 and 50-year-old, respectively. For patients at the median age level, reducing the current IMPT costs ($50,000) to a $30,000 level would make the minimum NTCP-reduction threshold for "cost-effective" decrease from 91.4 to 44.6%, at the current WTP of China (from 69.0 to 33.5%, at a WTP of $50,000 / QALY; and from 39.7 to 19.1%, at a WTP of $100,000 / QALY). CONCLUSIONS: Cost-effective scenarios of PBT exist in Chinese OPC patients at the current WTP of China. Considering a potential upcoming increase in PBT use in China, such cost-effective scenarios may further expand if a decrease of proton treatment costs occurs or an increase of WTP level.


Assuntos
Análise Custo-Benefício , Custos de Cuidados de Saúde/tendências , Neoplasias Orofaríngeas/economia , Neoplasias Orofaríngeas/radioterapia , Terapia com Prótons/economia , Terapia com Prótons/normas , Gerenciamento Clínico , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Prognóstico , Terapia com Prótons/métodos , Anos de Vida Ajustados por Qualidade de Vida
14.
Int J Ophthalmol ; 14(8): 1185-1191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414082

RESUMO

AIM: To compare visual field defects using the Swedish Interactive Thresholding Algorithm (SITA) Fast strategy with SITA Faster strategy, a newly developed time-saving threshold visual field strategy. METHODS: Ninety-three participants (60 glaucoma patients and 33 normal controls) were enrolled. One eye from each participant was selected randomly for the study. SITA Fast and SITA Faster were performed using the 24-2 default mode for each test. The differences of visual field defects between the two strategies were compared using the test duration, false-positive response errors, mean deviation (MD), visual field index (VFI) and the numbers of depressed test points at the significant levels of P<5%, <2%, <1%, and <0.5% in probability plots. The correlation between strategies was analyzed. The agreement between strategies was acquired by Bland-Altman analysis. RESULTS: Mean test durations were 246.0±60.9s for SITA Fast, and 156.3±46.3s for SITA Faster (P<0.001). The test duration of SITA Faster was 36.5% shorter than SITA Fast. The MD, VFI and numbers of depressed points at P<5%, <2%, <1%, and <0.5% in probability plots showed no statistically significant difference between two strategies (P>0.05). Correlation analysis showed a high correlation for MD (r=0.986, P<0.001) and VFI (r=0.986, P<0.001) between the two strategies. Bland-Altman analysis showed great agreement between the two strategies. CONCLUSION: SITA Faster, which saves considerable test time, has a great test quality comparing to SITA Fast, but may be not directly interchangeable.

15.
Clin Cancer Res ; 27(15): 4186-4194, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34083231

RESUMO

PURPOSE: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m2 has never been prospectively compared with standard once-a-week cisplatin regimen. PATIENTS AND METHODS: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m2 for two cycles or once-a-week cisplatin at 40 mg/m2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin. RESULTS: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of -0.2% (95% confidence interval, -6.3 to 5.9; P noninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group (P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3-4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039). CONCLUSIONS: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group.

16.
Am J Transl Res ; 13(5): 5720-5730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150181

RESUMO

BACKGROUND: The new S100 protein family member S100A16 is functionally expressed in various cancers. This study explored the prognostic value and potential role of S100A16 in pancreatic cancer (PC). METHODS: RNA-seq and clinical data were obtained from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) dataset to compare the expression level of S100A16 between groups. The genes co-expressed with S100A16 in TCGA-PAAD were analyzed using cBioPortal. Gene Ontology and Kyoto Encyclopedia of Genes and genomes enrichment analyses were also performed on these genes. Pathways related to S100A16 expression dysregulation were explored using gene set enrichment analysis. The Tumor Immune Estimation Resource was used to analyze the correlation between S100A16 and infiltrating immune cells. The Kaplan-Meier method and Cox analyses were used to assess the prognostic significance of S100A16 for PC. RESULTS: The S100A16 expression level was high in PC and increased with the degree of malignancy. The S100A16 functions in PC were mainly enriched in the immune modules, but negatively correlated with the immune activity (T-cell, cytokine, immune, co-receptor, signaling adaptor, cell adhesion molecule, chemokine, and JAK/STAT signaling) and infiltration level (T cells and macrophages). The strongest negative correlation was observed between the expression of CD8+ T cells and S100A16. Furthermore, high S100A16 expression also indicated worse overall survival and, therefore, worse prognosis of PC. CONCLUSION: S100A16 is a potential independent prognostic marker and immunotherapy target for PC. Mechanistically, S100A16 potentially affects prognosis by extensive immunosuppression, including the inhibition of the anti-tumor immune response of CD8+ T cells.

17.
Cancer Cell Int ; 21(1): 295, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098945

RESUMO

As the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and ß-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.

18.
Appl Opt ; 60(13): 3641-3646, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33983296

RESUMO

A $Q$-switched mode-locked square noise-like pulse (QMLSNLP) is generated in a nonlinear polarization rotation passively mode-locked fiber laser. When the pump power changes from 154 mW to 414 mW, the frequency of the $Q$-switched envelope varies from 21.7 kHz to 38.9 kHz, while the duration of the $Q$-switched envelope decreases from $5.1\,\,{\unicode{x00B5}\rm s}$ to $3.2{\unicode{x00B5}\rm s}$, correspondingly. In the meantime, QMLSNLP keeps the fundamental repetition rate constant, and the pulse duration increases from 3.4 ns to 6.7 ns. By inserting different lengths of single-mode fiber into the ring cavity, the evolutions of QMLSNLP are measured and analyzed. According to the cavity parameters and experimental results, impacts of the cavity length on QMLSNLP are investigated in detail.

19.
Front Pharmacol ; 12: 609059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841142

RESUMO

Tetrastigma hemsleyanum Diels et Gilg is a valuable Chinese medicinal herb with a long history of clinical application. Our previous study isolated and characterized a purified polysaccharide from the aerial part of Tetrastigma hemsleyanum (SYQP) and found it having antipyretic and antitumor effects in mice. A preliminary mechanistic study suggests these effects may be related to the binding of toll-like receptor (TLR4). The objective of this study is to further explore the detailed stimulating characteristics of SYQP on TLR4 signaling pathway and its in vivo immune regulating effect. We use HEK-BLUE hTLR4, mouse and human macrophage cell lines, as research tools. In vitro results show SYQP activated HEK-BLUE hTLR4 instead of HEK-BLUE Null cells. The secretion and the mRNA expression of cytokines related to TLR4 signaling significantly increased after SYQP treatment in both PMA-induced THP-1 and RAW264.7 macrophage cell lines. The TLR4 antagonist TAK-242 can almost completely abolish this activation. Furthermore, molecules such as IRAK1, NF-κB, MAPKs, and IRF3 in both the MyD88 and TRIF branches were all activated without pathway selection. In vivo results show SYQP enhanced antigen-specific spleen lymphocyte proliferation and serum IgG levels in OVA-immunized C57BL/6 mice. Orally administered 200 mg/kg SYQP induced obvious tumor regression, spleen weight increase, and the upregulation of the mRNA expression of TLR4-related cytokines in Lewis lung carcinoma-bearing mice. These results indicate SYQP can act as both a human and mouse TLR4 agonist and enhance immune responses in mice (p < 0.05). This study provides a basis for the development and utilization of SYQP as a new type of TLR4 agonist in the future.

20.
Indian J Microbiol ; 61(2): 195-202, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33927460

RESUMO

Biphenanthrene compound, 4, 8, 4', 8'-tetramethoxy (1, 1'-biphenanthrene)-2, 7, 2', 7'-tetrol (LF05), recently isolated from fibrous roots of Bletilla striata, exhibits antibacterial activity against several Gram-positive bacteria. In this study, we investigated the antibacterial properties, potential mode of action and cytotoxicity. Minimum inhibitory concentrations (MICs) tests showed LF05 was active against all tested Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA) and staphylococcal clinical isolates. Minimum bactericidal concentration (MBC) tests demonstrated LF05 was bactericidal against S. aureus ATCC 29213 and Bacillus subtilis 168 whereas bacteriostatic against S. aureus ATCC 43300, WX 0002, and other strains of S. aureus. Time-kill assays further confirmed these observations. The flow cytometric assay indicated that LF05 damaged the cell membrane of S. aureus ATCC 29213 and B. subtilis 168. Consistent with this finding, 4 × MIC of LF05 caused release of ATP in B. subtilis 168 within 10 min. Checkerboard test demonstrated LF05 exhibited additive effect when combined with vancomycin, erythromycin and berberine. The addition of rat plasma or bovine serum albumin to bacterial cultures caused significantly loss in antibacterial activity of LF05. Interestingly, LF05 was highly toxic to several tumor cells. Results of these studies indicate that LF05 is bactericidal against some Gram-positive bacteria and acts as a membrane structure disruptor. The application of biphenanthrene in the treatment of S. aureus infection, especially local infection, deserves further study.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...