Publications by authors named "Chong Zhao"

383 Publications

Effects of eliminating interactions in multi-layer culture on survival, food utilization and growth of small sea urchins Strongylocentrotus intermedius at high temperatures.

Sci Rep 2021 Jul 23;11(1):15116. Epub 2021 Jul 23.

Key Laboratory of Mariculture and Stock Enhancement in North China's Sea, Ministry of Agriculture and Rural Affairs, Dalian Ocean University, Dalian, 116023, China.

Poor growth and disease transmission of small sea urchins Strongylocentrotus intermedius in summer greatly hamper the production efficiency of the longline culture. Reducing the adverse effects of high stocking density while maintaining high biomass is essential to address these problems. Here, we conducted a laboratory experiment to simulate the multi-layer culture for sea urchins at ambient high temperatures (from 22.2 to 24.5 °C) in summer for ~ 7 weeks. Survival, body size, lantern growth, gut weight, food consumption, Aristotle's lantern reflex, 5-hydroxytryptamine concentration, pepsin activity and gut morphology were subsequently evaluated. The present study found that multi-layer culture led to significantly larger body size than those without multi-layer culture (the control group). This was probably because of the greater feeding capacity (indicated by lantern growth and Aristotle's lantern reflex) and food digestion (indicated by morphology and pepsin activity of gut) in the multi-layer cultured sea urchins. These results indicate that multi-layer is an effective approach to improving the growth efficiency of sea urchins at high temperatures. We assessed whether eliminating interaction further improve these commercially important traits of sea urchins in multi-layer culture. This study found that eliminating interactions displayed greater body size and Aristotle's lantern reflex than those not separated in the multi-layer culture. This approach also significantly reduced the morbidity compared with the control group. These novel findings indicate that eliminating interactions in multi-layer culture greatly contributes to the growth and disease prevention of sea urchins at high temperatures. The present study establishes a new technique for the longline culture of sea urchins in summer and provides valuable information into the longline culture management of other commercially important species (e.g. scallops, abalones and oysters).
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http://dx.doi.org/10.1038/s41598-021-94546-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302603PMC
July 2021

Nomograms for Predicting Recurrent Herniation in PETD with Preoperative Radiological Factors.

J Pain Res 2021 9;14:2095-2109. Epub 2021 Jul 9.

Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.

Purpose: To investigate the preoperative radiological risk factors for recurrent lumbar disc herniation (rLDH) within 1 year after percutaneous endoscopic transforaminal discectomy (PETD).

Patients And Methods: A retrospective case-control study was conducted. Between January 2013 and November 2019, a total of 1210 patients with single-level L4/5 LDH who underwent PETD were enrolled in the present study. In total, 62 rLDH patients were diagnosed and collected based on the clinical and radiological manifestations, and 224 non-rLDH controls were selected from the remaining 1148 patients. Preoperative radiological parameters were collected and measured. An age threshold to distinguish patients into subgroups was established using the Youden index. The relationships between the risk factors and rLDH were evaluated by univariate and multivariate analyses in two subgroups. Predictive models were established based on logistic analysis. The area under the curve (AUC) of receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) were used to assess the predictive models.

Results: In the present study, logistic analysis identified six significant predictors associated with rLDH in the young group: superior endplate concave angle (ECA), sacral slope, Modic changes, sagittal range of motion (sROM), extension intervertebral angle (IVA), and lumbar lordosis. Four significant predictors were identified in the elderly group: disc height index (DHI), retrolisthesis (posterior spondylolisthesis), sROM, and extension IVA. Validation of both models demonstrated excellent model discrimination (AUC= 0.940 and 0.946, respectively). DCA also showed excellent clinical utility and benefits.

Conclusion: The nomograms that we constructed could accurately predict individual patient recurrence risk. Individualized measures should be taken for patients of different ages with the above risk factors, and tailored postoperative surveillance of patients who underwent PETD can be planned.
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http://dx.doi.org/10.2147/JPR.S312224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277456PMC
July 2021

Combination of Palmitic Acid and Methylseleninic Acid Induces Mitochondria-Dependent Apoptosis via Attenuation of the IRE1α Arm and Enhancement of CHOP in Hepatoma.

ACS Omega 2021 Jun 8;6(24):15708-15715. Epub 2021 Jun 8.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Haidian District, Beijing100080, China.

The most common saturated fatty acid in the human diet is palmitic acid (PA), and emerging evidence suggests that it may have anticancer activity. Methylseleninic acid (MSeA), the most commonly used selenium derivative in humans, has specific cytotoxic effects on several cancer cells. However, it is generally considered that HepG2 cells are insensitive to MSeA-induced death. In our current research, we found that the addition of PA increased the sensitivity of HepG2 cells to low-dose MSeA-induced apoptosis. The anticancer efficacy of the MSeA/PA combination was also demonstrated in a HepG2 xenograft model. Further experiments revealed that IRE1 inhibition significantly enhanced the PA-induced apoptosis, indicating the prosurvival function of IRE1 in PA treatment of HepG2 cells. The combination of PA and MSeA attenuated the IRE1 pathway and increased the expressions of phospha-eIF2α and GADD153/C/EBP homologous protein (CHOP), contributing to the PA/MSeA combination-induced mitochondria-dependent apoptosis in HepG2 cells. In addition, PA downregulated the expression of the glucose transporter GLUT1 and restricted glucose metabolism, thus promoting the apoptosis of tumor cells. Considering the lipotoxicity of PA, L02 human normal hepatocytes were used to evaluate the effect of MSeA on the lipotoxicity caused by PA. Interestingly, MSeA prevented PA-induced lipotoxicity in L02 cells. Our findings provided evidence that PA may be a promising and excellent sensitizer for improving the anticancer effect of MSeA in hepatoma chemotherapy.
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http://dx.doi.org/10.1021/acsomega.1c00959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223223PMC
June 2021

Radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy with or without chemotherapy: Development of a nomogram based on the equivalent dose.

Oral Oncol 2021 Jun 23;120:105378. Epub 2021 Jun 23.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province 510060, China; Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province 510060, China. Electronic address:

Objective: The aim of this study was to establish a nomogram for predicting radiation-induced hypothyroidism (RHT) based on an equivalent dose at 2 Gy per fraction (EQD) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) with or without chemotherapy.

Methods: Two hundred forty-four eligible patients with NPC were recruited for this study. Patients' clinical factors and dose-volume parameters of the thyroid gland were retrieved from medical records and the IMRT treatment planning system, respectively. The irradiation doses were converted into EQD for analysis. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate logistic regression analysis were performed to identify optimal predictors of RHT for constructing the nomogram.

Results: With a median follow-up of 63.0 months, the cumulative incidence rates of RHT at 3 months and 1-, 2-, 3-, 4- and 5- year after IMRT were 10.2%, 36.2%, 47.6%, 54.2%, 58.8% and 69.4%, respectively. Four independent factors for predicting RHT, including gender, age, pretreatment volume of the thyroid gland and V of the thyroid gland, were identified and incorporated into the nomogram. The area under the ROC curve of the nomogram was 0.747 (95% confidence interval 0.685 - 0.809). Calibration curves and DCA curves showed that the nomogram was in good agreement with the actual observations and clinical usefulness.

Conclusions: The nomogram proposed in this study provides a reliable estimate of RHT risk in patients with NPC after IMRT and appears to have the potential to be a useful tool for widespread clinical applications.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105378DOI Listing
June 2021

Inhibition of cyclooxygenase-2 enhanced intestinal epithelial homeostasis via suppressing β-catenin signalling pathway in experimental liver fibrosis.

J Cell Mol Med 2021 Jun 19. Epub 2021 Jun 19.

Laboratory of Gastroenterology & Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

The intestinal barrier dysfunction is crucial for the development of liver fibrosis but can be disturbed by intestinal chronic inflammation characterized with cyclooxygenase-2 (COX-2) expression. This study focused on the unknown mechanism by which COX-2 regulates intestinal epithelial homeostasis in liver fibrosis. The animal models of liver fibrosis induced with TAA were established in rats and in intestinal epithelial-specific COX-2 knockout mice. The impacts of COX-2 on intestinal epithelial homeostasis via suppressing β-catenin signalling pathway were verified pharmacologically and genetically in vivo. A similar assumption was tested in Ls174T cells with goblet cell phenotype in vitro. Firstly, disruption of intestinal epithelial homeostasis in cirrhotic rats was ameliorated by celecoxib, a selective COX-2 inhibitor. Then, β-catenin signalling pathway in cirrhotic rats was associated with the activation of COX-2. Furthermore, intestinal epithelial-specific COX-2 knockout could suppress β-catenin signalling pathway and restore the disruption of ileal epithelial homeostasis in cirrhotic mice. Moreover, the effect of COX-2/PGE2 was dependent on the β-catenin signalling pathway in Ls174T cells. Therefore, inhibition of COX-2 may enhance intestinal epithelial homeostasis via suppression of the β-catenin signalling pathway in liver fibrosis.
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http://dx.doi.org/10.1111/jcmm.16730DOI Listing
June 2021

Mechanisms of Physical Fatigue and its Applications in Nutritional Interventions.

J Agric Food Chem 2021 Jun 14;69(24):6755-6768. Epub 2021 Jun 14.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China.

Physical fatigue during exercise can be defined as an impairment of physical performance. Multiple factors have been found contributing to physical fatigue, including neurotransmitter-mediated defense action, insufficient energy supply, and induction of oxidative stress. These mechanistic findings provide a sound theoretical rationale for nutritional intervention since most of these factors can be modulated by nutrient supplementation. In this review, we summarize the current evidence regarding the functional role of nutrients supplementation in managing physical performance and propose the issues that need to be addressed for better utilization of nutritional supplementation approach to improve physical performance.
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http://dx.doi.org/10.1021/acs.jafc.1c01251DOI Listing
June 2021

Acylglycerol kinase promotes paclitaxel resistance in nasopharyngeal carcinoma cells by regulating FOXM1 via the JAK2/STAT3 pathway.

Cytokine 2021 Jun 8:155595. Epub 2021 Jun 8.

Department of Otorhinolaryngology and Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. Electronic address:

Objective: Drug resistance is an important factor that impedes the treatment of nasopharyngeal cancer (NPC). Acylglycerol kinase (AGK) has been found to be overexpressed in NPC and correlates with poor prognosis. Our objective was to demonstrate the effect of AGK on paclitaxel resistance in NPC and determine the underlying mechanisms.

Methods: MTT assay was employed to determine the IC50 of paclitaxel in NPC cells after different treatments. Flow cytometry assays were employed to evaluate cell apoptosis. RT-qPCR and Western blot assays were used to detect alterations in mRNA and protein expression, respectively. Luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to determine the relationship between and the regulatory effect of STAT3 on the promoter of FOXM1.

Results: AGK was elevated in paclitaxel-resistant NPC cells, and knockdown of AGK suppressed the resistance of CNE1-TR and CNE2-TR cells to paclitaxel. Moreover, upregulation of FOXM1 rescued the effects of AGK knockdown. Furthermore, the JAK2/STAT3 signalling pathway was overactivated in CNE1-TR and CNE2-TR cells, and knockdown of AGK suppressed JAK2/STAT3 signalling. STAT3 was verified to bind to and activate the promoter region of FOXM1. An in vivo tumour xenograft assay also verified that AGK knockdown inhibited tumour growth and mitigated paclitaxel resistance by regulating the JAK2/STAT3/FOXM1 axis.

Conclusion: AGK levels were increased in paclitaxel-resistant NPC cells. AGK activates JAK2/STAT3 signalling, thus promoting FOXM1 transcription and eventually enhancing the drug resistance of NPC cells.
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http://dx.doi.org/10.1016/j.cyto.2021.155595DOI Listing
June 2021

Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-modulated Radiation Therapy: A Retrospective Study with 15-year Follow-up.

Cancer Res Treat 2021 Jun 7. Epub 2021 Jun 7.

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Purpose: To investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.

Materials And Methods: Totally 187 patients with newly diagnosed NPC and restaged AJCC/UICC 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT) ± chemotherapy (CT) from 2001 to 2010.

Results: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease specific survival (DSS) and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥52.0 could independently predict DMFS (p=0.036 and 0.011), DSS (p=0.014 and 0.026) and OS (p=0.002 and <0.001); Charlson comorbidity index <3 points could predict DSS (p=0.011); age >45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥240 U/L (p<0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%) and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p>0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity and cranial nerve injury (all p < 0.05) than IMRT alone group.

Conclusion: Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As chemotherapy would bring more toxicities, it should be carefully performed to stage II patients.
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http://dx.doi.org/10.4143/crt.2021.101DOI Listing
June 2021

Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially Enhancement of Bilirubin Reabsorption.

Front Pharmacol 2021 20;12:654808. Epub 2021 May 20.

Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Studies increasingly show that ulcerative colitis (UC) is a consequence of an imbalance between oxidative stress and antioxidant capacity. Bilirubin exerts an anti-inflammatory effect by scavenging reactive oxygen species (ROS), although the exact mechanism is not completely understood. The aim of this study was to determine the role of serum bilirubin in UC using patient data and a mouse model of dextran sodium sulfate (DSS)-induced colitis. We found that low levels of serum bilirubin correlated to a higher risk of UC in a retrospective case-control population. Pre-treatment with exogenous unconjugated bilirubin (UCB) significantly enhanced colonic bilirubin absorption in mice, and attenuated the DSS-induced body weight loss, colon shortening and histopathological damage. Mechanistically, bilirubin prevented the infiltration of inflammatory cells, and decreased the levels of myeloperoxidase and pro-inflammatory cytokines in the serum and colon. Moreover, bilirubin inhibited ROS and malondialdehyde production, scavenged superoxide anions (O ) from the colon and enhanced the total antioxidant capacity. In conclusion, exogenous UCB attenuated DSS-induced colitis by directly scavenging O and enhancing bilirubin reabsorption in the colon via enterohepatic cycling.
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http://dx.doi.org/10.3389/fphar.2021.654808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173062PMC
May 2021

A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer.

Clin Cancer Res 2021 Jun 3. Epub 2021 Jun 3.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.

Purpose: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m 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/m 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/m for two cycles or once-a-week cisplatin at 40 mg/m 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; = 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 ( = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; = 0.0022) and thrombocytopenia (1% vs. 5%; = 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%; = 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.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4532DOI Listing
June 2021

Food Sources of Selenium and Its Relationship with Chronic Diseases.

Nutrients 2021 May 20;13(5). Epub 2021 May 20.

College of Food Science and Nutritional Engineering, China Agricultural University, 17 Qinghua East Road, Haidian District, Beijing 100083, China.

Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.
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http://dx.doi.org/10.3390/nu13051739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160805PMC
May 2021

Carryover effects of long-term high water temperatures on fitness-related traits of the offspring of the sea urchin Strongylocentrotus intermedius.

Mar Environ Res 2021 Jul 20;169:105371. Epub 2021 May 20.

Key Laboratory of Mariculture & Stock Enhancement in North China's Sea, Ministry of Agriculture and Rural Affairs, Dalian Ocean University, Dalian, 116023, China. Electronic address:

It is important to study the fitness of marine invertebrates in exposure to high water temperature. We studied whether the long-term high temperatures work on the fitness-related traits (righting behavior, covering behavior, foraging behavior, Aristotle's lantern reflex, body size) of S. intermedius whose parents (males and females) were exposed to ambient or high temperatures (~3 °C higher than the ambient) for a long period of time. The present study found that test diameter, wet body weight and test weight of offspring were not significantly different between temperature treatments, indicating that the parental sea urchins in exposure to high temperatures develop no carryover effects on the body size of the offspring sea urchins. We found no significant difference in foraging behavior, Aristotle's lantern reflex, lantern length and lantern weight of sea urchins after their parents had experienced long-term high temperatures. In addition, no significant change was found in the righting and covering behaviors of sea urchins whose parents were at long-term high temperatures. These results indicate that no significant lasting effects exhibited in the fitness-related behaviors and tissue size after their parents were exposed to high temperatures for a long time. The crushing force of test and test thickness showed no significant difference in the offspring of S. intermedius, no matter whether their parents were exposed to long-term high temperatures or not. The current results enrich our understanding that the parental sea urchin experiencing long-term high temperatures probably develop no carryover effects on the test of their offspring. We found that sea urchins whose parents were exposed to long-term elevated temperatures showed a significantly higher lantern length/test diameter and a significantly lower test height/test diameter in offspring sea urchins due to the thermal experience of their parents, showing the plasticity of lantern and test of offspring sea urchins in response to the thermal experience of their parents. Together with our previous investigation, the present study indicates that small sea urchins are less susceptible to the carryover effects of high temperatures in comparison with the developmental stages of embryos and larvae.
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http://dx.doi.org/10.1016/j.marenvres.2021.105371DOI Listing
July 2021

Downregulation of USP18 reduces tumor-infiltrating activated dendritic cells in extranodal diffuse large B cell lymphoma patients.

Aging (Albany NY) 2021 05 17;13(10):14131-14158. Epub 2021 May 17.

Department of Hematology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Extranodal diffuse large B cell lymphoma (EN DLBCL) often leads to poor outcomes, while the underlying mechanism remains unclear. As immune imbalance plays an important role in lymphoma pathogenesis, we hypothesized that immune genes might be involved in the development of EN DLBCL. Ninety-three differentially expressed immune genes (DEIGs) were identified from 1168 differentially expressed genes (DEGs) between tumor tissues of lymph node DLBCL (LN DLBCL) and EN DLBCL patients in TCGA database. Nine prognostic immune genes were further identified from DEIGs by univariate Cox regression analysis. A multivariate predictive model was established based on these prognostic immune genes. Patients were divided into high- and low-risk groups according to the median model-based risk score. Kaplan-Meier survival curves showed that patients in the high-risk group had a shorter survival time than those in the low-risk group (P < 0.001). Ubiquitin-specific peptidase 18 (USP18) was further recognized as the key immune gene in EN DLBCL on the basis of coexpression of differentially expressed transcription factors (DETFs) and prognostic immune genes. USP18 exhibited low expression in EN DLBCL, which was regulated by LIM homeobox 2 (LHX2) (R = 0.497, P < 0.001, positive). The potential pathway downstream of USP18 was the MAPK pathway, identified by gene set variation analysis (GSVA), gene set enrichment analysis (GSEA) and Pearson correlation analysis (R = 0.294, P < 0.05, positive). The "ssGSEA" algorithm and Pearson correlation analysis identified that activated dendritic cells (aDCs) were the cell type mostly associated with USP18 (R = 0.694, P < 0.001, positive), indicating that USP18 participated in DC-modulating immune responses. The correlations among key biomarkers were supported by multiomics database validation. Indeed, the USP18 protein was confirmed to be expressed at lower levels in tumor tissues in patients with EN DLBCL than in those with LN DLBCL by immunohistochemistry. In short, our study illustrated that the downregulation of USP18 was associated with reduced aDC number in the tumor tissues of EN DLBCL patients, indicating that targeting USP18 might serve as a promising therapy.
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http://dx.doi.org/10.18632/aging.203030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202869PMC
May 2021

Interaction among sea urchins in response to food cues.

Sci Rep 2021 May 11;11(1):9985. Epub 2021 May 11.

Key Laboratory of Mariculture & Stock Enhancement in North China's Sea, Ministry of Agriculture and Rural Affairs, Dalian Ocean University, Dalian, 116023, China.

Interaction among sea urchins remains largely uninvestigated, although the aggregation of sea urchins is common. In the present study, 1, 15 and 30 sea urchins Strongylocentrotus intermedius (11.06 ± 0.99 mm in test diameter) were placed in a 1 m circular tank, respectively. Movement behaviors were recorded for 12 min to investigate potential interactions among sea urchins. After the 12-min control period, we added food cues into the tank and recorded the changes in sea urchins' behaviors. For the first time, we here quantified the interactions among sea urchins in laboratory and found that the interactions varied with food cues and with different densities. The sea urchins dispersed in random directions after being released. There was no significant difference in the movement speed and the displacement of sea urchins among the three density groups (1, 15 and 30 ind/m). The interaction occurred when sea urchins randomly contacted with the conspecifics and slowed down the movement speed. The speed of sea urchins after physical contacts decreased by an average of 40% in the density of 15 ind/m and 17% in the density of 30 ind/m. This interaction resulted in significantly higher randomness in the movement direction and lower movement linearity in 15 and 30 ind/m than in 1 ind/m. After the introduction of food cues, the movement speed, displacement and dispersal distance of sea urchin groups decreased significantly in all the three densities. The dispersal distance and expansion speed of sea urchins were significantly lower in 30 ind/m than those in 15 ind/m. The present study indicates that the interaction among sea urchins limits the movement of individual sea urchin and provides valuable information into how large groups of sea urchins are stable in places where food is plentiful.
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http://dx.doi.org/10.1038/s41598-021-89471-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113249PMC
May 2021

fMRI-based detection of alertness predicts behavioral response variability.

Elife 2021 May 7;10. Epub 2021 May 7.

Department of Biomedical Engineering, Vanderbilt University, Nashville, United States.

Levels of alertness are closely linked with human behavior and cognition. However, while functional magnetic resonance imaging (fMRI) allows for investigating whole-brain dynamics during behavior and task engagement, concurrent measures of alertness (such as EEG or pupillometry) are often unavailable. Here, we extract a continuous, time-resolved marker of alertness from fMRI data alone. We demonstrate that this fMRI alertness marker, calculated in a short pre-stimulus interval, captures trial-to-trial behavioral responses to incoming sensory stimuli. In addition, we find that the prediction of both EEG and behavioral responses during the task may be accomplished using only a small fraction of fMRI voxels. Furthermore, we observe that accounting for alertness appears to increase the statistical detection of task-activated brain areas. These findings have broad implications for augmenting a large body of existing datasets with information about ongoing arousal states, enriching fMRI studies of neural variability in health and disease.
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http://dx.doi.org/10.7554/eLife.62376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104962PMC
May 2021

Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation.

Front Microbiol 2021 12;12:658292. Epub 2021 Apr 12.

Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography-mass spectrometry (LC-MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with -containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.
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http://dx.doi.org/10.3389/fmicb.2021.658292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071877PMC
April 2021

miR-29c&b2 encourage extramedullary infiltration resulting in the poor prognosis of acute myeloid leukemia.

Oncogene 2021 May 22;40(19):3434-3448. Epub 2021 Apr 22.

Department of Hematology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Extramedullary infiltration (EMI), as a concomitant symptom of acute myeloid leukemia (AML), is associated with low complete remission and poor prognosis in AML. However, the mechanism of EMI remains indistinct. Clinical trials showed that increased miR-29s were associated with a poor overall survival in AML [14]. Nevertheless, they were proved to work as tumor suppressor genes by encouraging apoptosis and inhibiting proliferation in vitro. These contradictory results led us to the hypothesis that miR-29s may play a notable role in the prognosis of AML rather than leukemogenesis. Thus, we explored the specimens of AML patients and addressed this issue into miR-29c&b2 knockout mice. As a result, a poor overall survival and invasive blast cells were observed in high miR-29c&b2-expression patients, and the wildtype mice presented a shorter survival with heavier leukemia infiltration in extramedullary organs. Subsequently, we found that the miR-29c&b2 inside leukemia cells promoted EMI, but not the one in the microenvironment. The analysis of signal pathway revealed that miR-29c&b2 could target HMG-box transcription factor 1 (Hbp1) directly, then reduced Hbp1 bound to the promoter of non-muscle myosin IIB (Myh10) as a transcript inhibitor. Thus, increased Myh10 encouraged the migration of leukemia cells. Accordingly, AML patients with EMI were confirmed to have high miR-29c&b2 and MYH10 with low HBP1. Therefore, we identify that miR-29c&b2 contribute to the poor prognosis of AML patients by promoting EMI, and related genes analyses are prospectively feasible in assessment of AML outcome.
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http://dx.doi.org/10.1038/s41388-021-01775-9DOI Listing
May 2021

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

Lancet Oncol 2021 05 12;22(5):716-726. Epub 2021 Apr 12.

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China. Electronic address:

Background: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma.

Methods: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m on days 1 and 22, and fluorouracil 800 mg/m on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m on days 1 and 22, and fluorouracil 800 mg/m on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed.

Findings: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; p=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; p=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported.

Interpretation: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma.

Funding: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00075-9DOI Listing
May 2021

Low NLRP3 expression predicts a better prognosis of colorectal cancer.

Biosci Rep 2021 Apr;41(4)

Lab of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.

Background: NOD-like receptor pyrin domain-3 (NLRP3) inflammasome activation is a double-edged sword in tumorigenesis. Whether NLRP3 is involved in the progression and prognosis of colorectal cancer (CRC) remains elucidated and is the focus of the present study.

Methods: Immunohistochemistry (IHC) was applied on tissue microarray (TMA) to determine the expression of NLRP3 in CRC patients. All 100 patients were divided into the low NLRP3 group and the high NLRP3 group according to their NLRP3 IHC scoring. Additionally, CRC xenografts were established by injecting HCT116 or RKO cells subcutaneously into nude mice. Cell proliferation and apoptosis were determined in HCT116 cells after treatment with NLRP3 inhibitor MCC950.

Results: NLRP3 expression was up-regulated in colon adenocarcinoma tissues compared with that in paracancerous tissues in CRC patients, HCT116 xenograft, and RKO xenograft. High NLRP3 level correlated with the advanced TNM classification of malignant tumors, the occurrence of distant metastasis, vascular invasion, and positive lymph nodes. Furthermore, Kaplan-Meier survival analysis revealed that a high NLRP3 level was associated with a low 5-year survival rate and even a low 10-year survival rate. Moreover, the multivariable Cox proportional hazards regression model implied that NLRP3 expression level was an independent risk factor for CRC prognosis. Inhibition of NLRP3 by MCC950 suppressed cell proliferation, induced cell apoptosis, and decreased mRNA levels of interleukin 1β (IL1β) and interleukin 18 (IL18) in HCT116 cells.

Conclusions: High level of NLRP3 predicts poor survival in CRC patients. NLRP3 is a putative prognostic biomarker and a potential therapeutic target in CRC treatments.
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http://dx.doi.org/10.1042/BSR20210280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055799PMC
April 2021

Combining Patulin with Cadmium Induces Enhanced Hepatotoxicity and Nephrotoxicity In Vitro and In Vivo.

Toxins (Basel) 2021 03 18;13(3). Epub 2021 Mar 18.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-Thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China.

Food can be contaminated by various types of contaminants such as mycotoxins and toxic heavy metals. Therefore, it is very likely that simultaneous intake of more than one type of food contaminant by consumers may take place, which provides a strong rationale for investigating the combined toxicities of these food contaminants. Patulin is one of the most common food-borne mycotoxins, whereas cadmium is a representative of toxic heavy metals found in food. The liver and kidneys are the main target organ sites for both patulin and cadmium. We hypothesized that simultaneous exposure to patulin and cadmium could produce synergistic hepatotoxicity and nephrotoxicity. Alpha mouse liver 12 (AML12) and Human embryonic kidney (HEK) 293 (HEK293) cell lines together with a mouse model were used to explore the combination effect and mechanism. The results demonstrated, for the first time, that the co-exposure of liver or renal cells to patulin and cadmium caused synergistic cytotoxicity in vitro and enhanced liver toxicity in vivo. The synergistic toxicity caused by the co-administration of patulin and cadmium was attributed to the boosted reactive oxygen species (ROS) generation. c-Jun N-terminal kinase 1 (JNK1) and p53 as downstream mediators of oxidative stress contributed to the synergistic toxicity by co-exposure of patulin and cadmium, while p53/JNK1 activation promoted the second-round ROS production through a positive feedback loop. The findings of the present study extend the toxicological knowledge about patulin and cadmium, which could be beneficial to more precisely perform risk assessments on these food contaminants.
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http://dx.doi.org/10.3390/toxins13030221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003173PMC
March 2021

Relating molecular descriptors to frontier orbital energy levels, singlet and triplet excited states of fused tricyclics using machine learning.

J Mol Graph Model 2021 06 13;105:107891. Epub 2021 Mar 13.

Center of Image and Signal Processing, Faculty of Computer Science and Information Technology, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Fused tricyclic organic compounds are an important class of organic electronic materials. In designing molecules for organic electronics, knowing what chemical structure that be used to tune the molecular property is one of the keys that can help to improve the material performance. In this research, we applied machine learning and data analytic approaches in addressing this problem. The energy states (Lowest Unoccupied Molecular Orbital (HOMO), Highest Occupied Molecular Orbitals (LUMO), singlet (E) and triplet (E) energy) of more than 10 thousand fused tricyclics are calculated. Corresponding descriptors are also generated. We find that the Coulomb matrix is a poorer descriptor than high-level descriptors in a multilayer perceptron neural network. Correlations as high as 0.95 is obtained using a multilayer perceptron neural network with Mean Absolute Error as low as 0.08 eV. The descriptors that are important in tuning the energy levels are revealed using the Random Forest algorithm. Correlations of such descriptors are also plotted. We found that the higher the number of tertiary amines, the deeper are the HOMO and LUMO levels. The presence of NN in the aromatic rings can be used to tune the E. However, there is no single dominant descriptor that can be correlated with the E. A collection of descriptors is found to give a far better correlation with E. This research demonstrated that machine learning and data analytics in guiding how certain chemical substructures correlate with the molecule energy states.
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http://dx.doi.org/10.1016/j.jmgm.2021.107891DOI Listing
June 2021

Contralateral Lower Neck Sparing Radiotherapy in Stage N1 Nasopharyngeal Carcinoma: Long-Term Survival Outcomes and Late Toxicities.

Front Oncol 2021 25;11:628919. Epub 2021 Feb 25.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Purpose: To explore the feasibility of contralateral lower neck sparing radiotherapy for patients with stage N1 nasopharyngeal carcinoma (NPC) by analyzing long-term survival outcomes and late toxicities.

Methods: Data of patients with stage N1 NPC who were treated with contralateral lower neck sparing radiotherapy between January 2013 and December 2015 were analyzed. These patients were all staged by magnetic resonance imaging (MRI), and all received irradiation to the upper neck (levels II, III, and Va) bilaterally along with ipsilateral levels IV and Vb, without irradiation of the contralateral lower neck. Treatment outcomes, regional failure patterns, and late toxicities were examined.

Results: A total of 275 eligible patients with stage N1 NPC were included in the present study. The median follow-up period was 62 months (range, 3-93 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), locoregional recurrence-free survival (LRRFS), and progression-free survival (PFS) rates were 90.5, 91.3, 94.7, 95.3, 91.2, and 81.7%, respectively. A total of 13 patients (4.7%) developed regional recurrence, all of which occurred in the field and not out of the field. Among 254 patients with available data on late toxicities, the most common late toxicity was xerostomia. No late injuries occurred in the carotid arteries, brachial plexus, or spinal cord. In addition to one case (0.4%) of neck fibrosis and three cases (1.2%) of hearing loss, there were no other grade 3-4 late toxicities observed.

Conclusions: Contralateral lower neck sparing radiotherapy would be safe and feasible for patients with stage N1 NPC, with the potential to improve the long-term quality of life of patients.
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http://dx.doi.org/10.3389/fonc.2021.628919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947858PMC
February 2021

Development and Validation of Novel Nomograms for Predicting Specific Distant Metastatic Sites and Overall Survival of Patients With Soft Tissue Sarcoma.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821997828

Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Purpose: The goal of this study is to construct nomograms to effectively predict the distant metastatic sites and overall survival (OS) of soft tissue sarcoma (STS) patients.

Methods: STS case data between 2010 and 2015 for retrospective study were gathered from public databases. According to the chi-square and multivariate logistic regression analysis determined independent predictive factors of specific metastatic sites, the nomograms based on these factors were consturced. Subsequently, combined metastatic information a nomogram to predict 1-, 2-, and 3-year OS of STS patients was developed. The performance of models was validated by the area under the curve (AUC), calibration plots, and decision curve analyses (DCA).

Results: A total of 7001 STS patients were included in this retrospective study, including 4901 cases in the training group and the remaining 2,100 patients in the validation group. Three nomograms were established to predict lung, liver and bone metastasis, and satisfactory results have been obtained by internal and external validation. The AUCs for predicting lung, liver, and bone metastases in the training cohort were 0.796, 0.799, and 0.766, respectively, and in the validation cohort were 0.807, 0.787, and 0.775, respectively, which means that the nomograms have good discrimination. The calibration curves showed that the models have high precision, and the DCA manifested that the nomograms have great clinical application prospects. Through univariate and multivariate COX regression analyses, 8 independent prognosis factors of age, grade, histological type, tumor size, surgery, chemotherapy, radiatiotherapy and lung metastasis were determined. A nomogram was then constructed to predict the 1-, 2-, and 3-years OS, which has a good performance in both internal and external validations.

Conclusion: The nomograms for predicting specific metastatic sites and OS have good discrimination, accuracy and clinical applicability. The models could accurately predict the metastatic risk and survival information, and help clinical decision-making.
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http://dx.doi.org/10.1177/1533033821997828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958169PMC
March 2021

High VCAM-1 Predicts Poor Prognosis and is Associated with Chemotherapy Resistance in Nasopharyngeal Carcinoma.

Onco Targets Ther 2021 2;14:1633-1641. Epub 2021 Mar 2.

Department of Otolaryngology-Head and Neck Surgery, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, 646000, Sichuan, People's Republic of China.

Purpose: Nasopharyngeal carcinoma (NPC) is a malignant tumor endemic in southern China and Southeast Asia with a poor prognosis. Vascular cell adhesion protein 1 (VCAM-1) is highly expressed in NPC; however, it is unclear whether VCAM-1 is correlated with chemotherapy resistance and prognosis in NPC.

Patients And Methods: To further explore the role of VCAM-1 in chemotherapy resistance and prognosis in NPC, we examined the expression of VCAM-1, the sensitivity of chemotherapy drugs, and clinical follow-up data from 73 patients with NPC. Then, the results of VCAM-1 expression were analyzed in response to chemotherapy drugs, progression-free survival (PFS), and overall survival (OS).

Results: The expression of VCAM-1 protein in NPC was significantly higher than that in chronic inflammatory tissue. No significant differences in the expression of VCAM-1 among gender, age, pathologic classification, tumor classification, lymph node status, metastasis status, and overall clinical stage were found. The periods of PFS and OS in patients with high VCAM-1 expression were significantly shorter than those in patients with low VCAM-1 expression. The sensitivity rates of NPC to eight chemotherapy drugs were different; carboplatin and docetaxel showed the highest chemotherapy sensitivity and resistance rates, respectively. The resistance rates to paclitaxel were different between the patients with high VCAM-1 expression and those with low VCAM-1 expression.

Conclusion: Our data indicated that VCAM-1 was highly expressed in NPC. Patients with high VCAM-1 expression were more prone to shorter periods of PFS and OS. VCAM-1 could be a prognostic marker of NPC patients. The detection of VCAM-1 expression in NPC may be valuable for chemotherapy drug evaluation and management of patients with NPC in the clinic.
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http://dx.doi.org/10.2147/OTT.S292259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936694PMC
March 2021

Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion: Technique Note and Comparison of Early Outcomes with Minimally Invasive Transforaminal Lumbar Interbody Fusion for Lumbar Spondylolisthesis.

Int J Gen Med 2021 22;14:549-558. Epub 2021 Feb 22.

Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.

Purpose: To compare the preliminary postoperative outcomes of percutaneous endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of lumbar spondylolisthesis.

Methods: Sixty-two patients with single-segment lumbar spondylolisthesis received Endo-TLIF and MIS-TLIF were enrolled in present study. Perioperative parameters, including operation time, estimated blood loss (EBL), interoperative fluoroscopy time, ambulation time and operative complications were recorded, respectively. The results of clinical metrics such as the Visual Analog Scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI) and the Japanese Orthopaedic Association (JOA) score were obtained, respectively. Postoperative fusion rates were assessed by clinical fusion and CT at 12-month after surgery.

Results: No significant differences were found in the demographic data between the two groups. Compared with MIS-TLIF group, Endo-TLIF group had similar operative time, less intraoperative blood loss and shorter ambulation time but longer duration of X-ray radiation. The postoperative VAS scores of back pain, ODI and JOA score were significantly improved comparing with the preoperative scores in two groups, but the Endo-TLIF group showed more significant improvement in the early follow-up (P < 0.05, respectively). There were no significant differences in terms of the interbody fusion rate between the two groups. Meanwhile, no serious postoperative complications were observed in the study.

Conclusion: Compared with MIS-TLIF, Endo-TLIF technique showed relatively faster recovery and better outcomes in terms of early curative effect, especially in 6 months after operation. However, intraoperative repeated fluoroscopy could result in highly cumulative radiation and longer operation time.
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http://dx.doi.org/10.2147/IJGM.S298591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910530PMC
February 2021

Construction of a double-walled carbon nanoring.

Nanoscale 2021 Mar;13(9):4880-4886

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing 100190, China.

The nanoring structure of cycloparaphenylenes (CPPs) can be considered as the shortest fragment of a carbon nanotube. Herein, we successfully prepared a double-walled carbon nanoring of [6]CPP⊂[12]CPP, which can be regarded as the shortest double-walled carbon nanotube. [6]CPP⊂[12]CPP was constructed through the supramolecular assembly, and its crystallographic structure was unambiguously determined by single-crystal X-ray diffraction. The host-guest interaction and charge transfer in [6]CPP⊂[12]CPP were disclosed by UV-Vis absorption, fluorescence, and electrochemical studies. Electron paramagnetic resonance (EPR) spectroscopy disclosed the stability of the [6]CPP⊂[12]CPP cation radical, whose unpaired spin was fully delocalized on the inner [6]CPP and well protected by outer [12]CPP. Moreover, [6]CPP⊂[12]CPP shows highly enhanced photoconductivity and photocurrent under light irradiation compared to those of pristine monomers. The self-assembly behavior of [6]CPP⊂[12]CPP was also studied, and it was found that [6]CPP⊂[12]CPP molecules tend to form a square rod structure in the DMF solution. Thus, these results demonstrate that this double-walled carbon nanoring material has a great potential application in photoelectronic devices and organic semiconductors.
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http://dx.doi.org/10.1039/d0nr08931aDOI Listing
March 2021

PD-L1 positively regulates MET phosphorylation through inhibiting PTP1B.

Cancer Sci 2021 May 4;112(5):1878-1887. Epub 2021 Mar 4.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, Beijing, China.

Increasing bodies of evidence support the involvement of tumor-intrinsic action in PD-L1-mediated cancer progression. However, the mechanisms underlying the tumor-intrinsic function of PD-L1 are less well understood. In the present study, we found a positive correlation between PD-L1 expression and MET phosphorylation in lung cancer and melanoma cell lines. PD-L1 inhibition led to a decrease in MET phosphorylation, while PD-L1 induction by IFN-γ resulted in a PD-L1-dependent increase of MET phosphorylation both in vitro and in vivo. The results indicated that MET phosphorylation can be positively regulated by PD-L1. Furthermore, we identified PTP1B as a mediator contributing to the regulation of MET phosphorylation by PD-L1. In agreement with the induction of MET phosphorylation by PD-L1, inhibition of PD-L1 caused reduced phosphorylation of ERKs, a known downstream kinase of MET, and inhibited cell proliferation. Collectively, the present study demonstrated for the first time that the MET pathway, as a downstream of PD-L1, contributed to its tumor-intrinsic effect, and provided a novel mechanistic explanation for the tumor-intrinsic function of PD-L1 and a rationale for the combination of immunotherapy and MET-targeted therapy in cancer treatment.
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http://dx.doi.org/10.1111/cas.14844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088939PMC
May 2021

Celecoxib ameliorates liver cirrhosis via reducing inflammation and oxidative stress along spleen-liver axis in rats.

Life Sci 2021 May 10;272:119203. Epub 2021 Feb 10.

Lab. of gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China; Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background & Aims: Splenomegaly is usually taken as a consequence of liver cirrhosis. However, as a risk factor for cirrhosis, the impacts of spleen-liver axis on the development of cirrhosis are largely unknown. This study focused on the impacts of splenomegaly on the development of cirrhosis and assessment of the effects of celecoxib, a selective COX-2 inhibitor, on the splenomegaly and cirrhotic liver.

Materials And Methods: Liver cirrhosis was induced by thioacetamide (TAA). Sixty rats were randomly divided into control, TAA-16w, TAA + celecoxib groups and normal, TAA + sham, TAA + splenectomy groups. Hepatic stellate cells (HSCs) or hepatocytes were co-cultured with splenocytes from those groups.

Results: Splenocytes of cirrhotic rats stimulated the HSCs activation and induced hepatocyte apoptosis via enhancing oxidative stress. The hepatic levels of NOX-4 and the in situ O were profoundly reduced in TAA + splenectomy group by 50.6% and 18.5% respectively, p < 0.05. Celecoxib significantly decreased the hepatic fibrotic septa induced with TAA by 50.8%, p < 0.05. Splenic lymphoid tissue proliferation and proinflammatory cytokines of the cirrhotic rats were also obviously suppressed by celecoxib, p < 0.05. Compared with the HSC or hepatocyte cell line co-cultured with the cirrhotic splenocytes, the expression of alpha-SMA, NOX-4, in situ O or the levels of cleaved caspase3 and NOX-4 were significantly decreased in those cell lines co-cultured with cirrhotic splenocytes treated by celecoxib, p < 0.05.

Conclusion: Splenomegaly contributed to the development of liver cirrhosis through enhancing oxidative stress in liver. Celecoxib could effectively ameliorate liver cirrhosis via reducing inflammatory cytokines and immune cells derived from spleen and suppressing oxidative stress.
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http://dx.doi.org/10.1016/j.lfs.2021.119203DOI Listing
May 2021

Multifunctional Organic Fluorescent Probe with Aggregation-Induced Emission Characteristics: Ultrafast Tumor Monitoring, Two-Photon Imaging, and Image-Guide Photodynamic Therapy.

ACS Appl Mater Interfaces 2021 Feb 9;13(7):7987-7996. Epub 2021 Feb 9.

MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.

The development of multifunctional photosensitizers (PSs) with aggregation-induced emission (AIE) properties plays a critical role in promoting the progress of the photodynamic therapy (PDT). In this work, a multifunctional PS (named DSABBT NPs) with AIE activity has been designed and prepared to carry out ultrafast staining, excellent two-photon bioimaging, and high-efficiency image-guided PDT. Simply, DSABBT with AIE characteristic was synthesized by one-step Schiff reaction of 4-(diethylamino)-salicylaldehyde (DSA) and 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BBT). Then, DSABBT and DSPE-PEG-cRGD generate nanoparticles (NPs) easily in an ultrapure water/tetrahydrofuran mixture through a facile nanoprecipitation at room temperature. We found that DSABBT NPs exhibit bright solid-state fluorescence with large stokes shifts (180 nm) and two-photon absorption cross-section (1700 GM). Importantly, DSABBT NPs exhibited excellent ability of ultrafast staining and two-photon imaging, which can readily label suborganelles by subtly shaking the living cells for 5 s under mild conditions. Moreover, DSABBT NPs displayed high singlet oxygen (O) generation capacity and remarkable image-guided PDT efficiency. Therefore, DSABBT NPs can act as the promising candidate for multifunctional PSs, which can destroy cancer cells and block malignant tumor growth via the production of reactive oxygen species upon irradiation conditions. These outcomes provide us with a selectable strategy for developing multifunctional theranostic systems.
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http://dx.doi.org/10.1021/acsami.0c21309DOI Listing
February 2021

The effect of different combinations of antibiotic cocktails on mice and selection of animal models for further microbiota research.

Appl Microbiol Biotechnol 2021 Feb 29;105(4):1669-1681. Epub 2021 Jan 29.

Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, No. 1 Panfu Road, Guangzhou, 510180, Guangdong, China.

The gut microbiota is closely related to host health and disease. However, there are no suitable animal models available at present for exploring its functions. We analyzed the effect of 3 different antibiotic cocktails (ABx) via two administration routes on the composition of murine gut microbiota, as well as on the general physiological and metabolic indices. High-throughput 16S rRNA sequencing showed that ABx treatment altered the gut microbiota community structure, and also caused low-degree inflammation in the colon. In addition, ad libitum administration of antibiotics depleted the gut microbiota more effectively compared to direct oral gavage, especially with 3ABx. The ABx treatment also had a significant impact on renal and liver functions, as indicated by the altered serum levels of creatinine, urea, total triglycerides, and total cholesterol. Finally, Spearman's correlation analysis showed that the predominant bacterial genera resulting from ABx intervention, including Lactobacillus, Roseburia, and Candidatus-Saccharimonas, were negatively correlated with renal function indices. Taken together, different antibiotic combinations and interventions deplete the gut microbiota and induce physiological changes in the host. Our findings provide the basis for developing an adaptive animal model for studying gut microbiota. KEY POINTS: • Ad libitum administration of 3ABx can effectively deplete intestinal microbiota. • ABx treatment may have slight effect on renal and liver function. • The levels of urea and creatinine correlated with the growth of Roseburia.
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http://dx.doi.org/10.1007/s00253-021-11131-2DOI Listing
February 2021
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