After regular chemotherapy, the expression of programmed cell death ligand 1 (PD-L1) in almost all kinds of cancers is significantly increased, leading to reduced efficacy of T cell mediated immune ...killing in tumors. To solve this, a lot of PD-L1 antibodies were produced and used, but their high cost and serious toxic side effects still limit its usage. Recently, small molecule compounds that could effectively regulate PD-L1 expression possess the edges to solve the problems of PD-L1 antibodies. Chitosan oligosaccharide (COS), a biomaterial derived from the N-deacetylation product of chitin, has a broad spectrum of biological activities in treating tumors. However, the mechanism of its anti-cancer effect is still not well understood. Here, for the first time, we clearly identified that COS could inhibit the upregulated PD-L1 expression induced by interferon γ (IFN-γ) in various tumors via the AMPK activation and STAT1 inhibition. Besides, COS itself significantly restricted the growth of CT26 tumors by enhancing the T cell infiltration in tumors. Furthermore, we observed that combining COS with Gemcitabine (GEM), one of the typical chemotherapeutic drugs, leaded to a more remarkable tumor remission. Therefore, it was demonstrated that COS could be used as a useful way to improve the efficacy of existing chemotherapies by effective PD-L1 downregulation.
Background
Nasopharyngeal carcinoma (NPC) is cancer with high mortality and poor prognosis. Circular RNAs (circRNAs) have been identified in a wide variety of cancers. But the functional mechanism of ...circ_000285 in NPC remains unclear.
Purpose
To decipher the biological function and molecular mechanism of circ_000285 in NPC.
Methods
Quantitative PCR (RT-qPCR) was applied for detecting the expression of circ_0000285, miR-1278, and FNDC3B. Western blot was used to measure the protein levels of Fibronectin type III domain containing 3B (FNDC3B), Bcl2 associated X (Bax), and B cell leukemia/lymphoma 2 (Bcl2). Cell proliferation, migration, and invasion were analyzed by colony formation, 5-ethynyl-2′-deoxyuridine (EdU), and transwell assays. Cell apoptosis was detected by flow cytometry assays. ELISA assay was used to analyze Caspase-3 activity. Bioinformatics was used to predict, and the target relationship between miR-1278 and circ_0000285 or FNDC3B was verified by luciferase reporter assay. Tumor xenograft models were established to examine how circ_0000285 functions during the mediation of NPC tumor growth in vivo.
Results
Increased circ_0000285 and FNDC3B expressions, and a decreased miR-1278 expression were observed in NPC tissues and cell lines. Knockdown of circ_0000285 inhibited NPC cell proliferation, migration, invasion, and while promoting NPC cell apoptosis in vitro. Circ_0000285 knockdown-mediated anti-tumor effects in NPC cells could be largely reversed by silencing of miR-1278 or overexpression of FNDC3B. Circ_0000285 could up-regulate FNDC3B expression by sponging miR-1278 in NPC cells. Knockdown of circ_0000285 could inhibit tumor growth in vivo.
Conclusion
Circ_0000285 upregulates FNDC3B expression by adsorbing miR-1278 to promote NPC development.
Abstract
The screening of non-small cell lung cancer (NSCLC) tumors for anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is important because of the dramatically favorable ...therapy response to ALK inhibitor. However, the exact mechanism of poor survival in ALK fusion lung cancer patients without receiving targeted therapy is unclear. In this study, total of 521 tumor specimens from Chinese patients with lung cancer were screened for ALK fusion by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). As results, there were no cases of coexisting EGFR and ALK mutations identified. Fourteen cases (2.7%) harbored ALK fusion, including eight solid adenocarcinomas with signet ring cell features, four acinar adenocarcinomas with cribriform pattern containing mucin, one adenosquamous carcinoma and one micropapillary adenocarcinoma with mucin. Six (42.9%) of fourteen patients with ALK-positive lung cancer had stage IV disease, and five ALK-positive patients treated with platinum-based chemotherapy had poor outcome (all patients were dead and the mean survival time was 12 months), compared to 72 months for patients with ALK inhibitor therapy. Furthermore, Five ALK-positive cases were analyzed by whole exome sequencing (WES) and via direct transcript counting using a digital probe-base (NanoString) to explore the driver genes. Deregulation of PI3K/AKT signaling pathway in ALK-positive lung cancer was demonstrated by WES analysis, and significantly increased mRNA of ALK, ROS1, MET, SPP1 and PI3K signaling pathway was identified by NanoString assay. The concordance between NanoString, IHC and FISH methodologies for detecting ALK fusion was 100%. Significant overexpression of SPP1 protein in ALK-positive lung cancer was confirmed by IHC compared to paired adjacent normal tissues and ALK-negative cancers. Thus we concluded that SPP1 overexpression is associated with poor outcomes for patients with ALK fusion lung cancer without receiving targeted therapy and PI3K/AKT/SPP1 pathway may become the promising targets in patients with aggressive lung cancer.
Objective. Gastric cancer is a prevalent malignant tumor with high morbidity and poor prognosis. Asiaticoside (AC) has antitumor effects, while its role in gastric cancer is elusive. Thus, this study ...investigated the effect of AC on gastric cancer progression. Methods. Cell viability and migration were determined using the CCK-8 and Transwell migration assay. Endoplasmic reticulum stress was detected through measuring the expressions of GRP78, Chop, and hnRNPA1 by Western blot. The luciferase assay confirmed the relationship between miR-635 and High Mobility Group AT-Hook 1 (HMGA1). The effect of AC on tumor growth was evaluated by establishing a xenograft tumor. The survival rate of mice was analyzed by Kaplan-Meier analysis. Results. AC suppressed gastric cancer cell viability and restrained cell migration. AC inhibited the expressions of the cell proliferation marker PCNA and EMT-related marker N-cadherin and increased E-cadherin expression. AC elevated the levels of GRP78 and Chop and suppressed the level of hnRNPA1. In addition, AC restrained gastric cancer proliferation and migration ability and induced endoplasmic reticulum stress by upregulating miR-635 expression. Furthermore, HMGA1 was proven to be a target of miR-635. AC constrained gastric cancer cell proliferation and migration and promoted endoplasmic reticulum stress by regulating HMGA1. Moreover, AC suppressed in vivo tumor growth and improved the survival time of mice. Additionally, AC elevated the expressions of miR-635, E-cadherin, GRP78, and Chop and inhibited Ki-67, HMGA1, N-cadherin, and hnRNPA1 expressions in tumor tissues of mice. Conclusion. AC suppressed gastric cancer progression and induced endoplasmic reticulum stress via the miR-635/HMGA1 axis, providing a valuable drug against gastric cancer.
1 Evidence supports the positive effects of advanced CC on glucose control, quality of life, and food flexibility. There are currently no standardized nutritional knowledge tools for adults with ...T1DM. ...we aimed to develop and validate a questionnaire, the Nutrition and Advanced Carbohydrate Counting Questionnaire (NACQ), and to investigate its feasibility for use with adults with T1DM. The content domains consisted of three meaningful subscales: (1) healthy eating, (2) advanced CC including calculation of mealtime insulin doses, and (3) the impact of food on blood glucose. In the binary logistic regression analysis, the risk of poor glycemic control (HbA1c ≥7%) for patients with NACQ scores <17.6 was 2.857 times greater than that for patients with NACQ scores ≥17.6 (Odds ratio 2.857, 95% Confidence interval 1.294–6.308, P = 0.009) after adjustment for age, gender, duration of T1DM, and residence.
The Kyushu–Palau Ridge (KPR), an anti-S-shaped submarine highland at the center of the Philippine Sea Plate (PSP), is considered the residual arc of the Izu–Bonin–Mariana Island Arc, which retains ...key information about the cessation of the Western Philippine Basin (WPB) expansion and the Parece Vela Basin (PVB) breakup. Herein, using the new generation of satellite altimetry gravity data, high-precision seafloor topography data, and newly acquired ship-borne gravity data, the topographic and gravity characteristics of the KPR mid-southern section and adjacent region are depicted. The distribution characteristics of the faults were delineated using the normalized vertical derivative–total horizontal derivative method(NVDR-THDR) and the minimum curvature potential field separation method. The Moho depth and crustal thickness were inverted using the rapid inversion method for a double-interface model with depth constraints. Based on these results, the crust structure features in the KPR mid-southern section, and the “triangular” structure geological significance where the KPR and Central Basin Rift (CBR) of the WPB intersect are interpreted. The KPR crustal thickness is approximately 6–16 km, with a distinct discontinuity that is slightly thicker than the normal oceanic crust. The KPR mid-southern section crust structure was divided into four segments (S1–S4) from north to south, formed by the CBR eastward extension joint action and clockwise rotation of the PVB expansion axis and the Mindanao fault zone blocking effect.
A major barrier to human immunodeficiency virus (HIV) cure is the existence of viral reservoirs that lead to viral rebound following discontinuation of antiretroviral therapy (ART). We postulate that ...enhancing cytotoxic T lymphocytes (CTL) targeting conserved envelope (Env) regions can eliminate HIV infected cells in latency. Here, we evaluate the use of adoptively transferred HIV vaccine-induced subtype C Env-specific CTLs in a macaque subtype B simian-human immunodeficiency virus (SHIV) model to determine whether plasma viremia can be controlled after ART interruption. We demonstrate that adoptive cellular therapy (ACT) using autologous Env-specific T cells augmented by therapeutic vaccination can suppress ART-free viral rebound in the SHIV model. Furthermore, phenotypic and functional characterization of adoptively transferred cells in ACT-responsive and nonresponsive animals support a critical role for cross-reactive central memory T cells in viremia control. Our study offers an approach to potentiate immunological suppression of HIV in the absence of antiviral drugs.
To investigate the associations between insulin resistance (IR)-related features and cognitive function in type 1 diabetes (T1D).
A total of 117 adult patients with T1D were recruited in this ...cross-sectional study. IR-related features include overweight/obesity/central obesity, hypertension, atherogenic dyslipidemia, and decreased estimated insulin sensitivity (eIS). The Wechsler Memory Scale-Chinese Revision, Wisconsin Card Sorting Test, and Sustained Attention to Response Task was used to assess memory, executive function and sustained attention, respectively. A z-score was generated from each test, and a composite measure of global cognitive performance was calculated by averaging the z-scores of all tests. Cognitive differences were measured between T1D patients with and without IR-related features. The associations between IR-related features and and cognitive performance were analyzed using: logistic regression, partial correlation, and multivariate linear regression analysis.
A total of 53 (45.3%) T1D patients were defined as having IR-related features. Individuals with IR-related features displayed worse overall cognitive scores compared to those without and had a 4-fold increase in the risk for having global cognitive z-score < 0. Among the IR-related features, higher triglyceride (TG) and lower eIS showed linear correlation with lower global cognitive performance. And the subsequent regression analysis identified eIS as the factor independently associated with global cognitive performance.
We have provided evidence linking IR-related features to deteriorated cognitive function in adult patients with T1D. And eIS showed an independent positive correlation with global cognitive performance. Although no causal relationship can be drawn, IR emerges as an important factor reflecting cognitive function.
ClinicalTrials.gov NCT03610984.
Abstract
Background
The interscalene brachial plexus block (ISB) is a commonly used nerve block technique for postoperative analgesia in patients undergoing shoulder arthroscopy surgery; however, it ...is associated with potentially serious complications. The use of suprascapular nerve block (SSNB) has been described as an alternative strategy with fewer reported side effects for shoulder arthroscopy. This review aimed to compare the impact of SSNB and ISB during shoulder arthroscopy surgery.
Methods
A meta-analysis was conducted to identify relevant randomized controlled trials involving SSNB and ISB during shoulder arthroscopy surgery. Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database were searched from 2010 through March 2021.
Results
We identified 1255 patients assessed in 17 randomized controlled trials. Compared with the ISB group, the SSNB group had higher VAS at rest in PACU (
P
= 0.003), 1 h after operation (
P
= 0.005), similar pain score 2 h (
P
= 0.39), 3-4 h (
P
= 0.32), 6-8 h after operation (
P
= 0.05), then lower VAS 12 h after operation (
P
= 0.00006), and again similar VAS 1 day (
P
= 0.62) and 2 days after operation (
P
= 0.70). As for the VAS with movement, the SSNB group had higher pain score in PACU (
P
= 0.03), similar VAS 4-6 h after operation (
P
= 0.25), then lower pain score 8-12 h after operation (
P
= 0.01) and again similar VAS 1 day after operation (
P
= 0.3) compared with the ISB group. No significant difference was found for oral morphine equivalents use at 24 h (
P
= 0.35), duration of PACU stay (
P
= 0.65), the rate of patient satisfaction (
P
= 0.14) as well as the rate of vomiting (
P
= 0.56), and local tenderness (
P
= 0.87). However, the SSNB group had lower rate of block-related complications such as Horner syndrome (
P
< 0.0001), numb (
P
= 0.002), dyspnea (
P
= 0.04), and hoarseness (
P
= 0.04).
Conclusion
Our high-level evidence established SSNB as an effective and safe analgesic technique and a clinically attractive alternative to interscalene block with the SSNB’S advantage of similar pain control, morphine use, and less nerve block-related complications during arthroscopic shoulder surgery, especially for severe chronic obstructive pulmonary disease, obstructive sleep apnea, and morbid obesity. Given our meta-analysis’s relevant possible biases, we required more adequately powered and better-designed RCT studies with long-term follow-up to reach a firmer conclusion.
Ovary development is a complex process involving numerous genes; the molecular mechanism underlying the ovary development of carp is still unknown. Here we used Illumina HiSeq™ 2500 to explore the ...transcriptome of undifferentiated gland (PG), juvenile ovary (OJ) and adult ovary (OA) of Yellow River carp (Cyprinus carpio). A total of 58,749 unigenes were obtained, comprising 45,707 known genes and 13,042 new genes. We identified differentially-expressed genes (DEGs) during development and characterized the functional properties of DEGs by comparison with the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes databases. qRT-PCR was used to analyze the expression of 22 DEGs and the results corresponded with those of RNA-Seq. Among DEGs between PG and OJ, some upstream regulators of gonad development were upregulated in PG, such as cyp19a and sox9, while some oocyte-specific genes were upregulated in OJ, such as nobox, bmp15 and zp2. Among DEGs between OJ and OA, many oocyte physiological function-related genes were upregulated in OA, such as fem-1 and foxl2. GO analysis showed a higher number of DEGs from PG–OJ analysis were assigned to reproduction terms. Furthermore, our investigation has also revealed DEGs identified from PG–OJ analysis were enriched in several important functional pathways, such as Fanconi anemia and the notch signal pathway. These data suggested a dynamic shift in gene expression during ovary development, and DEGs between PG and OJ provided crucial candidate gene data for the study of ovarian differentiation. Additionally, a total of 1,776,769 single nucleotide polymorphisms and 157,279 INDEs were revealed from transcriptome data. This result will contribute to knowledge of ovary differentiation of Yellow River carp.
•This study provided the transcriptome data for three periods of ovarian development in carp.•Many genes and signal pathways related to ovary differentiation in carp were reported in this study.•These results provided invaluable new data for the in-depth study of candidate genes in breeding programs of carp.
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