Association of Fish Oil Supplementation with Risk of Coronary Heart Disease in Individuals with Diabetes and Prediabetes: A Prospective Study in the UK Biobank.

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

PD-1 and LAG-3-positive T cells are associated with clinical outcomes of relapsed/refractory multiple myeloma patients.

OBJECTIVE: To investigate the frequency of PD-1 and LAG-3-positive T cells in relapsed/refractory multiple myeloma (RRMM) patients and its clinical significance. METHODS: This prospective observational study enrolled a total of 71 RRMM patients, as well as 70 MM patients (non-refractory) and 70 healthy individuals during January 2018 to March 2021. The frequency of circulating CD4+ and CD8+ T cells expressing PD-1 and LAG-3 was analyzed using flow cytometry. Serum cytokines of IL-6, IL-17, CRP, TNF-α and TGF-ß were evaluated by enzyme linked immunosorbent assay (ELISA). RESULTS: Significant higher 1-year mortality rate was found in RRMM patients compared with the MM patients. In both CD4+ and CD8+ T cells, the frequencies of PD-1+, LAG-3+ and PD-1+/LAG-3+ T cells were markedly higher in the RRMM patients and the deceased patients, compared with the MM patients and the survival patients, respectively. All cytokines were remarkably higher in RRMM and MM patients than in the healthy control, while only serum levels of IL-6 and IL-17 were markedly higher in RRMM patients compared with the MM patients. Positive correlation was observed among the IL-6, IL-17 and the frequencies of circulating T cells in both CD4+ and CD8+ T cells in RRMM and MM patients. The frequency of CD8+PD-1+LAG-3+ T cells showed the best sensitivity 82.61% and specificity 76.06% for diagnosis of RRMM using ROC curve. Meanwhile, the frequency of CD4+PD-1+ cells showed the best sensitivity 84.00% and specificity 97.35% for prediction of patients' mortality by ROC curve. The frequencies of CD4+PD-1+, CD8+PD-1+/LAG-3+, as well as IL-6, IL-17 and TNF-α were found as risk factors for incidence of RRMM in all MM patients. CONCLUSION: The frequency of PD-1 and LAG-3-positive T cells is associated with the clinical severity and inflammation in RRMM patients, which may also serve as potential biomarkers for its diagnosis.

Long intergenic non-coding RNA LINC00662 contributes to malignant growth of colorectal cancer cells by upregulating c-myc via sponging microRNA-145.

Long non-coding RNAs (lncRNAs) have appeared as vital regulatory factors in different pathological processes, particularly in tumorigenesis. Increasing number of evidence has demonstrated that long intergenic non-coding RNA 00662 (LINC00662) is overexpressed in several types of cancers and promotes cancer initiation and development. However, whether LINC00662 participates in colorectal cancer (CRC) remains unclear. This study was aimed to explore the expression, biological function and regulatory mechanism of LINC00662 in CRC. Here, we found that LINC00662 expression was obviously upregulated in CRC tissues and cell lines. Down-regulation of LINC00662 dramatically inhibited the growth of CRC cells and increased CRC cell apoptosis.MicroRNA-145 (miR-145) was speculated as a target miRNA of LINC00662 by bioinformatics analysis. Luciferase reporter assays and RNA pull-down assays verified that LINC00662 directly interacted with miR-145. Expression of miR-145 was downregulated in CRC tissues and cell lines. Up-regulation of miR-145suppressed cell growth and promoted apoptosis in CRC cells. Suppression of miR-145markedly reversed the suppressive function of LINC00662 knockdown on CRC cell growth. In addition, c-myc was confirmed as a target gene of miR-145 in CRC cells.  Recover of c-myc expression partially reversed suppression effect mediated by LINC00662 downexpression or miR-145overexpressionon CRC cell growth. Taken together, our results indicate that LINC00662lead to the malignant behavior of CRC cells by upregulating c-myc via sponging miR-145, underlining the essential role of the LINC00662/miR-145/c-myc axis in regulating the growth of CRC cells.

The Effect of PEI-Mediated E1A on the Radiosensitivity of Hepatic Carcinoma Cells.

OBJECTIVE: The study was undertaken to investigate the effects of polyethyleneimine (PEI)-mediated adenovirus 5 early region 1A (E1A) on radiosensitivity of human hepatic carcinoma cell in vitro and to disclosure the underlying mechanism. MATERIALS AND METHODS: Human hepatic carcinoma SMMC-7721 cell line was transfected with E1A gene using PEI vector. Untransfected cells (SMMC-7721 group), cells transfected with blank-vector (SMMC-7721-vect group), and cells transfected with E1A gene (SMMC-7721-E1A group) were treated with 6 MV X-ray irradiation at doses of 0, 1, 2, 4, 8 and Gy, respectively. Radiosensitivity was determined by MTT assay and quantified by calculating the cell survival rate. Cell-cycle distribution and apotosis rate were monitored by flow cytometry. RESULTS: The survival rate of SMMC-7721-E1A was significantly lower than that of SMMC-7721 cell. Apoptosis rate of SMMC-7721-E1A group was significantly higher than that of SMMC-7721group (P<0.01).The ratio of S stage in cell cycle of SMMC-7721-E1A was significantly lower than that in SMMC-7721 cell. The ratio of G2/M stage in cell cycle of SMMC-7721-E1A was significantly higher than that in SMMC-7721 cell (P<0.01). CONCLUSION: PEI could transfect E1A gene into hepatic carcinoma cells PEI-mediated E1A could effectively enhance radiosensitivity of hepatic carcinoma cells which may be related to its effects on apoptosis promoting leading to S phase suppression and G2/M phase arrest.
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Research Progress on Long Non-Coding RNA and Radiotherapy.

d_abstr_R Long non-coding RNAs (lncRNAs), a group of non-protein-coding RNAs longer than 200 nucleotides, are involved in multiple biological and pathological processes, such as proliferation, apoptosis, migration, invasion, angiogenesis, and immune escape. Many studies have shown that lncRNAs participate in the complex network of cancer and play vital roles as oncogenes or tumor-suppressor genes in a variety of cancers. Moreover, recent research has shown that abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy may participate in the progression of cancers and affect the radiation sensitivity of malignant tumor cells mediated by specific signaling pathways or cell cycle regulation. In this review, we summarize the published studies on lncRNAs in radiotherapy regarding the biological function and mechanism of human cancers, including esophageal cancer, pancreatic cancers, nasopharyngeal carcinoma, hepatocellular carcinoma, cervical cancer, colorectal cancer, and gastric cancer.

Polyethylenimine (PEI)-Mediated E1A Increases the Sensitivity of Hepatocellular Carcinoma Cells to Chemotherapy.

BACKGROUND The aim of this study was to assess the ability of polyethylenimine (PEI) as an E1A plasmid vector to transfect hepatocellular carcinoma SMMC-7721 cells and to analyze the sensitization effect of E1A on various anti-tumor drugs. MATERIAL AND METHODS PEI-mediated recombinant plasmid psv-E1A with high expression of the E1A gene was introduced into hepatocellular carcinoma SMMC-7721 cells, and the effective transfection of E1A gene was determined by RT-PCR and Western blot analysis. The CCK8 method was used to detect the proliferation inhibition of docetaxel, epirubicin, gemcitabine, and 5-fluorouracil on SMMC-7721 cells before and after the transfection of the E1A gene. RESULTS RT-PCR and Western blot analysis showed that PEI could transfect plasmid psv-E1A with stable expression. After the transfection of E1A gene, the sensitivity of SMMC-7721 cells to docetaxel, epirubicin, gemcitabine, and 5-fluorouracil was increased (P<0.05), and the sensitivity to docetaxel was significantly improved (P<0.01). CONCLUSIONS PEI can transfect plasmid psv-E1A. The E1A gene can increase the sensitivity of hepatocellular carcinoma cells to chemotherapeutic drugs. The mechanism may be related to the increased ability of the E1A gene to inhibit proliferation of hepatocellular carcinoma cells and altering the cell cycle of hepatocellular carcinoma cells.

EGFR inhibitor C225 Increases the Radio-Sensitivity of Human Breast Cancer Cells

Objective: This study was undertaken to investigate the effect of C225 on the radio-sensitivity of MDA-MB-231 cells line and to disclosure underlying mechanism. Methods: CCK8 assay was used to measure the proliferation inhibition of C225 on MDA-MB-231 cells. The combined effects of C225 plus radiation on the proliferation of MDA-MB-231 cells were also evaluated by CCK-8 assay. The clonogenic assay was performed to evaluate the cell surviving fractions and to determine the radio-sensitizing effect of C225 on MDA-MB-231 cells. The apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blot analysis was used to detect the expression of p-EGFR, p-Akt, p-P38, and caspase-3. Results: C225 had an inhibiting effect on the proliferation of cells in a concentration-dependent manner. The cloning formation capacity was decreased in C225 plus radiation group. C225 increased radio-sensitivity of cells and led to cell cycle arrest in G0/G1 phase markedly. Cells treated with C225 and radiation predominantly exhibited G0/G1 phase arrest and significant decreased in the fraction of cells in the S phase. Moreover, C225 and radiation significantly increased the apoptosis rate of cells. Decreased cell proliferation was further supported by the down-regulation of p-EGFR and its downstream singling pathway proteins such as p-Akt and p-P38. The up-regulation of the Caspase-3 expression in C225 plus radiation group revealed that C225 could increase radiation-inducing cell apoptosis. Conclusion: C225 could increase the radio-sensitivity of cells, which may be due to the anti-proliferative synergistic effect between C225 and radiation as well as the down-regulation of the PI3K/Akt signaling pathway.

Clinical and molecular cytogenetic studies in ten patients with hematological malignancies characterized by t(20;21)(q11;q11) resulted from del(20q).

This study reports 10 patients with hematological malignances with t(20;21)(q11;q11) resulting from del(20q) (for example, der(20)del(20)(q11q13)t(20;21)(q11;q11) and der(21)t(20;21)(q11;q11)) and described their clinical features and the possible prognostic significance of this abnormality. The t(20;21)(q11;q11) was a rare but recurrent abnormality secondary to del(20q) besides i(20q-). The frequency of der(20)del(20)(q11q13)t(20;21)(q11;q11) among our patients with del(20q) was 2.4%. It was considered that the 20q deletion preceded translocation with chromosome 21. This abnormality is often cryptic, occurs predominantly in older men and is observed most often in myelodysplastic syndromes. Patients with this abnormality have an unfavorable prognosis, similar to patients with i(20q-). The molecular consequences of der(20)del(20)(q11q13)t(20;21)(q11;q11) may be different from patients with i(20q-). To the best of our knowledge this is the largest dataset published to date.

Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

BACKGROUND: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. MATERIALS AND METHODS: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. RESULTS: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. CONCLUSIONS: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.