Late-Night Overeating and All-Cause and Cardiovascular Disease Mortality in Adults Aged ≥ 50: A Cohort Study.

BACKGROUND: Late-night overeating (LNOE) is closely associated with many health risk factors, but whether LNOE can increase the risk of death remains unknown. Thus, the prospective cohort study aimed to investigate the relationship between LNOE and mortality using data from the National Health and Nutrition Examination Survey. METHODS: 11,893 participants aged 50 years and older were included in the study. Dietary information was obtained through 24-h dietary recall interviews. Cox regression, subgroup, sensitivity, and restricted cubic spline analyses were used to assess the association between LNOE and mortality. RESULTS: During a median follow-up of 8.3 years, 2,498 deaths occurred. After adjusting for major confounders, compared to the non-late-night eating (NLNE) group, the LNOE group was associated with higher risks of all-cause (HR = 1.47, 95% CI = 1.06-2.04) and cardiovascular disease (CVD) mortality (HR = 2.02, 95% CI = 1.13-3.60). No significant association was found between late-night eating (LNE) and mortality. Subgroup analyses showed that the LNOE group had a greater risk of all-cause and CVD mortality in participants older than 70 years, with alcohol consumption and hypertension and demonstrated an increased risk of all-cause mortality in males and higher CVD mortality in females. CONCLUSION: The habit of LNOE was an independent risk factor for all-cause and CVD mortality in US adults aged 50 years and older, which was also influenced by age, sex, alcohol consumption, and hypertension.

Long non-coding RNA ROR1-AS1 enhances colorectal cancer metastasis by targeting miR-375.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA ROR1-AS1 enhances colorectal cancer metastasis by targeting miR-375, by F.-Z. Wang, M.-Q. Zhang, L. Zhang, M.-C. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (16): 6899-6905-DOI: 10.26355/eurrev_201908_18729-PMID: 31486489" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18729.

Downregulated LINC00628 aggravates the progression of colorectal cancer via inhibiting p57 level.

OBJECTIVE: To uncover the potential function of LINC00628 in influencing the progression of colorectal cancer (CRC) and its underlying mechanism. PATIENTS AND METHODS: Relative levels of LINC00628 and p57 in CRC tissues and cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Regulatory effects of LINC00628 and p57 on proliferation, cell cycle, and apoptosis of SW480 and SW620 cells were assessed. Subcellular distribution of LINC00628 in CRC cells was analyzed. Moreover, the interaction between LINC00628 and enhancer of zeste homolog 2 (EZH2) was evaluated by the RNA Binding Protein Immunoprecipitation (RIP) assay. RESULTS: LINC00628 was downregulated in CRC tissues and cell lines. CRC patients expressing a low level of LINC00628 suffered worse prognosis. The. knockdown of LINC00628 enhanced proliferative ability, prolonged S phase in cell cycle progression, and inhibited apoptosis in SW480 and SW620 cells. LINC00628 was mainly distributed in the nucleus. The RIP assay demonstrated that LINC00628 could bind to EZH2 to upregulate the p57 level. Rescue experiments verified that the overexpression of p57 could reverse regulatory effects of downregulated LINC00628 on proliferative and apoptotic abilities of CRC. CONCLUSIONS: LINC00628 is downregulated in CRC. It aggravates the progression of CRC by binding to EZH2 to further inhibit the p57 level.

Long non-coding RNA ROR1-AS1 enhances colorectal cancer metastasis by targeting miR-375.

OBJECTIVE: Recent research has proved that long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. In this research, lncRNA ROR1-AS1 was explored to identify its role in the development of colorectal cancer (CRC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to measure ROR1-AS1 expression of CRC tissues. Besides, function assays including wound healing assay and transwell assay were conducted to detect the effect of ROR1-AS1 on the metastasis of CRC. Furthermore, Luciferase assays and RNA immunoprecipitation assay (RIP) were used to explore the underlying mechanism. RESULTS: By comparison with ROR1-AS1 expression in adjacent tissues, the ROR1-AS1 expression level was significantly higher in CRC samples. Moreover, loss of ROR1-AS1 inhibited cell migration and cell invasion of CRC cells. Besides, gain of ROR1-AS1 enhanced cell migration and cell invasion of CRC cells. Furthermore, it was found that ROR1-AS1 acted as a competing endogenous RNA via sponging miR-375 in CRC. CONCLUSIONS: The present study suggests that ROR1-AS1 could promote cell migration and invasion of CRC by sponging miR-375, which may offer a potential therapeutic target in CRC.

The impact of TRAIL on proliferation of secretory prostate cancer PC-3 cell and LMO2 gene expression.

OBJECTIVE: To determine the expressions of TRAIL protein and LMO2 gene in prostate cancer tissues with different differentiation degree and identify the influence of TRAIL on prostate cancer PC-3 cell proliferation. PATIENTS AND METHODS: Surgical specimens from a total of 30 prostate cancer patients with radical prostatectomy were collected. The subjects were divided into three groups according to the different degrees of differentiation. TRAIL positive rate was detected by immunohistochemistry (IHC). LMO2 expression was assessed by Real-time PCR and Western-blot. PC-3 cell proliferation was determined by CCK-8 assay. RESULTS: The positive rate of TRAIL protein was significantly higher in moderately differentiated group (80%) and well differentiated group (100%) compared with that in poorly differentiated group (54.55%), respectively (χ2 = 27.33, p < 0.05; χ2 = 40.12, p < 0.01). Streptavidin-peroxidase (SP) assay showed that TRAIL protein expression in well-differentiated group was significantly higher than that in moderately differentiated group and poorly differentiated group. qRT-PCR result demonstrated that LMO2 mRNA levels in moderately and well-differentiated group were significantly increased compared to that in poorly differentiated group (p < 0.001). Also, the proliferation rate of PC-3 cells in well-differentiated group was significantly higher than that in well-differentiated and moderately differentiated groups (p < 0.05). CONCLUSION: Our data indicated that the positive rate of TRAIL protein increased in a prostate cancer differentiation dependent manner.

[miR-218 Promoted the Apoptosis of Human Ovarian Carcinoma Cells via Suppression of the WNT/ß-Catenin Signaling Pathway].

MicroRNA-218 (miR-218) is a short, noncoding RNA, with multiple biological functions. In this study, we aimed to investigate the potential effects of miR-218 on the apoptosis of human ovarian carcinoma cells and the underlying mechanisms by which miR-218 exerted its actions. After over-expressing miR-218 in human ovarian carcinoma (OVCAR3) cells, cell viability was determined by MTT method, cell apoptosis was observed by flow cytometry (FCM), mRNA expression of miR-218, Bcl2, Bax was measured by RT-PCR and protein expression levels of Wnt, tankyrase and ß-catenin were quantified by Western blots. Over-expression of miR-218 potently suppressed cell viability and promoted the apoptosis of human ovarian carcinoma cells in a time-dependent manner. In addition, the down-regulation of tankyrase expression level was detected in miR-218-over-expressed cells. Following the block of the Wnt/ß-catenin signaling pathway using the inhibitor XAV-939, the effects of miR-218 on the proliferation and apoptosis of human ovarian carcinoma cells were significantly suppressed. Augmenting expression of miR-218 and/or miRNA-218 mimicking therapeutics may provide viable avenue for the treatment of ovarian cancer.

Clinical effects of bevacizumab targeted treatment on advanced colorectal cancer with liver metastasis.

OBJECTIVE: In this study, the clinical effect of bevacizumab targeted treatment on advanced colorectal cancer with liver metastasis were studied. PATIENTS AND METHODS: We consecutively selected 86 cases of patients with advanced colorectal cancer with liver metastasis, and divided them into the control group and observation group (n = 43 each). The FOLFOX chemotherapy scheme (oxaliplatin + fluorouracil + leucovorin) was given to the control group, FOLFOX plus bevacizumab treatment was given to the observation group. RESULTS: It was found that the progression-free survival period and median survival period was significantly prolonged in the observation group, the survival rate was increased within 1 year and 2 years (p < 0.05), also the comparison of 3-year survival rates was not statistically significant (p > 0.05). Moreover, the overall effective rates in the observation group were significantly higher that the control group (p < 0.05). In terms of the complication occurrence rates, the difference was not statistically significant. However, the rise time (RT) and mean transit time (mTT) in the observation group significantly increased with the time (p < 0.05). The RT and mTT were unchanged (p > 0.05) in the control group; the RT and mTT at each time point of the observation group were significantly higher than the control group (p < 0.05). CONCLUSIONS: The bevacizumab targeted treatment of advanced colorectal cancer with liver metastasis can improve the survival rate, prolong the survival period and cannot increase the complications, the CEUS quantitative indicator rise time and mean transit time were significantly changed, which can be used as an important indicator to predict responses.

The genetics of brown coat color and white spotting in domestic yaks (Bos grunniens).

Domestic yaks (Bos grunniens) exhibit two major coat color variations: a brown vs. wild-type black pigmentation and a white spotting vs. wild-type solid color pattern. The genetic basis for these variations in color and distribution remains largely unknown and may be complicated by a breeding history involving hybridization between yaks and cattle. Here, we investigated 92 domestic yaks from China using a candidate gene approach. Sequence variations in MC1R, PMEL and TYRP1 were surveyed in brown yaks; TYRP1 was unassociated with the coloration and excluded. Recessive mutations from MC1R, or p.Gln34*, p.Met73Leu and possibly p.Arg142Pro, are reported in bovids for the first time and accounted for approximately 40% of the brown yaks in this study. The remaining 60% of brown individuals correlated with a cattle-derived deletion mutation from PMEL (p.Leu18del) in a dominant manner. Degrees of white spotting found in yaks vary from color sidedness and white face, to completely white. After examining the candidate gene KIT, we suggest that color-sided and all-white yaks are caused by the serial translations of KIT (Cs6 or Cs29 ) as reported for cattle. The white-faced phenotype in yaks is associated with the KIT haplotype S(wf) . All KIT mutations underlying the serial phenotypes of white spotting in yaks are identical to those in cattle, indicating that cattle are the likely source of white spotting in yaks. Our results reveal the complex genetic origins of domestic yak coat color as either native in yaks through evolution and domestication or as introduced from cattle through interspecific hybridization.

Proline-rich tyrosine kinase 2 and its phosphorylated form pY881 are novel prognostic markers for non-small-cell lung cancer progression and patients' overall survival.

BACKGROUND: Our previous study revealed that proline-rich tyrosine kinase 2 (Pyk2) is implicated in both anchorage-independent growth and anoikis resistance in lung cancer cells. This study aims to explore the expression and clinical significance of Pyk2 and its phosphorylated forms in non-small-cell lung cancer (NSCLC). METHODS: The mRNA and protein levels of Pyk2 or cancer stem cell markers (ALDH1a1, ABCG2 and Bmi-1) were either examined by reverse transcription-PCR or western blotting. An immunohistochemistry (IHC) assay was conducted to analyse the expression of Pyk2 and its phosphorylated forms in 128 NSCLC cases. RESULTS: The levels of Pyk2 mRNA, total protein, and its phosphorylated form pY881 were higher in lung cancer lesions than in the paired noncancerous tissues. The IHC analysis showed the levels of the Pyk2 and Pyk2[pY881] proteins were highly expressed in 70 (54.7%) and 77 (60.2%) cases, respectively. Both Pyk2 and Pyk2[pY881] were independent prognostic factors for NSCLC patients. The gain and loss study of Pyk2 function revealed that Pyk2 could upregulate the expression of ALDH1a1, ABCG2 and Bmi-1 and enhance the ability of colony formation in soft agar assay in A549 and H460 cells. CONCLUSION: Both Pyk2 and phosphorylated Pyk2[pY881] are potential prognostic factors and therapeutic targets for NSCLC.

Bioequivalence and pharmacokinetic evaluation of two tablet formulations of carvedilol 25-mg: a single-dose, randomized-sequence, open-label, two-way crossover study in healthy Chinese male volunteers.

BACKGROUND: Carvedilol is a nonselective-blocking agent and is used in the treatment of hypertension and angina pectoris. OBJECTIVE: The aim of this study was to evaluate bioequivalence of two 25-mg tablet formulations of carvedilol following single oral dose in adult male volunteers. METHODS: This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 h after dosing. Plasma concentrations of Carvedilol were determined by using a validated LC-MS/MS method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0-24, and AUC0-∞ was conducted to determine bioequivalence. METHODS: 23 healthy male Chinese volunteers were enrolled in the study. The mean (SD) Cmax, AUC0-24, and AUC0-∞ values after administration of the test and reference formulations, respectively, were as follows: 73.71 (34.04) vs. 78.93 (43.64) ng/mL, 285.1 (147.0) vs. 296.9 (176.1) ng/mL · h, and 296.5 (161.4) vs. 303.4 (177.9) ng/mL · h. The 90% CIs of the ratios (test vs. reference) for the ln-transformed Cmax, AUC0-24, and AUC0 - ∞ were 85.3% to 114.3%, 90.4% to 107.6%, and 90.9% to 108.4%, respectively, meeting the criteria of SFDA, FDA and EMEA for bioequivalence. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study. CONCLUSIONS: The 90% CIs for the ratios of mean Cmax, AUC0-24, and AUC0-∞ met the regulatory criteria for bioequivalence.

A parallel design study to assess the bioequivalence of generic and branded hydroxychloroquine sulfate tablets in healthy volunteers.

Hydroxychloroquine (HCQ) is a racemic 4-aminoquinoline derivative that was first introduced as an antimalarial, and subsequently applied to the treatment of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Information on the pharmacokinetics of HCQ in healthy volunteers, especially in a Chinese population is limited, and this study was conducted to provide support for a generic product to obtain marketing authorization in China.The aim of the present study was to compare the pharmacokinetics and assess bioequivalence of a new generic test and the branded reference hydroxychloroquine sulfate tablets in healthy volunteers.This was a parallel, open-label, randomized, single-dose, 1-period fasting study. 54 healthy subjects were randomly assigned (1:1) to receive 200 mg hydroxychloroquine sulfate tablets of the test or the reference formulation. 15 blood samples were collected and whole blood concentrations of HCQ were determined by a validated liquid chromatography-isotopic dilution mass spectrometry method. Log-transformed Cmax and AUC0-24 values were used to test for bioequivalence. The 2 formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios of Cmax and AUC0-24 were within the predetermined bioequivalence range of 80-125%. Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and interviews with the subjects about adverse events.54 healthy subjects were enrolled and completed the study (mean [SD] age, height, body weight, and BMI were 23.9 [2.4] years, 168.9 [5.0] cm, 61.3 [5.4] kg, and 21.5 [1.7] kg/m2), 27 subjects per group. No formulation or sequence effects were observed. The mean values of Cmax and AUC0-24 for the test and reference formulations of HCQ (197.6 and 199.0 ng/mL, 2460.1 and 2468.3 ng/mL/h) were not significantly different. The 90% CIs of the ratios of Cmax and AUC0-24 were 99.3% (98.1-102.1%), 99.7% (98.9-101.4%), respectively. 4 subjects (7.41%) experienced a total of 4 mild AEs (headache and microscopic hematuria, 1 each; and increase in plasma triglycerides, 2).The results of this study suggest that the test and reference hydroxychloroquine sulfate tablets are bioequivalent. Both formulations were generally well tolerated.

Pharmacokinetics and bioequivalence of 2 tablet formulations of olanzapine in healthy Chinese volunteers: a randomized, open-label, single-dose study.

Olanzapine is a widely used agent for the treatment of schizophrenia.The aim of this study was to evaluate bioequivalence of two 10-mg tablet formulations of olanzapine following single oral dose in adult male volunteers.This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 72.0, 96.0, 120.0 and 144.0 h after dosing. Plasma concentrations of olanzapine were determined by using a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0-144, and AUC0-∞ was conducted to determine bioequivalence. Adverse events were monitored, recorded and evaluated by investigators throughout the study.24 healthy male Chinese volunteers between the ages of 18-40 years with a body mass index (BMI) between 19 and 24 kg/m2 were enrolled in the study. The mean (SD) Cmax, AUC0-144, and AUC0-∞ values after administration of the test and reference formulations, respectively, were as follows: 18.91 (5.320) vs. 18.44 (4.758) ng/mL, 582.9 (118.23) vs. 587.3 (127.12) ng/mL · h, and 615.4 (131.39) vs. 615.8 (137.45) ng/mL · h. The 90% CIs for the ratios of AUC0-144 and Cmax were 96.9% to 102.4% and 93.7% to 110.2%, respectively. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study.The 90% CIs for the ratios of mean Cmax, AUC0-144, and AUC0-∞ met the regulatory criteria for bioequivalence.

Correlated expression of gfp and Bt cry1Ac gene facilitates quantification of transgenic hybridization between Brassicas.

Gene flow from transgenic oilseed rape (BRASSICA NAPUS) might not be avoidable, thus, it is important to detect and quantify hybridization events with its relatives in real time. Data are presented showing the correlation between genetically linked green fluorescent protein (GFP) with BACILLUS THURINGIENSIS (Bt) CRY1AC gene expression in hybrids formed between transgenic B. NAPUS "Westar" and a wild Chinese accession of wild mustard (B. JUNCEA) and hybridization between transgenic B. NAPUS and a conspecific Chinese landrace oilseed rape. Hybrids were obtained either by spontaneous hybridization in the field or by hand-crossing in a greenhouse. In all cases, transgenic hybrids were selected by GFP fluorescence among seedlings originating from seeds harvested from B. JUNCEA and the Chinese oilseed rape plants. Transgenicity was confirmed by PCR detection of transgenes. GFP fluorescence was easily and rapidly detected in the hybrids under greenhouse and field conditions. Results showed that both GFP fluorescence and Bt protein synthesis decreased as either plant or leaf aged, and GFP fluorescence intensity was closely correlated with Bt protein concentration during the entire vegetative lifetime in hybrids. These findings allow the use of GFP fluorescence as an accurate tool to detect gene-flow in time in the field and to conveniently estimate BT CRY1AC expression in hybrids on-the-plant.

Modified gamma-cyclodextrins and their rocuronium complexes.

A series of per-6-substituted cyclodextrin derivatives was synthesized as synthetic host molecules for rocuronium, a steroidal muscle relaxant. By forming host-guest complexes with rocuronium, these cyclodextrin derivatives reverse the muscle relaxation induced by rocuronium in vitro and in vivo. The isothermal microcalorimetry data are consistent with the biological data supporting the encapsulation mechanism of action. Binary and biphasic complexes are reported with NMR experiments clearly showing free and bound rocuronium. [structure: see text]