[The characteristics and risk factors of cardiovascular diseases and psychological status in science and technologyists].

Objectives: To investigate the prevalence and related factors of cardiovascular diseases (CVD) and psychological problems in Chinese science and technology workers. Methods: The investigation was organized and conducted by the Innovative and Development Institute of China Association of Senior Scientists and Technologists and Capital Medical University Affiliated Beijing Anzhen Hospital, and included science and technology workers from research institutions and medical institutions in China by random sampling methods through face-to-face and online questionnaire investigation from July 1, 2019 to March 31, 2021. Information including age, sex, work stress status, CVD history, sleep, depression, and anxiety were included in the questionnaire. Results: This survey included 14 552 subjects. Among them, 25.5% were suffered from CVD, 48.6% were with insomnia, 28.8% experienced depression/anxiety (including only depression, only anxiety, depression combined with anxiety), and 15.6% had CVD in combined with depression/anxiety. Taking those without CVD and depression/anxiety as reference group, multiple logistic regression analyses showed that work stress increased the risk of depression/anxiety in subjects without CVD (manageable work stress, OR=2.253, 95%CI 1.583-3.206, overwhelming work stress OR=7.899, 95%CI 5.094-12.250), and drinking increased the risk of CVD (OR=1.978, 95%CI 1.382-2.833). Moreover, overwhelming work stress (OR=4.012, 95%CI 2.515-6.399) and smoking (OR=2.342, 95%CI 1.603-3.421) increased the risk of depression/anxiety in subjects with CVD (all P<0.001). Conclusion: The high morbidities of depression/anxiety, CVD, and CVD in combination with depression/anxiety urge us to take actions to protect the heart and mental health of scientific and technological workers.

Distribution of LIM domain kinase 1 in the olfactory bulb, cerebral cortex, hippocampus, and cerebellum of the App/PS+/- mice.

LIM domain kinase 1 (LIMK1), an actin-binding kinase, can phosphorylate and inactivate its substrates, and can regulate long-term memory and synaptic plasticity. Both ß-amyloid precursor protein (App) and presenilin (PS) are functional degeneration factors during early neuronal development, and are considered as potential factors that contribute to the development of Alzheimer's disease (AD). However, hardly any information is available about the distribution and expression of LIMK1. Thus, using the App and PS deficient mice, the role of LIMK1 was demonstrated in the absence of App and PS. Our results showed that LIMK1 was present in the nerve fiber layer and external plexiform layer of the olfactory bulb, as well as in the mitral cells and Purkinje cells of the cerebellum in App and PS deficient mice. Additionally, LIMK1 was concentrated in the granule cell layer of the olfactory bulb and cerebellum and LIMK1 positive cells were located in the CA1 region of the hippocampus. Our study indicates that there is a connection between LIMK1 and AD in the mouse model of AD. This might explain neurological problems such as cerebellar ataxia, impaired long-term memory, and impaired synaptic plasticity observed in AD.

Risk of postoperative deep venous thrombosis in patients with colorectal cancer treated with open or laparoscopic colorectal surgery: a meta-analysis.

INTRODUCTION: Whether the incidence rate of deep venous thrombosis (DVT) between laparoscopic and open colorectal cancer surgery the same or not were under the debated without conclusion. The aim of this study was to compare the incidence of DVT after laparoscopic or open colorectal cancer surgery by meta-analysis. MATERIALS AND METHODS: The open published articles comparing the incidence of DVT after laparoscopic or open colorectal cancer were collected in the data bases of Medline, the Cochrane central register of controlled trials and CNKI. The relative risk (RR) was pooled by using random or fixed effect mode to evaluate the incidence of DVT between laparoscopic or open colorectal cancer surgery. RESULTS: After searching the databases, 9 randomized clinical studies with 2606 colorectal cancer cases were included in this meta-analysis. The mean operation time was 201.8 ± 17.28 min with its range of 180.0-224.4 min in the laparoscopic surgery group and 148.1 ± 18.8 min with its range of 135.0-184.0 min in the open surgery group. The operation time for laparoscopic surgery group were significant lower than in the open surgery group (P < 0.05). The RR of DVT between the laparoscopy and open surgery groups was 0.71 with its 95% confidence interval of 0.35-1.45 (P = 0.35). CONCLUSIONS: The operation time in laparoscopic colorectal cancer surgery was statistical longer than in the open colorectal cancer surgery, but the DVT risk of the two surgery approach was not different according to this meta-analysis.

Prognostic significance of multidrug resistance protein in adult T-cell leukemia.

The response of adult T-cell leukemia (ATL) to chemotherapy is poor, and a major obstacle to successful treatment is intrinsic or acquired drug resistance. To determine the clinical significance of multidrug resistance protein (MRP) 1 in ATL, we studied MRP1 expression and its association with clinical outcome. The expression of MRP1 mRNA in leukemia cells from 48 ATL patients was studied by slot blot analysis. The expression level of MRP1 mRNA in chronic-type ATL was significantly higher than that in lymphoma-type ATL (P = 0.033). There was no correlation between MRP1 expression and age, gender, WBC count, LDH, hypercalcemia, blood urea nitrogen, or performance status. However, the expression of MRP1 mRNA correlated only with peripheral blood abnormal lymphocyte counts (P = 0.008). The transporting activity of MRP1 was assessed using membrane vesicles. Membrane vesicles prepared from ATL cells with high expression of MRP1 mRNA showed a higher ATP-dependent leukotriene C(4) uptake than did those with low expression of MRP1 mRNA. This uptake was almost completely inhibited by LTD(4) antagonists ONO-1078 and MK571. In acute- and lymphoma-type ATL, high expression of MRP1 mRNA at diagnosis correlated with shorter survival, and Cox regression analysis revealed that MRP1 expression was an independent prognostic factor. These findings suggest that functionally active MRP1 is expressed in some ATL cells and that it is involved in drug resistance and has a possible causal relationship with poor prognosis in ATL. Multidrug resistance-reversing agents, such as ONO-1078 and MK571, that directly interact and inhibit the transporting activity of MRP1 may be useful for treating ATL patients.

Reversal of drug resistance mediated by multidrug resistance protein (MRP) 1 by dual effects of agosterol A on MRP1 function.

We previously isolated agosterol A (AG-A) from a marine Spongia sp. and found that it completely reversed colchicine resistance in P-glycoprotein (Pgp)-over-expressing KB-C2 cells and vincristine resistance in multidrug-resistance protein (MRP)1-over-expressing CV60 cells. However, a tri-deacetylated derivative of AG-A (IAG-A) showed almost no activity in reversing Pgp- or MRP1-mediated drug resistance. In this study, we examined the mechanisms by which AG-A reverses MRP1-mediated drug resistance by investigating the interaction between agosterols and MRP1 in MRP1-over-expressing human KB carcinoma (KB/MRP) cells. [3H]-Leukotriene C4 (LTC4), [3H]-2,4-dinitrophenyl-S-glutathione uptake into membrane vesicles prepared from KB/MRP cells and intracellular [3H]-vincristine accumulation and efflux in KB/MRP cells were measured with or without AG-A and/or inactive IAG-A. AG-A reduced MRP1-mediated [3H]-LTC4 transport in a dose-dependent manner, but IAG-A did not. Inhibition by AG-A was competitive, with a K(i) value of 31 microM. AG-A at 10 microM enhanced the accumulation of [3H]-vincristine in KB/MRP cells to the level of that in control cells in the absence of the agent. Likewise, ATP-dependent efflux of [3H]-vincristine from KB/MRP cells was enhanced compared with KB-3-1 cells and inhibited by AG-A. In addition, AG-A reduced intracellular levels of glutathione, a compound required for MRP1-mediated transport of some anti-cancer drugs. These findings suggest that AG-A reverses MRP1-mediated drug resistance by directly inhibiting the capacity of MRP1 to transport drugs. In addition, the capacity of AG-A to reduce cellular glutathione levels may contribute to the modulating activity of MRP1.

Glutathione-dependent binding of a photoaffinity analog of agosterol A to the C-terminal half of human multidrug resistance protein.

MRP1 is a 190-kDa membrane glycoprotein that confers multidrug resistance (MDR) to tumor cells. MRP1 is characterized by an N-terminal transmembrane domain (TMD(0)), which is connected to a P-glycoprotein-like core region (DeltaMRP) by a cytoplasmic linker domain zero (L(0)). It has been demonstrated that GSH plays an important role in MRP1-mediated MDR. However, the mechanism by which GSH mediates MDR and the precise roles of TMD(0) and L(0) are not known. We synthesized [(125)I]11-azidophenyl agosterol A ([(125)I]azidoAG-A), a photoaffinity analog of the MDR-reversing agent, agosterol A (AG-A), to photolabel MRP1, and found that the analog photolabeled the C-proximal molecule of MRP1 (C(932-1531)) in a manner that was GSH-dependent. The photolabeling was inhibited by anticancer agents, reversing agents and leukotriene C(4). Based on photolabeling studies in the presence and absence of GSH using membrane vesicles expressing various truncated, co-expressed, and mutated MRP1s, we found that L(0) is the site on MRP1 that interacts with GSH. This study demonstrated that GSH is required for the binding of an unconjugated agent to MRP1 and suggested that GSH interacts with L(0) of MRP1. The photoanalog of AG-A will be useful for identifying the drug binding site within MRP1, and the role of GSH in transporting substrates by MRP1.

[Effect of jiaweiyiguanjian decoction on hypothalamus-pituitary-thyroid gland (HPT) in rat model with Yin-deficiency of liver and kidney induced by slow irritation].

OBJECTIVE: To explore the mechanism of Jiaweiyiguanjian decoction in nourishing the liver and kidney. METHOD: A rat model with Yin-deficiency of liver and kidney was made by way of slow irritation. Thyrotropin-releasing-hormone(TRH) of thyron and blood, TSH of pituitary and blood, thyroxine, 3,5,3',5-tetraiodothyronine(FT4) and 3,3',5-traiodothyronine(FT4), 3,3',5-traiodothyronine(rT3) were used as indexes to study the effect of the decoction on HPT. RESULT: The TRH Secretion from hypothalamus increased (P < 0.05), TSH of pituitary and blood reduced(P < 0.05), FT3 and FT4 of blood decreased at the same time and rT3 of blood, increased. The indexes of the treatment group were found almost the same as the those of the normal control group. CONCLUSION: Jiaweiyiguanjian Decoction could adjust HPT.

Functional comparison between YCF1 and MRP1 expressed in Sf21 insect cells.

YCF1 is a yeast vacuole membrane transporter involved in resistance to Cd(2+) and to exogenous glutathione S-conjugate precursors. MRP1 contributes to multidrug resistance (MDR) in tumor cells. MRP1 and YCF1 have extensive amino acid sequence homology (63% amino acid similarity). We expressed MRP1 or YCF1 in insect cell membranes and compared their functions to know more about their structure-function relationships. YCF1 and MRP1 with His epitopes were expressed in Sf21 insect cells; both of them in the plasma membrane. The ATP-dependent transport of [(3)H]LTC(4) in Sf/YCF1-His vesicles was osmotically sensitive and showed saturable kinetics with an apparent K(m) of 758 nM for LTC(4) and 94 microM for ATP which were similar to those in yeast cells. The K(m) of YCF1 for LTC(4) (758 nM) was sevenfold higher than that of MRP1 (108 nM). MK-571 and ONO-1078, reversing agents for MRP1-mediated MDR, considerably inhibited the transport of LTC(4) by both YCF1 and MRP1. However, PAK-104P, a pyridine analog that reverses MDR associated with P-gp and MRP1, inhibited the transporting activity of MRP1 stronger than that of YCF1. KE1, another MDR reversing agent, moderately inhibited the transport of LTC(4) by MRP1 but not that of YCF1. In conclusion, we successfully expressed yeast YCF1 in Sf21 insect cells and found that the localization of the protein was different from that in yeast. The function of YCF1 in Sf21 insect cells was similar but not identical to that of MRP1.

Hyperphosphorylation of keratins by treatment with okadaic acid of BALB/MK-2 mouse keratinocytes.

Protein hyper- or hypophosphorylation induced by okadaic acid (OA) treatment was examined using quiescent cultures of the BALB/MK-2 mouse epidermal keratinocytes. Treatment with OA enhanced the phosphorylation of five proteins with molecular weights of 65,000, 55,000, 50,000, 28,000 and 15,000 (p65, p55, p50, p28, and p15, respectively) and decreased that of two proteins with molecular weights of 22,000 and 20,000 (p22 and p20, respectively). The two major phosphorylated proteins, p65 and p55, were identified as type II and type I keratins, respectively, by immunoblotting and immunoprecipitation with keratin specific antibodies. Serine was the only phosphoamino acid residue in hydrolysates of the 32P-labeled keratins purified from OA-treated cells. Two-dimensional tryptic peptide maps of the phosphorylated keratins showed that the hyperphosphorylation was largely due to phosphorylation at several additional sites in both keratins. The hyperphosphorylation of keratins induced by OA treatment resulted in a drastic change in their solubility. This change closely correlated with reorganization of the keratin filament network, which finally collapsed into large perinuclear aggregates. Concomitantly the cells changed from a typical epithelial shape to a round shape. Of several protein kinase inhibitors tested, only staurosporine interfered with this OA-induced morphological change and reorganization of the keratin network.