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Cigarettes with pronounced astringency can diminish consumers' enjoyment. However, due to the complex composition of cigarettes, quantifying astringency intensity accurately has been challenging. To address this, research was conducted to develop a method for assessing astringency intensity in a simulated oral environment. The astringency intensity of four cigarette brands was determined using the standard sensory evaluation method. The mainstream smoke absorbing solution (MS) was prepared by simulating the cigarette smoking process, and its physicochemical properties (such as total phenol content and pH levels) were analyzed. The lubrication properties of the five solutions were tested using the MFT‐5000 wear tester, and factors influencing cigarette astringency were examined. The findings showed that total phenol content and pH of MS were positively and negatively correlated with astringency intensity, respectively. Particularly, the lubrication properties of MS were significantly correlated with astringency intensity, and the correlation coefficient was affected by load and speed during testing. The study concluded that coefficient of friction was a more reliable measure for assessing the extent of astringency in cigarettes than the total phenol content and pH of MS, offering new insights into astringency evaluation and development of high‐grade cigarettes. [ABSTRACT FROM AUTHOR]

Purpose: A substantial proportion of patients with major depressive disorder (MDD) does not respond or cannot tolerate to currently available treatments. This study was to assess the safety and tolerability of Remote Limb Ischemic Preconditioning (RLIPC) as an adjunctive therapy in patients with MDD. Patients and Methods: Enrolled patients underwent RLIPC, five cycles of simultaneous bilateral arm ischemia, 5 min and followed by reperfusion of each cycle, and once daily for eight consecutive weeks. Depression and anxiety severity, and quality of life were assessed every 2 weeks. Descriptive analysis was used for safety and tolerability data. Results: Thirty-seven participants completed at least one RLIPC. Twenty-four of them (64.9%) completed the study. Twelve patients prematurely discontinued the study due to poor adherence, and one due to a mild side effect. The changes in HRSD-17, GAD-7 and QOL-6 total scores from baseline to the endpoint were significant from the end of second week treatment onwards. The responder and remission rates were 59.46% (22/37) and 54.05% (20/37) at the endpoint, respectively. Conclusion: RLIPC was safe and well tolerated, and may be effective in reducing depressive symptoms in patients with MDD. Large studies are warranted to test its efficacy and safety as monotherapy or adjunctive therapy in the treatment of MDD. [ABSTRACT FROM AUTHOR]

Abstract: The efficiency of anticancer therapy is often restricted by the development of drug resistance. Here, we report that the doxorubicin (DOX)-resistant MCF-7/Adr cells were more resistant to DOX-treatment than MCF-7 cells. However, an alternative treatment of DOX/TNF-α enhanced the cytotoxic effect in multidrug resistant MCF-7/Adr cell line. Treatment of cells with TNF-α following doxorubicin (DOX) resulted in a decrease of the activated Rel A/p65 in nuclei. Histone deacetylase 1 (HDAC1) was found to interact with Rel A/p65 in the complex, suggesting that HDAC1 is involved in mediating nuclear export of Rel A/p65. The combined treatment of TNF-α/DOX also resulted in a significant decrease of mRNA levels of anti-apoptotic genes, such as the cellular inhibitor of apoptosis-1 (c-IAP1), and the long isoform of B cell leukemia/lymphoma x gene (Bcl-xL), leading to efficient induction of caspase-8 cleavage and cell death. In previous work, we demonstrated that TNF-α promotes DOX-induced cell death and anti-cancer effect through downregulation of p21 in p53-deficient tumor cells. Thus, we proposed that alternative administration of TNF-α and DOX may be a new and efficient therapeutic strategy for patients that develop resistance to cytotoxic treatment. [Copyright &y& Elsevier]

Abstract: The better adaptation of native Tibetans to hypoxia is thought to be partly due to improved umbilical circulation, which results in reduced pre- and postnatal fatalities. We hypothesized that the difference in umbilical circulation between native Tibetans and other high-altitude inhabitants was due to differences in the expression of hypoxia-induced factor (HIF-1) and its target genes vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). We tested this hypothesis by examining the effect of hypoxia on the expression of HIF-1α, VEGF, and iNOS in cultured umbilical venous endothelial cells (UVECs) from native Tibetans and immigrant Hans. UVECs were collected and cultured under hypoxic (0.5% oxygen) or normoxic conditions for 2, 4, 12 and 24 h. The mRNA levels of HIF-1α, VEGF, endothelial nitric oxide synthase (eNOS) and iNOS and the protein level of HIF-1α were determined with RT-PCR and Western blot analyses, respectively. In both immigrant Han and Tibetans, HIF-1α mRNA was constitutively expressed under normoxic condition, and remained constant after hypoxic exposure. In contrast, HIF-1α protein was undetectable under normoxic condition, but underwent dynamic changes in response to hypoxia. It was induced at 4 h, peaked at 12 h, and remained elevated at 24 h. Concurrent with the induction of HIF-1α protein, the mRNA levels of VEGF and iNOS were also up-regulated whereas that of eNOS was down-regulated. The lack of a hypoxia-related difference in the expression of HIF-1α and its target genes suggests that HIF-1α does not play a critical role in high altitude adaptation. Alternative mechanisms may be responsible for the better adaptation of native Tibetans. [Copyright &y& Elsevier]