Advancements in research on the association between the biological CLOCK and type 2 diabetes.

Due to the Earth's rotation, the natural environment exhibits a light-dark diurnal cycle close to 24 hours. To adapt to this energy intake pattern, organisms have developed a 24-hour rhythmic diurnal cycle over long periods, known as the circadian rhythm, or biological clock. With the gradual advancement of research on the biological clock, it has become increasingly evident that disruptions in the circadian rhythm are closely associated with the occurrence of type 2 diabetes (T2D). To further understand the progress of research on T2D and the biological clock, this paper reviews the correlation between the biological clock and glucose metabolism and analyzes its potential mechanisms. Based on this, we discuss the potential factors contributing to circadian rhythm disruption and their impact on the risk of developing T2D, aiming to explore new possible intervention measures for the prevention and treatment of T2D in the future. Under the light-dark circadian rhythm, in order to adapt to this change, the human body forms an internal biological clock involving a variety of genes, proteins and other molecules. The main mechanism is the transcription-translation feedback loop centered on the CLOCK/BMAL1 heterodimer. The expression of important circadian clock genes that constitute this loop can regulate T2DM-related blood glucose traits such as glucose uptake, fat metabolism, insulin secretion/glucagon secretion and sensitivity in various peripheral tissues and organs. In addition, sleep, light, and dietary factors under circadian rhythms also affect the occurrence of T2DM.

Habitual physical activity improves outcomes among patients with myocardial infarction.

Purpose: This study evaluates the association between habitual physical activity (HPA) and the outcomes of patients with myocardial infarction (MI). Methods: Patients newly diagnosed with MI were divided into two groups based on whether they engaged in HPA, defined as an aerobic activity with a duration of no less than 150 min/week, before the index admission. The primary outcomes included major adverse cardiovascular events (MACEs), cardiovascular (CV) mortality, and cardiac readmission rate 1 year following the index date of admission. A binary logistic regression model was applied to analyze whether HPA was independently associated with 1-year MACEs, 1-year CV mortality, and 1-year cardiac readmission rate. Results: Among the 1,266 patients (mean age 63.4 years, 72% male), 571 (45%) engaged in HPA, and 695 (55%) did not engage in HPA before MI. Patients who participated in HPA were independently associated with a lower Killip class upon admission (OR = 0.48: 95% CI, 0.32-0.71, p < 0.001) and a lower prevalence of 1-year MACEs (OR = 0.74: 95% CI, 0.56-0.98, p = 0.038) and 1-year CV mortality (OR = 0.50: 95% CI, 0.28-0.88, p = 0.017) than those who did not participate in HPA. HPA was not associated with cardiac-related readmission (OR = 0.87: 95% CI, 0.64-1.17, p = 0.35). Conclusions: HPA before MI was independently associated with a lower Killip class upon admission, 1-year MACEs, and 1-year CV mortality rate.

Synthesis of sophocarpine triflorohydrazone and its proliferation inhibition and apoptosis induction activity in myeloma cells through Notch3-p53 signaling activation.

Multiple myeloma is indicated by the presence of excessive monoclonal plasma cells in bone marrow, which result in the formation of osteolytic lesions. The present study investigated SCA as anti-proliferative agent for myeloma cells and explored the mechanism associated. Effect of SCA on viabilities of KRASA12 and AMO-1 cells was evaluated by MTT assay and apoptotic ratio using flow cytometry. Protein expression was investigated by western blotting and expression of genes related to Notch3-p53 signaling axis using RT-PCR assay. Increase in SCA concentration caused a significant (P < .01) reduction in KRASA12 and AMO-1 cell viability. The KRASA12 and AMO-1 cell viabilities were reduced to 29% and 21%, respectively on treatment with 21 µM doses of SCA. SCA treatment of KRASA12 and AMO-1 cells significantly (P < .05) increased apoptosis compared with untreated cells. The Bcl-2 (26 kDa) protein expression was reduced whereas the Bax (21 kDa) and cleaved caspase-3 levels elevated in SCA treated KRASA12 and AMO-1 cells. Treatment with SCA significantly promoted Hes1, p53 (53 kDa) and Hey1 mRNA expression in KRASA12 and AMO-1 cells. Treatment of KRASA12 and AMO-1 cells with SCA led to a marked reduction in Notch3 protein expression. SCA inhibits KRASA12 and AMO-1 myeloma cell proliferation by promoting pro-apoptotic proteins. Moreover, SCA treatment suppressed Hes1 and Hey1 mRNA expression and targeted Notch3 expression. Therefore, SCA may be studied further for development of treatment for myeloma.

Dihydroartemisinin treatment of multiple myeloma cells causes activation of c-Jun leading to cell apoptosis.

The aim of the present study was to investigate the effect of dihydroartemisinin (DHA) on a multiple myeloma cell line. An MTT assay, flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) were used for the analysis of cell viability, cell cycle distribution and c-Jun N-terminal kinase (JNK) expression, respectively. Treatment of U266 cells using DHA caused a significant (P<0.05) decrease in cell viability compared with the control cells. An increase in the concentration of DHA from 1 to 100 µmol/l reduced cell viability from 87 to 35% compared with 100% in the control cultures at 48 h. A significant (P<0.05) increase was observed in the sub-G0/G1 phase population of the U266 cells with an increase in DHA concentration from 1 to 100 µmol/l. Treatment with 1, 3, 10, 30 and 100 µmol/l concentrations of DHA increased the sub-G0/G1 phase cell population to 3.13, 8.25, 24.91, 31.47 and 38.54%, respectively. RT-PCR analysis of DHA-treated or -untreated U266 cells after 48 h demonstrated a significant (P<0.01) increase in caspase-3 expression. Treatment of the cells for 48 h with DHA led to a significant increase in c-Jun expression. DHA treatment at 1, 3, 10, 30 and 100 µmol/l concentrations caused an increase in the level of c-Jun by 0.174±0.001, 0.254±0.002, 0.387±0.001, 0.502±0.003 and 0.679±0.005, respectively, compared with 0.982±0.001 in the control cells. The addition of SP600125 to the cells incubated with DHA resulted in a significant decrease in the caspase-3 and c-Jun expression levels compared with those cells incubated with DHA alone. These findings confirm that treatment with DHA increased caspase-3 and c-Jun expression in the U266 cells through activation of the JNK signaling pathway. Thus, DHA inhibited proliferation of multiple myeloma cells by interfering with the JNK signaling pathway.

Continuous representation of human portraits and natural scenery in human ventral temporal cortex: evidence from functional magnetic resonance imaging.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has become a powerful tool for tracking human brain activity in vivo. This technique is mainly based on blood oxygenation level dependence (BOLD) contrast. In the present study, we employed this newly developed technique to characterize the neural representations of human portraits and natural sceneries in the human brain. METHODS: Nine subjects were scanned with a 1.5 T magnetic resonance imaging (MRI) scanner using gradient-recalled echo and echo-planar imaging (GRE-EPI) pulse sequence while they were visually presented with 3 types of white-black photographs: natural scenery, human portraits, and scrambled nonsense pictures. Multiple linear regression was used to identify brain regions responding preferentially to each type of stimulus and common regions for both human portraits and natural scenery. The relative contributions of each type of stimulus to activation in these regions were examined using linear combinations of a general linear test. RESULTS: Multiple linear regression analysis revealed two distinct but adjacent regions in both sides of the ventral temporal cortex. The medial region preferentially responded to natural scenery, whereas the lateral one preferentially responded to the human portraits. The general linear test further revealed a distribution gradient such that a change from portraits to scenes shifted areas of activation from lateral to medial. CONCLUSIONS: The boundary between portrait-associated and scenery-associated areas is not as clear as previously demonstrated. The representations of portraits and scenes in ventral temporal cortex appear to be continuous and overlap.