The clock gene PER1 plays an important role in regulating the clock gene network in human oral squamous cell carcinoma cells The clock gene PER1 plays an important role in regulating the clock gene network in human oral squamous cell carcinoma cells

As a rare lymphoproliferative disorder, many patients with HHV-8/HIV-negative Castleman disease (CD) have hypoalbuminemia. However, data is limited on whether hypoalbuminemia is an independent predictor of CD. We retrospectively collected data from 230 patients diagnosed at 12 medical centers in China and the U.S. Different classifications included 147 patients with unicentric CD (UCD) and 83 with idiopathic multicentric CD (iMCD). Adjusted smooth curve fitting showed that the relationship between albumin and all-cause death of patients with CD and iMCD was linear. Cox proportional hazards regression modeling showed a negative association between the risk of death and albumin level (hazard ratio [HR]: 0.84; 95% CI, 0.76, 0.93). Using the Kaplan–Meier method, we determined that hypoproteinemia was a risk factor for poorer prognosis in patients with CD, UCD, and iMCD. Albumin was independently and negatively associated with the risk of death in CD patients, especially those with iMCD.

The oncogenic bcr/abl1 fusion gene is a chronic myelogenous leukemia (CML)-specific antigen which is absent in normal tissues. This makes bcr/abl1 a perfect target for developing CML vaccines that elicit specific immune responses against minimal residual disease while sparing normal tissue. The aim of this study was to use different methods to induce dendritic cells (DCs) derived from patients with CML (CML-DCs) and analyze them for CML-specific tumor cytotoxicity for immune therapy. Bone marrow-derived mononuclear cells from ten CML patients were studied to induce CML-DC differentiation in the presence of recombinant human interleukin-4, rh-granulocyte-macrophage-colony stimulating factor, and tumor necrosis factor-alpha with either a total RNA-lipofectamine complex, total RNA or CML tumor lysate (freeze–thawed). CML-DC maturation, confirmed by expression of CD1α, CD40, CD80, CD83, CD86 and by real-time polymerase chain reaction, validated the CML-origin of these DC cells. CML-DCs stimulated cytotoxic T-cell (CTL) apoptosis, high levels of IL-12 secretion, and had significant inhibitory effect on K562 tumorigenicity in nude mice. CML-DCs pulsed with total RNA by lipofectamine transfection produced the strongest effect in tumor-specific CTL functions. These results indicate that CML-DCs transfected with total RNA by lipofectamine induce the strongest CTL cytotoxicity and have the greatest potential for CML immune therapy. This study holds promise for a DC-based strategy for inducing anti-leukemia responses and establishes a foundation for developing RNA vaccination against CML.

BACKGROUND: Endothelial-to-mesenchymal transition (EndMTE) is implicated in atherosclerosis by contributing to endothelial dysfunction (ED). SMS2 (sphingomyelin synthase 2), a key enzyme in sphingomyelin synthesis, plays a significant role in both ED and atherosclerosis. Nonetheless, the precise mechanisms of SMS2-associated ED, and its potential modulation via EndMT remain unexplored in the context of ED and atherosclerosis progression. METHODS: To investigate this, we inhibited SMS2 activity using the inhibitor Ly93 and performed RNA sequencing on human umbilical vein endothelial cells. Furthermore, we validated the potential mechanisms of EndMT in human umbilical vein endothelial cells, Apo E ^−/− mice, and human atherosclerotic plaques. RESULTS: SMS2 inhibition suppressed EndMT by blocking the Wnt/β-catenin pathway. This blockade attenuated PPARγ (peroxisome proliferator-activated receptor gamma) ubiquitination-mediated degradation via PPARγ-β-catenin interaction, ultimately reducing CPT1A expression and fatty acid oxidation. In vivo, endothelial cell-specific overexpression of SMS2 in ApoE ^−/− mice enhances atherosclerosis, and SMS2 positively correlates with Wnt/β-catenin, EndMT, and ED, but inversely correlates with PPARγ activity and fatty acid oxidation. Furthermore, in the unstable atherosclerosis plaques of humans, the expression of SMS2 in endothelial cells is significantly higher compared with that in stable plaques. The relationship between SMS2 and Wnt/β-catenin, EndMT, ED, PPARγ, and fatty acid oxidation aligns with the aforementioned findings. CONCLUSIONS: SMS2 can activate the Wnt/β-catenin pathway, which is inversely correlated with the activity of PPARγ and fatty acid oxidation. This process facilitates EndMT and ED, ultimately contributing to the initiation and development of atherosclerosis. These findings suggest that inhibition of endothelial SMS2 activity with Ly93 could be beneficial for the treatment of atherosclerosis.

To observe the effect of curcumin on the morphology of the hippocampus in young and aged rats with vascular dementia (VD) induced by chronic cerebral hypoperfusion, then further investigate whether the effect of curcumin have any differences in age. Both young and aged Male Sprague-Dawley rats were randomly divided into normal control group, sham-operated group, 2VO group, 2VO+curcumin 50mg/Kg group and 2VO+curcumin 100mg/Kg goup. Permanent occlusion of bilateral common carotid arteries ligation (2VO) method was used to establish chronic cerebral ischemia model. The rats were injected intraperitoneally with curcumin or DMSO once daily for 30d. The pathological changes of CA1 region of the hippocampus were measured by HE staining and Nissl staining. Chronic cerebral ischemia led to pathological changes of young and aged rats, but no significant differences were found between the two ages of rats (t=0.658，P=0.523). Furthermore, curcumin could reduce the pathological injury of CA1 region of the hippocampus in young and aged VD rats, no significant differences were found between the two ages of rats (P=0.384，P=0.380). Curcumin can reduce the brain damage in young and aged VD rats in dose-dependent manner but without age difference. Our study suggests that the pathological injury of the hippocampus might be one of the mechanisms of curcumin’s protection effect of VD rats.