Experience with primary malignant lymphoma in the breast at the Barnes Hospital is reviewed and analyzed. Sixteen cases were found which satisfied our criteria. Eleven were classified as malignant lymphoma, histiocytic type, and five as lymphocytic type. No cases of Hodgkin's disease were identified. Several intesting associations were noted. Two cases were associated with pregnancy. One case was preceded by carcinoma and another by cystic mastitis; both cases were proved by biopsy. Bilateral breast involvement by tumor was seen four times. Primary mammary lymphoma is an aggressive disease, with a high predilection for the right breast. Histologically, the tumor tends to infiltrate between mammary ducts without destroying them. In spite of various therapies, only three patients survived 5 years.

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The prevailing theory in non-alcoholic fatty liver disease (NAFLD) is the "two-hit" hypothesis. The first hit mainly consists of lipid accumulation, and the second is subsequent systemic inflammation. The current study was undertaken to investigate whether inflammatory stress exacerbates lipid accumulation in liver and its underlying mechanisms. We

MYB transcription factors have been demonstrated to play key regulatory roles in plant growth, development and abiotic stress response. However, knowledge concerning the involvement of rice MYB genes in salinity and drought stress resistance are largely unknown. In the present study, we cloned and characterized the OsMYB6 gene, which was induced by drought and salinity stress. Subcellular localization of OsMYB6-YFP fusion protein in protoplast cells indicated that OsMYB6 was localized in the nucleus. Overexpression of OsMYB6 in rice did not suggest a negative effect on the growth and development of transgenic plants, but OsMYB6 -overexpressing plants showed increased tolerance to drought and salt stress compared with wild-type plants, as are evaluated by higher proline content, higher CAT and SOD activities, lower REL and MDA content in transgenic plants under drought and salt stress conditions. In addition, the expression of abiotic stress-responsive genes were significantly higher in OsMYB6 transgenic plants than that in wild-type plants under drought and salt stress conditions. These results indicate that OsMYB6 gene functions as a stress-responsive transcription factor which plays a positive regulatory role in response to drought and salt stress resistance, and may be used as a candidate gene for molecular breeding of salt-tolerant and drought-tolerant crop varieties.

Background. Transcutaneous auricular vagus nerve stimulation (ta-VNS) could evoke parasympathetic activities via activating the brainstem autonomic nuclei, similar to the effects that are produced after vagus nerve stimulation (VNS). VNS modulates immune function through activating the cholinergic anti-inflammatory pathway. Methods. VNS, ta-VNS, or transcutaneous electrical acupoint stimulation (TEAS) on ST36 was performed to modulate the inflammatory response. The concentration of serum proinflammatory cytokines and tissue NF-kappa B p65 (NF-κB p65) were detected in endotoxaemia affected anesthetized rats. Results. Similar to the effect of VNS, ta-VNS suppressed the serum proinflammatory cytokines levels, such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as well as NF-kappa B p65 expressions of lung tissues. ST36 stimulation also decreases LPS-induced high TNF-α level and NF-κB signal, but it did not restrain proinflammatory cytokine IL-1β and IL-6. Neither ta-VNS nor ST36 stimulation could suppress LPS-induced TNF-α and NF-κB after vagotomy or with α7nAChR antagonist injection. Conclusions. The present paper demonstrated that ta-VNS could be utilized to suppress LPS-induced inflammatory responses via α7nAChR-mediated cholinergic anti-inflammatory pathway.

Objective-Although inflammation is a recognized feature of atherosclerosis, the impact of inflammation on cellular cholesterol homeostasis is unclear. This study focuses on the molecular mechanisms by which inflammatory cytokines disrupt low-density lipoprotein (LDL) receptor regulation. Methods and Results-IL-1␤ enhanced transformation of vascular smooth muscle cells into foam cells by increasing uptake of unmodified LDL via LDL receptors and by enhancing cholesterol esterification as demonstrated by Oil Red O staining and direct assay of intracellular cholesterol concentrations. In the absence of IL-1␤, a high concentration of LDL decreased LDL receptor promoter activity, mRNA synthesis and protein expression. However, IL-1␤ enhanced LDL receptor expression, overriding the suppression usually induced by a high concentration of LDL and inappropriately increasing LDL uptake. Exposure to IL-1␤ also caused overexpression of the sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP), and enhanced its translocation from the endoplasmic reticulum to the Golgi, where it is known to cleave SREBP, thereby enhancing LDL receptor gene expression. Key Words: atherosclerosis Ⅲ cytokine Ⅲ LDL receptor Ⅲ SREBP cleavage-activating protein Ⅲ vascular smooth muscle cells H yperlipidemia is a recognized risk factor for cardiovascular morbidity and mortality. Among plasma lipid components, increased serum levels of low-density lipoprotein (LDL) cholesterol have been most closely correlated with the incidence of cardiovascular disease, whereas high-density lipoprotein cholesterol (HDL) is considered protective. 1,2 A series of large-scale clinical trials have shown that lipidlowering therapy reduces morbidity and mortality from coronary heart disease (CHD). Statin therapy, which lowers plasma LDL cholesterol levels by 30% to 50%, reduced major coronary events by 27%. 3 Recent experimental evidence suggests that inflammation is an aggravating factor in atherogenesis, 4 as might be predicted from the fact that all the main cell types in an atherosclerotic lesion produce a variety of inflammatory cytokines. Elevated plasma levels of inflammatory cytokines have also been found in patients with established atherosclerotic disease, 5,6 whereas patients with elevated levels of acute-phase reactants (reflecting enhanced hepatic production in response to circulating inflammatory cytokines) have a less favorable clinical course than those with normal levels. 7 Furthermore, observational studies in patients with chronic inflammatory diseases have also shown an increased risk of premature cardiovascular disease morbidity and mortality. 8 The mechanisms by which activation of the inflammatory response may contribute to atherosclerosis are not fully understood but it is possible that inflammation interacts with other modifiable risk factors such as hypercholesterolemia in the initiation and progression of atherosclerotic lesions. Such interaction may help to explain why in patients with chronic activation of the inf...

Ma KL, Ruan XZ, Powis SH, Moorhead JF, Varghese Z. Antiatherosclerotic effects of sirolimus on human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 292: H2721-H2728, 2007. First published February 23, 2007 doi:10.1152/ajpheart.01174.2006.-Sirolimus is a potent immunosuppressive agent and has an anti-atherosclerotic effect through its anti-proliferative property. The present study was undertaken to investigate the effect of sirolimus on intracellular cholesterol homeostasis in human vascular smooth muscle cells (VSMCs) in the presence of inflammatory cytokine IL-1␤. We explored the effect of sirolimus on the lipid accumulation of VSMCs in the presence of IL-1␤, using Oil Red O staining and quantitative measurement of intracellular cholesterol. The effect of sirolimus on the gene and protein expression of lipoprotein receptors and ATP binding cassettes (ABCA1 and ABCG1) was examined by real-time PCR and Western blotting, respectively. Furthermore, the effect of sirolimus on cholesterol efflux from VSMCs in the presence or absence of IL-1␤ was also investigated using [ 3 H] cholesterol efflux. Finally, we examined the effect of sirolimus on the production of inflammatory cytokines in VSMCs using ELISA. Sirolimus reduced intracellular lipid accumulation in VSMCs mediated by IL-1␤ possibly due to the reduction of expression of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) receptors. Sirolimus increased cholesterol efflux from VSMCs and overrode the suppression of cholesterol efflux induced by IL-1␤. Sirolimus also increased ABCA1 and ABCG1 genes expression, even in the presence of IL-1␤. We further confirmed that sirolimus inhibited mRNA and protein expression of inflammatory cytokines IL-6, tumor necrosis factor-␣, IL-8, and monocyte chemoattractant protein-1. Inhibition of lipid uptake together with increasing cholesterol efflux and the inhibition of inflammatory cytokines are all important aspects of the anti-atherosclerotic effects of sirolimus on VSMCs. cholesterol homeostasis; foam cell; inflammatory cytokine ATHEROSCLEROSIS is a multifactorial disease; disordered lipid metabolism and chronic inflammation are important contributory factors (16,32). Vascular smooth muscle cells (VSMCs) play a key role during the pathogenesis of vascular lesion, although they are not always the main cell component of atherosclerotic lesions, especially in the early stages. In normal vessels, the majority of VSMCs reside in the media, where they are quiescent and possess a "contractile" phenotype characterized by the abundance of actin-and myosin-containing filaments (4, 33). In disease states, VSMCs reenter the cell cycle, proliferate, and migrate from media to intima (33). After vessel injury, intimal VSMCs have a synthetic phenotype, characterized by hyperplasia or hypertrophy and matrix protein accumulation in the intima and/or media with or without lipid deposition, resulting in thickening and stiffness of the arterial wall. Foam cells have traditionally been regarded as being derived f...

IntroductionEarly screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China.Research design and methodsThe study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation.ResultsIn total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups.ConclusionThis study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers.Trial registration numberNCT04240652.