Ractopamine at legal residue dosage accelerates atherosclerosis by inducing endothelial dysfunction and promoting macrophage foam cell formation.

Ractopamine, a synthetic ß-adrenoreceptor agonist, is used as an animal feed additive to increase food conversion efficiency and accelerate lean mass accretion in farmed animals. The U.S. Food and Drug Administration claimed that ingesting products containing ractopamine residues at legal dosages might not cause short-term harm to human health. However, the effect of ractopamine on chronic inflammatory diseases and atherosclerosis is unclear. Therefore, we investigated the effects of ractopamine on atherosclerosis and its action mechanism in apolipoprotein E-null (apoe-/-) mice and human endothelial cells (ECs) and macrophages. Daily treatment with ractopamine for four weeks increased the body weight and the weight of brown adipose tissues and gastrocnemius muscles. However, it decreased the weight of white adipose tissues in apoe-/- mice. Additionally, ractopamine exacerbated hyperlipidemia and systemic inflammation, deregulated aortic cholesterol metabolism and inflammation, and accelerated atherosclerosis. In ECs, ractopamine treatment induced endothelial dysfunction and increased monocyte adhesion and transmigration across ECs. In macrophages, ractopamine dysregulated cholesterol metabolism by increasing oxidized low-density lipoprotein (oxLDL) internalization and decreasing reverse cholesterol transporters, increasing oxLDL-induced lipid accumulation. Collectively, our findings revealed that ractopamine induces EC dysfunction and deregulated cholesterol metabolism of macrophages, which ultimately accelerates atherosclerosis progression.

Tuberculosis Surveillance in Taiwan Forensic Autopsy Cases: A Retrospective Analysis of 71 Cases From 2012 to 2017.

Tuberculosis (TB) is one of the most important public health issues worldwide, and global efforts have altered the TB epidemic. This study analyzed 71 cases of TB at autopsy notified via Taiwan Medical Examiner Surveillance for Lethal Infectious Disease (Taiwan Med-X) between 2012 and 2017 and applied immunohistochemistry to formalin-fixed lung tissue. Tuberculosis was present in 0.57% (71/12,369) forensic autopsy cases in the institute. Among the study cases, 30 (42.3%) cases were newly diagnosed with TB at autopsy, whereas 41 (57.7%) cases were notified before death and have still seen the TB pathological changes. Regarding the death investigation, cause of death was TB accounted for 46.5%, and non-TB, 53.5% (including trauma, 26.8%; other diseases, 19.7%; drowning, 4.2%; and drug abuse, 2.8%, respectively). Compared with the staining signal, immunohistochemistry has better sensitivity than acid-fast staining. This study provides a reassessment of the reference value to estimate the burden of disease caused by TB and emphasizes the importance of biosafety in an autopsy room.

Fatal parvovirus B19 infections: a report of two autopsy cases.

Parvovirus B19 (PVB19) commonly infects children and is usually asymptomatic. Lethal outcomes of PVB19 infection are unusual; nevertheless, the two cases reported here are rare examples of PVB19-induced hemophagocytic syndrome and myocarditis in infants and children. The two cases show the indisputable usefulness of immunohistochemistry and in situ hybridization in the detection of PVB19. In the death investigations, histopathological examinations provided stronger evidence than did serology or molecular biology. The cases also highlight the importance of forensic autopsy in vaccine-related death. As vaccine-related deaths are what people fear and may cause declines in vaccination rates, it is important to clarify deaths temporally or causally associated with vaccine administration.

Resveratrol inhibits alpha-melanocyte-stimulating hormone signaling, viability, and invasiveness in melanoma cells.

Melanoma is a malignancy with high potential to invasion and treatment resistance. The α -melanocyte-stimulating hormone ( α -MSH) signal transduction involving Wnt/ ß -catenin, c-Kit, and microphthalmia-associated transcription factor (MITF), a known pathway to produce melanin, has been demonstrated as one of cancer stem cell characteristics. This study was aimed to examine the effect of resveratrol, an abundant ingredient of grape and medicinal plants, on α -MSH signaling, viability, and invasiveness in melanoma cells. By α -MSH treatment, the melanin production in B16 melanoma cells was augmented as a validation for activation of α -MSH signaling. The upregulated expression of α -MSH signaling-related molecules ß -catenin, c-Kit, and MITF was suppressed by resveratrol and/or STI571 treatment. Nuclear translocation of MITF, a hallmark of α -MSH signaling activation, was inhibited by combined treatment of resveratrol and STI571. At effective concentration, resveratrol and/or STI571 inhibited cell viability and α -MSH-activated matrix metalloproteinase- (MMP-)9 expression and invasion capacity of B16 melanoma cells. In conclusion, resveratrol enhances STI571 effect on suppressing the α -MSH signaling, viability, and invasiveness in melanoma cells. It implicates that resveratrol may have potential to modulate the cancer stem cell characteristics of melanoma.