Phyllanthus urinaria Induces Apoptosis in Human Osteosarcoma 143B Cells via Activation of Fas/FasL- and Mitochondria-Mediated Pathways

Phyllanthus urinaria (P. urinaria), in this study, was used for the treatment of human osteosarcoma cells, which is one of the tough malignancies with few therapeutic modalities. Herein, we demonstrated that P. urinaria inhibited human osteosarcoma 143B cells growth through an apoptotic extrinsic pathway to activate Fas receptor/ligand expression. Both intracellular and mitochondrial reactive oxygen species were increased to lead to alterations of mitochondrial membrane permeability and Bcl-2 family including upregulation of Bid, tBid, and Bax and downregulation of Bcl-2. P. urinaria triggered an intrinsic pathway and amplified the caspase cascade to induce apoptosis of 143B cells. However, upregulation of both intracellular and mitochondrial reactive oxygen species and the sequential membrane potential change were less pronounced in the mitochondrial respiratory-defective 143Bρ0 cells compared with the 143B cells. This study offers the evidence that mitochondria are essential for the anticancer mechanism induced by P. urinaria through both extrinsic and intrinsic pathways

Type 1 diabetes mellitus with diabetic ketoacidosis after immune checkpoint inhibitor therapy

Treatment with immune checkpoint inhibitors (ICIs) has introduced a new era of cancer therapy. Although ICIs are not closely associated with the side effects associated with chemotherapy such as nausea, vomiting and cytopenia, there are still adverse effects which are related to the blockade of normal immune regulatory mechanisms. Herein, we report a patient with adenocarcinoma of the gastroesophageal junction with liver metastasis who developed diabetic ketoacidosis after ICI therapy even though he had no history of diabetes mellitus (DM). The acute onset of DM can occur in patients who receive ICI therapy. The possibility of developing such a hyperglycemic side effect should be kept in mind. Keywords: Immune checkpoint inhibitor, Immune-related adverse effect, Type 1 diabetes mellitu

The Frequency of Histologically Dysplastic Nevi in 199 Pediatric Patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75141/1/j.1525-1470.2000.01772.x.pd

Relative risk of end-stage renal disease requiring dialysis in treated ankylosing spondylitis patients compared with individuals without ankylosing spondylitis: A nationwide, population-based, matched-cohort study.

ObjectiveTo examine the relative risk of end-stage renal disease (ESRD) requiring dialysis among treated ankylosing spondylitis (AS) patients compared with non-AS individuals.MethodsWe used claims data from Taiwan's National Health Insurance Research Database obtained between 2003 and 2012, and enrolled 37,070 newly treated AS patients and randomly selected 370,700 non-AS individuals matched (1:10) for age, sex and year of index date. Those with a history of chronic renal failure or dialysis were excluded. After adjusting for age, sex, diabetes mellitus, hypertension, IgA nephropathy, frequency of serum creatinine examinations, use of methotrexate, sulfasalazine, ciclosporis, corticosteroid, aminoglycoside, amphotericin B, cisplatin, contrast agents and annual cumulative defined daily dose (cDDD) of traditional NSAIDs, selective cyclooxygenase-2 inhibitors (COX-2i) and preferential COX-2i, we calculated the adjusted hazard ratios (aHRs) with 95% confidence intervals using the Cox proportional hazard model to quantify the risk of ESRD in AS patients. We re-selected 6621 AS patients and 6621 non-AS subjects by further matching (1:1) for cDDDs of three groups of NSAIDs to re-estimate the aHRs for ESRD.ResultsFifty-one (0.14%) of the 37,070 AS patients and 1417 (0.38%) of the non-AS individuals developed ESRD after a follow-up of 158,846 and 1,707,757 person-years, respectively. The aHR for ESRD was 0.59 (0.42-0.81) in AS patients compared with non-AS individuals. However, after further matching for cDDD of NSAIDs, the aHR of ESRD was 1.02 (0.41-2.53). Significant risk factors included hypertension, IgA nephropathy and use of COX-2i.ConclusionsThe risk of ESRD was not significantly different between treated AS patients and non-AS individuals matched for age, sex, year of index date and dose of NSAID

Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling

Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is an important regulator of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), also known as fetal liver kinase receptor 1 (Flk-1). Resveratrol is an activator of PGC-1α. It has been suggested to provide neuroprotective effects in epilepsy, stroke, and neurodegenerative diseases. In the present study, we used microinjection of kainic acid into the left hippocampal CA3 region in Sprague Dawley rats to induce bilateral prolonged seizure activity. Upregulating the PGC-1α pathway will increase VEGF/VEGFR2 (Flk-1) signaling and further activate some survival signaling that includes the mitogen activated protein kinase kinase (MEK)/mitogen activated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways and offer neuroprotection as a consequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1α by siRNA against pgc-1α will inhibit VEGF/VEGFR2 (Flk-1) signaling and suppress pro-survival PI3K/AKT and MEK/ERK pathways that are also accompanied by hippocampal CA3 neuronal cell apoptosis. These results may indicate that the PGC-1α induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1α/VEGF/VEGFR2 (Flk-1) and the triggering of downstream PI3K/AKT and MEK/ERK signaling could be considered an endogenous neuroprotective effect against apoptosis in the hippocampus following status epilepticus

Guidelines of care for primary cutaneous melanoma

J Am Acad Dermatol 2001;45:579-86