The islet in type 2 diabetes (T2DM) and the brain in neurodegenerative diseases share progressive cell dysfunction, increased apoptosis, and accumulation of locally expressed amyloidogenic proteins (islet amyloid polypeptide (IAPP) in T2DM). Excessive activation of the Ca 2؉ -sensitive protease calpain-2 has been implicated as a mediator of oligomer-induced cell death and dysfunction in neurodegenerative diseases. To establish if human IAPP toxicity is mediated by a comparable mechanism, we overexpressed human IAPP in rat insulinoma cells and freshly isolated human islets. Pancreas was also obtained at autopsy from humans with T2DM and nondiabetic controls. We report that overexpression of human IAPP leads to the formation of toxic oligomers and increases beta cell apoptosis mediated by increased cytosolic Ca 2؉ and hyperactivation of calpain-2. Cleavage of ␣-spectrin, a marker of calpain hyperactivation, is increased in beta cells in T2DM. We conclude that overactivation of Ca 2؉ -calpain pathways contributes to beta cell dysfunction and apoptosis in T2DM. Hyperglycemia in type 2 diabetes mellitus (T2DM)3 is due to impaired insulin secretion in the setting of relative insulin resistance (1). The islets of Langerhans in T2DM are characterized by a deficit in beta cells, increased beta cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP), a 37-amino acid highly conserved peptide co-expressed and secreted with insulin by pancreatic beta cells (2, 3).The pathology of the islet in T2DM and brain in neurodegenerative diseases such as Alzheimer disease share several parallels. In both, the loss of functional tissue is associated with deposition of a locally expressed protein with the potential to form amyloid fibrils (Alzheimer beta protein in Alzheimer disease and IAPP in T2DM) (2, 4). In both T2DM and Alzheimer disease, there has been a debate as to whether the amyloid deposits contribute to cell loss (the so-called amyloid hypothesis) or are secondary to the processes leading to cell loss. Evidence against a direct role of amyloid deposits on cell loss is the poor correlation between the extent of amyloid deposits and the severity of disease in both human and animal models (3,5,6). Moreover, preformed amyloid fibrils are not cytotoxic when applied to cells (7).However, several lines of evidence are supportive of a role of cytotoxicity by amyloidogenic proteins. These include genetic predisposition in occasional families with mutations leading to increased amyloidogenicity of the amyloid protein (8) and reproduction of the disease phenotype in rodent models transgenic for the relevant human amyloidogenic protein (9). There is an increasing appreciation that the cytotoxic forms of amyloidogenic proteins are small nonfibrillar oligomers that may form in membranes and cause nonselective membrane permeability (7, 10, 11), the toxic oligomer hypothesis. Moreover, misfolding and aggregation of amyloidogenic proteins into toxic oligomers induce apoptosis through the mechanism of endoplasmic retic...

No abstract

Bacteria-induced thrombocytopenia is a common clinical disease that is often ignored by clinical and scientific research. Thus, exploring the mechanism and principle of bacteria-induced thrombocytopenia could facilitate the development of new diagnostic, preventative, and treatment modalities for thrombocytopenia. This case report describes a case of platelet phagocytosis by neutrophils and monocytes in a patient with cerebral hemorrhage and thrombocytopenia caused by gram-negative bacterial infection. After the infection was eradicated, platelet phagocytosis was alleviated, and his platelet count normalized. Cellular immunity may be an important cause of bacteria-induced thrombocytopenia in patients with cerebral hemorrhage.

Through density functional theory (DFT), the sensitivity of the Pt-doped and the pristine BC3 nanosheets to ibuprofen (IBP) was scrutinized. The IBP drug does not impact the electronic properties evaluated for the pristine BC3. However, its sensitivity and reactivity are increased to the IBP drug to a great extent after doping it by Pt. Unlike the pristine BC3, the adsorption of the IBP drug decreases the HOMO-LUMO gap associated with the Pt-doped BC3 sheet from 1.29 to 1.04 eV, which improves the electrical conductivity. In addition, the adsorption of the IBP drug will mainly impact the work function of the Pt-doped BC3 sheet, which in turn modifies the electron emission current from its sheet. This verifies that the Pt-doped BC3 sheet can be utilized as a work-function-type sensor to detect the IBP drug. For desorption of the IBP drug, the recovery time of the Pt-BC3 nanosheet is short, i.e., 5.65 ms, which is another advantage of this sheet.