Oxidized low‐density lipoprotein (Ox‐LDL)‐induced endothelial cell injury plays a crucial role in the pathogenesis of atherosclerosis (AS). Plasma galectin‐3 (Gal‐3) is elevated inside and drives diverse systemic inflammatory disorders, including cardiovascular diseases. However, the exact role of Gal‐3 in ox‐LDL‐mediated endothelial injury remains unclear. This study explores the effects of Gal‐3 on ox‐LDL‐induced endothelial dysfunction and the underlying molecular mechanisms. In this study, Gal‐3, integrin β1, and GTP‐RhoA in the blood and plaques of AS patients were examined by ELISA and western blot respectively. Their levels were found to be obviously upregulated compared with non‐AS control group. CCK8 assay and flow cytometry analysis showed that Gal‐3 significantly decreased cell viability and promoted apoptosis in ox‐LDL‐treated human umbilical vascular endothelial cells (HUVECs). The upregulation of integrinβ1, GTP‐RhoA, p‐JNK, p‐p65, p‐IKKα, and p‐IKKβ induced by ox‐LDL was further enhanced by treatment with Gal‐3. Pretreatment with Gal‐3 increased expression of inflammatory factors (interleukin [IL]‐6, IL‐8, and IL‐1β), chemokines(CXCL‐1 and CCL‐2) and adhesion molecules (VCAM‐1 and ICAM‐1). Furthermore, the promotional effects of Gal‐3 on NF‐κB activation and inflammatory factors in ox‐LDL‐treated HUVECs were reversed by the treatments with integrinβ1‐siRNA or the JNK inhibitor. We also found that integrinβ1‐siRNA decreased the protein expression of GTP‐RhoA and p‐JNK, while RhoA inhibitor partially reduced the upregulated expression of p‐JNK induced by Gal‐3. In conclusion, our finding suggests that Gal‐3 exacerbates ox‐LDL‐mediated endothelial injury by inducing inflammation via integrin β1‐RhoA‐JNK signaling activation.

Synaptic loss is the structural basis for memory impairment in Alzheimer's disease (AD). While the underlying pathological mechanism remains elusive, it is known that misfolded proteins accumulate as β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles decades before the onset of clinical disease. The loss of Pin1 facilitates the formation of these misfolded proteins in AD. Pin1 protein controls cell-cycle progression and determines the fate of proteins by the ubiquitin proteasome system. The activity of the ubiquitin proteasome system directly affects the functional and structural plasticity of the synapse. We localized Pin1 to dendritic rafts and postsynaptic density (PSD) and found the pathological loss of Pin1 within the synapses of AD brain cortical tissues. The loss of Pin1 activity may alter the ubiquitin-regulated modification of PSD proteins and decrease levels of Shank protein, resulting in aberrant synaptic structure. The loss of Pin1 activity, induced by oxidative stress, may also render neurons more susceptible to the toxicity of oligomers of Aβ and to excitation, thereby inhibiting NMDA receptor-mediated synaptic plasticity and exacerbating NMDA receptor-mediated synaptic degeneration. These results suggest that loss of Pin1 activity could lead to the loss of synaptic plasticity in the development of AD.

Exogenous hydrogen sulfide (H 2 S) protects kidneys from diabetic injuries in animal models. In order to explore the role of endogenous H 2 S in diabetic nephropathy, we determined the renal H2S producing enzymes in vivo and in vitro. In diabetic mice, H 2 S levels in blood and kidney were decreased while cystathionine β-synthase (CBS), mainly located in mouse renal proximal convoluted tubules (PCT), was reduced selectively. In cultured mouse PCT cells treated with high glucose, CBS protein and activity was reduced while ubiquitinated CBS was increased, which was abolished by a proteasome inhibitor MG132 at 1 hour; high glucose drove CBS colocalized with proteasome 26S subunit ATPase6, indicating an involvement of ubiquitination proteasome degradation. At 48 hours, high glucose also selectively decreased CBS protein, concentration-dependently, but increased the ubiquitination of CBS; silence of CBS by siRNA increased nitrotyrosine, a marker for protein oxidative injury. Nitrotyrosine was also increased by high glucose treatments. The increases of nitrotyrosine either by cbs-siRNA or by glucose were restored by GYY4137, indicating that the H 2 S donor may protect kidney from oxidative injury induced by CBS deficiency. In diabetic kidneys, ubiquitinated CBS and nitrotyrosine were increased but restored by GYY4137. The treatment also ameliorated albuminuria and renal morphologic changes in diabetic mice. Our findings suggest that high glucose induces reduction of renal CBS protein and activity in vivo and in vitro that is critical to the pathogenesis of diabetic kidney disease.

Alteration of behavior and PSD proteins in cerebral cortex and hippocampal synaptosome in the Alzheimer's disease (AD) mouse model were determined. AD was established by intraperitoneal injection of streptozotocin (STZ) in neonatal mice (intraperitoneal AD group) or intracerebroventricular injection of STZ in adult mice (intracerebroventricular AD group). Body weight and blood sugar level were measured. Following Morris water maze (MWM) test and fear-conditioning test, cerebral cortex and hippocampus tissues were collected and the levels of PSD95 and shank3 proteins in these tissues were measured by western blot analysis. The body weight was reduced and the blood sugar concentration was increased in the intraperitoneal AD group compared with the control group. In contrast, the body weight was reduced, while the blood sugar concentration was not increased in the intracerebroventricular AD group compared with the control group. Escape latency in both AD groups was extended compared with the control group. The freezing time in the intraperitoneal AD group was increased, while in the intracerebroventricular AD group, the freezing time was reduced. PSD95 and shank3 proteins in the cerebral cortex in both AD groups were decreased compared with the control group. PSD95 in the hippocampus was reduced in both AD groups compared with the control group. Shank3 in the hippocampus in the intracerebroventricular AD group was significantly reduced compared with the control group. Intraperitoneal injection of STZ in neonatal mice led to elevated blood sugar, impaired spatial memory and enhanced emotional memory when they become adults. In contrast, intracerebroventricular injection of STZ in adults directly led to deteriorated spatial and emotional memory without alteration of blood sugar content, which could be associated with the changes of PSD95 and shank3 proteins in hippocampus.

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