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Abstract Cataract, the leading cause of blindness worldwide, is caused by crystallin protein aggregation within the protected lens environment. Phase separation has been implicated as an important mechanism of protein aggregation diseases, such as neurodegeneration. Similarly, cataract has been proposed to be a protein condensation disease in the last century. However, whether crystallin proteins aggregate via a phase separation mechanism and which crystallin protein initiates the aggregation remain unclear. Here, we showed that all types of crystallin-GFP proteins remain soluble under physiological conditions, including protein concentrations, ion strength, and crowding environments. However, in age or disease-induced aberrant conditions, α-crystallin-GFP, including αA- and αB-crystallin-GFP, but not other crystallin-GFP proteins, undergo phase separation in vivo and in vitro. We found that aging-related changes, including higher crystallin concentrations, increased Na+, and decreased K+ concentrations, induced the aggregation of α-crystallin-GFP. Furthermore, H2O2, glucose, and sorbitol, the well-known risk factors for cataract, significantly enhanced the aggregation of αB-crystallin-GFP. Taken together, our results revealed that α-crystallin-GFP forms aggregates via a phase transition process, which may play roles in cataract disease. Opposite to the previously reported function of enhancing the solubility of other crystallin, α-crystallin may be the major aggregated crystallin in the lens of cataract patients.

Natural killer (NK)/T cell lymphoma of the female genital tract is extremely rare. We here report a case of 'nasal type' NK/T cell lymphoma arising in the uterus with adenomyosis in a 41-year-old woman with fever and hypogastralgia. The histologic analysis demonstrated a highly aggressive tumor with characteristic angiocentric/angiodestructive growth pattern and focal necrosis. The lymphoma cells displayed a CD3ε/CD56/TIA-1/granzyme-B/Perforinpositive and CD20/CD79a/CD4/CD8-negative immunophenotype and positive for Epstein- Barr virus by EBER in situ hybridization. Clinically, the disease was limited to the uterus at the initial diagnosis, but progressed rapidly. The patient died on day 54 after hysterectomy, irrespective of intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Ischaemia-reperfusion injury (IRI) is the predominant cause of acute kidney injury. Nevertheless, the underlying molecular mechanisms are still unclear. The current study investigated the effects of nicorandil on ATP-sensitive potassium (KATP) channels and the potential signal transduction pathway(s) in a rat kidney IRI model and in cultured tubular HK-2 cells subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) injury. The standard procedure for IRI was performed in newborn rat kidneys. Pretreatment with nicorandil (10 mg/kg) 2 h prior to induction of IRI improved renal function, attenuated tubule damage, and prevented apoptosis of tubule cells, infiltration of neutrophils and macrophages, and production of inflammatory cytokines interleukin (IL)-6, IL-17 and tumour necrosis factor-α. Ischaemia-reperfusion-induced reduction of KIR6.2 was restored to normal levels by nicorandil. The activation of the phosphoinositide-3-kinase (PI3K)-Akt-nuclear factor (NF)-κB axis was detected in this rat kidney IRI model, which was blocked by nicorandil. The renoprotection of nicorandil against IRI was abolished by its inhibitor glibenclamide (1 mg/kg). Similar results were obtained in OGD/R-damaged HK-2 cells. Taken together, our findings demonstrated the specific renoprotective role of nicorandil in the newborn rat IRI kidney by decreasing the production of inflammatory cytokines, and restoring the expression of KIR6.2 potentially through the PI3K-Akt-NF-κB axis. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]