Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.
A high proportion of healthy males in Chongqing area of southwest China had abnormal semen parameters values according to WHO criteria. The semen parameters in the study population were markedly different from those reported for the other Chinese, USA and European populations. The differences remain unexplained and may be due to demographic characteristics, lifestyle, environmental factors or genetic variation.
The ubiquitin-proteasome system (UPS) plays a vital role in maintaining protein homeostasis and regulating numerous cellular processes. The proteasome, a multi-protease complex, is the key component of the UPS and has been validated as a therapeutic target by the FDA's approval of bortezomib and carfilzomib. These proteasome inhibitor drugs have substantially improved outcomes in patients with hematological malignancies and are currently being investigated for other types of cancer as well as several other diseases. These approved proteasome inhibitors target the catalytic activity of both the constitutive proteasome and the immunoproteasome indiscriminately, and their inhibitory effects on the constitutive proteasome in normal cells are believed to contribute to unwanted side effects. In addition, selective immunoproteasome inhibition has been proposed to have unique effects on other diseases, including those involving aberrant immune function. Initially recognized for its role in the adaptive immune response, the immunoproteasome is often upregulated in disease states such as inflammatory diseases and cancer, suggesting functions beyond antigen presentation. In an effort to explore the immunoproteasome as a potential therapeutic target in these diseases, the development of immunoproteasome-specific inhibitors has become the focus of recent studies. Owing to considerable efforts by both academic and industry groups, immunoproteasome-selective inhibitors have now been identified and tested against several disease models. These inhibitors also provide a valuable set of chemical tools for investigating the biological function of the immunoproteasome. In this review, we will focus on the recent efforts towards the development of immunoproteasome-selective inhibitors.
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