다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

From a Novel

Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine.

Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory. However, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3 have provided greater insight into their mechanism of action. Here, the clinical efficacy of these agents in myeloma is reviewed and the structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis are discussed.

Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience

One of the most attractive areas in inorganic chemistry is the synthesis of polyoxometalates (POMs) exhibiting new properties and applications. Since the impact of POMs in biochemistry and related fields of research has increased in the last few years, there has been a special interest in this topic. Significant progress in biological applications has been made where the interaction of POMs with amino acids, peptides and proteins is relevant. Versatile POMs play a series of different roles in the interaction with these biomolecules as described in this review. Various types of interactions are established, depending on the POM shape and charge, the amino acid side chain, peptide sequence or protein structure. Experimental conditions such as temperature, acidity, solvent, etc. are also important factors that influence the binding/reactivity of POM with biomolecules, as described herein. This understanding allows the adequate design of the POM-biomolecule couple for tailoring and controlling mechanisms of action such as catalysis, inhibition, and aggregation, or the crystallising agent.

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A survey of the different roles of polyoxometalates in their interaction with amino acids, peptides and proteins

The immunomodulatory drug (IMiD) thalidomide and its structural analogs lenalidomide and pomalidomide are highly effective in treating clinical indications. Thalidomide binds to cereblon (CRBN), a substrate receptor of the cullin-4 really interesting new gene (RING) E3 ligase complex. Here, we examine the effect of thalidomide and its analogs on CRBN ubiquitination and its functions in human cell lines. We find that the ubiquitin modification of CRBN includes K48-linked polyubiquitin chains and that thalidomide blocks the formation of CRBN-ubiquitin conjugates. Furthermore, we show that ubiquitinated CRBN is targeted for proteasomal degradation. Treatment of human myeloma cell lines such as MM1.S, OPM2, and U266 with thalidomide (100 μM) and its structural analog lenalidomide (10 μM) results in stabilization of CRBN and elevation of CRBN protein levels. This in turn leads to the reduced level of CRBN target proteins and enhances the sensitivity of human multiple myeloma cells to IMiDs. Our results reveal a novel mechanism by which thalidomide and its analogs modulate the CRBN function in cells. Through inhibition of CRBN ubiquitination, thalidomide and its analogs allow CRBN to accumulate, leading to the increased cullin-4 RING E3 ligase-mediated degradation of target proteins.

A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function

Mitophagy induced by nanoparticle-peptide conjugates enabling an alternative intracellular trafficking route.

Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells

Quantitative proteomics and biochemical analyses reveal the role of endoplasmin in the regulation of the expression and secretion of A Disintegrin And Metalloproteinase 12.

Yanqing Zhou

Papers

A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function

Mitophagy induced by nanoparticle-peptide conjugates enabling an alternative intracellular trafficking route.

Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells

Quantitative proteomics and biochemical analyses reveal the role of endoplasmin in the regulation of the expression and secretion of A Disintegrin And Metalloproteinase 12.