No abstract

A covalent core–shell structured protein cluster composed of hemoglobin (Hb) at the center and human serum albumins (HSA) at the periphery, Hb-HSAm, is an artificial O2 carrier that can function as a red blood cell substitute. Here we described the preparation of a novel Hb-HSA3 cluster with antioxidant activities and its O2 complex stable in aqueous H2O2 solution. We used an approach of incorporating a Pt nanoparticle (PtNP) into the exterior HSA unit of the cluster. A citrate reduced PtNP (1.8 nm diameter) was bound tightly within the cleft of free HSA with a binding constant (K) of 1.1×107 M−1, generating a stable HSA-PtNP complex. This platinated protein showed high catalytic activities for dismutations of superoxide radical anions (O2 •–) and hydrogen peroxide (H2O2), i.e., superoxide dismutase and catalase activities. Also, Hb-HSA3 captured PtNP into the external albumin unit (K = 1.1×107 M−1), yielding an Hb-HSA3(PtNP) cluster. The association of PtNP caused no alteration of the protein surface net charge and O2 binding affinity. The peripheral HSA-PtNP shell prevents oxidation of the core Hb, which enables the formation of an extremely stable O2 complex, even in H2O2 solution.

A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core–shell structured hemoglobin-albumin cluster designated as “HemoAct”, is an O2-carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.

MicroRNAs (miRNAs) are small non-coding RNAs that function as endogenous silencers of numerous target genes. Hundreds of miRNAs have been identified in the human genome. miRNAs are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Aberrant expression of miRNAs may also contribute to the development and progression of human hepatobiliary and pancreatic cancers. Recent studies have shown that some miRNAs play roles as tumor suppressors or oncogenes in hepatobiliary and pancreatic cancers. miR-122, let-7 family, and miR-101 are down-regulated in hepatocellular carcinoma (HCC), suggesting that it is a potential tumor suppressor of HCC. miR-221 and miR-222 are up-regulated in HCC and may act as oncogenic miRNAs in hepatocarcinogenesis. miRNA expression profiling may be a powerful clinical tool for diagnosis and regulation of miRNA expression could be a novel therapeutic strategy for hepatobiliary and pancreatic cancers. In this review, we summarize current knowledge about the roles of important tumor suppressor microRNAs and oncogenic microRNAs in hepatobiliary and pancreatic cancers.

Abstract During irradiation sessions for brain tumors or head and neck cancers, some patients experience abnormal olfactory sensations. To date, the frequency of such sensations during these treatment sessions has not been investigated. We analyzed abnormal olfactory sensations in patients who underwent radiation therapy at our institution for primary brain tumors, excluding malignant lymphoma, between January 2009 and January 2018. A total of 191 patients who were awake during radiation treatment and capable of communicating were analyzed in this retrospective medical study. Of these patients, 7 were aware of olfactory sensations during irradiation. The median age of these 7 patients was 13 (range 8–47) years, Six were <20 years of age, accounting for 10% of the total population of similar age (n = 60). However, only 1 of 131 patients aged ≥20 years complained of strange olfactory sensations. Four of seven patients had germ cell tumors, but none had a medulloblastoma. We investigated patients who experienced light sensation, as an internal standard to ascertain the accuracy of this study. Only 10 patients experienced light sensation during their irradiation sessions. This suggests that the frequency of these sensations was possibly underestimated in our study. In conclusion, a considerable number of patients experienced unusual olfactory sensations during radiation treatment. Further prospective studies on abnormal olfactory sensations during irradiation are needed to clarify the underlying mechanism of this sensation.