The article by Shirasago et al demonstrated that the coffee-related compounds caffeic acid and tannic acid act on hepatitis C virus (HCV) particles and abrogate their infectivity. Particularly, the authors demonstrated that caffeic acid significantly reduced cellular attachment of HCV particles and their interaction with host apolipoprotein E, which is essential for HCV infectivity. Intake of coffee or the coffee-related compounds caffeic acid and tannic acid, which are inexpensive and easy to supply, might lead to prevention of HCV infection and slower disease progression after HCV infection.
growth-inhibitory effects of Am80 (tamibarotene), a specific retinoic acid
receptor (RAR) α/β agonist, in combination with a histone deacetylase (HDAC)
inhibitor, suberoylanilide hydroxamic acid (SAHA) on androgen receptor positive
or negative prostate cancer cell lines were investigated. Ishigami-Yuasa et al.
found that the combination therapy of Am80 and SAHA showed an enhanced
growth-inhibitory effect on LNCaP cells. Studies with various HDAC
isotype-selective inhibitors indicated that the Class IIb HDACs, especially
HDAC6, had significant roles in the enhanced effect of the combination. Thus, dual
targeting of Class IIb HDAC and RARα would be useful therapeutic strategy for
The delivery of hydrogen sulfide (H2S) to liver is expected for the treatment of hepatic diseases. K. Sakai et al. developed two types of sulfo-albumins, macromolecular H2S prodrugs, for hepatic and intrahepatic targeting of H2S. Sulfide groups (source of H2S) were covalently bound to succinylated (Suc) and galactosylated (Gal) bovine serum albumin (BSA) for targeted delivery of H2S to hepatic nonparenchymal cells and parenchymal cells, respectively. Their results demonstrated targeted delivery of H2S prodrug to a specific type of liver cells using the chemical modification of targeting ligands.
CXC chemokine ligand (CXCL) 10 is a chemokine that binds to CXCR3 expressed on natural killer (NK) cells and cytotoxic T lymphocytes. In this paper, Kikuchi et al. showed that forced expression of CXCL10 in murine colon carcinoma CT26 cells prevents their in vivo proliferation and liver metastasis by recruiting NK cells, suggesting that forced expression of CXCL10 in the colon tumors by gene delivery should lead to a favorable clinical outcome.
Fluorescein isothiocyanate (FITC)-induced contact hypersensitivity is a mouse model of skin allergy to chemicals. In this model, chemicals such as phthalate esters are known to enhance skin sensitization to FITC. The article by Matsuoka et al. demonstrated that butyl paraben (BP), a common preservative, enhances skin sensitization as revealed by ear-swelling response to FITC. Mechanistically, BP facilitates dendritic cell trafficking from skin to lymph nodes, and enhances cytokine production from lymph node cells. Their results provide direct in vivo evidence that BP, like phthalate esters, enhances sensitization to other chemicals.
How can you know the structural difference
between biosimilar and reference product? The structure of biosimilar products
is not the same as their original product because of post-translational
modifications. In the article by Tsuda et al., a valuable method with a papain
digestion and LC/TOF-MS analysis was established. Their new method can analyze
not only carbohydrate chains but also amino acids of bio-medicines including biosimilar
antibodies. This technology will provide a useful strategy to evaluate
bio-medicines including biosimilar antibodies.
Type 2 diabetes mellitus (T2DM) animal models are often used in basic research on diabetic osteoporosis. The article by Tanaka et al. elucidated hyperglycemia contributed to a decrease in bone metabolism turnover in the T2DM animal model NSY mice, resulting in a thinner and shorter femur, lower cortical and trabecular area, and lower bone mass. Their results suggest that these effects contribute to the deteriorated bone strength of the femur in NSY mice, and the NSY mouse could serve as an appropriate T2DM animal model for examining the specific effect of hyperglycemia on bone integrity, using the ICR mouse as a control.
(SeMet) is a major form of selenium compounds in foods. The article by Arakawa et al. demonstrated that ear thickness
was increased by repeated application of 2,4,6-trinitrochlorobenzene (TNCB) to the
ear, and SeMet significantly suppressed ear thickness in mice. SeMet inhibited
epidermal hyperplasia and dense infiltration of inflammatory cells. Serum total
immunoglobulin (Ig) E levels were suppressed by SeMet. Interleukin (IL) 4
expression in the ear and superficial parotid lymph node was inhibited by
SeMet. These results demonstrated that SeMet suppresses atopic dermatitis-like
skin lesions and inhibits the expression of total IgE and IL-4.
Exosomes are extracellular vesicles released by various types of cells, including immune cells and cancer cells. The article by Emam et al evaluated in vivo secretion of exosomes following intravenous injection of free doxorubicin (DXR) or liposomal DXR (Doxil®) was evaluated using normal mice. Free DXR treatment markedly increased the serum exosome level, while Doxil® treatment did not change. Interestingly, splenectomy significantly suppressed the exosomal secretions induced by free DXR treatment. Their results suggest that conventional anticancer agents induce the secretion of exosomes via stimulating immune cells of the spleen, and might contribute to the antitumor effect of chemotherapeutic agents.
The article by Ohsaki et al. proposed a novel mechanism of cytokine production in γ-irradiated cells. γ-Ray irradiation induced sustained IL-6 production in HaCaT epidermal cells from 33 h after irradiation. Extracellular ATP-induced activation of P2Y11 receptor was involved in the production of IL-6. At the downstream of P2Y11 receptor activation, the p38 MAPK and NF-kB signaling was involved in IL-6 production. The protein level of G9a, which inhibits IL-6 production, was decreased after g-irradiation. These findings should be helpful to understand the pathogenesis of radiation-induced inflammation, as well as the potential side effects of therapeutic irradiation.
Ipragliflozin is a selective sodium glucose cotransporter 2 inhibitor that increases urinary glucose excretion, and subsequently improves glucolipotoxicity. The article by Takasu et al. demonstrated that the treatment with ipragliflozin decreased pancreatic cells positive for 4-hydroxy-2-nonenal (4HNE), an oxidative stress marker, in obese type 2 diabetes mellitus (DM) db/db mice. Histopathological examination of pancreatic islet cells revealed strong insulin staining, whereas reduced glucagon staining, accordingly pancreatic insulin content tended to be higher in the ipragliflozin 10 mg/kg-treated group compared with the DM-control group. It was demonstrated that ipragliflozin has a protective effect on the pancreas by reducing oxidative stress.
Human immunodeficiency virus type 1 (HIV-1) recruits diverse cellular factors into viral particles during its morphogenesis, which apparently play roles in modulating its infectivity. The article by Mouree et al. evaluated that a key glycolytic protein, pyruvate kinase muscle type 2 (PKM2) is incorporated into viral particles. Furthermore, the virion-packaged PKM2 significantly reduces the viral infectivity by affecting the selective packaging of intravirion tRNALys3, which primes the initiation of reverse transcription, along with other nonpriming tRNAs, such as tRNALys1,2 and tRNAAsn, without affecting the cytoplasmic level of these tRNAs. These findings proposed that PKM2 is a vital host factor that negatively affects HIV-1 infectivity by targeting the tRNALys3-mediated initiation of reverse transcription in target cells.
oxidase (Nox) isozymes are implicated in the diseases associated with oxidative
stress, and search of their selective inhibitors has been a focus of attention.
By screening microbial metabolites, Nakano and colleagues identified a novel
Nox1 inhibitor (NOS31) produced from actinomyces. NOS31 inhibited Nox1-mediated
hydrogen peroxide production with high Nox1 selectivity and suppressed
proliferation of colon and gastric cancer cells that up-regulate Nox1. Thus,
NOS31 may have the therapeutic potential for treating cancer involving the
over-activation of Nox1.
Based on the binding characteristics, Kamei et al. attempted to increase the bound concentration of penetratin, cell-penetrating peptide (CPP), by increasing the concentration of mixed insulin, however the effect of L-penetratin on the oral absorption of insulin was not boosted by increasing the dose of insulin. The investigation in the gastric pH-neutralized mice showed that the dissociation of noncovalent complexes of insulin and CPPs at the low gastric pH was prevented in these mice, and clearly suggested that a noncovalent theoretical strategy with CPPs represents an effective approach for the L-form of CPP to attain greater absorption of insulin.
Because tyrosine kinases mainly localize to the cytoplasm or the plasma membrane, most studies have focused on their roles in the cytoplasm. However, emerging evidence has revealed that tyrosine kinases also localize to the nucleus and regulate nuclear events, such as DNA damage responses, gene expression, and chromatin structural changes. In this paper, Takakura et al. showed that the truncated isoform of the receptor tyrosine kinase ALK (ALK ATI), which only has the intracellular kinase domain, regulates chromatin structural changes, heterochromatinization, and gene expression in the nucleus. This paper is the first report shedding light on the nuclear roles of ALK.
hypertension induces renal injury via decreased blood flow in the renal artery.
Voltage-gated, delayed-rectifier K+ (KV) channels play
key roles in the regulation of vascular tone, and their dysfunction in arterial
myocytes may be involved in the higher vascular resistance. In their report, Ogiwara et al. described that there is a large
contribution of KV2.1 to the resting tension maintenance of renal
artery in Dahl salt-sensitive hypertensive rats and suggested the up-regulation
of the KV2.1 channel in renal artery might be involved in the
compensatory mechanisms against decreased renal blood flow in salt-sensitive
In their report, Kumeda et al. examined Membrane integrity and morphological stability of salivary exosomes using dipeptidyl peptidase IV and CD9 as membrane makers, and Alix and Tsg101 as lumen markers. Neither localization nor levels of these marker proteins were changed in isolated exosomes after long-term storage at 4°C or multiple freeze-thaw cycles. Moreover, intact exosomes could be isolated from whole saliva refrigerated for a month. Components inside the exosomes were stable even after solubilization of membrane components with detergents such as Triton X-100. These results indicate that human saliva-derived exosomes are very stable, maintaining their membrane integrity over a long storage period.
The composition of the adjuvant emulsions was 2.5% squalene, 6% detergents, 0.5% antioxidant – α-tocopherol or β-carotene and 91% water phase. Antioxidant effectivity was testing by determination of peroxide value. α-tocopherol acted as a prooxidant, β-carotene was an effective antioxidant. Effectiveness of rabies vaccine with squalene adjuvant was testing on mice. Adjuvanted vaccine with β-carotene was compared to vaccine without antioxidant and induced a slower but prolonged immunity response with protective levels of rabies antibodies (0.5 IU/mL).
In their report, Ibrahim et al. described that generating platinum chloroquine diphosphate dichloride (PtCQ)-loaded polyethylene glycol (PEG)-modified (PEGylated) cationic liposomes exhibiting high drug encapsulation and high drug retention. PtCQ was encapsulated in PEGylated cationic liposomes comprising various amounts of cationic lipids using the remote-loading method. PEGylated neutral liposomes and cationic liposomes exhibited minimum leakage of PtCQ after two months’ storage at 4˚C, and further exhibited little release under in vitro culture conditions at 37˚C for 72 hours. These results provide a useful framework for the design of future liposome-based in vivo drug delivery systems targeting the drug-resistant malaria parasite.