Mass spectrometry imaging of the capsaicin localization in the capsicum fruits

We succeeded in performing mass spectrometry imaging (MSI) of the localization of capsaicin in cross-sections of the capsicum fruits at a resolution of 250 µm using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Post source decay of protonated capsaicin ion revealed structural information of the corresponding acid amide of vanillylamide and C9 chain fatty acid. MALDI-TOF-MSI confirmed that localization of capsaicin in the placenta is higher than that in the pericarp. In addition, it revealed no localization of capsaicin in seed and the higher localization of capsaicin at placenta surface compared with that in the internal region. A quantitative difference was detected between localizations of capsaicin at placenta, pericarp and seed in the capsicum fruits. This imaging approach is a promising technique for rapid quality evaluation general food as well as health food and identification of medicinal capsaicin in plant tissues

Structures and mechanisms of actin ATP hydrolysis

The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) PG–O3B bond cleavage; 3) four concomitant events: W1–PO3− formation, OH− and proton cleavage, nucleophilic attack by the OH− against PG, and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi–bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes

Overexpression of the adiponectin gene mimics the metabolic and stress resistance effects of calorie restriction, but not the anti-tumor effect

Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12. weeks of age. Adipoq-RD and -HFD mice at 6. months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD. In the epididymal white adipose tissue in Adipoq mice, senescence-like changes such as upregulation of p53 protein and of biomarkers of inflammation, Cd68 and Ccl2 mRNA, were ameliorated compared with WT-RD and WT-HFD mouse tissues. Resistance to stress induced by lipopolysaccharide was also strengthened in Adipoq mice compared with WT mice. These metabolic changes and stress resistance were also noted in the WT-CR mice, suggesting that Adipoq plays a part in the effect of CR. In contrast, in an allograft tumor growth model, tumor growth was not inhibited in Adipoq mice. The present findings suggest that Adipoq plays a part in the anti-aging, but not in the anti-tumor, effects of CR

A Planar Gas Sensor Combined with Interdigitated Array Electrodes

Generally, the gap and width of the electrodes should be small in order to generate a large number of redox cycles. However, it was difficult to fabricate fine patterns on the gas-permeable membrane, because the membrane was flexible and its surface was not flat. On the other hand, it is already possible to fabricate fine IDA patterns on a hard and flat substrate and are already being marketed. However, if these electrodes fabricated on substrate are set in an electrolyte solution, they do not come into contact with the membrane. Therefore, it is said that the sensitivity and response speed are poor. Accordingly, we experimented with a new method of applying IDA electrodes to a gas-sens ing system. We call it a planar IDA gas sensor. A piece of filter paper containing an electrolyte solution was put on IDA electrodes, which were fabricated on a glass substrate. This gas sensor was very easy to construct. A similar planar sensor had been reported for amperometric sensing of oxygen.9 It was developed as a low-cost and disposable sensor, and applied to glucose sensing. A planar sensor is expected to be more useful in complicated detection systems i.e. using IDA electrodes, which was confirmed after being used in a hydrogen-detection system

A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice

金沢大学医薬保健研究域医学系Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic diseases due to their antioxidative effect. However, the effects of the extracts on the development of NASH have yet to be elucidated. Here, we demonstrated that supplementation with an oral porcine placental extract (PPE) attenuated lipid accumulation and peroxidation, insulin resistance, inflammatory and stress signaling, and fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat diet. The PPE reduced the number of M1-like liver macrophages, but increased the number of anti-inflammatory M2-like macrophages, resulting in a predominance of M2 over M1 macrophage populations in the liver of NASH mice. Accordingly, the PPE suppressed lipopolysaccharide-induced M1 polarization in isolated murine peritoneal macrophages, whereas it facilitated interleukin 4-induced M2 polarization. Furthermore, the PPE reduced the hepatic stellate cell (HSC) activation associated with the attenuated transforming growth factor-β/Smad3 signaling, both in the liver of NASH mice and in RI-T cells, a HSC line. The PPE may be a potential approach to prevent NASH by limiting lipid peroxidation, promoting M2 macrophage polarization, and attenuating HSC activation. © Xu et al

Relapsed urachal carcinoma responding to first‐line chemotherapy with capecitabine‐oxaliplatin plus bevacizumab

Introduction Advanced urachal carcinoma has a poor prognosis; however, a standard systemic treatment has not been established. We treated a patient with relapsed urachal carcinoma with capecitabine‐oxaliplatin plus bevacizumab, a standard regimen for colon cancer, and obtained favorable responses. Case presentation A 47‐year‐old woman presented with hematuria. Under the diagnosis of non‐metastatic urachal carcinoma, an extended partial cystectomy was performed. Histopathological examination revealed adenocarcinoma with negative surgical margins and lymph nodes. Thirty‐two months postoperatively, lung metastases and local recurrence were confirmed, along with elevated carcinoembryonic antigen levels, and nine chemotherapy cycles were administered. Subsequently, the recurrent lesion regressed, and tumor marker levels normalized. Fourteen months after treatment discontinuation, the disease remained stable without progression. Conclusion This is the first report of advanced urachal carcinoma treated with capecitabine‐oxaliplatin plus bevacizumab, demonstrating the potential of this treatment as first‐line chemotherapy for this disease

Dynamic expression and essential functions of Hes7 in somite segmentation

The basic helix–loop–helix (bHLH) gene Hes7, a putative Notch effector, encodes a transcriptional repressor. Here, we found that Hes7 expression oscillates in 2-h cycles in the presomitic mesoderm (PSM). In Hes7-null mice, somites are not properly segmented and their anterior–posterior polarity is disrupted. As a result, the somite derivatives such as vertebrae and ribs are severely disorganized. Although expression of Notch and its ligands is not affected significantly, the oscillator and Notch modulator lunatic fringe is expressed continuously throughout the mutant PSM. These results indicate that Hes7 controls the cyclic expression of lunatic fringe and is essential for coordinated somite segmentation