α-Smooth muscle actin expression in cancerassociated fibroblasts in canine epithelial tumors

Tumor tissues contain not only cancer cells but also other cell types including, fibroblasts, immune cells, and endothelial cells, which interact with cancer cells. In human medicine, cancer-associated fibroblasts (CAFs) have been reported to promote tumor growth. CAFs are known to express α-smooth muscle actin (α-SMA), and this expression is correlated with poor prognosis in humans with cancer. However, the role of CAFs in canines and α-SMA expression in canine CAFs remains unknown. This study evaluated whether CAFs are present within the stroma of various types of canine epithelial tumors, for example, mammary gland tumors, squamous cell carcinoma, and anal sac adenocarcinoma, and assessed α-SMA expression in CAFs isolated from canine epithelial tumors. α-SMA analysis of tumor tissues revealed a cytoplasmic localization with variable levels of expression. α-SMA was detected in 60.9% (14/23) of epithelial tumor tissues and in 80% (8/10) of anal sac adenocarcinoma tissues. CAFs and normal fibroblasts (NFs) were isolated from tumor and skin tissues. The size of CAFs was variable, and most CAFs had large cell volume, in contrast to NFs. Most CAFs expressed α-SMA stress fibers and had higher α-SMA protein levels than NFs. Taken together, our findings provide evidence that canine CAFs express α-SMA in various canine epithelial tumors. Further studies are required to investigate the correlation between canine CAFs and clinical parameters and to elucidate the mechanisms underlying the effects of CAFs on cancer progression

Molecular cloning of a cDNA encoding human ribosomal protein L39

A cDNA clone encoding a human ribosomal protein L39 (hRPL39) was isolated through a random cDNA sequencing approach to a cDNA library constructed from a human colon carcinoma cell line of COLO 205. Although levels of hRPL39 mRNA were different in several cell lines including carcinoma cell lines from different tissues, they were shown not to be cell cycle-dependent in a human fibroblast cell line of TIG-1

TNP-470 Suppresses the Tumorigenicity of HT1080 Fibrosarcoma Tumor Through the Inhibition of VEGF Secretion From the Tumor Cells

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer. TNP-470, a systemic analogue of fumagillin, is an angiogenesis inhibitor capable of suppressing the tumorigenicity in several animal models even though the mechanisms of action have not been completely clarified. In the current study, we investigated the effects of TNP-470 on human fibrosarcoma cells in vivo and in vitro. The administration of TNP-470 could suppress the tumorigenicity of HT1080 fibrosarcoma tumor. The conditioned medium from HT1080 fibrosarcoma cells treated with TNP-470 inhibited the proliferation and migration of human endothelial cell line, HUVEC and ECV304. The concentration of VEGF in the conditioned medium from HT1080 cells treated with TNP-470 was lower than that of the cells without TNP-470 treatment, indicating that TNP-470 downregulates the secretion of VEGF from HT1080 cells. These findings strongly suggest that the direct action of TNP-470 on sarcoma cells inhibits angiogenesis through the downregulation of VEGF secretion and this angiogenesis suppression resulted in the inhibition of tumorigenicity of HT1080 fibrosarcoma tumo

Photocatalysis in the Skin Related to UVA Photoaging

Skin aging is classified into chronological aging and photoaging, involving ultraviolet radiation (UV), visible light, and others. UVA and UVA-photosensitizers (involving photocatalysis) contribute to the production of chronically induced skin damage that results in photoaging, especially wrinkles that are associated with histopathological actinic elastosis in the dermis. Hydrogen peroxide produced by the photosensitization involving photocatalysis, such as flavin, has been proposed as a risk factor for photoaging. It was also revealed that hydrogen peroxide production by UVA is amplified through the following reactions. The photosensitization of type I and type II by riboflavin as an initiator oxidizes coexisted amino acids and vitamins. The oxidized amino acids and vitamins produce reactive oxygen species (ROS), including hydrogen peroxide, through secondary UVA-photosensitization. Finally, we proposed a screening method for detecting the effects of antioxidants on UVA-photosensitization. In our previous study, histidine and other antioxidants did not inhibit UVA-photosensitized by riboflavin, even though they have been reported to scavenge singlet oxygen and superoxide. In contrast, we demonstrated that ergothioneine suppressed the production of hydrogen peroxide by UVA-photosensitization. The purpose of this report is to provide new findings for the prevention of photoaging by discussing the characteristics of UVA-photocatalysts in the skin

Emergent cholecystectomy in patients on antithrombotic therapy

The Tokyo Guidelines 2018 (TG18) recommend emergent cholecystectomy (EC) for acute cholecystitis. However, the number of patients on antithrombotic therapy (AT) has increased significantly, and no evidence has yet suggested that EC should be performed for acute cholecystitis in such patients. The aim of this study was to evaluate whether EC is as safe for patients on AT as for patients not on AT. We retrospectively analyzed patients who underwent EC from 2007 to 2018 at a single center. First, patients were divided into two groups according to the use of antithrombotic agents: AT; and no-AT. Second, the AT group was divided into three sub-groups according to the use of single antiplatelet therapy (SAPT), double antiplatelet therapy (DAPT), or anticoagulant with or without antiplatelet therapy (AC +/- APT). We then evaluated outcomes of EC among all four groups. The primary outcome was 30- and 90- day mortality rate, and secondary outcomes were morbidity rate and surgical outcomes. A total of 478 patients were enrolled (AT, n=123, no-AT, n=355) patients. No differences in morbidity rate (6.5% vs. 3.7%, respectively; P=0.203), 30-day mortality rate (1.6% vs. 1.4%, respectively; P=1.0) or 90-day mortality rate (1.6% vs. 1.4%, respectively; P=1.0) were evident between AT and no-AT groups. Between the no-AT and AC +/- APT groups, a significant difference was seen in blood loss (10mL vs. 114mL, respectively; P=0.017). Among the three AT sub-groups and the no-AT group, no differences were evident in morbidity rate (3.7% vs. 8.9% vs. 0% vs. 6.5%, respectively; P=0.201) or 30-day mortality (1.4% vs. 0% vs. 0% vs. 4.3%, respectively; P=0.351). No hemorrhagic or thrombotic morbidities were identified after EC in any group. In conclusion, EC for acute cholecystitis is as safe for patients on AT as for patients not on AT

Heterogeneous hydraulic properties of an insular aquifer clarified by a tidal response method with simple decomposition techniques

Two simple frequency decomposition techniques were used as part of a tidal response method to derive the hydraulic diffusivities of a freshwater-lens aquifer. Digital high-pass filtering can separate the tidal components of diurnal and shorter periods from longer-period components. Discrete Fourier transform can be used to isolate a specific tidal component. These techniques are easy to practice using the built-in functions of spreadsheet software. The applied techniques were each optimized for the frequencies of known major tidal components. Isolation of the specific tidal signals helps to reduce the errors of a basic tidal response method that uses in its calculations the amplitude attenuation and phase lag of a simple sinusoidal wave of groundwater fluctuations. Another advantage of the present tidal method is the utilization of two groundwater time series collected from near-shore and relatively inland sites affected by the same ocean tide. The method does not use surface-water observation, thus avoiding errors derived from generally possible surface-water/groundwater boundary effects.The tidal response method with simple decomposition techniques was used to investigate the aquifer properties of an uplifted limestone island located in a subtropical region of Japan. A freshwater lens is the principal water resource for this island and its sustainable development is desired. Significant hydraulic layering has not been reported in the limestone aquifer. Pairs of groundwater-level time-series data collected by simultaneous observations at near-shore and inland sites were analysed by the tidal response method. The results demonstrated heterogeneous aquifer diffusivity on the island, typically with larger values in the southeastern coastal part than in the northwestern coastal part, which is consistent with the planar distribution of the entire freshwater lens and the position of its maximum thickness that are slightly biased toward the northwestern side.</p

Transcriptionally linked simultaneous overexpression of P450 genes for broad-spectrum herbicide resistance

雑草が獲得した最強の除草剤抵抗性メカニズムの解明 --解毒酵素の一斉活性化--. 京都大学プレスリリース. 2023-06-14.Broad-spectrum herbicide resistance (BSHR), often linked to weeds with metabolism-based herbicide resistance, poses a threat to food production. Past studies have revealed that overexpression of catalytically promiscuous enzymes explains BSHR in some weeds; however, the mechanism of BSHR expression remains poorly understood. Here, we investigated the molecular basis of high-level resistance to diclofop-methyl in BSHR late watergrass (Echinochloa phyllopogon) found in the United States, which cannot be solely explained by the overexpression of promiscuous cytochrome P450 monooxygenases CYP81A12/21. The BSHR late watergrass line rapidly produced 2 distinct hydroxylated diclofop acids, only 1 of which was the major metabolite produced by CYP81A12/21. RNA-seq and subsequent reverse transcription quantitative PCR (RT-qPCR)-based segregation screening identified the transcriptionally linked overexpression of a gene, CYP709C69, with CYP81A12/21 in the BSHR line. The gene conferred diclofop-methyl resistance in plants and produced another hydroxylated diclofop acid in yeast (Saccharomyces cerevisiae). Unlike CYP81A12/21, CYP709C69 showed no other herbicide-metabolizing function except for a presumed clomazone-activating function. The overexpression of the 3 herbicide-metabolizing genes was also identified in another BSHR late watergrass in Japan, suggesting a convergence of BSHR evolution at the molecular level. Synteny analysis of the P450 genes implied that they are located at mutually independent loci, which supports the idea that a single trans-element regulates the 3 genes. We propose that transcriptionally linked simultaneous overexpression of herbicide-metabolizing genes enhances and broadens the metabolic resistance in weeds. The convergence of the complex mechanism in BSHR late watergrass from 2 countries suggests that BSHR evolved through co-opting a conserved gene regulatory system in late watergrass

The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese

The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese.BackgroundA considerable diversity in prognosis is seen with lupus glomerulonephritis (LGN). Hence, the clinical usefulness of a recent International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification to judge the long-term outcome of human LGN has been investigated.MethodsWe studied retrospectively 60 subjects with LGN (7 males, 53 females, mean age of 33 years old) who underwent renal biopsies and were followed from 1 to 366 months, with a mean of 187 months. We diagnosed renal pathology as classes, active and sclerosing lesions, according to the new and WHO1995 classification of LGN, and analyzed the clinicopathologic factors affecting to the prognosis of LGN.ResultsNew classification got much higher consensus in the judgment of classes (98% vs. 83%, P = 0.0084). The group of Class IV-S (N = 6) or IV-G (N = 17) at initial biopsies showed higher rate of end-stage renal failure (ESRF) compared with that of Class I, II, III or V (40.9% vs. 2.6%, P < 0.001). The mean 50% renal survival time of Class IV was 189 ± 29 months, and patients with Class IV-S tended to have a poorer prognosis (95 ± 22 months for IV-S vs. 214 ± 35 months for IV-G, P = 0.1495). Class IV was also selected as the most significant risk factor for ESRF by stepwise model (P = 0.002). In subanalysis for ESRF in Class IV (-S or –G), treatment including methylprednisolone pulse therapy was only selected as a significant improving factor for primary outcome (P = 0.034). In addition, activity index was the significant risk factor of death and/or ESRF after initial renal biopsies (P = 0.043). As for actuarial patient death during all follow-up periods, complications with anti-phospholipid syndrome or nephrotic syndrome were significant risk factors (P = 0.013, P = 0.041, respectively).ConclusionNew ISN/RPS 2003 classification provided beneficial pathologic information relevant to the long-term renal outcome and the optimal therapy preventing ESRF and/or death in patients with LGN

Common Peak Approach Using Mass Spectrometry Data Sets for Predicting the Effects of Anticancer Drugs on Breast Cancer

We propose a method for biomarker discovery from mass spectrometry data, improving the common peak approach developed by Fushiki et al. (BMC Bioinformatics, 7:358, 2006). The common peak method is a simple way to select the sensible peaks that are shared with many subjects among all detected peaks by combining a standard spectrum alignment and kernel density estimates. The key idea of our proposed method is to apply the common peak approach to each class label separately. Hence, the proposed method gains more informative peaks for predicting class labels, while minor peaks associated with specific subjects are deleted correctly. We used a SELDI-TOF MS data set from laser microdissected cancer tissues for predicting the treatment effects of neoadjuvant therapy using an anticancer drug on breast cancer patients. The AdaBoost algorithm is adopted for pattern recognition, based on the set of candidate peaks selected by the proposed method. The analysis gives good performance in the sense of test errors for classifying the class labels for a given feature vector of selected peak values

Study of Phonon Dispersion of Iridium Oxide Ca5Ir3O12 with Strong Spin–Orbit Interaction

In this study, we report the results of experiments and calculations of phonon dispersion of iridium oxide with a strong spin–orbit interaction (SOI). Using inelastic X-ray scattering (IXS), we measured the IXS spectra of Ca5Ir3O12 along Γ–A, Γ–M, and Γ–K–M directions in the Brillouin zone of a hexagonal lattice at room temperature. We also show ab initio density-functional phonon dispersions based on local density approximation and generalized gradient approximation (GGA) considering SOI. By comparing the experimental and calculated results, we found that the GGA phonon dispersion with SOI is in very good agreement with the experimental results. The phonon calculation was performed for supercells of 1 × 1 × 3 and preliminary 2 × 2 × 1. We found no phonon instability within these supercells. Low-energy phonon properties such as Debye temperature, specific heat, and sound velocity are also discussed