Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc.

Despite the high prevalence of intervertebral disc disease, little is known about changes in intervertebral disc cells and their regenerative potential with ageing and intervertebral disc degeneration. Here we identify populations of progenitor cells that are Tie2 positive (Tie2+) and disialoganglioside 2 positive (GD2+), in the nucleus pulposus from mice and humans. These cells form spheroid colonies that express type II collagen and aggrecan. They are clonally multipotent and differentiated into mesenchymal lineages and induced reorganization of nucleus pulposus tissue when transplanted into non-obese diabetic/severe combined immunodeficient mice. The frequency of Tie2+ cells in tissues from patients decreases markedly with age and degeneration of the intervertebral disc, suggesting exhaustion of their capacity for regeneration. However, progenitor cells (Tie2+GD2+) can be induced from their precursor cells (Tie2+GD2-) under simple culture conditions. Moreover, angiopoietin-1, a ligand of Tie2, is crucial for the survival of nucleus pulposus cells. Our results offer insights for regenerative therapy and a new diagnostic standard

植物繊維原料の醗酵精練について(第 17 報) : 一細菌のペクチン質分解酵素について(農芸化学部門)

亜麻の浸漬醗酵液中よりペクチン質分解酵素を強く生成する一細菌を見出しNo. 431菌と名称しその菌学的性質を検討した。本菌の生成するペクチナーゼは強力なるペクチン粘度降下作用を示すが, 糖化作用及びメチルエステラーゼ作用は殆んど示さなかった。本菌の麩麹抽出液からアセトン40∿60%濃度で沈澱する区分をとり更にpH 8.0でCM-セルロースカラムで精製を行なってほぼ純粋な酵素標品を得た。本酵素の作用最適pHは9.0付近にあり, ペクチンに強く作用して粘度降下作用を示すと共に微量の不飽和ガラクツロニドを生成するが, ペクチン酸にはその様な顕著な作用を示さなかった。したがってNo. 431菌の生成する酵素はエンド型のペクチントランスエリミナーゼ(endo-pectintranseliminase)であろうと推論した。We isolated some bacteria showing a strong activity of pectinase action from flax fermentating solution. One of these strain, No. 431,acted strongly to pectin and the taxonomic properties of the strain were researched. The pectinase produced by strain was partialy purified by ionexchange column-chromatography with CM-cellulose. It was recognized that this enzyme, showed much activity for viscosity reduction to pectin solution, but little to pectic acid solution. On each decomposition of pectic substances by this enzyme the galacturonate or the homologue was not producted from the materials and we could explain that the enzyme showed strong transe-liminase action to pectin but little to pectic acid

A stable association with PME‐1 may be dispensable for PP2A demethylation – implications for the detection of PP2A methylation and immunoprecipitation

Reversible methyl‐esterification (methylation) of Leu309 in the protein phosphatase 2A catalytic subunit (PP2Ac) is essential for proper biogenesis of the PP2A holoenzyme. Accumulating evidence links PP2Ac methylation to diseases, including cancer and neurodegenerative disorders. Protein phosphatase methyl‐esterase (PME‐1) specifically catalyzes PP2Ac demethylation. We demonstrate that PP2Ac is demethylated in cell extracts even at 0 °C unless prevented by a PME‐1 methyl‐esterase inhibitor. This promotes dissociation of PP2A heterotrimers with B55 or PR72 subunits, but not those with B56 subunits. These results reveal differential sensitivity of ABC heterotrimers to methylation status of the C subunit. Our study advocates caution when interpreting earlier findings, offers an effective protocol for preserving PP2A complexes, and reveals key distinctions between B subunits and their interactions with the AC core dimer of PP2A

Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease.

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection

Real-world effects of once-daily inhaled steroid (fluticasone furoate) combined with long-acting beta-2 agonist (vilanterol) and long-acting muscarinic antagonist (umeclidinium) on lung function tests of asthma patients in Japan

Background: The Japanese drug use system allowed the once-daily use of inhaled corticosteroid fluticasone furoate (FF) combined with a long-acting beta-2 agonist vilanterol (VI) and a long-acting muscarinic antagonist umeclidinium (UMEC) against asthma on 18 February 2021. We investigated the real-world effects of these drugs (FF/UMEC/VI) mainly on lung function tests.Methods: This was an open-label, uncontrolled, within-group time-series (before-after) study. Prior asthma treatment (inhaled corticosteroid with/without a long-acting beta-2 agonist with/without a long-acting muscarinic antagonist) was switched to FF/UMEC/VI 200/62.5/25 μg. Subjects were evaluated by lung function tests prior to, and 1–2 months after, initiation of FF/UMEC/VI 200/62.5/25 μg. Patients were asked questions regarding the asthma control test and preference for drugs.Results: Overall, 114 asthma outpatients (97% Japanese) were enrolled from February 2021 to April 2022: 104 subjects completed the study. Forced expiratory volume in 1 s, peak flow, and asthma control test score of FF/UMEC/VI 200/62.5/25 μg-treated subjects were significantly increased (p < 0.001, p < 0.001, and p < 0.01, respectively). In contrast with FF/VI 200/25 μg, instantaneous flow at 25% of the forced vital capacity and expiratory reserve volume were significantly increased by FF/UMEC/VI 200/62.5/25 μg (p < 0.01, p < 0.05, respectively). Sixty-six percent of subjects declared they wanted to continue FF/UMEC/VI 200/62.5/25 μg in the future. Adverse effects, mainly local, were seen in 30% of patients, but no serious adverse effects were seen.Conclusion: Once-daily FF/UMEC/VI 200/62.5/25 μg was effective against asthma without serious adverse events. This is the first report that demonstrated FF/UMEC/VI dilated peripheral airways using lung function tests. This evidence on drug effects may improve our understanding of pulmonary physiology and the pathophysiology of asthma

Severity by National Institute of Health Stroke Scale Score and Clinical Features of Stroke Patients with Patent Foramen Ovale Stroke and Atrial Fibrillation

The comparative severity of patent foramen ovale (PFO)-related stroke in patients without atrial fibrillation (AF) and AF-related stroke in patients without PFO is unknown. Therefore, we compared the severity of PFO-related stroke and AF-related stroke. Twenty-six patients who underwent transesophageal echocardiography (TEE) were diagnosed with cardioembolic stroke from July 2018 to March 2020. Cases with AF detected by electrocardiograms or thrombus in the left atrium or left atrial appendage on TEE were included in the AF-related stroke group. Cases with a positive microbubble test on the Valsalva maneuver during TEE, and with no other factors that could cause stroke, were included in the PFO-related stroke group. This study was designed as a single-center, small population pilot study. The stroke severity of the two groups by the National Institute of Health Stroke Scale (NIHSS) score was compared by statistical analysis. Of the 26 cases, five PFO-related stroke patients and 21 AF-related stroke patients were analyzed. The NIHSS score was 2.2 ± 2.8 and 11.5 ± 9.2 (p-value < 0.01), the rate of hypertension was 20.0% and 85.7% (p-value = 0.01), and the HbA1c value was 5.5 ± 0.2% and 6.3 ± 1.3% (p-value = 0.02) in the PFO-related and AF-related stroke groups, respectively. Compared with AF-related stroke patients, stroke severity was low in PFO-related stroke patients