Impact of Travel Distance on Surgical Outcomes of Patients Surgically Treated for Non-Small Cell Lung Cancer: A Single-Center Study in Ehime, Japan.

Travel burden is a poor prognostic factor for many cancers worldwide because it hinders optimal diagnosis and treatment planning. Currently, the impact of travel burden on survival after surgery for non-small cell lung cancer (NSCLC) in Japan is largely unexplored. We examined the impact of travel distance on the postoperative outcomes of patients with NSCLC in Ehime Prefecture, Japan. The data of 1212 patients who underwent surgical resection for NSCLC were retrospectively reviewed. Patients were divided into quartiles based on the travel distance from their home to the hospital (≤ 13 km, 13-40 km, 40-57 km, and > 57 km) in Ehime Prefecture. We found no significant differences among the quartiles in baseline clinicopathological characteristics, including sex, smoking status, histology, surgical procedure, clinical stage, and pathological stage. Overall survival (OS) and relapse-free survival (RFS) also were not significantly different among the travel distance quartiles. We conclude that travel distance did not impact OS or RFS among patients with NSCLC who underwent surgical resection at our institution.

Benign Mesothelial Cells in transbronchial biopsy specimens: A potential diagnostic pitfall for lung cancer.

Bronchoscopy is a common diagnostic procedure used to identify lung cancer. Specimens acquired through transbronchial biopsy are pivotal in the diagnosis and molecular characterization of this disease. The occurrence of benign mesothelial cells during a transbronchial biopsy (TBB) is relatively rare. Furthermore, these lesions can sometimes be erroneously identified as malignant, potentially resulting in unwarranted or inappropriate treatment for patients with and without lung cancer. In this retrospective analysis, we examined 619 TBB cases at our institute from 2019 to 2021. Benign mesothelial cells were identified via immunohistochemical studies in eight (1.3%) of 619 cases. These cells were classified into three patterns based on their cellular morphology: monolayer, lace, and cobblestone. Recognizing this phenomenon during the procedure is crucial to accurately distinguish benign mesothelial cells from their cancerous counterparts.

Dietary apple polyphenols increase skeletal muscle capillaries in Wistar rats.

Dietary apple polyphenols (AP) have been shown to exhibit beneficial effects on muscle endurance. Fast-to-slow change in the composition of myosin heavy chains was known as one of the molecular mechanisms. Here, we examined the effects of dietary AP on the capillaries and mitochondria in the rat skeletal muscle to elucidate the mechanisms underlying muscular endurance enhancement. Twenty-four Wistar male rats were divided into three groups, namely, the control group, 0.5% AP group, and 5% AP group (n = 8 in each group). After a feeding period of 4 weeks, rats were dissected, gastrocnemius muscles were removed, and the density of capillaries and levels of mitochondrial proteins were analyzed. Capillary density of the gastrocnemius increased to 17.8% in rats fed with 5% AP as compared to the control rats. No significant change was observed in the mitochondrial content and dynamics (fusion/fission) of regulatory proteins. To investigate the mechanisms underlying the increase in the capillary density, positive (vascular endothelial cell growth factor, VEGF) and negative (thrombosponsin-1, TSP-1) factors of angiogenesis were analyzed. TSP-1 expression significantly decreased in rats fed with 0.5% AP and 5% AP by approximately 25% and 40%, respectively, as compared with the control rats. There were no significant differences in VEGF expression. Thus, dietary AP may increase the muscle capillary density by decreasing TSP-1 expression. We concluded that the increase in the capillary density and the fast-to-slow change in myosin heavy chains by AP feeding are the main causes for muscle endurance enhancement in Wistar rats.

Apple procyanidins promote mitochondrial biogenesis and proteoglycan biosynthesis in chondrocytes.

Apples are well known to have various benefits for the human body. Procyanidins are a class of polyphenols found in apples that have demonstrated effects on the circulatory system and skeletal organs. Osteoarthritis (OA) is a locomotive syndrome that is histologically characterized by cartilage degeneration associated with the impairment of proteoglycan homeostasis in chondrocytes. However, no useful therapy for cartilage degeneration has been developed to date. In the present study, we detected beneficial effects of apple polyphenols or their procyanidins on cartilage homeostasis. An in vitro assay revealed that apple polyphenols increased the activities of mitochondrial dehydrogenases associated with an increased copy number of mitochondrial DNA as well as the gene expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), suggesting the promotion of PGC-1α-mediated mitochondrial biogenesis. Apple  procyanidins also enhanced proteoglycan biosynthesis with aggrecan upregulation in primary chondrocytes. Of note, oral treatment with apple procyanidins prevented articular cartilage degradation in OA model mice induced by mitochondrial dysfunction in chondrocytes. Our findings suggest that apple procyanidins are promising food components that inhibit OA progression by promoting mitochondrial biogenesis and proteoglycan homeostasis in chondrocytes.

Ninety-day dietary toxicity study of apple polyphenol extracts in Crl: CD (SD) rats.

To examine the safety of Dietary Applephenon® (AP) in feed, Crl: CD (SD) rats of each sex were divided into four groups and given diets containing AP at 0%, 1.25%, 2.5%, or 5.0% for 90 days. All rats survived and toxic changes were not observed throughout the study. Body weight and food efficiency in the 5.0% AP group of both sexes were significantly decreased compared with that in controls. These changes were considered to be caused by the physiological effects of AP (including the inhibitory effects on pancreatic lipase activity). Slight hypertrophy in acinar cells in the parotid and submandibular glands appeared in the 2.5% and 5.0% groups. These were suggested not to be toxicological but physiologic adaptive responses to oral stimuli by the lower pH of AP-containing diets. In conclusion, dietary AP in feed, up to a maximum level of 5.0% for 90 days, given to rats did not induce toxicological effects.

Isolation and structure elucidation of tetrameric procyanidins from unripe apples (Malus pumila cv. Fuji) by NMR spectroscopy.

Procyanidins are plant secondary metabolites widely consumed and known to have various physiological functions, but their bioavailability and mechanism of action are still unclear especially for larger oligomers. One of the reasons is scarce information about the detailed structure of oligomeric procyanidins. As for apple, structures of procyanidin components larger than trimers are scarcely known. In this study, 11 tetrameric procyanidins including two known compounds were isolated from unripe apples (Malus pumila cv. Fuji) and identified by NMR spectroscopic analysis and phloroglucinol degradation. As a result, the detailed structural diversity of tetrameric procyanidins in apple was established.

A procyanidin trimer, C1, promotes NO production in rat aortic endothelial cells via both hyperpolarization and PI3K/Akt pathways.

Procyanidins, which are condensed catechins, have been elucidated as absorbable polyphenols, but their health-benefits remain unclear. The aim of this study was, thus, to clarify the efficacy and mechanism of each procyanidin oligomer in NO activation in rat aortic endothelial cells (RAECs). Treatment of RAECs with 50µM procyanidin C1 (4ß→8 trimer) resulted in a time- and dose-dependent hyperpolarization using the membrane potential-sensitive probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, while no effect was observed for (-)-epicatechin (a monomer) and procyanidin B2 (4ß→8 dimer). The C1-induced hyperpolarization was inhibited by iberiotoxin, a specific inhibitor of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, as well as 2-aminoethyl diphenylborinate (2-APB), a store-operated Ca(2+) entry inhibitor. Procyanidin C1 caused a significant increase in NO production from RAECs via phosphorylation of both eNOS and Akt, and the effect was completely inhibited by N(G)-monomethyl-l-arginine or combined treatment with iberiotoxin and the phosphatidylinositol 3-kinase (PI3K) specific inhibitor, wortmannin, as well as combined treatment with 2-APB and wortmannin. Taken together, these findings provide critical evidence that procyanidin C1, but not B2, has potential to induce NO production in RAECs via both Ca(2+)-dependent BK(Ca) channel-mediated hyperpolarization and Ca(2+)-independent PI3K/Akt pathways.