Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage.     

携带碘125粒子食管支架治疗食管癌的临床研究

目的:探究携带碘125粒子食管支架治疗食管癌的临床效果。方法:选择2010年1月至2018年1月于本院收治食管癌患者160例，按照随机数字表法分为观察组与对照组2组，对照组采用常规食管支架置入治疗，观察组采用携带碘125粒子食管支架治疗，评估两组患者吞咽困难及生活质量改善情况，并观察术后并发症及平均生存期。结果:术后两组患者Stooler评分均较术前降低，且观察组Stooler评分于术后1、3、6、12个月均显著低于对照组（P＜0.05）；术后3个月观察组吞咽困难、进食不适、疼痛、咽口水困难、吞咽梗阻、口干、言语评分均显著低于对照组（P＜0.05），而反流、味觉改变、咳嗽比较，差异无统计学意义（P＞0.05）；观察组术后1个月并发症发生率16.25%显著低于对照组31.25%（P＜0.05）；观察组平均生存期显著高于对照组（P＜0.05）。结论:携带碘125粒子食管支架治疗食管癌效果显著，可改善患者吞咽困难症状，提高生活质量，延长生存期，值得临床应用推广。     

Contribution of equilibrative nucleoside transporters 1 and 2 to gemcitabine uptake in pancreatic cancer cells

Hepatic arterial infusion (HAI) chemotherapy is expected to be a more effective and safer method to treat the hepatic metastasis of pancreatic cancer than intravenous (iv) administration because of higher tumor exposure and lower systemic exposure. To clarify the uptake mechanism of nucleoside anticancer drugs, including gemcitabine (GEM), in pancreatic cancer, we investigated the uptakes of radiolabeled uridine (a general substrate of nucleoside transporters) and GEM in pancreatic cancer cell lines MIA‐PaCa2 and As‐PC1. Uridine uptake was inhibited by non‐labeled GEM and also by S‐(4‐nitrobenzyl)‐6‐thioinosine (NBMPR; an inhibitor of equilibrative nucleoside transporters, ENTs) in a concentration‐dependent manner, suggesting that ENTs contribute to uridine uptake in pancreatic cancer cells. As for GEM, saturable uptake was mediated by high‐ and low‐affinity components with K_m values of micromolar and millimolar orders, respectively. Uptake was inhibited in a concentration‐dependent manner by NBMPR and was sodium ion‐independent. Moreover, the concentration dependence of uptake in the presence of 0.1 μM NBMPR showed a single low‐affinity site. These results indicated that the high‐ and low‐affinity sites correspond to hENT1 and hENT2, respectively. The results indicated that at clinically relevant hepatic concentrations of GEM in GEM‐HAI therapy, the metastatic tumor exposure of GEM is predominantly determined by hENT2 under unsaturated conditions, suggesting that hENT2 expression in metastatic tumor would be a candidate biomarker for indicating anticancer therapy with GEM‐HAI.     

6,7-Dehydroroyleanone diterpene derived from Tetradenia riparia essential oil modulates IL-4/IL-12 release by macrophages that are infected with Leishmania amazonensis

Parasitology Research - The treatment of cutaneous leishmaniasis in associated with several adverse effects and therapeutic failure, resulting in patients’ abandonment of treatment. Research...     

Effect of compressive force on the expression of inflammatory cytokines and their receptors in osteoblastic Saos-2 cells

OBJECTIVE: In orthodontic tooth movement, some cytokines released from periodontal ligament fibroblasts and alveolar bone osteoblasts on the pressure side can alter the normal processes of bone remodelling, resulting in physiological bone resorption. We examined the effect of compressive force and interleukin (IL)-1 type I receptor antagonist (IL-1ra) on the expression of inflammatory cytokines that promote osteoclast formation, as well as on their receptors, in osteoblastic Saos-2 cells. DESIGN: The cells were cultured in Dulbecco's modified Eagle medium containing 10% fetal bovine serum with or without continuous compressive force (0.5-3.0 g/cm(2)) and/or IL-1ra for up to 24h. The gene expression levels of the cytokines and their receptors were estimated by determining mRNA levels using real-time PCR; the protein levels were determined using ELISA or immunohistochemical staining. RESULTS: The expression of IL-1beta, IL-1 receptor, IL-6, IL-6 receptor, IL-8 receptor, IL-11 and tumor necrosis factor-alpha (TNFalpha) increased depending on the strength and duration of the compressive force, whereas the expression of IL-8, IL-11 receptor and TNFalpha receptor did not change with the application of compressive force. The expression of cytokines and their receptors produced by 3.0 g/cm(2) of compressive force decreased with the simultaneous addition of IL-1ra and the decrease was remarkable in IL-8 receptor, IL-11 and TNFalpha. CONCLUSION: These results indicate that mechanical stress induces the production of inflammatory cytokines and their receptors in osteoblasts and the phenomenon is enhanced by the autocrine action of IL-1beta, which is increased in amount by mechanical stress.     

Purification and characterization of a trypsin-like protease from the culture supernatant of Actinobacillus actinomycetemcomitans Y4

We purified and characterized a protease from Actinobacillus actinomycetemcomitans. The protease was isolated from the culture supernatant by sonication in phosphate-buffered 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). The protease was purified by acetone precipitation, followed by column chromatography with Arginine Sepharose 4B, DEAE Sepharose CL-6B, Sephacryl S-200HR and HiTrap Q. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified protease showed a clear band at approximately 50 kDa. The protease showed trypsin-like activity with hydrolytic activity for the synthetic substrates N alpha-benzoyl-DL-arginine p-nitroanilide (BApNA) and N alpha benzoyl-DL-lysine p-nitroanilide (BLpNA). The activity of the protease was stable at pH 7.0 to approximately 8.0. The activity of the protease was inhibited by leupeptin, phenylmethylsulfonyl fluoride (PMSF), and EDTA, but was not affected by dithiothreitol (DTT), cysteine, 2-mercaptoethanol, pepstatin or soybean trypsin inhibitor. These data suggest that this protease is a serine protease or metallo protease. This enzyme extensively degraded collagen type I and fibronectin.     

Relationship between masseter muscle size and maxillary morphology

The aim of this study was to investigate the relationship between masseter muscle size and craniofacial morphology, focusing on the maxilla. Twenty-four patients (11 males and 13 females; mean age 27.6 ± 5.6 years) underwent cephalometric analyses. Ultrasonography was used to measure the cross-sectional area (CSA) of the masseter muscle and bite force was measured using pressure sensitive film. The results showed that CSA-relaxed was positively correlated with upper anterior face height (UAFH)/total anterior face height (TAFH) and negatively with lower anterior face height (LAFH)/TAFH and LAFH (P < 0.05). CSA-clenched was correlated positively with SN-palatal, FH-palatal, UAFH/TAFH, and lower posterior face height (LPFH)/total posterior face height (TPFH) and negatively with LAFH/TAFH, LAFH, upper posterior face height (UPFH)/TPFH, and UPFH (P < 0.05). Bite force was positively correlated with LPFH/TPFH and negatively with UPFH/TPFH (P < 0.05). As the masseter became larger, the anterior maxillary region tended to shift downwards relative to the cranial base, whereas the posterior region tended to shift upwards. The decrease in LAFH/TAFH and increase in LPFH/TPFH as the size of the masseter muscle increases may be influenced not only by the inclination of the mandibular plane but also by the clockwise rotation of the maxilla.     

Neural hyperplasia in maxillary bone of multiple endocrine neoplasia type 2B patient

Multiple endocrine neoplasia (MEN) type 2B is the rarest and most aggressive form of MEN syndrome. MEN 2B patients manifest characteristic oral and facial features besides the neural crest cell-derived tumors, including medullary carcinoma, pheochromocytoma, mucosal neuroma, and ganglioneuromatosis of the gut. We report a case of MEN 2B diagnosed on the basis of the warning signs of mucosal neuroma and multiple neural hyperplasias in the maxillary bone resected during orthognathic surgery. A subsequent systemic examination under the pathologic diagnosis of neural lesions revealed medullary thyroid carcinoma, megacolon, thickened corneal nerves, and RET gene mutation, thus verifying the diagnosis of MEN 2B. An immunohistochemical study revealed an increased number of unmyelinated Schwann cells in the hyperplastic nerves. We suggest that intraosseous neural hyperplasia is a specific finding of the MEN 2B syndrome in addition to the known oral and facial manifestations.