Ron receptor tyrosine kinase signaling as a therapeutic target

Introduction: Since its discovery nearly 20 years ago, the Ron receptor tyrosine kinase has been extensively studied. These studies have elucidated many of the major signaling pathways activated by Ron. In the context of the inflammation and cancer, studies have shown that Ron plays differential roles; Ron activation limits the inflammatory response, whereas in cancer, Ron activation is associated with increased metastases and poor prognosis.

Areas covered: This review discusses the current literature with regard to Ron signaling and consequences of its activation in cancer as well as its role in cancer therapy. Further, we discuss the mechanisms by which Ron influences the inflammatory response and its role in chronic inflammatory diseases. Finally, we discuss Ron's connection between chronic inflammation and progression to cancer.

Expert opinion: The complex nature of Ron's signaling paradigm necessitates additional studies to understand the pathways by which Ron is functioning and how these differ in inflammation and cancer. This will be vital to understanding the impact that Ron signaling has in disease states. Additional studies of targeted therapies, either alone or in conjunction with current therapies are needed to determine if inhibition of Ron signaling will provide long-term benefits to cancer patients.     

Ornithine ingestion improved sleep disturbances but was not associated with correction of blood tryptophan ratio in Japanese Antarctica expedition members during summer

Members of expeditions to Antarctica may show changes in biological and physiological parameters involved in lipid, glucose, and thyroid hormone metabolism as they adapt to the environment; however, alterations in amino acid (AA) levels and sleep among expedition members in Antarctica have yet to be fully elucidated. We hypothesized that there would be alterations of blood AA levels, and ornithine (Orn) ingestion would affect biological parameters and sleep in Japanese expedition members during the summer in Antarctica. Japanese Antarctica Research Expedition members (22 people) who stayed in Antarctica for 3 months from December 2010 were examined, and a randomized double-blind study of Orn ingestion (400 mg/d) for 4 weeks was performed. Sleep conditions were evaluated subjectively by the Oguri-Shirakawa-Azumi (brief version) questionnaire. The blood of Japanese Antarctica Research Expedition members in Antarctica showed higher creatine kinase, lactate dehydrogenase, and ammonia levels than that in Japan. On blood AA analysis, aspartate, Orn, and serine were significantly higher, and alanine and tryptophan (Trp) were significantly lower in Antarctica than in Japan. The Trp ratio, the value of Trp divided by the sum of phenylalanine, tyrosine, and branched-chain AAs, was significantly lower in Antarctica than in Japan. Although sleep deteriorated during the stay in Antarctica, Orn ingestion, to some extent, improved sleep compared with the placebo group in Antarctica, suggesting that Orn is effective for people with heavy physical workloads in places such as Antarctica.     

胃癌组织中RUNX3的表达与c—Met的相关性研究

目的：探讨RUNX3及c—Met在胃癌组织中的表达以及与胃癌临床病理特征之间的关系。方法：以56例胃癌患者为研究对象,采用SP免疫组化法研究RUNX3及c—Met在正常胃黏膜及不同分期,不同分化程度各组胃癌标本中的表达。结果：胃癌组织中RUNX3的表达明显降低,c—Met的表达显著提高。RUNX3的表达与胃癌浸润深度、远隔转移、临床分期呈负相关（P〈0．05）,与胃癌病理分化程度呈正相关,与胃癌病灶大小,淋巴结有无转移,患者性别,年龄无相关性。c—Met的阳性表达率与胃癌的浸润深度、淋巴转移、远隔转移、临床分期呈正相关,与肿瘤分化程度、肿瘤大小、患者性别、年龄无相关性。RUNX3与c—Met的表达有相关性（P〈0．05）。结论：胃癌组织中RUNX3表达下调,提示其在胃癌发生,发展中起重要作用,c—Met的表达与RUNX3表达的存在相关性。     

Two different modes of enzymatic changes in serum with progression of Duchenne muscular dystrophy

Nineteen serum enzymes from patients with Duchenne muscular dystrophy and asthma, and normal subjects were studied. These enzymes include aminopeptidases, cathepsin C, angiotensin-converting enzyme, serine proteinase, sulphatase, phosphatase, esterases and ribonuclease. The enzymatic changes in dystrophic patients were related to two parameters: severity of the disease as judged from symptomatology, and duration of the disease. Most of the enzyme levels tested were increased in milder cases, but they tended to decrease with severity of the disease. On the other hand, there was a group of enzymes showing just opposite tendencies: serine proteinase, cathepsin C and ribonuclease. Even when viewed from the relationship to duration of the disease, the above mentioned grouping of enzymes was generally valid. Most of the enzyme levels, including those routinely applied as clinical parameters, tended to decrease, logarithmically, with an increase in duration of the disease. On the contrary, some others, including serine proteinase, cathepsin C and ribonuclease, tended to increase toward their control levels. Such tendencies were not found in the patients with asthma. The discrepancy between the above two groups of enzymes may have some implications for the process of protein degradation in dystrophic patients.     

BDNF Val66Met,stress, and positive mothering: Differential susceptibility model of adolescent trait anxiety

Etiological research has indicated the gene–environment interaction (G × E) on adolescent anxiety. This study aimed to examine how the BDNF Val66Met polymorphism interacted with stressful life events and positive mothering to influence youth trait anxiety. The study sample included 780 community adolescents of Chinese Han ethnicity (M = 13.6, 51.3% females). Participants’ trait anxiety, exposure to stressful life events, and mother's warmth-reasoning were assessed by self-reported questionnaires. We found that BDNF Val66Met polymorphism significantly moderated the influences of stressful life events and mother's warmth-reasoning on adolescent anxiety. The influences were significantly greater in adolescents carrying one or two Val allele than those with Met/Met genotype. Moreover, the G × E interactions were more consistent with the differential susceptibility than the diathesis–stress model. Adolescents carrying Val allele who were more susceptible to adversity were also more likely to benefit from supportive experiences. These findings provide novel evidence for the role of BDNF Val66Met as a genetic susceptibility modulating the influences of stressful life events and mother's warmth-reasoning on adolescent anxiety. We speculate that BDNF Val66Met may moderate anxious youths’ responses to mindfulness-based stress reduction program and family-based treatment targeting the enhancement of positive parenting.     

COMT Val158Met polymorphism influences the susceptibility to framing in decision‐making: OFC‐amygdala functional connectivity as a mediator

Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this “framing effect.” Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene–behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene–behavior association was mediated by resting‐state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision‐making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene–behavior association. Hum Brain Mapp 37:1880–1892, 2016. © 2016 Wiley Periodicals, Inc .