S100A8, S100A9 and S100A8/A9 heterodimer as novel cachexigenic factors for pancreatic cancer-induced cachexia.

BACKGROUND: Cancer cachexia, occurring in ~ 80% pancreatic cancer (PC) patients overall, is a paraneoplastic syndrome mediated by cancer-induced systemic inflammation and characterized by weight loss and skeletal muscle wasting. Identifying clinically relevant PC-derived pro-inflammatory factors with cachexigenic potential may provide novel insights and therapeutic strategies. METHODS: Pro-inflammatory factors with cachexigenic potential in PC were identified by bioinformatic analysis. The abilities of selected candidate factors in inducing skeletal muscle atrophy were investigated. Expression levels of candidate factors in tumors and sera was compared between PC patients with and without cachexia. Associations between serum levels of the candidates and weight loss were assessed in PC patients. RESULTS: S100A8, S100A9, and S100A8/A9 were identified and shown to induce C2C12 myotube atrophy. Tumors of PC patients with cachexia had markedly elevated expression of S100A8 (P = 0.003) and S100A9 (P < 0.001). PC patients with cachexia had significantly higher serum levels of S100A8, S100A9 and S100A8/A9. Serum levels of these factors positively correlated with percentage of weight loss [correlation coefficient: S100A8: 0.33 (P < 0.001); S100A9: 0.30 (P < 0.001); S100A8/A9: 0.24 (P = 0.004)] and independently predicted the occurrence of cachexia [adjusted odds ratio (95% confidence interval) per 1ng/ml increase: S100A8 1.11 (1.02-1.21), P = 0.014; S100A9 1.10 (1.04-1.16), P = 0.001; per 1 µg/ml increase: S100A8/A9 1.04 (1.01-1.06), P = 0.009]. CONCLUSIONS: Atrophic effects of S100A8, S100A9, and S100A8/A9 indicated them as potential pathogenic factors of PC-induced cachexia. In addition, the correlation with the degree of weight loss and prediction of cachexia in PC patients implicated their potential utility in the diagnosis of PC-induced cachexia.

RNA binding protein SAMD4: current knowledge and future perspectives.

SAMD4 protein family is a class of novel RNA-binding proteins that can mediate post-transcriptional regulation and translation repression in eukaryotes, which are highly conserved from yeast to humans during evolution. In mammalian cells, SAMD4 protein family consists of two members including SAMD4A/Smaug1 and SAMD4B/Smaug2, both of which contain common SAM domain that can specifically bind to different target mRNAs through stem-loop structures, also known as Smaug recognition elements (SREs), and regulate the mRNA stability, degradation and translation. In addition, SAMD4 can form the cytoplasmic mRNA silencing foci and regulate the translation of SRE-containing mRNAs in neurons. SAMD4 also can form the cytosolic membrane-less organelles (MLOs), termed as Smaug1 bodies, and regulate mitochondrial function. Importantly, many studies have identified that SAMD4 family members are involved in various pathological processes including myopathy, bone development, neural development, and cancer occurrence and progression. In this review, we mainly summarize the structural characteristics, biological functions and molecular regulatory mechanisms of SAMD4 protein family members, which will provide a basis for further research and clinical application of SAMD4 protein family.

FAM96A and FAM96B function as new tumor suppressor genes in breast cancer through regulation of the Wnt/ß-catenin signaling pathway.

AIMS: Family with sequence similarity 96 member A and B (FAM96A and FAM96B) are two highly conserved homologous proteins belonging to MIP18 family. Some studies have shown that FAM96A and FAM96B are significantly down-regulated in human gastrointestinal stromal tumors, colon cancer, and liver cancer. However, the molecular mechanisms of FAM96A/B in breast cancer are unknown. This work aims to explore the roles of FAM96A/B in breast cancer progression. MAIN METHODS: Specific siRNAs were used to down-regulate FAM96A/B expression, and recombinant plasmids were used to up-regulate FAM96A/B expression in breast cancer cells. Cell proliferation was measured using MTT and colony formation. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion were examined by wound healing and transwell assays. The relationships among FAM96A/B, EMT and Wnt/ß-catenin pathway were determined by analyzing expression changes of classical markers. KEY FINDINGS: We found that FAM96A/B expression was down-regulated in breast cancer. FAM96A/B overexpression suppressed breast cancer cell proliferation, invasion and migration, induced cell apoptosis and caused cell cycle arrest. Conversely, FAM96A/B knockdown exhibited the opposite effects. Moreover, our data demonstrated that FAM96A/B overexpression suppressed EMT and Wnt/ß-catenin pathway, while FAM96A/B knockdown showed the promoting effects on EMT and Wnt/ß-catenin pathway. Furthermore, a Wnt pathway inhibitor, XAV-939 reversed the promoting effects of FAM96A/B knockdown on breast cancer progression. SIGNIFICANCE: Our findings suggest that FAM96A/B may function as new tumor suppressor genes and inhibit breast cancer progression via modulating Wnt/ß-catenin pathway, which can provide the potential markers for breast cancer diagnosis and therapy.

[Comparison of integration processing technology of origin and traditional cutting processing technology of Moslae Herba for lung-Yang deficiency rats].

To compare the effect of integration processing technology of origin (IPTO) and traditional cutting processing technology (TCPT) of Moslae Herba for lung-Yang deficiency rats caused by complex factors, analyze the mechanism, and provide the modern pharmacology basis for the implementation of IPTO of Moslae Herba. The rat models of lung-Yang deficiency were established by smoking + swimming in ice water + drinking ice water. The model rats were randomly divided into different groups, and were treated with intragastric administration for 30 d. Then the general signs, anal temperature and autonomic activity of the rats were observed. The pathological morphology of lung tissues was observed, and the positive expression of tumor necrosis factor (TNF-α) was observed by immunohistochemical method, and the hematological indexes were determined. Enzyme linked immunosorbent assay (ELISA) method was used to detect serum nitric oxide (NO), immunoglobulin G (IGG), malondialdehyde (MDA), thromboxane B2 (TXB2) and interleukin-8 (IL-8) level, and the organ coefficients of heart, liver, spleen, lung, kidney and other organs were calculated. According to the results, Moslae Herba volatile oil and decoction could improve the general signs and autonomic activities of lung-Yang deficiency rats, improve the body weight, rectal temperature, and the content of IGG in serum of lung-Yang deficiency rats, reduce organ coefficients of heart, liver, spleen, lung and kidney, serum NO, MDA, TXB2, IL-8 contents, white blood cell and TNF-α mean optical density in the lung tissues of rats. witg statistically significant difference (P<0.01 or P<0.05). The effects of IPTO volatile oil and water decoction were slightly higher. Therefore, Moslae Herba has therapeutic effect on lung-Yang deficiency rats, and ICPT has better effect, whose mechanism may be related to the intervention of TNF-α expression, improving the level of IGG, and inhibiting NO, MDA, IL-8, and TXB2 levels.

[Acceptability and related factors on male circumcision among young men with Yi ethnicity in one county of Sichuan province.].

OBJECTIVE: To explore the acceptability of male circumcision (MC) as an HIV prevention method and its related factors among young men of Yi ethnicity in Liangshan prefecture. METHODS: 446 young men were selected in Butuo county, under stratified sampling method. Using a self-designed questionnaire, face to face interviews were taken to collect HIV-related risk behaviors, knowledge and acceptability of MC. RESULTS: After an introduction on MC by interviewers, 40.6% of the interviewees expressed their willingness in taking this surgery. The main reason for acceptance was that they felt this surgery might reduce the risk of HIV infection (90.1%). For those who refused to take this surgery, most of them thought it was too sensitive and embarrassing (52.5%) and were afraid that it might affect their procreation ability. Data from logistic regression analysis indicated that the acceptability of MC was associated with the following factors as:age, income, experience of commercial sexual behavior. They also felt that messages related to male MC surgery could reduce the risk of being infected with HIV/STDs or induce pain when having sexual intercourse, or it might cause partial infection after surgery, or they might be mocked at if taking the surgery. CONCLUSION: It is the prerequisite in helping young people of Yi ethnicity to have a good understanding on MC as for Yi people, embarrassment attitudes towards sex appears to be one of the big obstacles against the popularization of this surgery. The operation should be provided by trained and professional doctors, with standardized procedure, in good sanitary conditions and free for service.

[Determination of perfluoropropane in canine whole blood by purge and trap concentrator-GC-MS].

AIM: To develop a method for direct determination of perfluoropropane in canine whole blood and to study its pharmacokinetics after a suspension of perfluoropropane-containing albumin microcapsules was administered intravenously. METHODS: Perfluoropropane-containing albumin microcapsule suspension was administered intravenously to anesthetized canines at the dosage of 0.6 mL x kg(-1). Whole blood samples were collected and added directly into the purging glass tube in Tekmar 3000 Purge and Trap Concentrator coupled with a GC-MS for the determination of perfluoropropane. The pharmacokinetic parameters of perfluoropropane were calculated by non-compartment model statistics. RESULTS: The linear range was 0.0168-4.03 mg x L(-1). The main pharmacokinetic parameters of perfluoropropane was obtained as follows: mean residence time (MRT) was (63 +/- 5) s, T1/2 was (44 +/- 4) s, Tmax was 30 s, Cmax was (2.20 +/- 0.20) mg x L(-1), AUC0-infinity was (96 +/- 11) mg x s x L(-1). CONCLUSION: The method is sensitive, specific and simple. It can be used to determine fluorocarbon contained in microcapsule ultrasound contrast agents for studying its pharmacokinetics.

[Pharmacokinetics and targeting characteristics of adriamycin after canine hepatic arterial embolization with adriamycin-lipiodol emulsion].

OBJECTIVE: To study the phamacokinetics and targeting characteristics of adriamyin in dogs following embolization of hepatic artery with adriamyin-lipiodol emulsion (AD-E). METHODS: After injection of adriamycin solution and the emulsion, respectively, into the hepatic artery via a femoral artery of the dogs, the concentration of adriamycin in the peripheral venous blood and hepatic tissue were determined by high-performance liquid chromatography. RESULTS: The concentration of adriamycin in peripheral venous blood was significantly lowered after AD-E embolization in comparison with that after adriamycin solution injection. Adriamycin concentration in the hepatic tissue at 10, 24, and 48 h after AD-E embolization was 5.42, 3.33 and 2.38 times that of adrimycin solution group, respectively. CONCLUSION: Compared to adriamycin solution, AD-E as an embolic agent can significantly alter the serum pharmacokinetics and liver targeting characteristics of adriamycin.