ShenQi FuZheng Injection ameliorates fatigue-like behavior in mouse models of cancer-related fatigue.

Cancer-related fatigue (CRF) not only has a negative impact on work, daily activities and social relationships, but also be a predictor of cancer patients' survival. And it has no FDA-approved therapy. ShenQi FuZheng Injection (SFI) is clinically used for adjuvant treatment of lung cancer and gastric cancer. And we found that SFI can improve the incidence of CRF in patients with gastric cancer. However, its efficacy against CRF remains to be elucidated. In the present study we established a tumor-bearing mouse fatigue model, conducted the forced swim test (FST) and grip strength measurements to evaluate the therapeutic effect of SFI. Additionally, we detected inflammation and immune indicators. The result showed that SFI administration could reduce depressive-like behaviors in tumor-bearing mice and inhibit tumor growth. In addition, SFI might improve fatigue symptoms by inhibiting pro-inflammatory cytokines produced by peripheral immune cells, restrain the dysfunction of exhausted T cells and improve the anti-tumor immunity through the targets of PDL1, TIM3 and FOXP3. These data suggested that SFI might be useful in alleviating CRF and provide further support to confirm SFI as a potential therapy for CRF in humans.

Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis.

Some studies reported a significant association between polycystic ovary syndrome (PCOS) and risk of cardiovascular disease (CVD). However, the results are controversial. A systematic search was conducted in the PubMed, Science Direct, EMBASE, and Cochrane Library databases. Five case-control studies and 5 cohort studies were selected, involving a total of 104392 subjects in this meta-analysis. PCOS was significantly associated with the increased risk of CVD (OR = 1.30; 95% CI 1.09 - 1.56; P = 0.004). In the subgroup analysis of study design, both case-control studies and prospective cohort studies showed significant results (OR = 1.79; 95% CI 1.16 - 2.77; P = 0.009; OR = 1.20; 95% CI 1.06 - 1.37; P = 0.005), while retrospective cohort studies did not show positive result (OR = 0.91; 95% CI 0.60 - 1.40; P = 0.68). In a further stratified analysis by type of CVD, a significant association was found between PCOS and coronary heart disease (CHD) (OR = 1.44; 95% CI 1.13 - 1.84; P = 0.004). However, no significant association was observed between PCOS and myocardial infarction (MI) (OR = 1.01; 95% CI 0.68 - 1.51; P = 0.95). In conclusion, this meta-analysis suggested that PCOS is significantly associated with increased CHD risk.

Diabetes mellitus and the risk of glioma: a meta-analysis.

Some studies reported a statistically significant inverse association between diabetes mellitus (DM) and risk of gliomas. However, the result is still controversial. We thus did a meta-analysis and summarized the evidence on the incidence of gliomas that has been studied in its association with DM. Seven case-control studies and 4 cohort studies were selected in this meta-analysis (n = 5898251). DM was significantly associated with decreased risk of gliomas (OR = 0.79; 95% CI 0.67 - 0.93; P = 0.004; I2 = 59%). In the subgroup analysis of race, Caucasians of DM showed decreased risk of gliomas (OR = 0.81; 95% CI 0.69 - 0.94; P = 0.007). In the subgroup analysis of design, a statistically significant protective effect of DM on gliomas was observed in case-control studies (OR = 0.68; 95 % CI, 0.53-0.87; P = 0.002), while no such effect was observed in cohort studies (OR = 0.97; 95 % CI, 0.83-1.13; P = 0.70). In a further stratified analysis by gender, a significant association was found among males with DM (OR = 0.83; 95 % CI, 0.70-0.99; P = 0.04). No significant association was found between females with DM and gliomas (OR = 0.97; 95 % CI, 0.78-1.21; P = 0.81). In summary, this meta-analysis of current evidence suggests that DM is significantly associated with decreased gliomas risk in Caucasian and males.

Angiotensin-converting enzyme I/D polymorphism is a genetic biomarker of diabetic peripheral neuropathy: evidence from a meta-analysis.

The Angiotensin-converting enzyme (ACE) I/D polymorphism has been indicated to be correlated with peripheral neuropathy (PN) susceptibility, but study results are still debatable. Thus, a meta-analysis was conducted. Databases including PubMed, Embase and CNKI were searched. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Eight studies with 1430 cases and 1873 controls were included in this meta-analysis. The association between ACE I/D polymorphism and PN risk was significant (OR = 1.25; 95% CI 1.05-1.48; P = 0.01). When stratified by ethnicity, the significantly increased PN risk was observed in Caucasians (OR = 1.24; 95% CI 1.05-1.47; P = 0.01). In conclusion, this meta-analysis suggested that ACE I/D polymorphism was a risk factor for PN.

Gross alpha and beta activity analyses in urine-a routine laboratory method for internal human radioactivity detection.

The aim of this work was to develop a method to provide rapid results for humans with internal radioactive contamination. The authors hypothesized that valuable information could be obtained from gas proportional counter techniques by screening urine samples from potentially exposed individuals rapidly. Recommended gross alpha and beta activity screening methods generally employ gas proportional counting techniques. Based on International Standards Organization (ISO) methods, improvements were made in the evaporation process to develop a method to provide rapid results, adequate sensitivity, and minimum sample preparation and operator intervention for humans with internal radioactive contamination. The method described by an American National Standards Institute publication was used to calibrate the gas proportional counter, and urine samples from patients with or without radionuclide treatment were measured to validate the method. By improving the evaporation process, the time required to perform the assay was reduced dramatically. Compared with the reference data, the results of the validation samples were very satisfactory with respect to gross-alpha and gross-beta activities. The gas flow proportional counting method described here has the potential for radioactivity monitoring in the body. This method was easy, efficient, and fast, and its application is of great utility in determining whether a sample should be analyzed by a more complicated method, for example radiochemical and/or γ-spectroscopy. In the future, it may be used commonly in medical examination and nuclear emergency treatment.Health Phys. 106(5):000-000; 2014.

Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with type 2 diabetes risk.

A number of studies were performed to assess the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and susceptibility to type 2 diabetes (T2DM). However, the results were inconsistent and inconclusive. In the present study, the possible association was investigated by a meta-analysis. Eligible articles were identified for the period up to June 2013. Pooled odds ratios (OR) with 95% confidence intervals (CI) were appropriately derived from random-effects models or fixed-effects models. Fourteen case-control studies with a total of 2487 cases and 3538 controls were eligible. In recessive model, PAI-1 4G/5G polymorphism was associated with T2DM risk (OR = 1.23; 95% CI 1.07-1.41; P = 0.004). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR = 1.27; 95% CI 1.08-1.51; P = 0.005). This meta-analysis suggested that PAI-1 4G/5G polymorphism may be associated with T2DM development.

miR-200c enhances radiosensitivity of human breast cancer cells.

Due to the intrinsic resistance of many tumors to radiotherapy, current methods to improve the survival of cancer patients largely depend on increasing tumor radiosensitivity. It is well-known that miR-200c inhibits epithelial-mesenchymal transition (EMT), and enhances cancer cell chemosensitivity. We sought to clarify the effects of miR-200c on the radiosensitization of human breast cancer cells. In this study, we found that low levels of miR-200c expression correlated with radiotolerance in breast cancer cells. miR-200c overexpression could increase radiosensitivity in breast cancer cells by inhibiting cell proliferation, and by increasing apoptosis and DNA double-strand breaks. Additionally, we found that miR-200c directly targeted TANK-binding kinase 1 (TBK1). However, overexpression of TBK1 partially rescued miR-200c mediated apoptosis induced by ionizing radiation. In summary, miR-200c can be a potential target for enhancing the effect of radiation treatment on breast cancer cells.

Hydrogen-rich saline protects spermatogenesis and hematopoiesis in irradiated BALB/c mice.

BACKGROUND: Recent studies show that molecular hydrogen (dihydrogen, H2) has potential as an effective and safe radioprotective agent through reducing oxidative stress. The aim of this study was to investigate whether H2 is able to protect spermatogenesis and hematopoiesis from radiation-induced injuries. MATERIAL/METHODS: H2 was dissolved in physiological saline using an apparatus produced by our department. -60Co-gamma rays in the irradiation centre were used for irradiation. Spermatid head counts and histological analysis were used to evaluate spermatogenesis. Endogenous hematopoietic spleen colony formation (endoCFUs), bone marrow nucleated cells (BMNC) and peripheral blood (PB) leukocytes were used to evaluate hemopoiesis. RESULTS: This study demonstrates that treating mice with H2 before ionizing radiation (IR) can increase the spermatid head count and protect seminiferous epithelium from IR. This study also demonstrates that H2 could significantly increase the number of endoCFUs, BMNC and PB leukocyte. CONCLUSIONS: This study suggests that hydrogen-rich saline could partially protect spermatogenesis and hematopoiesis in irradiated mice.

Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals.

Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.

A possible prevention strategy of radiation pneumonitis: combine radiotherapy with aerosol inhalation of hydrogen-rich solution.

Radiotherapy is an important modality of cancer treatment. Radiation pneumonitis is a major obstacle to increasing the radiation dose in radiotherapy, and it is important to prevent this radiation-induced complication. Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention strategy for radiation pneumonitis (hydrogen is explosive, while a hydrogen-rich solution such as physiological saline saturated with molecular hydrogen is safer).

MiR-21 plays an important role in radiation induced carcinogenesis in BALB/c mice by directly targeting the tumor suppressor gene Big-h3.

Dysregulation of certain microRNAs (miRNAs) in cancer can promote tumorigenesis, metastasis and invasion. However, the functions and targets of only a few mammalian miRNAs are known. In particular, the miRNAs that participates in radiation induced carcinogenesis and the miRNAs that target the tumor suppressor gene Big-h3 remain undefined. Here in this study, using a radiation induced thymic lymphoma model in BALB/c mice, we found that the tumor suppressor gene Big-h3 is down-regulated and miR-21 is up-regulated in radiation induced thymic lymphoma tissue samples. We also found inverse correlations between Big-h3 protein and miR-21 expression level among different tissue samples. Furthermore, our data indicated that miR-21 could directly target Big-h3 in a 3'UTR dependent manner. Finally, we found that miR-21 could be induced by TGFß, and miR-21 has both positive and negative effects in regulating TGFß signaling. We conclude that miR-21 participates in radiation induced carcinogenesis and it regulates TGFß signaling.

Gamma-ray irradiation impairs dendritic cell migration to CCL19 by down-regulation of CCR7 and induction of cell apoptosis.

Dendritic cells (DCs) are the most potent antigen-presenting cells and play a crucial role in the regulation of immune response and migration of DCs into secondary lymphoid tissues also play an important role in the initiation of innate and adaptive immunity. Radiation therapy is now a routine treatment for certain types of cancer and over 20 percent of cancer patients will require radiation therapy during the treatment of their disease. However, the influence of ionizing irradiation on the migratory ability of DCs is largely unknown. In this article, we report that γ ray irradiation can significantly inhibit LPS-triggered up regulation of CCR7 expression and PGE2 production by DC, thus impairing DC migration towards CCL19 in vitro and in vivo. Moreover, γ ray exposed DC also displayed an increased apoptosis rate and decreased cell viability. Furthermore, we demonstrate that exogenous PGE2 can partly reduce the gamma-ray induced migratory impairment and restored CCR7 expression of DC. Our work suggests that γ irradiation affects DC function at multiple steps during the immune response including DC migration, and that PGE2, via control of CCR7 expression, is an important regulator of DC migration.

MiR-34a in age and tissue related radio-sensitivity and serum miR-34a as a novel indicator of radiation injury.

MiR-34a, a direct target of p53, has shown to exert potent anti-proliferative effects. It has also been found that miR-34a can be induced by irradiation in vitro and in vivo. However, the relationship between miR-34a and radio-sensitivity, and its potential diagnostic significance in radiation biology, remain unclear. This study found that differing responses to ionizing radiation (IR) of young and adult mice were related to miR-34a. First, we found that miR-34a could be induced in many organs by radiation of both young and adult mice. However, the level of miR-34a induced by young mice was much higher when compared to adult mice. Next, we found that miR-34a played a critical role in radio-sensitivity variations of different tissues by enhancing cell apoptosis and decreasing cell viability. We also found that the induction of miR-34a by radiation was in a p53 dependent manner and that one possible downstream target of miR-34a that lead to different radio-sensitivity was the anti-apoptosis molecular Bcl-2. However, over-expression of miR-34a and knockdown of Bcl-2 could significantly enhance the radio-sensitivity of different cells while inhibition of miR-34a could protect cells from radiation injury. Finally, we concluded that miR-34a could be stable in serum after IR and serve as a novel indicator of radiation injury. Taken together, this data strongly suggests that miR-34a may be a novel indicator, mediator and target of radiation injury, radio-sensitivity and radioprotection.

Hydrogen protects mice from radiation induced thymic lymphoma in BALB/c mice.

Ionizing radiation (IR) is a well-known carcinogen, however the mechanism of radiation induced thymic lymphoma is not well known. Moreover, an easy and effective method to protect mice from radiation induced thymic lymphoma is still unknown. Hydrogen, or H(2), is seldom regarded as an important agent in medical usage, especially as a therapeutic gas. Here in this study, we found that H(2) protects mice from radiation induced thymic lymphoma in BALB/c mice.