Striatal Isolated from Cyathus striatus Extracts Induces Apoptosis in Human Pancreatic Cancer Cells.

The aim of the present study was to identify the structure of active compounds in Cyathus stratus that previously demonstrated anti-pancreatic cancer activity. The active compounds were purified from a crude extract by a series of RP-18 preparative chromatography using homemade octadecyl silica gel column. HPLC injection of the crude extract revealed a chromatogram with three main peaks with retention times (RT) 15.6, 18.2, and 22.5 min. Each fraction that exhibited promising activity in vitro was further separated using various available chromatographic techniques. The purified compound with the ultimate anti-cancer activity appeared at RT of 15.8 in the HPLC chromatogram with more than 90% purity. The main peak at the mass spectra appeared at m/z = 446.2304 with the calculated molecular formula of C25H34O7. One- and two-dimensional NMR analyses indicated that the structure of the active molecule (peak 15.8 min in HPLC) was identified as striatal C. Exposure of human pancreatic cancer cells to purified striatal C resulted in induction of apoptosis. Further studies are needed in order to develop a method for the synthesis of striatal in order to use it in clinical studies for treatment of cancer.

Metabolomic Characterization of a cf. Neolyngbya Cyanobacterium from the South China Sea Reveals Wenchangamide A, a Lipopeptide with In Vitro Apoptotic Potential in Colon Cancer Cells.

Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A (1). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC50 = 38 µM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1, here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues.

Endothelial nitric oxide synthase polymorphism and prognosis in systolic heart failure patients.

BACKGROUND: The endothelial nitric oxide synthase (eNOS) gene single nucleotide polymorphism G894T is associated with thrombotic vascular diseases. However, its functional significance is controversial and data are scarce concerning its influence in heart failure (HF). METHODS: We studied 215 patients with chronic systolic HF. DNA was analyzed for eNOS gene G894T polymorphism using PCR and DNA sequencing. Evaluation of clinical characteristics and analysis of factors associated with 2-year mortality were performed for the homozygous G-allele G894T variant (GG), relative to the TT and GT variants. RESULTS: The genotype distributions of eNOS G894T alleles were: GG 135 patients (63%) and TT/GT 80 (37%). Two-year mortality was significantly higher in the GG variant (48%) than the combined TT/GT group (32%). The usage of nitrates was associated with increased 2-year mortality (HR 2.0, 95% CI 1.28-3.17; p = 0.003), which was most significant in the GG group treated with nitrates (73.5%) in comparison to the TT/GT group not treated with nitrates (34%); HR 2.75, 95% CI 1.57-4.79, P < 0.001. CONCLUSIONS: Homozygosity for the G allele of the eNOS G894T polymorphism was associated with worse survival in systolic HF patients, especially in those treated with nitrates. ENOS polymorphism may result in different mechanistic interactions in HF than in thrombotic vascular diseases, suggesting that overexpression of NO may be associated with deleterious effects in systolic HF.

Absence of the α(2c)-adrenoceptor Del322-325 allele is associated with increased mortality in patients with chronic systolic heart failure.

OBJECTIVE: The Del322-325 polymorphism of the α(2c)-adrenoceptor is considered to be a possible risk factor for heart failure (HF). We investigated the possible clinical association between the presence or absence of the deletion allele and mortality. METHODS AND RESULTS: Of 261 chronic systolic HF patients evaluated, 216 (83%) carried no α(2c)-adrenoceptor Del322-325 alleles (designated II); 28 patients (11%) were heterozygous (ID) and 17 patients (6%) homozygous (DD) for the deletion. Similar genetic distribution of α(2c)-adrenoceptor Del322-325 subgroups was found in a control group of 96 healthy individuals. Mortality was significantly higher in HF patients in whom the deletion allele was absent than in HF patients who carried it: 67 (31%) patients in the II subgroup died compared with 7 (15.5%) in the ID/DD subgroup (P = .01). The odds ratio for death in HF patients who carried no α(2c)-adrenoceptor Del322-325 alleles compared with HF patients with ≥1 allele was 2.45 (95% confidence interval 1.04‒5.74). There were no differences in other relevant clinical parameters between the 2 subgroups of HF patients. CONCLUSIONS: The mortality rate of chronic systolic HF patients carrying no α(2c)-adrenoceptor Del322-325 alleles was significantly higher (almost 2.5-fold) than that of HF patients carrying ≥1 allele.

Photoperiodicity and increasing salinity as environmental cues for reproduction in desert adapted rodents.

Understanding the ways environmental signals, regulate reproduction and reproductive behavior of desert adapted rodents is a major gap in our knowledge. In this study, we assessed the roles of photoperiod and diet salinity, as signals for reproduction. We challenged desert adapted common spiny mice, Acomys cahirinus, males and females with osmotic stress, by gradually increasing salinity in their water source - from 0.9% to 5% NaCl under short and long days (SD and LD, respectively). Photoperiodicity affected testosterone levels, as under LD-acclimation, levels were significantly (p<0.05) higher than under SD-acclimation. Salinity treatment (ST) significantly reduced SD-acclimated male body mass (W(b)) and testis mass (p<0.005; normalized to W(b)). ST-LD-females significantly (p<0.005) decreased progesterone levels and the numbers of estrous cycles. A reduction in white adipose tissue (WAT) to an undetectable level was noted in ST-mice of both sexes under both photoperiod regimes. Receptors for vasopressin (VP) and aldosterone were revealed on testes of all male groups and on WAT in control groups. Our results suggest that photoperiod serves as an initial signal while water availability, expressed by increased salinity in the water source, is an ultimate cue for regulation of reproduction, in both sexes of desert-adapted A. cahirinus. We assume that environmental changes also affect behavior, as water seeking behavior by selecting food items, or locomotor activity may change in extreme environment, and thus indirectly affect reproduction and reproductive behavior. The existence of VP and aldosterone receptors in the gonads and WAT suggests the involvement of osmoregulatory hormones in reproductive control of desert adapted rodents.

Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment.

Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.

The effect of culture liquid ethyl acetate mycelium extracts of medicinal mushrooms on the viability of human pancreatic cancer cells.

Pancreatic cancer, one of the deadliest of all solid malignancies, is one of the leading causes of cancer death worldwide, with 232,000 new cases and 213,000 deaths reported each year. These unfortunate statistics reflect the advanced stage at which most patients with pancreatic cancer are diagnosed and the paucity of effective chemotherapeutic regimens. Fungal metabolites have been gaining scientific interest because of their medicinal properties. In the present study, 31 different mushroom extracts of 12 medicinal mushroom species were screened for their effect on the viability of human pancreatic adenocarcinoma cells. Extraction procedures were executed with organic solvents--ethanol (EAL), ethyl acetate (EAC), and chloroform (CHL). In some cases, culture liquid (CL) extraction was also performed. All extracts were diluted to a concentration of 50 mg/mL dimethyl sulfoxide. Extract effects on cell viability were examined in human pancreatic adenocarcinoma cells HPAF-II (well differentiated) and PL5 (porrly differentiated), using XTT assay and crystal violet assay (CV). Furthermore, extract effects on LDH leakage were also studied in order to exclude necrotic damage of the extract. The screening phase revealed that among the total 31 extracts examined with various treatment doses (50-500 µg/mL) administered for 72 h, the CL extract of the mushroom Cyathus striatus exhibited the most prominent decrease in cell viability. Moreover, exposure of cells to lower concentrations then the above (1, 2.5, 5, 7.5, 10, 15, 20, and 50 µg/mL) for 24, 48, and 72 h showed a significant decrease in cell viability. Crystal violet results support these findings, and LDH levels measured suggest the lack of a necrotic effect of the extract. Our results indicate that C. striatus CL extract inhibits the viability of human pancreatic adenocarcinoma cells; HPAF-II and PL45. Growth inhibition can be achieved in low concentrations of the extract and a short exposure period. This effect can be mediated through apoptosis induction and/or cell cycle arrest; therefore, additional experiments are needed in order to elucidate the extract mechanism of action. These findings may lead to the development of new therapeutic strategies for the treatment of pancreatic cancer.

The Effect of Natural-Based Formulation (NBF) on the Response of RAW264.7 Macrophages to LPS as an In Vitro Model of Inflammation.

Macrophages are some of the most important immune cells in the organism and are responsible for creating an inflammatory immune response in order to inhibit the passage of microscopic foreign bodies into the blood stream. Sometimes, their activation can be responsible for chronic inflammatory diseases such as asthma, tuberculosis, hepatitis, sinusitis, inflammatory bowel disease, and viral infections. Prolonged inflammation can damage the organs or may lead to death in serious conditions. In the present study, RAW264.7 macrophages were exposed to lipopolysaccharide (LPS; 20 ng/mL) and simultaneously treated with 20 µg/mL of natural-based formulation (NBF), mushroom-cannabidiol extract). Pro-inflammatory cytokines, chemokines, and other inflammatory markers were analyzed. The elevations in the presence of interleukin-6 (IL-6), cycloxygenase-2 (COX-2), C-C motif ligand-5 (CCL5), and nitrite response, following exposure to LPS, were completely inhibited by NBF administration. IL-1ß and tumor necrosis factor alpha (TNF-α) release were inhibited by 3.9-fold and 1.5-fold, respectively. No toxic effect of NBF, as assessed by lactate dehydrogenase (LDH) release, was observed. Treatment of the cells with NBF significantly increased the mRNA levels of TLR2, and TLR4, but not NF-κB. Thus, it appears that the NBF possesses anti-inflammatory and immunomodulatory effects which can attenuate the release of pro-inflammatory markers. NBF may be a candidate for the treatment of acute and chronic inflammatory diseases and deserves further investigation.

In vitro mitochondrial effects of PK 11195, a synthetic translocator protein 18 kDa (TSPO) ligand, in human osteoblast-like cells.

The role of the TSPO in metabolism of human osteoblasts is unknown. We hypothesized that human osteoblast metabolism may be modulated by the TSPO. Therefore we evaluated the presence of TSPO in human osteoblast-like cells and the effect of its synthetic ligand PK 11195 on these cells. The presence of TSPO was determined by [(3)H]PK 11195 binding using Scatchard analysis: Bmax 7682 fmol/mg, Kd 9.24 nM. PK 11195 did not affect significantly cell proliferation, cell death, cellular viability, maturation, [(18)F]-FDG incorporation and hexokinase 2 gene expression or protein levels. PK 11195 exerted a suppressive effect on VDAC1 and caused an increase in TSPO gene expression or protein levels. In parallel there was an increase in mitochondrial mass, mitochondrial ATP content and a reduction in ΔΨm collapse. Thus, it appears that PK11195 (10(-5) M) stimulates mitochondrial activity in human osteoblast-like cells without affecting glycolytic activity and cell death.

A Novel Follitropin Analog Inhibits Follitropin Activity In Vitro.

Follitropin (FSH) is a heterodimeric protein composed of an α subunit that is shared with the glycoprotein hormone family, including lutropin (LH), thyrotropin (TSH), human choriogonadotropin (hCG), and a unique ß specific subunit. Both α and FSHß subunits contain two sites of N-linked oligosaccharides, which are important for its function. FSH has a crucial function in the reproductive process in mammals. However, there are some clinical conditions, such as menopausal osteoporosis or adiposity, associated with increased FSH activity. Moreover, in some cases, carcinogenesis is evidently associated with activation of FSH receptor. Therefore, developing a follitropin antagonist might be beneficial in the treatment of these conditions. Here, we describe a novel, engineered, non-glycosylated single-chain FSH variant, prepared by site-directed mutagenesis and fusion of the coding genes of the α and ß subunits. The designed variant was expressed in Chinese hamster ovary (CHO) cells and successfully secreted into the culture medium. We found that the non-glycosylated single-chain FSH analog binds with high affinity to FSH receptor and efficiently inhibits FSH activity in vitro. This variant acts at the receptor level and has the potential to serve as a follitropin antagonist for clinical applications in the future.

5-aza-2'-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line.

Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, resulting in over 600,000 new diagnoses annually. Traditionally, HNCC has been related to tobacco and alcohol exposure; however, over the past decade, a growing number of head and neck cancers are attributed to human papillomavirus (HPV) infection. 5-Aza-2'-deoxycytidine (5-AzaD) was demonstrated as an effective chemotherapeutic agent for acute myelogenous leukaemia. Preclinical data revealed that 5-aza inhibits growth and increases cell death of HPV(+) cancer cells. These effects are associated with reduced expression of HPV genes, stabilization of TP53, and activation of TP53-dependent apoptosis. The aim of the present study is to test the effect of 5-AzaD on growth of human squamous cell carcinoma (FaDu), a HPV(-) and p53 mutated cells, in vitro and in vivo. The effect of 5-AzaD on cell viability, cell cycle progression and induction of apoptosis was tested in vitro. The effect of 5-AzaD on tumour growth in vivo was tested using xenograft mice inoculated with FaDu cells. The results indicated that 5-AzaD reduced cell viability and induced apoptosis in FaDu cells in vitro. In vivo studies revealed that 5-AzaD suppresses the growth of tumours in xenograft mice inoculated with FaDu cells through inhibition of proliferation and induction of apoptosis. These findings may emphasis that 5-AzaD is effective in treatment of HPV(-) HNSCC tumours through TP53 independent pathway. Future studies are needed in order to clarify the molecular mechanism of action of 5-AzaD in HPV(-) cancer cells.

Cyathus striatus Extract Induces Apoptosis in Human Pancreatic Cancer Cells and Inhibits Xenograft Tumor Growth In Vivo.

Pancreatic cancer is a highly lethal disease with limited options for effective therapy and the lowest survival rate of all cancer forms. Therefore, a new, effective strategy for cancer treatment is in need. Previously, we found that a culture liquid extract of Cyathus striatus (CS) has a potent antitumor activity. In the present study, we aimed to investigate the effects of Cyathus striatus extract (CSE) on the growth of pancreatic cancer cells, both in vitro and in vivo. The proliferation assay (XTT), cell cycle analysis, Annexin/PI staining and TUNEL assay confirmed the inhibition of cell growth and induction of apoptosis by CSE. A Western blot analysis demonstrated the involvement of both the extrinsic and intrinsic apoptosis pathways. In addition, a RNAseq analysis revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. The anticancer activity of the CSE was also demonstrated in mice harboring pancreatic cancer cell line-derived tumor xenografts when CSE was given for 5 weeks by weekly IV injections. Our findings suggest that CSE could potentially be useful as a new strategy for treating pancreatic cancer.

Author Correction: The REGγ inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The REGγ inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells.

A major challenge in chemotherapy is chemotherapy resistance in cells lacking p53. Here we demonstrate that NIP30, an inhibitor of the oncogenic REGγ-proteasome, attenuates cancer cell growth and sensitizes p53-compromised cells to chemotherapeutic agents. NIP30 acts by binding to REGγ via an evolutionarily-conserved serine-rich domain with 4-serine phosphorylation. We find the cyclin-dependent phosphatase CDC25A is a key regulator for NIP30 phosphorylation and modulation of REGγ activity during the cell cycle or after DNA damage. We validate CDC25A-NIP30-REGγ mediated regulation of the REGγ target protein p21 in vivo using p53-/- and p53/REGγ double-deficient mice. Moreover, Phosphor-NIP30 mimetics significantly increase the growth inhibitory effect of chemotherapeutic agents in vitro and in vivo. Given that NIP30 is frequently mutated in the TCGA cancer database, our results provide insight into the regulatory pathway controlling the REGγ-proteasome in carcinogenesis and offer a novel approach to drug-resistant cancer therapy.

Dynamic modification strategy of the Israeli carrier screening protocol: inclusion of the Oriental Jewish Group to the cystic fibrosis panel.

PURPOSE: A retrospective population study was conducted to determine the carrier frequencies of recently identified mutations in Oriental Jewish cystic fibrosis patients. METHODS: Data were collected from 10 medical centers that screened the following mutations: two splice site mutations-3121-1G>A and 2751 + 1insT-and one nonsense mutation-the Y1092X in Iraqi Jews. One missense mutation, I1234V, was screened in Yemenite Jews. RESULTS: A total of 2499 Iraqi Jews were tested for one, two, or all three mutations. The 3121-1G>A, Y1092X, and 2751 + 1insT mutations had a carrier frequency of 1:68.5, 1:435, and 0, respectively. In 1435 Yemenite Jews screened, I1234V had a carrier frequency of 1:130. CONCLUSION: The 0.84% allele frequency of the three Iraqi founder mutations falls within the Israeli Society of Medical Geneticists' inclusion criteria for screening of 1:60 carrier frequency; hence, Iraqi Jews were added to the carrier screening policy with a panel including the three Iraqi founder mutations in addition to the five Ashkenazi mutations previously detected in Eastern Jews. 2751 + 1insT that was detected in patients only was included in the screening panel to increase the detection rate. I1234V does not meet the inclusion criteria but is now offered on a diagnostic basis and can be added to the screening panel for individuals whose mixed origin includes Yemenite, in addition to protocol-recommended origins. This study demonstrates the dynamic modifications of the Israeli carrier cystic fibrosis screening protocol based on newly detected founder mutations in a large cohort, taking into account mutation impact and intercommunal admixture.

Effect of increased dietary salinity on the reproductive status and energy intake of xeric and mesic populations of the spiny mouse, Acomys.

The possible role of increased dietary salinity as a proximate regulator of reproduction in xeric population of golden spiny mice (Acomys russatus) and mesic population of common spiny mice (A. cahirinus) was tested. In the wild, as the dry season progresses, evaporative water loss in the vegetation increases. This leads to increase in particle concentration of plant tissues. Thus, species consuming a plant diet are exposed to increased dietary salinity. Both male and female individuals of A. russatus were subjected to gradually increasing dietary salinity (0.9%, 2.5%, 3.5%, and 5%) while those of A. cahirinus only up to 3.5% for a total period of 8 and 6 weeks, respectively. Urine osmolarity showed a significant increase under 3.5% and 5% salinity in A. russatus and 2.5% and 3.5% in A. cahirinus. Testis mass and spermatogenesis were significantly reduced while uterine mass and vaginal estrus cycles were not affected in A. russatus. None of the parameters was significantly affected in A. cahirinus. Increase in salinity also significantly reduced body mass in A. russatus but not in A. cahirinus. Mass-specific daily digestible energy intake was not significantly affected by increased salinity in both species. Recovery individuals regained body mass quickly and surpassed initial values after four weeks. However, testis mass and spermatogenesis did not show recovery. The results suggest that increase in dietary salinity could be used as a proximate signal to regulate reproduction in A. russatus by halting it in males, as the dry season progresses while such role in the mesic population of A. cahirinus is unlikely.

Development of long-acting recombinant glycoprotein hormones by increasing the carbohydrate content.

Therapeutic recombinant glycoproteins are important for both the biotechnological industry and clinical purposes. Given the rapid clearance of these proteins from the circulation, they have to be injected frequently to obtain optimal therapy. Several strategies have been developed to overcome this limitation, aiming to increase the half-life of such proteins in the circulation. These strategies included chemical attachment of polyethylene glycol, nanocapsulation, fusion to immunoglobulins or to albumin as protein carriers, or enrichment of the carbohydrate content. Here, we describe a strategy for increasing the half-life of recombinant proteins using gene fusion to increase the carbohydrate content of the protein backbone.

Epigenetic modification in 4T1 mouse breast cancer model by artificial light at night and melatonin - the role of DNA-methyltransferase.

Currently, one of the most disputed hypotheses regarding breast cancer (BC) development is exposure to short wavelength artificial light at night (ALAN) as multiple studies suggest a possible link between them. This link is suggested to be mediated by nocturnal melatonin suppression that plays an integral role in circadian regulations including cell division. The objective of the research was to evaluate effects of 1 × 30 min/midnight ALAN (134 µ Wcm-2, 460 nm) with or without nocturnal melatonin supplement on tumor development and epigenetic responses in 4T1 tumor-bearing BALB/c mice. Mice were monitored for body mass (Wb) and tumor volume for 3 weeks and thereafter urine samples were collected at regular intervals for determining daily rhythms of 6-sulfatoxymelatonin (6-SMT). Finally, mice were sacrificed and the tumor, lungs, liver, and spleen were excised for analyzing the total activity of DNA methyltransferases (DNMT) and global DNA methylation (GDM) levels. Mice exposed to ALAN significantly reduced 6-SMT levels and increased Wb, tumor volume, and lung metastasis compared with controls. These effects were diminished by melatonin. The DNMT activity and GDM levels showed tissue-specific response. The enzymatic activity and GDM levels were lower in tumor and liver and higher in spleen and lungs under ALAN compared with controls. Our results suggest that ALAN disrupts the melatonin rhythm and potentially leading to increased BC burden by affecting DNMT activity and GDM levels. These data may also be applicable to early detection and management of BC by monitoring melatonin and GDM levels as early biomarker of ALAN circadian disruption.

Inula Viscosa Extract Inhibits Growth of Colorectal Cancer Cells in vitro and in vivo Through Induction of Apoptosis.

Colorectal cancer (CRC) is the second most common cancer in females and the third in males worldwide. Conventional therapy of CRC is limited by severe side effects and by the development of resistance. Therefore, additional therapies are needed in order to combat the problem of selectivity and drug resistance in CRC patients. Inula viscosa (IV) is a well-known medicinal perennial herb in traditional medicine. It is used for different therapeutic purposes, such as; topical anti-inflammatic, diuretic, hemostatic, antiseptic, antiphlogistic, and in the treatment of diabetes. Several studies attempted to reveal the anti-cancer activity of different extracts prepared by different organic solvents from different parts of the IV plant. The aim of the present study is to examine the potential beneficial effects of IV leaf aqueous extract on the growth of colon cancer cells in vitro and in vivo. The results indicated that exposure of colorectal cancer cells to IV extract, significantly reduced cell viability in a dose and time dependent manner. Moreover, treatment of cells with 300 µg/ml of IV extract induced apoptosis, as it was detected by Annexin V/FITC/PI, TUNEL assay, and the activation of caspases. In vivo studies revealed that treatment with 150 or 300 mg/kg IV extract inhibited tumor growth in mice transplanted with MC38 cells. Tumors' weight and volume were significantly (P < 0.001) reduced when compared to untreated-control group. Staining of the paraffin section of tumors revealed that IV treatment inhibited cell proliferation and induced apoptosis. Additionally, no side effects such as; weight loss, behavior changes, ruffled fur or changes in kidney, and liver functions were observed. These results may indicate that active doses of IV extract are not toxic. Further studies are needed in order to identify the structure of the active compounds. Results from this study may contribute to the development of new and efficient strategies for treatment of human colon cancer.

A differential response in the reproductive system and energy balance of spiny mice Acomys populations to vasopressin treatment.

Increased dietary salinity suppressed reproduction of the xeric adapted golden spiny mouse, Acomys russatus. Testicular and uterine mass were reduced, suppressed spermatogenesis and vaginal closure were observed. The anti-diuretic hormone, vasopressin (VP), was suggested to mediate such effects. However, increased dietary salinity did not affect reproductive status of a mesic adapted population of the common spiny mouse, A. cahirinus. In the present study, the effect of exogenous VP on the reproductive status and energy balance of both males and females of A. russatus and of a mesic population of A. cahirinus was tested. Vasopressin (Sigma, 50 microg/kg) was injected intraperitoneally in three-day intervals for four weeks. In VP-treated A. russatus, spermatogenesis was significantly suppressed while the change in testis mass did not show significant difference. Both control and VP-treated females lost body mass (W(b)) significantly and the latter also exhibited a higher energy expenditure compared to their male counterparts. VP did not affect reproductive status in both sexes of A. cahirinus. Also it did not have a significant effect on W(b), energy intake, and energy expenditure in this species. Our results support the idea that VP mediates the effects of increased diet salinity on reproduction in A. russatus. The results also reinforce previous knowledge that different physiological systems could be integrated by a single biochemical signal.