Search

The growth and progression of cancers are crucially regulated by the tumor microenvironment where tumor cells and stromal cells are mutually associated. In this study, we found that stomatin expression was markedly upregulated by the interaction between prostate cancer cells and stromal cells. Stomatin suppressed cancer cell proliferation and enhanced apoptosis in vitro and inhibited xenograft tumor growth in vivo. Stomatin inhibited Akt activation, which is mediated by phosphoinositide-dependent protein kinase 1 (PDPK1). PDPK1 protein stability was maintained by its binding to HSP90. Stomatin interacted with PDPK1 and interfered with the PDPK1–HSP90 complex formation, resulting in decreased PDPK1 expression. Knockdown of stomatin in cancer cells elevated Akt activation and promoted cell increase by promoting the interaction between PDPK1 and HSP90. Clinically, stomatin expression levels were significantly decreased in human prostate cancer samples with high Gleason scores, and lower expression of stomatin was associated with higher recurrence of prostate cancer after the operation. Collectively, these findings demonstrate the tumor-suppressive effect of stromal-induced stomatin on cancer cells.Significance:These findings reveal that interactions with stromal cells induce expression of stomatin in prostate cancer cells, which suppresses tumor growth via attenuation of the Akt signaling axis.

Supplementary Table S2

Supplementary Materials & Methods and Figures

The growth and progression of cancers are crucially regulated by the tumor microenvironment where tumor cells and stromal cells are mutually associated. In this study, we found that stomatin expression was markedly upregulated by the interaction between prostate cancer cells and stromal cells. Stomatin suppressed cancer cell proliferation and enhanced apoptosis in vitro and inhibited xenograft tumor growth in vivo. Stomatin inhibited Akt activation, which is mediated by phosphoinositide-dependent protein kinase 1 (PDPK1). PDPK1 protein stability was maintained by its binding to HSP90. Stomatin interacted with PDPK1 and interfered with the PDPK1–HSP90 complex formation, resulting in decreased PDPK1 expression. Knockdown of stomatin in cancer cells elevated Akt activation and promoted cell increase by promoting the interaction between PDPK1 and HSP90. Clinically, stomatin expression levels were significantly decreased in human prostate cancer samples with high Gleason scores, and lower expression of stomatin was associated with higher recurrence of prostate cancer after the operation. Collectively, these findings demonstrate the tumor-suppressive effect of stromal-induced stomatin on cancer cells. Significance: These findings reveal that interactions with stromal cells induce expression of stomatin in prostate cancer cells, which suppresses tumor growth via attenuation of the Akt signaling axis.

Heart failure is one of the leading causes of death worldwide. RhoA, a small GTPase, governs actin dynamics in various tissue and cell types, including cardiomyocytes; however, its involvement in cardiac function has not been fully elucidated. Here, we generated cardiomyocyte-specific RhoA conditional knockout (cKO) mice, which demonstrated a significantly shorter lifespan with left ventricular dilation and severely impaired ejection fraction. We found that the cardiac tissues of the cKO mice exhibited structural disorganization with fibrosis and also exhibited enhanced senescence compared with control mice. In addition, we show that cardiomyocyte mitochondria were structurally abnormal in the aged cKO hearts. Clearance of damaged mitochondria by mitophagy was remarkably inhibited in both cKO cardiomyocytes and RhoA-knockdown HL-1 cultured cardiomyocytes. In RhoA-depleted cardiomyocytes, we reveal that the expression of Parkin, an E3 ubiquitin ligase that plays a crucial role in mitophagy, was reduced, and expression of N-Myc, a negative regulator of Parkin, was increased. We further reveal that the RhoA-Rho kinase axis induced N-Myc phosphorylation, which led to N-Myc degradation and Parkin upregulation. Re-expression of Parkin in RhoA-depleted cardiomyocytes restored mitophagy, reduced mitochondrial damage, attenuated cardiomyocyte senescence, and rescued cardiac function both in vitro and in vivo. Finally, we found that patients with idiopathic dilated cardiomyopathy without causal mutations for dilated cardiomyopathy showed reduced cardiac expression of RhoA and Parkin. These results suggest that RhoA promotes Parkin-mediated mitophagy as an indispensable mechanism contributing to cardioprotection in the aging heart.

Diabetes mellitus (DM) causes injury to tissues and organs, including to the heart and kidney, resulting in increased morbidity and mortality. Thus, novel potential therapeutics are continuously required to minimize DM-related organ damage. We have previously shown that dipeptidyl peptidase III (DPPIII) has beneficial roles in a hypertensive mouse model, but it is unknown whether DPPIII has any effects on DM. In this study, we found that intravenous administration of recombinant DPPIII in diabetic db/db mice for eight weeks suppressed the DM-induced cardiac diastolic dysfunctions and renal injury without alteration of the blood glucose level. This treatment inhibited inflammatory cell infiltration and fibrosis in the heart, and blocked the increase in albuminuria by attenuating the disruption of the glomerular microvasculature and inhibiting the effacement of podocyte foot processes in the kidney. The beneficial role of DPPIII was, at least in part, mediated by the cleavage of a cytotoxic peptide, named Peptide 2, which was increased in db/db mice compared with normal mice. This peptide consisted of nine amino acids, was a digested fragment of complement component 3 (C3), and had an anaphylatoxin-like effect determined by the Miles assay and chemoattractant analysis. The effect was dependent on its interaction with the C3a receptor and protein kinase C-mediated RhoA activation downstream of the receptor in endothelial cells. In conclusion, DPPIII plays a protective role in the heart and kidney in a DM animal model through cleavage of a peptide that is a part of C3.

MiR-335-3p, a neuron-enriched microRNA, has been reported to be involved in aging and age-related neurological diseases. However, the role of miR-335-3p in cholesterol metabolism of astrocytes, and whether it affects neuronal functions, particularly during aging process, largely remains unknown. In this study, we uncover that miR-335-3p is significantly increased in aged cultured astrocytes and aged hippocampal brains, accompanied by decreased cellular cholesterol and diminished expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) and 3-hydroxy-3-methylglutaryl-CoA synthase-1 (HMGCS1), both step-limiting enzymes in cholesterol synthesis pathway. We also demonstrate that miR-335-3p suppresses HMGCS1 post-transcriptionally by directly binding to its 3'UTR, and HMGCR through binding mediated by SFRS2. More importantly, aged mice with miR-335-3p deficiency in hippocampal brains exhibit improved learning and memory, accompanied by enhanced levels of postsynaptic density protein 95 (PSD95). We further reveal that the level change of PSD95 is resulted from altered cholesterol metabolism. Our findings provide a novel insight into the regulatory role of miR-335-3p in cholesterol metabolism in astrocytes, and consequently cognitive functions during aging.

Demand of energy is increasing in the whole part of the world, it is estimated that in near future a significant energy crisis will be occurred. Furthermore, fossil fuels play a noticeable role for environmental pollutions. So, an alternative clean and environmental amiable renewable energy source is the most significant demand for the modern scientists. Bio-fuel cell especially microbial fuel cell can partially eliminate this crisis by producing electricity from biodegradable waste. Considering this aspect we produced double chamber MFCs where Zinc and copper plates are used as anode and cathode materials. In this study urine and fish waste mixed waste water are used as a source of substrate, aerobic bacteria helps to decompose it, in anode chamber where oxygen amplifies the reduction reaction in cathode chamber. To find out the effects of urine and fish waste on the performance of voltage, current and power we used digital multimeter and Hantek 365A data logger. Urine mixed waste water gives the maximum voltage 1.02 V, current 1.67 mA and power 1.7034 mW, whereas, for fish mixed waste water these values were 0.968 V, 1.365 mA and 1.3213 mW respectively. The whole operation we done batch wise, initial pH 8 and cell volume was 5 liter.

The degradation of Methylene Blue (MB) in aqueous solution has been investigated in a photocatalytic reactor under UV radiation and in presence of zinc oxide (ZnO). The photodegradation kinetics follows pseudo-first order reaction. The effect of process parameters such as catalyst loading and initial concentration of MB on the degradation is investigated. The results show that the degradation rate is affected insignificantly by the increases in the catalyst dosage. Batch test, however, shows that with an increase in the initial concentration the apparent rate constant gradually decreases. The first results with a continuous reactor with a diluted feed solution show inspiring dye removal. DOI: http://dx.doi.org/10.3329/jce.v28i1.18110 Journal of Chemical Engineering, Vol. 28, No. 1, December 2013: 41-44

Aegle marmelos is a popular medicinal plant in the Ayurvedic and siddha systems of medicine and folk medicines used to dreat a wide variety of ailments. Aegle marmelos is locally known as “Bael” found everywhere in Bangladesh and many other countries of the world. The nutritional composition of Aegle marmelos leaves was determined by standard method. The proximate composition of leaves revealed moisture (infant 37.80 gm%, mature 40.01 gm% and ripen 32.50 gm%), ash (infant 0.012 gm%, mature 0.82 gm% and ripen 0.75 gm%), pH (infant 6.30, mature 6.00 and ripen 6.15), total sugar (infant 0.9 gm%, mature 1.9 gm% and ripen 1.7 gm%), reducing sugar (infant 0.30 gm%, mature 0.90 gm% and ripen 0.75 gm%), non-reducing sugar (infant 0.57 gm% mature 0.95 gm% and ripen 0.90 gm %), starch (infant 0.8 gm%, mature 2.5 gm% and ripen 2.0 gm%), crude fiber (infant 8.1 gm%, mature 11.0 gm% and ripen 9.5 gm%). Vitamin C for (infant, mature and ripen leaves contain 3.5 gm%, 7.1 gm%, 6.0 gm%) respectively. Total phenol present in (1.9 gm%, 5.01 gm%, 3.99 gm% for infant, mature and ripen) respectively. The leaves also contain negligible amount of cholesterol. The leaves also contain sodium (infant 2.5%, mature 7.0% and ripen 6.5%), Potassium (infant 1.52%, mature 5.001% and ripen 3.99%), Calcium (infant 0.001%, mature 0.25% and ripen 0.21%), Phosphorous (infant 3.5%, mature 7.82% and ripen 7.11%) etc. This experiment also showed significantly reduction of blood glucose level of diabetic rats (P

The major goals of the poultry industry are to increase the carcass yield and to reduce carcass fatness, mainly the abdominal fat pad. Chicken meat is generally thought to be health friendly due to its favorable fatty acid composition leading to an antiatherogenic lipidemic status. Beneficial effect of the chicken oil on hyperglycemia has also been claimed through its effect on oxidative stress and insulin resistance. The macro and micronutrient contents of these two chicken species (10 chickens of each species) were also compared. All macronutrients such as ash, moisture, total protein, total carbohydrate and total lipid were found to be high for the hybrid chicken. Lipid content was significantly higher (around 50%) in hybrid chicken than that of domestic chicken. Except for potassium and manganese which were found to be high in hybrid chicken (127.8 and 9.74 μ/kg respectively) than domestic chicken (86.83 and 6.74 μ/kg respectively), all other micronutrients such as iron, calcium, zinc and lead were higher for domestic chicken. Zinc content of hybrid chicken was significantly lower (around 50%) than that of domestic chicken. The average amount if oil content of two species were extracted with soxlet apparatus using n-hexane as an extracting solvent and it was found to be 3.54% for domestic chicken and 4.84 for hybrid chicken. Chemical characteristics of the extracted oil were investigated by analyzing various parameters such as iodine value, saponification value, acid value, peroxide value and percentage free fatty acid. Iodine value and unsaponifiable matter were higher for hybrid chicken (77.92 and 11.14% respectively) than those of domestic chicken (60.56% and 3.5% respectively). Again saponification value, acid value, peroxide value and percentage free fatty acid were higher for domestic chicken than hybrid chicken. This experiment also showed significantly reduction of blood glucose level of diabetic mice (p

Fishes are rich sources of different types of nutrients. Some species are found in marine water; on the other hand some varieties are available in fresh water. Consumption of fish is very beneficial to the health and development of the human body and fish becomes an integral part of the food culture of populations in many countries. They provide essential nutrients to the human. The aim of this study was to estimate the nutritional status of the selected fish species, to extract and characterize the fish oil and lecithin. Fish oil contains higher amount of polyunsaturated fatty acids which have significant effect in maintaining a healthy cardiac life. Biochemical composition of shoul (Channa striata) was determined. It was found that fishes are rich sources of protein and other nutrients. All the other parameters such as, moisture, protein, lipid, total sugar and ash were found in significant amount in shoul. Shoul fish oil was extracted using n-hexane by soxhlet apparatus. The percentage of oil from shoul fish powder was 12.64 (g% w/w). Lecithin was also extracted from this fish fleshes before and after oil extraction. Lecithin was 2.07 (g% w/w) and 3.10 (g% w/w) before and after oil extraction. It was found that percentage of lecithin was increased after oil extraction. The physicochemical properties of fish oil and lecithin were investigated. The higher saponification value and iodine value indicates that oil and lecithin contains shorter fatty acid chain length with lower molecular weight and the presence of higher amounts of unsaturated fatty acids in the samples. Low acid value and peroxide value indicate higher quality index of fish oil and lecithin. The oxidative stability of shoul fish lecithin was also measured by thiocyanate (TC) method and thiobarbituric acid (TBA) method. Shoul fish lecithin showed higher oxidative stability due to the presence of natural antioxidant. Fatty acid composition of shoul fish oil and lecithin was measured by gas chromatography (GC). The important polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were found to be 0.49% and 1.37% in fish oil. But lecithin contains only 7.8% DHA and other monounsaturated fatty acids. This fish oil and lecithin also contain higher amount of monounsaturated fatty acid and average amount of polyunsaturated fatty acids. Fish oil and lecithin also act as sources of essential fatty acid. Therefore, we can use this fish oil and lecithin in edible purpose, food industry and pharmaceutical industry.