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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.

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.

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.