Effects of fungal based bioactive compounds on human health: Review paper.

Since the first years of history, microbial fermentation products such as bread, wine, yogurt and vinegar have always been noteworthy regarding their nutritional and health effects. Similarly, mushrooms have been a valuable food product in point of both nutrition and medicine due to their rich chemical components. Alternatively, filamentous fungi, which can be easier to produce, play an active role in the synthesis of some bioactive compounds, which are also important for health, as well as being rich in protein content. Therefore, this review presents some important bioactive compounds (bioactive peptides, chitin/chitosan, ß-glucan, gamma-aminobutyric acid, L-carnitine, ergosterol and fructooligosaccharides) synthesized by fungal strains and their health benefits. In addition, potential probiotic- and prebiotic fungi were researched to determine their effects on gut microbiota. The current uses of fungal based bioactive compounds for cancer treatment were also discussed. The use of fungal strains in the food industry, especially to develop innovative food production, has been seen as promising microorganisms in obtaining healthy and nutritious food.

Fungal-based bioactive compounds have various health benefits.Prebiotic fungi play an active role in the regulation of gut microbiota.Anti-tumor effective fungal components will contribute to alternative medicine.Beta-glucan and chitin are the most promising fungal metabolites for cancer treatment.

Monosodium glutamate restricts the adipogenic potential of 3T3-L1 preadipocytes through mitotic clonal expansion.

Recent epidemiologic studies pointed out a significant correlation between dietary monosodium glutamate (MSG) and increased body mass index. Corroborating evidences came from animal studies depicting a clear association between dietary MSG intake and increased abdominal fat, dyslipidemia, adipocyte hypertrophy, and total body weight gain. Taken together with the inferred absence of conspicuous hypothalamic neuropathies the hallmark of disease etiopathogenesis in MSG-obese animals, these animal studies with dietary MSG strongly argue for the presence of an alternative non-neuronal route for MSG to mediate its adipose tissue-specific phenotype and body weight gain. On the basis of this hypothesis, we investigated the direct effect of physiologically relevant low (100 µM), moderate (250 µM), and high dosages (2.5 and 25 mM) of MSG on distinct phases of adipocyte differentiation. MSG-dependent changes in cell proliferation and lipid accumulation were analyzed by cell proliferation assays, flow cytometry, and biochemical methods, respectively. Physiologically relevant high dosages MSG demonstrated a significant potential in reducing MCE and thereof adipogenic capacity of preadipocytes in a dose-dependent manner by restricting the availability of critical mitogenic proteins, CCAAT/enhancer-binding protein ß (CEBPß), and the mitotic cyclin B. Our findings warrant further investigations to unravel the effect of long-term dietary MSG intake on capacity of preadipocytes in different fat depots to undergo mitotic clonal expansion and hyperplasia in rodent models and human subjects, respectively.

SIK2 is involved in the negative modulation of insulin-dependent muller cell survival and implicated in hyperglycemia-induced cell death.

PURPOSE: To investigate the role of the serine/threonine kinase SIK2, a member of the salt-inducible kinase (SIK) family, in insulin-dependent cell survival and hyperglycemia-induced cell death in Müller glia. METHODS: Expression studies were performed by RT-PCR, immunostaining, Northern blotting, and immunoblotting. Insulin-dependent changes in SIK2 activity were investigated by in vitro kinase assays in MIO-M1 Müller cell line. Akt activation was studied by immunoblotting and cell death by TUNEL assay. The potential role of SIK2 in insulin signaling was explored by overexpression and sh-RNA knock-down approaches. Effects of hyperglycemia were studied in vitro and in vivo in streptozotocin-injected rats. RESULTS: SIK2 expression was detected throughout adult retina, except for the outer nuclear layer. Insulin stimulation of MIO-M1 cells resulted in a rapid 2-fold increase of SIK2 activity, increased insulin receptor substrate 1 (IRS1)-SIK2 interaction, and reduced cell death. pAkt levels following insulin treatment were modulated by SIK2 activity. Under hyperglycemia, increased SIK2 activity/expression was concomitant to decreased Akt activation and enhanced apoptosis; whereas knockdown of SIK2 under normo- and hyperglycemic conditions resulted in a rapid increase in pAkt levels and blunted cell death. SIK2 overexpression under normoglycemia had an opposite effect. SIK2 activity increased significantly within 2 weeks of induction of hyperglycemia in the rat retina. CONCLUSIONS: Results indicate that SIK2 functions as a negative modulator of the insulin-dependent survival pathway and contributes to hyperglycemia-induced cell death of Müller glia in vitro. Although still hypothetical at this point, our study suggests that SIK2 could serve a similar role during the development of diabetic retinopathy in vivo and that it represents a potential target to control disease progression.

On the nature of low- and high-affinity EGF receptors on living cells.

The small subpopulation of high-affinity EGF receptors (EGFRs) on living cells revealed by Scatchard analysis of (125)I-EGF binding results was discovered nearly three decades ago, yet not much is known about the underlying mechanism. After the determination of the structure of different forms of EGFR extracellular domain it was proposed that the monomeric tethered configuration corresponds to the majority of low-affinity receptors, whereas the extended dimeric configuration corresponds to the minority of the high-affinity class of EGFRs. Mathematical modeling of EGF-binding experiments to different conformational mutants of EGFR has shown that the high-affinity class of EGFR on living cells does not correspond to the extended configuration of EGFR and can only be accounted for by including in the mathematical model an additional binding event that is attributed to the dynamic nature of EGFR on living cells. To circumvent this problem we have performed similar experiments in the background of an EGFR mutant that does not form high-affinity sites. Quantitative analysis and mathematical modeling of these data show that release of the intramolecular tether causes a 2-fold increase in EGF-binding affinity, whereas elimination of the dimerization arm reduces EGF-binding affinity by approximately 6-fold. These experiments confirm the salient features of the structural model for EGFR regulation and argue further that the intramolecular tether provides only limited autoinhibitory control of EGFR activity and that the low-affinity class of EGF-binding sites on living cells reflects interconverting, tethered, and extended receptor configurations.

Expression and possible function of fibroblast growth factor 9 (FGF9) and its cognate receptors FGFR2 and FGFR3 in postnatal and adult retina.

Fibroblast growth factors (FGFs) are important regulators of retinal development and survival. We examined the expression and distribution of FGF9 and its preferred receptors FGFR2IIIc and FGFR3IIIc in this tissue. FGF9 transcripts in whole rat retina were detected by RT-PCR but were not present in purified cultured Muller glia. Transcripts appeared as 3.2-kb and 4.0-kb bands on Northern blots, and Western blotting of whole retina revealed FGF9-immunoreactive bands at 30 and 55 kDa. FGF9 mRNA demonstrated a biphasic expression profile, elevated at birth and adulthood, but relatively decreased during terminal retinal differentiation (4-14 days postnatal). Antibody labeling broadly reflected these findings: staining in vivo was observed mainly in the inner retina (and outer plexiform layer in adults) whereas FGF9 was not detectable in cultured Muller glia. In adults, FGF9 in situ hybridization also showed a detectable signal in inner retina. FGFR2IIIc and FGFR3IIIc were detected by RT-PCR, and Western blotting showed both FGFRs existed as multiple forms between approximately 100-200 kDa. FGFR2 and FGFR3 antibodies showed prominent labeling in the inner retina, especially in proliferating cultured Muller glia. Exogenous FGF9 elicited a dose-dependent increase in Muller glial proliferation in vitro. These data suggest a role for FGF9 in retinal differentiation and maturation, possibly representing a neuronally derived factor acting upon glial (and other) cells.