Influence of Agar on the Morphology and Pigmentation of Streptomycetes

The effect of various agar preparations in a chemically defined medium on promoting the development of taxonomic characteristics of streptomycetes was studied. Various agar products gave different results. Agar purified to a certain extent was favorable for good, constant development of such characteristics. The presence of certain metals played a great role in this domain. Agar purified to a high degree may give poor results unless supplemented with the proper metals. Recommendations were made for the standardization of agar media used for the study of characteristics of streptomycetes.     

Dietary fructooligosaccharides induce immunoregulation of intestinal IgA secretion by murine Peyer's patch cells

Probiotic supplements induce immunological responses in the host, and dietary fructooligosaccharides (FOS) stimulate the growth of selected intestinal microflora. In this study we investigated the immunological influences of orally administrated FOS. BALB/c mice were orally administered 0-7.5% FOS for 6 weeks, and the intestinal mucosal immune responses were measured. In the 2.5%-FOS group, fecal IgA was significantly increased. IgA secretion by Peyer's patch (PP) cells was upregulated in a dose-dependent way in response to FOS and CD4+ T cells from PP showed a dose-dependent increase in production of interferon-gamma and interleukin (IL) 10, and a high response in production of IL-5 and IL-6. In contrast, FOS suppressed serum IgG1. Our findings suggest that FOS supplementation changes the intestinal environment of microflora, and leads to upregulation of IgA secretion in CD4+ PP cells in intestinal mucosa, and to suppression of the systemic immune response to type 2 helper T (Th2) dominant.     

Inhibitory control of shivering and nonshivering thermogenesis by preoptic warm-sensitive neurons

To investigate the characteristics of efferent projections from the preoptic area for the control of shivering and nonshivering thermogenesis, we tested the effects of thermal stimulation and injecting excitatory substances into the preoptic area on shivering and nonshivering thermogenesis in anesthetized rats. Preoptic warming and injection of glutamate suppressed shivering at ambient temperatures of 15–21°C. Likewise, preoptic warming and d,l-homocysteic acid injection suppressed nonshivering thermogenesis elicited by electrical stimulation of the ventromedial hypothalamic nucleus. Inhibitory signals from warm-sensitive neurons, thus, contribute a larger efferent signal for heat production than do signals from cold-sensitive neurons.     

Host range factor 1 from Lymantria dispar Nucleopolyhedrovirus (NPV) is an essential viral factor required for productive infection of NPVs in IPLB-Ld652Y cells derived from L. dispar

Host range factor 1 (HRF-1) of Lymantria dispar multinucleocapsid nucleopolyhedrovirus promotes Autographa californica MNPV replication in nonpermissive Ld652Y cells derived from L. dispar. Here we demonstrate that restricted Hyphantria cunea NPV replication in Ld652Y cells was not due to apoptosis but was likely due to global protein synthesis arrest that could be restored by HRF-1. Our data also showed that HRF-1 promoted the production of progeny virions for two other baculoviruses, Bombyx mori NPV and Spodoptera exigua MNPV, whose replication in Ld652Y cells is limited to replication of viral DNA without successful production of infectious progeny virions. Thus, HRF-1 is an essential viral factor required for productive infection of NPVs in Ld652Y cells.     

Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model

Involvement of impaired peritoneal immunosurveillance systems has been well established in the pathology of endometriosis. On the other hand, it has been observed that peritoneal administration of IL-12 suppress development of endometriotic lesions in a mouse endometriosis model. We investigated the effect of peritoneal administration of IL-12 on the peritoneal immunosurveillance system regarding NK cells in the mouse model. Treating the endometrial-tissue challenged mice with IL-12 for 5 consecutive days, from day -2 to day 2 (implantation of the endometrial tissues was done on day 0), cytotoxicity of splenic NK cells was enhanced immediately after the administration, on day 3, and development of the endometriotic lesions was reduced on day 21. In vivo NK cell depletion by administration of anti-IL-2Rβ mAb resulted in reduction of the cytotoxicity of splenic NK cells concomitant with a significant attenuation of suppressive effect of IL-12 on development of endometriotic lesions. Therefore, it was suggested that IL-12 suppresses development of endometriotic lesions via activation of NK cells, and that NK cells are involved in the primary defense for the development of endometriotic lesions.     

Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of beta-tubulin

Allyl sulfides are characteristic flavor components obtained from garlic. These sulfides are thought to be responsible for their epidemiologically proven anticancer effect on garlic eaters. This study was aimed at clarifying the molecular basis of this anticancer effect of garlic by using human colon cancer cell lines HCT-15 and DLD-1. The growth of the cells was significantly suppressed by diallyl trisulfide (DATS, HCT-15 IC50 = 11.5 microM, DLD-1 IC50 = 13.3 microM); however, neither diallyl monosulfide nor diallyl disulfide showed such an effect. The proportion of HCT-15 and that of DLD-1 cells residing at the G1 and S phases were decreased by DATS, and their populations at the G2/M phase were markedly increased for up to 12 h. The cells with a sub-G1 DNA content were increased thereafter. Caspase-3 activity was also dramatically increased by DATS. Fluorescence-activated cell sorter analysis performed on the cells arrested at the G1/S boundary revealed cell cycle-dependent induction of apoptosis through the transition of the G2/M phase to the G1 phase by DATS. DATS inhibited tubulin polymerization in an in vitro cell-free system. DATS disrupted microtubule network formation of the cells, and microtubule fragments could be seen at the interphase. Peptide mass mapping by liquid chromatography-tandem mass spectrometry analysis for DATS-treated tubulin demonstrated that there was a specific oxidative modification of cysteine residues Cys-12beta and Cys-354beta to form S-allylmercaptocysteine with a peptide mass increase of 72.1 Da. The potent antitumor activity of DATS was also demonstrated in nude mice bearing HCT-15 xenografts. This is the first paper describing intracellular target molecules directly modified by garlic components.     

Fatty acid binding protein 3 as a potential mediator for diabetic nephropathy in eNOS deficient mouse

In human diabetic nephropathy, glomerular injury was found to comprise lipid droplets, suggesting that abnormal lipid metabolism might take place in the development of diabetic glomerular injury. However, its precise mechanism remains unclear. Fatty acid binding protein (FABP) is currently considered as a key molecule for lipid metabolism. Since diabetic eNOS knockout (KO) mouse is considered to be a good model for human diabetic nephropathy, we here investigated whether FABP could mediate glomerular injury in this model. We found that glomerular injuries were associated with inflammatory processes, such as macrophage infiltration and MCP-1 induction. Microarray assay with isolated glomeruli revealed that among 10 isoforms in FABP family, FABP3 mRNA was most highly expressed in diabetic eNOSKO mice compared to non-diabetic eNOSKO mice. FABP3 protein was found to be located in the mesangial cells. Overexpression of FABP3 resulted in a greater response to palmitate, a satulated FA, to induce MCP-1 in the rat mesangial cells. In turn, the heart, a major organ for FABP3 protein in normal condition, failed to alter its expression level under diabetic condition in either wild type or eNOSKO mice. In conclusion, FABP3 is induced in the mesangial cells and likely a mediator to induce MCP-1 in the diabetic nephropathy.     

Telomere Shortening in Human HL60 Cells by Treatment with 3′-Azido-2′,3′-Dideoxynucleosides and Telomerase Inhibition by Their 5′-Triphosphates

Telomerase is thought to play an important role in the mechanism of tumor cell immortalization by maintenance of telomere length. To obtain information on the susceptibility of telomerase to nucleoside analogues, the effects of base-modified 3′-azido-2′,3′-dideoxynucleoside triphosphates on the enzyme were investigated. It is suggested that the 2-amino group of the nucleotide purine nucleus is important for the inhibitory activity. Telomere shortening caused by long-term treatment with these nucleosides is also described.     

Thiosulfate promotes hair growth in mouse model

The present study describes the hair growth-promoting effects of sodium thiosulfate (STS), a widely used compound, in mice. STS accelerated hair growth in the “telogen model”, suggesting that it stimulates telogen hair follicles to reenter the anagen phase of hair growth. In the same model, STS potentiated hair growth in an additive manner with minoxidil (MXD), a drug used for the treatment of androgenic alopecia. Furthermore, in the “anagen model”, STS promoted hair growth, probably by promoting hair follicle proliferation. Since STS elevated the skin surface temperature, its hair growth-promoting activity may be partly due to vasorelaxation, similar to MXD. In addition, STS is known to generate a gaseous mediator, H₂S, which has vasorelaxation and anti-inflammatory/anti-oxidative stress activities. Therefore, STS and/or provisionally its metabolite, H₂S, may aid the hair growth process. Collectively, these results suggest that salts of thiosulfate may represent a novel and beneficial remedy for hair loss.     

Telomere shortening in human HL60 cells by treatment with 3'-azido-2',3'-dideoxynucleosides and telomerase inhibition by their 5'-triphosphates

Telomerase is thought to play an important role in the mechanism of tumor cell immortalization by maintenance of telomere length. To obtain information on the susceptibility of telomerase to nucleoside analogues, the effects of base-modified 3'-azido-2',3'-dideoxynucleoside triphosphates on the enzyme were investigated. It is suggested that the 2-amino group of the nucleotide purine nucleus is important for the inhibitory activity. Telomere shortening caused by long-term treatment with these nucleosides is also described.