Phenylethanoid glycosides from Scutellaria galericulata

From the aerial parts of Scutellaria galericulata L., four phenylethanoid glycosides, 2-(4-hydroxyphenyl)-ethyl-(6-O-caffeoyl)-\beta -D-glucopyranoside (1), calceolarioside B (2), osmanthuside E (3) and martynoside (4), were isolated. The structure elucidations of the isolated compounds were performed by spectroscopic (UV, IR, ESI-MS, 1D- and 2D-NMR) methods. Compounds 1-4 demonstrated scavenging properties toward the 1,1-diphenyl-1-picrylhydrazyl (DPPH) radical in TLC autographic assays

Expression of a catalytically inactive mutant form of glutathione peroxidase 4 (Gpx4) confers a dominant-negative effect in male fertility.

The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 (mGpx4) was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with targeted mutation of the active site selenocysteine (Sec) of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4-/- embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breedings and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoan midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mGpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared to Sec at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Since the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and being a structural protein, tightly controlled expression of functional Gpx4 emerges being key for full male fertility

Luddin type anthraquinone glycosides from Putoria calabrica

Two new lucidin type anthraquinone glycosides, putorinoside A (1) and putorinoside B (2) were isolated from Putoria calabrica, in addition to two known anthraquinone glycosides, lucidin 3-O-β-glucopyranoside (3) and lucidin 3-O-primeveroside (4). Based on spectroscopic data, putorinosides A and B were identified as 2-hydroxymethyl-1-methoxy-3,5,6-trihydroxyanthraquinone 3-O-β-glucopyranoside and 2-hydroxymethyl-1-methoxy-3,6-dihydroxyanthraquinone 3-O-β-glucopyranoside, respectively

Validating Entrepreneurial Intentions Questionnaire to Assess the Impact of Entrepreneurship Education

Entrepreneurship education plays an important role in social and economic development of a society through providing self-employment and job opportunities for others. Entrepreneurship education can catalyse entrepreneurial mindset through developing entrepreneurial intentions of graduates. Current study aims to validate entrepreneurial intentions questionnaire in order to study the impact of entrepreneurship education on student's intentions to become an entrepreneur. The question under study is "does entrepreneurship education impact entrepreneurial intentions of the students?" Study has the following objectives; 1) to study the impact of entrepreneurship education on attitude of the students to become an entrepreneur; 2) to find out perceived behavioural control of the entrepreneurship education students to become an entrepreneur; 3) to understand the impact of subjective norms on entrepreneurship education students to become an entrepreneur; 4) to assess the impact of entrepreneurship education on entrepreneurial intentions of the students. This study will utilize theory of planned behaviour as theoretical framework of the study. According to theory of planned behaviour entrepreneurial intentions of a person are formed through a complex process with some antecedents. The antecedents of entrepreneurial intentions are comprised of attitude of the persons towards entrepreneurship; Subjective norms of a person towards entrepreneurship; and perceived behavioural control of a person towards entrepreneurial intentions. It is a quantitative study based on casual comparative research design. Entrepreneurial Intentions Questionnaire was developed based on theory of planned behaviour. It was pilot tested on students (n=60) for reliability and validation tests. It was validated to make a comparison between technology education students' (n=240) who have participated in entrepreneurship education and technology education students' (n=302) who have not participated in entrepreneurship education. The findings of the study have shown appropriateness of theory of planned behaviour to measure entrepreneurial intentions of the students. Students who have participated in entrepreneurship education have shown higher intentions than non participants. Study was concluded with the fact entrepreneurship education does not impact directly to the intentions of the students but it has influence on entrepreneurial intentions of the students through antecedents of intentions. The questionnaire validated for study can be useful for further measurement of entrepreneurial intentions of the students. Cronbach's Alpha was used to test reliability of questionnaire. Factor analysis was used to test validity of the questionnaire. t-test was applied to find out difference in intentions between entrepreneurship education participants and non participants. Structural equation model (SEM)was used to find out relationship between entrepreneurship education and antecedents of entrepreneurial intentions. This study was knowledge addition about entrepreneurial intentions of the students in Pakistani context and impact of entrepreneurship education. Future study can be conducted to study the new venture creation process of the students with high entrepreneurial intentions.Peer reviewe

Induction of Isochromanones by Co-Cultivation of the Marine Fungus Cosmospora sp. and the Phytopathogen Magnaporthe oryzae

Microbial co-cultivation is a promising approach for the activation of biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. As part of our project aiming at the discovery of marine-derived fungal agrochemicals, we previously used four phytopathogens as model competitors in the co-cultivation of 21 marine fungal strains. Based on comparative untargeted metabolomics analyses and anti-phytopathogenic activities of the co-cultures, we selected the co-culture of marine Cosmospora sp. with the phytopathogen Magnaporthe oryzae for in-depth chemical studies. UPLC-MS/MS-based molecular networking (MN) of the co-culture extract revealed an enhanced diversity of compounds in several molecular families, including isochromanones, specifically induced in the co-culture. Large scale co-cultivation of Cosmospora sp. and M. oryzae resulted in the isolation of five isochromanones from the whole co-culture extract, namely the known soudanones A, E, D (1-3) and their two new derivatives, soudanones H-I (4-5), the known isochromans, pseudoanguillosporins A and B (6, 7), naphtho-γ-pyrones, cephalochromin and ustilaginoidin G (8, 9), and ergosterol (10). Their structures were established by NMR, HR-ESIMS, FT-IR, electronic circular dichroism (ECD) spectroscopy, polarimetry ([α]D), and Mosher’s ester reaction. Bioactivity assays revealed antimicrobial activity of compounds 2 and 3 against the phytopathogens M. oryzae and Phytophthora infestans, while pseudoanguillosporin A (6) showed the broadest and strongest anti-phytopathogenic activity against Pseudomonas syringae, Xanthomonas campestris, M. oryzae and P. infestans. This is the first study assessing the anti-phytopathogenic activities of soudanones

Mitochondrial control of cell death induced by hyperosmotic stress

HeLa and HCT116 cells respond differentially to sorbitol, an osmolyte able to induce hypertonic stress. In these models, sorbitol promoted the phenotypic manifestations of early apoptosis followed by complete loss of viability in a time-, dose-, and cell type-specific fashion, by eliciting distinct yet partially overlapping molecular pathways. In HCT116 but not in HeLa cells, sorbitol caused the mitochondrial release of the caspase-independent death effector AIF, whereas in both cell lines cytochrome c was retained in mitochondria. Despite cytochrome c retention, HeLa cells exhibited the progressive activation of caspase-3, presumably due to the prior activation of caspase-8. Accordingly, caspase inhibition prevented sorbitol-induced killing in HeLa, but only partially in HCT116 cells. Both the knock-out of Bax in HCT116 cells and the knock-down of Bax in A549 cells by RNA interference reduced the AIF release and/or the mitochondrial alterations. While the knock-down of Bcl-2/Bcl-XL sensitized to sorbitol-induced killing, overexpression of a Bcl-2 variant that specifically localizes to mitochondria (but not of the wild-type nor of a endoplasmic reticulum-targeted form) strongly inhibited sorbitol effects. Thus, hyperosmotic stress kills cells by triggering different molecular pathways, which converge at mitochondria where pro- and anti-apoptotic members of the Bcl-2 family exert their control

Bisabolane type sesquiterpenes from a marine Didiscus sponge

Two bisabolane type sesquiterpene phenols, (+)-curcuphenol (1) and (+)-curcudiol (2), were isolated from a Philippine marine sponge, Didiscus sp., in addition to b -sitosterol (3) and phenethylamine (4). The structures of the metabolites were established on the basis of spectral evidence (1D- and 2D NMR, [a]D, EIMS). (+)-Curcuphenol (1) showed cytotoxicity, which is indicative of a p53 independent mechanism

Pyrenosetin D, a new pentacyclic decalinoyltetramic acid derivative from the algicolous fungus Pyrenochaetopsis sp. FVE-087

The fungal genus Pyrenochaetopsis is commonly found in soil, terrestrial, and marine environments, however, has received little attention as a source of bioactive secondary metabolites so far. In a recent work, we reported the isolation and characterization of three new anticancer decalinoyltetramic acid derivatives, pyrenosetins A–C, from the Baltic Fucus vesiculosus-derived endophytic fungus Pyrenochaetopsis sp. FVE-001. Herein we report a new pentacyclic decalinoylspirotetramic acid derivative, pyrenosetin D (1), along with two known decalin derivatives wakodecalines A (2) and B (3) from another endophytic strain Pyrenochaetopsis FVE-087 isolated from the same seaweed and showed anticancer activity in initial screenings. The chemical structures of the purified compounds were elucidated by comprehensive analysis of HR-ESIMS, FT-IR, [α]D, 1D and 2D NMR data coupled with DFT calculations of NMR parameters and optical rotation. Compounds 1–3 were evaluated for their anticancer and toxic potentials against the human malignant melanoma cell line (A-375) and the non-cancerous keratinocyte cell line (HaCaT). Pyrenosetin D (1) showed toxicity towards both A-375 and HaCaT cells with IC50 values of 77.5 and 39.3 µM, respectively, while 2 and 3 were inactive. This is the third chemical study performed on the fungal genus Pyrenochaetopsis and the first report of a pentacyclic decalin ring system from the fungal genus Pyrenochaetopsis

Cytotoxic bromoindole derivatives and terpenes from the Philippine marine sponge Smenospongia sp.

A detailed chemical analysis of a Philippine marine sponge Smenospongia sp. has been performed. This study yielded four new metabolites, 5-bromo-l-tryptophan (1), 5-bromoabrine (2), 5,6-dibromoabrine (3) and 5-bromoindole-3-acetic acid (4). The pyrroloiminoquinone alkaloid, makaluvamine O (5) as well as 5,6-dibromotryptamine (6), aureol (7) and furospinulosin 1 (8) were also isolated. Although 1 and 4 have been synthesized previously, this is the first report on the isolation of these compounds from a natural source. The furanosesterterpene furospinulosin 1 (8) was obtained for the first time from the genus Smenospongia. The structures of all compounds were established by spectroscopic methods (UV, IR, 1D and 2D NMR, MS, [α]D). The cytotoxic potential of 1Ð8 was evaluated in a panel of isogenic HCT-116 human colon tumor cell lines