Identification of cancer inhibitors from Hystrix brachyura bezoar extracts using LC - MS multivariate data analysis and in silico evaluation on Bcl - 2, cyclin B/CDK1, VEGF and NM23 - H1 / Identificación de inhibidores de cáncer a partir de extractos de bezoar de Hystrix branchyura usando análisis multivariado LC - MS y evaluación in silico en Bcl - 2, cyclin B/CDK1, VEGF, y NM23 - H1

Hystrix brach yura bezoar is calcified undigested material found in the gastrointestinal tract known for various medicinal benefits including as an anticancer agent. However, the H. brachyura population has been declining due to its demand and is under Malaysian law pro tection. Therefore, present study aimed to identify bezoar anticancer active compounds through metabolomics and in - silico approaches. Five replicates of bezoar powder were subjected to extraction using different solvent ratios of methanol - water (100, 75, 5 0, 25, 0% v/v). Cytotoxicity and metabolite profiling using liquid chromatography - mass spectrometry were conducted. Putative compounds identified were subjected to in - silico analysis with targeted anticancer proteins namely, Bcl - 2, Cyclin B/CDK1 complex, V EGF and NM23 - H1. The correlation of LC - MS and cytotoxicity profile pinpointed two compounds, mangiferin and propafenone. In - silico study showed both compounds exerted good binding scores to all proteins with hydrophobic interaction dominating the ligand - pr otein complex binding, suggesting the ligands act as hydrophobes in the interactions.

El bezpar de Hystrix branchyura es material calcificado sin digerir encontr ados en el tracto gastrointestinal, conocido por sus variados beneficios médicos, incluyendo propiedades anticancerosas. De todas formas, la población de H. Branchyura ha ido declinando debido a su demanda y está bajo la protección de la ley de Malasia. Po r esto, este estudio busca identificar los componentes activos anticancerosos del bezoar mediante abordajes metabolómico e in silico. Cinco réplicas de polvo de bezoar fueron sometidos a extracción usando solventes con diferentes proporciones metanol - agua (100, 75, 50, 25, 0% v/v). Se hicieron perfiles de citotoxicidad y de metabolitos usando cromatografía líquida - espectrometría de masa ( LC - MS ). Se identificaron compuestos putativos yse sometieron a a nálisis in silico, buscando las proteínas anticancerosas B cl - 2, complejo Cyclin B/CDK1, VEGF, y NM23 - H1. La correlación LC - MS y el perfil de citotoxicidad identificaron dos compuestos: mangiferina y propafenona. El estudio in silico mostró que ambos compuestos tenían buenos índices de enlace con todas las proteín as con interacción hidrofóbica dominando el enlace complejo proteína - ligando, sugeriendo que los ligandos actúan como hidrófobos en las interacciones

Anticancer activity of grassy Hystrix brachyura bezoar and its mechanisms of action: An in vitro and in vivo based study.

Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine's (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 µg/mL and 30.12 ± 3.25 µg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 µg/mL and 58.7 ± 5.0 µg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent.

Tricobezoar gigante sin clínica obstructiva / Giant trichobezoar with no clinical signs of obstruction

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ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure.

BACKGROUND: Premature ovarian failure (POF) is a complex and heterogeneous disorder that is influenced by multiple genetic components. Numerous candidate gene studies designed to identify POF susceptibility loci have been published, but most positive findings have not been confirmed in follow up studies. We sought to determine if sequence variants previously associated with age at natural menopause (AANM) or early menopause (EM) contribute as well to genetic susceptibility to POF. METHODS: Our study was performed on 371 unrelated idiopathic women with POF and 800 women controls, all Chinese Han. Thirty six SNPs from previous genome-wide association studies (GWAS) responsible for AANM or EM and 3 additional SNPs in ESR1, and 2 additional SNPs in PTHB1 were tested using the Sequenom MassARRAY iPLEX platform for genotyping. RESULTS: Three SNPs - rs2278493 in HK3, rs2234693 in ESR1 and rs12611091 in BRSK1 - showed nominally significant association with POF. Thus, a plausible relationship could exist between ESR1, BRSK1, HK3 and POF. CONCLUSIONS: This largest association study undertaken to determine correlation between POF and AANM/EM revealed three significant SNPs (rs2278493, rs2234693, and rs12611091). All are associated with not only AAWM and EM but also POF. Insights into shared genetic susceptibility between POF and AANM/EM will provide novel entry points for unraveling genetic mechanism involved in ovarian reserve and oocyte aging processes.

Physical structure and chemical composition of abomasal phytobezoars of goats and sheep.

The diameters of fibres from phytobezoars varied between 2 and 30 microns, with an average 58% measuring less than < 15 microns, 36% between 15 and 23 microns, and 6% greater than 23 microns. These diameters were very similar to those of the pappus hairs surrounding the seeds of the Karoo bushes Chrysocoma ciliata, Eriocephalus ericoides and Gnidia polycephala (means of 6.06 microns, 16.67 microns and 22.73 microns respectively). The microscopic structure and ultrastructure of these pappus hairs moreover closely resembled the fibres of bezoars but were quite distinct from that of hair or wool. Of particular interest was the presence of annular thickenings as well as terminal hooks on both bezoar fibres and pappus hairs, both of which structures are believed to be involved in the formation of bezoars. This close similarity between the fibres in bezoars and those of pappus hairs in the 3 plant species studied, leads to the conclusion that the bezoars consisted largely of pappus hairs of these and possibly other species. The chemical composition of bezoars found in goats and sheep, resembled that of pappus hairs and stems of the Karoo bushes Eriocephalus ericoides and Gnidia polycephala more closely than that of mohair. Ash, nitrogen, phosphorus and zinc concentrations in both bezoars and plant material were similar, but very different to that of mohair; however, the calcium, magnesium, potassium and manganese levels of bezoars were more similar to mohair than plant matter. This may have been due to a leaching effect.

Pharmacological study of a traditional Chinese medicine: effect of bezoar bovis on the irregular beating pattern of cultured mouse myocardial cells.

The water-extract from "Bezoar bovis", a drug used in Chinese traditional medicine, was examined for its ability to alter the beating pattern of spontaneously contracting cultured embryonic mouse myocardial cells following changes in extracellular calcium (Ca2+). Incubation of the cells with medium containing low Ca2+ concentration (0.4 mM) caused the number of beating cells and beating rate to decrease and the number of arrhythmic cells to increase. By contrast, the number of beating cells decreased while beating rate and the number of arrhythmic cells increased at high Ca2+ (20 mM). Addition of Bezoar bovis extract to the medium attenuated the response to varying Ca2+ concentration. One of the major constituents of Bezoar bovis extract, taurine, was effective in protecting against the abnormal beating pattern induced by high Ca2+. Since beta-alanine, an inhibitor of taurine transport, antagonized the protective effects of both Bezoar bovis and taurine, it is likely that the effect of Bezoar bovis is partially mediated by taurine.