Translational models of tumor angiogenesis: A nexus of in silico and in vitro models

Emerging evidence shows that endothelial cells are not only the building blocks of vascular networks that enable oxygen and nutrient delivery throughout a tissue but also serve as a rich resource of angiocrine factors. Endothelial cells play key roles in determining cancer progression and response to anti-cancer drugs. Furthermore, the endothelium-specific deposition of extracellular matrix is a key modulator of the availability of angiocrine factors to both stromal and cancer cells. Considering tumor vascular network as a decisive factor in cancer pathogenesis and treatment response, these networks need to be an inseparable component of cancer models. Both computational and in vitro experimental models have been extensively developed to model tumor-endothelium interactions. While informative, they have been developed in different communities and do not yet represent a comprehensive platform. In this review, we overview the necessity of incorporating vascular networks for both in vitro and in silico cancer models and discuss recent progresses and challenges of in vitro experimental microfluidic cancer vasculature-on-chip systems and their in silico counterparts. We further highlight how these two approaches can merge together with the aim of presenting a predictive combinatorial platform for studying cancer pathogenesis and testing the efficacy of single or multi-drug therapeutics for cancer treatment.     

Comparing the Recurrence of Vulvovaginal Candidiasis in Patients Undergoing Prophylactic Treatment with Probiotic and Placebo During the 6 Months

This is a randomized, double-blind, clinical/comparative trial study, involving the recurrence of vaginal candidiasis (VVC) after initial treatment with oral fluconazole in patients undergoing prophylactic management with a probiotic and placebo for 6 months. Fifty-nine VVC patients who were diagnosed based on their history, physical examination, and culture of vaginal discharge were initially treated by a single dose of 150 mg fluconazole. According to the table of random numbers, the sample was divided into two groups. The patients from one group took probiotics, while those from the other group took a placebo, with all of them being continuously monitored for 6 months. The patients complaining of vaginal candidiasis symptoms, such as burning, pruritus, and a vaginal (curd-like) discharge, were examined and the discharge was cultured for candida. The positive cultures were considered to be recurring for the patients in each group. Thirty-one cases from the placebo group and 28 cases from the probiotic group were carefully observed. In total, the 6-month recurrence in the control group was eleven (35.5 %) and in the research group was two (7.2 %). The results from Fisher’s exact test for the value p = 0.01 and OR 0.14 95 % CI (0.028–0.7) showed significant recurrence in the placebo group. The findings demonstrated that taking probiotics withazole antifungal drugs could be highly effective in treating VVC, resulting in a lower recurrence rate as well.     

Description and genetic characterisation of Hysterothylacium (Nematoda: Raphidascarididae) larvae parasitic in Australian marine fishes

Nematodes belonging to the genus Hysterothylacium (family Raphidascarididae) infect various species of marine fish in both the larval and adult stages. Humans can be accidentally infected upon eating infected seafood. In spite of their importance, relatively little is known of their occurrence and systematics in Australia. An examination of various species of marine teleosts in Australian waters revealed a high prevalence of Hysterothylacium larval types. In the present study, seven previously undescribed Hysterothylacium larval morphotypes (V to VII and IX to XII) were discovered. In total we found 10 different morphotypes and we genetically characterised nine morphotypes identified. A morphological dichotomous identification key has been established to differentiate these morphotypes. Since some larvae of Hysterothylacium from marine fishes cannot be differentiated morphologically from other nematode larvae, such as Paraheterotyphlum, Heterotyphlum, Iheringascaris and Lapetascaris, the first and second internal transcribed spacers (ITS-1 and ITS-2) of nuclear ribosomal DNA (rDNA) of these larvae were characterised to confirm their taxonomic status. This genetic characterisation implied that some distinct morphotypes belong to different developmental stages of the same species. In addition, it revealed that some morphotypes can comprise distinct genotypes. No match was found between ITS-1 and ITS-2 sequences obtained from larvae in the present study and those from adults available in the GenBank, highlighting the lack of knowledge on occurrence of adult nematodes infecting Australian fish.     

Antioxidant properties of a human neuropeptide and its protective effect on free radical‐induced DNA damage

Human catestatin CgA_352–372 (SL21) is an endogenous neuropeptide with multiple biological functions. The present study aimed to evaluate the antioxidant, antibacterial, cytotoxic, and DNA damage protective effects of SL21 neuropeptide. SL21 neuropeptide generated from the C‐terminus of chromogranin A (CgA) was synthesized by solid‐phase method. Synthetic peptide was subjected to various in vitro antioxidant assays including the scavenging of 1,1‐diphenyl‐2‐pycryl‐hydrazyl (DPPH), 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS^·+), and hydroxyl free radicals, metal ion chelation, inhibition of lipid peroxidation, and reducing power. Moreover, protective effect of SL21 on H₂O₂‐induced DNA damage was analyzed using pTZ57/RT plasmid. Methylthiazoltetrazolium assay was also performed to study the cytotoxic effect of SL21 neuropeptide on human peripheral blood mononuclear cells. Furthermore, antibacterial and hemolysis assays were conducted. The results demonstrated high activities of SL21 in scavenging free radicals (DPPH, ABTS^·+, and hydroxyl), chelating of Cu²⁺/Fe²⁺ metal ions, reducing power, and inhibition of lipid peroxidation in a concentration‐dependent manner. SL21 neuropeptide revealed a protective effect on DNA damage caused by hydroxyl radicals. Interestingly, the peptide exhibited no significant cytotoxicity towards peripheral blood mononuclear cells. Furthermore, SL21 peptide displayed antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa without any hemolytic activity on human red blood cells. Conclusively, the present study established SL21 (catestatin) as a novel antioxidative peptide that could further be investigated for its potential use as a pharmaceutical agent. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.     

Sequence,expression divergence,and complementation of homologous <Emphasis Type="Italic">ALCATRAZ</Emphasis> loci in <Emphasis Type="Italic">Brassica napus</Emphasis>

The genomic era provides new perspectives in understanding polyploidy evolution, mostly on the genome-wide scale. In this paper, we show the sequence and expression divergence between the homologous ALCATRAZ (ALC) loci in Brassica napus, responsible for silique dehiscence. We cloned two homologous ALC loci, namely BnaC.ALC.a and BnaA.ALC.a in B. napus. Driven by the 35S promoter, both the loci complemented to the alc mutation of Arabidopsis thaliana, yet only the expression of BnaC.ALC.a was detectable in the siliques of B. napus. Sequence alignment indicated that BnaC.ALC.a and BolC.ALC.a, or BnaA.ALC.a and BraA.ALC.a, possess a high level of similarity. The understanding of the sequence and expression divergence among homologous loci of a gene is of due importance for an effective gene manipulation and TILLING (or ECOTILLING) analysis for the allelic DNA variation at a given locus. S. Hua and I. H. Shamsi contributed equally to this work.     

Age‐based life history parameters and status assessments of by‐catch species (Lethrinus borbonicus,Lethrinus microdon,Pomacanthus maculosus and Scolopsis taeniatus) in the southern Arabian Gulf

Life history and demographic parameters for Lethrinus borbonicus, Lethrinus microdon, Pomacanthus maculosus and Scolopsis taeniatus in the southern Arabian Gulf were estimated using a combination of size frequency, biological and size‐at‐age data. Defined structural increments consisting of alternating translucent and opaque bands in transverse sections of sagittal otoliths were validated as annuli. The maximum age estimates ranged from 5 years for Scolopsis taeniatus to 36 years for Pomacanthus maculosus. The size‐at‐age relationships were highly asymptotic in form with the majority of growth being achieved early in life. There were significant differences in the growth characteristics between sexes for Pomacanthus maculosus, with males approaching a larger asymptotic size at a faster rate than females. With the exception of Scolopsis taeniatus, the mean age at which fish became vulnerable to capture was lower than the mean age at first sexual maturity. The stocks of L. microdon, P. maculosus and S. taeniatus were exploited within sustainable limits, conversely, L. borbonicus was found to be overexploited and recruitment overfishing may have occurred as the relative spawner biomass per recruit was below 30% of the unexploited state.     

Reproductive biology and implications for management of the painted sweetlips Diagramma pictum in the southern Arabian Gulf

The reproductive biology of the painted sweetlips Diagramma pictum was determined from 487 individuals collected between January and December 2010 in the southern Arabian Gulf. There was no evidence of sex change and the combination of histological results with the sex composition of the size and age structures indicated a gonochoristic sexual pattern. There were peaks in gonado-somatic indices for females in March and October with spawning occurring during two seasons (April to May and November). The mean size and age at sexual maturity (L(m50) and A(m50) ) were 35·7 cm fork length (L(F) ) and 2·9 years for females and 26·7 cm L(F) and 0·5 years for males. The maximum recorded age (11 years) and small mean size and young age at sexual maturity for males may be a direct result of intensive demersal fishing in the southern Arabian Gulf. There was an exponential increase in the cumulative reproductive potential with size and a linear increase with age for both sexes. The mean L(F) (L(c50) ) at which D. pictum became vulnerable to capture was 33·3 cm, which corresponded to only 3 and 7% of the cumulative reproductive potential of males and females, respectively. Size-specific and age-specific reproductive potential indicated that conventional regulations that equate the mean size at first capture to sexual maturation are unsuitable for the management of D. pictum.     

Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction

Male infertility is a multi‐factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non‐azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males. Mol. Reprod. Dev. 79: 637–650, 2012. © 2012 Wiley Periodicals, Inc.