The yin and yang of 15-lipoxygenase-1 and delta-desaturases: Dietary omega-6 linoleic acid metabolic pathway in prostate

One of the major components in high-fat diets (Western diet) is the omega (ω, n)-6 polyunsaturated fatty acid (PUFA) called linoleic acid (LA). Linoleic acid is the precursor for arachidonic acid (AA). These fatty acids are metabolized to an array of eicosanoids and prostaglandins depending upon the enzymes in the pathway. Aberrant expression of the catabolic enzymes such as cyclooxygenases (COX-1 and/or -2) or lipoxygenases (5-LO, 12-LO, 15-LO-1, and 15-LO-2) that convert PUFA either AA and/or LA to bioactive lipid metabolites appear to significantly contribute to the development of PCa. However, PUFA and its cellular interactions in PCa are poorly understood. We therefore examined the mRNA levels of key enzymes involved in the LA and AA pathways in 18 human donor (normal) prostates compared to 60 prostate tumors using the Affymetrix U95Av2 chips. This comparative (normal donor versus prostate cancer) study showed that: 1) the level of 15-LO-1 expression (the key enzyme in the LA pathway) is low (P < 0.001), whereas the levels of delta-5 desaturase (P < 0.001, the key enzyme in the AA pathway), delta-6 desaturase (P = 0.001), elongase (P = 0.16) and 15-lipoxygenase-2 (15-LO-2, P = 0.74) are higher in donor (normal) prostates, and 2) Contrary to the observation in the normal tissues, significantly high levels of only 15-LO-1; whereas low levels of delta-6 desaturase, elongase, delta-5 desaturase and 15-LO-2 respectively, were observed in PCa tissues. Although the cyclooxygenase (COX)-1 and COX-2 mRNA levels were high in PCa, no significant differences were observed when compared in donor tissues. Our study underscores the importance of promising dietary intervention agents such as the omega-3 fatty acids as substrate competitors of LA/AA, aimed primarily at high 15-LO-1 and COX-2 as the molecular targets in PCa initiation and/or progression

Immunohistochemical profiles of claudin-3 in primary and metastatic prostatic adenocarcinoma

Background\ud Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).\ud \ud Methods\ud Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays.\ud \ud Results\ud PCa and Mets had the highest absolute staining for claudin-3. Both had significantly higher staining than BPH (p < 0.05 in both cases) and NAC (p < 0.05 in both cases). PIN had a lower, but non-significant, staining score than PCa and Mets, but a statistically higher score than both BPH and NAC (p < 0.05 for both cases). No significant differences were observed between PCa, Mets, and PIN.\ud \ud Conclusions\ud To our knowledge, this represents one of the first studies comparing the immunohistochemical profiles of claudin-3 in PCa and NAC to specimens of PIN, BPH, and Mets. These findings provide further evidence that claudin-3 may serve as an important biomarker for prostate cancer, both primary and metastatic, but does not provide evidence that claudin-3 can be used to predict risk of metastasis

Gonadotrophin-mediated miRNA expression in testis at onset of puberty in rhesus monkey: Predictions on regulation of thyroid hormone activity and DLK1-DIO3 locus

Molecular mechanisms responsible for the initiation of primate spermatogenesis remain poorly characterized. Previously, 48 h stimulation of the testes of three juvenile rhesus monkeys with pulsatile LH and FSH resulted in down-regulation of a cohort of genes recognized to favor spermatogonia stem cell renewal. This change in genetic landscape occurred in concert with amplification of Sertoli cell proliferation and the commitment of undifferentiated spermatogonia to differentiate. In this report, the non-protein coding small RNA transcriptomes of the same testes were characterized using RNA sequencing: 537 mature micro-RNAs (miRNAs), 322 small nucleolar RNAs (snoRNAs) and 49 small nuclear RNAs (snRNAs) were identified. Pathway analysis of the 20 most highly expressed miRNAs suggested that these transcripts contribute to limiting the proliferation of the primate Sertoli cell during juvenile development. Gonadotrophin treatment resulted in differential expression of 35 miRNAs, 12 snoRNAs and four snRNA transcripts. Ten differentially expressed miRNAs were derived from the imprinted delta-like homolog 1-iodothyronine deiodinase 3 (DLK1-DIO3) locus that is linked to stem cell fate decisions. Four gonadotrophin-regulated expressed miRNAs were predicted to trigger a local increase in thyroid hormone activity within the juvenile testis. The latter finding leads us to predict that, in primates, a gonadotrophin-induced selective increase in testicular thyroid hormone activity, together with the established increase in androgen levels, at the onset of puberty is necessary for the normal timing of Sertoli cell maturation, and therefore initiation of spermatogenesis. Further examination of this hypothesis requires that peripubertal changes in thyroid hormone activity of the testis of a representative higher primate be determined empirically.Fil: Aliberti, Paula. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sethi, Rahil. University of Pittsburgh; Estados UnidosFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chandran, Uma R.. University of Pittsburgh; Estados UnidosFil: Plant, Tony M.. University of Pittsburgh; Estados UnidosFil: Walker, William H.. University of Pittsburgh; Estados Unido

Determining genetic variability of traits in backcross populations of sweet corn (Zea mays L. var. Saccharata)

To understand the nature of the traits in breeding programme, knowledge on heritability, genetic advance and genetic variability are inevitable. The paramount aim of the present study was to estimate the heritability, genetic advance and genetic variability of the backcross and selfed population of sweet corn and β-carotene rich inbred combinations viz., USC1-2-3-1× UMI1230β+ and SC1107× UMI1230β+ in order to identify the plants with superior trait combinations. The study involved the recording of fourteen biometrical traits in both the cross combinations which revealed that in backcross and selfed populations, the phenotypic coefficient of variation (PCV) was found to be greater than the genotypic coefficient of variation (GCV) indicating the probable influence of environment in the expression of the traits evaluated. High heritability was recorded for the important trait single plant yield in both the cross combinations of BC2F2 generation. Further, high heritability and high genetic advance as percent of mean was noticed for the traits like plant height, cob length, leaf length and single plant yield under both the cross combinations of BC2F2 generation indicates the governance of additive genes in expression of these traits. Hence, selection for these traits would be effective in developing a genotype with improved yield

Bumper landings of skipjack tuna (Katsuwonus pelamis) by hooks and lines at Visakhapatnam Fishing Harbour

Bumper landings of skipjack tuna, Katsuwonus pelamis was observed at Visakhapatnam Fishing Harbour on 28th October 2011, wherein about 42 t were landed by hooks and line

Long lining for deep sea sharks at Malpe — A lucrative fishery

Recent introduction of long lining for deep sea sharks at Malpe Kolam found as considerable success venture. This is particularly significant at a time when there is no scops for further expansion of trawl or purse seine fishery along this coast. Moreover, this diversification of fishing effort for the exploitation of the unexploited resources of the deep sea sharks of the inshore and offshore waters of the South Kanara coast is a new development

Crohn\u27s disease-associated ATG16L1 T300A genotype is associated with improved survival in gastric cancer

BACKGROUND: A non-synonymous single nucleotide polymorphism of the ATG16L1 gene, T300A, is a major Crohn\u27s disease (CD) susceptibility allele, and is known to be associated with increased apoptosis induction in the small intestinal crypt base in CD subjects and mouse models. We hypothesized that ATG16L1 T300A genotype also correlates with increased tumor apoptosis and therefore could lead to superior clinical outcome in cancer subjects. METHODS: T300A genotyping by Taqman assay was performed for gastric carcinoma subjects who underwent resection from two academic medical centers. Transcriptomic analysis was performed by RNA-seq on formalin-fixed paraffin-embedded cancerous tissue. Tumor apoptosis and autophagy were determined by cleaved caspase-3 and p62 immunohistochemistry, respectively. The subjects\u27 genotypes were correlated with demographics, various histopathologic features, transcriptome, and clinical outcome. FINDINGS: Of the 220 genotyped subjects, 163 (74%) subjects carried the T300A allele(s), including 55 (25%) homozygous and 108 (49%) heterozygous subjects. The T300A/T300A subjects had superior overall survival than the other groups. Their tumors were associated with increased CD-like lymphoid aggregates and increased tumor apoptosis without concurrent increase in tumor mitosis or defective autophagy. Transcriptomic analysis showed upregulation of WNT/β-catenin signaling and downregulation of PPAR, EGFR, and inflammatory chemokine pathways in tumors of T300A/T300A subjects. INTERPRETATION: Gastric carcinoma of subjects with the T300A/T300A genotype is associated with repressed EGFR and PPAR pathways, increased tumor apoptosis, and improved overall survival. Genotyping gastric cancer subjects may provide additional insight for clinical stratification

Garlic (Allium sativum L.) Bioactives and Its Role in Alleviating Oral Pathologies

Garlic (Allium sativa L.) is a bulbous flowering plant belongs to the family of Amaryllidaceae and is a predominant horticultural crop originating from central Asia. Garlic and its products are chiefly used for culinary and therapeutic purposes in many countries. Bulbs of raw garlic have been investigated for their role in oral health, which are ascribed to a myriad of biologically active compounds such as alliin, allicin, methiin, S-allylcysteine (SAC), diallyl sulfide (DAS), S-ally-mercapto cysteine (SAMC), diallyl disulphide (DADS), diallyl trisulfide (DATS) and methyl allyl disulphide. A systematic review was conducted following the PRISMA statement. Scopus, PubMed, Clinicaltrials.gov, and Science direct databases were searched between 12 April 2021 to 4 September 2021. A total of 148 studies were included and the qualitative synthesis phytochemical profile of GE, biological activities, therapeutic applications of garlic extract (GE) in oral health care system, and its mechanism of action in curing various oral pathologies have been discussed. Furthermore, the safety of incorporation of GE as food supplements is also critically discussed. To conclude, GE could conceivably make a treatment recourse for patients suffering from diverse oral diseases

Immunohistochemical staining of radixin and moesin in prostatic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Some members of the Protein 4.1 superfamily are believed to be involved in cell proliferation and growth, or in the regulation of these processes. While the expression levels of two members of this family, radixin and moesin, have been studied in many tumor types, to our knowledge they have not been investigated in prostate cancer.</p> <p>Methods</p> <p>Tissue microarrays were immunohistochemically stained for either radixin or moesin, with the staining intensities subsequently quantified and statistically analyzed using One-Way ANOVA or nonparametric equivalent with subsequent Student-Newman-Keuls tests for multiple comparisons. There were 11 cases of normal donor prostates (NDP), 14 cases of benign prostatic hyperplasia (BPH), 23 cases of high-grade prostatic intraepithelial neoplasia (HGPIN), 88 cases of prostatic adenocarcinoma (PCa), and 25 cases of normal tissue adjacent to adenocarcinoma (NAC) analyzed in the microarrays.</p> <p>Results</p> <p>NDP, BPH, and HGPIN had higher absolute staining scores for radixin than PCa and NAC, but with a significant difference observed between only HGPIN and PCa (p = < 0.001) and HGPIN and NAC (p = 0.001). In the moesin-stained specimens, PCa, NAC, HGPIN, and BPH all received absolute higher staining scores than NDP, but the differences were not significant. Stage 4 moesin-stained PCa had a significantly reduced staining intensity compared to Stage 2 (p = 0.003).</p> <p>Conclusions</p> <p>To our knowledge, these studies represent the first reports on the expression profiles of radixin and moesin in prostatic adenocarcinoma. The current study has shown that there were statistically significant differences observed between HGPIN and PCa and HGPIN and NAC in terms of radixin expression. The differences in the moesin profiles by tissue type were not statistically significant. Additional larger studies with these markers may further elucidate their potential roles in prostatic neoplasia progression.</p