Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness

BackgroundAlthough estrogen (ERα/ERβ), progesterone (PGR), and androgen (AR) receptors are pathologically altered in colorectal cancer (CRC), their simultaneous expression within the same cohort of patients was not previously measured.MethodsERα/ERβ/PGR/AR proteins were measured in archived paired normal and malignant colon specimens (n =120 patients) by immunohistochemistry, and results were analyzed by gender, age (≤50 vs. ≥60 years), clinical stages (early-stage I/II vs. late-stage III/IV), and anatomical location (right; RSCs vs. left; LSCs). Effects of 17β-estradiol (E2), progesterone (P4), and testosterone alone or combined with the specific blockers of ERα (MPP dihydrochloride), ERβ (PHTPP), PGR (mifepristone), and AR (bicalutamide) on cell cycle and apoptosis were also measured in the SW480 male and HT29 female CRC cell lines. ResultsERα and AR proteins increased, whilst ERβ and PGR declined markedly in malignant specimens. Moreover, male neoplastic tissues showed highest AR expression, whilst ERβ and PGR weakest alongside ERα strongest expression was seen in cancerous tissues from women aged ≥60 years. Late-stage neoplasms also revealed maximal alterations in the expression of sex steroid receptors. By tumor location, LSCs disclosed significant elevations in ERα with marked declines in PGR compared with RSCs, and ERα strongest alongside PGR weakest expression was detected in advanced LSCs from women aged ≥60 years. Late-stage LSCs from females aged ≥60 years also showed weakest ERβ and strongest AR expression. In contrast, male RSC and LSC tissues exhibited equal ERβ and AR expression in all clinical stages. ERα and AR proteins also correlated positively, whereas ERβ and PGR inversely, with tumor characteristics. Concomitantly, E2 and P4 monotherapies triggered cell cycle arrest and apoptosis in the SW480 and HT29 cells, and while pre-treatment with ERα-blocker enhanced the effects of E2, ERβ-blocker and PGR-blocker suppressed the E2 and P4 anti-cancer actions, respectively. In contrast, treatment with the AR-blocker induced apoptosis, whilst co-treatment with testosterone hindered the effects. ConclusionsThis study advocates that protein expression of sex steroid receptors in malignant tissues could represent prognostic markers, as well as hormonal therapy could provide an alternative strategy against CRC, and their efficacies could be dependent on gender, clinical stage, and tumor location

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Rapid Identification of Aphid Species by Headspace GC-MS and Discriminant Analysis

Aphids are a ubiquitous group of pests in agriculture that cause serious losses. For sustainable aphid identification, it is necessary to develop a precise and fast aphid identification tool. A new simple chemotaxonomy approach to rapidly identify aphids was implemented. The method was calibrated in comparison to the established phylogenetic analysis. For chemotaxonomic analysis, aphids were crushed, their headspace compounds were collected through closed-loop stripping (CLS) and analysed using gas chromatography—mass spectrometry (GC-MS). GC-MS data were then subjected to a discriminant analysis using CAP12.exe software, which identified key biomarkers that distinguish aphid species. A dichotomous key taking into account the presence and absence of a set of species-specific biomarkers was derived from the discriminant analysis which enabled rapid and reliable identification of aphid species. As the method overcomes the limits of morphological identification, it works with aphids at all life stages and in both genders. Thus, our method enables entomologists to assign aphids to growth stages and identify the life history of the investigated aphids, i.e., the food plant(s) they fed on. Our experiments clearly showed that the method could be used as a software to automatically identify aphids.publishe

Green Assessment of Chromatographic Methods Used for the Analysis of Four Methamphetamine Combinations with Commonly Abused Drugs

Numerous agents with anxiolytic or stimulant effects have the potential to be overused, and their misuse is associated with serious side effects. In Saudi Arabia, the estimated percentage of Saudis who abuse drugs is around 7–8% and the age range is 12–22 years. Methamphetamine, captagon, tramadol, heroin, and cannabis/cannabinoids have been proven to be the most commonly abused drugs in Saudi Arabia, with methamphetamine being at the top of the list. The present study focuses on the chromatographic analytical methods used for the analysis of methamphetamine in combination with commonly abused drugs, aiming to point out the greenest among them. These mixtures have been chosen as they are analyzed periodically and frequently in criminal evidence and forensic medicine. Therefore, the chances of hazards for analysts and the environment are high if the mixtures are not handled appropriately. This study aims to compare 23 chromatographic methods used for the analysis of methamphetamine mixtures in four major combinations, and to assess their greenness by using three greenness assessment tools, namely, NEMI, ESA and AGREE, to recommend the greenest analytical method. The NEMI results were proven to have low discriminating abilities and, accordingly, the comparisons are based on ESA and AGREE scores. The analysis results show that the safest methods with the most eco-friendly results (based on ESA and AGREE) are the GC-MS method proposed by Mohammed et al. to analyze methamphetamine and captagon mixtures (ESA = 79 and AGREE = 0.57), the UHPLC–MS-MS method proposed by Busardò et al. to analyze methamphetamine and cannabis/cannabinoid mixtures (ESA = 78 and AGREE = 0.57), the LC-MS method proposed by Herrin et al. to analyze methamphetamine and tramadol mixtures (ESA = 81 and AGREE = 0.56), and the LC-MS method proposed by Postigo-et al to analyze methamphetamine and heroin mixtures (ESA = 76 and AGREE = 0.58)

Green Assessment of Chromatographic Methods Used for the Analysis of Four Methamphetamine Combinations with Commonly Abused Drugs

Numerous agents with anxiolytic or stimulant effects have the potential to be overused, and their misuse is associated with serious side effects. In Saudi Arabia, the estimated percentage of Saudis who abuse drugs is around 7–8% and the age range is 12–22 years. Methamphetamine, captagon, tramadol, heroin, and cannabis/cannabinoids have been proven to be the most commonly abused drugs in Saudi Arabia, with methamphetamine being at the top of the list. The present study focuses on the chromatographic analytical methods used for the analysis of methamphetamine in combination with commonly abused drugs, aiming to point out the greenest among them. These mixtures have been chosen as they are analyzed periodically and frequently in criminal evidence and forensic medicine. Therefore, the chances of hazards for analysts and the environment are high if the mixtures are not handled appropriately. This study aims to compare 23 chromatographic methods used for the analysis of methamphetamine mixtures in four major combinations, and to assess their greenness by using three greenness assessment tools, namely, NEMI, ESA and AGREE, to recommend the greenest analytical method. The NEMI results were proven to have low discriminating abilities and, accordingly, the comparisons are based on ESA and AGREE scores. The analysis results show that the safest methods with the most eco-friendly results (based on ESA and AGREE) are the GC-MS method proposed by Mohammed et al. to analyze methamphetamine and captagon mixtures (ESA = 79 and AGREE = 0.57), the UHPLC–MS-MS method proposed by Busardò et al. to analyze methamphetamine and cannabis/cannabinoid mixtures (ESA = 78 and AGREE = 0.57), the LC-MS method proposed by Herrin et al. to analyze methamphetamine and tramadol mixtures (ESA = 81 and AGREE = 0.56), and the LC-MS method proposed by Postigo-et al to analyze methamphetamine and heroin mixtures (ESA = 76 and AGREE = 0.58)

Predicting the Consistency of Pituitary Macroadenomas: The Utility of Diffusion-Weighted Imaging and Apparent Diffusion Coefficient Measurements for Surgical Planning

Understanding the consistency of pituitary macroadenomas is crucial for neurosurgeons planning surgery. This retrospective study aimed to evaluate the utility of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) as non-invasive imaging modalities for predicting the consistency of pituitary macroadenomas. This could contribute to appropriate surgical planning and therefore reduce the likelihood of incomplete resections. The study included 45 patients with pathologically confirmed pituitary macroadenomas. Conventional MRI sequences, DWIs, ADC maps, and pre- and post-contrast MRIs were performed. Two neuroradiologists assessed all of the images. Neurosurgeons assessed the consistency of the tumor macroscopically, and histopathologists examined it microscopically. The MRI findings were compared with postoperative data. According to the operative data, macroadenomas were divided into the two following categories based on their consistency: aspirable (n = 27) and non-aspirable tumors (n = 18). A statistically significant difference in DWI findings was found when comparing macroadenomas of different consistencies (p −3 mm2/s, the ADC showed a sensitivity of 85.7% and a specificity of 75% for the detection of non-aspirable macroadenomas (AUC, 0.946). The study concluded that DWI should be routinely performed in conjunction with ADC measurements in the preoperative evaluation of pituitary macroadenomas. This approach may aid in surgical planning, ensure that appropriate techniques are utilized, and reduce the risk of incomplete resection

<i>Moringa oleifera</i> and <i>Azadirachta indica</i> Leaves Enriched Diets Mitigate Chronic Oxyfluorfen Toxicity Induced Immunosuppression through Disruption of Pro/Anti-Inflammatory Gene Pathways, Alteration of Antioxidant Gene Expression, and Histopathological Alteration in <i>Oreochromis niloticus</i>

Our goal in this study was to determine the effect of dietary supplementation with Moringa oleifera (M. oleifera), and Azadirachta indica (A. indica) leaves in mitigating the effects of chronic oxyfluorfen (OXY) toxicity on the health status, expressions of immune and antioxidant genes, and tissue morphological alterations in Oreochromis niloticus. In this study, we used 370 healthy O. niloticus (average weight = 25.35 ± 0.29 g). We used 70 fish to study the 96 h lethal concentration 50 (LC50) of OXY. We assigned another 300 fish into six equal groups with five replicates (50 fish/group, 10 fish/replicate) to determine the chronic OXY toxicity for 60 days. The 96 h LC50 of OXY for O. niloticus was 6.685 mg/L. Exposure to 1/10 96 h LC50 of OXY (0.668 mg/L) had health impacts and pathological changes in the main tissues. In addition, the expressions of oxidant and immune genes were disrupted. Dietary supplementation with both M. oleifera and A. indica efficiently mitigated the toxic effects of OXY in the treated groups. Comparing the palliative efficiency of M. oleifera and A. indica, the results showed that M. oleifera was more potent in alleviating the toxic effects of OXY