Human Drug Pollution in the Aquatic System: The Biochemical Responses of Danio rerio Adults

To date, drug pollution in aquatic systems is an urgent issue, and Danio rerio is a model organism to study the toxicological effects of environmental pollutants. The scientific literature has analyzed the effect of human drug pollution on the biochemical responses in the tissues of D. rerio adults. However, the information is still scarce and conflicting, making it difficult to understand its real impact. The scientific studies are not consistent with each other and, until now, no one has grouped their results to create a baseline of knowledge of the possible impacts. In this review, the analysis of literature data highlights that the effects of drugs on adult zebrafishes depend on various factors, such as the tissue analyzed, the drug concentration and the sex of the individuals. Furthermore, the most influenced biochemical responses concern enzymes (e.g., antioxidants and hydrolase enzymes) and total protein and hormonal levels. Pinpointing the situation to date would improve the understanding of the chronic effects of human drug pollution, helping both to reduce it in the aquatic systems and then to draw up regulations to control this type of pollution

Cytotoxic Potential of the Coelomic Fluid Extracted from the Sea Cucumber Holothuria tubulosa against Triple-Negative MDA-MB231 Breast Cancer Cells

Growing evidence has demonstrated that the extracts of dierent holothurian species exert beneficial effects on human health. Triple negative breast cancers (TNBC) are highly malignant tumors that present a poor prognosis due to the lack of effective targeted therapies. In the attempt to identify novel compounds that might counteract TNBC cell growth, we studied the effect of the exposure of the TNBC cell line MDA-MB231 to total and filtered aqueous extracts of the coelomic fluid obtained from the sea cucumber Holoturia tubulosa, a widespread species in the Mediterranean Sea. In particular, we examined cell viability and proliferative behaviour, cell cycle distribution, apoptosis, autophagy, and mitochondrial metabolic/cell redox state. The results obtained indicate that both total and fractionated extracts are potent inhibitors of TNBC cell viability and growth, acting through both an impairment of cell cycle progression and mitochondrial transmembrane potential and a stimulation of cellular autophagy, as demonstrated by the increase of the acidic vesicular organelles and of the intracellular protein markers beclin-1, and total LC3 and LC3-II upon early exposure to the preparations. Identification of the water-soluble bioactive component(s) present in the extract merit further investigation aiming to develop novel prevention and/or treatment agents efficacious against highly metastatic breast carcinoma

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy

Obesity is associated with\ua0non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with\ua0chronic liver disease\ua0of different aetiologies (eg\ua0HCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery

Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy

Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative diabetic retinopathy, the latter characterized by retinal abnormal angiogenesis. Pharmacological management of retinal angiogenesis employs expensive and invasive intravitreal injections of biologic drugs (anti-vascular endothelial growth factor agents). To search small molecules able to act as anti-angiogenic agents, we focused our study on axitinib, which is a tyrosine kinase inhibitor and represents the second line treatment for renal cell carcinoma. Axitinib is an inhibitor of vascular endothelial growth factor receptors, and among the others tyrosine kinase inhibitors (sunitinib and sorafenib) is the most selective towards vascular endothelial growth factor receptors 1 and 2. Besides the well-known anti-angiogenic and immune-modulatory functions, we hereby explored the polypharmacological profile of axitinib, through a bioinformatic/molecular modeling approach and in vitro models of diabetic retinopathy. We showed the anti-angiogenic activity of axitinib in two different in vitro models of diabetic retinopathy, by challenging retinal endothelial cells with high glucose concentration (fluctuating and non-fluctuating). We found that axitinib, along with inhibition of vascular endothelial growth factor receptors 1 (1.82 ± 0.10; 0.54 ± 0.13, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively) and vascular endothelial growth factor receptors 2 (2.38 ± 0.21; 0.98 ± 0.20, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively), was able to significantly reduce (p < 0.05) the expression of Nrf2 (1.43 ± 0.04; 0.85 ± 0.01, protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively) in retinal endothelial cells exposed to high glucose, through predicted Keap1 interaction and activation of melanocortin receptor 1. Furthermore, axitinib treatment significantly (p < 0.05) decreased reactive oxygen species production (0.90 ± 0.10; 0.44 ± 0.06, fluorescence units in high glucose vs. axitinib 1 µM, respectively) and inhibited ERK pathway (1.64 ± 0.09; 0.73 ± 0.06, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively) in HRECs exposed to high glucose. The obtained results about the emerging polypharmacological profile support the hypothesis that axitinib could be a valid candidate to handle diabetic retinopathy, with ancillary mechanisms of action

A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement. Materials and methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota. Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m2, HbA1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P<0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P<0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales_uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA1c, triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40_7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients. Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature

Retinal Protection and Distribution of Curcumin in Vitro and in Vivo

Diabetic retinopathy (DR), a secondary complication of diabetes, is a leading cause of irreversible blindness accounting for 5% of world blindness cases in working age. Oxidative stress and inflammation are considered causes of DR. Curcumin, a product with anti-oxidant and anti-inflammatory properties, is currently proposed as oral supplementation therapy for retinal degenerative diseases, including DR. In this study we predicted the pharmacodynamic profile of curcumin through an in silico approach. Furthermore, we tested the anti-oxidant and anti-inflammatory activity of curcumin on human retinal pigmented epithelial cells exposed to oxidative stress, human retinal endothelial and human retinal pericytes (HRPCs) cultured with high glucose. Because currently marketed curcumin nutraceutical products have not been so far evaluated for their ocular bioavailability; we assessed retinal distribution of curcumin, following oral administration, in rabbit eye. Curcumin (10 μM) decreased significantly (p &lt; 0.01) ROS concentration and TNF-α release in retinal pigmented epithelial cells and retinal endothelial cells, respectively. The same curcumin concentration significantly (p &lt; 0.01) protected retinal pericytes from high glucose damage as assessed by cell viability and LDH release. Among the tested formulations, only that containing a hydrophilic carrier provided therapeutic levels of curcumin in rabbit retina. In conclusion, our data suggest that curcumin, when properly formulated, may be of value in clinical practice to manage retinal diseases

Compound drivers behind new record high temperatures and surface melt at the Antarctic Peninsula in February 2022

The Antarctic Peninsula (AP) experienced a new extreme warm event and record high surface melt inFebruary 2022, rivaling the recent temperature records from 2015 and 2020, and contributing to analarming series of extreme warm events there. The northern/northwestern AP was directly impactedby an intense atmospheric river (AR) bringing anomalous heat and rainfall, while AR-enhanced foehneffect further warmed its northeastern side. The event was triggered by multiple large-scaleatmospheric circulation patterns linking the AR formation to tropical convection anomalies andstationary Rossby waves, with anomalous Amundsen Sea low and record-breaking blocking high. Thecascade of impacts culminated in widespread and intensive surface melt across the AP. The event wasstatistically attributed to global warming. Increasing frequency of such events can undermine thestability of the AP ice shelves, with multiple local to global impacts, including acceleration of the APice mass loss and changes in sensitive ecosystems.Fil: Gorodetskaya, Irina. Universidad de Porto; PortugalFil: Durán Alarcón, Claudio. Universidade de Aveiro. Centro de Estudos Do Ambiente E Do Mar.; PortugalFil: Gonzalez Herrero, Sergi. Universidade de Aveiro. Centro de Estudos Do Ambiente E Do Mar.; PortugalFil: Clem, Kyle. Universidad de Porto. Facultad de Ciências. Centro Interdisciplinar de Investigação Marinha E Ambiental.; PortugalFil: Rodriguez Imazio, Paola Carolina. Ministerio de Defensa. Secretaria de Planeamiento. Servicio Meteorológico Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santos, Christophe Leroy Dos. European Southern Observatory Chile.; ChileFil: Campos, Diego Rodrigo. European Southern Observatory Chile.; ChileFil: Zou, Xun. Universidad Mayor de San Andrés; BoliviaFil: Dutrievoz, Niels. Universidad Nacional San Antonio Abad del Cusco; PerúFil: Rowe, Penny. Washington State University. School Of Earth & Environmental Sciences; Estados UnidosFil: Wille, Jonathan. Universidad Mayor de San Andrés; BoliviaFil: Favier, Vincent. Laboratoire D´ Oceanographie Et Climat, Experimentation Et Approches Numerique ; Institut Pierre Simon la Place ; Campus Pierre Et Marie Curie ; Sorbonne University;Fil: Blanchet, Juliette. Universite Grenoble Alpes.; FranciaFil: Chyhareva, Anastasiia. Universidad de Santiago de Chile. Instituto de Estudios de Posgrado E Investigación.; ChileFil: Cordero, Raul. Universidad de Santiago de Chile. Facultad de Ciencias; ChileFil: Park, Sang Jong. Korea Polar Research Institute; Corea del SurFil: Colwell, Steve. British Antartic Survey; Reino UnidoFil: Lazzara, Matthew. University of Wisconsin; Estados UnidosFil: Carrasco, Jorge. Universidad de Magallanes; ChileFil: Gulisano, Adriana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentina. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Krakovska, Svitlana. Universidad de Santiago de Chile. Facultad de Ciencias; ChileFil: Ralph, F. Martin. University of Washington; Estados UnidosFil: Pohl, Benjamin. Universidad Industrial Santander; Colombi

Winter Targeted Observing Periods during the Year of Polar Prediction in the Southern Hemisphere (YOPP-SH)

The Year of Polar Prediction in the Southern Hemisphere (YOPP-SH) held seven targeted observing periods (TOPs) during the 2022 austral winter to enhance atmospheric predictability over the Southern Ocean and Antarctica. The TOPs of 5–10-day duration each featured the release of additional radiosonde balloons, more than doubling the routine sounding program at the 24 participating stations run by 14 nations, together with process-oriented observations at selected sites. These extra sounding data are evaluated for their impact on forecast skill via data denial experiments with the goal of refining the observing system to improve numerical weather prediction for winter conditions. Extensive observations focusing on clouds and precipitation primarily during atmospheric river (AR) events are being applied to refine model microphysical parameterizations for the ubiquitous mixed-phase clouds that frequently impact coastal Antarctica. Process studies are being facilitated by high-time-resolution series of observations and forecast model output via the YOPP Model Intercomparison and Improvement Project (YOPPsiteMIIP). Parallel investigations are broadening the scope and impact of the YOPP-SH winter TOPs. Studies of the Antarctic tourist industry’s use of weather services show the scope for much greater awareness of the availability of forecast products and the skill they exhibit. The Sea Ice Prediction Network South (SIPN South) analysis of predictions of the sea ice growth period reveals that the forecast skill is superior to the sea ice retreat phase