Site-selective installation of BASHY fluorescent dyes to Annexin V for targeted detection of apoptotic cells

Fluorophores are indispensable for imaging biological processes. We report the design and synthesis of azide-tagged boronic acid salicylidenehydrazone (BASHY) dyes and their use for site-selective labelling of Annexin V. The Annexin V-BASHY conjugate maintained function and fluorescence as demonstrated by the targeted detection of apoptotic cells.We thank FCT Portugal (Doctoral Fellowship, SFRH/BD/94779/2013 to F. M. F. S., Postdoctoral Fellowship, SFRH/BPD/103172/2014 to P. M. S. D. C.; projects PTDC/QUI-QUI/118315/2010 and PTDC/BBB BQB/0506/2012; PTDC/QEQ-QOR/1434/2014: PTDC/SAUFAR/119389/2010; FCT Investigator to G. J. L. B. and P. M. P. G.; iMed.ULisboa grant UID/DTP/04138/2013), EU (Marie-Curie CIG to G. J. L. B.; Marie-Sklodowska Curie ITN ProteinConjugates to G. J. L. B. and P. M. P. G.), DFG (SI 2117/1-1 to F. S.), CNPq Brazil (fellowship 200456/2015-6 to J. B. B.); Ministerio de Economía y Competitividad, Madrid, Spain (grant CTQ2014-54729-C2-1-P), Junta de Andalucía (grant P12-FQM-2140) and the EPSRC (G. J. L. B.) for financial support. G. J. L. B. is a Royal Society University Research Fellow and the recipient of a European Research Council Starting Grant (TagIt)

Photoluminescence and electrical study of fluctuating potentials in Cu2ZnSnS4-based thin films

status: publishe

Site-selective installation of BASHY fluorescent dyes to Annexin V for targeted detection of apoptotic cells

Fluorophores are indispensable for imaging biological processes. We report the design and synthesis of azide-tagged boronic acid salicylidenehydrazone (BASHY) dyes and their use for site-selective labelling of Annexin V. The Annexin V-BASHY conjugate maintained function and fluorescence as demonstrated by the targeted detection of apoptotic cells

Larvicidal activity of the water extract of Moringa oleifera seeds against Aedes aegypti and its toxicity upon laboratory animals

In this work, biological effects of the water extract of Moringa oleifera seeds (WEMOS) were assessed on eggs and 3rd instar larvae of Aedes aegypti and on its toxicity upon laboratory animals (Daphnia magna, mice and rats). Crude WEMOS showed a LC50 value of 1260µg/mL, causing 99.2 ± 2.9% larvae mortality within 24 h at 5200µg/mL, though this larvicidal activity has been lost completely at 80ºC/10 min. WEMOS did not demonstrate capacity to prevent egg hatching. After extensive dialyses of the crude WEMOS into watersoluble dialyzable (DF) and nondyalizable (NDF) fractions, only DF maintained its efficacy to kill larvae. Acute toxicity evaluations on daphnids (EC50 of 188.7µg/mL) and mice (LD50 of 446.5 mg/kg body weight) pointed out to low toxicity. Despite the thymus hypertrophy, WEMOS revealed to be harmless in orally and subacutelytreated rats. In conclusion, WEMOS has thermostable bioactive compounds against Ae. aegypti larvae with apparent molecular mass lower than 12 kDa and moderately toxic potential.<br>Neste trabalho, o extrato aquoso das sementes de Moringaoleifera (EASMO) foi avaliado quanto aos seus efeitos biológicos sobre ovos e larvas de Aedes aegypti no 3ºestágio de desenvolvimento e sua toxicidade sobre animais de laboratório(Daphnia magna, camundongos e ratos). O EASMO bruto revelou uma CL50 de 1.260 µg/mL, causando 99, 2 ± 2, 9% de mortalidade em 24 h na concentração de 5.200 µg/mL, embora o mesmo não tenha sido capaz de impedir a eclosão dos ovos. A atividade larvicida extinguiu-se após aquecimento do extrato a 80ºC/10 min. Diálises sucessivas do EASMO bruto resultaram em duas frações solúveis em água (Fração dializável, FD; Fração nãodializável, FND), dentre as quais apenas a FD mostrou ação larvicida. Testes de toxicidade aguda realizadosem dáfnias (CE50 de 188, 7 µg/mL) e camundongos (DL50 de446,5 mg/kg de peso corpóreo) evidenciaram baixa toxicidade. Apesar da hipertrofia tímica, o EASMO mostrou ser atóxicoapós tratamento subagudo via oral em ratos. Conclui-se, portanto, que o EASMO apresenta substâncias com capacida de larvicida contra Ae. aegypti, as quais possuem massa molecular aparente menor que 12 kDa e potencial tóxico moderado

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus

Background: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. Methods: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction ( 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.This article publication was funded by Sociedade Brasileira de Diabetes (SBD)