Article
Biology
Tomoaki Tatsumi, Toshiyuki Oshitari, Yoko Takatsuna, Ryoichi Ishibashi, Masaya Koshizaka, Yuki Shiko, Takayuki Baba, Koutaro Yokote, Shuichi Yamamoto
Summary: This study found that systemic SGLT2i can reduce DMEs, suggesting that SGLT2i may be an additional treatment option to anti-VEGF treatments for eyes with DMEs.
Article
Biochemistry & Molecular Biology
Cheng-Yang Hsieh, Sheng-Feng Sung
Summary: Chronic kidney disease (CKD) is a significant risk factor for stroke and cerebrovascular disease, yet the interaction between the brain and kidneys has received less attention compared to the interaction between the heart and kidneys. This article focuses on the potential of SGLT2 inhibitors, a class of oral anti-diabetic drugs, in preventing strokes and improving the cerebro-renal interaction, regardless of diabetes status. The authors propose the roles of baseline renal functions and dual inhibition of SGLT1/2 in stroke prevention, as well as the additional benefits of reducing atrial fibrillation and hemorrhagic stroke.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Weronika Frak, Joanna Hajdys, Ewa Radzioch, Magdalena Szlagor, Ewelina Mlynarska, Jacek Rysz, Beata Franczyk
Summary: Cardiovascular diseases (CVD) are a major global health concern, and sodium/glucose cotransporter 2 (SGLT2) inhibitors have emerged as a promising class of medications for managing CVD. In this paper, we discuss the role of various SGLT-2 inhibitors as potential therapeutic targets for cardiovascular diseases, highlighting their significant cardiovascular benefits and renal protection. These novel therapeutic approaches aim to improve patient outcomes and reduce the burden of these conditions, but further studies are needed to explore the scientific advancements and mechanisms.
Review
Pharmacology & Pharmacy
Lei Tian, Sinan Ai, Huijuan Zheng, Hanwen Yang, Mengqi Zhou, Jingyi Tang, Weijing Liu, Wenjing Zhao, Yaoxian Wang
Summary: SGLT2 inhibitors have beneficial effects on cardiovascular and renal outcomes in patients with T2DM, reducing all-cause mortality, cardiovascular mortality, hospitalization for heart failure, and renal composite outcomes. Among them, Canagliflozin, Empagliflozin, and Dapagliflozin showed better efficacy in reducing different outcomes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Seung Eun Lee, Hyewon Nam, Han Seok Choi, Hoseob Kim, Dae-Sung Kyoung, Kyoung-Ah Kim
Summary: Comparison between SGLT-2i and TZD in T2DM patients showed comparable risk of stroke, but a significant decrease in hospitalization for heart failure in the SGLT-2i-treated group.
DIABETES & METABOLISM JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Kim A. Connelly, C. David Mazer, Pankaj Puar, Hwee Teoh, Chao-Hung Wang, Tamique Mason, Farhad Akhavein, Ching-Wen Chang, Min-Hui Liu, Ning- Yang, Wei-Siang Chen, Yu-Hsiang Juan, Erika Opingari, Yaseen Salyani, William Barbour, Aryan Pasricha, Shamon Ahmed, Andrew Kosmopoulos, Raj Verma, Michael Moroney, Ehab Bakbak, Aishwarya Krishnaraj, Deepak L. Bhatt, Javed Butler, Mikhail N. Kosiborod, Carolyn S. P. Lam, David A. Hess, Otavio Rizzi Coelho-Filho, Myriam Lafreniere-Roula, Kevin E. Thorpe, Adrian Quan, Lawrence A. Leiter, Andrew T. Yan, Subodh Verma
Summary: This study aimed to evaluate the effect of sodium-glucose cotransporter 2 inhibition with empagliflozin on left ventricular mass in individuals without diabetes or significant heart failure. The results showed that after 6 months of treatment with empagliflozin, there was no significant reduction in left ventricular mass index. The findings suggest that empagliflozin may not have meaningful benefits on cardiac remodeling in this population.
Article
Medicine, General & Internal
Daria M. Keller, Natasha Ahmed, Hamza Tariq, Malsha Walgamage, Thilini Walgamage, Azad Mohammed, Jadzia Tin-Tsen Chou, Marta Kaluzna-Oleksy, Maciej Lesiak, Ewa Straburzynska-Migaj
Summary: SGLT2 inhibitors not only show excellent performance in improving glycemic control, but also have a positive impact on cardiovascular and renal outcomes. New guidelines recommend SGLT2 inhibitors as first-line treatment for heart failure patients, bringing new hope for the treatment of heart failure patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Maria Rosaria Rizzo, Irene Di Meo, Rita Polito, Maria Chiara Auriemma, Antonio Gambardella, Gabriella di Mauro, Annalisa Capuano, Giuseppe Paolisso
Summary: Gliflozins are a novel class of oral anti-diabetic drugs that inhibit sodium-glucose co-transporters and have potential effects on cognitive dysfunction in Type 2 Diabetes mellitus patients. Further research is needed to fully understand their impact on cognitive decline.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Muthiah Vaduganathan, Silvio E. Inzucchi, Naveed Sattar, David H. Fitchett, Anne Pernille Ofstad, Martina Brueckmann, Jyothis T. George, Subodh Verma, Michaela Mattheus, Christoph Wanner, Bernard Zinman, Javed Butler
Summary: Empagliflozin delays insulin initiation and reduces the need for substantial increases in insulin dose in patients with type 2 diabetes and cardiovascular disease, while also facilitating sustained reductions in insulin requirements over time.
DIABETES OBESITY & METABOLISM
(2021)
Letter
Cardiac & Cardiovascular Systems
Bo Liang, Ning Gu
Summary: The 2022 AHA/ACC/HFSA guideline for heart failure management recommends the use of sodium-glucose co-transporter-2 inhibitors in patients with heart failure and type 2 diabetes to manage hyperglycemia and reduce heart failure-related morbidity and mortality. However, it should be noted that this recommendation is based on specific trials and does not include recently published studies.
CARDIOVASCULAR DIABETOLOGY
(2022)
Review
Endocrinology & Metabolism
Xindong Liu, Ying Chen, Tao Liu, Ling Cai, Xiaofeng Yang, Chuan Mou
Summary: This study systematically evaluated the effect of SGLT2 inhibitors on adipose tissue in patients with type 2 diabetes. Meta-analysis results showed that the use of these inhibitors significantly reduced visceral adipose tissue, subcutaneous adipose tissue, body weight, and triglycerides in type 2 diabetes patients, which may be attributed to their protective effect on the cardiovascular system.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Louise E. Bechmann, Frida Emanuelsson, Borge G. Nordestgaard, Marianne Benn
Summary: A functional genetic variant in SLC5A2, mimicking SGLT2-inhibition, was associated with a lower risk of heart failure, myocardial infarction, ischaemic heart disease, and all-cause mortality. However, the effects were minimally mediated through lower plasma glucose.
CARDIOVASCULAR RESEARCH
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Barbara Katharina Geist, Helmut Brath, Lucia Zisser, Josef Yu, Barbara Fueger, Lukas Nics, Eva Maria Patronas, Alexandra Kautzky-Willer, Marcus Hacker, Sazan Rasul
Summary: This study investigated the affinity of alpha-methyl-4-deoxy-4-[F-18]fluoro-d-glucopyranoside (Me4FDG) for SGLT1 and SGLT2 proteins, and its role in predicting response to SGLT2 inhibitors in patients with type 2 diabetes. The results showed that Me4FDG excretion is a reliable predictor of the therapeutic effectiveness of SGLT2 inhibitors.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Cardiac & Cardiovascular Systems
Milton Packer, Javed Butler, Faiez Zannad, Gerasimos Filippatos, Joao Pedro Ferreira, Stuart J. Pocock, Peter Carson, Inder Anand, Wolfram Doehner, Markus Haass, Michel Komajda, Alan Miller, Steen Pehrson, John R. Teerlink, Sven Schnaidt, Cordula Zeller, Janet M. Schnee, Stefan D. Anker
Summary: Empagliflozin significantly reduced the risk of heart failure-related inpatient and outpatient events in patients with heart failure with preserved ejection fraction, including cardiovascular death, heart failure hospitalization, and urgent visits, while also decreasing total heart failure hospitalizations and intensive care admissions. Patients receiving empagliflozin may experience improved New York Heart Association functional class levels.
Article
Pharmacology & Pharmacy
Mayada M. Samkari, Neda'a S. Bokhari, Raghad Alhajaji, Malaz E. Ahmed, Ahmad Al Raddadi, Alaa K. Bahget, Sarah F. Saleh, Faisal Aljehani, Saud H. Alzahrani, Sarah S. Alsifyani, May M. Samkari, Aisha F. Badr, Mai Alalawi, Khalid Al Sulaiman
Summary: This study aims to assess the safety and tolerability of Empagliflozin in Muslim patients with type 2 diabetes during Ramadan. The results show that patients who received Empagliflozin had a lower risk of hypoglycemia symptoms and higher tolerability during Ramadan.
SAUDI PHARMACEUTICAL JOURNAL
(2023)
Article
Chemistry, Physical
Naeem Asad, Davide Deodato, Sangram Gore, Timothy M. Dore
Summary: By functionalizing four derivatives, the release of tertiary amines via two-photon excitation (2PE) was studied. These derivatives exhibited good properties in biological settings and an optimized photoremovable protecting group (PPG) mediated the efficient photoactivation of various biological effectors.
Article
Chemistry, Medicinal
Rita Goncalves-Pereira, Jose A. Figueiredo, Susana D. Lucas, Maria I. Garcia-Moreno, Carmen O. Mellet, Amelia P. Rauter, Maria I. Ismael
Summary: Alzheimer's disease is a multifactorial syndrome that causes memory loss, dementia, and eventually death. Acetylcholinesterase inhibitors are the main drugs used for symptomatic treatment of the disease. This study reports a new synthetic route for producing sugar amides that act as acetylcholinesterase inhibitors.
MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Rajani Ravishankar, Emily R. Hildebrandt, Grace Greenway, Nadeem Asad, Sangram Gore, Timothy M. Dore, Walter K. Schmidt
Summary: CAAX proteins undergo various posttranslational modifications, and this study used a proteolysis-resistant CAAX sequence to investigate Saccharomyces cerevisiae Ras2 GTPase. The results showed that the type of CAAX motif affected Ras2 protein levels, localization, and function.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Ignazio Schino, Mariangela Cantore, Modesto de Candia, Cosimo D. Altomare, Catarina Maria, Joao Barros, Vasco Cachatra, Patricia Calado, Karina Shimizu, Adilson A. Freitas, Maria C. Oliveira, Maria J. Ferreira, Jose N. C. Lopes, Nicola A. Colabufo, Amelia P. Rauter
Summary: Alzheimer's Disease (AD) is characterized by an imbalance in cholinergic neurotransmission, and the inhibition of acetylcholinesterase (AChE) and increase of butyrylcholinesterase (BChE) activity. Novel 6-benzamide purine nucleosides that selectively target BChE and possess chelating properties were synthesized. These compounds show potential as dual target compounds for the treatment of AD.
Article
Biochemistry & Molecular Biology
Antonio Barreira, Andreia F. M. Santos, Madalena Dionisio, Ana R. Jesus, Ana Rita C. Duarte, Zeljko Petrovski, Ana B. Paninho, Marcia G. Ventura, Luis C. Branco
Summary: In this study, ionic liquids were synthesized to improve the solubility of levothyroxine (T4), and [C(2)OHMiM][T4] was found to be a promising alternative with good bioavailability and no significant cytotoxicity observed against cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Nuno F. B. Oliveira, Filipe E. P. Rodrigues, Joao N. M. Vitorino, Patricia F. N. Faisca, Miguel Machuqueiro
Summary: Protein aggregation is a complex process influenced by environmental conditions and structurally heterogeneous. It is important to understand the role of certain properties of the dimer in self-association. A simple model and computational method were used to investigate the effect of modulations in the dimer's interfacial region on its growth mode.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Maria Joao Alvaro-Martins, Violeta Railean, Filomena Martins, Miguel Machuqueiro, Rita Pacheco, Susana Santos
Summary: Cancer is a major cause of death worldwide and melanoma and breast cancer are two aggressive types of cancer that require urgent treatment options. In this study, new thiobenzanilide derivatives were synthesized and evaluated for their cytotoxic potential against melanoma and breast cancer cells. The results showed promising compounds that could be further developed as anticancer agents.
Article
Forestry
Luciana Silva, Sofia Oriskova, Diogo Goncalves, Ivo Paulo, Jose Condeco, Miguel Monteiro, Nuno M. Xavier, Amelia P. Rauter, Joao M. Bordado, Rui Galhano dos Santos
Summary: Eucalyptus globulus sawdust, a residue from the pulp and paper industry, can be recycled through thermochemical liquefaction to produce bio-oil. The aqueous extract of the bio-oil contains carbohydrates, particularly fructose and glucose, which can be used in the industry to produce sustainable materials. The sugar composition of the aqueous extract was identified and quantified using analytical techniques such as HPLC, HSQC-NMR, FTIR-ATR, and elemental analysis.
Review
Chemistry, Multidisciplinary
Elisabete Lima, Amelia P. Rauter, Jorge Medeiros
Summary: The development of multitarget-directed ligands (MTDLs) is urgently needed to combat the multifactorial Alzheimer's disease (AD). Flavonoids from natural sources have shown activity on mechanisms associated with AD and have potential as anti-AD agents. The most active flavonoids against several clinical indications (CIs) of AD are flavanols and flavonols, which have specific structural features.
APPLIED SCIENCES-BASEL
(2023)
Article
Pharmacology & Pharmacy
Celia Sarmento, Hugo Monteiro, Alexandre Paiva, Ana Rita C. Duarte, Ana Rita Jesus
Summary: The goal of this study was to explore the potential of natural deep eutectic systems (NADES) as new media for ocular drug formulations. Different NADES compositions were prepared and characterized for their rheological and physicochemical properties. The results showed that 5-10% (w/v) aqueous solutions of NADES had suitable viscosity, osmolarity, and pH for ocular drug incorporation. By using NADES, the solubility of a highly insoluble drug, acetazolamide, was significantly increased, making it more suitable for ocular drug formulation. Cytotoxicity assays demonstrated that NADES were biocompatible and did not affect cell viability when dissolved in aqueous solutions.
Article
Chemistry, Multidisciplinary
Pedro M. S. Suzano, Ines D. S. Pires, Tomas F. D. Silva, Nuno F. B. Oliveira, Pedro B. P. S. Reis, Miguel Machuqueiro
Summary: In molecular dynamics simulations of membrane systems, evaluating the interactions between membrane bilayers and other molecules is crucial. Understanding and characterizing local deformations caused by these interactions is essential, as they can affect membrane property calculations.
JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Catarina Maria, Amelia P. Rauter
Summary: Nucleosides have attracted attention since the discovery of DNA structure. Nucleoside analogues can be synthesized through multiple pathways, with N-glycosylation of a nucleobase being the most common method. This review focuses on the synthesis and therapeutic applications of FDA approved nucleoside analogues as antiviral and anticancer agents, as well as their potential as antibacterial and anti-Alzheimer's disease agents.
CARBOHYDRATE RESEARCH
(2023)
Article
Chemistry, Medicinal
Tomaas F. D. Silva, Hannah Visca, Craig Klumpp, Oleg A. Andreev, Yana K. Reshetnyak, Miguel Machuqueiro
Summary: Most processes at the water-membrane interface involve protonation events in proteins or peptides, which trigger important biological functions. The pHLIP peptide technology works by protonating a key aspartate residue, which induces membrane insertion and increases thermodynamic stability. In this study, the microenvironment of the aspartate residue was modulated by a point mutation of an arginine residue, altering the stability and kinetics of peptide insertion and exit from the membrane. This finding has implications for the pH response of pHLIP peptides in clinical applications.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Ricardo G. Teixeira, Iris C. Salaroglio, Nuno F. B. Oliveira, Joao G. N. Sequeira, Xavier Fontrodona, Isabel Romero, Miguel Machuqueiro, Ana Isabel Tomaz, M. Helena Garcia, Chiara Riganti, Andreia Valente
Summary: The urgent need to find more effective and selective drugs to overcome cancer multidrug resistance has led to the development and characterization of a new series of ruthenium-cyclopentadienyl (RuCp) compounds. These compounds were found to exhibit better cytotoxicity than the first-line chemotherapeutic drug cisplatin in non-small cell lung cancer cells. Furthermore, two specific compounds were shown to inhibit the activity of P-gp and MRP1 efflux pumps, providing potential candidates to circumvent cancer multidrug resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Beatriz Bueschbell, Pedro R. Magalhaes, Carlos A. V. Barreto, Rita Melo, Anke C. Schiedel, Miguel Machuqueiro, Irina S. Moreira
Summary: In this study, a computational framework was developed to generate models of GPCR dimers and identify their likely interfaces. Using the dopamine receptor D2 (D2R) homodimer as a case study, the study found that specific transmembrane domains are important at the dimer interface and provide insights into the conformational status of the receptor.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)