Marine mussels have attracted attention in the last years due to their incredible ability to stick to various organic and inorganic substrates in harsh environments. This capacity has been attributed ...to specific proteins secreted by marine mussels, known as marine mussel adhesive proteins (MAPs). These proteins have in their constitution an unusual amino acid, 3,4-dihydroxyphenylalanine (DOPA).
Many efforts have been made to produce materials with adhesive properties equivalent to those shown by MAPs for biomedical applications. Therefore, distinct polymeric biomaterials, either with two-dimensional or three-dimensional structures, have been developed trying to mimic this incredible adhesive performance.
In this review, an overview of the application of MAPs and their adhesive properties on the development of distinct biomaterials based on both natural and synthetic polymers will be presented, namely on films and hydrogels production. The variety of biomedical applications of these bioinspired materials will be also discussed.
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•The development of multifunctional biomaterials inspired by the marine mussel adhesive proteins is presented.•The diverse biomedical applications of bioinspired adhesive materials are analyzed.•Recent data on mechanical adhesion obtained are summarized.
Aims
Non‐alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in Western countries and a common comorbidity with type 2 diabetes (T2D). It lacks effective ...pharmacotherapy. We aimed to summarize the evidence on the effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on liver structure and function.
Materials and methods
Meta‐analysis of randomized clinical trials in PubMed, Web of Science and ClinicalTrials.gov from their inception to April 2019. Trials evaluating liver function and/or structure and comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs in patients with T2D were included. Twenty studies (from 3033) were included. A total of 1950 patients with T2D, with or without NAFLD, were treated with SGLT2 inhibitors for at least 8 weeks, and 1900 patients were used as controls. Independent extraction was carried out by two observers. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analysis.
Results
SGLT2 inhibitors induced a significant decrease in serum alanine (−7.43U/L, 95%CI −12.14, −2.71, p < 0.01), in aspartate aminotransferases (−2.83U/L, −4.71, −0.95, p < 0.01), as well as in gamma glutamyl transferase (−8.21U/L, −9.52, −6.91, p < 0.01), and an increase in total plasma bilirubin (8.19% 0.79, 15.59, p < 0.01), comparing with placebo or other oral antidiabetic drugs. SGLT2 inhibitors treatment was associated with a decrease in liver steatosis (−3.39% −6.01, −0.77, p < 0.0.1).
Conclusions
Treatment with SGLT2 inhibitors improves liver structure and function in patients with T2D. This meta‐analysis suggests that SGLT2 inhibitors are a promising pharmacological approach for treatment of NAFLD.
The Role of Thyroid Hormones in Heart Failure Vale, Catarina; Neves, João Sérgio; von Hafe, Madalena ...
Cardiovascular drugs and therapy,
04/2019, Letnik:
33, Številka:
2
Journal Article
Recenzirano
Cardiovascular diseases are the leading cause of death worldwide. Heart failure is the terminal manifestation of cardiovascular diseases, and its morbidity and mortality remain high. The prevalence ...of heart failure with preserved ejection fraction (HFpEF) among heart failure patients remains uncertain. However, recent studies have found that it ranged from 40 to 71%. There is still no effective treatment for HFpEF. Thyroid hormones (TH) have central regulatory actions in the cardiovascular system, particularly in the heart. Changes in plasmatic or tissue thyroid hormone levels are associated with significant alterations in cardiovascular function. A significant proportion of patients with heart failure presents some form of thyroid dysfunction including hypothyroidism, hyperthyroidism, and low T3 syndrome. Furthermore, thyroid hormones can vary at a local level independently of the serum TH levels. This may lead to local cardiac hypothyroidism in heart failure. Based on these findings and the role that TH play in cardiovascular regulation, they were proposed as a potential target for heart failure therapy. Several clinical and experimental studies have shown beneficial effects of TH supplementation. Data from epidemiological studies supports a higher risk of heart failure and a worse prognosis in heart failure patients with low levels of TH. In addition, animal studies and small clinical studies suggest that TH supplementation may improve cardiac function in heart failure. Although further studies are needed to evaluate the safety and efficacy of TH in this context, the available evidence suggests that TH modulation is a promising therapeutic approach to heart failure.
The adhesive capabilities of marine mussel proteins are well-known, exhibiting the ability to stick to different underwater substrates, either inorganic or organic. These unique adhesive properties ...are due to the high levels of amino acid, 3,4-dihydroxyphenyl-l-alanine (DOPA), which presents the reactive catechol group. Herein, novel antibacterial free-standing (FS) films were developed with natural polymers, namely chitosan (CHT) and hyaluronic acid (HA), being the catechol-functionalized hyaluronic acid (HA-DN) also included to provide wet adhesive properties. In order to obtain composite films, silver doped bioglass nanoparticles (Ag-BGs) were incorporated to promote bactericidal and bioactive properties, being tested four distinct formulations of FS films. Their surface morphology and topography, wettability, weight loss, swelling, mechanical, adhesion and bioactivity was analyzed. In particular, bioactivity tests revealed that upon immersion in simulated body fluid, there was the formation of a bone-like apatite layer. Moreover, upon 16 h in direct contact with Staphylococcus aureus and Escherichia coli cultures, these FS films exhibited a clear antibacterial effect. Therefore, such bioactive, antibacterial and adhesive free-standing films could potentially be used as temporary guided bone regeneration films, in particular to regenerate small bone defects and also periodontal tissues.
FS films containing Ag-BGs, upon immersion in simulated body fluid for 14 days, revealed the formation of a bone-like apatite layer. In addition, upon 16 h in direct contact with S. aureus and E. coli cultures, these FS films exhibited a clear inhibition zone of bacterial growth. Display omitted
Chitosan and hyaluronic acid are the most attractive natural polysaccharides used for tissue regeneration, herein innovative orthopedic coatings were constructed by dip-coating technique. Inspired by ...the tough nacre-like structure, multifunctional (MF) films were constructed using bioactive glass nanoparticles (BGNPs) as the inorganic phase and hyaluronic acid (HA) and chitosan (CHT) polymers as the organic phase. Polymeric (CTR) films were also built with both polysaccharides. Inspired by the marine mussel's adhesive proteins, it was the first time that multilayered coatings containing both HA and CHT catechol conjugates were combined with BGNPs. Both catechol-conjugates were successful synthesized and, particularly for HA, it was possible to achieve the double of the substitution degree varying the reaction time. Prior to the LbL build-up, viscosity and Zeta potential measurements of the polyelectrolytes were conducted. The in-situ LbL growth of the films was monitored by quartz crystal microbalance with dissipation monitoring. It was found that the combination of both catechol conjugates resulted in a more compact LbL structure. It was also shown that MF evidenced bioactivity, CTR presented an improved adhesion, and preliminary cellular tests confirmed the biomedical potential of these multilayered coatings being used in orthopedic implants.
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Reporta-se um caso clínico de sialoadenite esclerosante crónica focando aspetos clínicos, laboratoriais e histológicos, e realiza-se uma revisão da literatura com discussão da abordagem clínica ...multidisciplinar desta patologia. A sialoadenite esclerosante crónica é uma doença inflamatória crónica, incomum, que se integrou recentemente no espectro de doenças associadas à IgG4. Esta patologia simula patologia neoplásica cervical e o seu diagnóstico definitivo é difícil. A sua etiologia, tratamento e evolução são na atualidade temas de debate científico.
Thyroid hormones have a central role in cardiovascular homeostasis. In myocardium, these hormones stimulate both diastolic myocardial relaxation and systolic myocardial contraction, have a ...pro-angiogenic effect and an important role in extracellular matrix maintenance. Thyroid hormones modulate cardiac mitochondrial function. Dysfunction of thyroid axis impairs myocardial bioenergetic status. Both overt and subclinical hypothyroidism are associated with a higher incidence of coronary events and an increased risk of heart failure progression. Endothelial function is also impaired in hypothyroid state, with decreased nitric oxide-mediated vascular relaxation. In heart disease, particularly in ischemic heart disease, abnormalities in thyroid hormone levels are common and are an important factor to be considered. In fact, low thyroid hormone levels should be interpreted as a cardiovascular risk factor. Regarding ischemic heart disease, during the late post-myocardial infarction period, thyroid hormones modulate left ventricular structure, function and geometry. Dysfunction of thyroid axis might even be more prevalent in the referred condition since there is an upregulation of type 3 deiodinase in myocardium, producing a state of local cardiac hypothyroidism. In this focused review, we summarize the central pathophysiological and clinical links between altered thyroid function and ischemic heart disease. Finally, we highlight the potential benefits of thyroid hormone supplementation as a therapeutic target in ischemic heart disease.
Thyroid hormones are important modulators of cardiovascular function. Both hypothyroidism and hyperthyroidism are known to contribute to an increased cardiovascular risk. It remains uncertain whether ...thyroid hormones level within the euthyroid range are associated with cardiometabolic risk. We aimed to evaluate the association between thyroid function levels within the euthyroid range and cardiovascular risk in a population-based cohort.
Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto population-based cohort were included. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range, or with previous cardiovascular or thyroid disease. The associations between thyroid function, cardiovascular risk factors and the 10-year estimated risk of cardiovascular events (using SCORE2 and SCORE2-OP) were evaluated in linear and logistic regression models, crudely and adjusting for age, sex, BMI, diabetes, and smoking.
The mean age of the participants was 61.5 (SD 10.5) years and 38.9% were men. Eleven percent of the participants had diabetes, 47.8% had dyslipidemia, and 54.8% had hypertension. The mean body mass index (BMI) was 27.4 (SD 4.6) kg/m
, and the median (percentile25-75) 10-year risk of cardiovascular events was 5.46% (2.92, 10.11). Participants with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. Lower FT3/FT4 ratio and higher FT4 levels were associated with higher prevalence of diabetes and more adverse lipid profile. Higher TSH, lower FT3 and lower FT3/FT4 ratio were associated with lower eGFR. Lower FT3, lower FT3/FT4 ratio and higher FT4 were associated with an increased 10-year risk of cardiovascular events.
In a population-based study, variations of thyroid function within the euthyroid range were associated with cardiovascular risk factors. On one hand, individuals with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. On the other hand, a decreased conversion of T4 to T3 (lower FT3, lower FT3/FT4 ratio and/or higher FT4) was associated with a higher prevalence of diabetes, a more adverse lipid profile, a lower eGFR and an increased 10-year risk of cardiovascular events.
Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with high mortality for which there is no proven therapy to improve its prognosis. Thyroid dysfunction is common in heart ...failure (HF) and is associated with worse prognosis. In this review, we discuss the cardiovascular effects of thyroid hormones, the pathophysiology of HFpEF, the prognostic impact of thyroid function, and the potential of thyroid hormones for treatment of HFpEF. Thyroid hormones have a central role in cardiovascular homeostasis, improving cardiac function through genomic and non-genomic mechanisms. Both overt and subclinical hypothyroidism are associated with increased risk of HF. Even when plasmatic thyroid hormones levels are normal, patients with HF may have local cardiac hypothyroidism due to upregulation of type 3 iodothyronine deiodinase. Thyroid hormones improve several pathophysiological mechanisms of HFpEF, including diastolic dysfunction and extra-cardiac abnormalities. Supplementation with thyroid hormones (levothyroxine and/or liothyronine), modulation of deiodinase activity, and heart-specific thyroid receptor agonists are potential therapeutic approaches for the treatment of HFpEF. Further preclinical and clinical studies are needed to clarify the role of thyroid hormones in the treatment of HFpEF.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD often occurs associated with endocrinopathies. Evidence suggests that endocrine dysfunction may play an ...important role in NAFLD development, progression, and severity. Our work aimed to explore and summarize the crosstalk between the liver and different endocrine organs, their hormones, and dysfunctions. For instance, our results show that hyperprolactinemia, hypercortisolemia, and polycystic ovary syndrome seem to worsen NAFLD's pathway. Hypothyroidism and low growth hormone levels also may contribute to NAFLD's progression, and a bidirectional association between hypercortisolism and hypogonadism and the NAFLD pathway looks likely, given the current evidence. Therefore, we concluded that it appears likely that there is a link between several endocrine disorders and NAFLD other than the typically known type 2 diabetes mellitus and metabolic syndrome (MS). Nevertheless, there is controversial and insufficient evidence in this area of knowledge.
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