Advanced Hydrogels for the Controlled Delivery of Insulin

Insulin is a peptide hormone that is key to regulating physiological glucose levels. Its molecular size and susceptibility to conformational change under physiological pH make it challenging to orally administer insulin in diabetes. The most effective route for insulin delivery remains daily injection. Unfortunately, this results in poor patient compliance and increasing the risk of micro- and macro-vascular complications and thus rising morbidity and mortality rates in diabetics. The use of 3D hydrogels has been used with much interest for various biomedical applications. Hydrogels can mimic the extracellular matrix (ECM) and retain large quantities of water with tunable properties, which renders them suitable for administering a wide range of sensitive therapeutics. Several studies have demonstrated the fixation of insulin within the structural mesh of hydrogels as a bio-scaffold for the controlled delivery of insulin. This review provides a concise incursion into recent developments for the safe and effective controlled delivery of insulin using advanced hydrogel platforms with a special focus on sustained release injectable formulations. Various hydrogel platforms in terms of their methods of synthesis, properties, and unique features such as stimuli responsiveness for the treatment of Type 1 diabetes mellitus are critically appraised. Key criteria for classifying hydrogels are also outlined together with future trends in the field.

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Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases

Current Medicinal Chemistry ◽

10.2174/0929867324666171023163752 ◽

2019 ◽

Vol 26 (23) ◽

pp. 4323-4354 ◽

Cited By ~ 9

Author(s):

Ana Cristina Lima Leite ◽

José Wanderlan Pontes Espíndola ◽

Marcos Veríssimo de Oliveira Cardoso ◽

Gevanio Bezerra de Oliveira Filho

Keyword(s):

Biologically Active ◽

Neglected Diseases ◽

Financial Return ◽

Drug Candidates ◽

Lead Compounds ◽

Wide Range ◽

Methods Of Synthesis ◽

Current Therapies ◽

Resistant Strains ◽

Privileged Structures

Background: Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND). Methods: Based on the literature search from 2002 to 2016, we discuss how six privileged motifs, focusing phthalimide, isatin, indole, thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in compounds active against some of neglected diseases. Results: It was observed that attention was paid particularly for Chagas disease, malaria, tuberculosis, schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among the ND, antitrypanosomal and antiplasmodial activities were between the most searched. Besides, thiosemicarbazone moiety seems to be the most versatile and frequently explored scaffold. As well, phthalimide, isatin, thiazole, and thiazolidone nucleus have been also explored in the ND field. Conclusion: Some described compounds, appear to be promising drug candidates, while others could represent a valuable inspiration in the research for new lead compounds.

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Occupational hazard in Malaysian traffic police: special focus on air pollutants

Reviews on Environmental Health ◽

10.1515/reveh-2020-0107 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Putri Anis Syahira Mohamad Jamil ◽

Karmegam Karuppiah ◽

Irniza Rasdi ◽

Vivien How ◽

Shamsul Bahri Mohd Tamrin ◽

...

Keyword(s):

Occupational Injuries ◽

Indicator System ◽

Control Measures ◽

Special Focus ◽

Safety Measures ◽

Traffic Police ◽

Wide Range ◽

And Control ◽

Risk Occupation ◽

High Risk Occupation

Abstract This paper provides a specific deliberation on occupational hazards confronted daily by Malaysian Traffic Police. Traffic police is a high-risk occupation that involves a wide range of tasks and, indirectly, faced with an equally wide variety of hazards at work namely, physical, biological, psychosocial, chemical, and ergonomic hazards. Thereupon, occupational injuries, diseases, and even death are common in the field. The objective of this paper is to collate and explain the major hazards of working as Malaysian traffic police especially in Point Duty Unit, their health effects, and control measures. There are many ways in which these hazards can be minimised by ensuring that sufficient safety measures are taken such as a wireless outdoor individual exposure indicator system for the traffic police. By having this system, air monitoring among traffic police may potentially be easier and accurate. Other methods of mitigating these unfortunate events are incorporated and addressed in this paper according to the duty and needs of traffic police.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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SGLT2 inhibitors: a narrative review of efficacy and safety

Journal of Osteopathic Medicine ◽

10.1515/jom-2020-0153 ◽

2021 ◽

Vol 121 (2) ◽

pp. 229-239

Author(s):

Donald S. Nelinson ◽

Jose M. Sosa ◽

Robert J. Chilton

Keyword(s):

Adverse Events ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Narrative Review ◽

Atherosclerotic Cardiovascular Disease ◽

Comorbid Conditions ◽

Postprandial Plasma Glucose ◽

Renal Outcomes ◽

Glucose Levels ◽

Wide Range

Abstract Type 2 diabetes mellitus (T2DM) is a cardio-renal-metabolic condition that is frequently associated with multiple comorbidities, including atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). The sodium-glucose co-transporter-2 (SGLT2) inhibitors, which lower glycated hemoglobin, fasting and postprandial plasma glucose levels, body weight, and blood pressure, as well as reduce the risk of a range of cardiovascular and renal outcomes without increasing hypoglycaemic risk, have heralded a paradigm shift in the management of T2DM. These drugs are compatible with most other glucose-lowering agents and can be used in patients with a wide range of comorbid conditions, including ASCVD, HF, and CKD, and in those with estimated glomerular filtration rates as low as 30 mL/min/1.73 m2. However, there are misunderstandings surrounding the clinical implications of SGLT2 inhibitors’ mechanism of action and concerns about the key adverse events with which this class of drugs has been associated. This narrative review summarizes the data that support the efficacy of SGLT2 inhibitors in reducing the risks of cardiovascular and renal outcomes in patients with T2DM and comorbid conditions and clarifies information relating to SGLT2 inhibitor-related adverse events.

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New Target Genes for the Peroxisome Proliferator-Activated Receptor-γ(PPARγ) Antitumour Activity: Perspectives from the Insulin Receptor

PPAR Research ◽

10.1155/2009/571365 ◽

2009 ◽

Vol 2009 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Daniela P. Foti ◽

Francesco Paonessa ◽

Eusebio Chiefari ◽

Antonio Brunetti

Keyword(s):

Insulin Receptor ◽

Target Genes ◽

Tumour Progression ◽

Antitumour Activity ◽

Peptide Hormone ◽

Nuclear Hormone Receptor ◽

Peroxisome Proliferator ◽

Preclinical Research ◽

Peroxisome Proliferator Activated Receptor ◽

Wide Range

The insulin receptor (IR) plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγis a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγagonists—besides their known action and clinical use as insulin sensitizers—have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγand activators affect tumours by different mechanisms, involving cell proliferation and differentiation, apoptosis, antiinflammatory, and antiangiogenic effects. We recently provided evidence that PPARγand agonists inhibit IR by non canonical, DNA-independent mechanisms affecting IR gene transcription. We conclude that IR may be considered a new PPARγ“target” gene, supporting a potential use of PPARγagonists as antiproliferative agents in selected neoplastic tissues that overexpress the IR.

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Diet and general cognitive ability in the UK Biobank dataset

Scientific Reports ◽

10.1038/s41598-021-91259-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Piril Hepsomali ◽

John A. Groeger

Keyword(s):

Cognitive Ability ◽

Dietary Patterns ◽

Red Meat ◽

Milk Intake ◽

Special Focus ◽

General Cognitive Ability ◽

Food Groups ◽

Uk Biobank ◽

Wide Range ◽

The Uk

AbstractAccumulating evidence suggests that dietary interventions might have potential to be used as a strategy to protect against age-related cognitive decline and neurodegeneration, as there are associations between some nutrients, food groups, dietary patterns, and some domains of cognition. In this study, we aimed to conduct the largest investigation of diet and cognition to date, through systematically examining the UK Biobank (UKB) data to find out whether dietary quality and food groups play a role on general cognitive ability. This cross-sectional population-based study involved 48,749 participants. UKB data on food frequency questionnaire and cognitive function were used. Also, healthy diet, partial fibre intake, and milk intake scores were calculated. Adjusted models included age, sex, and BMI. We observed associations between better general cognitive ability and higher intakes of fish, and unprocessed red meat; and moderate intakes of fibre, and milk. Surprisingly, we found that diet quality, vegetable intake, high and low fibre and milk intake were inversely associated with general cognitive ability. Our results suggest that fish and unprocessed red meat and/or nutrients that are found in fish and unprocessed red meat might be beneficial for general cognitive ability. However, results should be interpreted in caution as the same food groups may affect other domains of cognition or mental health differently. These discrepancies in the current state of evidence invites further research to examine domain-specific effects of dietary patterns/food groups on a wide range of cognitive and affective outcomes with a special focus on potential covariates that may have an impact on diet and cognition relationship.

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Abstract 17853: Activation of AMP-activated Protein Kinase (AMPKα) by AICAR Attenuates Klotho Deficiency-induced Endothelial Dysfunction, Arterial Stiffening and Hypertension

Circulation ◽

10.1161/circ.130.suppl_2.17853 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Yi Lin ◽

Zhongjie Sun

Keyword(s):

Blood Pressure ◽

Blood Glucose ◽

Endothelial Dysfunction ◽

Protein Expression ◽

Normal Diet ◽

Collagen I ◽

Daily Injection ◽

Arterial Stiffening ◽

Glucose Levels ◽

Amp Activated Protein Kinase

Background: Arterial stiffening and hypertension are progressive aging-related disorders. Klotho (KL) is a recently-discovered anti-aging gene but its role in the pathogenesis of endothelial dysfunction, arterial stiffening and hypertension is not fully understood. Methods and Results: Heterozygous Klotho deficiency ( KL +/- ) mice and WT littermate mice were fed on high fat diet (HFD) or normal diet (ND). Plasma KL in KL heterozygeous mice (+/-) is about a half of that of the WT mice. Pulse wave velocity (PWV), an index of arterial stiffening, was increased in KL +/- mice but not in WT mice fed on HFD for 4 weeks. Systolic blood pressure and blood glucose levels were increased earlier with greater magnitudes in KL +/- mice than in WT mice fed on HFD. Notably, protein expression of collagen I, Runx2, and TGFβ1 were increased but protein expression of phosphorylated AMPKα (pAMPKα), phosphorylated eNOS (peNOS), and Mn-SOD were decreased in aortas of KL +/- mice fed on HFD for 5 weeks. Interestingly, daily injection of AICAR, an activator of AMPK, abolished the increases in PWV, blood pressure, and blood glucose in KL +/- mice fed on HFD. AICAR not only abolished the downregulation of pAMPKα, peNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, Runx2, TGFβ1 and superoxide, elastic lamellae breaks, and calcification in aortas in KL +/- mice fed on HFD. Conclusions: Klohto deficiency promotes HFD-induced endothelial dysfunction, arterial stiffening and hypertension. The promoting effects of klotho deficiency on arterial stiffening may be due to downregulation of endothelial AMPKα activity.

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Two-Side Laser Processing Method for Producing High Aspect Ratio Microholes

Journal of Micro and Nano-Manufacturing ◽

10.1115/1.4037645 ◽

2017 ◽

Vol 5 (4) ◽

Cited By ~ 8

Author(s):

Vahid Nasrollahi ◽

Pavel Penchev ◽

Stefan Dimov ◽

Lars Korner ◽

Richard Leach ◽

...

Keyword(s):

Cross Sections ◽

Laser Processing ◽

Industrial Applications ◽

Laser Drilling ◽

Special Focus ◽

Geometrical Accuracy ◽

Aspect Ratios ◽

Wide Range ◽

High Flexibility ◽

Accuracy And Repeatability

Laser microprocessing is a very attractive option for a growing number of industrial applications due to its intrinsic characteristics, such as high flexibility and process control and also capabilities for noncontact processing of a wide range of materials. However, there are some constrains that limit the applications of this technology, i.e., taper angles on sidewalls, edge quality, geometrical accuracy, and achievable aspect ratios of produced structures. To address these process limitations, a new method for two-side laser processing is proposed in this research. The method is described with a special focus on key enabling technologies for achieving high accuracy and repeatability in two-side laser drilling. The pilot implementation of the proposed processing configuration and technologies is discussed together with an in situ, on-machine inspection procedure to verify the achievable positional and geometrical accuracy. It is demonstrated that alignment accuracy better than 10 μm is achievable using this pilot two-side laser processing platform. In addition, the morphology of holes with circular and square cross sections produced with one-side laser drilling and the proposed method was compared in regard to achievable aspect ratios and holes' dimensional and geometrical accuracy and thus to make conclusions about its capabilities.

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Excitation-Dependent Fluorescence Quantum Yield for Freshwater Chromophoric Dissolved Organic Matter from Northern Russian Lakes

Journal of Spectroscopy ◽

10.1155/2018/3168320 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Svetlana Patsaeva ◽

Daria Khundzhua ◽

Oleg A. Trubetskoj ◽

Olga E. Trubetskaya

Keyword(s):

Organic Matter ◽

Quantum Yield ◽

Dissolved Organic Matter ◽

Fluorescence Quantum Yield ◽

Molecular Size ◽

Reversed Phase ◽

Chromophoric Dissolved Organic Matter ◽

Excitation Wavelength ◽

Fluorescence Detector ◽

Wide Range

Advanced fluorescence analysis within the wide range of excitation wavelengths from 230 to 510 nm accompanied with chromatography was used to study natural chromophoric dissolved organic matter (CDOM) from three freshwater Karelian lakes. The influence of excitation wavelength (λex) on fluorescence quantum yield and emission maximum position was determined. The CDOM fluorescence quantum yield has reached a minimum at λex∼270–280 nm and a maximum at λex∼340–360 nm. It was monotonously decreasing after 370 nm towards longer excitation wavelengths. Analytical reversed-phase high-performance liquid chromatography with multiwavelength fluorescence detector characterized distribution of fluorophores between hydrophilic/hydrophobic CDOM parts. This technique revealed “hidden” protein-like fluorophores for some CDOM fractions, in spite of the absence of protein-like fluorescence in the initial CDOM samples. The humic-like fluorescence was documented for all hydrophilic and hydrophobic CDOM chromatographic peaks, and its intensity was decreasing along with peaks’ hydrophobicity. On contrary, the protein-like fluorescence was found only in the hydrophobic peaks, and its intensity was increasing along with peaks’ hydrophobicity. This work provides new data on the CDOM optical properties consistent with the formation of supramolecular assemblies controlled by association of low-molecular size components. In addition, these data are very useful for understanding the CDOM function in the environment.

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Exosome-Mediated Insulin Delivery for the Potential Treatment of Diabetes Mellitus

Pharmaceutics ◽

10.3390/pharmaceutics13111870 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1870

Author(s):

Belén Rodríguez-Morales ◽

Marilena Antunes-Ricardo ◽

José González-Valdez

Keyword(s):

Diabetes Mellitus ◽

Human Insulin ◽

Insulin Delivery ◽

Dermal Fibroblasts ◽

Therapeutic Drug ◽

Extracellular Medium ◽

Glucose Levels ◽

Wide Range ◽

Diabetes Mellitus Treatment

Exosomes are extracellular nanovesicles between 30 and 150 nm that serve as essential messengers for different biological signaling and pathological processes. After their discovery, a wide range of applications have been developed, especially in therapeutic drug delivery. In this context, the aim of this work was to test the efficiency of exosome-mediated human insulin delivery using exosomes extracted from three different cell lines: hepatocellular carcinoma (HepG2); primary dermal fibroblasts (HDFa) and pancreatic β cells (RIN-m); all are related to the production and/or the ability to sense insulin and to consequently regulate glucose levels in the extracellular medium. The obtained results revealed that the optimal insulin loading efficiency was achieved by a 200 V electroporation, in comparison with incubation at room temperature. Moreover, the maximum in vitro exosome uptake was reached after incubation for 6 h, which slightly decreased 24 h after adding the exosomes. Glucose quantification assays revealed that exosome-mediated incorporation of insulin presented significant differences in HDFa and HepG2 cells, enhancing the transport in HDFa, in comparison with free human insulin effects in the regulation of extracellular glucose levels. No significant differences were found between the treatments in RIN-m cells. Hence, the results suggest that exosomes could potentially become a valuable tool for stable and biocompatible insulin delivery in diabetes mellitus treatment alternatives.

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