Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival.

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.

Spatially resolved distribution of pancreatic hormones proteoforms by MALDI-imaging mass spectrometry.

Zinc plays a crucial role both in the immune system and endocrine processes. Zinc restriction in the diet has been shown to lead to degeneration of the endocrine pancreas, resulting in hormonal imbalance within the ß-cells. Proteostasismay vary depending on the stage of a pathophysiological process, which underscores the need for tools aimed at directly analyzing biological status. Among proteomics methods, MALDI-ToF-MS can serve as a rapid peptidomics tool for analyzing extracts or by histological imaging. Here we report the optimization of MALDI imaging mass spectrometry analysis of histological thin sections from mouse pancreas. This optimization enables the identification of the major islet peptide hormones as well as the major accumulated precursors and/or proteolytic products of peptide hormones. Cross-validation of the identified peptide hormones was performed by LC-ESI-MS from pancreatic islet extracts. Mice subjected to a zinc-restricted diet exhibited a relatively lower amount of peptide intermediates compared to the control group. These findings provide evidence for a complex modulation of proteostasis by micronutrients imbalance, a phenomenon directly accessed by MALDI-MSI.

Relevance of Oxocyclam from Palladium(II) Coordination to Radiopharmaceutical Development.

We provide a comprehensive study of the coordination of oxocyclam with palladium(II), including presentation of a novel bifunctional analogue, p-H2N-Bn-oxocyclam, bearing an aniline pendant. The complexation of palladium(II) with oxocyclam was examined by various techniques, including NMR analysis and potentiometric titrations which revealed that the Pd(II) complex can adopt different configurations such as trans-I and trans-III. In addition, oxocyclam forms a thermodynamically stable palladium(II) complex, the stabilization being attributed to the deprotonation of the amide function. The crystal structures of [Pd(H-1oxocyclam)]+ and [Pd(oxocyclam)]2+ were obtained, revealing the structural details previously anticipated, including, in the second case, the presence of the proton on the carbonyl oxygen atom. Additionally, the study explored the redox behavior of the Pd(II)-oxocyclam complex through reduction and oxidation voltammograms at different pH values. Successful 109Pd-labeling of oxocyclam and p-H2N-Bn-oxocyclam at pH 3.5 demonstrated high labeling efficiencies, whatever the species formed. The stability of the radiocomplexes was assessed and moderate transchelation toward EDTA was observed. Overall, oxocyclam displayed favorable properties for Pd(II) coordination and radiolabeling, suggesting its potential as a chelating agent for this metal in palladium-based applications.

Early Life Trauma, Emotion Dysregulation and Hormonal Sensitivity Across Female Reproductive Life Events.

PURPOSE OF REVIEW: To explore the relationship between early life trauma, hormonal sensitivity, and psychiatric disorders across female-reproductive life events, with a focus on the neurobiological mechanisms. RECENT FINDINGS: Childhood trauma significantly increases the risk of subsequent mood disorders during periods of intense hormonal fluctuation such as premenstrual, pregnancy, postpartum, and perimenopause. Neurobiological changes resulting from early trauma influence emotion regulation, which emerges as a key predisposing, exacerbating, and perpetuating factor to hormonal sensitivity and subsequent psychiatric symptoms. We identified altered stress response and allopregnanolone imbalance, bias in cognitive processing of emotions, neuroimage correlates and sleep disturbances as potential underlying neurobiological mechanisms. This review integrates cumulative findings supporting a theoretical framework linking early life trauma to hormonal sensitivity and mood disorders. We propose that some women might be more susceptible to such hormonal fluctuations because of emotion dysregulation following significant early life trauma.

Applications of Mass Spectrometry in the Characterization, Screening, Diagnosis, and Prognosis of COVID-19.

Mass spectrometry (MS) is a powerful analytical technique that plays a central role in modern protein analysis and the study of proteostasis. In the field of advanced molecular technologies, MS-based proteomics has become a cornerstone that is making a significant impact in the post-genomic era and as precision medicine moves from the research laboratory to clinical practice. The global dissemination of COVID-19 has spurred collective efforts to develop effective diagnostics, vaccines, and therapeutic interventions. This chapter highlights how MS seamlessly integrates with established methods such as RT-PCR and ELISA to improve viral identification and disease progression assessment. In particular, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) takes the center stage, unraveling intricate details of SARS-CoV-2 proteins, revealing modifications such as glycosylation, and providing insights critical to formulating therapies and assessing prognosis. However, high-throughput analysis of MALDI data presents challenges in manual interpretation, which has driven the development of programmatic pipelines and specialized packages such as MALDIquant. As we move forward, it becomes clear that integrating proteomic data with various omic findings is an effective strategy to gain a comprehensive understanding of the intricate biology of COVID-19 and ultimately develop targeted therapeutic paradigms.

Bigger Calves from Doing Higher Resistance Training Volume?

We compared the effects of different weekly calf training sets on muscle size changes. Sixty-one untrained young women performed a calf training program for 6 weeks, 3 d·wk-1, with differences in resistance training volume. The participants were randomly assigned to one of the three groups: 6-SET, 9-SET, and 12-SET weekly calf training sets. The calf raise exercise was performed in sets of 15-20 repetitions maximum. The muscle thickness measurements of medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL) were taken via B-mode ultrasound. We used the sum of the three-muscle thickness as a proxy for the triceps surae (TSSUM). The 12-SET group elicited greater increases than the 6-SET in LG (6-SET=+ 8.1% vs. 12-SET=+ 14.3%; P=0.017), SOL (6-SET=+ 6.7% vs. 12-SET=+ 12.7%; P=0.024), and TSSUM (6-SET=+ 6.9% vs. 12-SET=+ 12.0%; P=0.005), but there was no significant difference in MG changes (6-SET=+ 6.6% vs. 12-SET=+ 9.9%; P=0.067). There were no significant differences when comparing 9-SET vs. 6-SET and 12-SET (P≥0.099). Although all groups experienced calf muscle hypertrophy, our results suggest that the higher dose range may optimize triceps surae muscle size gains.

ABCB1 C1236T, G2677TA and C3435T Genetic Polymorphisms and Antidepressant Response Phenotypes: Results from a Portuguese Major Depressive Disorder Cohort.

P-glycoprotein (P-GP) is a transporter molecule expressed on the apical surface of capillary endothelial cells of the Blood-Brain Barrier (BBB), whose activity heavily influences drug distribution, including antidepressants. This transporter is encoded by ABCB1 gene, and genetic variations within ABCB1 gene have been proposed to affect drug efflux and have been previously associated with depression. In this context, we aimed to evaluate the role of C1236T, G2677TA and C3435T ABCB1 genetic polymorphisms in antidepressant treatment phenotypes from a cohort of patients harboring Major Depressive Disorder. Patients enrolled in the study consisted of 80 individuals with Major Depressive Disorder, who took part in a 27-month follow-up study at HML, Portugal. To investigate the correlation between ABCB1 polymorphisms and antidepressant response phenotypes, DNA was extracted from peripheral blood, and C1236T, C3435T and G2677TA polymorphisms were genotyped with TaqMan® SNP Genotyping Assays. Despite the fact that the evaluated polymorphisms (C1236T, C3435T and G2677TA) were not associated with treatment resistant depression, or relapse, we observed that patients carrying TT genotype of the C3435T polymorphism remit earlier than the ones carrying CC or CT genotypes (10.2 weeks vs. 14.9 and 21.3, respectively, p = 0.028, Log-rank test). Since we found an association with C3435T and time to remission, and not to the absence of remission, we suggest that this polymorphism could have an impact on antidepressant drug distribution, and thus influence on the time to remission will occur, without influencing the risk of remission itself.

Aberrantly Glycosylated GLUT1 as a Poor Prognosis Marker in Aggressive Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer.

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

Zinc deficiency disrupts pain signaling promoting nociceptive but not inflammatory pain in mice.

Zinc (Zn) is an essential micronutrient involved in the physiology of nervous system and pain modulation. There is little evidence for the role of nutritional Zn alternations to the onset and progression of neuropathic (NP) and inflammatory pain. The study investigated the effects of a zinc restricted diet on the development of pain. Weaned mice were submitted to a regular (38 mg/kg of Zn) or Zn deficient (11 mg/kg of Zn) diets for four weeks, pain responses evaluated (mechanical, cold and heat allodynia; formalin- and carrageenan-induced inflammatory hypernociception), plasma and tissues collected for biochemical and metabolomic analysis. Zn deficient diet inhibited animal growth (37%) and changed mice sensitivity pattern, inducing an intense allodynia evoked by mechanical, cold and heat stimulus for four weeks. The inflammatory pain behavior of formalin test was drastically reduced or absent when challenged by an inflammatory stimulus. Zn restriction also reduce plasma TNF, increase neuronal activation, oxidative stress, indicating a disruption of the immune response. Liver metabolomic analyses suggest a downregulation of lipid metabolism of arachidonic acid. Zn restriction since weaned disrupts pain signaling considerably and reduce inflammatory pain. Zn could be considered a predisposing factor for the onset of chronic pain such as painful neuropathies.

MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening-A Comprehensive Review.

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers.

The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes.

This study aimed to investigate the influence of genetic variants in neuroplasticity-related genes on antidepressant treatment phenotypes. The BDNF-TrkB signaling pathway, as well as the downstream kinases Akt and ERK and the mTOR pathway, have been implicated in depression and neuroplasticity. However, clinicians still struggle with the unpredictability of antidepressant responses in depressed patients. We genotyped 26 polymorphisms in BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 in 80 patients with major depressive disorder treated according to the Texas Medical Algorithm for 27 months at Hospital Magalhães Lemos, Porto, Portugal. Our results showed that BDNF rs6265, PTEN rs12569998, and SYN1 rs1142636 SNP were associated with treatment-resistant depression (TRD). Additionally, MAPK1 rs6928 and GSK3B rs6438552 gene polymorphisms were associated with relapse. Moreover, we found a link between the rs6928 MAPK1 polymorphism and time to relapse. These findings suggest that the BDNF, PTEN, and SYN1 genes may play a role in the development of TRD, while MAPK1 and GSK3B may be associated with relapse. GO analysis revealed enrichment in synaptic and trans-synaptic transmission pathways and glutamate receptor activity with TRD-associated genes. Genetic variants in these genes could potentially be incorporated into predictive models of antidepressant response.

Lower bone density and microarchitecture alterations in HIV-infected Brazilian men aged 50 years and older are associated with estradiol levels.

OBJECTIVE: Combination antiretroviral treatment (cART) allows for longer survival for people living with HIV and hence long-term complications of both disease and treatment are common. Our purpose was to evaluate bone alterations in men living with HIV (MLWH) and receiving cART and to identify associated factors that can be corrected or mitigated. PATIENTS AND DESIGN: Thirty MLWH and 36 healthy controls (≥50 years) were studied for areal bone mineral density (aBMD) and body composition (dual-energy X-ray absorptiometry), volumetric bone mineral density (vBMD) and bone microstructure (high-resolution peripheral quantitative computed tomography [HR-pQCT]), serum calcium, phosphate, parathyroid hormone, 25(OH)D, testosterone (T), estradiol (E2 ), glucose, creatinine, and albumin levels. RESULTS: The proportion of patients classified as osteoporosis (according to the lowest aBMD T-score) was higher among MLWH as compared to controls (17.9% vs. 5.9%, p = .011). The MLWH showed significant alterations in cortical and trabecular bone on HR-pQCT, which were not associated with the duration of HIV infection or cART. These differences in vBMD and bone microstructure seen in HR-pQCT persisted in the nonosteoporotic MLWH as compared to nonosteoporotic control subjects. Body mass index (BMI) and fat mass were lower in MLWH and positively associated with total vBMD, cortical bone area, and thickness. E2 and E2 /T ratios were lower in MLWH than in controls and significantly correlated with several cortical and trabecular bone parameters. Multivariate regression analysis entering simultaneously age, BMI, and E2 defined that E2 is an independent influence on bone parameters evaluated by HR-pQCT. CONCLUSION: MLWH have alterations in bone volumetric density and microstructure when compared with controls, irrespective of aBMD, which are associated with lower E2 and BMI.

Relevance of Palladium to Radiopharmaceutical Development Considering Enhanced Coordination Properties of TE1PA.

The limited use of palladium-103 and -109 radionuclides for molecular radiotherapy is surely due to the lack of appropriate ligands capable of fulfilling all criteria required for application in nuclear medicine. Furthermore, the thermodynamic properties of these complexes in solution remain difficult to establish. The challenge is compounded when considering that radiolabeling of compounds for translation to clinical trials requires fast complexation. Thus, the coordination of Pd(II) and 103/109 Pd-nuclides is a huge challenge in terms of molecular design and physicochemical characterization. Herein, we report a comprehensive study highlighting TE1PA, a monopicolinate cyclam - already established in nuclear imaging with 64 Cu-PET (positron emission tomography) imaging tracers - as a highly relevant chelator for natural Pd and subsequently 109 Pd-nuclide. The structural, thermodynamic, kinetic and radiolabeling studies of Pd(II) with TE1PA, as well as the comparison of this complex with three structurally related derivatives, support palladium-TE1PA radiopharmaceuticals as leading candidates for targeted nuclear medicine.

Relevance of Palladium to Radiopharmaceutical Development Considering Enhanced Coordination Properties of TE1PA.

Invited for the cover of this issue are the group of Raphaël Tripier and Nathalie Le Bris at the University of Brest (UMR CNRS 6521 CEMCA; France), Cathryn H. S. Driver from the South African Nuclear Energy Corporation in Pretoria (South Africa), and their collaborators. The image depicts the beginning of a new area of research into palladium and complexation of its radioisotopes for applications in nuclear medicine. Read the full text of the article at 10.1002/chem.202200942.

The reproducible normality of the crystallographic B-factor.

Reproducibility determines the utility of a measurement. In structural biology the reproducibility permeate areas such as mechanics, data measurement, data analysis and refinement. In order to access the reproducibility of the combined contribution of these sources in uncertainties of protein crystallography we evaluated four groups of parameters from data collection to final structural model. We used lysozyme as a model, with 20 datasets collected at 1.6 Å resolution using two dissimilar x-ray diffraction setups and refined through a single automatic pipeline without arbitrary interpretation. Besides statistical differences in some structural parameters, the reproducibility of the final refined models allowed the determination of positional uncertainty, in good agreement with the Luzzati coordinate error. While the raw B-factor was found non-reproducible, an empirical scaling/normalization resulted in reproducible B-factors. The validity of this empirical scaling was corroborated by the reproducibility of normalized B-factors of independently solved datasets from proteins (insulin and myoglobin) from varying space groups available from structural database. The reproducibility of normalized B-factor may reposition this displacement parameter in the analysis of chemical (ligands, pH) and physical (pressure, temperature, space groups) variables.

Microarchitectural parameters and bone mineral density in patients with tumour-induced osteomalacia by HR-pQCT and DXA.

INTRODUCTION: Tumour-induced osteomalacia (TIO) is a rare paraneoplastic condition characterised by decreased tubular phosphate reabsorption. The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in six TIO patients, compared with 18 healthy controls. METHODS: Volumetric BMD and microarchitecture were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and areal BMD by dual-energy X-ray absorptiometry (DXA). Differences between groups were significant for p < .05. RESULTS: All TIO subjects were healthy until the development of diffuse bone pain and multiple skeletal fractures and deformities. At baseline, sPi and TmPi/GFR were low and patients were on vitamin D and phosphate replacement at the study. Compared with controls, TIO patients had lower aBMD at lumbar spine and hip, and lower vBMD at trabecular, cortical and entire bone, at distal radius (R) and distal tibia (T): trabecular vBMD (R = 118.3 × 177.1; T = 72.3 × 161.3 gHA/cm3 ); cortical vBMD (R = 782.3 × 866.5; T = 789.1 × 900.9 gHA/cm3 ); total region vBMD (R = 234.5 × 317; T = 167.1 × 295.8 gHA/cm3 ). Bone microarchitecture was very heterogeneous among patients and significantly different from controls: lower cortical thickness (R = 0.59 × 0.80; T = 0.90 × 1.31 mm), bone volume-to-total volume ratio (R = 0.09 × 0.14; T = 0.06 × 0.13) and Tb.N (R = 1.46 × 2.10; T = 0.93 × 1.96 mm-1 ) and also higher Tb.Sp (R = 0.70 × 0.41; T = 1.28 × 0.45 mm) and Tb.1/N.SD (R = 0.42 × 0.18; T = 0.87 × 0.20 mm). CONCLUSION: In this original study of TIO patients, DXA and HR-pQCT evaluation identified lower areal and volumetric BMD and severely impaired microarchitecture at cortical and trabecular bones, which probably contribute to bone fragility and fractures.

Coarse-Grained Parameterization of Nucleotide Cofactors and Metabolites: Protonation Constants, Partition Coefficients, and Model Topologies.

Nucleotides are structural units relevant not only in nucleic acids but also as substrates or cofactors in key biochemical reactions. The size- and timescales of such nucleotide-protein interactions fall well within the scope of coarse-grained molecular dynamics, which holds promise of important mechanistic insight. However, the lack of specific parameters has prevented accurate coarse-grained simulations of protein interactions with most nucleotide compounds. In this work, we comprehensively develop coarse-grained parameters for key metabolites/cofactors (FAD, FMN, riboflavin, NAD, NADP, ATP, ADP, AMP, and thiamine pyrophosphate) in different oxidation and protonation states as well as for smaller molecules derived from them (among others, nicotinamide, adenosine, adenine, ribose, thiamine, and lumiflavin), summing up a total of 79 different molecules. In line with the Martini parameterization methodology, parameters were tuned to reproduce octanol-water partition coefficients. Given the lack of existing data, we set out to experimentally determine these partition coefficients, developing two methodological approaches, based on 31P-NMR and fluorescence spectroscopy, specifically tailored to the strong hydrophilicity of most of the parameterized compounds. To distinguish the partition of each relevant protonation species, we further potentiometrically characterized the protonation constants of key molecules. This work successfully builds a comprehensive and relevant set of computational models that will boost the biochemical application of coarse-grained simulations. It does so based on the measurement of partition and acid-base physicochemical data that, in turn, covers important gaps in nucleotide characterization.

On the Aromatic Stabilization of Fused Polycyclic Aromatic Hydrocarbons.

The thermodynamic properties and band gap energies were evaluated for six ortho- and peri-fused polycyclic aromatic hydrocarbons (PAHs): triphenylene; benzo[a]pyrene; benzo[e]pyrene; perylene; benzo[ghi]perylene; coronene. The standard molar enthalpies of formation in the crystalline state and the standard molar enthalpies of sublimation were measured by high precision combustion calorimetry and Knudsen effusion methodology, respectively. The combination of the molar enthalpies of formation in the crystalline state with the respective enthalpies of sublimation was used to evaluate the energetics of the progressive peri-fusion of the aromatic moieties from triphenylene to coronene aiming to investigate the hypothetical superaromaticity character of coronene. The linear trend of the enthalpy of formation in crystalline and gaseous phases in the series (from benzo[e]pyrene to coronene) is an irrefutable indication of a non-superaromaticity character of coronene. High accurate thermodynamic properties of sublimation (volatility, enthalpy, and entropy of sublimation) were derived by the measurement of vapor pressures as a function of temperature, using a Knudsen/quartz crystal effusion methodology. Furthermore, the π-electronic conjugation of these compounds was explored by evaluation of the optical band gaps along with this series of compounds. The morphology of perylene, benzo[ghi]perylene, and coronene thin films, deposited by physical vapor deposition onto transparent conductive oxide substrates (ITO and FTO), was used to analyze the nucleation and growth mechanisms. The morphologies observed were found to be related to the cohesive energy and entropy of the bulk.

Polymeric microparticle systems for modified release of glucagon-like-peptide-1 receptor agonists.

Type 2 diabetes is a fast-growing worldwide epidemic. Despite the multiple therapies available to treat type 2 diabetes, the disease is not correctly managed in over half of patients, mainly due to non-compliance with prescribed treatment regimes. The development of analogues to the glucagon-like peptide 1 (GLP-1) has resulted in the extension of its half-life and associated benefits. Further benefits in the use of peptide-based GLP-1 receptor agonists have been achieved by the use of controlled-release systems based on polymeric microparticles. In this review, we focus on commercially available formulations and others that remain in development, discussing the preparation methods and the relationship between in vitro and in vivo kinetic release behaviours.