May 18th, 2022 - Diabetes-associated osteoporosis are partly caused by accumulation of advanced glycation endproducts (AGEs). Glucagon-like peptide-1 (GLP-1) has been shown to regulate bone turnover. Here we explore whether GLP-1 receptor agonist (GLP1RA) can have a beneficial effect on bone in diabetes by ameliorating AGEs. In the present study, we evaluated the effects of the GLP-1 receptor agonist liraglutid...

May 14th, 2022 - Aberrations in cyclooxygenase and lipoxygenase (LOX) pathways in non-neoplastic, normal appearing mucosa from patients with colorectal neoplasia (CRN), could hypothetically qualify as predisposing CRN-markers. To test this hypothesis, biopsies were obtained during colonoscopy from macroscopically normal colonic mucosa from patients with and without CRN. Prostaglandin E2 (PGE2) receptors, EP1-4,...

May 14th, 2022 - The cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients. PubMed and Embase were search...

May 14th, 2022 - SignificanceGlucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious in the treatment of type 2 diabetes and obesity. While most clinically used agents require subcutaneous injection, Boc5, as the first orthosteric nonpeptidic agonist of GLP-1R, suffers from poor oral bioavailability that hinders its therapeutic development. The cryoelectron microscopy structures of Boc5 and its close...

May 14th, 2022 - Pseudomonas aeruginosa is a common respiratory pathogen that causes injurious airway inflammation during acute pneumonia. Peroxisome proliferator-activated receptor (PPAR)-γ is involved in the regulation of metabolic and inflammatory responses in different cell types and synthetic agonists of PPAR-γ exert anti-inflammatory effects on myeloid cells in vitro and in models of inflammation in vivo....

May 11th, 2022 - To determine national prevalence of sodium-glucose contransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1RA) use among adults with type 2 diabetes mellitus (T2DM). We studied adults with T2DM and eGFR ≥ 30 mL/min/1.73 m2 who participated in the cross-sectional National Health and Nutrition Examination Survey (NHANES), focusing on the 2017-2020 examination cycle, ...

May 3rd, 2022 - Benzotriazole UV stabilizers (BUVSs) are widely used as additives in various materials, including plastics, to prevent damage from UV-irradiation. However, despite the extensive usage of BUVSs, information on their toxicological properties is limited. In this study, we investigated the effect of BUVSs on the immune regulatory system via the aryl hydrocarbon receptor (AhR). A cell-based transact...

May 2nd, 2022 - Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition that affects nearly one billion people globally, characterized by triacylglycerol accumulation in the liver as a consequence of metabolic abnormalities (obesity and impaired glucose regulation). Low-grade inflammation, oxidative stress, mitochondrial dysfunction, and dysbiosis in gut microbiota are involved in t...

Apr 30th, 2022 - Angiogenesis is vital during pregnancy for remodeling and enhancing vasodilation of maternal uterine arteries, and increasing uterine blood flow. Abnormal angiogenesis is associated with decreased uteroplacental blood flow and development of pregnancy disorders such as gestational hypertension, preeclampsia, fetal growth restriction, preterm delivery, stillbirth, and miscarriage. The mechanisms...

Apr 29th, 2022 - Resiniferatoxin (RTX), an extract from the spurge plant Euphorbia resinifera, is a potent agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1), mainly expressed on peripheral nociceptors-a prerequisite for nociceptive heat perception. Systemic overdosing of RTX can be used to desensitize specifically TRPV1-expressing neurons, and was therefore utilized here to...

Apr 29th, 2022 - In an endeavour to understand metastasis from oral squamous cell carcinomas, we characterised the metastatic potential of a human tongue derived cell line (SCC-4 cells) and compared this phenotype to pre-cancerous dysplastic oral keratinocyte (DOK) cells derived from human tongue and primary gingival keratinocytes (PGK). We demonstrate that SCC-4 cells constitutively synthesize and release sign...

Apr 28th, 2022 - Despite strong evidence of benefit, uptake of newer glucose-lowering medications that reduce cardiovascular risk has been low. We sought to examine global trends and predictors of use of SGLT2i and GLP-1 RA in patients with type 2 diabetes. DISCOVER is a global, prospective, observational study of patients with diabetes enrolled from 2014-16 at initiation of second-line glucose-lowering therapy...

Apr 28th, 2022 - Background Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) mitigate cardiovascular risk in individuals with type 2 diabetes, but most eligible patients do not receive them. We characterized temporal trends in SGLT2i and GLP-1RA use by cardiologists compared with other groups of clinicians. Methods and Results We conducted a descriptiv...

Apr 27th, 2022 - Menopausal hormone therapy (MHT) is recommended for only five years to treat vasomotor symptoms and vulvovaginal atrophy because of safety concerns with long-term treatment. We investigated the ability of 2',3',4'-trihydroxychalcone (2',3',4'-THC) to modulate estrogen receptor (ER)-mediated responses in order to find drug candidates that could potentially prevent the adverse effects of long-ter...

Apr 24th, 2022 - The overall response rate to checkpoint blockade remains unsatisfactory, partially due to the immune-suppressive tumor microenvironment. A retinoic acid-related orphan receptor γt (RORγt) agonist (LYC-55716) is currently used in clinical trials combined with anti-PD-1, but how the Th17 cell transcription factor RORγt enhances antitumor immunity of PD-1 in the tumor microenvironment remains elus...

Apr 23rd, 2022 - A key challenge for the development of a cure to HIV-1 infection is the persistent viral reservoir established during early infection. Previous studies using Toll-like receptor 7 (TLR7) agonists and broadly neutralizing antibodies (bNAbs) have shown delay or prevention of viral rebound following antiretroviral therapy (ART) discontinuation in simian-human immunodeficiency virus (SHIV)-infected ...

Apr 23rd, 2022 - Activation of the aryl hydrocarbon receptor (AhR) can alter diurnal rhythms including those for innate lymphoid cell numbers, cytokine and hormone levels, and feeding behaviors. Because immune responses and antibody levels are modulated by exposure to AhR agonists, we hypothesized that some of the variation previously reported for the effects of AhR activation on fecal secretory immunoglobulin ...

Apr 22nd, 2022 - Thrombopoietin receptor agonists (TPO-RAs) are approved for immune thrombocytopenia (ITP), but their impact on health-related quality of life (HRQoL) remains poorly investigated in clinical practice. This observational study aimed to gain insight into real-world patient-reported experiences of the burden of ITP and TPO-RAs. An online questionnaire of closed questions was used to collect views o...

Apr 21st, 2022 - Opioid receptor agonists are effective analgesic agents. Central activation of the mu and/or kappa opioid receptors (KOR) is associated with CNS side effects, which limits their effectiveness. Recent studies indicated that peripherally restricted, selective KOR agonists were potent analgesics and devoid of CNS-related side effects. To confirm this hypothesis, we designed a novel, potent, and pe...

Apr 16th, 2022 - Transdermal fentanyl is widely used in the treatment of severe pain because of convenience, safety, and stable blood concentrations. Nevertheless, patients often develop tolerance to fentanyl, necessitating the use of other opioids; transdermal buprenorphine patch is widely used as an analgesic agent, though available formulation does not provide comparable analgesic effect as transdermal fenta...