Search Results (36)

Background/Objectives: Osteoporosis is highly prevalent and contributes substantially to morbidity and mortality, yet long-term concerns about pharmacologic therapies leave a major treatment gap. Soy isoflavones have been investigated as safer alternatives, but results across trials are inconsistent. A key unresolved issue is the equol-producer phenotype, the gut microbial ability to convert daidzein to S-equol, the most bioactive isoflavone metabolite, which may explain much of this variability. This narrative review synthesizes mechanistic, translational, and clinical evidence to clarify the potential skeletal relevance of S-equol. Methods: Literature was identified through PubMed and Scopus searches (January 2000–October 2025) for experimental, mechanistic, and clinical studies examining S-equol, estrogen receptor β (ERβ), and bone metabolism, with emphasis on equol-producing status, bone strength and bone microarchitecture. Results: S-equol acts as a high-affinity ERβ agonist with antioxidant and anti-inflammatory properties but lacks the carcinogenic or thrombotic risks linked to ERα activation. In estrogen-deficient rodent models, S-equol improves trabecular bone volume by 10–20%, increases trabecular number, and enhances biomechanical strength. These findings align with preclinical evidence demonstrating that S-equol preserves trabecular microarchitecture, enhances bone strength, and reduces bone turnover. A limited number of human trials show reductions in bone resorption by 20% at a daily dose of 10 mg S-equol. In contrast, trials of soy isoflavones in humans have produced inconsistent findings, partly because of substantial variability in equol-producer phenotype among participants and the reliance on dual-energy X-ray absorptiometry, which cannot distinguish trabecular from cortical compartments. Advanced bone imaging and microbiome-informed approaches enable the precise evaluation of S-equol’s skeletal effects on trabecular bone and cortical bone, separately. Conclusions: S-equol represents a promising model for “precision nutrition,” where microbiome, hormonal, and host factors converge with potential to prevent age-related bone fragility. Rigorous trials that integrate microbiome phenotyping and advanced imaging are needed to validate this approach, translate mechanistic promise into clinical benefit, and better define safety. Full article

Tirzepatide is a long-acting agonist for the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors approved for the treatment of type 2 diabetes mellitus, weight management in obese patients, or overweight patients with at least one weight-related comorbid condition. The clinical effects of tirzepatide are demonstrated by improved glycemic control, reduced overall appetite, decreased food intake, and body weight. Several studies indicated that the vasculoprotective effects and anti-atherosclerotic potential of tirzepatide extend far beyond glycemic control. Tirzepatide stimulates the mobilization and function of endothelial progenitor cells, which facilitates vascular repair and mitigates hyperglycemia-induced damage. Tirzepatide enhances the activity of endothelial nitric oxide synthase, reduces the activity of endothelial activation molecules such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, promotes vasodilation, and reduces peripheral vascular resistance. Furthermore, the drug inhibits inflammation by suppressing the expression of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-1β, and interleukin-6. Moreover, tirzepatide improves lipid profiles by decreasing total cholesterol, low-density lipoprotein cholesterol, and triglycerides, while increasing high-density lipoprotein cholesterol. By improving endothelial function, reducing inflammation, and lowering body weight, tirzepatide lowers both systolic and diastolic blood pressure. This article summarizes the data with special emphasis on the mechanisms underlying the anti-atherosclerotic and vasoprotective effects of tirzepatide, based on studies conducted to date. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is characterized by progressive β-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may enhance β-cell function. Semaglutide, a long-acting GLP-1 RA, improves glycemic control and weight, but its direct effects on β-cell function remain uncertain. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251034071). PubMed, Embase, and Scopus were searched through April 2025 for randomized controlled trials evaluating semaglutide’s effects on β-cell function in adults with T2DM. Primary outcomes included HOMA-B, HOMA-IR, and the proinsulin/insulin ratio; secondary outcomes included insulin secretion rate, insulinogenic index, and C-peptide. Two reviewers independently performed data extraction and risk-of-bias assessment using the Cochrane RoB 1 tool. Random-effects models were used for pooling. Certainty of evidence was evaluated using GRADE. Results: Sixteen trials (n = 6591) met inclusion criteria, with nine included in the meta-analysis. Semaglutide improved β-cell function (HOMA-B log ratio of means 1.50, 95% confidence interval [CI]: 1.25–1.80) and reduced insulin resistance (HOMA-IR ratio 0.82, 95% CI: 0.73–0.94) compared with placebo or active comparators. The pooled treatment ratio for proinsulin/insulin was 0.70 (95% CI: 0.63–0.79). However, risk of bias was generally high due to open-label designs, and certainty of evidence for all primary outcomes was rated very low. Conclusions: Semaglutide appears to improve β-cell function and insulin sensitivity in adults with T2DM, but conclusions remain uncertain given the very low certainty of evidence and substantial heterogeneity. High-quality trials with standardized β-cell outcomes are needed to confirm these findings. Full article

In chronic obstructive pulmonary disease (COPD), dysregulated calcium homeostasis, oxidative stress, and mucus hypersecretion converge to suppress ciliary beat frequency (CBF), thereby compromising mucociliary clearance (MCC). These mechanisms are subject to pharmacological modulation. Long-acting muscarinic antagonists (LAMAs) exert direct cilia-stimulatory effects and may counteract pathogen-induced mucin overproduction without impairing clearance. Long-acting β₂-agonists (LABAs) enhance ciliary activity through the cAMP–PKA–dynein (cyclic adenosine monophosphate–protein kinase A–dynein) signalling pathway. Inhaled corticosteroids (ICSs), although largely neutral on CBF, provide indirect protection by suppressing IL-13–driven inflammation. Phosphodiesterase (PDE)-4 inhibitors sustain intracellular cAMP and promote ciliary motility, though their clinical use remains limited by adverse effects. Emerging evidence suggests that dual and triple therapies may provide additive or synergistic benefits for preserving mucociliary function. Clinically, ex vivo CBF interpretation may be influenced by ongoing pharmacotherapy and tissue sampling site. Nasal brush samples may predominantly reflect systemic rather than inhaled therapy. Moreover, differences in PDE isoform expression between nasal and bronchial epithelium further complicate direct extrapolation of results. Rigorous patient stratification by treatment regimen is therefore essential to reconcile inconsistencies reported across studies. Ultimately, preservation of MCC in COPD depends on a delicate balance between oxidative stress and pharmacological modulation of ciliary function. Full article

Background: The core management of most individuals with asthma and COPD is daily treatment with inhalers such as inhaled corticosteroids (ICS) and long-acting bronchodilators. The two main types of inhalers used are pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Different studies have shown low adherence to inhaler treatments among subjects with asthma and COPD. In this study, we explored the differences in adherence between pMDIs and DPIs of combined ICS and long-acting β₂-agonist inhalers (ICS + LABA) in a large cohort, free from commercial biases. Methods: In this historical prospective study, we included all adult subjects with asthma and/or COPD who acquired at least one ICS + LABA inhaler between 2016 and 2019. We carried out propensity score matching and then compared the maximal number of pMDIs and DPIs purchased in any continuous 12 months during the study period. We also compared once-a-day DPIs with twice-a-day DPIs. Results: Of the 36,998 matched subjects, 5897 (15.9%) purchased pMDIs. The overall median [IQR] inhalers purchased for pMDIs and DPIs were 1 [1, 4] and 3 [1, 8], respectively; for subjects with asthma, 1 [1, 3] and 2 [1, 6]; for subjects with COPD, 1 [1, 3] and 3 [1, 10]; and for subjects with asthma–COPD overlap, 2 [1, 7] and 6 [2, 12]. For all the comparisons, p < 0.001. The once-a-day DPI group had a slight but significantly better adherence than the twice-a-day DPI group. Conclusions: For ICS + LABA therapy, the number of DPIs purchased was significantly greater than the number of pMDIs purchased, as well as the once-a-day DPI relative to the other DPIs. Overall, subjects with asthma and/or COPD had low adherence to all inhalers, with the highest adherence observed among subjects with asthma–COPD overlap. Full article

Background/Objectives: Diabetes mellitus (DM) is an increasingly prevalent endocrine disorder affecting humans and companion animals. Type 1 DM (T1DM) and type 2 DM (T2DM) are well characterized in humans, and canine DM most often resembles T1DM, marked by insulin dependence and β-cell destruction. Conversely, feline DM shares key features with human T2DM, including insulin resistance, obesity-related inflammation, and islet amyloidosis. This review provides a comprehensive comparative analysis of antidiabetic therapies in humans, dogs, and cats, focusing on three core areas: disease pathophysiology, pharmacological and delivery strategies, and translational implications. In human medicine, a wide array of insulin analogs, oral hypoglycemic agents, and incretin-based therapies, including glucagon-like peptide-1 receptor agonists (liraglutide) and sodium-glucose cotransporter-2 inhibitors (empagliflozin), are available. Veterinary treatments remain limited to species-adapted insulin formulations and off-label use of human drugs. Interspecies differences in gastrointestinal physiology, drug metabolism, and behavioral compliance influence therapeutic efficacy and pharmacokinetics. Recent innovations, such as microneedle patches for insulin delivery and continuous glucose monitoring systems, show promise in humans and animals. Companion animals with naturally occurring diabetes serve as valuable models for preclinical testing of novel delivery platforms and long-acting formulations under real-world settings. While these technologies show potential, challenges remain in regulatory approval and behavioral adaptation in animals. Conclusions: Future research should prioritize pharmacokinetic bridging studies, veterinary-specific formulation trials, and device validation in animal models. By highlighting shared and species-specific characteristics of DM pathogenesis and treatment, this review advocates a One Health approach toward optimized antidiabetic therapies that benefit human and veterinary medicine. Full article

Background: Japanese guidelines recommend the addition of a long-acting muscarinic antagonist for patients with asthma uncontrolled on inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) therapy, the effectiveness of which is evaluated here. Methods: Retrospective, observational, single-arm cohort study in patients with asthma initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) following ICS/LABA, using independently analyzed data from Japanese claims databases: JMDC and Medical Data Vision (MDV). The index date was that of the first FF/UMEC/VI prescription. Outcomes were assessed during a 12-month follow-up versus a 12-month pre-index period (baseline) and included asthma exacerbations, oral corticosteroid (OCS) use, and short-acting β₂-agonist (SABA) use. P-values associated with rate ratios (RRs) were estimated using Conditional Poisson regression. Results: Overall, 3229 patients in the JMDC database and 1135 in the MDV database were included. Following FF/UMEC/VI initiation, the total annualized moderate–severe asthma exacerbation rate in the JMDC database reduced from 0.50 to 0.40 per-person-per-year (PPPY) (RR [95% confidence interval]: 0.78 [0.73, 0.84]; p < 0.001), with similar reductions in the MDV database: 0.53 to 0.42 PPPY (0.79 [0.70, 0.89]; p < 0.001). In both databases, there was a 20% reduction (JMDC: 0.80 [0.73, 0.88]; p < 0.001; MDV: 0.80 [0.68, 0.94]; p = 0.005) in patients with ≥1 OCS prescription after FF/UMEC/VI initiation. The proportion of patients with ≥1 SABA canister prescription dropped by 31% 0.69 [0.57, 0.84]; p < 0.001) in the JMDC database and 23% (0.77 [0.66, 0.90]; p < 0.001) in the MDV database. Conclusions: This suggests FF/UMEC/VI is effective in improving asthma exacerbations and reducing OCS and SABA use in Japanese patients previously using ICS/LABA in real-world clinical practice. Full article

Background: Asthma significantly impacts global health, necessitating effective management strategies. A combination of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABA) is recommended for patients with inadequately controlled asthma. Method: This prospective, open-label, multicenter study (PROMISING-SHIFT) study evaluated the safety and efficacy of once-daily Indacaterol/Mometasone (IND/MF) dry powder inhaler (DPI) in Indian asthma patients (≥12 years), inadequately controlled with prior therapies. Patients received IND/MF DPI in three strengths (150/80 mcg, 150/160 mcg, 150/320 mcg) over 12 weeks. Results: The study included a total of 174 participants, and 27 adverse events (AEs) in 25 patients (14.37%) were reported, primarily mild to moderate, with no serious adverse events (SAEs). Drug-related treatment-emergent adverse events (TEAEs) were observed in 11 patients. Significant improvements were noted in the mean trough FEV1 and FVC, increasing from baseline to week 4 and week 12 (p < 0.001). The mean ACQ-5 score significantly decreased from 3.0 ± 0.73 baseline to 2.50 ± 0.53 (16.67%) at week 4 and further to 1.73 ± 0.35 at week 12, along with reduced exacerbations (p < 0.001). The need for rescue medication declined from 13.79% to 8.62%, and 96.55% of patients reported treatment satisfaction by study completion. Conclusion: Once-daily IND/MF DPI demonstrated a favorable safety profile with marked improvements in lung function, asthma control, and patient satisfaction, making it a promising option for long-term asthma management in Indian patients. Full article

Background/Objectives: Numerous European countries, including Romania, are facing the concern of rapid ageing of their populations. Moreover, Romania’s life expectancy ranks among the lowest in the European Union. In light of this, it is imperative that the assessment of medication-related harm be given national priority in order to secure and enhance pharmacotherapy and the medical act. In this study, we sought to describe and evaluate the under-prescribing practices among the Romanian elderly population. Methods: We conducted a cross-sectional study in urban areas of two counties in Western Romania (Timis and Arad) from November 2017 to February 2019. We collected chronic electronic prescriptions issued for elderly patients (>65 years old) with chronic conditions. The medication was prescribed by generalist or specialist physicians for periods ranging between 30 and 90 days. To assess inappropriate prescribing behaviours, a multidisciplinary team of specialists applied the Screening Tool of Older Persons’ Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) v.2 criteria to the collected prescriptions. Results: Within the 1498 prescriptions included in the study, 57% were issued to females, the mean age was 74.1 ± 6.95, and the average number of medicines per prescription was 4.7 ± 1.51. The STOPP criteria most commonly identified were the (1) long treatment duration (23.6%) and (2) prescription of neuroleptics (14.6%) or zopiclone (14.0%) as medications that increase the risk of falls. According to START criteria, the following medicines were under-prescribed: (1) statins (47.4%), (2) beta-blockers (24.5%), (3) antiresorptive therapy (10.0%), and (4) β2-agonists and muscarinic antagonists for chronic obstructive pulmonary disease (COPD) (4.5%). Within our study group, the prevalence of potentially inappropriate medications was 18.58%, whereas the prevalence of potential prescribing omissions was 49.2%. Conclusions: To decrease medication-related harm and morbid-mortality, and to increase the quality of life for elderly people in Romania, immediate actions are needed from national authorities. These actions include reinforcing primary care services, providing periodic training for physicians, implementing medication review services by pharmacists, and utilising electronic health records at their full capacity. Full article

In recent years, some new concepts have been added to asthma treatment such as “anti-inflammatory reliever” (β2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population. Full article

Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the β2-adrenergic receptor (β2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified β2-AR signaling on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting β2-AR agonist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct region, modified fatty acid metabolism, and reduced foam cell formation. However, it did not reduce markers of post-stroke neurodegeneration or improve recovery. Although our findings indicate that enhancing MB in myeloid cells can aid in the processing of brain lipid debris after stroke, it is important to note that boosting MB alone may not be sufficient to significantly impact stroke recovery. Full article

Lung cancer frequently affects patients with Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS) fosters cancer progression by increasing oxidative stress and by modulating epithelial-mesenchymal transition (EMT) processes in cancer cells. Formoterol (FO), a long-acting β2-agonist widely used for the treatment of COPD, exerts antioxidant activities. This study explored in a lung adenocarcinoma cell line (A549) whether FO counteracted the effects of cigarette smoke extract (CSE) relative to oxidative stress, inflammation, EMT processes, and cell migration and proliferation. A549 was stimulated with CSE and FO, ROS were evaluated by flow-cytometry and by nanostructured electrochemical sensor, EMT markers were evaluated by flow-cytometry and Real-Time PCR, IL-8 was evaluated by ELISA, cell migration was assessed by scratch and phalloidin test, and cell proliferation was assessed by clonogenic assay. CSE significantly increased the production of ROS, IL-8 release, cell migration and proliferation, and SNAIL1 expression but significantly decreased E-cadherin expression. FO reverted all these phenomena in CSE-stimulated A549 cells. The present study provides intriguing evidence that FO may exert anti-cancer effects by reverting oxidative stress, inflammation, and EMT markers induced by CS. These findings must be validated in future clinical studies to support FO as a valuable add-on treatment for lung cancer management. Full article

Long-acting muscarinic antagonists (LAMAs) are a class of inhalers that has recently been included as add-on therapy in the GINA guidelines, either in a single inhaler device with inhaled corticosteroids plus long-acting β2-agonists (ICS + LABA) (closed triple inhaler therapy) or in a separate one (open triple inhaler therapy). This review summarizes the existing evidence on the addition of LAMAs in patients with persistently uncontrolled asthma despite ICS + LABA treatment based on clinical efficacy in the reduction of asthma symptoms and exacerbations, the improvement in lung function, and its safety profile. Full article

Inhaled corticosteroids (ICSs) are widely used in chronic obstructive pulmonary disease (COPD) and in combination with long-acting β2 agonists (LABAs) to reduce exacerbations and improve patient lung function and quality of life. However, ICSs have been associated with an increased risk of pneumonia in individuals with COPD, although the magnitude of this risk remains unclear. Therefore, it is difficult to make informed clinical decisions that balance the benefits and adverse effects of ICSs in people with COPD. There may be other causes of pneumonia in patients with COPD, and these causes are not always considered in studies on the risks of using ICSs in COPD. We consider it very useful to clarify these aspects in assessing the influence of ICSs on the incidence of pneumonia and their role in the treatment of COPD. This issue has important implications for current practice and the evaluation and management of COPD, since COPD patients may benefit from specific ICS-based treatment strategies. Many of the potential causes of pneumonia in patients with COPD can act synergistically, so they can be included in more than one section. Full article

Emergency care for asthma is provided by general practitioners, pulmonologists, and emergency departments (EDs). Although it is known that patients presenting to EDs with acute asthma exacerbations are a vulnerable population and that this mode of presentation is a risk marker for more severe complications, research on this population is scarce. We conducted a retrospective study on patients with asthma exacerbations who presented to the ED of the University Hospital Basel, Switzerland, during 2017–2020. Of the last 200 presentations, 100 were selected and analyzed to assess demographic information, the use of previous and ED-prescribed asthma medication, and clinical outcomes after a mean period of time of 18 months. Of these 100 asthma patients, 96 were self-presenters, and 43 had the second highest degree of acuity (emergency severity index 2). Global Initiative for Asthma (GINA) step 1 and step 3 were the most common among patients with known GINA levels, accounting for 22 and 18 patients, respectively. A total of 4 patients were undergoing treatment with oral corticosteroids at presentation, and 34 were at discharge. At presentation, 38 patients used the combination therapy of inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA), and 6 patients underwent ICS monotherapy. At discharge, 68 patients were prescribed with ICS/LABA. At entry to the ED, about one-third of patients did not use any asthma medication. In total, 10 patients were hospitalized. None of them needed invasive or non-invasive ventilation. A follow-up for the study was precluded by the majority of patients. This group of asthma patients seemed particularly vulnerable as their asthma medication at presentation was often not according to guidelines or even lacking, and almost all the patients had self-presented to the ED without any reference from a physician. The majority of patients did not give consent to the collection of any follow-up information. These medical shortcomings reflect an urgent medical need to improve care for patients at high risk of asthma exacerbations. Full article