Search Results (4,433)

Background: Managing neuropathic pain (NP) is particularly challenging in the context of opioid use, and the mechanisms behind chronic pain remain unclear. Objective: This study evaluated the impact of turmeric bioactive compounds on brain regions including frontal cortex (FC), hippocampus (HPC), and hypothalamus (HPT) in the spinal nerve ligation (SNL) in a rat model of NP. Methods: Twenty-four SD rats were assigned to four groups (N = 6 per group), namely sham+vehicle (Sham-V), SNL+vehicle (SNL-V), SNL + 100 mg/kg curcumin (SNL+100CUR), and SNL + 50 mg/kg bisdemethoxycurcumin (SNL+50BDMC), treated daily for four weeks via oral gavage. Gene expression levels related to neuroinflammation, oxidative stress, and mitochondrial homeostasis were measured using qRT-PCR. Protein-level or functional mitochondrial assays were not performed due to limited sample availability. Results: In the FC, SNL decreased the expression level of NRF1 and OPA1, but only OPA1 was increased by BDMC. In the HPC, SNL increased CD11b, NRF2, and MFN1; BDMC decreased CD11b and increased IBA1, NRF1, TFAM, PGC1α and Complex I; and CUR increased NRF1, TFAM, DRP1 and Complex I levels. In the HPT, SNL decreased GFAP and MFN1, with CUR and BDMC further decreasing GFAP but not affecting MFN1. Additionally, CUR and BDMC decreased the expression of several key markers of neuroimmune signaling and mitochondrial homeostasis, including IBA1, CD11b, NFkB, NRF1/2, DRP1, OPA1, PGC1α, TFAM, and PINK1. Conclusions: CUR and BDMC induced region-specific transcriptional remodeling of mitochondrial homeostasis across FC, HPC, and HPT in SNL rats, with somewhat limited effects in the FC, mixed effects in the HPC, and broader downregulation in the HPT. Full article

Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed DNA, histones, and proteins released by activated neutrophils. Originally identified as an innate defense mechanism against pathogens, NETs have since been implicated in cancer progression and immune evasion. Within the tumor microenvironment (TME), NETs suppress anti-tumor immunity through multiple mechanisms, including the physical exclusion of CD8⁺ cytotoxic T lymphocytes from the tumor interior and upregulation of exhaustion markers via checkpoint ligands. This review synthesizes current preclinical and clinical evidence on the interplay between NETs and CD8⁺ T cells across multiple malignancies, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, bladder cancer, hepatocellular carcinoma, skin cancer, and penile cancer. Cancer-specific mechanisms of NET-mediated immune suppression are discussed, including IL-8, IL-17, CXCL6, and TGF-β-driven NETosis pathways. Clinical data consistently demonstrate that elevated NET levels correlate with reduced CD8⁺ T cell infiltration, T cell dysfunction, and worse patient outcomes. Emerging therapeutic strategies targeting this axis are reviewed, including DNase I-mediated NET degradation, Peptidyl arginine deiminase 4 (PAD4) inhibition, CXCR2 blockade, and combination approaches with immune checkpoint inhibitors. These interventions have shown promise in restoring CD8⁺ T cell cytotoxicity and overcoming immunotherapy resistance in preclinical models. Collectively, the evidence supports the NET-CD8⁺ T cell axis as a promising prognostic and therapeutic target warranting further clinical investigation. Full article

Pancreatic ductal adenocarcinoma (PDAC) is increasingly recognized as a systemic malignancy, characterized by profound alterations in tumor–host interactions. Small extracellular vesicles (sEVs) in peripheral blood may reflect these alterations and represent a promising minimally invasive source of biomarker information. In this proof-of-principle study, plasma-derived sEVs from patients with PDAC, healthy controls, and a comparative cohort with neuroendocrine lung cancer (NLC) were isolated by differential ultracentrifugation and characterized by western blotting and nanoparticle tracking analysis. Surface marker profiling was performed using the MACSPlex EV Kit IO, followed by univariate, multivariate, and machine-learning-based analyses. PDAC samples exhibited a distinct sEV immunophenotype with coordinated enrichment of angiogenesis-related markers (including CD105 and CD146), immune-regulatory markers (including CD25 and CD40), the coagulation-related marker CD142 and the invasion-associated marker MCSP. Principal component analysis, hierarchical clustering, and Random Forest classification showed exploratory separation of PDAC patients from healthy controls and NLC, supporting the presence of disease-specific vesicle surface marker patterns. In a very small subset of paired samples, descriptive longitudinal analyses illustrated measurable intra-individual changes during chemotherapy. Plasma sEV immunophenotyping is a technically feasible approach for capturing systemic disease-associated alterations in PDAC and provides a foundation for future biomarker-oriented validation studies. Full article

Botulinum toxin type A (BoNT-A) is an established treatment for cervical dystonia (CD), but objective neurophysiological markers across the injection cycle and between preparations are not well defined. We assessed afferent conduction (captured by CSP parameters), efferent conduction (captured by F-wave parameters) and clinical severity (TWSTRS) in 28 patients with caput-type cervical dystonia during waning (>14 weeks post-injection) and peak (4–6 weeks) phases, comparing onabotulinumtoxinA (ONA) and abobotulinumtoxinA (ABO). F-wave measures changed only modestly: F–M latency increased with ONA, while F-wave persistence decreased with ABO. In contrast, CSP measures consistently increased at peak in both groups (CSP end latency and CSP duration; both p ≤ 0.001). Overall, BoNT-A treatment phase is better reflected by CSP-derived inhibitory measures than by F-wave indices. TWSTRS improved at peak for both toxins, with no difference between ONA and ABO in clinical change (ΔTWSTRS p = 0.5514). Full article

Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, immune dysregulation, and increased susceptibility to infections. Obesity may influence these processes and has been proposed as a potential contributor to the so-called “obesity paradox”, although its effects on immune competence, viral burden, and survival are not yet fully understood. Seventy patients with severe to very severe COPD (GOLD stage 3–4) were stratified according to BMI (<30 vs. ≥30 kg/m²). Clinical and functional parameters were assessed together with biomarkers of oxidative stress, DNA damage, systemic inflammation, and T-cell subsets. A comprehensive viral panel, including Torque Teno virus (TTV), was also analyzed. Five-year survival was evaluated using Kaplan–Meier curves and Cox regression models. Patients with BMI ≥ 30 showed higher lymphocyte counts and increased CD4⁺ and CD8⁺ T-cell levels, accompanied by lower systemic inflammatory indices. No significant differences were observed in oxidative stress or DNA damage markers. In addition, TTV viremia (≥4 log₁₀ copies/mL) was more frequently observed among patients with lower BMI. Despite these differences, five-year survival did not significantly differ between the two groups. These findings suggest that BMI alone may have limited value as a predictor of outcomes in patients with advanced COPD. Conversely, immune-inflammatory indices and viral burden, particularly TTV viremia, could provide complementary information for risk assessment and may deserve further investigation as potential tools for personalized patient stratification. Full article

Background: Multiparameter flow cytometry is widely used in the diagnosis of acute leukemia, allowing for rapid identification of leukemic cells based on their immunophenotype. The EuroFlow Acute Leukemia Orientation Tube was designed as a standardized screening tool to support early diagnostic orientation and guide further, more targeted testing. In this study, we assessed the diagnostic performance of the ALOT panel in pediatric patients with suspected acute leukemia. Methods: A total of 254 pediatric patients (0–18 years) with suspected acute leukemia were analyzed. Bone marrow samples were assessed using multiparameter flow cytometry with the EuroFlow ALOT panel, comprising eight markers (MPO, cyCD79a, CD34, CD19, CD3, cyCD3, CD7, and CD45). Final diagnoses were established using extended immunophenotypic panels and additional diagnostic methods when required. Samples were processed according to EuroFlow standard operating procedures and acquired on FACSCanto II and FACSCanto 10-color flow cytometers (BD Biosciences). Diagnostic performance was assessed by calculating sensitivity, specificity, precision, accuracy, and negative predictive value. Results: Among 254 patients, 234 were diagnosed with hematologic disorders, while 20 had normal bone marrow findings. The ALOT panel correctly identified all pathological samples and did not misclassify any normal sample, resulting in 100% sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for discrimination between abnormal and normal samples. In terms of exact diagnostic orientation, ALOT correctly classified 244 of 254 cases (96.1%) using a single-tube approach. The remaining 10 cases (3.9%), including rare entities such as Burkitt leukemia, chronic myeloid leukemia, and transient myeloproliferative syndrome, required extended immunophenotypic evaluation. Importantly, these cases were not false negative results, as all were correctly identified as abnormal. Conclusions: The EuroFlow ALOT panel is a reliable screening tool for rapid diagnostic orientation in pediatric acute leukemia. Its implementation facilitates targeted selection of extended immunophenotypic panels, improving the efficiency and cost-effectiveness of diagnostic workflows. Full article

Background: Torque teno virus (TTV) is a ubiquitous, non-pathogenic component of the human virome whose role in people living with HIV (PLWH), particularly during antiretroviral therapy (ART)-mediated immune reconstitution, remains unclear. This systematic review aimed to synthesize available evidence on TTV viral load in PLWH, focusing on its relationship with immunological markers. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted in MEDLINE, Web of Science, and Scopus in January 2026 to identify studies assessing plasma TTV viral load before and/or during ART and reporting immunological outcomes. Eligible studies included prospective and retrospective longitudinal studies, cross-sectional studies, and mixed designs assessing plasma TTV viral load in relation to ART status and immune recovery markers. Results: Thirteen studies (n = 1700 PLWH) were included, predominantly observational and conducted in adult populations. Most studies (76.9%) reported a significant inverse association between TTV viral load and CD4 T-cell count, while all studies assessing HIV viral load found a direct correlation with TTV levels. An inverse relationship with the CD4/CD8 ratio was consistently observed where evaluated. Higher TTV loads were reported in ART-naïve individuals and in those with advanced immunosuppression, with longitudinal studies indicating a general decline during ART. Overall, methodological heterogeneity and moderate risk of bias were common. Conclusions: TTV viral load shows a consistent inverse association with CD4 cell count and may reflect global immune dysfunction in PLWH beyond conventional markers. However, its clinical utility remains investigational due to the heterogeneity in the study design, limited data on longitudinal dynamics, and lack of standardized assays and thresholds. Full article

Artisanal and small-scale gold mining (ASGM) generates complex metal mixtures, yet their biological effects remain poorly characterized in high-altitude populations, where occupational exposure occurs against a hypoxic environmental background. This study evaluated 49 occupationally exposed gold miners from the Vetas–California mining district, near the Santurbán páramo in Colombia, and 25 non-exposed individuals from a comparable high-altitude area. Hair concentrations of essential and toxic elements were quantified by ICP-MS, and serum catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG), and the GSH/GSSG ratio were assessed. Miners showed a distinct multielement profile, with a higher toxic-metal burden and a dominant mixture mainly characterized by Fe, Mn, As, Pb, Cd, and Hg. CAT and SOD activities did not differ markedly between groups, although SOD activity decreased along the main exposure gradient among exposed workers. In contrast, glutathione-related biomarkers showed a more consistent exposure-related pattern, with higher GSSG and a lower GSH/GSSG ratio, suggesting a shift toward a more oxidized glutathione redox status. Together with positive within-group associations between selected elements and the GSH/GSSG ratio, these results are consistent with a mixture-associated perturbation of glutathione redox homeostasis, with heterogeneous adaptive responses. Overall, this study supports the use of integrated biomonitoring strategies and highlights glutathione-related markers as potential indicators of early redox perturbation in high-altitude mining populations. Full article

Background: The tumor immune microenvironment, particularly the role of cytotoxic CD8+ T lymphocytes, is crucial in cancer progression but remains poorly understood in pituitary neuroendocrine tumors (PitNETs). The significance of CD8+ cell infiltration varies across PitNET subtypes, suggesting a complex interplay with tumor cell lineage. This study aimed to characterize the distribution of CD8+ tumor-infiltrating lymphocytes across different PitNET subtypes defined by the current WHO classification and to explore their association with clinicopathological features. Methods: We conducted a retrospective study on 40 surgically resected PitNETs. All cases were classified based on immunohistochemical expression of pituitary hormones and lineage-specific transcription factors (PIT-1, TPIT, SF-1). CD8+ lymphocyte density was quantified using immunohistochemistry and calculated as cells/mm². Exploratory statistical analysis was performed based on non-parametric tests to compare CD8+ cell density across tumor subtypes and with parameters like tumor size, invasiveness (Knosp grade), and proliferation index (Ki-67). Findings are to be treated as observational trends. Results: The highest density of CD8+ lymphocytes was observed in plurihormonal PIT-1-positive tumors [17.61 cells/mm² (IQR: 17.61–60.36)], followed by somatotroph [13.2 (6.6–15.72)] and mammosomatotroph [13.83 (0–21.38)] tumors. A difference in CD8+ density was found between PIT-1-positive and PIT-1-negative tumors (n1 = 34, n2 = 6, U = 49.5, p_exact = 0.050, r = 0.33); the medium effect size indicates a possible lineage-related trend. Another difference was observed between SF-1-positive and SF-1-negative tumors (p = 0.025), with SF-1 lineage tumors showing the lowest infiltration. No correlations were found between CD8+ density and tumor size, Knosp grade, or Ki-67 index. Conclusions: The distribution of intratumoral CD8+ T lymphocytes in PitNETs is highly heterogeneous and appears to be strongly dictated by the transcription factor-defined tumor lineage rather than by traditional clinicopathological markers of aggressiveness. PIT-1 lineage tumors harbor a more active immune microenvironment, while SF-1 lineage tumors are relatively ‘immune-poor’. These findings highlight the immunological diversity of PitNETs and support further investigation of the tumor immune landscape. Collaborative multi-institutional studies are required to validate these trends. Full article

Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut–heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management. Full article

Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S/R)-ginsenoside Rh1 in suppressing colorectal cancer through the regulation of gut microbiota and Trp metabolism. Azoxymethane/dextran sulfate sodium (AOM/DSS)was employed to induce a CRC mouse model, followed by treatment with 20(S/R)-ginsenoside Rh1 at 100 mg·kg⁻¹·day⁻¹ for 6 weeks. 20(S/R)-ginsenoside Rh1 significantly reduced the disease activity index (DAI) score, restored colon length, and decreased tumor count. 20(S/R)-Ginsenoside Rh1 ameliorated gut dysbiosis by increasing gut microbial diversity and elevating the prevalence of beneficial bacteria, including Lactobacillus, and stimulated the production of indole derivatives, including indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), and indole-3-lactic acid (ILA) by enriching Trp -metabolizing bacteria such as Lactobacillus reuteri. These changes further activated the AhR/CYP1A1/IL-22 and PXR/TLR4 pathways, upregulated the expression of intestinal tight junction proteins, suppressed the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IFN-γ, and elevated the levels of the anti-inflammatory cytokine IL-10. Furthermore, 20(S/R)-ginsenoside Rh1 reduces the serum kynurenine (Kyn)/Trp ratio, downregulates the expression of forkhead box P3 (FoxP3), a marker of regulatory T (Treg) cells, and increases the number of CD8⁺ T cells by inhibiting the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in colonic tissue. In conclusion, 20(S/R)-ginsenoside Rh1 showed potential anti-CRC activity, with our study observing links between its action and gut microbiota structure regulation, Trp metabolism modulation, AhR/PXR-mediated intestinal barrier activation, and IDO1-related immune suppression reversal. Full article

Extracellular vesicles (EVs) have become a key area of research, as scientists study their role in various biological processes. These vesicles appear to play a key role in the use of mesenchymal signaling cells (MSCs, formerly known as mesenchymal stem cells) to treat various diseases, such as osteoarthritis (OA), and other degenerative conditions. In our experiments, we examined EVs formed by canine mesenchymal signaling cells (MSCs) to identify them according to current guidelines and define their content, particularly the microRNA (miRNA) they contain, for future research projects. After obtaining the EVs, we demonstrated via Western blotting and transmission electron microscopy that the nanoparticles visible in the nanotracking analysis were positive for CD9 and ALIX and positive for CD9 and CD81, respectively. Markers for nanoparticles that do not represent extracellular particles—tested here as cytochrome C for mitochondrial particles and histones for nuclear particles—were negative. Finally, we detected a total of 85 different miRNAs in the negative controls. To determine the potential influence of various cell stimulations intended to induce osteoarthritis (e.g., interleukin-1β stimulation) or a possible treatment (e.g., shockwave therapy), or the influence of ITS prior to extracellular vesicle extraction, we detected a total of 208 different miRNAs. These results demonstrate how canine EVs from MSCs can be detected in vitro and how the EVs’ miRNA profile changes after stimulation of the producing cells. This information may provide valuable insight into the understanding and treatment of osteoarthritis. Additionally, we demonstrated that using ITS instead of FCS to produce EVs should be reconsidered due to the significant change in miRNA expression levels. Full article

Background/Objectives: Endodontic perforation repair requires biomaterials that balance sealing ability with minimal cellular injury. AH Plus (epoxy resin-based) remains widely used despite cytotoxicity concerns. CeraSeal (calcium silicate-based bioceramic) is a potentially more biocompatible alternative. However, comparative data on sealer-induced cytotoxicity and inflammatory responses remain limited. This study compared the cytotoxicity and inflammatory profiles of CeraSeal and AH Plus using in vitro and in vivo approaches. Methods: Human periodontal ligament stem cells (hPDLSCs) were exposed to sealer extracts (1:4 AH Plus, 1:8 CeraSeal) for 120 h. Cell death was assessed by MTT, Live/Dead, LDH release, and Annexin V/PI flow cytometry. Oxidative stress was quantified via ROS generation (DCFH-DA). In a rat furcation perforation model (n = 8 teeth/group), inflammatory markers (TNF-α, IL-1β, CD68), osteogenic activity (ALP), and osteoclasts (TRAP) were evaluated. Results: AH Plus was associated with significantly greater necrotic cell death (357.6 ± 47.6% LDH release vs. CeraSeal 128.8 ± 37.5%; p = 0.0079) and reduced hPDLSC viability at all time points (p < 0.0001). ROS generation was comparable between sealers (~32–35%, p > 0.05). In vivo, IL-1β was higher in AH Plus-treated tissues (52.25 vs. 24.88 cells/mm²; p = 0.0002), while TNF-α and CD68 were greater in CeraSeal (p ≤ 0.0011). ALP was higher in AH Plus (median 6.15 vs. 3.68; p = 0.0002), with no difference in TRAP-positive osteoclasts. Morphometric analysis showed superior cellular preservation with CeraSeal (p = 0.0079), while inflammatory infiltration was higher in CeraSeal (p = 0.0002). Conclusions: AH Plus was associated with a necrotic-inflammatory profile with elevated IL-1β and higher ALP expression. CeraSeal demonstrated better cellular preservation, lower LDH release, and a distinct inflammatory signature (higher TNF-α and CD68). These findings establish comparative response profiles for the two sealers and support CeraSeal as a potentially biocompatible alternative, though further mechanistic studies are warranted. Full article

Background and Objectives: Intestinal barrier dysfunction is increasingly recognized as a contributor to inflammatory bowel disease (IBD) pathophysiology. Zonulin, a regulator of epithelial tight-junction permeability, has emerged as a potential non-invasive biomarker; however, its clinical relevance remains uncertain. This study evaluated whether fecal zonulin levels reflect clinical disease activity in inflammatory bowel disease and explored their association with ileal involvement in Crohn’s disease (CD). Materials and Methods: Forty-six consecutive IBD patients (26 CD, 20 UC) were prospectively included. Fecal zonulin was measured using a commercially available ELISA. In this study, the term “fecal zonulin” refers to ELISA-detected zonulin-related proteins. Clinical disease activity was assessed using CDAI for CD and the Mayo score for UC. Standard blood and fecal inflammatory markers were obtained, and subgroup analyses were performed according to disease type and location. Results: Fecal zonulin levels were significantly higher in active IBD compared with remission (106.37 vs. 53.80 ng/mL, p = 0.002). Patients with CD had higher zonulin concentrations than those with UC (91.4 vs. 51.0 ng/mL, p = 0.001). Zonulin showed a moderate positive correlation with fecal calprotectin (r = 0.338; p = 0.021). In multivariable analysis, clinical disease activity remained independently associated with zonulin levels, whereas ileal involvement was no longer statistically significant. Conclusions: Fecal zonulin is associated with disease activity in IBD, suggesting that fecal zonulin-related proteins may represent a potential adjunctive marker of epithelial barrier dysfunction and clinical disease activity in IBD. However, these findings should be considered exploratory and require validation in larger, longitudinal multicenter studies using standardized assays and endoscopic correlation. Full article

Background: Ascophyllan, a sulfated polysaccharide extracted from brown seaweed, has shown immunomodulatory and antioxidant effects in preclinical studies, yet human clinical evidence remains scarce. This randomized, double-blind, placebo-controlled pilot trial evaluated the safety and exploratory biological effects of daily ascophyllan supplementation in healthy adults. Methods: Twelve participants were randomized to receive either ascophyllan (n = 6) or placebo (n = 6) for 28 days. Safety was monitored through adverse event reporting and repeated laboratory assessments, including hematology, biochemistry, and inflammatory markers. Immune cell populations were analyzed via serial flow cytometry, serum total antioxidant capacity was measured at multiple time points, and gut microbiome composition was profiled using 16S rRNA gene sequencing. All analyses were exploratory in nature. Results: Ascophyllan supplementation proved well tolerated, with no adverse events observed and stable hematologic, renal, and biochemical parameters throughout the study. Exploratory longitudinal analyses suggested directional modulation of NK-cell-associated phenotypes during ascophyllan supplementation, including directional changes in CD57⁺, NKp46⁺, and NKG2D⁺ NK-cell phenotypes; however, group × time interaction analyses did not remain statistically significant after correction for multiple comparisons. Serum antioxidant capacity showed inter-individual variability with a directional but non-significant increase in the ascophyllan group at intermediate time points. Exploratory microbiome analyses suggested modest directional compositional differences involving members of the Bacteroidaceae and Bifidobacteriaceae families; however, no taxon remained statistically significant after correction for multiple comparisons. Conclusions: These preliminary findings indicate that ascophyllan is safe and well tolerated in healthy adults and may be associated with modulation of innate immune phenotypes, subtle microbiome compositional differences, and directional changes in antioxidant capacity. Larger, adequately powered clinical trials are warranted to confirm these observations and further investigate potential biological and clinical effects. Full article