Search Results (41)

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Background and Objectives: Periodontal regeneration involves techniques intended at restoring the lost supporting tissue around a periodontally weakened tooth. These regenerative methods frequently utilize periosteal grafts to stimulate the evolvement of vital adjacent tissues. This paper intended to evaluate the use of autogenous periosteal grafts in treating grade II furcation defects (Glickman Classification 1953) in patients with chronic periodontitis. Materials and Methods: The databases MEDLINE (via PubMed), Cochrane, EBSCO, and Google Scholar were searched for papers published in English from January 1991 till December 2022. Three individuals examined the reclaimed articles according to the inclusion norms. Randomized controlled trials (RCTs) assessing the efficacy of autogenous periosteal grafts for treating Grade II furcation defects in chronic periodontitis patients were involved. Only four related studies were identified for data extraction, involving 80 patients aged 18 to 52 years. Outcome variables measured included horizontal bone loss (HD), vertical bone loss (VD), pocket depth (PD), clinical attachment level (CAL), bone height (BH), gingival recession (GR), plaque index (PI), and gingival index (GI). Data were examined using RevMan 5.4.1 software. Mean differences and 95% confidence intervals were employed to estimate effect sizes. Results: Both groups showed similar results for reductions in PI, GI, and BOP. However, The periosteal graft also yielded better outcomes for CAL gain, BH, and GR. The meta-analysis showed a significant overall effect of Periosteal Barrier Membrane (PBM) on horizontal and vertical bony change levels, but subgroup differences between unilateral and bilateral applications were not statistically significant due to high heterogeneity. Although the bilateral subgroup demonstrated significant benefits of PBM treatment, the overall findings across the clinical attachment level group remain inconclusive. Conclusion: Current evidence suggests that while PBM may benefit bilateral mandibular sites, and autogenous periosteal grafts offer no added advantage over OFD alone in Grade II furcation defects, the overall findings remain inconclusive. Full article

Background: Lipid-lowering therapies are an option for stabilizing lipid levels. Icosapent ethyl (IPE) is a highly purified formulation of eicosapentaenoic acid, which can reduce lipid action, improve plaque stabilization, reduce platelet aggregation, lower TG, and prevent cardiovascular events. IPE is frequently used with statins to manage elevated TG levels. However, the evidence on IPE as a lipid-lowering agent is limited, and no updated systematic review and meta-analysis have been published considering the recent advancements in the field and newly published studies. Therefore, we aim to fill this gap. Methods: We used the PRISMA guidelines and the PICO (Population, Intervention, Comparison, and Outcome) framework to conduct this review, aiming to answer the question, “Can IPE benefit patients at cardiovascular risk?” GRADE was used to evaluate evidence levels to adhere to the highest criteria. Results: Predominantly, the evaluated population presented TG levels between ≥135 mg/dL and 500 mg/dL and LDL-C levels between >40 mg/dL and ≤100 mg/dL. The included studies showed a reduction in TG and LDL-C and a decrease in cardiovascular events. It means that, according to our systematic review evidence analysis, IPE has been effective in lowering blood lipid levels, including TG, and reducing cardiovascular death and events, such as non-fatal stroke or hospitalization for unstable angina. However, it is worth noting that these results were primarily from patients undergoing statin therapy. According to our meta-analysis, IPE may not be considered a lipid-lowering drug, as limited action associated with its use was evident in the quantitative results. However, caution is necessary, as only two studies were suitable for inclusion due to the differing outcomes in the analyzed samples. Conclusions: Despite the quantitative synthesis, IPE possesses anti-inflammatory, anti-thrombotic, and anti-atherogenic properties, highly related to cardiovascular protection. Based on our included studies, IPE was considered a promising therapy for atherosclerotic cardiovascular disease in conjunction with other lipid-lowering therapies, particularly statins, for patients with extremely high TG levels. The limitations of the reviewed studies may include small sample sizes, varying outcomes, and a small duration of interventions. Future clinical trials with similar outcomes, sample sizes, and intervention durations must be designed, and updated meta-analyses must be published in the following years to fully assess the effects of IPE as a lipid-lowering and cardiovascular protector drug. Full article

Background: Respiratory viruses spread through airborne droplets and aerosols, causing highly contagious acute respiratory syndromes in humans. This study evaluated the antiviral potential of vapours of catmint-oil-based formulations against respiratory viruses. Methods: The antiviral activity of formulations with or without catmint oil (CO) in solution or in aerosolised form was determined against influenza virus H1N1 ATCC VR-1469 and mouse hepatitis virus (MHV-1) ATCC/VR261. In solution, both viruses were exposed to CO formulations for 2–3 h. In aerosolised form, H1N1 was exposed to formulations for 2 min in a closed cylinder and MHV-1 for 10 min in a booth. The antiviral effect of the formulations was evaluated by growing H1N1 in a Madin–Darby canine kidney (MDCK; ATCC-CRL-2936) and MHV-1 in A9 ATCC/CCL 1.4 cells using TCID50 and a plaque assay, respectively. Transmission electron microscopy (TEM) was conducted to investigate the mode of action of the formulations. Results: In solution, the formulation containing hydrogenated CO (HCO), bromelain, N-acetylcysteine and Tween 20 (Formulation (1)) reduced the viability of H1N1 by 2.6 ± 0.07 log₁₀ (p = 0.025) and MHV-1 by 4.5 ± 0.14 log₁₀ (p = 0.014) within 2–3 h. In vapourised form, Formulation (1) produced similar antiviral effects against H1N1, reducing it by 3.00 ± 0.07 log₁₀ (p = 0.002) within 2 min, and Formulation (1) produced a 3.00 ± 0.07 log₁₀ reduction of MHV-1 (p < 0.001) within 10 min (the minimum time needed to detect infective viral particles in the experimental set-ups). Formulation (3) (without bromelain) reduced H1N1 by 1.57 ± 0.14 log₁₀ (p = 0.008) after 2 min and MHV-1 by 1.3 ± 0.04 log₁₀ (p = 0.057) after 10 min. In the absence of catmint oil (Formulation (4)) or in the absence of catmint oil and bromelain (Formulation (5)), there were only slight reductions in the viability of aerosolised H1N1 (1.00 ± 0.14 log₁₀, p = 0.046; <1 log₁₀, p = 0.966, respectively) and MHV-1 (1.07 ± 0.02 log₁₀, p = 0.013; 0.16 ± 0.03 log₁₀, p = 0.910, respectively). The TEM analysis showed that the formulation disrupted the H1N1 envelopes and caused a reduction in size of the viral particles. Conclusions: The catmint-oil-based formulations reduced the H1N1 and MHV-1 by disrupting the vial envelopes. Full article

A phage–antibiotic synergy could be an alternative in urinary tract infection (UTI) therapy, as it leads to the elimination of bacteria and to the reduction in variants resistant to phages and antibiotics. The aims of the in vitro study were to determine whether phages vB_Efa29212_2e and vB_Efa29212_3e interact synergistically with selected antibiotics in the treatment of E. faecalis infections, to optimize antibiotic concentrations and phage titers for the most effective combinations, and to assess their impact on the number of spontaneous resistant variants and on the phages’ reproductive cycles. The modified double-layer disc diffusion method, checkboard, time–kill assays, one-step growth method and the double agar overlay plaque assay were implemented. Synergistic interactions were most often observed after the combined action of phages 2e or 3e and β-lactam antibiotics on E. faecalis strains. The beneficial effects depended on the bacterial strain, phage and antibiotic used. The lowest minimum inhibitory concentration (MIC₅₀) values of the antibiotics were recorded, after the application of low titers of phage 2e, and high titers of phage 3e. The combined use of the tested agents resulted in a significant reduction in the number of resistant variants and had an impact on the reproductive cycle of the tested phages, e.g., a 50% increase in burst size, and a 5 min reduction in the latency period of 2e were observed. The study confirmed beneficial interactions between phages and β-lactam antibiotics against E. faecalis growth. Full article

Background: The purpose of this study is to examine the combination of the mechanical effects of penile therapy with vacuum erection devices (VEDs) plus PDE5i, which improve clinical outcomes after extracorporeal shockwave therapy (ESWT) in men affected by erectile dysfunction (ED) associated with Peyronie’s disease (PD). Methods: A total of 153 medical records of patients affected by PD in stable stage with ED and treated with ESWT were divided into two groups. Group A (GA) included 72 men treated with ESWT, mechanical stretching with VEDs and PDE5ì (Tadalafil 5 mg), and Group B (GB) included 81 men who received only ESWT plus Tadalafil 5 mg with the same protocol of GA. The patients in both groups were assessed at baseline and follow-up for erectile function, painful erections, penile plaque size, and penile curvature. The results were evaluated at baseline and 3, 6, and 12 months after the treatments. Results: Three months after the treatment, GA patients had a reduction in penile curvature degree from a mean ± SD of 33.91 ± 8.34° at baseline to a mean ± SD of 19.46 ± 7.15° after 12 months, whereas pain in an erection or during intercourse was resolved completely in 88.9% of the patients. The mean ± SD IIEF-15 score of patients affected by severe/moderate ED further improved significantly in the GA group (p < 0.001) after 3, 6, and 12 months of treatment. There were no permanent adverse sequelae after treatments. Conclusions: The regular use of a VED plus Tadalafil in patients who had undergone ESWT significantly provided more benefit in patients with PD in terms of penile deformity, pain, and erectile function. Full article

SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient—who did mount a SARS-CoV-2 IgM response—showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population. Full article

S. salivarius M18 administration has been proven to provide positive effects on periodontal health; however, there is still no consensus on the optimum duration of probiotic administration. This study aimed to evaluate the effect of three months of probiotic supplementation on bleeding on probing, signs of gingival inflammation, and dental biofilm. Sixty-two eligible individuals with gingivitis were enrolled in this placebo-controlled, double-blind trial and randomly allocated to the M18 or control groups. Primary outcomes were changes in gingival condition (gingival index, GI; gingival bleeding index, GBI) after 1, 2, and 3 months of lozenges administration and after a one-month washout. Secondary outcomes included changes in the Quigley–Hein plaque index (modified by Turesky et al.) after 1, 2, and 3 months of lozenges administration and after a washout. In total, 60 individuals completed the study (31 and 29 in the M18 group and the control group, respectively). No severe adverse events were reported. Probiotic supplementation resulted in a significant decrease in gingival bleeding at 1 month (effect size 1.09 [CI95%: 0.55–1.63]), 2 months (effect size 0.78 [CI95%: 0.26–1.30]), and 3 months (effect size 0.67 [CI95%: 0.15–1.18]) and a significant reduction in dental plaque accumulation at 2 months (effect size 0.63 [CI95%: 0.12–1.14]) and 3 months (effect size 0.55 [CI95%: 0.03–1.05]). A three-month supplementation with the probiotic resulted in a significant reduction in gingival bleeding and biofilm accumulation; however, a long-lasting effect is not expected, indicating the need for probiotic intake on a long-term basis. Full article

Periodontitis, a prevalent inflammatory condition, affects the supporting structures of teeth, leading to significant oral health challenges. Traditional treatments have primarily focused on mechanical debridement, antimicrobial therapy, and surgery, which often fail to restore lost periodontal structures. Emerging as a novel approach in regenerative medicine, extracellular vesicle (EV) therapy, including exosomes, leverages nano-sized vesicles known for facilitating intercellular communication and modulating physiological and pathological processes. This study is a proof-of-concept type that evaluates the clinical efficacy of EV therapy as a non-surgical treatment for stage I–III periodontitis, focusing on its anti-inflammatory and regenerative potential. The research involved seven patients undergoing the therapy, and seven healthy individuals. Clinical parameters, including the plaque index, bleeding on probing, probing depth, and attachment level, were assessed alongside cytokine levels in the gingival crevicular fluid. The study found significant improvements in clinical parameters, and a marked reduction in pro-inflammatory cytokines post-treatment, matching the levels of healthy subjects, underscoring the therapy’s ability to not only attenuate inflammation and enhance tissue regeneration, but also highlighting its potential in restoring periodontal health. This investigation illuminates the promising role of EV therapy in periodontal treatment, advocating for a shift towards therapies that halt disease progression and promote structural and functional restoration of periodontal tissues. Full article

Despite decades of rigorous research and numerous clinical trials, Alzheimer’s disease (AD) stands as a notable healthcare challenge of this century, with effective therapeutic solutions remaining elusive. Recently, the endocannabinoid system (ECS) has emerged as an essential therapeutic target due to its regulatory role in different physiological processes, such as neuroprotection, modulation of inflammation, and synaptic plasticity. This aligns with previous research showing that cannabinoid receptor ligands have the potential to trigger the functional structure of neuronal and brain networks, potentially impacting memory processing. Therefore, our study aims to assess the effects of prolonged, intermittent exposure (over 90 days) to JWH-133 (0.2 mg/kg) and an EU-GMP certified Cannabis sativa L. (Cannabixir^® Medium Flos, 2.5 mg/kg) on recognition memory, as well as their influence on brain metabolism and modulation of the expanded endocannabinoid system in APP/PS1 mice. Chronic therapy with cannabinoid receptor ligands resulted in reduced anxiety-like behavior and partially reversed the cognitive deficits. Additionally, a reduction was observed in both the number and size of Aβ plaque deposits, along with decreased cerebral glucose metabolism, as well as a decline in the expression of mTOR and CB2 receptors. Furthermore, the study revealed enlarged astrocytes and enhanced expression of M1 mAChR in mice subjected to cannabinoid treatment. Our findings highlight the pivotal involvement of the extended endocannabinoid system in cognitive decline and pathological aspects associated with AD, presenting essential preclinical evidence to support the continued exploration and assessment of cannabinoid receptor ligands for AD treatment. Full article

Fire blight, caused by the bacterium Erwinia amylovora, is a major threat to pear production worldwide. Bacteriophages, viruses that infect bacteria, are a promising alternative to antibiotics for controlling fire blight. In this study, we isolated a novel bacteriophage, RH-42-1, from Xinjiang, China. We characterized its biological properties, including host range, plaque morphology, infection dynamics, stability, and sensitivity to various chemicals. RH-42-1 infected several E. amylovora strains but not all. It produced clear, uniform plaques and exhibited optimal infectivity at a multiplicity of infection (MOI) of 1, reaching a high titer of 9.6 × 10⁹ plaque-forming units (PFU)/mL. The bacteriophage had a short latent period (10 min), a burst size of 207 PFU/cell, and followed a sigmoidal one-step growth curve. It was stable at temperatures up to 60 °C but declined rapidly at higher temperatures. RH-42-1 remained viable within a pH range of 5 to 9 and was sensitive to extreme pH values. The bacteriophage demonstrates sustained activity upon exposure to ultraviolet radiation for 60 min, albeit with a marginal reduction. In our assays, it exhibited a certain level of resistance to 5% chloroform (CHCl₃), 5% isopropanol (C₃H₈O), and 3% hydrogen peroxide (H₂O₂), which had little effect on its activity, whereas it showed sensitivity to 75% ethanol (C₂H₅OH). Electron microscopy revealed that RH-42-1 has a tadpole-shaped morphology. Its genome size is 14,942 bp with a GC content of 48.19%. Based on these characteristics, RH-42-1 was identified as a member of the Tectiviridae family, Alphatectivirus genus. This is the first report of a bacteriophage in this genus with activity against E. amylovora. Full article

Herpes simplex virus (HSV) is known to cause cold sores and various diseases in humans. Importantly, HSV infection can develop latent and recurrent infections, and it is also known to cause inflammation. These infections are difficult to control, and effective treatment of the disease remains a challenge. Thus, the search for new antiviral and anti-inflammatory agents is a necessity. Melittin is a major peptide that is present in the venom of the honeybee. It possesses a number of pharmacological properties. In this study, the effects of the melittin peptides from A. mellifera (MEL-AM) and A. florea (MEL-AF) against HSV-1 and HSV-2 were evaluated at different stages during the viral multiplication cycle in an attempt to define the mode of antiviral action using plaque reduction and virucidal assays. The results revealed a new finding that melittin at 5 µg/mL demonstrated the highest inhibitory effect on HSV through the direct inactivation of viral particles, and MEL-AF displayed a greater virucidal activity. Moreover, melittin was also observed to interfere with the process of HSV attachment to the host cells. MEL-AM exhibited anti-HSV-1 and anti-HSV-2 effects with EC₅₀ values of 4.90 ± 0.15 and 4.39 ± 0.20 µg/mL, while MEL-AF demonstrated EC₅₀ values of 4.47 ± 0.21 and 3.95 ± 0.61 µg/mL against HSV-1 and HSV-2, respectively. However, non-cytotoxic concentrations of both types of melittin produced only slight degrees of HSV-1 and HSV-2 inhibition after viral attachment, but melittin at 5 µg/mL was able to reduce the plaque size of HSV-2 when compared to the untreated group. In addition, MEL-AM and MEL-AF also exhibited anti-inflammatory activity via the inhibition of nitric oxide production in LPS-stimulated RAW 264.7 macrophage cells, and they were also found to down-regulate the expressions of the iNOS, COX-2 and IL-6 genes. The highest inhibition of IL-6 mRNA expression was found after treatment with 10 µg/mL of MEL-AM and MEL-AF. Therefore, melittin peptides have displayed strong potential to be used as an alternative treatment for HSV infection and inflammatory diseases in the future. Full article

Alzheimer’s disease (AD) is the most common type of dementia, characterized by the abnormal accumulation of protein aggregates in the brain, known as neurofibrillary tangles and amyloid-β (Aβ) plaques. It is believed that an imbalance between cerebral and peripheral pools of Aβ may play a relevant role in the deposition of Aβ aggregates. Therefore, in this study, we aimed to evaluate the effect of the removal of Aβ from blood plasma on the accumulation of amyloid plaques in the brain. We performed monthly plasma exchange with a 5% mouse albumin solution in the APP/PS1 mouse model from 3 to 7 months old. At the endpoint, total Aβ levels were measured in the plasma, and soluble and insoluble brain fractions were analyzed using ELISA. Brains were also analyzed histologically for amyloid plaque burden, plaque size distributions, and gliosis. Our results showed a reduction in the levels of Aβ in the plasma and insoluble brain fractions. Interestingly, histological analysis showed a reduction in thioflavin-S (ThS) and amyloid immunoreactivity in the cortex and hippocampus, accompanied by a change in the size distribution of amyloid plaques, and a reduction in Iba1-positive cells. Our results provide preclinical evidence supporting the relevance of targeting Aβ in the periphery and reinforcing the potential use of plasma exchange as an alternative non-pharmacological strategy for slowing down AD pathogenesis. Full article

Antimicrobial photodynamic treatment (aPDT) with visible light plus water-filtered infrared-A irradiation (VIS-wIRA) and natural single- or multi-component photosensitizers (PSs) was shown to have potent antimicrobial activity. The aim of this study was to obtain information on the antimicrobial effects of aPDT-VIS-wIRA with lingonberry extract (LE) against bacteria that play a role in oral health. Planktonic bacterial cultures of the Gram-positive E. faecalis T9, S. mutans DSM20523, S. oralis ATCC 35037 and S. sobrinus PSM 203513, the Gram-negative N. oralis 14F2 FG-15-7B, F. nucleatum ATCC 25586, and V. parvula DSM, the anaerobic F. nucleatum ATCC 25586 and V. parvula DSM 2008, and the total mixed bacteria from pooled saliva and supra- and subgingival plaques of volunteers were all treated and compared. aPDT-VIS-wIRA with LE as PS significantly (p < 0.008) reduced the growth of all tested Gram-positive, Gram-negative, as well as aerobic and anaerobic bacterial strains, whereas without irradiation no reductions were seen (p < 0.0001). NaCl, with or without irradiation, was ineffective. After treatment with CHX 0.2%, the highest killing rate (100%) was observed, and no bacteria (0 log10 CFU) were cultivable. The method also significantly reduced all of the bacteria present in saliva and in the gingival biofilms. Three-dimensional visualization of viable and non-viable microorganisms revealed that LE penetrated deeper into the cell wall layers than CHX 0.2%. LE was an appropriate PS for eradicating microorganisms with VIS-wIRA, either in their planktonic form or in saliva and gingival plaque biofilms. These results encourage further investigation in order to determine which LE compounds contribute to the photosensitizing effect and to evaluate the size of the effect on maintaining oral health. Full article

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs. Full article