Search Results (97)

Periodontitis is a chronic, multifactorial inflammatory disease characterized by the progressive destruction of the periodontal supporting tissues, including alveolar bone, potentially resulting in tooth loss. Etiopathogenesis involves a dysbiotic shift in the subgingival microbiota where the presence of pathogenic species such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola has been documented. This disbalance is combined with an inadequate host immune response, often exacerbated by other systemic comorbidities including diabetes mellitus and cardiovascular diseases. Conventional therapy typically comprises mechanical debridement and adjunctive local or systemic antimicrobials, but emerging antibiotic resistance highlights a need for alternative adjuvant therapeutic strategies. The present descriptive analysis of microbiome and clinical trends study evaluated the adjuvant effects of a clinoptilolite-based zeolite material, namely PMA-zeolite, with professional prophylaxis on clinical and microbiological parameters in patients with chronic periodontitis over a 10-week period. Clinical assessment revealed significant reductions in bleeding on probing (BoP) and periodontal pocket depth (PD), indicating improved inflammatory status. Microbiome profiling demonstrated a marked decrease in key periodontal pathogens, suggesting that PMA-zeolite can help rebalance the oral microbiome. These findings suggest that the combined therapy exhibits promising anti-inflammatory and antimicrobial properties, indicating its role in promoting microbial homeostasis and reducing periodontal inflammation. However, further investigation through larger, controlled clinical trials is needed to validate the efficacy of the therapy. Full article

Aluminum (Al) is one of the most abundant metals on Earth and is well known as an environmental neurotoxic agent in the pathogenesis of Alzheimer’s disease. Aluminum toxicity is associated with oxidative stress, reduction of antioxidant enzymes, and disruption of the balance of cellular metals, such as iron (Fe), calcium (Ca), and copper (Cu), which causes structural and functional changes in the nervous tissue of the brain or peripheral nervous system. The intake of functional foods, rich in antioxidants, such as quercetin, may be beneficial in combating oxidative stress and neurodegenerative changes in the brain. The aim of this study was to provide deeper insight into the cellular and molecular neuroprotective effects of quercetin in regulating amyloid-beta (Aβ) accumulation, tau pathology, and neuroinflammation in the Al/D-galactose-induced rat model (Al/D-gal) of AD. The results showed that quercetin successfully modulated the impaired homeostatic and neuropathological consequences of aluminum chloride and D-galactose administration over 28 days: it directly protected neurons by regulating the level of oxidative stress and antioxidants, reduced Aβ aggregation by inhibiting the activity of acetylcholinesterase (AChE), increased the survival, growth, and differentiation of nerve cells by maintaining the level of brain-derived neurotrophic factor (BDNF), and regulated microglial immunoreactivity and neuroinflammation by reducing the level of proinflammatory cytokines. The multiple effects confirm that quercetin can be applied as an alternative non-pharmaceutical approach in reducing Al-induced neurotoxicity and maintaining adaptive homeostasis, which consequently affects the functioning of the central nervous system and the whole organism. Full article

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article

Background/Objectives: Schizophrenia and nicotine misuse are a comorbid condition that frequently develops during adolescence. Considering the role of the nucleus accumbens (NAcc) as a common neurobiological substrate for these psychiatric disorders, label-free proteomics was employed to identify NAcc deregulated proteins in male and female mouse models of schizophrenia with a history of adolescent nicotine exposure. Methods: Phencyclidine was used to model schizophrenia, and minipump infusions were used to model nicotine misuse. Results: Enrichment Reactome pathway and protein–protein interaction analyses showed that the cytoskeleton and associated synaptic plasticity mechanisms, energy metabolism, and nervous system development were affected in both sexes. In particular, Ncam1 (Neural cell adhesion molecule 1) could be of interest as a candidate marker of synaptic plasticity disbalance. Its deregulation in the NAcc of both sexes suggests that it lies at the core of the comorbidity pathophysiology. When considering sex-selective effects, Cs (Citrate synthase) and Mapk3 (Mitogen-activated protein kinase 3) were identified as exclusively deregulated in female and male mice, respectively. Since both proteins were previously shown to be exclusively deregulated in the medial prefrontal cortex of co-modeled mice, a common mesocortical and mesolimbic system effect can be inferred, supporting the role of aberrant energy metabolism and synaptic plasticity in the comorbidity model. Conclusions: The current data provide insights into the NAcc proteome disbalance in an adolescent preclinical model of combined schizophrenia and nicotine misuse, pointing to relevant pathways and early markers of the comorbidity. Full article

Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut–liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD. Full article

Running-induced fatigue affects several biomechanical parameters, and yet few studies are focused on the acceleration spikes’ asymmetries. This study aimed to evaluate the effects of a 30 min run on lower limbs spikes’ asymmetries. Eighteen recreational runners (35.6 ± 7.5 years; seven women) performed a treadmill running protocol at a moderate speed and acceleration spikes’ asymmetries and kinematic (temporal) parameters were measured via accelerometers—on the tibias and sacrum—and photogrammetry. Acceleration spikes’ parameters were continuously measured and averaged per minute to assess the relationship between fatigue and acceleration spike asymmetries via a linear regression model. Right tibial acceleration spikes increased over time (r = 0.9; p < 0.001) and left tibia spikes decreased (r = 0.78; p < 0.001), with a rise in tibial load asymmetry from 9% to 25% at the end (r = 0.98; p < 0.001). This study suggest that fatigue affects the acceleration spikes of the two legs differently, with increasingly greater acceleration spikes in the right (dominant) leg. These findings should be considered, as greater asymmetries are related to overuse injuries and lower efficiency. Also, in studies focusing on running mechanics with fatigue, it is recommended that researchers collect data from both limbs, and not only from the right (dominant) leg. Full article

The cultivation of excitable cells typically profits from continuous electrical stimulation, but electrochemical consequences are mostly harmful and must be minimized. The properties of the electrode materials and stimulation impulses are key. Here, we developed an easy method to analyze the electrochemical impact of biphasic, current-controlled impulses, applied via graphite electrodes, using phenol red as the redox indicator. We also tested the stimulation conditions for the long-term cultivation of myocardial tissue. The colorimetric assay was able to detect ±0.2% deviations in typical positive and negative pulse charges. Phenol red was best preserved (20% degradation over 24 h) by impulses of equivalent positive and negative charges (full charge balance), generated with either manual calibration, capacitive electrode coupling, or feedback regulation of electrode polarization. Feedback regulation established full charge balance at pre-pulse voltages of about 300 mV, but also provided the option to selectively compensate irreversible electrode reactions. Modifications to shape and timing did not affect the electrochemical effects of symmetric impulses. Charge-balanced stimulation maintained more than 80% of the contractility of porcine left ventricular myocardium after 10 days of culture, whereas disbalances of 2–4% provoked weakening and discoloration of the tissues. Active polarization regulation, in contrast to capacitive electrode coupling, reproduced the biological advantages of full charge balance. Full article

Considering the mutual relationship between redox disbalance and inflammation in Helicobacter pylori (HP) infection, we aimed to evaluate whether the polymorphisms in antioxidant glutathione transferases genes (GSTP1 rs1695, GSTP1rs1138272, GSTO1 rs4925 and GSTO2 rs156697) modify susceptibility to HP infection, as well as the severity of HP-associated gastric manifestation development. Therefore, GST gene polymorphisms were determined via the appropriate PCR in 101 HP-positive and 107 HP-negative patients. Our results show that carriers of the GSTP1*G/G variant genotype (rs1695) or at least one GSTP1*T variant allele (rs1138272) were more prone to the development of HP-positive gastritis compared with reference allele carriers (OR = 3.21, 95%CI = 1.15–8.91, p = 0.025 and OR = 2.31, 95%CI = 1.14–4.89, p = 0.021, respectively), which was confirmed by haplotype analysis. HP-positive carriers of the GSTO1*A variant allele showed increased risk of developing gastric atrophy and precancerous gastric lesions compared with the reference one (OR = 2.49, 95%CI:1.04–5.96, p = 0.04 and OR = 2.98, 95%CI = 1.21–7.34, p = 0.018, respectively). HP-positive carriers of the GSTO2*G variant allele were less prone to developing moderate/severe inflammatory infiltration (OR = 0.35, 95%CI = 1.04–5.96, p = 0.04), whereas the GSTP1*T variant allele was significantly associated with active inflammation (OR = 4.09, 95%CI = 1.04–5.96, p = 0.042). In conclusion, antioxidant GST genetic propensity seems to have an important impact on both acute and chronic forms of HP infection. Full article

Mechanisms of action attributed to feed additives are of continuous research interest, increasing our knowledge about the side effects (direct or indirect) of their application. The primary role of organically modified clinoptilolite is to bind multiple polar and non-polar mycotoxins contaminating the feed and remove them during the digestion process and through feces, therefore preventing adsorption and consequences of mycotoxicosis on fish health. However, it is not fully understood if this binding action can influence bacterial communities in the fish digestive tract and possibly other organs, as well as the aquatic environment. Therefore, in this study, Nile tilapias (Oreochromis niloticus) (average weight: 30 ± 2 g; n = 48) were simultaneously exposed to low-level mycotoxins (AFB1 40 µg/kg, FB 600 µg/kg, ZEN 50 µg/kg, and DON 150 µg/kg) added to diet, with and without supplementation of commercially available organically modified clinoptilolite feed additive (MinazelPlus^®, 2 g/kg). After 42 days of continuous exposure, gill tissue, feces, and water were collected, and DNA was extracted from the samples. Results of RT-PCR analysis have revealed significant changes in microbiomes in fish from different groups, most prominently in mycotoxin-exposed fish. No significant changes were detected in water samples between the control and MinazelPlus^® groups, confirming the safety of MinazelPlus^® for aquatic microbial communities. MinazelPlus^® addition to the mycotoxin spiked diet, stabilized fish natural microbiota, and prevented the disbalance of microbial homeostasis observed in fish exposed to dietary mycotoxins. Full article

This study aims to scientifically justify the identification of suitable urban properties for urban green infrastructure (UGI) interventions to optimize its natural regulating functions for long-term pollution mitigation and secondary dust reduction. This study adheres to the perception that planning urban transformations to improve ambient air quality (AQ) requires a thorough understanding of urban structural heterogeneity and its interrelationship with the local microclimate. We apply an approach in which UGI and its potential multifunctionality are explored as a structural–functional element of urban local climatic zones. The same (100 × 100 m) spatial framework is used to develop place-based adapted solutions for intervention in UGI. A complex geospatial analysis of Burgas City, the second largest city (by area) in Bulgaria, was conducted by integrating 12 indicators to reveal the spatial disbalance of AQ regulation’ demand and UGI’s potential to supply ecosystem services. A total of 174 municipally owned properties have been identified, of which 79 are of priority importance, including for transport landscaping, inner-quarter spaces, and social infrastructure. Indicators of population density and location of social facilities were applied with the highest weight in the process of prioritizing sites. The study relies on public data and information from the integrated city platform of Burgas, in cooperation with the city’s government. The results have been discussed with stakeholders and implemented by the Municipality of Burgas in immediate greening measures in support of an ongoing program for Burgas Municipality AQ improvement. Full article

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae. Full article

Balanced territorial development and improving living conditions have become the focus of rural development policies. As the number of young people moving to cities or other countries is increasing, rural settlements face serious demographic disbalances and aging societies. Quality of life and place attachment are both key variables in enhancing the social and economic capacities of rural and undeveloped communities and reducing youth out-migration. However, this topic remains underexplored, especially among younger generations, who are critical for further socio-economic sustainability. Thus, the main goal of this study was to explore young residents’ perceptions about quality of life, level of attachment to their rural homes, and their interrelationship. This study was conducted among 299 participants in rural areas of Serbia and Croatia. The results identified two quality of life factors: (1) satisfaction with the quality of infrastructure and (2) satisfaction with culture and education. Three attachment factors were extracted, among which place identity was the strongest. Additionally, the influence of quality of life and socio-demographic characteristics on place attachment was confirmed. These results provide new insights that could be very useful in creating strategies and initiatives for rural planning and strengthening rural areas’ social, economic, and environmental sustainability. Full article

(1) Background: Impaired nutritional status in systemic sclerosis (SSc) is prevalent. (2) Objective: This study aimed to identify pre-cachexia and malnutrition in SSc patients and to estimate the effectiveness of a high-protein oral nutritional supplement (ONS) in improving their nutritional status. (3) Materials and methods: The SSc population comprised 56 patients and a control group of 49 healthy persons. After a baseline clinical evaluation, bioelectrical impedance analysis (BIA), and laboratory tests, SSc patients were divided into well-nourished, pre-cachectic, and malnourished categories. SSc patients with a nutritional disbalance received a high-protein ONS once daily for 3 months. Patients were reassessed at 3 and 12 months after inclusion in the study. (4) Results: SSc patients, in comparison to the control group, had a significantly lower seven-point SGA value [6(0) vs. 7(1), p < 0.001)], lean tissue mass [LTM, 35.1 (10.5) vs. 40.1 (10.10), p = 0.008], and lean tissue index [LTI, 13.5 (3) vs. 14.9 (4), p = 0.009]. Of the 56 SSc patients, 40 (71.4%) were well nourished, 5 (8.9%) had pre-cachexia, and 11 (19.7%) were malnourished. A high-protein ONS in the pre-cachexia group stabilized the SGA value, anthropometric measurements, and BIA after 3 and 12 months. In malnourished patients, it significantly improved the SGA value [5(0) vs. 6(0), p = 0.002], LTI [12.1 (2.1) vs. 12.7 (3.2), p = 0.021] and LTM [31.1 (7.7) vs. 35.1 (9.1), p = 0.021], and that effect remained stable at 12 months. (5) Conclusion: Malnutrition is a common complication of SSc that can be improved with nutritional intervention. Full article

Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system’s role in OC progression and treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management. Full article

Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate variability (HRV) was only examined while resting. So far, it remains unclear whether the dysbalance of the ANS in patients with MDD is restricted to resting or whether it is also evident during sympathetic and parasympathetic activation. The aim of this study was to compare the responses of the ANS to challenges that stimulated the sympathetic and, respectively, the parasympathetic nervous systems in patients with MDD. Forty-six patients with MDD (female 27 (58.7%), mean age 44 ± 17 years) and 46 healthy controls (female 26 (56.5%), mean age 44 ± 20 years) underwent measurement of time- and frequency-dependent domains of HRV at rest, while standing (sympathetic challenge), and during slow-paced breathing (SPB, vagal, i.e., parasympathetic challenge). Patients with MDD showed a higher heart rate, a reduced HRV, and a diminished vagal tone during resting, standing, and SPB compared to controls. Patients with MDD and controls responded similarly to sympathetic and vagal activation. However, the extent of modulation of the ANS was impaired in patients with MDD, who showed a reduced decrease in the vagal tone but also a reduced increase in sympathetic activity when switching from resting to standing. Assessing changes in the ANS during sympathetic and vagal activation via respective challenges might serve as a future biomarker and help to allocate patients with MDD to therapies like HRV biofeedback and psychotherapy that were recently found to modulate the vagal tone. Full article