Search Results (978)

The term ‘dementia’ encompasses a diverse group of progressive neurodegenerative disorders, the common feature of which is the deterioration of higher cortical functions. This process not only involves memory deficits and language communication disorders, but also executive dysfunction and loss of emotional control, which ultimately leads to a complete loss of the patient’s independence. Within this group of disorders, Alzheimer’s disease (AD) presents the most serious clinical challenge, characterized by a unique neuropathological triad: the presence of extracellular β-amyloid plaques, intracellular neurofibrillary tangles of tau protein, and widespread dysfunction of cholinergic transmission. The cholinergic hypothesis remains the cornerstone of the current understanding of cognitive impairment in AD. It posits that progressive dementia is caused by the selective degeneration of neurons in the anterior basal forebrain, resulting in a drastic reduction in acetylcholine (ACh) levels in the synaptic cleft. In the absence of a causal treatment, acetylcholinesterase inhibitors (AChEIs) remain the standard of care. Their pharmacological action is based on the inhibition of the AChE enzyme, which allows neurotransmission deficits to be compensated for by prolonging the half-life of acetylcholine at the synapse. This literature review presents a synthesis of the efficacy and safety of classic and novel AChEIs. A comprehensive search of the PubMed, Scopus, and Cochrane Library databases was conducted for clinical data published up to 2026. Evidence from key trials indicates that standard AChEIs induce significant cognitive stabilization compared to placebo, with rivastigmine maximizing daily living parameters via transdermal delivery. However, their therapeutic impact remains strictly symptomatic without arresting neurodegeneration. Conversely, emerging agents like huperzine A and the translation-blocker Posiphen demonstrate disease-modifying potential by modulating CSF biomarkers associated with amyloid and tau proteins. Clinically, while traditional regimens are limited by gastrointestinal toxicities, transitioning toward innovative multi-target structures represents a necessary shift to address both cognitive decline and neurodegeneration. Full article

Deep dermatophytosis is a rare, life-threatening fungal infection characterised by the invasion of dermatophytes beyond the superficial layers of keratinised tissue into the dermis and subcutaneous tissues. The present review aimed to identify the current knowledge on the role of Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in the pathogenesis, clinical spectrum, diagnosis, and management of deep dermatophytosis. For innate immune activation, CARD9 acts as an adaptor molecule. Basically, CARD9 helps mediate the connection between the fungal pattern recognition receptor (Dectin-1) and the NF-κB and MAPK signalling pathways, and it mediates cytokine production, thereby activating phagocytic activities. Thereby, any change or mutation in the CARD9 gene may disrupt these pathways, leading to dysfunctional neutrophils and impaired Th17-mediated antifungal immunity. Clinically, patients with CARD9 deficiency are immunocompetent but susceptible to recurrent and/or severe fungal infections [Candida, dermatophytes (Trichophyton spp.), and phaeohyphomycetes]. Deep dermatophytosis in these patients is usually chronic, treatment-resistant, and characterized by erythematous papules, nodules, plaques, ulcers, or necrotic lesions, most of which occur on the lower limbs. It usually occurs in adulthood and is more common in males. There have been instances of geographic clustering of CARD9 deficiency in Asia, North Africa, and the Middle East. Early recognition and genetic diagnosis of CARD9 mutations in patients with recurrent or atypical deep dermatophytosis. Although antifungal therapy is essential, hematopoietic stem cell transplantation can be a definitive treatment for selected patients with CARD9 deficiency. Thus, CARD9 deficiency is a critical factor in the better management of patients but remains an underrecognized cause of severe, treatment-resistant deep dermatophytosis, and early genetic diagnosis is essential for guiding targeted management and improving patient outcomes. This review emphasises the importance of CARD9 in antifungal immunity and underscores the need for greater clinical awareness and the incorporation of genetic evaluation into the management of deep dermatophytosis. Full article

Background: Cardiovascular (CV) risk is increased in psoriatic arthritis (PsA), yet vascular assessment has largely focused on carotid arteries, potentially underestimating systemic atherosclerosis. Objective: The objective of this study was to characterize the distribution and concordance of atherosclerotic plaques across carotid, femoral, and aortic territories in PsA and evaluate their incremental value over SCORE2. Methods: In this cross-sectional study, 250 unselected patients with PsA underwent carotid and femoral ultrasound and abdominal X-ray. Plaque prevalence and multiterritorial involvement (≥2 vascular beds) were assessed. Agreement between territories was evaluated using Cohen’s κ. In patients aged 50–69 years, the incremental value of vascular territories over SCORE2 was evaluated using ROC curves, bootstrap-corrected decision curve analysis (DCA), and reclassification metrics (IDI and continuous NRI). Results: Plaques were detected in carotid (36.0%), femoral (62.8%), and aortic (31.6%) territories, with multiterritorial involvement in 43.2%. Agreement between vascular beds was moderate (κ ≈ 0.35). Notably, 48.1% of patients without carotid plaques had femoral involvement. SCORE2 categories showed a strong gradient with plaque prevalence (p < 0.0001). In patients aged 50–69 years, adding vascular imaging improved discrimination for multiterritorial disease (AUC 0.73 vs. 0.86–0.90). Reclassification analyses demonstrated that carotid plaque substantially improved the identification of multiterritorial atherosclerosis (IDI 0.32, 95% CI 0.18–0.50; continuous NRI 1.33, 95% CI 1.08–1.60), with similar results observed for aortic plaque (IDI 0.33, 95% CI 0.20–0.50; continuous NRI 1.24, 95% CI 0.99–1.48). Femoral plaque provided a more modest improvement (IDI 0.26, 95% CI 0.16–0.37; continuous NRI 1.11, 95% CI 0.80–1.33). Conversely, when the outcome was defined as the presence of any plaque, femoral plaque provided the greatest incremental value over SCORE2 (AUC 0.96, 95% CI 0.93–0.99). Bootstrap-corrected DCA confirmed improved net benefit. Conclusions: The incremental value of vascular imaging over SCORE2 appears to be phenotype-dependent. Femoral plaque provided the greatest improvement for detecting the presence of subclinical atherosclerosis, whereas carotid and aortic plaques offered greater incremental value for identifying multiterritorial vascular involvement. These findings support a tailored, multiterritorial approach to cardiovascular risk assessment in patients with PsA. Full article

Alzheimer’s disease and related dementias (ADRD) are neurodegenerative conditions characterized by progressive cognitive and functional decline. AD pathology is associated with extracellular amyloid-β plaques, intracellular tau neurofibrillary tangles, synaptic dysfunction, and neuronal loss. AD accounts for approximately 60–80% of dementia cases globally. In 2022, AD was the seventh leading cause of death in the United States, and the number of Americans aged 65 and older living with Alzheimer’s dementia is projected to increase substantially by 2060. Despite decades of research, AD/ADRD data resources remain fragmented across clinical, imaging, genetic, genomic, and therapeutic domains. This paper addresses that gap by providing a centralized review of widely used AD/ADRD databases and computational methods. We first summarize computational approaches used to analyze these datasets, including machine learning (ML), natural language processing (NLP), and biomedical imaging. We then review eight databases classified into three categories: Clinical and Population Data, Genetics and Genomics, and Drug Discovery and Therapeutics. Finally, we discuss real-world applications, including early diagnosis, clinical decision support, personalized medicine, and drug-mechanism analysis. This review identifies opportunities for future work in data harmonization, cross-database compatibility, and robust, generalizable AI models for AD/ADRD research. Full article

Atherosclerosis is a progressive vascular disease characterized by lipid-rich plaque accumulation, oxidative stress, and chronic inflammation, contributing to coronary heart disease, stroke, and peripheral arterial disease. This study investigated the impact of inflammation, vascular calcification, and statin therapy on redox balance in blood and carotid artery plaques, aiming to identify potential biomarkers for disease assessment. Thirty-two patients undergoing carotid endarterectomy provided 34 plaque samples. Enzyme activities in plaque/erythrocytes and –SH group concentration in plasma/plaque were measured. Pathological analysis was performed to determine inflammation/calcification grade, the presence of mast cells and plaque composition. The results showed that mast cells were associated with reduced non-protein –SH groups, indicating selective thiol consumption and serving as a qualitative marker of oxidative burden. Reduced catalase activity in erythrocytes was associated with advanced calcification, pointing to long-standing systemic oxidative stress. Statin therapy enhanced systemic superoxide-dismutase 1 activity, increased –SH groups, and modulated plaque-specific glutathione reductase activity, attenuating sex-related differences in redox regulation. These findings highlight the complex interplay between systemic and local oxidative processes in atherosclerosis through alterations in redox-related biomarkers such as plasma –SH group concentrations and catalase activity. Full article

COVID-19, caused by the SARS-CoV-2 virus, has become a global public health crisis with diverse clinical manifestations affecting multiple organ systems, including the integumentary system. One notable cutaneous manifestation, referred to as “COVID toes,” involves the development of pernio-like chilblains, characterized by red-to-violet macules, plaques, or nodules, primarily on toes and fingers. This characteristic clinical feature gained significant attention due to its apparent association with COVID-19, especially during the early stages of the pandemic when individuals with mild or asymptomatic cases exhibited these symptoms. Concurrently, digital platforms such as Google Trends have emerged as tools for tracking public interest in health-related topics, offering insights into real-time patterns of disease awareness. Previous research has demonstrated that Google Trends data may correlate with the incidence of infectious diseases, suggesting that search interest can be a proxy for disease outbreaks. In this study, we sought to explore the potential relationship between public interest in COVID toes, as reflected in Google Trends, and the incidence and mortality rates of COVID-19. Specifically, we examined whether peaks in search interest for “COVID toes” corresponded with surges in COVID-19 cases and deaths. By analyzing trends in search data, we aimed to assess the utility of digital platforms as an epidemiological tool for monitoring disease progression and public awareness. Our findings provide insights into the potential role of digital search data in forecasting outbreaks and highlight the interplay between public perception and the clinical burden of COVID-19, emphasizing the importance of real-time data in public health surveillance and response. Full article

Multivessel coronary artery disease is observed in a substantial proportion of patients presenting with ST-segment elevation myocardial infarction (STEMI) and identifies a higher-risk phenotype characterized by larger atherosclerotic burden, recurrent ischemic events, and greater need for subsequent revascularization. Over the past decade, randomized evidence has progressively shifted the interventional paradigm from culprit-lesion-only primary percutaneous coronary intervention (PCI) toward complete revascularization in hemodynamically stable STEMI patients with suitable non-culprit lesions. Nevertheless, several clinically relevant questions remain unresolved, including the optimal criteria for selecting non-culprit lesions, the relative value of angiography, coronary physiology, and intracoronary imaging, the timing of complete revascularization, and the management of patients presenting with cardiogenic shock. Angiography-guided complete revascularization has the strongest evidence base, while physiology-guided approaches may reduce unnecessary PCI but have not demonstrated superiority over angiography-guided strategies in direct randomized comparisons. Intracoronary imaging offers unique information on plaque vulnerability and PCI optimization, although dedicated outcome trials in STEMI remain limited. The timing of complete revascularization has also evolved, with contemporary trials supporting early treatment in selected stable patients but not establishing a universal immediate strategy. This review summarizes current evidence, unresolved controversies, and emerging directions regarding strategies and timing of complete revascularization in STEMI patients with multivessel disease. Full article

Effective hand washing takes time and hand sanitizers that contain alcohol have a number of drawbacks, and frequent use of alcohol may cause skin damage. The objective of this study is to formulate nanostructured lipid carrier systems containing chlorhexidine digluconate to be applied topically for hand hygiene, especially for people sensitive to alcohol. A cytotoxicity experiment was conducted to ascertain the safe dosage for each of the three nano-cream formulas (F1, F2 and F3). Following each treatment, the viral titer was assessed using tissue culture infectious dose₅₀ and standard plaque assays. The selected formulation was characterized rheologically. Furthermore, fifteen volunteers of various ages and genders participated in the vivo antimicrobial test of the selected formulation as a hand sanitizer. All of the formulas were found to be safe. Using the disc diffusion method, the three formulations exhibited in vitro antimicrobial effects against different microbes. F1 showed biphasic release, reasonable skin deposition and spherical droplets under a microscope. F1 exhibited a non-Newtonian shear thinning flow behavior. After 30 min, the reduction values for rotavirus and Phix-174 were 21 and 4%, respectively. Additionally, the impact of F1 was assessed on the infectivity of simian rotavirus sa-11 (ds RNA) and Phix-174 (ss DNA) bacteriophage. According to the findings of the in vivo study, the percentage of total bacterial counts that were removed varied from 91 to 100%. Moreover, the range of the removal percentage of total fungi was 95.38 to 100%. In summary, F1 can be used as an economic, safe, and effective hand antiseptic. It can also completely replace alcohol in the market. Full article

Herpes simplex virus type 1 (HSV-1) remains a significant pathogen, particularly in immunocompromised patients. The emergence of drug-resistant strains necessitates alternative therapeutic agents. Lentinula edodes (LE), Hypsizygus marmoreus, and Pleurotus eryngii are edible mushrooms with recognized medicinal properties. However, their effects on drug-resistant HSV-1 remain unclear. This study characterized metabolites from high-temperature/high-pressure (121 °C) water extracts of fresh and dried fruiting bodies and evaluated anti-HSV-1 activities using in vitro and in silico approaches. Metabolic profiles were analyzed by electrospray ionization–quadrupole time-of-flight mass spectrometry. Antiviral activity against HSV-1 KOS (wild-type) and HSV-1 dxpiii (drug-resistant) strains was assessed by plaque assays and qPCR. Molecular docking and network pharmacology were performed on candidate compounds. LE extract from dried mushroom tended to show the highest levels of selected major bioactive constituents, along with greater antioxidant activities. All extracts significantly inhibited viral infection and gene expression in both strains. LE extract from dried mushroom modulated the expression of NFKB1 and IL6. Molecular docking analysis revealed that eritanidine showed a predicted binding affinity to HSV-1 DNA polymerase (−7.95 kcal/mol). Additionally, eritanidine, 5′-methylthioadenosine, and 3-indoleacrylic acid were predicted to interact with TNF and MAPK1. Several compounds also demonstrated favorable drug-likeness properties. Overall, these mushroom extracts are promising natural sources of antiviral agents against HSV-1, including drug-resistant variants. Full article

Background: Coronary bifurcation lesions represent one of the most technically demanding scenarios in coronary artery disease (CAD), associated with higher procedural complexity, restenosis, and periprocedural complications. Recent advances in coronary computed tomography angiography (CCTA) have markedly improved its ability to visualize complex coronary anatomy, assess plaque morphology, and guide revascularization. Objectives: This review summarizes (1) technological advances in CCTA over the last decade, (2) its role in evaluating bifurcation stenosis, (3) assessment of plaque morphology and distribution, (4) quantification of bifurcation geometry, and (5) emerging evidence supporting its application in revascularization planning and guidance. Findings: Modern wide-detector and dual-source CT systems, iterative and deep-learning reconstruction algorithms, and photon-counting CT (PCCT) have significantly improved temporal and spatial resolution, reduced blooming artifacts, and lowered radiation dose. CCTA now reliably quantifies bifurcation stenosis and plaque distribution, characterizes high-risk plaque features, and accurately measures bifurcation angles. The integration of CT-derived fractional flow reserve (FFR-CT) and artificial intelligence (AI)-based plaque quantification further strengthens its diagnostic and prognostic performance. CCTA-derived bifurcation scores and 3D modelling support procedural strategy selection, stent sizing, and side-branch (SB) protection. Conclusions: CCTA has evolved into a comprehensive tool for non-invasive diagnosis, physiological assessment, and pre-procedural planning of bifurcation disease. With the advent of PCCT and AI-enhanced quantitative tools, CCTA is poised to become a central component of revascularization decision-making in complex coronary bifurcations. Full article

Acute cardiovascular events driven by atherosclerosis primarily originate from thrombosis triggered by vulnerable plaque rupture or endothelial erosion. Endothelial barrier destabilization—characterized by glycocalyx impairment, intercellular junction disassembly, and abnormal cytoskeletal tension—is a core upstream pathological stage that promotes atherogenic lipoprotein leakage, inflammatory cell infiltration, and matrix degradation. Hemodynamics, primarily through wall shear stress (WSS), shape the spatial distribution and plaque phenotypes of atherosclerosis; notably, low or oscillatory shear stress is associated with, and in experimental systems can promote, pro-inflammatory, pro-oxidant and pro-permeability endothelial phenotypes that contribute to plaque initiation and vulnerability. Conversely, regular exercise training, as an intervention that modulates hemodynamics, is widely suggested to promote anti-inflammatory, antioxidant, and antithrombotic endothelial phenotypes by significantly increasing antegrade shear stress and reducing detrimental retrograde/oscillatory shear stress. With a central focus on the axis of “exercise-shear stress-glycocalyx-cytoskeleton/junction-permeability-plaque stability,” this review integrates evidence from in vitro flow chambers, animal models and human studies to critically discuss: (1) the spatiotemporal heterogeneity of WSS and its relationship with plaque vulnerability; (2) the composition, barrier function, and plasticity of the glycocalyx as the primary interface for shear stress; (3) the mechanosensory complexes at the glycocalyx and junctions that transduce shear stimuli to protective pathways such as Phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2), thereby stabilizing adherens/tight junctions; (4) how improved barrier homeostasis promotes the maintenance of the fibrous cap collagen scaffold by reducing lipoprotein leakage and dampening the inflammation–matrix metalloproteinase (MMP) axis. Finally, this review highlights the boundary conditions of the biological effects of shear stress: low/oscillatory shear stress is primarily associated with plaque initiation and susceptible sites, whereas focal, extremely high WSS in established stenotic lesions may contribute to late-stage high-risk remodeling. Therefore, the protective hemodynamic adaptations induced by exercise should not be simply equated with the pathologically high WSS found at stenotic sites. Full article

Carotid artery disease has traditionally been assessed according to luminal stenosis, although plaques with similar narrowing may differ substantially in biological activity and clinical risk. Intraplaque neovascularization is a key feature of plaque vulnerability, reflecting microvascular proliferation and its association with inflammation, hemorrhage, and structural destabilization. Dynamic contrast-enhanced ultrasound (DCE-US) offers a real-time, radiation-free method for evaluating intraplaque enhancement kinetics using strictly intravascular microbubble agents. However, its broader use in carotid plaque imaging remains limited by variability in acquisition protocols, contrast administration, signal processing, curve fitting, and parameter interpretation. This technical review clarifies the main analytical approaches used in carotid DCE-US, distinguishing bolus-based wash-in/wash-out analysis from destruction–replenishment modeling. Bolus analysis describes first-pass microbubble transit through the plaque microvasculature and commonly provides parameters such as peak intensity, wash-in slope, area under the curve, and time to peak. Destruction–replenishment analysis evaluates post-destruction refill under stable or quasi-stable contrast conditions and relies on model-based estimation of plateau intensity and the replenishment rate. Because these approaches interrogate different kinetic regimes, their outputs should not be considered interchangeable, even when similar terms are used across studies. Particular emphasis is placed on the operational meaning of quantitative and semi-quantitative parameters, the assumptions underlying curve modeling, and the methodological consequences of ROI placement, motion correction, acoustic settings, and fitting constraints. Rather than proposing a universal acquisition protocol, this article provides practical principles for acquisition, analysis, and reporting, helping radiologists, neuroradiologists, neurologists, and vascular imaging specialists understand the processing steps, algorithmic assumptions, and model-dependent choices underlying software-derived curves and parameters. By making this analytical layer more explicit, the review seeks to support a transparent, reproducible, and biologically coherent approach to quantitative carotid plaque characterization. Full article

Background/Objectives: The management of moderate-to-severe psoriasis in patients with a recent history of internal malignancy is a clinical challenge, as systemic immunosuppressive therapies are often avoided because of concerns about cancer recurrence. While Psoralen and Ultraviolet A (PUVA) photochemotherapy remains a valuable non-immunosuppressive alternative, regional variations in therapeutic response are not well-characterized in this population. This study aimed to evaluate total and segmental Psoriasis Area and Severity Index (PASI) responses to PUVA in patients with chronic plaque psoriasis and recent internal organ malignancy. Methods: This prospective, single-center, real-world cohort study enrolled 20 adults with moderate-to-severe chronic plaque psoriasis and a recent (<5 years) diagnosis of internal organ malignancy in complete remission. Participants received oral PUVA three times weekly for up to 30 sessions. Primary and secondary outcomes included changes in total PASI, segmental PASI (head/neck, trunk, upper limbs, and lower limbs), and Dermatology Life Quality Index (DLQI) at baseline, completion of therapy, and 6 months post-treatment. Results: PUVA led to a significant reduction in mean total PASI from 18.6 ± 3.2 at baseline to 5.7 ± 6.0 at treatment completion (69% reduction; p < 0.001). However, regional responses differed significantly: the head and neck improved the most (80.4%), followed by the trunk (72.2%) and upper limbs (72.3%), while the lower limbs showed the weakest response (59.5%; p < 0.001). At baseline, trunk contributed the most to total PASI (38%), while post-treatment, lower-limb lesions accounted for approximately 47% of the remaining total disease burden, showing the highest contribution to total PASI of all body regions. At 6 months, the lower limbs remained the most affected area, with significantly lower improvement (52.9%) compared to other regions. Mean DLQI also improved significantly from 17.2 ± 2.8 to 5.6 ± 2.6 (p < 0.001). Conclusions: PUVA is an effective and safe treatment for patients with psoriasis and a recent history of malignancy. Nevertheless, lower-limb psoriasis is relatively recalcitrant and contributes disproportionately to residual disease burden and relapse. These findings support the use of regional PASI assessment to guide individualized management and clinical expectations in this complex patient group. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) and the accumulation of tau in the brain, which triggers robust innate immune responses. Growing evidence indicates that neuroinflammation contributes to AD progression by overactivating microglia through the release of cytokines and chemokines. In general, chemokines can disrupt neuronal communication and promote blood–brain barrier permeability. Peripheral immune cells are mobilized into the brain by a gradient of chemokines. These processes link peripheral immune responses with substantial T-cell infiltration into the CNS parenchyma, leptomeninges and cerebrospinal fluid of both AD mice and AD patients. This finding underscores the relevance of the adaptive immune system, particularly T and B cells, in AD neuropathology. T-cell infiltration into the brain can influence amyloid clearance through chemokine signalling. However, chemokines play a critical role in AD by either promoting or suppressing disease progression. The infiltration of peripheral T and B cells into the brain parenchyma can exacerbate neuronal loss, yet it may also exert neuroprotective effects. Despite the presence of CD4⁺ and CD8⁺ T cells in postmortem brains of AD patients, debate continues about their role in AD brains, in terms of whether they are protective or detrimental. Understanding the complex role of chemokines in controlling innate and adaptive immune responses by modulating neuron–glia interactions (involving astrocytes and microglia) may provide novel therapeutic approaches for AD. Targeting chemokine signalling or treating with drugs that can prevent the recruitment of immune cells may be promising strategies for treating AD neuropathology. Therapies that prevent the overactivation of T cells in the brain could lead to protective strategies against AD. In fact, regulatory T cells (Tregs) could delay the onset of cognitive symptoms, because they suppress inflammation and slow the accumulation of Aβ plaques and p-Tau in the brain. Complementary strategies, such as photobiomodulation, nanoparticle, and T-cell-based approaches, could mitigate AD progression in patients. Full article

Background/Objectives: Orthodontic treatment induces controlled mechanical forces that alter the periodontal environment, including changes in oral microbiota composition and activation of local inflammatory pathways. Despite the widespread and growing use of orthodontic appliances across all age groups, the magnitude, timing, and multi-domain biological impact of these changes have not been comprehensively quantified in a single systematic synthesis. This systematic review and meta-analysis aimed to synthesize the available evidence on periodontal clinical parameters, oral microbiota composition, and local inflammatory biomarkers associated with orthodontic treatment using fixed appliances and clear aligners, and to provide a structured, GRADE-rated evidence base for clinical practice. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to March 2026. Prospective cohort studies, longitudinal clinical studies, and randomized controlled trials evaluating periodontal parameters, oral microbiota, and inflammatory biomarkers during orthodontic treatment were included. Quantitative synthesis was performed using mean differences or standardized mean differences with 95% confidence intervals, primarily assessing within-group (pre–post) changes. Results: Eighteen studies (n = 812 patients; follow-up 3–12 months) met inclusion criteria. Fixed orthodontic appliances were consistently associated with transient increases in plaque index (MD 0.45, 95% CI 0.32–0.58; I² = 62%), gingival index (MD 0.38, 95% CI 0.25–0.51; I² = 55%), and bleeding on probing (MD 15.2%, 95% CI 10.1–20.3%; I² = 48%), particularly during early treatment phases. Microbiological analyses demonstrated within-group shifts toward increased prevalence of periodontopathogenic species (Streptococcus mutans OR 2.45, 95% CI 1.89–3.18; Porphyromonas spp. OR 2.14, 95% CI 1.67–2.75) in patients treated with fixed appliances. Local inflammatory responses were characterized by elevated IL-1β (MD 1.2, 95% CI 0.8–1.6) and IL-6 (MD 0.9, 95% CI 0.6–1.2) in gingival crevicular fluid. Certainty of evidence was rated moderate for plaque and gingival indices and low for microbiological and inflammatory outcomes (GRADE). Conclusions: Orthodontic treatment—particularly with fixed appliances—is associated with transient, reversible deterioration of periodontal indices, shifts toward a more dysbiotic oral microbiome, and elevation of local inflammatory mediators in gingival crevicular fluid during active treatment phases. These changes are manageable through structured preventive protocols and regular periodontal monitoring. Future prospective studies with concurrent control groups and standardized multi-domain outcome measures are needed to better define the magnitude and reversibility of these biological responses. PROSPERO: CRD420261336117. Full article