Search Results (1,459)

Background and Objectives: Periodontitis is a chronic inflammatory disease that leads to progressive destruction of periodontal tissues and remains a significant global health burden. While conventional therapies such as scaling and root planning offer short-term improvements, they often fall short in maintaining long-term microbial control, underscoring the need for adjunctive strategies. This study evaluated the clinical and microbiological effects of a novel essential oil (EO)-based gel—SmartGel OV—formulated with Origanum vulgare. Materials and Methods: Thirty adults with periodontitis were enrolled in a 4-month observational study, during which SmartGel OV was applied daily via gingival massage. Clinical outcomes and bacterial profiles were assessed through probing measurements and real-time PCR analysis. Additionally, a pilot AI-based tool was explored as a supplemental method to monitor inflammation progression through intraoral images. Results: Significant reductions were observed in Fusobacterium nucleatum and Capnocytophaga spp., accompanied by improvements in clinical markers, including probing depth, bleeding on probing, and plaque index. The AI framework successfully identified visual inflammation changes and supported early detection of non-responsiveness. Conclusions: SmartGel OV demonstrates promise as a natural adjunctive treatment for periodontitis and AI monitoring was included as an exploratory secondary tool to assess feasibility for future remote tracking. Full article

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Platelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence, may be a critical but overlooked factor influencing therapeutic efficacy. Senescent platelets display reduced granule content, impaired responsiveness, and heightened pro-inflammatory behavior, all of which can compromise tissue repair and regeneration. This review explores the mechanisms underlying platelet aging, including oxidative stress, mitochondrial dysfunction, and systemic inflammation, and examines how these factors influence PRP performance across diverse clinical contexts. We discuss the functional consequences of platelet senescence, the impact of comorbidities and aging on PRP quality, and current tools to assess platelet functionality, such as HLA-I–based flow cytometry. In addition, we present strategies for pre-procedural optimization, advanced processing techniques, and adjunctive therapies aimed at enhancing platelet quality. Finally, we challenge the prevailing emphasis on high-volume blood collection, highlighting the limitations of quantity-focused protocols and advocating for a shift toward biologically precise, function-driven regenerative interventions. Recognizing and addressing platelet senescence is a key step toward unlocking the full therapeutic potential of PRP-based interventions. Full article

Triclabendazole (TCBZ) is the gold standard treatment for fascioliasis. However, reports on resistance are increasing, emphasizing the need for alternative therapy. Combining TCBZ with ivermectin (IVM) was found to be effective for treating animal fascioliasis. Building on this, we aimed to evaluate the efficacy of the TCBZ/IVM combination therapy for human fascioliasis. This study enrolled 136 patients with Fasciola from Upper Egypt, and they were divided into the first group (n = 65), who received TCBZ monotherapy, and the second group (n = 71), who received the TCBZ/IVM combination. Assessments were to evaluate treatment response based on clinical, eosinophilic, and radiological parameters. Chronic fasciolosis was diagnosed in 17 patients (12.5%). No differences were observed in age and sex. Significant improvements were noted in all parameters in both groups, with more pronounced effects observed in the second group. A significantly higher complete response, including clinical, eosinophilic, and radiological improvements, was reported in the combined therapy group, with 53.3% compared to 26.2% in the monotherapy group (p < 0.001). A high baseline eosinophilic count was significantly associated with response. The efficacy of the TCBZ/IVM combination for treating human fascioliasis suggested a possible boosting effect, which can benefit regions of TCBZ failure. Further large-scale randomized studies are warranted to confirm these findings. Full article

Glioma is a type of neoplasia that spontaneously arises from the glial cells of the brain in humans and dogs, and its prognosis is grave. Current treatment options for glioma include surgery, radiation therapy, chemotherapy, or symptomatic treatment. Evidence has shown that cannabidiol (CBD) may have anticancer, anti-angiogenic, and anti-inflammatory properties in both in vitro and in vivo studies. In this in vivo murine experiment, the canine glioma cell line J3TBG was injected into the frontoparietal cortex of immunodeficient mice using xenogeneic tissue transplantation. A total of 20 mice were randomly assigned to one of four treatment groups—Control group (C), CBD group (CBD), Radiation Therapy group (RT), and CBD plus Radiation Therapy group (CBD + RT). After transplantation of J3TBG, a single fraction of 5.5 Gy RT was administered to the RT and CBD + RT groups, and CBD was administered daily to the CBD and CBD + RT groups. Necropsies were performed to collect blood and brain tissue. Although there was not a statistically significant difference, the survival time among mice were longer in the CBD + RT group than the RT group. These results indicate that CBD may be used as an adjunctive therapy to enhance RT treatment. Larger cohort studies are required to substantiate the hypothesis. Full article

Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor for hyperlipidemia—has garnered interest for its potential anticancer effects. This study investigates the therapeutic potential of Simvastatin in triple-negative breast cancer (TNBC). The results demonstrate that Simvastatin significantly inhibits the proliferation of TNBC cells, particularly MDA-MB-231, in a dose- and time-dependent manner. Mechanistically, Simvastatin primarily induces G1 phase cell cycle arrest to exert its antiproliferative effects, with no significant evidence of apoptosis or necrosis. These findings support the potential repositioning of Simvastatin as a therapeutic agent to suppress TNBC cell growth. Further analysis shows that Simvastatin downregulates cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle transition and a known marker of poor prognosis in breast cancer. These findings highlight a novel, apoptosis-independent mechanism of Simvastatin’s anticancer action in TNBC. Importantly, given that many breast cancer patients also suffer from hyperlipidemia, Simvastatin offers dual therapeutic benefits—managing both lipid metabolism and tumor cell proliferation. Thus, Simvastatin holds promise as an adjunctive therapy in the treatment of TNBC and warrants further clinical investigation. Full article

Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional and neuroplastic effects of CE rehabilitation post-ACLR. Following PRISMA-ScR and JBI guidelines, PubMed, Scopus, Web of Science, and PEDro were searched up to February 2025. A bibliometric analysis was also conducted to report keyword co-occurrence and identify trends in this line of research. Of 333 screened references, 14 studies (price index: 43% and low-to-moderate risk of bias) involving 721 participants (aged 17–45 years) met inclusion criteria. CE protocols (6–12 weeks; 2–5 sessions/week) incorporating isometric, concentric, and eccentric exercises demonstrated strength gains (10–31%) and strength preservation, alongside improved limb symmetry (5–14%) and dynamic balance (7–18%). There is growing interest in neuroplasticity and corticospinal excitability, although neuroplastic changes were assessed heterogeneously across studies. Findings support CE as a feasible and low-cost strategy to complement early-stage ACLR rehabilitation, especially when direct loading of the affected limb is limited. Standardized protocols for clinical intervention and neurophysiological assessment are needed. Full article

Background/Objectives: Nelumbo nucifera Gaertn. (lotus) seeds have traditionally been used to treat hypertension, though their mechanisms remain unclear. This study investigated the antihypertensive effects of lotus seed extract (LSE) and its mechanisms in rats with N^ω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Methods: Male Sprague Dawley rats received L-NAME (40 mg/kg/day) in drinking water and were treated orally with LSE (5, 10, or 100 mg/kg/day), captopril (5 mg/kg/day), or a combination of LSE and captopril (2.5 mg/kg/day each) for 5 weeks. Hemodynamic parameters and histological changes in the left ventricle and aorta were assessed. Mechanistic studies included measurements of plasma nitric oxide (NO) metabolites, malondialdehyde (MDA), superoxide dismutase (SOD) activity, angiotensin II (Ang II), angiotensin-converting enzyme (ACE) activity, and protein expression via western blot. Results: L-NAME elevated systolic blood pressure and induced cardiovascular remodeling, oxidative stress, and renin-angiotensin system activation. LSE treatment reduced blood pressure, improved antioxidant status, increased NO bioavailability, and downregulated gp91^phox and AT₁R expression. The combination of low-dose LSE and captopril produced stronger effects than LSE alone, with efficacy comparable to captopril. Conclusions: These findings suggest that LSE exerts antihypertensive effects via antioxidant activity and inhibition of the renin-angiotensin system, supporting its potential as an adjunct therapy for hypertension. Full article

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder frequently associated with metabolic and inflammatory disturbances. Due to its antioxidant and anti-inflammatory properties, pomegranate juice has been proposed as a potential adjunctive therapy in managing PCOS. To evaluate the effects of pomegranate juice on hormonal, inflammatory, and lipid parameters and body mass index (BMI) in women with PCOS. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. Comprehensive searches were performed in electronic databases including Medline, Scopus, Web of Science, Cochrane CENTRAL, and Embase from inception to July 2025, using keywords and MeSH terms related to “polycystic ovary syndrome” and “pomegranate juice” without language restrictions. The primary outcomes were changes in serum testosterone, luteinizing hormone (LH), high-sensitivity C-reactive protein (hs-CRP), lipid profile parameters (HDL, LDL, triglycerides, and total cholesterol), and body mass index (BMI). Results: Four RCTs published between 2020 and 2023, encompassing 128 women with PCOS, were included. The meta-analysis revealed significant reductions in testosterone (MD: −0.05; 95% CI: −0.07 to −0.03; p < 0.0001; I² = 0%, two studies, 85 participants) and hs-CRP (SMD: −0.85; 95% CI: −1.35 to −0.35; p = 0.0009; I² = 20%, two studies, 85 participants), along with increases in HDL (MD: 6.21; 95% CI: 2.43 to 10.00; p = 0.001; I² = 0%, two studies, 85 participants) and reductions in triglycerides (MD: −23.30; 95% CI: −45.19 to −1.42; p = 0.04; I² = 0%, two studies, 85 participants). No significant changes were observed in LH, LDL, total cholesterol, or BMI. Conclusions: Pomegranate juice demonstrates promising effects as an adjunctive intervention in women with PCOS, improving androgen levels, inflammatory markers, and certain lipid parameters. Further long-term studies are needed to confirm these findings. Full article

Background/Objectives: Nonoperative management (NOM) of patients with locally advanced rectal cancer (LARC) who achieve a complete clinical response (cCR) to total neoadjuvant therapy (TNT) has been shown to be oncologically safe and is an attractive treatment option for patients. However, identifying responders to TNT that may benefit from nonoperative management is clinically challenging. Circulating tumor DNA (ctDNA) testing has shown promise in detecting minimal residual disease but has not yet been studied extensively within this clinical context. Methods: This is a single-institution retrospective case series study of LARC patients treated with TNT from 2019 to 2023 who underwent ctDNA testing as an adjunct to standard clinical response assessments. Results: A total of 28 patients had ctDNA testing as part of their response assessments after TNT. In total, 9 patients had positive ctDNA, and 19 patients had negative ctDNA during surveillance. Baseline characteristics of these two groups were not different. In this study, 6/9 (67%) patients who had positive ctDNA required surgery for residual rectal cancer, whereas only 4/19 (21%) patients who had negative ctDNA required surgery (p = 0.035). Conclusions: ctDNA testing has the potential to detect MRD in LARC patients treated with TNT. Full article

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, microbiome interactions, and molecular dysregulations involving gangliosides and sphingolipids. Current diagnostic strategies, including imaging, histopathology, immunohistochemistry, and emerging liquid biopsy techniques, are explored for their role in improving early detection and monitoring. Treatment remains challenging, with standard therapies—surgery, radiotherapy, and temozolomide—offering limited survival benefits. Innovative therapies are increasingly being explored and implemented, including immune checkpoint inhibitors, CAR-T cell therapy, dendritic and peptide vaccines, and oncolytic virotherapy. Advances in nanotechnology and personalized medicine, such as individualized multimodal immunotherapy and NanoTherm therapy, are also discussed as strategies to overcome the blood–brain barrier and tumor heterogeneity. Additionally, stem cell-based approaches show promise in targeted drug delivery and immune modulation. Non-conventional strategies such as ketogenic diets and palliative care are also evaluated for their adjunctive potential. While novel therapies hold promise, GBM’s complexity demands continued interdisciplinary research to improve prognosis, treatment response, and patient quality of life. This review underscores the urgent need for personalized, multimodal strategies in combating this devastating malignancy. Full article

Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential given the increasing use of dental implants in cancer survivors. The study aimed to observe the influence of tamoxifen on human osteosarcoma (SAOS-2) cells lines, as well on the osseointegration of titanium implants in ovariectomized female rats. Methods: SAOS-2 cells were incubated with Dulbecco’s modified growth medium. Six titanium (Ti) disks were used at each time point. The samples were divided into groups with the presence (TAM, n = 36) or not (CTR, n = 36) of tamoxifen in a concentration of 2 μM. In vivo, 72 animals were divided in groups with bilateral ovariectomy or SHAM and tamoxifen administration or not (15 mg/kg). Cell viability, mineralization rate, and collagen synthesis were assessed, as well as bone/implant contact (BIC) and bone ingrowth (BIN). Results: Tamoxifen caused a decrease in SAOS-2 viability, although an increase in the mineralization rate was observed. In vivo, the TAM groups presented higher BIC and BIN when compared to their control, but a lower percentage of mature collagen cells. Conclusions: Based on our findings, in vitro, the therapy with TAM slightly reduced the viability of SAOS-2 cells while significantly increasing the mineralization rate. In vivo, the therapy positively influenced BIC and BIN during the osseointegration phase. Full article

Background: Obstructive sleep apnea (OSA) is a prevalent disorder in both pediatric and adult populations, characterized by substantial morbidity encompassing cardiovascular, neurocognitive, and metabolic impairments. Management strategies vary by age group and underlying etiology, with orthodontic and non-orthodontic interventions playing key roles. This narrative review synthesizes the current evidence on orthodontic and non-orthodontic therapies for OSA in pediatric and adult populations, emphasizing individualized, multidisciplinary care approaches and highlighting future research directions. Methods: A narrative review was conducted using PubMed, Scopus, and Google Scholar to identify studies on diagnosis and management of OSA in children and adults from 2000 to 2025. Results: In pediatric patients, treatments such as rapid maxillary expansion (RME), mandibular advancement devices (MADs), and adenotonsillectomy have shown promising outcomes in improving airway dimensions and reducing apnea–hypopnea index (AHI). For adults, comprehensive management includes positive airway pressure (PAP) therapy, oral appliances, maxillomandibular advancement (MMA) surgery, and emerging modalities such as hypoglossal nerve stimulation. Special attention is given to long-term treatment outcomes, adherence challenges, and multidisciplinary approaches. Conclusions: The findings highlight the need for individualized therapy based on anatomical, functional, and compliance-related factors. As the understanding of OSA pathophysiology evolves, orthodontic and adjunctive therapies continue to expand their role in achieving durable and patient-centered outcomes in sleep apnea management. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article