Search Results (7,812)

Background and Objectives: Endometrial adenocarcinoma is among the most prevalent malignancies of the female reproductive system, and therapeutic options remain limited, particularly in advanced stages. In recent years, natural agents, especially flavonoids, have gained considerable interest for their capacity to enhance the effectiveness of chemotherapeutic drugs and modulate tumor-related molecular mechanisms. Hesperidin, a citrus-derived flavonoid, is recognized for its antioxidant and anti-inflammatory effects, while Gemcitabine, a nucleoside analog, is widely used in cancer treatment. Investigating their combined effects on endometrial carcinoma cells could yield novel insights into multimodal therapeutic development. This current study aimed to assess the impact of Hesperidin (Hes) and Gemcitabine (Gem) on ISHIKAWA cells, a human endometrial adenocarcinoma model, with particular attention to pathways associated with hypoxia, angiogenesis, apoptosis, and oxidative stress. Materials and Methods: ISHIKAWA cells were treated with varying concentrations of Hes (50–200 µM) and Gem (10–50 nM), either individually or together, for 24 and 48 h. Cell viability was determined using the MTT assay, while apoptosis was measured by Caspase-3/7 activity and NucBlue nuclear staining. Intracellular reactive oxygen species (ROS) generation was quantified via DCFH-DA fluorescence. Expression levels of HIF-1α, VEGF, Bax, Bcl-2, and Caspase-3 were examined by RT-qPCR. Synergistic interactions were analyzed with the Chou–Talalay combination index. Biological enrichment was further explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Both Hes and Gem significantly decreased ISHIKAWA cell viability in a concentration- and time-dependent manner (p < 0.001). The combined treatment induced stronger apoptotic effects, as reflected by increased Caspase-3/7 activity and nuclear morphological changes. RT-qPCR demonstrated upregulation of Bax and Caspase-3, together with downregulation of Bcl-2, HIF-1α, and VEGF. While Hes reduced intracellular ROS, Gem elevated it; their combination produced a balanced oxidative response. All dose combinations displayed strong synergism (CI < 1). GO and KEGG enrichment confirmed the involvement of apoptosis-, angiogenesis-, and hypoxia-related pathways. Conclusions: Co-treatment with Hes and Gem exhibits synergistic anticancer activity in endometrial cancer cells by promoting apoptosis, suppressing angiogenesis- and hypoxia-related gene expression, and modulating oxidative stress. This combined therapeutic approach highlights its potential as a promising adjuvant option, warranting further evaluation in in vivo and translational studies. Full article

The H9N2 virus has severely harmed the livestock and bird farming industry. Currently, it is mainly prevented through vaccination immunization. However, conventional vaccines often fail to induce durable immune responses and long-lasting immunoprotection. In this research, we used Simvastatin (Sim) and CpG as adjuvants for the H9N2 inactivated vaccine to evaluate the vaccine’s immunogenicity in chickens. We evaluate vaccine immunogenicity through antibody testing, T lymphocyte phenotyping, and RNA-sequencing analysis. The results indicated that the Sim + CpG/H9N2 formulation significantly enhanced specific IgY and hemagglutination inhibition (HI) antibody titers. It also increased the proportions of CD4⁺ T cells and CD8⁺ T cells, promoted immune organ development, and stimulated the formation of germinal centers. RNA-sequencing analysis revealed that Sim + CpG/H9N2 vaccination significantly upregulated immune-related genes, which were enriched in pathways associated with stress response activation, immune cell recruitment, and inflammatory signaling. Overall, these findings demonstrate that Sim + CpG/H9N2 markedly enhances the immunogenicity of the inactivated H9N2 vaccine and provides new insights into the application of vaccine adjuvants for improved immune protection. Full article

To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both cell lines’ median, maximum, and minimum α and β parameters to achieve an LSR probability of close to 100% in a five-fraction schedule. Based on these findings, fifteen treatment plans were created for BC to simulate the proposed dose schedule. For the MDA-MB-231 cell line, the α/β ratios were 3.79 Gy (minimum), 15 Gy (maximum), and 7 Gy (median). For the BT-549 cell line, the α/β ratios were 5.95 Gy (minimum), 22.93 Gy (maximum), and 16.51 Gy (median). To achieve an LSR probability of close to 100%, the required doses per fraction were 5.2 Gy, 5.3 Gy, and 7.3 Gy for MDA-MB-231 and 8 Gy, 9.1 Gy, and 9.9 Gy for BT-549. We selected the highest dose per fraction, 9.9 Gy × 5, to simulate the worst-case scenario. To achieve 100% cell death effectiveness in TNBC, it is likely that higher radiation doses are required—doses that are not feasible within the setting of adjuvant whole-breast irradiation. Our model, which relies on the intrinsic biological features of the tumor, paves the way to reach more tailored RT plans and to improve the classic LQ model. Full article

This study focuses on the issue of whether orally administered zinc (gluconate) (26 mg BID) can induce the remodeling of gastrointestinal barrier function and reduce passive leak across the human intestinal mucosal barrier in situ. Increased transmucosal leak has been implicated in diseases as diverse and seemingly unconnected as Inflammatory Bowel Disease (IBD), Celiac Disease, Autism Spectrum Disorders and Alzheimer’s Dementia. Our current investigation represents the first patient-based study to examine the effect of zinc on gastrointestinal epithelial tight junctions and gastrointestinal barrier leak in otherwise healthy test subjects. Using independent test subject groups for each endpoint, three separate molecular analyses indicated that zinc treatment can achieve a positive outcome: (1) RNA-seq analyses of intestinal biopsies showed salutary patterns of gene transcription changes dealing with not only transcripts of junctional proteins but also transcripts mitigating the proinflammatory state, as well as dedifferentiation (both modulators of tight junction permeability); (2) Western immunoblot analyses of intestinal tissue indicated that tight junctional protein expression was being modified by the administered zinc, most notably Claudin-2 and Tricellulin; (3) zinc treatment induced a reduction in serum levels of a functional marker of passive intestinal leak, namely the GI microbiome metabolite D-Lactate. The data collectively suggest that orally administered zinc can induce remodeling of the intestinal epithelial barrier, resulting in the reduction in GI barrier leak. The overall safety and economy of supplement levels of zinc suggest that this micronutrient could be efficacious as an adjuvant therapy to reduce the condition known as leaky gut, and possibly therefore be protective regarding diseases postulated to involve leaky gut. Full article

Background/Objectives: Pemphigus is a rare blistering disease characterized by a chronic course, associated with significant mortality and morbidity. This review article aims to delve into three Pemphigus subtypes: Pemphigus Vulgaris, Pemphigus Foliaceus and Paraneoplastic Pemphigus, including the safety and efficacy of their treatment options. Methods: A thorough literature search was conducted using PubMed, EMBASE, Medline and Cochrane Library to collate data on pharmaceutical treatments of Pemphigus. Studies were selected based on predefined inclusion criteria, which included English language, peer-reviewed articles published in the date range January 2000 to May 2025. Eligible studies involved adults diagnosed with Pemphigus Vulgaris, Pemphigus Foliaceus or Paraneoplastic Pemphigus who were treated with Glucocorticoids, Mycophenolate mofetil, azathioprine or rituximab. The focus was on identifying adverse effects, complete remission and relapse rates. Results: The analysis revealed that glucocorticoid is the first-line treatment for Pemphigus. However, low remission rates of 34% along with steroid-related adverse effects indicate the use of Mycophenolate and azathioprine as steroid-sparing adjuvant therapies. Emerging treatments with rituximab have demonstrated 90% remission rates, indicating promising results with a comparatively mild side effect profile. Conclusions: The findings highlight the importance of ongoing evaluation of treatment modalities for Pemphigus subtypes to optimise remission rates and minimise adverse effects. Ultimately, studies often fail to isolate specific Pemphigus subtypes owing to the scarcity of literature. There is also a crucial need to address the lack of a standardised grading system for the side effects of glucocorticoids and long-term safety data for rituximab in further longitudinal research. Full article

Monkeypox (Mpox), a re-emerging zoonotic disease, has garnered global attention due to its evolving epidemiology, diverse clinical manifestations, and significant public health impact. The rapid international spread of the Mpox prompted the World Health Organization to designate the outbreak as a Public Health Emergency of International Concern. Accurate and timely diagnosis is hindered by its critical resemblance to other orthopoxviruses and viral exanthems, underscoring the need for improved diagnostic tools. Point-of-care diagnostic innovations, including CRISPR-based and smartphone-integrated technologies, have revolutionized outbreak management, offering rapid and accurate detection critical for containment and treatment. The effective control of Mpox outbreak underscores the necessity of strengthened global surveillance, equitable healthcare access, rapid diagnostics, the prompt isolation of infected individuals, and the implantation of ring vaccination strategies. The integration of a “One Health” framework that links human, animal, and environmental health is vital for sustained preparedness. Advances in vaccine development, including novel bionic self-adjuvating vaccines and platforms utilizing DNA, mRNA, and viral vectors, highlight promising prevention efforts. However, issues such as vaccine hesitancy, limited immunization coverage and accessibility in resource-constrained regions remain significant barriers. Therapeutic interventions like tecovirimat and the JYNNEOS vaccine demonstrate efficacy but face challenges in scalability and deployment. To address these multifaceted challenges, this review delves into the molecular insights, clinical features, epidemiological trends, and diagnostic challenges posed by Mpox. This review further highlights the critical need for robust scientific evidence and sustained research to inform effective, evidence-based responses, and long-term management strategies for Mpox outbreaks. Full article

Half of all Canadians will develop cancer at some point in their lifetimes. These rates have increased substantially over the last decade alongside increasing effectiveness and complexity of treatment options. Therefore, the need for patients to receive both an early diagnosis and ongoing care has never been so important. In Alberta, referrals to oncology specialty care have increased 18% in the last 7 years with no commensurate increase in the number of oncology health care professionals. Challenges with oncologic care access and provider recruitment are not unique to Alberta. In 2004, Cancer Care Alberta, specifically the Cross Cancer Institute (CCI), embarked on an initiative focusing on nurse practitioner (NP) care provision, aiming to address these gaps. The purpose of this article is a description of four distinct NP care models: the Assigned model, Consultative model, Partner model, and Most Responsible Provider (MRP model) significantly contributing to enhanced and expanded cancer care delivery at CCI. To the best of our knowledge, we are the first to demonstrate how NPs can significantly address the rapidly expanding demands for specialist oncology care. This work highlights roles and exemplars of NP care to meet the evolving needs of cancer patients, the multidisciplinary care team and the health system. Full article

Background: Conservative mastectomy with prepectoral breast reconstruction is becoming increasingly widespread and validated in recent years. Today, while aesthetic advantages and improvement in quality-of-life outcomes are widely acknowledged, oncological safety remains subject of debate. There is limited evidence on residual breast tissue after conservative mastectomy, and it still represents an unknown risk for local recurrence. The recent spread of this surgical technique precludes a standardized surgical approach in case of local recurrence of ipsilateral breast cancer, and the lack of evidence in the literature complicates the decision-making process. The objective of this study is to describe the surgical treatment of local relapses for breast cancer patients following conservative mastectomy and prepectoral implant-based reconstruction. Methods: Between January 2018 and May 2024 at a single institution, 648 consecutive patients underwent conservative mastectomy and prepectoral reconstruction as their primary treatment. We identified 12 patients with T1-2 breast cancer who subsequently had histologically confirmed ipsilateral breast cancer recurrence and a local wide excision or radical mastectomy were performed. Each clinical case was discussed in a multidisciplinary meeting to define the most appropriate surgical treatment. At time of diagnosis of recurrence, patients with lymph node metastasis or systemic involvement were excluded from the study. Results: Among 648 consecutive patients who underwent conservative mastectomy, 12 with histologically confirmed ipsilateral breast cancer recurrence were included. The mean interval to recurrence was 43 months (range 10–76 months) from the primary operation. Recurrence sites were as follows: upper outer quadrant in four patients (33.4%), upper inner quadrant in three (25.0%), lower inner quadrant in two (16.6%), lower outer quadrant in one (8.4%), and central quadrant with nipple involvement in two (16.6%). Of the 12 patients, 9 (75%) underwent wide local excision, including 2 who also received partial capsulectomy, while 3 (25%) required radical mastectomy with implant removal. Adjuvant radiation therapy was administered to 6 patients (50%)—5/6 (83.3%) in the excision group and 1/6 (16.7%) in the mastectomy group. No significant differences were observed in distant disease–free survival or overall survival between the two groups. Conclusions: Currently, surgical treatment of ipsilateral breast tumor recurrence following conservative mastectomy and prepectoral breast reconstruction is not reported in the literature, and this study represents the first instance where wide local excision is described. The management of ipsilateral recurrence should be discussed in multidisciplinary meetings and could be performed safely in selected cases, sparing the prosthesis and avoiding radical mastectomy. Full article

Current aftercare after early breast cancer overlooks recent evidence on circulating free tumor DNA (ctDNA). In this case report, we present a patient with low-risk hormone-receptor-positive breast cancer. ctDNA was first detected using a tumor-informed approach 12 months after the initial diagnosis and remained positive throughout adjuvant therapy with letrozole, while routine staging examinations showed no signs of relapse. Clinical relapse was ultimately identified nearly six years after the initial diagnosis, resulting in a lead time of four years and nine months. Current studies on ctDNA in the adjuvant setting have been conducted in high-risk cohorts and have shown a median molecular lead time of 8.9–12.4 months. Our study supports the need for large randomized clinical trials involving low-risk breast cancer patients to drive changes in clinical practice. Full article

Background/Objectives: Influenza poses a substantial global public health challenge, disproportionately affecting vulnerable populations. Vaccination is the most effective preventive measure, and recent strategies in Italy emphasize the principle of “appropriateness”—the alignment of specific vaccine formulations (e.g., adjuvanted or high-dose) with targeted risk groups to optimize protection. Nevertheless, challenges persist in ensuring the consistent administration of the most suitable vaccine, particularly among high-risk individuals who would benefit most. Methods: A retrospective descriptive study was conducted using data from the 2023–2024 and 2024–2025 influenza vaccination campaigns of the Local Health Authority of Catania. Vaccination data were analyzed by age group and vaccine type, based on national immunization guidelines. Population categories included individuals ≥ 65 years, adults 60–64 years, adults 18–59 years (with/without chronic conditions), children, and pregnant/postpartum women. Vaccine types analyzed were aQIV, QIV-HD, QIV-SD, QIVcc, and LAIV. Descriptive statistics were used, and Relative Risk (RR) with 95% Confidence Intervals (CI) was calculated using the 60–64 age group as a reference. Analyses were performed with Stata 18.0. Results: In 2023–2024, 78.8% of individuals ≥ 65 received recommended vaccines, compared to 100% in the 60–64 group (RR = 0.23; 95% CI: 0.225–0.231). Adults 18–59, children, and pregnant/postpartum women showed ≥99% adherence. In 2024–2025, appropriateness in the ≥65 group improved to 96.1% (RR = 0.12; 95% CI: 0.118–0.128). All other groups maintained high adherence (≥99%), except for 6.2% of children aged 6 months–2 years who inappropriately received LAIV. Conclusions: Despite dramatically improved vaccination appropriateness in the elderly, a persistent and critical safety issue--inappropriate administration LAIV use in 6.2% of young children—highlights the need for targeted interventions to ensure complete patient safety. Full article

Background: Cardiac glycosides such as digoxin have been commonly used for patients with heart failure; however, their toxicity remains a main concern. 17βH-neriifolin (SNA209), a cardiac glycoside compound, has been recently isolated from Ceberra odollum Gaertn and was shown to improve the heart’s pumping ability in failing hearts ex vivo. Thus, this study aimed to investigate the potential use of SNA209 as a treatment for isoprenaline (ISO)-induced heart failure in rats. Methods: Forty male Wistar rats were randomly divided into five groups. Heart failure was induced by isoprenaline (ISO, 10 mg/kg/s.c) for 14 days daily, followed by SNA209 treatment (5 mg/kg; p.o) for another 14 days daily. Control rats were given saline as a vehicle for ISO and DMSO as a vehicle for SNA209. Results: Systolic and diastolic blood pressure (SBP and DBP) in all ISO-treated groups were significantly increased compared to the control group (p < 0.05), and SNA209 treatment managed to reduce the SBP and DBP. Additionally, SNA209 treatment significantly increased the heart rate and normalized the ECG parameters in ISO-treated rats. Pro-B-type natriuretic peptide and troponin T level, a cardiac injury markers, was remarkably reduced by SNA209 in the ISO-treated group. Cardiac hypertrophy was evident in increased cardiomyocyte size in ISO groups; however, SNA reduced the cardiomyocyte size. The left ventricular developed pressure (LVDP) in ISO treated with SNA209 was significantly raised, indicating a chronotropic effect. Cardiac Na⁺/K⁺-ATPase expression of the α1 subunit, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a (SERCA2a), and sodium–calcium exchanger subunit were significantly increased in the SNA treatment groups. Conclusions: The SNA 209 treatment improved cardiac function and structure, likely via modulating intracellular calcium management, so underscoring its potential as an adjuvant therapy for heart failure. Full article

Influenza vaccines are the primary strategy to prevent severe influenza disease; however, their efficacy is often suboptimal, particularly in older adults (OAs). LiteVax Adjuvant (LVA), a novel adjuvant containing carbohydrate fatty-acid monosulphate ester (CMS) as the active ingredient, has demonstrated a favourable safety profile and enhanced immunogenicity when combined with a low-dose seasonal influenza vaccine in adults aged 18 to 50 years in a first-in-human phase 1 study. The present study investigates the reactogenicity and immunogenicity of CMS-based adjuvanted seasonal influenza vaccine in OAs, with a comparison to responses in younger adults (YAs). In this phase 1b, double-blind, active-controlled clinical trial, 36 YAs (18–50 years) and 48 OAs (≥60 years) were randomized (1:1:1) to receive either 0.5 mg or 1 mg LVA combined with VaxigripTetra, or VaxigripTetra alone. Solicited adverse events (AEs) were recorded using an electronic diary for 7 days following vaccination. Hemagglutination inhibition (HI) titers against four influenza strains were measured at baseline (pre-vaccination) and at 7-, 28-, and 180-days post-vaccination. All 24 YAs and 31 out of 32 OAs receiving CMS-based adjuvanted vaccines reported pain post-vaccination, compared to 8/12 YAs and 4/16 OAs receiving VaxigripTetra. Systemic AEs were more frequently reported among YAs receiving CMS-based adjuvanted vaccines (22/24) compared to those receiving VaxigripTetra (8/12). In OAs, the number of systemic AEs was similar regardless of CMS-based adjuvant administration. Most AEs were mild to moderate and resolved within 3 days. Both CMS-based adjuvanted formulations elicited increased HI titers at Day 7, peaking at Day 28, with a decline thereafter that remained above baseline at Day 180. In YAs, HI titers were comparable between the CMS-based adjuvanted and non-adjuvanted vaccines across all strains and timepoints. In contrast, CMS-based adjuvanted vaccination in OAs induced higher HI titers at Days 28 and 180 for all influenza strains tested. LVA shows an acceptable safety profile in both age cohorts and enhances humoral immune responses in older adults. The 1 mg dose of LVA was more immunogenic, highlighting its potential utility in this target population. Future research will focus on elucidating the mechanisms underlying the immunostimulatory effect of the CMS-based adjuvant. Full article

Background: Hormone receptor-positive (HR+), HER2-negative breast cancer accounts for the majority of breast cancer diagnoses. While outcomes have improved with neoadjuvant and adjuvant therapies, the risk of late recurrence persists, and there remains a critical need for reliable biomarkers to guide prognosis and post-treatment surveillance. Circulating tumor DNA (ctDNA), detectable via liquid biopsy, has emerged as a promising tool for monitoring minimal residual disease and predicting survival outcomes. This systematic review evaluates the association between ctDNA detection during neoadjuvant or adjuvant treatment and survival outcomes in early-stage HR+/HER2− breast cancer. Methods: This systematic review was conducted in accordance with PRISMA guidelines. A comprehensive literature search of Ovid MEDLINE and Embase was conducted to identify studies published through 3 May 2024 that evaluated ctDNA as a prognostic biomarker in stage I–III HR+/HER2− breast cancer. We included studies reporting recurrence-free survival, invasive disease-free survival, or overall survival and excluded non-original studies, conference abstracts, and non-English articles. Data extraction and qualitative synthesis were performed, and the risk of bias was qualitatively assessed across studies. No review protocol was registered. Results: Eleven studies comprising 1644 patients met the inclusion criteria. In the neoadjuvant setting, ctDNA positivity prior to treatment initiation was associated with inferior survival outcomes. In the adjuvant setting, detection of ctDNA during or after treatment was consistently linked to poorer recurrence-free and invasive disease-free survival. Across studies, ctDNA detection was a significant negative prognostic marker. Conclusions: This systematic review supports the prognostic value of ctDNA in HR+/HER2− early-stage breast cancer. Limitations include small sample sizes, observational study designs, and heterogeneity in ctDNA assays. Standardization of ctDNA testing methods and further prospective trials are needed to validate its clinical utility and explore its potential role in guiding therapeutic interventions. Full article

Background: Breast cancer is frequently diagnosed in older women. However, the impact of surgery on survival is not well studied and prognosis for women ≥ 80 years of age is progressively depending on comorbidities. Methods: Medical records of consecutive women aged ≥ 80 years diagnosed with primary breast cancer treated with upfront surgery at two Breast Centers from 2011 to 2021 were retrospectively analyzed. Results: A total of 553 consecutive women with a median age of 83 years and a median tumor diameter of 21 mm were analyzed (574 lesions). Clinical Stages II or III were found in 263/574 (46%) and 101/574 cases (18%), respectively. Axillary staging was completely omitted for 94/542 invasive lesions (17%), and this increased over time from 2% to 33% (p < 0.001). Adjuvant hormone therapy and radiotherapy were omitted in 134/490 (27%) and in 122/420 patients (29%), respectively, while only 26/195 (13%) of patients with a clear clinical indication received adjuvant chemotherapy. At a median follow-up of 61 months (6–147) the 5- and 10-years overall survival (OS) were 64% and 21%, while breast cancer-specific survival (BCSS) at 5 and 10 years were 94% and 78%, respectively. Adjuvant therapies were not associated with a significant improvement in BCSS, while worse OS was associated with older age or more comorbidities as measured by the Charlson Comorbidity Index (CCI) (p < 0.001 and p = 0.012, respectively). Conclusions: Breast surgery, when possible, has a primary role even for women > 80 years of age, and it is associated with a reasonable BCSS. De-escalation of adjuvant therapies should be considered in this setting because survival is largely determined by age and co-morbidities. Full article

Background: Helicobacter pylori (H. pylori) is a major pathogen associated with a variety of gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. As a natural bioactive product, propolis exhibits multifaceted and multi-mechanistic effects. Due to its immunomodulatory, anti-inflammatory, and antioxidant properties, propolis has emerged as a promising therapeutic alternative, offering an innovative approach to managing H. pylori infections and providing new insights into addressing antibiotic resistance. Methods: This comprehensive review, synthesizing data from PubMed, ScienceDirect, and SciFinder, examines the mechanisms by which propolis combats H. pylori. Results: Propolis has demonstrated significant antibacterial efficacy against H. pylori in both in vitro and in vivo models. Its multitargeted mechanisms of action include direct inhibition of bacterial growth, interference with the expression of virulence factors, suppression of virulence-associated enzymes and toxin activity, immunomodulation, and anti-inflammatory effects. These combined actions alleviate gastric mucosal inflammation and damage, reduce bacterial colonization, and promote mucosal healing through antioxidant and repair-promoting effects. Furthermore, propolis disrupts oral biofilms, restores the balance of the oral microbiome, and exerts bactericidal effects in the oral cavity. Synergistic interactions between propolis and conventional medications or other natural agents highlight its potential as an adjunctive therapy. Conclusions: Propolis demonstrates dual functionality by inhibiting the release of inflammatory mediators and suppressing H. pylori growth, highlighting its potential as an adjuvant therapeutic agent. However, clinical translation requires standardized quality control and higher-level clinical evidence. Future research should focus on validating its clinical efficacy and determining optimal dosing regimens, and exploring its role in reducing H. pylori recurrence. Full article