Search Results (10,020)

Endothelial dysfunction (ED) is an early event in cardiovascular and metabolic diseases, including atherosclerosis, diabetes, and hypertension. Emerging evidence highlights the interplay between chronic inflammation and oxidative stress, collectively termed OxInflammation, as a major driver of vascular injury and impaired tissue repair. Among the key mediators of this response is the Nod like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex that promotes the release of inflammatory cytokines, including Interleukin 1β (IL-1β) and Interleukin-18 (IL-18), and induces gasdermin D-mediated pyroptotic cell death. Activation of NLRP3 disrupts endothelial function, reduces nitric oxide availability, and accelerates vascular inflammation and injury. This review discusses current evidence on pharmacological strategies targeting NLRP3 inflammasome signaling using both natural and synthetic inhibitors. Studies have shown that inhibiting NLRP3 can reduce inflammation and oxidative stress, preserve endothelial integrity, improve vascular function, and support tissue repair. Several NLRP3-targeting compounds have advanced into early-phase clinical trials, showing encouraging safety profiles and efficacy in individuals with cardiovascular risk factors. By integrating the emerging concept of OxInflammation with endothelial dysfunction, this review critically evaluates the therapeutic and translational potential of NLRP3 inflammasome inhibition in cardiovascular and metabolic disorders. Collectively, the available evidence supports NLRP3 as a promising therapeutic target for restoring endothelial homeostasis and promoting vascular repair. However, further clinical studies are needed to establish long-term efficacy, optimal dosing strategies, and appropriate patient selection criteria. Full article

Hypertension is among the most important modifiable risk factors associated with heart failure with preserved ejection fraction (HFpEF) development and progression, yet guideline-directed blood pressure (BP) targets (<130/80 mmHg) and sodium–glucose co-transporter 2 inhibitor (SGLT2i) therapies lack dedicated randomized controlled trials (RCTs) in this specific group of patients. This narrative review synthesizes 2024 ESC/ESH and 2025 JSH meta-analyses, discussing the proposed pathophysiological framework linking hypertension-associated remodeling with HFpEF. Post hoc analyses from landmark trials (EMPEROR-Preserved, DELIVER) demonstrate consistent heart failure (HF) event reductions with SGLT2i (pooled HR 0.79, 95% CI 0.67–0.93), complemented by modest systolic BP lowering (−2.3 mmHg) and biomarker insights. Soluble ST2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) may contribute to risk stratification in HFpEF populations when interpreted in conjuction with imaging findings and clinical context; however, neither biomarker is specific for hypertension-mediated remodeling. Critical evidence gaps persist: heterogeneous BP thresholds across international guidelines, limited device therapy data (renal denervation showing −8.5 mmHg sustained reduction), and real-world implementation barriers among elderly/comorbid Europeans (adherence < 50%, polypharmacy risks). Hellenic HF Registry data highlight frailty prevalence (68% in patients > 75 years) complicating aggressive BP management. The review addresses phenotype-specific challenges through precision medicine approaches incorporating phenomapping and multi-biomarker panels (NRI 0.28 improvement). We advocate for dedicated HFpEF RCTs evaluating intensive vs. standard BP targets, SGLT2i sequencing with antihypertensives, and European real-world registries to bridge the translational gap. These strategies aim to transform guideline recommendations into optimized, patient-centered care for the rapidly expanding hypertensive HFpEF population. Full article

Alkaline water is increasingly marketed for musculoskeletal and recovery benefits, yet its relevance to healthy aging, sarcopenia prevention, and functional capacity in older adults remains largely unexplored. This systematic evidence map and translational appraisal examined whether the available comparative human evidence on alkaline water is applicable to aging populations and longevity research. Following PRISMA guidance, PubMed and Scopus were searched from January 2005 to September 2025. Eligible studies were controlled or comparative observational human studies reporting muscle strength, physical performance, or recovery outcomes. Risk of bias was assessed using RoB 2, ROBINS-I, and JBI criteria; evidence certainty was judged narratively using GRADE-informed principles. Ten studies met the inclusion criteria. Most enrolled young athletic populations; only two had partial relevance to aging cohorts. Crucially, no study included participants aged 65 years or older or assessed primary sarcopenia-relevant endpoints such as appendicular lean mass, gait speed, or chair-rise performance; this total absence of data in the target demographic represents the central limitation of the current literature. Risk of bias ranged from some concerns to serious. The most consistent signals were short-term improvements in lactate clearance and perceived exertion in young male athletes. Evidence for strength, functional performance, and safety in older adults was absent or indirect. Current evidence, rated low to very low certainty for aging-relevant outcomes, does not support alkaline water as an evidence-based strategy for healthy aging or muscle preservation in older adults. Age-appropriate trials using EWGSOP2-aligned outcomes are urgently needed. Full article

Background: BCMA-targeted Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). However, the disease is not curable and progression after CAR T-cell treatment remains a challenge. Clonal hematopoiesis, specifically mutations in the DNA damage response gene PPM1D, has been linked to therapy resistance and inferior survival in lymphoma patients undergoing cellular therapy. The impact of PPM1D mutations on MM patient outcome after CAR T-cell therapy remains undefined. Methods: We conducted a retrospective single-center study of 83 patients with RRMM patients treated with idecabtagene vicleucel or ciltacabtagene autoleucel between 2022 and 2025. Next-generation sequencing was performed on peripheral blood mononuclear cells collected prior to CAR T-cell infusion to identify PPM1D exon 6 mutations (variant allele frequency > 0.01). We analyzed associations between mutational status, clinical characteristics, toxicity, and survival. Results: PPM1D mutations were detected in 14.5% (12/83) of patients. PPM1D-mutated patients had fewer prior autologous stem cell transplantation compared to wild-type patients (50% vs. 82%, p = 0.02) and presented more advanced disease burden and adverse prognostic features (R-ISS stage III 58% vs. 20%, p = 0.05). Notably, PPM1D status did not impact initial efficacy; complete remission rates were comparable between groups (67% vs. 69%). However, PPM1D mutations were significantly associated with inferior progression-free survival (PFS) (median PFS: 6 months vs. 16 months, p = 0.04). Regarding toxicity, the mutated subgroup exhibited significantly higher rates of grade ≥2 cytokine release syndrome and a trend toward increased neurotoxicity (25% vs. 7%). Conclusions: PPM1D clonal hematopoiesis is frequent in RRMM and despite deep initial responses, patients harboring PPM1D mutations face a significantly higher risk of early relapse. PPM1D mutations may serve as a biomarker for poor durability of response and should be further evaluated in larger, prospective trials. Full article

Diabetic kidney disease (DKD) represents the single most common etiology of chronic kidney disease and end stage kidney disease globally, a burden that continues to expand in direct proportion to the worldwide growth of the diabetes epidemic. The pathogenesis of DKD is multifactorial, involving metabolic, hemodynamic, inflammatory, and fibrotic pathways. Among these, aldosterone has emerged as a key mediator of kidney injury, extending beyond its traditional role in sodium balance and blood pressure regulation. Through activation of both MR-dependent transcriptional processes and MR-independent signaling cascades, aldosterone drives a coordinated pattern of renal injury encompassing oxidative stress generation, endothelial dysfunction, podocyte damage, inflammatory cell recruitment, and progressive interstitial fibrosis. Current therapies targeting the renin–angiotensin–aldosterone system (RAAS), including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists, have significantly improved outcomes in DKD. Despite these advances, a considerable degree of residual cardiovascular and renal risk persists, attributable in part to the incomplete attenuation of aldosterone activity and the well-characterized phenomenon of aldosterone escape under sustained RAAS blockade. Aldosterone synthase inhibitors (ASIs) represent a mechanistically distinct therapeutic approach that targets aldosterone overproduction at its enzymatic source, potentially addressing both MR-dependent and independent pathways. Early clinical trials evaluating the efficacy of ASIs have demonstrated promising effects on blood pressure and albuminuria. This review summarizes the role of aldosterone in DKD pathogenesis, evaluates current therapeutic approaches, and discusses emerging evidence supporting ASIs as a potential addition to the evolving treatment landscape. Full article

Background: Insomnia and stress-related sleep disorders are increasingly recognized as systemic conditions linked to the microbiota–gut–brain axis (MGBA). With growing clinical interest in natural products that modulate the gut environment, this systematic review evaluates the efficacy and mechanisms of non-pharmacological interventions, specifically probiotics, prebiotics, dietary indices, and botanicals, in alleviating insomnia, restoring circadian rhythms, and modulating neurochemical markers. Methods: In strict accordance with PRISMA 2020 guidelines, we searched PubMed, ScienceDirect, Scopus, and The Cochrane Library for English language studies published from inception to March 31, 2026. Eligibility was restricted to studies with rigorously controlled designs, specifically randomized controlled trials (RCTs) and controlled in vivo animal studies. Interventions had to target the gut microbiota, with primary outcomes measuring sleep quality (subjective or objective) or sleep-related neurochemical markers. We excluded uncontrolled, single-arm, or observational designs; in vitro studies; non-original research; and studies involving subjects with severe medical or psychiatric comorbidities (e.g., cancer, ADHD, severe psychiatric disorders) to prevent confounding variables, though mild-to-moderate anxiety and depression were permitted. Risk of bias was assessed using the Cochrane RoB 2.0 and SYRCLE tools. Due to significant methodological heterogeneity, a narrative synthesis stratified by intervention and population was conducted. This review was not registered in PROSPERO. Results: A total of 56 studies (33 humans, 23 animals) met the inclusion criteria. Taxonomic nomenclature was updated to reflect 2020 reclassifications (e.g., Lactiplantibacillus plantarum). In human trials, interventions significantly improved subjective sleep metrics (PSQI, ISI). Recent additions demonstrated the efficacy of the Dietary Index for Gut Microbiota (DI-GM) and the improvement in N3 sleep latency by yeast mannan. Furthermore, whole-food patterns (e.g., the MIND diet) and Traditional Chinese Medicine (TCM) decoctions successfully enriched beneficial taxa, such as Bacteroides coprophilus, and increased short-chain fatty acid (SCFA) production. Animal models demonstrated that “psychobiotic” strains (Bifidobacterium breve, Lacticaseibacillus paracasei), prebiotics (GOS/PDX), and TCM formulas effectively restored GABA/5-HT profiles, lowered morning cortisol, and facilitated REM rebound in PCPA-induced models, while also consolidating non-rapid eye movement (NREM) sleep and downregulating clock genes (Per1/Per2). Conclusions: Psychobiotics, prebiotics, and botanicals represent a highly viable non-pharmacological strategy for treating insomnia. However, current evidence is constrained by a heavy reliance on subjective human questionnaires, short follow-up durations limiting insight into long-term stability, and a substantial translational gap between mechanistic rodent models and human clinical outcomes. Full article

Background: Cancer-related cognitive impairment is a frequent and clinically relevant concern among women with breast cancer, particularly during active oncological treatment, with potential consequences for memory, attention, executive functioning, daily autonomy, emotional well-being, and quality of life. This study aims to evaluate the effectiveness of the Playful Attention and Active Memory intervention (ALMA) on cognitive functioning in women with breast cancer undergoing active oncological treatment. Methods: This single-centre, three-arm, parallel-group randomized controlled trial at the University Healthcare Complex of Salamanca (Spain) will evaluate 63 women with breast cancer undergoing active oncological treatment. Participants will be randomized (1:1:1) into a health education control group, an individual non-tailored cognitive training group, or the ALMA multidimensional group intervention (two 120 min face-to-face sessions/week for four months, combining psychoeducation, targeted cognitive stimulation, and group feedback). Assessments will occur at baseline and post-intervention. The primary outcome is objective global cognitive performance (Montreal Cognitive Assessment). Secondary outcomes include perceived cognitive function, everyday cognition, functional autonomy, anxiety, sleep quality, performance status, and everyday memory failures. Intention-to-treat analysis using linear mixed models will perform prespecified comparisons of ALMA versus both other groups. Expected results: This study is designed to provide evidence on the potential value of a structured, multidimensional cognitive intervention delivered during active breast cancer treatment. By comparing ALMA with both health education and individual cognitive training, the trial may clarify whether the integration of psychoeducation, ecological cognitive stimulation, and group-based support offers additional benefits beyond cognitive practice alone. The inclusion of objective, subjective, and functionally oriented outcomes strengthens the clinical relevance of the protocol and may contribute to the development of more comprehensive supportive care strategies for cancer-related cognitive impairment. Trial registration: This protocol is registered at ClinicalTrials.gov under the identifier NCT07165912. Full article

Background: Anti-amyloid monoclonal antibodies represent the first disease-modifying therapeutic strategy targeting amyloid-β pathology in early Alzheimer’s disease (AD). Although several agents have demonstrated the ability to reduce cerebral amyloid burden, their clinical efficacy and safety remain subjects of substantial scientific and regulatory debate. This study aimed to synthesize randomized evidence evaluating the benefit–risk profile of anti-amyloid monoclonal antibodies in biomarker-confirmed early AD. Methods: A systematic review and classical pairwise meta-analysis of randomized controlled trials (RCTs) was conducted following the PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for phase III placebo-controlled trials evaluating lecanemab, donanemab, aducanumab, and gantenerumab in patients with mild cognitive impairment due to AD or mild AD dementia with biomarker confirmation of amyloid pathology. The primary outcome was change from baseline in the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at the longest available follow-up. Safety outcomes included amyloid-related imaging abnormalities with edema or effusion (ARIA-E), amyloid-related imaging abnormalities with hemorrhage (ARIA-H), serious adverse events, and treatment discontinuation. Random-effects meta-analyses were performed. Results: Six randomized comparisons derived from four phase III trials involving 7695 participants met the eligibility criteria. Anti-amyloid monoclonal antibodies were associated with a statistically significant slowing of clinical progression compared with placebo (pooled mean difference in CDR-SB: −0.42 points; 95% CI −0.59 to −0.25; I² = 78%). The observed effect was primarily driven by trials of lecanemab and donanemab, whereas aducanumab demonstrated discordant results across trials and gantenerumab showed no clinically meaningful benefit. Despite statistical significance, the magnitude of the pooled effect approached the lower boundary of the minimal clinically important difference reported for CDR-SB in early AD. Treatment was associated with a markedly increased risk of ARIA-E (pooled risk ratio 10.1; 95% CI 7.8–13.0), with moderate heterogeneity across studies. Most ARIA-E events were asymptomatic and detected through protocol-mandated MRI monitoring. Conclusions: In biomarker-confirmed early Alzheimer’s disease, anti-amyloid monoclonal antibodies produce a statistically significant but modest slowing of clinical decline accompanied by a substantially increased risk of ARIA. The benefit–risk profile appears heterogeneous across individual antibodies and may reflect pharmacological differences in amyloid targeting and clearance mechanisms. These findings support cautious, individualized use of anti-amyloid therapies and highlight the need for longer-term studies to determine whether short-term slowing of decline translates into clinically meaningful disease modification. Full article

The rising prevalence of neurodevelopmental, emotional, and behavioral disorders in children has prompted interest in dietary strategies that target neuroinflammation, oxidative stress, and gut dysbiosis. Blueberries (Vaccinium spp.) contain substantial amounts of anthocyanins and other neuroactive polyphenols that may confer neuroprotective effects. We summarize the literature published between 2016 and 2025 to examine how the bioactives in blueberries affect symptoms relevant to children with diagnosed neurodevelopmental or emotional–behavioral disorders, including ADHD, mood problems, and cognitive difficulties. Mechanistically, anthocyanins appear to modulate gut microbial composition, modulate neuroinflammation and alleviate oxidative stress via the Nrf2 pathway, and support synaptic plasticity and neurogenesis. Clinical trials, although limited in number and sample size, have reported modest improvements in mood and verbal memory in typically developing children and adolescents, with some gains in attention and executive function. However, direct trials in children with diagnosed neurodevelopmental or emotional–behavioral conditions remain scarce. There are substantial hurdles to translating these findings. Anthocyanins have poor physicochemical stability and low bioavailability, and routine food processing degrades their activity. Emerging solutions such as green extraction from agricultural by-products, colon-targeted microencapsulation, and zero-waste engineering could address these limitations. Rigorous randomized controlled trials in children with diagnosed neurodevelopmental or emotional–behavioral disorders are essential, as are advances in food engineering. Both are needed to move blueberry-based interventions from the laboratory to application. Full article

Background: In youth football, sprint performance depends on the capacity to produce and orient force horizontally during acceleration. Resisted sprinting may preferentially target the force end of the sprint force–velocity profile, whereas free sprinting may favour velocity-oriented adaptations. Purpose: To compare the effects of resisted versus non-resisted sprint training on sprint performance and sprint force–velocity variables in youth footballers, while monitoring countermovement jump (CMJ) as a secondary outcome. Methods: This parallel-group randomised controlled trial included 44 players from two age categories (U14, n = 21; Youth, n = 23). Within each category, players were randomly allocated to resisted sprint training (RST; U14 n = 11, Youth n = 12) or non-resisted sprint training (NRST; U14 n = 10, Youth n = 11). Both groups completed two supervised sessions per week for six weeks. Outcomes were CMJ and sprint-derived variables including maximal theoretical horizontal force (F0), maximal theoretical velocity (V0), maximal power (Pmax), measured maximal sprint velocity (Vmax), peak ratio of horizontal force (RFpeak), decrease in RF with increasing velocity (DRF), and force–velocity slope (FV). Results: CMJ remained essentially unchanged in both age categories. Sprint performance improved over time, with the pattern of adaptation generally favouring RST for force-oriented sprint mechanical variables (F0, Pmax and RFpeak), whereas improvements in Vmax were observed in both groups. In the Youth category, the FV slope differed between groups post-test (p = 0.002). Overall, resisted sprint training tended to produce larger improvements in acceleration-oriented mechanical qualities, while non-resisted sprint training was associated with more velocity-oriented adaptations. Conclusions: Low-volume resisted sprint training using a sled load of ~20% body mass was associated with more favourable adaptations in force-oriented sprint mechanical variables, whereas non-resisted sprint training tended to favour velocity-oriented characteristics. CMJ performance remained unchanged in both groups. These findings should be interpreted cautiously given the small age-stratified subgroup sizes and the single-club nature of the study. Trial registration: This study was retrospectively registered at ClinicalTrials.gov (NCT07418892). Full article

Food allergy is an increasingly prevalent global health condition characterized by immune-mediated reactions to dietary antigens and a substantial clinical burden. Growing understanding of IgE-mediated mechanisms has highlighted the central role of type 2 inflammation, effector-cell activation, and impaired immune regulation. These advances have prompted the development of disease-modifying therapies beyond allergen avoidance. This narrative review summarizes recent advances in the therapeutic management of IgE-mediated food allergy. A structured PubMed search was performed to identify clinical trials, randomized studies, and meta-analyses published within the last five years. Both allergen-specific and non-allergen-specific interventions were evaluated. Current evidence supports oral immunotherapy as the most effective strategy for increasing reaction thresholds and inducing desensitization in peanut, milk, and egg allergies. However, safety concerns remain, and sustained unresponsiveness after treatment discontinuation is achieved inconsistently. Sublingual and epicutaneous immunotherapy show improved safety but lower efficacy. Modified allergen approaches, including baked milk and processed peanut products, may improve tolerability and facilitate immune modulation in selected patients. Biologic therapies, particularly anti-IgE agents, demonstrate efficacy both alone and when combined with immunotherapy. Emerging approaches include peptide vaccines, DNA immunization, microbiome-targeted interventions, and early dietary modulation. These strategies may improve durable immune tolerance through personalized, mechanism-based therapeutic approaches. Future progress will depend on optimizing safety, identifying predictive biomarkers, and integrating multimodal approaches to achieve durable immune tolerance. Full article

Introduction: Fish skin is the first line of defense against the aquatic environment, acting as a physical, chemical, and immunological barrier. In addition to preventing pathogen entry, the skin and its mucus contribute to osmoregulation, innate immunity, and redox balance. Skin lesions—caused by mechanical damage, parasites, environmental stress, or handling—disrupt this barrier, increasing susceptibility to infections, inflammation, and production losses. Thus, efficient skin regeneration is essential for fish welfare and performance. Nutrition plays a key role in this process by providing substrates for epithelial repair, immune function, and antioxidant defense. Among dietary factors, zinc (Zn) is particularly important due to its involvement in cell proliferation, enzymatic activity, and maintenance of skin integrity. Objective: Our objective is to assess the effectiveness of image-based analysis in quantifying the skin healing process in Atlantic salmon fed diets supplemented with zinc. Methodology: The trial comprised three dietary treatments: a control diet with 42 mg Zn per kg (D1), and two diets supplemented up to 120 mg/kg of zinc, derived from inorganic (D2) or organic (D3) forms. Pit-tagged fish with an initial body weight (78 ± 0.1 g) were fed the diets for 75 days. After 15 days of experimental feeding, a standardized wound lesion (2.5 mm diameter × 0.5 mm depth) was inflicted in deeply anesthetized fish, with a disposable biopsy punch, in the dorsal area. After wound infliction, the fish resumed their normal feeding regime for the rest of the trial days. The progression of skin wound healing was assessed using standardized digital image analysis. High-resolution photographs of individual wounds were collected 8, 16, 24 and 32 days post-wounding. All images were acquired under standardized conditions with the inclusion of ArUco identifiers to enable a subsequent computer-assisted comparison. Morphometric parameters (wound width, diameter, perimeter and area) were used to assess wound contraction and closure over time. In parallel, a semi-quantitative visual scoring system was applied to each wound image to capture qualitative aspects of healing that are not fully described by morphometric data alone. Results: Full data analysis is currently underway, but the first results show beneficial effects of dietary zinc supplementation on the skin regenerative process. Conclusions: The combined use of objective digital measurements and standardized visual scoring enabled a comprehensive evaluation of wound healing progress, bridging quantitative tissue remodeling with biologically relevant phenotypic outcomes. This image-based framework provides a sensitive and reproducible approach for assessing dietary interventions targeting skin regeneration and barrier restoration in Atlantic salmon. Full article

Background: Vertebrogenic low back pain (LBP) is a distinct subtype of chronic LBP (cLBP) arising from nociceptive sensitization of the basivertebral nerve (BVN) within pathologically altered vertebral endplates. Modic type 1 and type 2 changes on MRI are primary imaging biomarkers for patient selection. Basivertebral nerve ablation (BVNA), a minimally invasive intraosseous radiofrequency procedure, has emerged as a targeted treatment for this condition. This narrative review aims to synthesize current evidence on the pathophysiology of vertebrogenic LBP, patient selection criteria, procedural outcomes, safety profile, and cost-effectiveness of BVNA. Methods: We conducted this narrative review of the literature, encompassing randomized controlled trials (including the SMART and INTRACEPT studies), prospective registries, and real-world cohort studies evaluating BVNA for vertebrogenic LBP. Clinical and imaging-based selection criteria, procedural techniques, outcome measures, adverse events, opioid utilization, and healthcare utilization data were examined. Results: Evidence demonstrates consistent and durable reductions in pain and disability following BVNA, with a favorable safety profile. Complication rates are low, with vertebral compression fracture and procedure-related radicular pain reported as the most frequent adverse events. BVNA is associated with reduced opioid consumption and decreased overall healthcare utilization. Moreover, emerging data suggest efficacy beyond originally defined inclusion criteria, including cases of osteoporosis, multilevel Modic changes, adult spinal deformity, and complex comorbid presentations. Conclusions: BVNA represents an effective and safe treatment option within the multimodal management of vertebrogenic LBP. Current evidence supports a gradual expansion of procedural indications, with implications for healthcare resource optimization and opioid stewardship. Full article

Background/Objectives: Cancer, a multifactorial disease with uncontrolled cell growth, oxidative stress, inflammation, genomic instability, and molecular signaling pathways, is a global health concern, leading to the ~20 million newly diagnosed cases annually. Although conventional therapy has been shown to enhance the survival rates of cancer patients, its clinical efficacy is limited by certain side effects that occur as a result of treatment, thus necessitating the exploration of plant-derived bioactive compounds for their potential as safer and alternative supportive therapeutic agents. Aloe vera, known as the plant of immortality, comprises phytochemicals, such as anthraquinones (aloe-emodin, emodin, and aloin), polysaccharides (acemannan), flavonoids, and phenolic acids, which contribute to the pharmacological effect of the compound. Methods: This review summarizes the anticancer potential of Aloe vera, and the data were retrieved from databases, such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Wiley Online Library, during the time period of 2015 to 2025. Results: The literature revealed that Aloe vera and its bioactive compounds have dose-dependent cytotoxic and anti-proliferative properties against hepatocellular, cervical, colorectal, lung, breast, prostate, and hematological cancers, which are significantly mediated by apoptosis and pyroptosis induction, reactive oxygen species (ROS) production, mitochondrial dysfunction, inhibition of angiogenesis and metastasis, and the modulation of key signaling pathways, particularly PI3K/Akt, MAPK, NF-кB, p53, and Wnt/β-catenin. Furthermore, anthraquinones, including Aloe-emodin, demonstrate potent anticancer effects at micro-molar doses, and polysaccharides increase immune reactions and provide tumor immunity. Conclusions: Conclusively, Aloe vera is a promising multi-target natural compound, particularly efficient in the treatment of cancer. However, despite significant therapeutic potential, more research on pharmacokinetics, standard dose, and controlled clinical trials of Aloe vera is required to validate clinical applicability. Full article

Ventilator-associated pneumonia (VAP) is linked to high mortality rates, especially in developing countries. This cross-sectional survey study was conducted across three central hospitals in the Hail region of Saudi Arabia, King Salman Specialist Hospital, Hail General Hospital, and King Khalid Hospital, to assess the knowledge and adherence of intensive care unit (ICU) healthcare practitioners to the ventilator bundle (VB) for VAP prevention. It also looked at the practitioners’ perceived barriers to effective VB deployment. The study (n = 86) revealed significant disparities in VAP prevention knowledge across educational levels regarding the recommended degree of head-of-bed (HOB) elevation (p < 0.001), the use of endotracheal tubes with extra lumens for subglottic drainage (p < 0.001), and the protective effects of 0.12% chlorhexidine gluconate antiseptic oral rinse (p = 0.019). Professional experience significantly influenced knowledge of non-standard VB components (p < 0.001), the recommended frequency of awakening and spontaneous breathing trials (SBTs) (p < 0.001), and knowledge of extra-lumen tubes (p = 0.038) and kinetic beds vs. standard beds (p = 0.005). Significant differences were found between professional categories regarding knowledge of hand hygiene performance (p = 0.032), the correct degree of HOB elevation (p = 0.007), and patient positioning (semi-recumbent vs. supine) (p = 0.023). Years of experience significantly impacted reported compliance with institutional VB (p = 0.013), adherence to oral care protocols (p = 0.035), and the assessment of sedation depth (p = 0.002). While basic measures like HOB elevation practice and DVT prophylaxis showed universal reported compliance (100%), significant performance gaps were identified in more complex tasks, such as interrupting continuous sedative infusions and performing SBTs as recommended (p < 0.001), particularly among novice practitioners. The primary implementation barrier preventing full compliance with the VB was identified as educational deficit, which was prioritized as the most important area for quality improvement, highlighting the need for targeted training for newly hired ICU staff. Full article