Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder marked by progressive cognitive decline and pathological hallmarks such as amyloid-β plaques and neurofibrillary tangles. Despite current therapies, effective treatments remain elusive. Phytochemicals have emerged as promising neuroprotective agents, while transgenic models such as 5xFAD mice enable rigorous preclinical evaluation.

This study aimed to evaluate the pharmacokinetic properties, predicted molecular targets, and behavioral effects of seven phytochemical extracts derived from Rubus fruticosus (FT, FH, and LH), Abutilon pannosum (A2), Abutilon grandifolium (A1), Rheum palmatum (R), and Zingiber officinale (G), using a 5xFAD murine model expressing five AD mutations.

Pharmacokinetic parameters, including gastrointestinal absorption, blood–brain barrier (BBB) permeability, cytochrome P450 interactions, and P-glycoprotein efflux, were predicted using SwissADME and ADMETlab. Molecular interactions with AD-relevant targets, including β-secretase, acetylcholinesterase, GSK3β, Aβ, and tau, were assessed via SwissDock and SwissTargetPrediction.

In vivo, 5xFAD mice (n = 80) were divided into treatment groups (n = 10 per extract, administered at 50 mg/kg and 100 mg/kg) and controls (NaCl, n = 5; Galantamine, n = 5). Extracts were administered via oral gavage for seven consecutive days and one hour prior to behavioral testing. Cognitive and anxiety- and depression-related behaviors were assessed using the Y-Maze, Open Field, Novel Object Recognition, Elevated Plus Maze, Forced Swimming, and Radial Arm Maze tests.

Our results revealed extract-specific behavioral effects. Rubus fruticosus extracts exhibited an inverse dose-dependent profile, with lower doses yielding superior cognitive performance and improvements in anxiety- and depression-related behaviors, often outperforming Galantamine. FH and A2 showed classical dose-responsiveness, with enhanced cognition at higher doses and increased locomotor activity at lower ones.

These findings underscore the neurotherapeutic potential of selected plant extracts—especially Rubus, Abutilon, and Zingiber—and highlight the value of integrating in silico and behavioral methodologies in AD research. Future work will include biochemical, genetic, and histological analyses to validate these preliminary findings and further investigate underlying mechanisms.

Background: CD47 has emerged as a significant therapeutic target in breast cancer (BC) treatment due to its role in immune evasion, with recent studies suggesting enhanced macrophage phagocytic activity through CD47 blockade. This study aims to provide a secondary analysis of CD47 blockade in the treatment of BC.
Methodology: Following the PRISMA2020 guidelines, Medline (via PubMed), Web of Science, and Scopus were systematically searched using keywords and MeSH terms representing CD47, integrin-associated protein, thrombospondin-1, SIRPα, BC, and their equivalents. The results were screened, and irrelevant studies, preprints, review articles, and studies focusing solely on other tumors, secondary BC, or BC metastases were removed.
Results: From the 874 screened records, 20 records were finally included. Studies reported CD47 blockade using various agents, including Hu5F9-G4, MIAP301, MIAP410, and B6H12 antibodies; anti-CD47 siRNA nanoparticles; and tumor vaccines loaded with CD47-targeting agents. Most studies reported the combination of CD47 blockade with other treatment modalities. All studies reporting the dual blockade of CD47 and HER2 using trastuzumab showed significant synergistic effects. CD47-targeting regimens demonstrate their effectiveness through the regulation of cAMP, the suppression of EGF signaling pathways, and an effect on the tumor microenvironment through M2 macrophages and regulatory T-cell depletion, resulting in the activation of an antitumor innate immune response, improved antitumor responses, and a reduction in tumor growth and proliferation, especially in triple-negative BC. So far, the dual CD47/HER2-targeting IMM2902 has shown significant antitumor effects, along with acceptable safety and tolerability.
Conclusions: CD47 targeting is a promising anticancer approach to BC. The optimum effects of CD47 blockade are mostly observed when it is administered in combination with other treatment modalities. Specifically, CD47 blockade has shown potential in the treatment of HER2+ BC—regardless of whether the tumor is trastuzumab-resistant or -sensitive. Future studies are required to evaluate its effectiveness in terms of its statistical significance, the optimum combination therapy regimens, and the treatment toxicities.

Background: Atezolizumab, a PD-L1-targeting monoclonal antibody, has been increasingly utilized in the treatment of various malignancies, including lung cancer. Despite its clinical benefits, adverse events such as fatigue are commonly reported. Our study aimed to quantify the prevalence of fatigue among lung cancer patients undergoing treatment with atezolizumab.
Methodology: A comprehensive literature search was conducted using Medline (via PubMed), Scopus, Web of Science, and Cochrane Library, using free keywords and MeSH terms related to atezolizumab, fatigue, lung cancer, and adverse events. Clinical studies reporting the epidemiology of fatigue among lung cancer patients treated with atezolizumab were included. Data extraction and quality assessment were independently performed by two reviewers using the JBI extraction and critical appraisal tools. Prevalence rates were pooled using a random-effects model due to expected heterogeneity. This study's reporting adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.
Results: Eight clinical trials were identified. All included studies were phase I or II clinical trials, predominantly of non-small-cell lung cancer patients. The prevalence of all-grade fatigue was found to be 25.56% (95%CI: 17.14% – 36.3%; I2 = 83.52, p < 0.01), with grade 3 or higher fatigue reported in 2.55% (95%CI: 1.25% – 5.13%; I2 = 0, p = 0.55) of the patients. Although subgroup pooling was not attainable due to high heterogeneity, the comparative analysis favored a higher prevalence of fatigue among patients with small-cell lung cancer (SCLC).
Conclusions: Fatigue is a prevalent adverse event in lung cancer patients treated with atezolizumab, affecting approximately one in every four patients. Reports of severe fatigue warrant careful monitoring and management. Further studies are required to determine the underlying mechanisms and develop effective interventions to prevent or manage this adverse effect properly.

Background: Rheumatoid arthritis (RA) is an inflammatory disease characterized by erosive changes in bone and cartilage, which can lead to severe deformities and disabilities, adversely impacting muscle strength, endurance, range of motion, and overall quality of life [1,2]. Objective: Our aim was to evaluate pharmacological therapy and quality of life in patients with RA. Methodology: This study followed an exploratory, cross-sectional, and descriptive design, focusing on patients with RA in the Bragança district who are treated at the Rheumatology Service of the Unidade Local de Saúde do Nordeste E. P. E. (ULSNe). The study aimed to collect sociodemographic and therapy-related data and administer validated questionnaires to assess quality of life, using the EQ-5D Health Quality of Life Assessment and evaluate the complexity of pharmacotherapy using the ICFT Pharmacotherapy Complexity Index. Statistical data processing was conducted using IBM SPSS version 30. 0. 0. 0. The project was approved by the ULSNe Ethics Committee. Results: A total of 61 individuals were surveyed; the majority were female (85%), with an average age of 65 years, and primary school was the most common level of education (39%). The EQ-5D results indicated that 54% of participants experience moderate pain/discomfort, while the ICFT produced a score of 29.3, which is considered highly complex pharmacotherapy regarding daily chronic therapy [3]. The medications most frequently reported included DMARDs (Disease Modifying Anti-Rheumatic Drugs, 10.4%) such as Methotrexate in tablet form (5.2%) or injectable (5.2%), and Anti-Anemic drugs (10,8%) like Folic Acid (10.4%), and Corticosteroids (5%) such as Prednisolone (4.5%). Conclusions: This study highlights higher pharmacological complexity compared to previous studies [3,4], which could lead to polypharmacy, thereby increasing the exposure of patients to potential drug interactions and adverse reactions [3]. Patients continue to experience moderate pain and discomfort, despite the prescribed treatment for RA, highlighting the need to improve strategies for better therapy management.

Authors: Mayra Alejandra Mafla España, Maria Dolores Torregrosa Maicas and Omar Cauli

Although the role of androgens in prostate cancer has been extensively investigated, the possible involvement of estrogens, such as estradiol and estrone, in the localized and metastatic stages of this disease remains little explored. The aim of this study was to analyze the association between plasma estradiol and estrone levels and different indicators of geriatric assessments in men diagnosed with prostate cancer, both in the localized and metastatic stages. Methods: We included 67 men with a confirmed diagnosis of prostate cancer, divided into two groups: 34 with localized disease and 33 with metastatic disease. The comprehensive geriatric assessment included evaluations of sleep quality (using the Athens Insomnia Scale), depressive symptoms (using the Yesavage Geriatric Depression Scale), cognitive function (using the Mini-Mental State Examination, MMSE) and perception of general health status. Results: In the metastatic group, statistically significant correlations were observed between estradiol levels and the Gleason index (Rho = 0.49, p = 0.03), the Charlson comorbidity index (Rho = 0.51, p = 0.01) and the subscale of the Athens Scale assessing difficulty sleeping through the night (Rho = -0.62, p = 0.003). No significant correlations were found between estrone levels and any of the parameters evaluated. In the group with localized disease, a significant correlation was found between estradiol levels and the Charlson index (Rho = -0.46; p = 0.02), with no associations observed with the other geriatric variables or with estrone levels. Conclusion: Estradiol shows relevant correlations with indicators of tumor progression, comorbidity and sleep quality in prostate cancer patients, particularly in the metastatic stage. These results suggest the need to deepen the potential role of estrogens in the clinical and geriatric context of this disease.

Although the role of androgens in prostate cancer has been extensively investigated, the possible involvement of estrogens, such as estradiol and estrone, in the localized and metastatic stages of this disease remains little explored. The aim of this study was to analyze the association between plasma estradiol and estrone levels and different indicators of geriatric assessment in men diagnosed with prostate cancer, both in localized and metastatic stages. Methods: We included 67 men with a confirmed diagnosis of prostate cancer, divided into two groups: 34 with localized disease and 33 with metastatic disease. Comprehensive geriatric assessment included evaluation of sleep quality (Athens Insomnia Scale), depressive symptoms (Yesavage Geriatric Depression Scale), cognitive function (Mini-Mental State Examination, MMSE) and perception of general health status. Results: In the metastatic group, statistically significant correlations were observed between estradiol levels and Gleason index (Rho = 0.49, p = 0.03), Charlson comorbidity index (Rho = 0.51, p = 0.01) and the subscale of the Athens Scale assessing difficulty sleeping through the night (Rho = -0.62, p = 0.003).No significant correlations were found between estrone levels and any of the parameters evaluated.In the group with localized disease, a significant correlation was found between estradiol levels and the Charlson index (Rho = -0.46; p = 0.02), with no associations observed with the other geriatric variables or with estrone levels. Conclusion: Estradiol shows relevant correlations with indicators of tumor progression, comorbidity and sleep quality in prostate cancer patients, particularly in the metastatic stage. These results suggest the need to deepen the potential role of estrogens in the clinical and geriatric context of this disease.

Recent advances in immunotherapy have transformed cancer treatment, particularly through the development of bispecific antibodies and T-cell engagers (TCEs) targeting antigens such as CD3 and DLL3. These therapies, currently administered primarily within the clinical trial setting, offer new hope to patients with aggressive tumors and limited treatment options, such as high-grade neuroendocrine carcinomas or certain resistant and aggressive solid tumors.

However, their mechanism of action—based on redirected T-cell activation—can lead to novel immune-mediated toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require early detection and appropriate management to ensure patient safety.

The aim of this study is to identify the most incident AEs in patients treated with bispecific antibodies (CD3/DLL3) and T-cell engagers in order to improve nurses' knowledge of this emerging therapy and facilitate the early detection and management of these events.

A literature review was conducted in this study. The research was carried out using different databases. After applying the PRISMA methodology and discarding preclinical-phase studies, the sample was 38.

The most incident and common adverse events during treatment with these emergent drugs were obtained, as well the degree of each of them. How these events are handled was reviewed in the literature, but it was hardly described, evidencing the need for further research.

These drugs, with new therapeutic targets, represent a new opportunity for this type of patient with a poor prognosis, requiring the development of a good safety profile.

Within this evolving therapeutic landscape, specialized nursing care is essential. Nurses are responsible for continuous clinical monitoring, recognizing the early signs of toxicity, and implementing timely interventions. Promoting continuous education and nursing-led research will be key to improving patient outcomes and developing evidence-based practices tailored to these new treatments.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a major global impact. Due to the limitations of current treatments and adverse effects, there is increasing interest in natural compounds with therapeutic potential. Mansorina (MA), a coumarin from Mansonia gagei, has antioxidant and anti-inflammatory properties. The present study aims to evaluate the effects of MA on memory, using zebrafish as a preclinical model for AD.

To induce an Alzheimer's disease-like amnesia model, zebrafish (Danio rerio) were exposed to okadaic acid (OKA, 10 nM) for 4 days. Six groups (n = 10/group) were formed: control (DMSO), GAL (1 mg/L), OKA, and OKA co-treated with mansorine (MA) at 1, 3, or 6 μg/L. MA was administered for 7 days, every 3 days, during water changes. Cognitive functions were assessed by Y-maze tests (spatial memory and locomotor activity) and novel object recognition (NOR). Behavioral data were analyzed with one-way ANOVA and Tukey's test (GraphPad Prism 9, p < 0.05).

OKA treatment significantly impaired spatial memory and object recognition in zebrafish, as evidenced by decreased time spent in the novel arm (Y-maze) and novel object preference (NOR) (p < 0.0001). GAL improved both parameters, confirming its cognitive effects. Co-treatment with MA (3 and 6 μg/L) significantly reversed these deficits (p < 0.001 – p < 0.00001), increasing exploration of the novel arm and object. MA also increased locomotor activity, suggesting a stimulant effect. The results support the neuroprotective role of MA.

The results of this study show that the administration of mansorine (MA) to okadaic acid (OKA)-treated fish increased exploratory behavior, as evidenced by novel arm preference in the Y-maze test, and improved recognition memory in the NOR test. MA also contributed to the restoration of cholinergic deficit and the improvement of dementia symptoms, supporting its neuroprotective potential.

Introduction
In ART (Assisted Reproductive Technology), the origin of the sperm as well as its condition before retrieval impact fertilization and pregnancy rates. The objective of this study was to assess the clinical and biological results of ICSI cycles based on the sperm source in a Moroccan fertility center. The sperm sources included fresh and frozen–thawed ejaculated sperm along with frozen testicular sperm.

Methods
This was a retrospective study at Boudra Fertility Center, Fez, Morocco, which included all ICSI cycles completed between January 2019 and December 2024. A total of 745 ICSI cycles from 502 infertile couples were analyzed. Cycles were classified into three groups based on the sperm sources: fresh ejaculated sperm: 662 cycles; frozen–

thawed ejaculated sperm: 24 cycles; and frozen testicular sperm obtained via biopsy: 59 cycles. The outcomes included rates of fertilization, embryo development, clinical pregnancy, and live births.

Results:

The rates of fertilization were as follows: fresh sperm: 59.83%; frozen sperm: 48.53%; and testicular sperm: 45.96%. The clinical pregnancy rates were 32.63% with fresh sperm, 25.00% with frozen sperm, and 25.42% with testicular sperm. Birth rates were 30.36% (fresh sperm), 25.00% (frozen sperm), and 20.34% (testicular sperm). While outcomes were slightly lower with frozen and testicular sperm, viable pregnancies and live births were achieved across all groups.

Conclusion:

This five-year analysis shows that ICSI outcomes are affected by the origin and cryopreservation of the sperm used. Fresh sperm clearly had the highest rates of fertilization and live births; however, clinical outcomes maternally and perinatally, as concerns maternal health, were satisfactory with both frozen and testicular sperm. These findings allow for increasing the use of cryopreserved and testicular sperm in ART for fresh cases when samples are not available.

Introduction: Early experiences of abuse, neglect, parental conflict, a parent's addiction to substances, or conditions of relational and emotional instability can impair the normal development of emotional self-regulation. If not processed, this fragility can lead to a resort to dysfunctional coping strategies, including substance abuse, problematic alcohol use, and behavioral dependence on the Internet or other compensatory stimuli.

Method: The current study used a convenience sampling method and recruited 50 young adult participants (18-30 years old) who completed Adverse Childhood Experiences (ACE), Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), Internet Addiction Test (IAT), and The Love Addiction Inventory (LAI) and Yale Food Addiction Scale (YFAS).

Results: Person Correlation analyses showed significant links between adverse childhood experiences and various forms of substance use: alcohol (r=0.38, p=0.0078), drug use (r=0.54, p<0.0001), and food addiction (r=0.35, p=0.0124). Additionally, food addiction showed a strong correlation with internet addiction (r=0.48, p=0.0004) and love addiction (r=0.30, p=0.037). However, no significant associations were found between Internet or love addiction and substance use. These patterns suggest that there are distinct clusters between substance-related and behavioral dependencies.

Discussion: Findings indicate that early adverse experiences are more closely linked to substance-related and food-related dependencies, suggesting a compensatory function for unprocessed emotional dysregulation. Behavioral addictions such as Internet and Love addiction appear to operate through different psychological mechanisms, possibly linked to unmet relational needs rather than trauma-related self-regulation deficits. Gender differences also emerged: males were more likely to struggle with substance-related dependencies, while females showed a higher prevalence of behavioral addictions. These differences suggest that gender might play a role in how individuals choose to cope with their emotional challenges.