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- Curcumins-Loaded ZIF-8 Nanoparticles-Embedded Transdermal Polymeric Patches Increase Apoptosis and Reduce Necrosis in a Dose-Dependent Manner in MCF-7 CellsPublication . Kiyak-Kirmaci, Humeysa; Aydin, Saliha; Yekeler, Humeyra Betul; Guler, Ece; Kayaci, Ayse Beyza; Gurer, Zeynep; Yilmaz-Goler, Ayse Mine; Erkmen, Ziya Engin; Duygulu, Ozgur; Bostan, Muge Sennaroglu; Martins, Diana; Mendes, Fernando; Eroglu, Mehmet Sayip; Edirisinghe, Mohan; Cam, Muhammet EminCurcumin(Cur)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (Cur@ZIF-8 NPs) were produced to increase the anticancer activity of Cur. Cur@ZIF-8 NPs were embedded in polycaprolactone (PCL) fibers as transdermal polymeric patches via a pressured gyration (PG) method to provide controlled release. Cur@ZIF-8 NPs and Cur@ZIF-8 NPs-embedded PCL fibers were characterized for physical, chemical, mechanical, and thermal properties, also biological activities were examined with in vitro tests. Cur@ZIF-8 NPs were produced homogeneously with a size of ∼200 nm and a zeta potential of ∼−19 mV. Cur had better stability inside Cur@ZIF-8 NPs than its powder form. Cur@ZIF-8 NPs were successfully loaded in PCL fibers with a size of∼7 µm, and Cur@ZIF-8 NPs were dispersed amorphously in fibers. Cur was released in a controlled manner, and its efficiency was increased in the acidic microenvironment that is characteristic of cancer. Cur@ZIF-8 NPs have more bioavailability than powdered Cur and can penetrate the cells to deliver their anticancer effects on MCF-7 human breast cancer cells. Cur@ZIF-8 NPs-embedded transdermal polymeric patches promote apoptosis in MCF-7 cells by reducing necrosis, particularly under acidic conditions. This work presents a release system with synergistic anticancer effects, offering a novel approach for Cur’s clinical application in breast cancer through enhanced targeting.
- Auditory attention in primary school-aged childPublication . Soares, Constança; Serrano, MargaridaIntrodução: A atenção auditiva é um processo multimodal complexo, essencial para o desenvolvimento cognitivo, académico e socioeducativo das crianças. Défices nesta competência podem comprometer a comunicação e a aprendizagem. A evidência proveniente das neurociências indica que o tálamo, bem como os córtices pré-frontal, parietal e auditivo, desempenham papéis fundamentais na sua regulação. Do ponto de vista funcional, a atenção auditiva é classificada em seletiva, sustentada, alternada e dividida — todas cruciais para o funcionamento quotidiano. Objetivo: Avaliar o desempenho da atenção auditiva em crianças do 1.º ao 4.º ano do ensino básico. Materiais e Métodos: Participaram no estudo 35 crianças (com idades entre 6 e 9 anos), de ambos os sexos, com audição normal e matriculadas no ensino básico. A avaliação recorreu a dois instrumentos: um objetivo — o Teste de Habilidade de Atenção Auditiva Sustentada (P-THAAS) — aplicado às crianças, e um subjetivo — a subescala de atenção auditiva do Pediatric Children’s Auditory Performance Scale (P-CHAPPS) — preenchida pelos professores. Resultados: O progresso no nível de escolaridade esteve associado a um menor número de erros e a uma maior estabilidade na vigilância auditiva, conforme avaliado pelo P-THAAS. Por outro lado, os resultados da subescala do P-CHAPPS apresentaram maior variabilidade entre os diferentes anos de escolaridade. Conclusões: Os resultados sugerem um desenvolvimento gradual da atenção auditiva ao longo dos primeiros anos de escolaridade. A combinação de instrumentos objetivos (P-THAAS) e subjetivos (P-CHAPPS) revela-se fundamental para uma avaliação abrangente e contextualizada desta função no ambiente escolar.
- The role of the gut microbiome in clinical outcomes of colorectal cancer: a systematic review (2020–2025)Publication . Santos, Iara; Liberal, Joana; Teixeira, Paulo; Martins, Diana; Mendes, FernandoABSTRACT: Background: The Colorectal Cancer (CRC) pathogenesis and therapeutic efficacy are influenced by the gut microbiome, making it a promising biomarker for predicting treatment responses and adverse effects. This systematic review aims to outline the gut microbiome composition in individuals with CRC undergoing the same therapeutic regimen and evaluate interindividual microbiome profile variations to better understand how these differences may influence therapeutic outcomes. Methods: Key studies investigating the microbiome’s role in therapeutic approaches for CRC were searched in both PubMed and Cochrane databases on 12 and 22 March 2025, respectively. Eligible studies included free full-text English-language randomized clinical trials and human observational studies reporting on gut microbiome composition and treatment outcomes. RoB 2 and ROBINS-I were employed in the evaluation of bias for randomized trials and observational studies, respectively. Data extracted was narratively analyzed. Results: Six studies involving a total of 361 individuals were included. Therapeutic interventions, either standard treatments and/or those targeting the gut microbiome, generally increased probiotic taxa and reduced pro-carcinogenic bacteria. However, no consistent pattern of improved clinical outcomes was observed, suggesting that treatment mechanisms, the tumor’s nature, and individual characteristics play critical roles in microbiome modulation. Conclusion: The gut microbiome holds significant potential in clinical settings. Nonetheless, further research is needed to better understand its functional aspects and to consider the influence of treatment mechanisms, the tumor’s nature, and individual characteristics as modulators, in order to optimize clinical outcomes
- Unveiling the anticancer potential of urolithin A in colorectal cancer: a systematic reviewPublication . Francisco, Mariana; Mendes, Fernando; Martins, Diana; Liberal, JoanaObjectives: Colorectal cancer (CRC) is a major global health burden, and Urolithin A (Uro-A) has emerged as a promising anticancer agent. This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC, highlighting effective concentration ranges, exposure times, relevant outcomes, and underlying molecular mechanisms. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Scopus, and Web of Science using the following strategy: (colorectal cancer) AND (urolithin a) OR (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one). Eligibility criteria were defined by the PICO framework: (P) in vitro CRC cell models; (I) Uro-A alone or combined treatments; (C) No intervention, vehicle or other treatments; (O) Relevantanticancer outcomes of Uro-A in CRC. Only original, full-text, in vitro studies in English were included. Risk of bias was assessed using ToxRTool. A qualitative synthesis was performed due to the heterogeneity of the included studies. Results: Fifteen studies met inclusion criteria, involving CRC cell lines (Caco-2, HCT-116, HT-29, SW480, SW620) and normal colon fibroblasts (CCD18-Co). Uro-A inhibited CRC cell proliferation, clonogenic growth, cancer stem cells properties, migration, and invasion, and induced cell cycle arrest, apoptosis, autophagy, and senescence, through modulation of key signaling pathways and proteins. Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects. Discussion: The findings support Uro A’s potential as a preventive or adjuvant agent in CRC treatment. However, preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts. Human clinical trials are necessary to overcome these limitations. Other: This review was registered in PROSPERO (CRD420251070874) and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020. Institutional.
- An update on the role of immune checkpoint inhibitors in lung cancer: a narrative systematic reviewPublication . Sousa, Inês; Martins, Diana; Mendes, FernandoIntroduction: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, and its aggressive nature necessitates the development of alternative therapeutic strategies. Immune checkpoint inhibitors (ICIs) have shown remarkable success in LC treatment. Despite advances with programmed cell death protein-1/programmed cell death ligand-1 inhibitors, many patients experience limited or short-lived responses, prompting interest in novel ICIs such as T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain (TIGIT), lymphocyte-activation gene 3 (LAG-3), and indoleamine 2,3-dioxygenase 1 (IDO-1). Objectives: This narrative systematic review aimed to assess the clinical efficacy and safety of these novel ICIs compared to standard ICI therapy in LC. Methods: A systematic literature search was conducted across PubMed, Web of Science, and ClinicalTrials.gov. The search covered studies published from January 2020 to January 2025, to identify randomized controlled trials (RCTs) evaluating novel ICIs in LC. Due to substantial heterogeneity in study design, intervention targets, and outcome reporting, findings were synthesized narratively in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using RoB 2. Results: Five RCTs involving a total of 825 patients were included. TIGIT inhibition demonstrated benefit in progression-free survival and response rate. LAG-3 inhibitors showed mixed efficacy, with potential dose-related differences. IDO-1 inhibitors failed to improve outcomes compared with standard ICI. Reporting quality varied, with concerns regarding incomplete outcome data in some trials. Conclusion: These findings suggest promise for novel ICIs but are limited by small study numbers, methodological bias, and clinical heterogeneity. Larger, well-designed Phase III trials are required to validate these results.
- Association between dietary intake and the expression of clock genes in adults: a brief reportPublication . Lages, Marlene; Correia, Joana; Caseiro, Armando; Carmo-Silva, Sara; Barros, Renata; Ferreira-Marques, Marisa; Guarino, Maria P.Background: The circadian system regulates several physiological processes, including energy metabolism, through the expression of core clock genes. Animal studies suggest that dietary composition can influence circadian gene expression; however, evidence in humans remains limited. Objective: This study aimed to explore the association between dietary macronutrient intake and the expression of circadian clock genes in the whole blood of adults with distinct metabolic profiles. Methods: Nineteen adults (94.7% female; 43.4 ± 16.05 years) were categorized into healthy-weight and overweight/obesity groups based on BMI. Dietary intake was assessed using a 3-day food diary, and clock gene expression (CLOCK, BMAL1, PER2, CRY) was evaluated in whole blood samples collected between 08:00 a.m. and 04:00 p.m. Statistical analyses included group comparisons and correlation analyses between macronutrient intake and gene expression. Results: No statistically significant differences were observed in the clock gene expression between BMI groups, although group-level trends were noted, particularly in PER2 and CRY expression. The overweight/obesity group exhibited a significantly higher percentage of energy intake from protein. Correlation analyses revealed several time-dependent associations between macronutrient intake and clock gene expression. Notably, in the healthy BMI group, BMAL1 and CRY expression correlated with lipid and protein intake, while in the overweight/obesity group, CLOCK expression was strongly associated with both lipid and carbohydrate intake. Conclusion: These findings suggest that macronutrient composition may influence peripheral circadian gene expression in a time- and BMI-dependent manner. Further research is necessary to confirm these associations in larger and more diverse populations and to investigate the potential for chrononutrition strategies to support metabolic health
- Listening effort, an overview of App validation and testing by the audiology 4 all ProjectPublication . Passadouro, Luísa; Silva, Carla Matos; Reis, Cláudia; Nazaré, Cristina; Paulo, Sergio; Serrano, Margarida; July 17, 2023Objective: To describe an application’s development and validation process that aims to track hearing difficulties in adverse environments (a listening effort application). Design: 71 subjects were evaluated, divided into two groups: 30 subjects aged between 18 and 30, and 41 subjects aged between 40 and 65. All subjects had European Portuguese as their native language; the Montreal Cognitive Assessment (MOCA) scored above 24, and all could read and write. All subjects performed the intelligibility test in noise and the test of listening effort. The two tests were randomly applied in the free field in the audiometric cabin and the application. Results: There were no statistically significant differences between the results of the two methods (p>0.05). For the group aged between 40 and 65 years old, the ROC curve showed that intelligibility inferior to 68.5% and the number of correct answers lower than 1,5 in the listening effort test are the optimal cut-off for referral to further management. Both tests showed low sensitivity and specificity regarding individuals between 18 and 30 years old, indicating that the application is inappropriate for this age group. Conclusions: The application is valid and can contribute to the screening and self-awareness of listening difficulties in middle age, with a reduction in the prevalence of dementia soon.
- Development of a speech-in-noise test in european portuguese based on QuickSIN: a pilot studyPublication . Serrano, Margarida; Simões, Jéssica; Vicente, Joana; Ferreira, Maria; Murta, Ana; Ferrão, João TiagoBackground and Objectives: Speech-in-noise testing is essential for evaluating functional hearing abilities in clinical practice. Although the Quick Speech-in-Noise test (QuickSIN) is widely used, no equivalent tool existed for European Portuguese. This study aimed to develop a Speech-in-Noise Test for European Portuguese (SiN-EP), linguistically adapted and calibrated for native speakers, to support clinical assessment of speech perception in realistic listening environments. Materials and Methods: The SiN-EP was developed through a multi-stage process. Sentences were drafted to reflect natural speech patterns and reviewed by native speakers for clarity and grammatical accuracy. Selected sentences were recorded by a female native speaker in a controlled acoustic environment and mixed with multi-talker babble at signal-to-noise ratios (SNR (dB)) from 25 to 0 SNR (dB). A pre-test in a free-field setting at 65 dB SPL was conducted with fifteen normal-hearing young adults. Participants repeated each sentence, and their responses were analyzed to refine list composition, adjust difficulty, and ensure phonetic balance. Results: Intelligibility decreased systematically as SNR (dB) worsened, with ceiling effects at 25 and 20 SNR (dB). At 5 SNR (dB), high variability was observed, with set 5 showing disproportionate difficulty and set 14 containing an incomplete sentence; both were removed. At 0 SNR (dB), all sets demonstrated expected low intelligibility. The final test comprises thirteen lists of six sentences, each maintaining stable intelligibility, phonetic representativeness, and consistent difficulty across SNRs (dB). Conclusions: The SiN-EP provides a linguistically appropriate, phonetically balanced, and SNR (dB) calibrated instrument for assessing speech-in-noise perception in European Portuguese. The refinement process improved reliability and list equivalence, supporting the test’s clinical and research applicability. The SiN-EP fills a critical gap in assessing speech-in-noise perception in European Portuguese speakers, providing a reliable tool for both clinical and research applications.
- Exploring the link between stress and working memory in adultsPublication . Carvalho, Constança; Reis, Cláudia; Serrano, MargaridaBackground: Working memory (WM) is essential for reasoning, learning, and everyday cognitive tasks and can be influenced by stress. This study investigated the relationship between perceived stress and auditory working memory in 24 adults (16 women, 8 men; median age = 22). Methods: Participants completed the Perceived Stress Scale (PSS-10) and a pseudoword span task assessing auditory memory under phonologically demanding conditions. Results: Participants with higher stress levels exhibited greater variability and a decline in performance across pseudowords sets, particularly in the final set. Correlational analyses revealed that higher PSS-10 scores were significantly associated with lower accuracy on the most demanding memory set (r = −0.467, p = 0.021) and with younger age (r = −0.489, p = 0.015). These findings suggest that elevated stress may impair auditory working memory, with younger adults reporting higher perceived stress. Conclusions: This study highlights the importance of considering stress levels in cognitive assessments and supports the hypothesis that stress negatively affects working memory efficiency, particularly in tasks requiring phonological processing.
- Association between shift work and auditory–cognitive processing in middle-aged healthcare workersPublication . Roque, Margarida; Marques, Tatiana; Serrano, MargaridaBackground/Objectives: Shift work in healthcare professionals affects performance in high cognitive processing, especially in complex environments. However, the beneficial effects that working in complex environments may have on auditory–cognitive processing remain unknown. These professionals face increased challenges in decision-making due to factors such as noise exposure and sleep disturbances, which may lead to the development of enhanced auditory–cognitive resources. This study aims to investigate the associations between shift work and auditory–cognitive processing in middle-aged healthcare workers. Methods: Thirty middle-aged healthcare workers were equally allocated to a shift worker(SW) or a fixed-schedule worker (FSW) group. Performance on a cognitive test, and in pure-tone audiometry, speech in quiet and noise, and listening effort were used to explore whether correlations were specific to shift work. Results: Exploratory analyses indicated that shift workers tended to perform better in visuospatial/executive function, memory recall, memory index, orientation, and total MoCA score domains compared to fixed schedule workers. In the SW group, hearing thresholds correlated with memory recall and memory index. In the FSW group, hearing thresholds correlated with orientation, memory index, and total MoCA score, while listening effort correlated with naming, and speech intelligibility in quiet correlated with total MoCA scores. Conclusions: These exploratory findings suggest that shift work may be linked to distinct auditory–cognitive patterns, with potential compensatory mechanisms in visuospatial/executive functions and memory among middle-aged healthcare workers. Larger, longitudinal studies are warranted to confirm whether these patterns reflect true adaptive mechanisms.