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- A narrative review on breast cancer treatment supported by focused and systemic phytotherapyPublication . Machado, Helena; Machado, Jorge; Alves, Christian; Monteiro, Maria do Céu; Cruz, Agostinho; Pinho, Cláudia; Soares, Cristina; Grosso, Clara; Rodrigues, Jorge Magalhães; Criado, Maria Begoña; Pinho, Cláudia; Cruz, AgostinhoCancer remains a persistent global health challenge, continuously driving the search for novel and effective therapeutic strategies. In the case of breast cancer, treatment decisions are primarily guided by factors such as the disease stage, histological grade, molecular receptor status, and the presence of genetic mutations. Understanding these parameters is crucial for tailoring interventions and improving clinical outcomes. To enhance prognostic and diagnostic accuracy, attention has increasingly turned to identifying molecular targets that play key roles in breast cancer development. Currently, standard treatments include surgery, chemotherapy, and radiotherapy. However, these approaches are often associated with significant side effects and a diminished quality of life. As a result, many breast cancer patients are turning to complementary therapies—including phytotherapy, nutritional interventions, and dietary supplements—to support conventional treatment, alleviate adverse effects, and improve overall well-being. Within the vast realm of medicinal flora, anticancer plants represent a compelling area of study, serving as a rich reservoir of bioactive compounds. These compounds have demonstrated significant promise in the ongoing battle against cancer. Often highlighted in traditional medicinal practices, these plants harbor a wide array of phytochemicals, such as alkaloids, flavonoids, polyphenols, and terpenoids. These phytochemicals manifest diverse biological activities, notably exhibiting pronounced anticancer properties. The exploration of these natural compounds has opened new avenues for developing innovative and targeted therapeutic strategies in cancer treatment. They achieve definitive chemotherapeutic and chemopreventive roles by integrating with specific molecular signals. Their multiple biological functions include antimutagenic, antiproliferative, antimetastatic, anti-angiogenesis, anti-inflammatory, antioxidant, and immunomodulatory properties, which collectively enable them to control cancer progression and intervene at various stages of cancer cell development. Moreover, these compounds are involved in regulating the cell cycle and microRNA, ultimately leading to cancer cell death by promoting apoptosis and autophagy, often mediated through ROS signaling. Thus, based on a large theoretical revision, we conclude that high-quality evidence is necessary in order to advise these products concerning their efficacy and safety. Also, clinical evidence should be supported by a comprehensive individual diagnosis and adequate research protocols in order to evaluate whether the benefits of these plant-produced interventions can outweigh their harms.
- A comprehensive analysis of viability assays for Giardia lamblia and Trichomonas vaginalis trophozoites: a systematic reviewPublication . Sequeira, Susie; Sousa, Mariana; Cruz, AgostinhoGiardia lamblia and Trichomonas vaginalis are flagellated protozoan parasites that often cause asymptomatic infections but may lead to gastrointestinal or genitourinary symptoms. Improved treatment options are needed due to emerging resistance. However, selecting an appropriate method for assessing the in vitro susceptibility of G. lamblia and T. vaginalis in the presence of potential therapeutic compounds remains challenging due to the variability in these methods. This study aimed to provide an overview of commonly employed methods for determining trophozoite viability in the presence of potential therapeutic compounds and to propose a standardized viability assay for susceptibility testing for G. lamblia and T. vaginalis. A systematic literature review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement, using databases including MEDLINE, ScienceDirect, and Web of Science, with the following search equation: “in vitro” AND “method” AND (“susceptibility” OR “viability” OR “sensitivity”) AND (“giardia” OR “trichomonas”). The search identified 32 experimental studies with diverse viability assays. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, adherence inhibition assay, and [3H]-thymidine incorporation assay were prominent for G. lamblia. The trypan blue assay, motility assessment, and resazurin assay were frequently used for T. vaginalis. These findings underscore the diversity in viability assessment methods, highlighting the importance of standardizing viability assays to ensure accurate and reproducible results in drug susceptibility studies. The fluorometric resazurin assay has emerged as a suitable choice for standardization in both parasites, offering cost-effectiveness, reliability, and ease of use.
- Comparative effectiveness of different probiotic delivery methods in oral Candidiasis: A Systematic ReviewPublication . Ashouritoustani, Reihaneh; Pinho, Cláudia; Oliveira, Ana Isabel; Barros, Piedade; Cruz, Agostinho; Cruz, Agostinho; Gonçalves de Barros, Piedade AuroraOral candidiasis, mainly from Candida albicans, affects immunocompromised individuals, the elderly, and denture wearers. Probiotics offer immunomodulatory and microbiota-balancing benefits as potential antifungal alternatives. However, the comparative impact of different probiotic delivery methods remains inadequately explored. This systematic review evaluated the effectiveness of various probiotic delivery methods in reducing Candida colonization and clinical symptoms in oral candidiasis. Following PRISMA 2020 guidelines, a systematic review search across multiple databases included human clinical studies based (Medline, Web of Science, ScienceDirect, and ProQuest) on PICO criteria across all age groups. Outcomes assessed included Candida load, oral microbiota changes, symptom improvement, and disease recurrence. Of 297 articles screened, 10 met inclusion criteria. Delivery methods investigated included lozenges, capsules, yogurt, and cheese. Most studies reported reductions in Candida colony-forming units (CFUs) or prevalence, mainly for C. albicans and for non-albicans species, with probiotics such as Lactobacillus reuteri, L. rhamnosus, L. acidophilus, and Bifidobacterium strains. Some studies reported improved immunological markers, while symptom relief, especially when probiotics were combined with antifungals. Probiotics reduce Candida colonization and symptoms, with potential prolonged effects. They show promise as adjunctive therapies, but standardized, large-scale trials are needed for optimization.
- Dose-dependent pharmacological mechanisms within the Neuroscience-based Nomenclature: a new concept to facilitate neuroscience-based prescribingPublication . Zemach, Sasson; Zohar, Joseph; Correll, Christoph U.; Stahl, Stephen M.; Drago, Filippo; Goodwin, Guy M.; Moller, Hans-Jurgen; Uchida, Hiroyuki; Siafis, Spyridon; Santos, Marlene; Blier, Pierre; Santos, MarleneIn this Personal View, we introduce the concept of different dosage different pharmacology (DDDP), which describes how certain psychotropic medications have distinct therapeutic effects at low and high doses due to differing neurobiological mechanisms. Using the Neuroscience-based Nomenclature (NbN) framework, which classifies drugs by pharmacology and modes of action, we identified ten agents demonstrating DDDP in a comprehensive expert-based consensus process: amisulpride, amitriptyline, aripiprazole, brexpiprazole, cariprazine, doxepin, mirtazapine, quetiapine, risperidone, and trazodone. These medications show clearly demarcated dose-dependent effects, with changes in pharmacological action. For example, some drugs show anxiolytic or hypnotic effects at low doses (via histamine H1 or noradrenergic α1 antagonism) and antidepressant effects at high doses (via reuptake inhibition of serotonin or norepinephrine). Understanding these differences supports more rational prescribing (eg, increasing dopamine partial agonist doses beyond the optimal range might reduce efficacy). DDDP, within the NbN framework, offers a neuroscience-based approach to more precise psychopharmacology.
- Integrating PET for tumour hypoxia in radiotherapy planning: Insights from Portuguese radiotherapy and nuclear medicine technologistsPublication . Sousa, Ruben Diogo Oliveira; Faria, Brígida Mónica; Bravo, Isabel; Costa, Pedro; Costa, Pedro; Faria, Brigida MonicaIn the era of personalised medicine, tumour hypoxia (TH) is critical in radiotherapy (RT) response due to its role in tumour resistance. Positron Emission Tomography (PET) enables non-invasive assessment of TH and supports heterogeneous dose-escalation to hypoxic sub-volumes, improving treatment efficacy. This study explores Nuclear Medicine Technologists (NMT) and Radiotherapy Technologists (RTT) perceptions of PET-based TH (PET-TH) assessment and implementation in RT planning in Portugal. We conducted an observational cross-sectional survey of RTTs and NMTs currently working in Portuguese healthcare institutions. Statistical tests were used to assess associations and compare distributions using IBM® SPSS®. A total of 66 participants, 57 (86.4 %) females, with a mean age of 33.68 (±8.13) years, were included: 23 (34.8 %) NMTs and 43 (65.2 %) RTTs. While 65.2 % of NMT departments had PET scans with RT-compatible settings, only 8.7 % had performed PET-TH studies. Among RTTs, 88.4 % reported that their treatment planning systems were compatible with PET/CT fusion, yet only 9.3 % had used PET in RT planning. RTTs received more training in TH (p = 0.006) and rated their knowledge higher than NMTs (p = 0.042). Greater professional experience and higher perceived knowledge were associated with better performance on evaluation items (p = 0.027; p = 0.037). Regardless of institution type, 92.4 % expressed interest in interprofessional collaboration to support individualised planning. The assessed departments possess infrastructures for PET-TH integration, yet clinical implementation remains limited. Knowledge and professional experience are associated with competency. Targeted training for Technologists and interdisciplinary workflows may improve PET-TH adoption. Addressing knowledge and workflow could facilitate PET integration into RT planning and potentially enhance treatment outcomes. Future efforts should focus on interdisciplinary collaboration.
- Effectiveness of an intervention program for informal carers of children admitted to a rehabilitation centrePublication . Morais, Sónia; Pimenta, Rui Esteves; Morais, Carminda; Macedo, Rui; Ribeiro, Inês; Ferreira, Pedro Lopes; Pimenta, Rui; Macedo, RuiHealth literacy improves informal caregivers’ knowledge and ability to provide care. The aim of this study is to analyze the impact of a group-based intervention on the health literacy of informal caregivers of children with special health needs (SHNs). The intervention focuses on movement, hydrotherapy, walking, and relaxation, with three evaluation stages. Participants included 34 informal caregivers of children with SHNs, recruited at a Physical Medicine and Rehabilitation Service. We collected sociodemographic data of the participants and measured their health literacy through the short-form version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). Around 70% of the participants were female, with a mean age of 41.06 ± 4.98 years, and nearly 85% were married or in a de facto union. About 26% were unemployed, and more than 65% had completed secondary education or higher. The mean scores of the HLS-EU-Q16 were statistically significantly higher throughout the intervention, with differences over the evaluation stages [F(2,56) = 75.55; p < 0.05]. A structured, dynamic, and group-based intervention plan showed improvements in the health literacy of the participants, with an increase in the percentage of participants with sufficient and excellent levels of health literacy at the end of the intervention.
- 3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanismPublication . Vieira, Joana Pereira; Preto, Ana; Granja, Sara; Queirós, Odília; Celeiro, Sónia Pires; Ko, Young Hee; Casal, Margarida; Matos, Catarina Barbosa; Baltazar, Fátima; Granja, SaraAcute myeloid leukemia (AML) comprises a diverse group of blood cancers with varying genetic, phenotypic, and clinical traits, making development of targeted therapy challenging. Metabolic reprogramming in AML has been described as relevant for chemotherapy effectiveness. 3-Bromopyruvate (3-BP) is an anticancer agent that undermines energy metabolism of cancer cells. However, the effect of 3-BP in hematologic malignancies, such as AML, needs further investigation. Thus, we aimed to explore 3-BP as a chemo-sensitizing agent in AML. Different approaches of combining 3-BP with classical chemotherapy (daunorubicin and cytarabin) were tested in diverse AML cell lines. Cell sensitivity to the different drug combinations was analyzed by Trypan blue staining. The effect of pre-treatment with a non-toxic concentration of 3-BP was assessed on the AML cell metabolic profile (Western blot and immunofluorescence), mitochondrial activity (cytometry flow), and antioxidant capacity (colorimetric detection kit). KG-1 and MOLM13 cells showed increased sensitivity to chemotherapy (decreased EC 50 values) after exposure to a non-toxic concentration (5 μ M) of 3-BP. In both cell lines, 5 glucose consumption without changing extracellular lactate levels. 5 μ μ M 3-BP decreased M 3-BP treatment increased reactive oxygen species levels and decreased cell antioxidant capacity by depleting reduced glutathione levels in both KG-1 and MOLM13 cells. Our results demonstrate that non-toxic concentrations of 3-BP enhance the effect of classical chemotherapy in AML cells through a pro-oxidant mechanism. These data unveiled a new approach for AML treatment, using 3-BP or other pro-oxidant agents as co-adjuvants of chemotherapy, subsiding chemotherapy- induced side effects.
- MCT1 is a new prognostic biomarker and its therapeutic inhibition boosts response to Temozolomide in human glioblastomaPublication . Gonçalves, Vera Miranda; Gonçalves, Céline S.; Granja, Sara; Castro, Joana Vieira de; Reis, Rui M.; Costa, Bruno M.; Baltazar, Fátima; Granja, SaraGlioblastoma, the brain tumour with highest prevalence and lethality, exhibits a characteristic glycolytic phenotype with increased lactate production. Recently, we reported a MCT1 overexpression in GBMs tumours, being associated to tumour growth and aggressiveness. Thus, we aimed to disclose the role of MCT1 in GBM prognosis and in vivo therapy response. Importantly, MCT1 overexpression is associated with poor prognosis of GBM. Moreover, MCT1 inhibition retards GBM tumour growth and boosts response to temozolomide treatment.
- Metabolism-targeted therapy in NSCLC – A new theranostics inhalation approach using lactate functionalized and selenium-chrysin loaded nanoparticles (SeChry@PUREG4-LA24)Publication . Mendes, Cindy; Martins, Filipa; Granja, Sara; Gonçalves, Joana; Barros, Hélio; Casimiro, Teresa; Ricardo, Ana Aguiar; Silva, Fernanda; Abreu, Bruna; Cristovão, Miguel; André, Saudade; Pereira, Sofia A.; Baltazar, Fátima; Marques, Helena Cabral; Gaspar, Maria Manuela; Gonçalves, Luís G.; Bonifácio, Vasco D. B.; Serpa, Jacinta; Granja, SaraLung cancer is one of the most lethal cancers globally, primarily due to delayed diagnosis and lack of specific and effective therapy. Increased lactate production and consumption, along with cysteine metabolic reliance, are features identified in NSCLC in our recent studies. Cancer metabolic remodeling leads to excessive ROS production, triggering oxidative stress, promoting angiogenesis, causing cellular and tissue damage, and contributing to various pathophysiological changes. This study aimed to investigate the therapeutic potential of selenium–chrysin (SeChry), a cysteine metabolism inhibitor, and its delivery targeted at MCT1 by encapsulation in fourth-generation polyurea dendrimers functionalized with lactic acid (PUREG4-LA24), the nanoformulation SeChry@PUREG4-LA24, in NSCLC. We explored the impact of SeChry nanoformulation on cell death mechanisms, including ferroptosis, and its influence on angiogenesis in in vitro and in vivo models. SeChry@PUREG4-LA24 induces cell death through the induction of intracellular ROS and lipid peroxides, resulting in distinct expression patterns of ferroptosis-associated genes across cell lines. Experiments using chicken embryo chorioallantoic membrane (CAM) and mouse orthotopic xenograft models revealed a trend toward decreased tumor growth and angiogenesis with SeChry@PUREG4-LA24 administration. These findings suggest the potential of SeChry@PUREG4-LA24 as an innovative therapeutic approach for NSCLC, highlighting its impact on cell death mechanisms and anti-angiogenic effects.
- Medication review improves pain management and quality of life in chronic pain: a pilot randomized controlled studyPublication . Duarte, Nuno; Martins, João Paulo; García-Domingo, Mónica; A. García-Pedraza, Jose; Santos, Marlene; Santos, Marlene; Oliveira Martins, João Paulo; Duarte, NunoChronic pain is a complex condition that benefits from a multidisciplinary approach. This pilot parallel-group single-blinded randomized controlled study evaluated the feasibility, acceptability and adherence by patients and physicians of pharmacist-led medication review on chronic pain patients. Trends in pain intensity, quality of life and patient satisfaction were examined. Twenty adults were recruited from two primary care units in Porto, Portugal, and randomly assigned to either the medication review (MR) group, (n=10) using the Dader method, or the usual care (UC) group, (n=10) and given general advice, for 16-weeks. Pain intensity decreased by 2.07 (MR group) and increased by 0.52 (UC group), yielding an adjusted mean difference of 2.77 (95% CI, -4.93 to -0.62; p=0.008). Pain relief was reported by 62.5% in the MR group versus 37.5% in UC (p=0.357). The MR group showed significant improvement in physical functioning (p=0.019) and higher treatment satisfaction (p=0.029). The acceptance rate of MR interventions was 71%, which resolved 63% of negative medication outcomes. Acceptability was high (>90% of planned interviews). Conducting pharmacist led MR for chronic pain management in primary care is feasible and well accepted by patients and physicians. Observed trends toward improved pain and QoL warrant confirmation in a larger trial. This pilot trial was registered in clinicaltrials.gov (NCT06997861).