Luiza Breitenfeld

The numerous health benefits associated with the use of plants in traditional medicine can be linked to secondary metabolites in the products obtained through the hydrodistillation process, such as hydrolates and essential oils (EOs). This study aimed to assess the chemical profile and the antioxidant, antimicrobial, cytotoxic, and anti-inflammatory activities of two hydrodistillation products obtained from four plants belonging to two distinct families: chamomile (Matricaria chamomilla), purple coneflower (Echinacea purpurea), conehead thyme (Thymbra capitata), and basil (Ocimum basilicum). The EOs were found to be more effective than hydrolates in inhibiting microorganisms’ growth, registering MIC values equal to or higher than 50% (v/v), except for T. capitata. Only T. capitata demonstrated the ability to reduce NO levels with both hydrolate and EO. Moreover, it inhibited the cell growth of RAW 264.7, 3T3, and HaCaT lines at the tested concentrations. In contrast, O. basilicum EO did not affect the cell proliferation of the tested cell lines in concentrations below 0.063% (v/v) and showed a significant reduction in the macrophage NO production at all concentrations. Thus, EOs showed a superior biological activity than hydrolates. In particular, O. basilicum EO was found to be a promising candidate for therapeutic applications on the skin.

Background/Objectives: Thyroid hormones (THs) regulate almost all physiological processes in vertebrates via specific mechanisms exercised spatiotemporally throughout the lifespan. The TH signalling can be impaired by thyroid-disrupting chemicals (TDCs) capable of disrupting the hypothalamic–pituitary–thyroid (HPT) axis. Octyl methoxycinnamate (OMC) (also designated octinoxate), one of the most widely used ultraviolet (UV) filters, has emerged as an environmental contaminant and has raised significant concerns recently due to its disruptive effects as TDC on humans and animals. Although the disruption of TH homeostasis has been reported, its exact modes of action (MoA) remain largely unknown. Our study aimed to provide a comparative information on the molecular interactions of OMC on TH signalling in humans and zebrafish. Methods: In silico approaches were performed comparing OMC with endogenous thyroid hormone T3 and the anti-thyroid drug propylthiouracil (PTU). Results: Our findings suggested a key role of OMC on the corticotrophin-releasing hormone receptor (crhr2), thyrotropin receptor (TSHR/tshr), and thyroid nuclear receptors (TR/tr-α and -β). At the hypothalamic level, a favourable binding of OMC to zebrafish crhr2 was found, involving ALA86, CYS44, HIS89, ILE63, ILE64, LEU92, PRO87, PRO88, SER48, and THR47. At the pituitary level, OMC was bound to human TSHR by the amino acid residues ASN590, GLU506, ILE583, ILE640, LEU570, MET572, PRO571, SER505, TYR667, VAL502, VAL586, ALA644, LEU587, MET637, SER641, and TYR582 and to zebrafish tsrh by ASN589, ILE639, MET636, ILE582, LEU569, LEU586, VAL501, and VAL585. Concerning nuclear receptors, OMC showed a more favourable binding energy of T3, involving the shared residues PHE218 and MET259 with T3 in both species. For human TRβ, OMC shared T3 with residues ILE 275, ILE276, LEU346, PHE269, PHE272, THR273, ALA279, ASN331, HIS435, LEU330, MET310, MET313, and PHE455. No similar residues were obtained for zebrafish trβ compared with the humans. Conclusions: Overall, the action of OMC seems to agree with primary hypothyroidism (anti-thyroid action) mimicking the T3 hormone. This investigation demonstrates that OMC acts as a potential TDC and provides new insights into its disruptive action on the HPT axis.

Tripleurospermum disciforme (C.A.Mey.) Sch. Bip. is known as the “Plain Chamomile” of the Asteraceae family, the most prominent plant family and one that has been studied extensively due to its numerous genera and species. In traditional herbal medicine, T. disciforme has been used to treat digestive, neurological, and skin disorders. This study aimed to document ethnobotanical knowledge and assess the pharmacological potential of medicinal plants, specifically T. disciforme, across the provinces of Guilan, Alborz, and Qazvin in Iran, through ethnobotanical surveys. These surveys identified the most utilized plant families as Lamiaceae, Asteraceae, and Theaceae, with T. disciforme cited by 42% of participants, emphasizing its significance in local traditional medicine. Given its high relative frequency of citation and reported medicinal applications, T. disciforme extracts were subjected to UHPLC–timsTOF–MS analysis for further phytochemical profiling and a series of biological assays. Several phenolic compounds such as neochlorogenic acid, caffeic acid, and p-hydroxyphenylethanol acetate were recurrently detected across extracts. The ethyl acetate extract demonstrated potent antioxidant activity in the DPPH assay (IC₅₀ = 12.496 µg/mL) and exhibited antimicrobial activity against Bacillus cereus (MIC = 312 µg/mL). Additionally, the hexane extract revealed notable cytotoxic effects against MCF-7 human breast cancer cells. To the best of our knowledge, to date, this is the first investigation of T. disciforme to integrate ethnobotanical and ethnopharmacological approaches to medicinal plant research in these regions of Iran.

Background: Human papillomavirus (HPV), a leading cause of cervical cancer, is present in most cases of the disease and ranks as the fourth most common cancer in women globally. Among the HPV types, fourteen (HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68) are recognized as high-risk (hrHPV), each with varying levels of oncogenic potential. Detecting and genotyping these hrHPV types in cervical lesions is crucial, requiring the development of new diagnostic methods. Methods: This study focuses on a retrospective analysis conducted on 44 women from the Cova da Beira Local Health Unit. We used the Anyplex™ II hrHPV Detection kit for hrHPV genotyping from paraffin-embedded cervical tissue samples. Results: hrHPV types were identified in 38 out of the 44 women. Genotyping revealed HPV-16 (55.3%), HPV-18/39/56/58/59 (5.3%), HPV-31 (21.1%), HPV-35 (7.9%), HPV-51/66 (2.6%), and HPV-52 (10.5%). Conclusions: This study demonstrates that the Anyplex™ II hrHPV Detection kit, originally designed for cervical cancer screening, is also effective for hrHPV genotyping in histological analyses. This methodology offers a simpler and more cost-effective approach for cervical cancer risk stratification. Its implementation in clinical practice could enhance the detection of hrHPV in cervical lesions, thereby contributing to more precise diagnoses and potentially more informed treatment strategies.

Clinical Pathways in Oncology can benefit patients using organized interventions to standardize and increase care efficiency. Healthcare systems should have tools to identify their oncological clinical pathways for a better institutional organization to reduce mortality rates and contain costs without compromising quality. Our objective is to determine the regional Oncology Clinical Pathway from a first basic hypothesis using questionnaires directed to healthcare professionals considered key deciders within the Pathway. Study design consisted of data analysis of two structured region-wide questionnaires; built using available literature on Oncology Clinical Pathways, in a Portuguese Healthcare context and pre-tested in a focus group of key deciders (Physicians and nurses with management functions) from which a design was created. Queries analyzed the patients: tumor staging at service arrival; time intervals on tumor suspicion/diagnosis confirmation and diagnosis/first treatment; referral pathway; diagnostic networks and patient Follow-up. One questionnaire was sent to key deciders directly involved with Oncology patients at a Regional Hospital. 15 physicians and 18 nurses of this sample answered the questionnaire (approx. response rate = 67%). Another questionnaire sent to healthcare professionals in Primary Healthcare Centers yielded response rate 19.2%, N = 29 physicians and 46 nurses. Finally, we performed a descriptive analysis and a Cronbach Alpha reliability analysis. Our findings reveal: different appreciations of tumor staging at arrival in Primary Healthcare Centers and Regional Hospitals (the latter receiving more metastatic cases); approximately 4 weeks between tumor suspicion-diagnostic and divided opinions regarding diagnostic-treatment time intervals. Primary Healthcare Centers depend on private laboratories for diagnostics confirmation, while the Hospitals resolve this locally. Referral pathways indicate almost half of the patients being sent from primary healthcare centers to National Reference Hospitals instead of a Regional Hospital. Patient follow-up is developed throughout the institutions, however, is more established at Regional Hospitals. As patients advance through the Oncology Clinical Pathway and toward treatment stages the number of healthcare professionals involved reduce. Our questionnaires enable us to understand the real pathway between the different institutions involved and the main entry points of the patients into the Oncology Clinical Pathway.

Oxidative stress has a fundamental role in the pathophysiology of various conditions, like infertility. This case-control study was performed to assess the potential role of CYP19A1, GSTM1, and GSTT1 in modifying individual predisposition to female infertility. Genotyping of 201 women with established infertility and 161 fertile female controls was performed, and statistical associations were analyzed. For carriers of GSTM1 null genotype along with CYP19A1 C allele, there is a significant association with female infertility risk (OR 7.023; 95% CI (3.627–13.601; p < 0.001), and, also for carriers of GSTT1 null genotype along with the CYP19A1 TC/CC genotype (OR 24.150; 95% CI (11.148–52.317; p < 0.001). A positive association with female infertility risk for carriers of the C allele in CYP19A1 and null genotypes in GTSM1 (OR 11.979; 95% CI (4.570–31.400; p < 0.001) or GSTT1 (OR 13.169; 95% CI (4.518–38.380; p < 0.001) was found. When both GSTs are deleted, the risk of developing female infertility is significant, independently of the CYP19A1 genotype; when all the presumed high-risk genotypes are present, we found a significant association with female infertility risk (OR 47,914; 95% CI (14,051–163,393; p < 0.001).

Cell-free DNA fragments detected in blood and in other biological fluids are released from apoptotic/necrotic cells. In this study, we analyzed cfDNA levels in follicular fluid (FF) samples from patients with infertility. Samples were collected from 178 infertile women and cfDNA was extracted and quantified by qPCR, using ALU115 and ALU247 primers, and statistical correlations were performed. We found that cfDNA concentration was significantly higher in FF pools from women aged 35 and over than in women under 35 years of age (p = 0.017). We also found that q247 cfDNA levels were significantly higher in women with an associated female factor, such as endometriosis, PCOS and POF, compared with women with no specific cause of infertility (p = 0.033). The concentration of cfDNA did not vary significantly in each group of women with an associated female factor. The concentration of cfDNA was significantly higher in the FF of women that obtained embryos with a high fragmentation rate, compared to embryos with a low fragmentation rate (p = 0.007). Finally, we found that women who did not become pregnant during IVF treatments had higher q247 cfDNA levels (p = 0.043). The quantification of cfDNA could be an important biomarker of follicular micro-environment quality to predict embryo quality and the success of IVF, making them more specific and effective.

Due to its high prevalence, infertility has become a prominent public health issue, posing a significant challenge to modern reproductive medicine. Some clinical conditions that lead to female infertility include polycystic ovary syndrome (PCOS), endometriosis, and premature ovarian failure (POF). Follicular fluid (FF) is the biological matrix that has the most contact with the oocyte and can, therefore, be used as a predictor of its quality. Volatilomics has emerged as a non-invasive, straightforward, affordable, and simple method for characterizing various diseases and determining the effectiveness of their current therapies. In order to find potential biomarkers of infertility, this study set out to determine the volatomic pattern of the follicular fluid from patients with PCOS, endometriosis, and POF. The chromatographic data integration was performed through solid-phase microextraction (SPME), followed by gas chromatography–mass spectrometry (GC-MS). The findings pointed to specific metabolite patterns as potential biomarkers for the studied diseases. These open the door for further research into the relevant metabolomic pathways to enhance infertility knowledge and diagnostic tools. An extended investigation may, however, produce a new mechanistic understanding of the pathophysiology of the diseases.

The COVID-19 pandemic has changed the way cancer patients should be managed. Using published literature on best practices on oncology patient management, we developed checklists to establish which recommendations were followed and differences between healthcare staff and institutions in a local health unit (overseeing two regional hospitals and 14 primary Healthcare Centers) in an interior region in Portugal. Checklists were delivered and completed by 15 physicians, 18 nurses and 5 pharmacists working at the Hospitals, and 29 physicians and 46 nurses from primary healthcare centers. Hospital staff do not show statistically significant differences regarding most proposed recommendations for the oncology clinical pathway, human resources, treatments, patient management and service management. Primary healthcare centers seem to follow a similar trend. As a local health unit, general recommendations for Oncology Patient Management show statistically significantly different values on education of suspected cases, identification, isolation procedures and samples collection; extension of work schedules; and education on cancer patient and COVID-19 positive referral procedures. All the checklists indicated good-to-high internal consistency. Our analysis showed cohesive work between groups regarding control and prevention of sources of infection; therefore, it is considered the highest priority to ensure that all other services, including oncology, continue functioning. Patient management measures such as adjustments in treatments, analysis, patient care, referrals and emergencies were not ranked higher by responders.