Stress and exhaustion among medical students: a prospective longitudinal study on the impact of the assessment period on medical education.

BACKGROUND: Stress significantly affects both the physical and emotional health of individuals, particularly students in health-related fields. Medical students in Brazil face unique challenges due to the demanding nature of their studies, especially during assessment periods, which heighten academic pressure. These pressures often lead to poor coping strategies and mental health concerns. It is crucial to understand the complex dynamics of stress within medical education to develop strategies that improve student well-being and promote a healthier academic environment. This study aims to investigate the intricate relationship between assessment periods and stress levels among medical students. It seeks to understand how academic demands and sociodemographic factors contribute to stress dynamics during these periods. METHODS: An online observational, longitudinal, and prospective study was conducted from February to October 2022. Medical students were recruited through snowball sampling and participated in surveys administered via Google Forms at two timepoints: before (T1) and during (T2) assessment periods. The surveys collected sociodemographic data and stress symptoms using Lipp's Inventory of Stress Symptoms for Adults (LSSI). RESULTS: The transition from T1 to T2 was defined by a rise in the prevalence of stress from 59.6 to 84.2% (p = 0.001) and a decline in symptom-free students from 40.4 to 15.8% (p = 0.001). There was a significant increase in exhaustion, from 12.3 to 31.6% (p = 0.0001). Higher stress levels were notably more prevalent among younger students (≤ 24 years), females, those from wealthier families, students without scholarships, those without prior degrees, and those in the clinical phase of their studies. However, non significant correlations were found between these sociodemographic and academic factors and the increase in stress. CONCLUSION: The findings highlight significant concerns regarding the mental health of medical students during assessment periods, marked by increased stress and exhaustion levels. These results emphasize the need for proactive interventions to manage stress effectively in medical education, considering its profound impact on students' well-being.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Potential availability of metals in anaerobic mono- and co-digestion of pig manure and maize.

This study aims to analyse the potential availability of essential metals including as Co, Fe, Ni, Zn, Mn, and Cu and non-essential metals such as Pb, Cr, and Cd within anaerobic mono- and co-digestion of pig manure and maize. The metals partitioning was determined using the Modified BCR (European Community Bureau of Reference) sequential extraction at defined intervals over a 45-days period, correlating changes in metals speciation with key digestion variables. The findings revealed that Cr, Cu, Fe, and Pb were predominantly associated with the oxidisable fraction, while Zn, Mn, and Cd were potentially available in both processes. Notably, NH4+-N and the VFAs, except propionic acid, correlated significantly with the available fractions of Co, Mn, Ni, Zn, Cr, and Pb during mono-digestion of pig manure. The wider pH range and the chemical properties of the feedstock in co-digestion resulted in varied correlations between the metals availability and the digestion variables.

Proteomic Analysis of a Rat Streptozotocin Model Shows Dysregulated Biological Pathways Implicated in Alzheimer's Disease.

Alzheimer's Disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracerebroventricular (ICV) injection of low to moderate doses of streptozotocin (STZ) in adult male Wistar rats can reproduce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, knowledge regarding the molecular aspects of the ICV-STZ model is still incipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on mass spectrometry (MS). To achieve that, samples from the pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differential protein abundance, pathway, and network analysis were performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in the early stages of late-onset Alzheimer's disease (LOAD), based on differentially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further investigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.

Application of nanoformulations as a strategy to optimize chemotherapeutic treatment of glioblastoma: a systematic review.

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.

Advances in Antitumor Effects Using Liposomal Citrinin in Induced Breast Cancer Model.

The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); (3) citrinin, CIT (2 mg/kg), (4) cyclophosphamide, CPA (25 mg/kg), (5) liposomal citrinin, LP-CIT (2 µg/kg), and (6) LP-CIT (6 µg/kg). Metabolic, behavioral, hematological, biochemical, histopathological, and toxicogenetic tests were performed. DMBA and cyclophosphamide induced behavioral changes, not observed for free and liposomal citrinin. No hematological or biochemical changes were observed for LP-CIT. However, free citrinin reduced monocytes and caused hepatotoxicity. During treatment, significant differences were observed regarding the weight of the right and left breasts treated with DMBA compared to negative controls. Treatment with CPA, CIT, and LP-CIT reduced the weight of both breasts, with better results for liposomal citrinin. Furthermore, CPA, CIT, and LP-CIT presented genotoxic effects for tumor, blood, bone marrow, and liver cells, although less DNA damage was observed for LP-CIT compared to CIT and CPA. Healthy cell damage induced by LP-CIT was repaired during treatment, unlike CPA, which caused clastogenic effects. Thus, LP-CIT showed advantages for its use as a model of nanosystems for antitumor studies.

Molecular genetic association of rs8099917 and rs1800795 polymorphisms in the progression of hepatitis Delta virus liver disease.

Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon. Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method. Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05). Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population.

Molecular genetic association of rs8099917 and rs1800795 polymorphisms in the progression of hepatitis Delta virus liver disease

Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon. Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method. Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05). Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population.

Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variants.

Germline pathogenic variants in the exonuclease domain of the replicative DNA polymerase Pol ε encoded by the POLE gene, predispose essentially to colorectal and endometrial tumors by inducing an ultramutator phenotype. It is still unclear whether all the POLE alterations influence similar strength tumorigenesis, immune microenvironment, and treatment response. In this review, we summarize the current understanding of the mechanisms and consequences of POLE mutations in human malignancies; we highlight the heterogeneity of mutation rate and cancer aggressiveness among POLE variants, propose some mechanistic basis underlining such heterogeneity, and discuss novel considerations for the choice and efficacy of therapies of POLE tumors.

Pacientes em pós-operatório imediato: recepção na unidade clínico-cirúrgica / Patients in the immediate postoperative period: admission to the clinical and surgical unit

Objetivo: Analisar a demanda de enfermagem nos cuidados de pacientes em pós-operatório imediato, desde sua recepção do centro cirúrgico até sua acomodação ao leito na unidade de internação. Métodos: Estudo prospectivo e analítico. A população foi constituída por pacientes adultos, egressos do centro cirúrgico. A amostra foi calculada considerando-se que o serviço realiza uma média de 118 cirurgias ao mês. Considerando que a amostra mínima seria de 91 pacientes com um intervalo de confiança de 95%, optou-se por trabalhar com amostra de 100 pacientes. Os dados foram coletados no momento em que os pacientes eram recebidos da SRPA. Resultados: Os grupos cirúrgicos Angiologia, Coloproctologia, Otorrinolaringologia e Urologia demandaram no máximo dois profissionais de enfermagem. Os grupos de Cirurgia de Cabeça e Pescoço, Cirurgia Plástica, Nefrologia e Ortopedia demandaram pelo menos dois profissionais. O grupo da Coloproctologia teve maior média de tempo de acomodação ao leito. Cerca de 15% dos pacientes demandaram oxigenoterapia, quase 50% receberam analgésicos e 34% estavam usando cateter vesical de demora. Conclusão: O tempo destinado à acomodação dos pacientes variou de 5 a 30 minutos, com média de 15,19 ± 4,7. Não há indícios de que mais ou menos profissionais atuando juntos alterem o tempo de acomodação do paciente. Descritores: Admissão do paciente; Transferência do paciente; Cuidados de enfermagem; Enfermagem perioperatória.

Objective: To analyze the nursing demand in the care of patients in the immediate postoperative period, from their admission to the surgical center to their accommodation in bed in the admission unit. Methods: Prospective and analytical study. The population consisted of adult patients, discharged from the surgical center. The sample was calculated considering that the service performs an average of 118 surgeries per month. Considering that the minimum sample would be 91 patients at a 95% confidence interval, we chose to work with a sample of 100 patients. Data were collected at the time patients were received from the PACU. Results: The Angiology, Coloproctology, Otorhinolaryngology and Urology surgical groups required a maximum of two nursing professionals. The Head and Neck Surgery, Plastic Surgery, Nephrology and Orthopedics groups required at least two professionals. The Coloproctology group had a higher average time of accommodation in bed. About 15% of the patients required oxygen therapy, almost 50% received analgesics and 34% were using an indwelling urinary catheter. Conclusion: The time allocated to the accommodation of patients ranged from 5 to 30 minutes, with an average of 15.19 ± 4.7. There are no indications that a greater or lesser number of professionals acting together alter the accommodation time of the patient. Descriptors: Patient admission; Patient transfer; Nursing care; Perioperative nursing.

RESECTION OF ANKLE TUMOR LESION AND RECONSTRUCTION WITH THE USE OF ALLOGRAFT.

Reconstruction of the distal third of the tibia due to resection of a malignant tumor has some hindering factors, such as a thin subcutaneous layer, neurovascular bundles that cross compartments, prolonged operative duration, specific orthopedic material, and a trained multidisciplinary team. Allografting with material from tissue banks is part of this orthopaedic arsenal. OBJECTIVE: To describe the protocol used at Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. METHODS: Series of six cases subjected to resection with oncologic margins, allograft reconstruction, and use of a retrograde ankle nail as limb-salvage surgery. Three of the six patients were women, the lesions were on average 9.3 cm long, and the average operative duration was 3.25 hours. RESULTS: The main short-term complication (≤ 30 days) was peroneal nerve palsy, while the main long-term complication (> 30 days) was surgical site infection (two cases). Consolidation of the two foci occurred in three patients, and two patients developed asymptomatic pseudoarthrosis of the proximal focus with consolidation of the distal focus. CONCLUSION: Despite the complications, the proposed surgery gives patients the chance to preserve their limb in the face of immediate radical surgery. Level of Evidence IV, Case Series.

A reconstrução do terço distal da tíbia devido à ressecção de tumor maligno apresenta alguns fatores que dificultam sua realização, como camada subcutânea delgada, feixes neurovasculares que transpassam os compartimentos, tempo cirúrgico prolongado, material ortopédico específico e equipe multidisciplinar treinada. O aloenxerto de banco de tecido faz parte deste arsenal ortopédico. Objetivo: Descrever o protocolo realizado no Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. Métodos: Série de seis casos submetidos à ressecção com margens oncológicas, reconstrução com aloenxerto e uso de haste retrógrada de tornozelo como cirurgia preservadora do membro. Três dos seis pacientes eram do sexo feminino, as lesões tinham em média 9,3 cm de comprimento e o tempo cirúrgico médio foi de 3,25 horas. Resultados: A principal complicação de curto prazo (≤ 30 dias) foi a paralisia do nervo fibular, enquanto a principal complicação de longo prazo (> 30 dias) foi a infecção do sítio cirúrgico (dois casos). A consolidação dos dois focos ocorreu em três pacientes, e dois pacientes evoluíram para pseudoartrose assintomática do foco proximal com consolidação do foco distal. Conclusão: Apesar das complicações, a cirurgia proposta permite ao paciente a chance de preservar seu membro diante de uma cirurgia radical imediata. Nível de Evidência IV, Série de Casos.

Prognostic Factors and Markers in Non-Small Cell Lung Cancer: Recent Progress and Future Challenges.

Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting.

Rest and Stress Left Atrial Dysfunction in Patients with Atrial Fibrillation.

BACKGROUND: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. AIM: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. METHODS: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. RESULTS: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). CONCLUSIONS: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Buthionine sulfoximine and chemoresistance in cancer treatments: a systematic review with meta-analysis of preclinical studies.

Buthionine sulfoximine (BSO) is a synthetic amino acid that blocks the biosynthesis of reduced glutathione (GSH), an endogenous antioxidant cellular component present in tumor cells. GSH levels have been associated with tumor cell resistance to chemotherapeutic drugs and platinum compounds. Consequently, by depleting GSH, BSO enhances the cytotoxicity of chemotherapeutic agents in drug-resistant tumors. Therefore, the aim of this study was to conduct a systematic review with meta-analysis of preclinical studies utilizing BSO in cancer treatments. The systematic search was carried out using the following databases: PubMed, Web of Science, Scopus, and EMBASE up until March 20, 2023, in order to collect preclinical studies that evaluated BSO, alone or in association, as a strategy for antineoplastic therapy. One hundred nine investigations were found to assess the cytotoxic potential of BSO alone or in combination with other compounds. Twenty-one of these met the criteria for performing the meta-analysis. The evidence gathered indicated that BSO alone exhibits cytotoxic activity. However, this compound is generally used in combination with other antineoplastic strategies, mainly chemotherapy ones, to improve cytotoxicity to carcinogenic cells and treatment efficacy. Finally, this review provides important considerations regarding BSO use in cancer treatment conditions, which might optimize future studies as a potential adjuvant antineoplastic therapeutic tool.

Development of quantitative multiplex RT-qPCR one step assay for detection of hepatitis delta virus.

Hepatitis Delta is a disease caused by exposure to hepatitis B (HBV) and hepatitis D (HDV) viruses, usually with a more severe clinical outcome when compared to an HBV monoinfection. To date, the real prevalence of HDV infection is underestimated and detection methods are poorly available, especially in more endemic regions. Therefore, a one-step RT-qPCR method for quantification of HDV-RNA was developed. Biological samples were selected between 2017 and 2023 from patients at the Ambulatório Especializado em Hepatites Virais of the Centro de Pesquisa em Medicina Tropical de Rondônia and Serviço de Assistência Especializada and underwent the test developed by this study and a second quantitative RT-qPCR assay. The slope of the initial quantitative assay was - 3.321 with an efficiency of 100.04% and amplification factor equal to 2. Analysis of the repeatability data revealed a Limit of Quantification of 5 copies/reaction and Limit of Detection (95%) of 2.83 copies per reaction. In the diagnostic sensitivity tests, there was an accuracy of 97.37% when compared to the reference test. This assay proved to be highly efficient and reproducible, making it a valuable tool to monitor hepatitis Delta patients and assess the risk of disease progression, as well as the effectiveness of treatment.

Development of conversion factors to estimate the concentrations of heavy metals in manure-derived digestates.

During biogas production, a residual by-product rich in organic matter, nutrients, and trace elements - called digestate - is generated. Due to the nature of the anaerobic digestion process (i.e., conversion of organic matter into biogas) and the non-digestibility of trace elements, metal concentrations are higher in digestate than initially in the treated feedstock, resulting in a detrimental effect on the environment when directly applied as fertiliser on the soil. This study aims to predict the concentration of heavy metals in digestate through four different process parameters (Biogas yield - M1, Biodegradable fraction - M2, Dry matter - M3 and Power generation - M4) in full-scale biogas plants. For the validation of the process parameters, the predictions were compared against laboratory analyses of feedstocks and digestates samples from mono- and co-digestion processes. The convergence between the conversion factors based on laboratory data and process parameters (CLD and CFA, respectively) ranged in the following order: M3 > M2 > M1 > M4. Based on laboratory analyses, better predictions were obtained for Al, Cr, Cu, Fe, Mn, and Zn employing M3. Moreover, a robust convergence was achieved between the CLD and CFA conversion factors for the mono-digestion process. Further assessment of a diverse range of feedstocks is needed to increase the convergence between the conversion factors based on process parameters and laboratory data, specifically for the co-digestion process M3. The concentrations of Cd, Co, Ni, and Pb elements were below the detection limits, whereas Cr, Cu, and Zn did not exceed the legal threshold limits of the legislations.

Anticancer effects of phytol against Sarcoma (S-180) and Human Leukemic (HL-60) cancer cells.

Phytol (Pyt), a diterpenoid, possesses many important bioactivities. This study evaluates the anticancer effects of Pyt on sarcoma 180 (S-180) and human leukemia (HL-60) cell lines. For this purpose, cells were treated with Pyt (4.72, 7.08, or 14.16 µM) and a cell viability assay was performed. Additionally, the alkaline comet assay and micronucleus test with cytokinesis were also performed using doxorubicin (6 µM) and hydrogen peroxide (10 mM) as positive controls and stressors, respectively. Results revealed that Pyt significantly reduced the viability and rate of division in S-180 and HL-60 cells with IC50 values of 18.98 ± 3.79 and 1.17 ± 0.34 µM, respectively. Pyt at 14.16 µM exerted aneugenic and/or clastogenic effects in S-180 and HL-60 cells, where the number of micronuclei and other nuclear abnormalities (e.g., nucleoplasmic bridges and nuclear buds) were frequently observed. Moreover, Pyt at all concentrations induced apoptosis and showed necrosis at 14.16 µM, suggesting its anticancer effects on the tested cancer cell lines. Taken together, Pyt showed promising anticancer effects, possibly through inducing apoptosis and necrosis mechanisms, and it exerted aneugenic and/or clastogenic effects on the S-180 and HL-60 cell lines.

Bromelain supplementation and inflammatory markers: A systematic review of clinical trials.

BACKGROUND AND AIMS: The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults. METHODS: The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish. RESULTS: 1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1ß, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated. CONCLUSION: The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated.