Francisco Washington Araújo Barros

Introduction: Systematic reviews occupy a central position in evidence hierarchies, providing structured syntheses intended to inform clinical decision‐making and health policy. However, the rapid expansion of artificial intelligence (AI) tools in literature searching, screening, data extraction, and manuscript drafting is transforming how these reviews are produced. Concurrently, the number of prospectively registered systematic reviews has grown substantially, with recent increases in PROSPERO registrations highlighting an accelerating output of evidence syntheses. While technological advances promise efficiency and scalability, they also raise concerns regarding methodological rigor, redundancy, and transparency. Methods: This viewpoint argues that the current reporting and governance frameworks for systematic reviews remain largely anchored in pre‐AI workflows. Results: Ongoing updates to reporting standards, including PRISMA revisions, have yet to fully address key challenges introduced by AI‐assisted methodologies, such as algorithmic bias, auditability, reproducibility limitations of proprietary models, and the need to document human oversight. The absence of explicit guidance for reporting AI use creates a critical transparency gap, potentially undermining confidence in systematic reviews and increasing the risk of superficial or duplicated syntheses. Conclusion: We propose that the evidence‐synthesis ecosystem requires urgent adaptation, including the development of a PRISMA‐AI extension, strengthened metadata requirements in registries such as PROSPERO, and updated editorial policies for AI‐assisted reviews. Safeguarding rigor in the age of automated science is essential to maintain the credibility and clinical utility of systematic reviews.

Tithonia diversifolia is a perennial bushy plant found in South America with significant ethnopharmacological importance as an antimalarial, antidiabetic, antibacterial, and anticancer agent. The aim of the present study was to determine the cytotoxicity of the ethanolic extract from leaves of T. diversifolia (TdE) on human cancer cell lines (HCT-116, SNB-19, NCIH-460 and MCF-7), as well as the mechanism of action involved in cell death and cellular modulation of oxidative stress. The TdE exhibited significant activity with IC₅₀ values ranging from 7.12 to 38.41 μg/ml, with HCT-116 being the most sensitive cell line. Subsequent experiments were conducted with HCT-116 cell line. TdE decreased the number of viable cells, followed by induction of apoptotic events, increase in mitochondrial membrane permeabilization, and enhanced G₂/M phase of the cell cycle. Pro-oxidative effects including elevated acidic vesicular organelle formation, lipid peroxidation, and nitric oxide by-products, as well as reduced levels of intracellular glutathione and reactive oxygen species production were also observed following incubation with TdE, which may lead to DNA damage followed by apoptotic cell death. These results demonstrate the potential of TdE ethanolic leaf extraction for biological activity and enhance the importance of continuing to study natural sources of plants for the development of anticancer agents.

Oncocalyxone A, a 1,4-benzoquinone derived from Cordia oncocalyx, exhibits anti-inflammatory, antimicrobial and antidiabetic properties. The aim of this study was to (1) examine the cytotoxic actions of oncocalyxone A on human normal and tumor cell lines and (2) determine mechanistic actions underlying effects upon leukemia cells using cellular and molecular techniques. Antiproliferative studies on cancer cell lines, peripheral blood mononuclear cells, and human erythrocytes were performed using colorimetric assays. To understand cytotoxicity, assessments were performed with HL-60 leukemia cells (8, 16.5, or 33 µM) after 24 hr incubation using light and fluorescence microscopy, trypan blue, flow cytometry, Comet assay, western blot of caspases and poly-ADP-ribose polymerase (PARP), and effects on topoisomerase I and II. Oncocalyxone A exhibited cytotoxic action upon HL-60 cells and dividing leukocytes, but minimal hemolytic action on erythrocytes. Mechanistic investigations demonstrated reduction of cell viability, loss of membrane integrity, cell shrinking, chromatin condensation, blebbings, externalization of phosphatidylserine, caspase activation, PARP cleavage, mitochondrial depolarization, and DNA damage. Pre-treatment with N-acetylcysteine 4 mM significantly reduced DNA damage and prevented membrane integrity loss. Oncocalyxone A displayed free radical dependent antileukemic activity via apoptotic pathways and induced DNA damage in HL-60 cells. Oncocalyxone A possesses structural chemical simplicity enabling it to be a cost-effective alternative. These properties justify further improvements to enhance activity and selectivity and the development of pharmaceutical formulations. Abbreviations Acridine orange, AO; ANOVA, analysis of variance; BSA, bovine serum albumin; DI, Damage Index; DMSO, dimethylsulfoxide; EC₅₀, effective concentration 50%; EDTA, ethylenediamine tetraacetic acid; EB, ethidium bromide; HCT-116, colon carcinoma line; HL-60, promyelocytic leukemia line; IC₅₀, inhibitory concentration 50%; MTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; OVCAR-8, ovarian carcinoma line; NAC, N-acetylcysteine, PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; PI, propidium iodide; PARP, poly-ADP-ribose polymerase; RPMI-1640, Roswell Park Memorial Institute medium; SF-295, glioblastoma line; ROS, reactive oxygen species; 7-AAD, 7-amino-actinomycin D; H₂-DCF-DA, 7′-dichlorodihydrofluorescein diacetate.

The tambjamines are a small group of bipyrrolic alkaloids that, collectively, display a significant range of biological activities including antitumor, antimicrobial and immunosuppressive properties. The key objective of the present study was to undertake preclinical assessments of tambjamine J (T‐J) so as to determine its in vivo antitumor effects. To that end, sarcoma 180 cells were transplanted in mice and the impacts of the title compound then evaluated using a range of protocols including hematological, biochemical, histopathological, genotoxic and clastogenic assays. As a result it was established that this alkaloid has a significant therapeutic window and effectively reduces tumor growth (by 40 % and 79 % at doses of 10 and 20 mg/kg/day, respectively). In this regard it displays similar antitumor activity to the anticancer agent cyclophosphamide and alters animal weight in an analogous manner.

Objetivo: identificar interações medicamentosas potenciais em prontuários de pacientes de um hospital e maternidade de um município brasileiro. Métodos: estudo documental, retrospectivo, com abordagem quantitativa, realizado entre janeiro e junho de 2017, em um hospital filantrópico do Estado do Ceará, Brasil. A fonte documental foram os prontuários de 167 pacientes. Os dados foram analisados por estatística descritiva com frequência absoluta e relativa. As interações medicamentosas potenciais foram verificadas por meio do Sistema Micromedex. Resultados: dos 167 prontuários, 80 (48%) eram de pacientes do sexo masculino e 87 (52%) do sexo feminino. Identificou-se que 24 das interações medicamentosas foram “potenciais maiores”, presentes, sobretudo, na associação dos seguintes fármacos: dipirona/ibuprofeno, dipirona/prednisona, dipirona/diclofenaco. Conclusão: o estudo mostra a necessidade de maior cautela na prescrição de dipirona com outros medicamentos, haja vista um maior envolvimento dele em interações medicamentosas potenciais.

A automedicação é uma resultante de inúmeros fatores, dentre eles se destacam a dificuldade do acesso aos serviços de saúde e a necessidade de aliviar sintomas. Os universitários são umas das conjunturas sociais que mais praticam automedicação, onde a busca por meios que amenizem perturbações causadas ou intensificadas por razões emocionais. Os objetivos do estudo foram avaliar a frequência da automedicação praticada e descrever quais medicamentos foram os mais utilizados pela classe discente de uma Instituição de Ensino Superior no Estado do Ceará. Participaram da pesquisa 120 discentes. Para a coleta dos dados aplicaram-se três questionários: um questionário sobre o perfil sócio demográfico, um questionário semiestruturado a respeito da prática da automedicação e para avaliar as manifestações de estresse utilizou-se o Inventário de Sintomas de Estresse de Lipp. Destes, 96 alunos afirmaram fazer uso de medicamentos sem prescrição médica, correspondendo a 80% da amostra avaliada; enquanto 24 afirmaram que não, correspondendo a 20% dos discentes. Os medicamentos mais apontados foram os analgésicos e os AINES. O uso de fármacos para reversão de sintomas de manifestação de estresse é elevado nos discentes da instituição onde o presente estudo foi desenvolvido.

Seven β-aryl-substituted γ-alkylidene-γ-lactone analogues of rubrolides were synthesized from mucochloric acid and converted into their corresponding γ-hydroxy-γ-lactams (76–85%) by a reaction with isobutylamine and propylamine. Further dehydration of the γ-hydroxy-γ-lactams led to the corresponding (Z)- and (E)-γ-alkylidene-γ-lactams (23–45%). All compounds were fully characterized by spectroscopic methods. These 14 compounds, together with 32 other rubrolide analogues, were assayed against four human tumor cell lines (HL-60, leukaemia; HCT-116, colon; SF-295, central nervous system; and OVCAR-8, ovarian). Of the 46 compounds assayed, 7 caused a large reduction in cell viability (% RCV > 80%) in the tested cell lines and the most active compounds had halogen substituents on the aromatic ring. Compounds 10a and 14i were the most active (RC₅₀ = 3.00 and 3.58 μM, respectively) against HL-60 and were not cytotoxic to L929 normal cells at the concentrations tested (RC₅₀ > 50 μM). To further understand the mechanism underlying the cytotoxicity of 10a and 14i, studies involving DNA fragmentation, cell cycle analysis, phosphatidyl serine externalization and mitochondrial depolarization were performed in the HL-60 cells, using doxorubicin as a positive control. The results indicated that the cytotoxicity of 10a and 14i involved the induction of cell death by apoptosis. The cell cycle analysis showed that 14i caused the accumulation of cells in the G0/G1 phase at 2.5 and 5 μM.

The current study describes that nor-β-lapachone and its arylamino derivatives, iodinated and methylated naphthoquinones and nor-β-lapachone-based 1,2,3-triazoles exhibited pronounced cytotoxic effects against four human leukemia cell lines (HL-60, K562, Molt-4 and Jurkat). Nor-β-lapachones arylamino substituted with potent activity were identified, revealing themselves as potential prototypes against tumor cell lines. Moreover, cells treated with these compounds showed DNA damage according to the standard comet assay, a finding that was, at least in part, due to increased intracellular levels of ROS. HL-60 cells were chosen to study the underlying molecular mechanisms of cytotoxicity. Drug-induced apoptosis in HL-60 cells was observed by flow cytometry analyses. Strains of Saccharomyces cerevisiae were used for a preliminary investigation into the mechanism of drug action on DNA topoisomerases. These results suggested that the cytotoxicity of these compounds apparently does not involve topoisomerase inhibition, but that treatment impairs DNA repair activity, thus triggering cell death. Considering their pro-oxidant properties, we investigated the ability of these compounds to induce apoptosis and chromosomal aberrations as micronuclei in Chinese hamster lung fibroblasts (V79 cells). Morphological apoptotic nuclei and micronuclei induction following drug treatment were observed, suggesting a correlation between DNA damage and apoptosis.