Ethanolic extract from leaves of tithonia diversifolia induces apoptosis in HCT-116 cells through oxidative stress.

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.

Effect of CYB2B6 (c.516G>T), CYP2C9 (c.1075A>C) and UGT1A9 (c.98T>C) polymorphisms on propofol pharmacokinetics in patients submitted to colonoscopy: a cohort study.

BACKGROUND: The aim of this study was to investigate the effect of CYB2B6 (c.516G>T, rs3745274), CYP2C9 (c.1075A>C, rs1057910) and UGT1A9 (c.98T>C, rs72551330) polymorphisms on the pharmacokinetics of single-drug propofol in adult patients undergoing intravenous sedation. METHODS: In this prospective clinical study, a total of 124 patients undergoing anaesthesia with propofol, as a single drug, were evaluated when undergoing colonoscopy procedure. Clinical variables were obtained from the patient's anamnesis prior to performing the anaesthetic procedure, in the moment of the patient's loss of consciousness, during the colonoscopy exam (recorded every 5 min) and in the awakening time. RESULTS: Polymorphic genotypes for the rs3745274 and rs1057910 polymorphisms were associated with bispectral index, target-controlled infusion (TCI)/effector concentration of propofol and TCI/plasma concentration of propofol values. Based on multivariate analysis, it was observed that weight, age, surgery time, systolic blood pressure and the rs1057910 polymorphism corresponded to predictive values for the dose of propofol used. Weight (B = 4.807±0.897), age (B = 1.834±0.834) and duration of surgery (B = 8.164±1.624) corresponded to factors associated with increased propofol dose, while systolic blood pressure (B = -1.892±0.679) and the genotypes (AA vs CA) of the single nucleotide polymorphism (SNP) rs1057910 CYPP2C9 gene (B = -74.161±26.820) decreased the total dose of propofol used. CONCLUSION: We concluded that the rs1057910 and rs3745274 polymorphisms affect the metabolism of propofol in patients exclusively submitted to this drug. Thus, the knowledge of the polymorphic genotypes of the CYPP2C9 and CYB2B6 genes may be predictive of different metabolising phenotypes, suggesting expected behaviours of BIS parameter in the anaesthetic procedure, which contributes to safer monitoring by anaesthesiologists during the clinical intervention.

Outcomes of Apert Syndrome Hand Reconstruction With Tilapia Skin: A Prospective Study.

BACKGROUND: Tilapia skin has already been used in various medical scenarios, but there are no studies showing the use of tilapia skin for hand reconstruction in Apert syndrome. The objective of this study is to determine whether the use of tilapia skin during graft bed preparation for children with Apert syndrome can shorten wound reepithelialization intervals, reduce the number of dressing changes, and decrease patient discomfort. METHODS: This is a prospective study on consecutive patients with Apert syndrome who underwent hand reconstruction at our Hospital. Patients were divided into 2 groups: (1) a control group consisting of patients who underwent conventional digit separation hand reconstruction surgery (2) an experimental group consisting of patients who underwent similar digit separation hand reconstruction surgery that commenced with the placement of a thin layer of tilapia skin at the raw commissures during a first operation, which was subsequently replaced by an autologous skin graft during a second operation staged 10 days postoperatively. Pain assessment was performed using the Visual Analog Scale. The number of dressing changes was also assessed. A T test compared the total number of dressings changes and pain data. RESULTS: Experimental group patients (n = 8) required an average of 9.4 days of daily dressing changes, and control group patients (n = 5) required an average of 20.8 days of daily dressing changes ( P < 0.05) and tended to experience significantly less pain when compared with patients in the control group ( P = 0.079). CONCLUSION: Tilapia skin can shorten wound reepithelialization intervals by reducing the total number of dressing changes.

Neovaginoplasty With Nile Tilapia Skin: Cytological and Microbiota Evaluation.

OBJECTIVES: To study the clinical, cytological, and vaginal microbiota findings in patients with Mayer-Rokitansky-Küster-Hauser syndrome who underwent neovaginoplasty using Nile tilapia fish skin. METHODS: This is a cross-sectional study with 7 cisgender women with Mayer-Rokitansky-Küster-Hauser syndrome who had previously undergone neovagina reconstruction using Nile tilapia fish skin at a university hospital. Local institutional review board approval and written permission from the patient were obtained. Between August 2019 and November 2021, within 12 to 24 months after surgery, vaginal specimens were obtained for conventional oncotic and hormonal cytology, and for Gram staining. The Nugent scores were calculated. Colposcopy was also performed. RESULTS: Squamous cells without atypia were found in all patients. Five patients had intermediate vaginal microbiota (Nugent score of 4), which was determined by the presence of few lactobacilli on Gram staining. In hormonal cytology, 4 patients presented with findings compatible with menacme. No colposcopic change was observed. When postsurgical dilation was performed correctly, a mean vaginal length of 8.3 cm was maintained after 1 year of follow-up. CONCLUSIONS: Squamous cells without atypia were present in neovaginas with Nile tilapia fish skin. Most vaginal contents revealed intermediate microbiota and hormonal results compatible with menacme. Studies with a greater number of patients are necessary for a more comprehensive understanding of the microbiome in neovaginas with this new technique, thereby providing support for the treatment and prevention of associated pathologies.

The Role of WRAP53 in Cell Homeostasis and Carcinogenesis Onset.

The WD repeat containing antisense to TP53 (WRAP53) gene codifies an antisense transcript for tumor protein p53 (TP53), stabilization (WRAP53α), and a functional protein (WRAP53ß, WDR79, or TCAB1). The WRAP53ß protein functions as a scaffolding protein that is important for telomerase localization, telomere assembly, Cajal body integrity, and DNA double-strand break repair. WRAP53ß is one of many proteins known for containing WD40 domains, which are responsible for mediating a variety of cell interactions. Currently, WRAP53 overexpression is considered a biomarker for a diverse subset of cancer types, and in this study, we describe what is known about WRAP53ß's multiple interactions in cell protein trafficking, Cajal body formation, and DNA double-strand break repair and its current perspectives as a biomarker for cancer.

Neovaginoplasty with tilapia fish skin: a series of eleven cases.

INTRODUCTION AND HYPOTHESIS: Mayer-Rokitansky-Küster-Hauser syndrome affects about 1 in 5000 live female births and is associated with gonadal dysgenesis and primary amenorrhea. Neovaginoplasty has been established as an appropriate treatment option for patients who have failed or denied dilation therapy. In search of accessible, economical material with low risk of complications, the team proposed the use of Nile tilapia fish skin (NTFS) as an innovative biomaterial in the neovaginoplasty procedure for vaginal agenesis management. NTFS has noninfectious microbiota, morphologic structure comparable to human skin and high in vivo bioresorption. METHODS: In this descriptive study, the method offered an anatomical and functional neovagina to 11 patients efficiently, quickly and safely. Correct post-surgical dilation is still extremely important to keep the neovagina's size > 6 cm. RESULTS: Histological and immunohistochemical analysis demonstrated the formation of a stratified squamous epithelium with strong marking for cytokeratins, FGF and EGFR, similar to healthy adult vaginal tissue. CONCLUSIONS: Since NTFS is a low cost and easily accessible biomaterial, this technique proves to be an inexpensive therapeutic possibility for the health system with excellent advantages for patients.

Effect of CYB2B6 (c.516G>T), CYP2C9 (c.1075A>C) and UGT1A9 (c.98T>C) polymorphisms on propofol pharmacokinetics in patients submitted to colonoscopy: a cohort study.

BACKGROUND: The aim of this study was to investigate the effect of CYB2B6 (c.516G>T, rs3745274), CYP2C9 (c.1075A>C, rs1057910) and UGT1A9 (c.98T>C, rs72551330) polymorphisms on the pharmacokinetics of single-drug propofol in adult patients undergoing intravenous sedation. METHODS: In this prospective clinical study, a total of 124 patients undergoing anaesthesia with propofol, as a single drug, were evaluated when undergoing colonoscopy procedure. Clinical variables were obtained from the patient's anamnesis prior to performing the anaesthetic procedure, in the moment of the patient's loss of consciousness, during the colonoscopy exam (recorded every 5 min) and in the awakening time. RESULTS: Polymorphic genotypes for the rs3745274 and rs1057910 polymorphisms were associated with bispectral index, target-controlled infusion (TCI)/effector concentration of propofol and TCI/plasma concentration of propofol values. Based on multivariate analysis, it was observed that weight, age, surgery time, systolic blood pressure and the rs1057910 polymorphism corresponded to predictive values for the dose of propofol used. Weight (B = 4.807±0.897), age (B = 1.834±0.834) and duration of surgery (B = 8.164±1.624) corresponded to factors associated with increased propofol dose, while systolic blood pressure (B = -1.892±0.679) and the genotypes (AA vs CA) of the single nucleotide polymorphism (SNP) rs1057910 CYPP2C9 gene (B = -74.161±26.820) decreased the total dose of propofol used. CONCLUSION: We concluded that the rs1057910 and rs3745274 polymorphisms affect the metabolism of propofol in patients exclusively submitted to this drug. Thus, the knowledge of the polymorphic genotypes of the CYPP2C9 and CYB2B6 genes may be predictive of different metabolising phenotypes, suggesting expected behaviours of BIS parameter in the anaesthetic procedure, which contributes to safer monitoring by anaesthesiologists during the clinical intervention.

Role of miRNAs in Human T Cell Leukemia Virus Type 1 Induced T Cell Leukemia: A Literature Review and Bioinformatics Approach.

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients' samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-ß, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs' roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.

Circadian Rhythm Dysregulation and Leukemia Development: The Role of Clock Genes as Promising Biomarkers.

The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC's interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers.

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution.

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients' prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones' survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host's immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.

Male-to-Female Gender-Affirming Surgery Using Nile Tilapia Fish Skin as a Biocompatible Graft.

STUDY OBJECTIVE: Insufficient penile skin is common during vaginoplasty for male-to-female transition. This issue may be compensated by a scrotal skin flap, with the drawback of hair growth [1]. In recent studies, Nile tilapia skin was successfully used for the surgical management of Mayer-Rokitansky-Küster-Hauser syndrome [2,3] and vaginal stenosis [4,5]. This study aims to describe a novel technique for primary vaginoplasty in male-to-female gender-affirming surgery using Nile tilapia skin as a biocompatible graft to ensure adequate vaginal depth. DESIGN: Stepwise demonstration of the procedure with narrated video footage. SETTING: Transgender health clinic. INTERVENTIONS: A 29-year-old patient with gender dysphoria was referred to our office because of a desire for gender-affirming surgery. A physical examination revealed normal male genitalia with a 14-cm-long penis. Before surgery, approval from the institutional review board and written permission from the patient were obtained. After orchiectomy, penile disassembly, perineal dissection, and urethroplasty were performed, and a hollow Nile tilapia skin mold was prepared and sutured to the distal edge of the remaining penile skin. This structure was inverted, covering the newly created canal. The neocavity was then filled with a handmade inflatable vaginal mold, held in place by sutures in the labia majora. Finally, labiaplasty and clitoroplasty were conducted. After 7 days, the inflatable mold was removed, and the use of progressively larger dilators was initiated. After 3 weeks, a neovagina that was 16 cm long and able to accommodate the width of 2 fingers was detected. At that time, the Nile tilapia skin was completely reabsorbed into the neovaginal mucosa. There were no complications in the early postsurgical period. CONCLUSION: Nile tilapia skin, a safe, low-cost, and easy-to-use biocompatible material, may be an alternative option to scrotal skin grafts for neovaginal augmentation in primary vaginoplasty for male-to-female gender transition. However, further studies are needed to confirm this assertive.

Lyophilised tilapia skin as a xenograft for superficial partial thickness burns: a novel preparation and storage technique.

Despite a considerable decrease in its incidence worldwide, burns remain the fourth most common type of trauma. The majority of burns are small, with 75% of injuries treated on an outpatient basis. Tilapia skin, as a biological material, has been suggested as an option for the management of burn wounds. After good results were obtained with the use of a glycerolised version of tilapia skin in burned children and adults, it was hypothesised that similar outcomes could be achieved with the use of a lyophilised version of tilapia skin. We report the case of a 33-year-old female patient with scalds to the upper abdomen, and both breasts, arms and forearms. Involvement of 10% of total body surface area with superficial partial thickness burns was calculated. The good adherence of tilapia skin to the wound bed, a 10-day period for complete re-epithelialisation of the wounds and the absence of side effects suggested that the lyophilised version of tilapia skin is effective for burn treatment. Compared with glycerolisation, lyophilisation is thought to permit extended storage of sterile tissue and decreased costs related to distribution and transport, but further studies are needed to confirm this.

Endosuture trainer box simulator as a tool for training and teaching in bariatric laparoscopic surgery.

BACKGROUND: Video surgery requires acquisition of psychomotor skills that are different from those required for open surgery. The aim of this study was to assess the EndoSuture Trainer Box Simulator (ESTBS), a new bariatric laparoscopic skills simulator, as a tool for surgical education, comparing it with a standard laparoscopic trainer (SLT). METHODS: A randomized prospective crossover study was designed to compare ESTBS versus SLT as a tool for training bariatric laparoscopic skills. Participants were assigned to perform a task simulating Nissen fundoplication operation. All subjects evaluated the simulators concerning to their performance on simulating laparoscopic procedures by the use of a questionnaire comparing: triangulation, resistance and resilience, spatial perception (stereotaxy), ergonomics and positioning, inverted movements, visibility, design, technical and technological resources for training and education. The overall score was defined as the median value obtained. A total of 37 participants were enrolled in the study, including 29 experienced surgeons (78.37%) and 08 surgical residents (21.63%). RESULTS: A superior performance was observed with ESTBS as compared to SLT upon 7 of the 10 items evaluated in the questionnaire. Additionally, the overall score of ESTBS (median of 4, very good) was significantly higher (P < 0.0001) than that of SLT (median of 3, good). For the items, triangulation, resistance and resilience, ergonomics, design, training, technology and teaching, the evaluation for the ESTBS was very good and excellent, which was significantly higher than obtained by SLT. Also, ESTBS was cheaper. CONCLUSIONS: The ESTBS was shown to present excellent technical and technological performances and appears to constitute a useful cost-effective promising instrument for teaching and training bariatric surgical laparoscopic skills.

Comparison of the effects of pulmonary rehabilitation with chest physical therapy on the levels of fibrinogen and albumin in patients with lung cancer awaiting lung resection: a randomized clinical trial.

BACKGROUND: Systemic inflammation plays an important role in the initiation, promotion, and progression of lung carcinogenesis. In patients with non-small cell lung cancer (NSCLC), fibrinogen levels correlate with neoplasia. Here we compared the effects of pulmonary rehabilitation (PR) with chest physical therapy (CPT) on fibrinogen and albumin levels in patients with LC and previous inflammatory lung disease awaiting lung resection. METHODS: We conducted a randomized clinical trial with 24 patients who were randomly assigned to Pulmonary Rehabilitation (PR) and Chest Physical Therapy (CPT) groups. Each group underwent training 5 days weekly for 4 weeks. All patients were assessed before and after four weeks of training through clinical assessment, measurement of fibrinogen and albumin levels, spirometry, 6-minute Walk Test (6MWT), quality of life survey, and anxiety and depression scale. PR involved strength and endurance training, and CPT involved lung expansion techniques. Both groups attended educational classes. RESULTS: A mixed between-within subjects analysis of variance (ANOVA) revealed a significant interaction between time (before and after intervention) and group (PR vs. CPT) on fibrinogen levels (F(1, 22)=0.57, p<0.0001) and a significant main effect of time (F(1, 22)=0.68, p=0.004). Changes in albumin levels were not statistically significant relative to the interaction effect between time and group (F(1, 22)=0.96, p=0.37) nor the main effects of time (F(1, 22)=1.00, p=1.00) and group (F(1, 22 )=0.59, p=0.45). A mixed between-within subjects ANOVA revealed significant interaction effects between time and group for the peak work rate of the unsupported upper limb exercise (F(1, 22)=0.77, p=0.02), endurance time (F(1, 22)=0.60, p=0.001), levels of anxiety (F(1, 22)=0.60, p=0.002) and depression (F(1, 22)=0.74, p=0.02), and the SF-36 physical component summary (F(1, 22)=0.83, p=0.07). CONCLUSION: PR reduced serum fibrinogen levels, improved functional parameters, and quality of life of patients with LC and inflammatory lung disease awaiting lung resection. TRIAL REGISTRATION: Current Controlled Trials RBR-3nm5bv.

Antifungal activity of a trypsin inhibitor from Salvia hispanica L. (chia) seeds against fluconazole-resistant strains of Candida spp. and evaluation of its toxicity in vitro.

The incidence of Candida species resistant to traditional antifungal drugs is increasing globally. This issue significantly impacts patients' lives and increases healthcare expenses, confirming the need to develop novel therapeutic strategies. Recently, a thermostable trypsin inhibitor named ShTI (11.558 kDa), which has antibacterial effects on Staphylococcus aureus, was isolated from Salvia hispanica L. (chia) seeds. This study aimed to assess the antifungal effect of ShTI against Candida species and its synergism with fluconazole and to evaluate its mode of action. Preliminary toxicological studies on mouse fibroblasts were also performed. ShTI exhibited antifungal effects against C. parapsilosis (ATCC® 22,019), C. krusei (ATCC® 6258), and six clinical fluconazole-resistant strains of C. albicans (2), C. parapsilosis (2), and C. tropicalis (2). The minimum inhibitory concentration (MIC) values were 4.1 µM (inhibiting 50% of the isolates) and 8.2 µM (inhibiting 100% of the isolates). Additionally, when combined with fluconazole, ShTI had a synergistic effect on C. albicans, altering the morphological structure of the yeast. The mode of action of ShTI against C. krusei (ATCC® 6258) and C. albicans involves cell membrane permeabilization, the overproduction of reactive oxygen species, the formation of pseudohyphae, pore formation, and consequently, cell death. In addition, ShTI (8.65 and 17.3 µM) had noncytotoxic and nongenotoxic effects on L929 mouse fibroblasts. These findings suggest that ShTI could be a promising antimicrobial candidate, but further research is necessary to advance its application as a novel antifungal agent.

Validation of Endogenous Control Genes by Real-Time Quantitative Reverse Transcriptase Polymerase Chain Reaction for Acute Leukemia Gene Expression Studies.

Reference genes are used as internal reaction controls for gene expression analysis, and for this reason, they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute leukemia patients, a panel of genes commonly used as endogenous controls was selected from the literature for stability analysis: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Abelson murine leukemia viral oncogene human homolog 1 (ABL), Hypoxanthine phosphoribosyl-transferase 1 (HPRT1), Ribosomal protein lateral stalk subunit P0 (RPLP0), ß-actin (ACTB) and TATA box binding protein (TBP). The stability of candidate reference genes was analyzed according to three statistical methods of assessment, namely, NormFinder, GeNorm and R software (version 4.0.3). From this study's analysis, it was possible to identify that the endogenous set composed of ACTB, ABL, TBP and RPLP0 demonstrated good performances and stable expressions between the analyzed groups. In addition to that, the GAPDH and HPRT genes could not be classified as good reference genes, considering that they presented a high standard deviation and great variability between groups, indicating low stability. Given these findings, this study suggests the main endogenous gene set for use as a control/reference for the gene expression in peripheral blood and bone marrow samples from patients with acute leukemias is composed of the ACTB, ABL, TBP and RPLP0 genes. Researchers may choose two to three of these housekeeping genes to perform data normalization.

Molecular and Clinical Insights in the Increasing Detection of BCR::ABL1 p190+ in Adult Acute Myeloid Leukemia Patients.

BACKGROUND/AIM: Acute myeloid leukemia (AML) is a myeloproliferative neoplasm marked by abnormal clonal expansion of hematopoietic progenitor cells, displaying karyotypic aberrations and genetic mutations as prognostic indicators. The World Health Organization (WHO) and the European LeukemiaNet guidelines categorize BCR::ABL1 p190+ AML as high risk. This study explored the identification of the increased incidence of BCR::ABL1 p190+ in our AML population. PATIENTS AND METHODS: This study included 96 AML patients stratified according to WHO guidelines. Subsequently, patients were screened for genetic abnormalities, such as BCR::ABL1 p 190+, PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11 by quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis. RESULTS: Among 96 AML patients, 36 displayed BCR::ABL1 p190+, overcoming the expected global incidence. Age variations (19 to 78 years) showed no significant laboratory differences between BCR::ABL1 p190+ and non-BCR::ABL p190+ cases. The overall survival analysis revealed no statistically significant differences among the patients (p=0.786). CONCLUSION: The analyzed population presented a higher frequency of BCR::ABL1 p190+ detection in adult AML patients when compared to what is described in the worldwide literature. Therefore, more studies are needed to establish the reason why this incidence is higher and what the best treatment approach should be in these cases.

Association of CD38+ Immunophenotyping Biomarker With a Better Prognosis in Elderly Acute Myeloid Leukemia Patients.

BACKGROUND/AIM: The relevance of cytogenetic markers as prognostic risk factors has been demonstrated in a vast number of studies, with many prognostication tools utilizing these factors to determine treatment approaches. Patients aged above 60 years represent an important subgroup of acute myeloid leukemia (AML) patients, especially because they usually exhibit a poorer cytogenetic landscape and are less suitable for intensive treatments. The importance of evaluating prognostic parameters in AML, especially in low-income countries, prompted an investigation into CD38 expression and its effects. PATIENTS AND METHODS: Medical records of AML patients aged above 60 years from three hospitals in Brazil's northwest region were analyzed. A total of 67 patients were evaluated in terms of overall survival and factors predicting worse outcomes. The risk stratification was performed based on the European LeukemiaNet 2022 guidelines. The analysis of immunophenotyping markers was conducted using multi-parametric flow cytometry. RESULTS: The overall survival of CD38-positive AML patients was higher than that of patients with CD38-negative AML, with survival rates of 15.6 months versus 4 months, respectively (p-value=0.026). The impact of CD38 positivity was relevant also in multivariable Cox proportional hazards regression, demonstrating a positive effect on overall survival, with a hazard ratio of 0.33 (95%CI=0.13-0.79; p-value=0.014). CONCLUSION: Expression of CD38 in patients with AML was associated with better overall survival and serves as a relevant predictor of improved outcome in patients aged above 60 years.

Vasorelaxant effect of Alpinia zerumbet's essential oil on rat resistance artery involves blocking of calcium mobilization.

Alpinia zerumbet is a plant from the Zingiberaceae family, popularly used for hypertension treatment. Several studies have demonstrated Alpinia zerumbet vasodilator effect on conductance vessels but not on resistance vessels. Thereby, the aim of this study was to verify the vasodilator effect of the essential oil of Alpinia zerumbet (EOAz) on isolated rat resistance arteries and characterize its mechanism of action. Therefore, the effect of EOAz (3 to 3000 µg/mL) was verified in second-order branches of the mesenteric artery (SOBMA) pre-contracted by KCl and U46619. To study the mechanism of action, the influence of several inhibitors (TEA, 4-AP, Glibenclamide, Atropine, L-NAME, ODQ and indomethacin) on the vasodilator effect of EOAz was evaluated. Some protocols were also performed aiming to study the effect of EOAz on Ca2+ influx and release from intracellular storage. Furthermore, the binding energy of the main constituents with calcium channels were evaluated by molecular docking. Results showed an endothelium-independent vasorelaxant effect of EOAz on SOBMA, and only ODQ and L-NAME produced significant alteration on its pEC50. Regarding the calcium assays, contraction reduction caused by incubation with EOAz was observed in all three protocols. Hence, our results suggest that EOAz has a vasodilator effect mediated by inhibition of Ca2+ influx and release from intracellular storage, as well as an activation of the NOS/sGC pathway.