A chemical-ecology approach has been used to screen plants growing in Guyana Highlands as an indicator of production of biologically active secondary metabolites. Extracts of leaves from 19 species, most of them endemic in this area, and collected at the top of Roraima Tepui (2,723 m) were screened in vitro at different concentrations for their potential cytotoxic activity against three tumour cell lines: HT29 (colon), A549 (lung) and MDA-MB-231 (breast). MTT (tetrazolium blue) colorimetric assay was employed as cytotoxicity test. Extracts of nine species caused less than 30% growth in at least one cell line. From these species, high cytotoxic activity was detected in Casearia sylvestris var. lingua and Ledotamnus sessiliflorus extracts; medium activity was found in Cyathea sp. Two other species, Cyrilla racemiflora and Heliamphora minor showed lower but significant cytotoxicity. Further cytotoxicity-directed fractionation of these extracts would be advisable to isolate and identify the active principles of these plants.
Cytotoxicity ; Aspects of disease screening ; Cell Line ; MB-2 ; Employed

Gastric cancer (GC) is an aggressive disease and the fifth most common cancer worldwide with a variable geographical distribution. GC has a very low survival rate, mainly because of its heterogeneous presentation, multifactorial etiology, and late diagnosis. It is well established that various risk factors contribute to the development of the disease, including salty diet, smoking, and excessive alcohol consumption. Importantly, interactions between genetic and environmental traits trigger the activation of key signaling pathways, influencing gastric cell behavior towards neoplastic transformation and progression. Despite important advances in our understanding of GC, it remains a major health burden owing to epidemiological and therapeutic limitations. This study aimed to provide a comprehensive overview of the genetic landscape of GC phenotypes and molecular biomarkers for diagnosis and prognosis. In particular, we discuss the advances in genomic knowledge and technology that have yielded comprehensive information on the genetics of GC and classified it from a histological to a molecular perspective. Therefore, targeted and immune-based therapies have been developed, highlighting the challenges associated with intratumoral and interpatient heterogeneity. Finally, we explored potential research avenues on the intricacies of GC and identified accurate biomarkers for improved cancer screening and stratification. The development of innovative approaches to tackle relevant molecules is needed for GC management.

No abstract available.
Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Iron* ; Plasma*

Background/Aims: The study objective is to investigate the ultrasound features that allow suspecting the presence of submucosal fat deposition, called the fat halo sign (FHS), in the intestinal wall of patients with Crohn’s disease. Methods: Computed tomography (CT) examinations over a period of 10 years were reviewed for the presence of the FHS in the bowel wall. A measurement of less than –10 Hounsfield units was regarded as indicative of fat. We included only patients who had undergone ultrasound examinations 3 months before or after CT. The study cohort group comprised 68 patients. Wall and submucosal thickness were measured on longitudinal ultrasound sections. A receiver operating characteristic curve was constructed to determine the best cutoff of ultrasound submucosal wall thickness value for predicting FHS in the bowel wall determined on CT. Results: The FHS was present in 22 patients (31%) on CT. There were significant differences between submucosal thickness of patients with FHS and patients without FHS (4.19 mm vs. 2.41 mm). From the receiver operating characteristic curve, a threshold value of 3.1 mm of submucosal thickness had the best sensitivity and specificity to suspect FHS (95.5% and 89.1%, respectively; area under the curve, 0.962), with an odds ratio of 172. All of 16 patients with a submucosal thickness >3.9 mm had FHS. Conclusions FHS in patients with Crohn’s disease can be suspected on ultrasound in cases with marked thickening of the submucosa layer. In these cases, the activity of the disease should be measured by other parameters such as the color Doppler.

Objective: Assess and evaluate the different indicators of oral health-related quality of life (OHRQoL) among patients treated with clear aligners (CAs) versus those treated with conventional fixed orthodontics (FAs). Methods: An electronic search was performed on the database is Web of Science, Scopus, and Embase databases. Randomized and non-randomized control trials, cross-sectional, prospective cohort and retrospective trials were included. Quality was assessed with risk of bias tool and risk of bias in non-randomised studies. Meta-analyses were performed with random effects models, estimating the standardized and non-standardized mean differences, odds ratio and risk ratio as the measure of effect. The effect on time was determined using a meta-regression model. Results: Thirty one articles were included in the qualitative synthesis and 17 in the meta-analysis. CAs had a significantly lower negative impact on QoL, with an “important” effect size, while the influence of time was not significant.Periodontal indicators plaque index (PI), gingival index (GI), probing depth (PD), and bleeding on probing show significantly better values in patients treated with CAs, with moderate to large effect sizes. PI and GI have a significant tendency to improve over time. In microbiological indicators, CAs present a lower biofilm mass without differences in the percentage of patients with high counts of Streptococcus mutans and Lactobacilli bacteria. The risk of white spot lesion onset is ten times lower in carriers of CAs. Conclusions Patients wearing CAs show better periodontal indicators, less risk of white spot development, less biofilm mass and a better QoL than patients with FAs.

Cetuximab (CTX) is a potent chimeric mouse/human monoclonal antibody (mAb) approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per-formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor-mance liquid chromatography with diode array detection ((RP)HPLC/DAD) is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo-nization guidelines (ICH) for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci-sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre-hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de-monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc-cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.

AIM: To report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).METHODS: The present study was retrospective about non-randomized interventional case series. Fifty-one consecutive eyes with subfoveal (all types) CNV associated with AMD were treated by PDT and intravitreal (19.4±2.1)mg per 0.1mL TA at the Alicante Institute of Ophthalmology. The appearance of macular choriocapillaris and retinal pigment epithelium (RPE) atrophy was considered at two years follow-up. Thirty consecutive eyes treated by PDT alone, matched for age, sex, and type and size of CNV were considered as control group. RESULTS: Twenty-one of 47 eyes in the study group (45%) and 7 of 30 eyes in the control group (23%) developed macular RPE and choriocapillaris atrophy in the treated area at month 24 (P =0.04, Chi-square test). The greatest diameter of the atrophic areas averaged (5 044±1 666)μm in the study groupvs(4 345±1 550)μm in the control group. Mean final best corrected visual acuity (logarithm of minimal angle of resolution) was (0.87±033) in the cases with RPE atrophyvs(0.66±0.26) in the cases with no RPE atrophy in the study group (P=011, Mann-Whitney U test). CONCLUSION: The association of high doses of intravitreal TA and PDT may increase the risk for RPE and choriocapillaris atrophy.

AIM: To report the use of intravitreal bevacizumab associated with cataract surgery to prevent the re-activation of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).METHODS: Twelve eyes from 12 patients who had been previously treated for wet AMD and presented cataracts were operated on by clear cornea phacoemulsification with intraocular lens implantation, and an intravitreal injection of 1.25mg (0.05mL) bevacizumab was performed by the end of the procedure. The results were evaluated in terms of visual acuity improvement and reactivation of CNV, as determined by the appearance of fluid in optical coherence tomography (OCT). RESULTS: Best-corrected visual acuity(BCVA) significantly improved after surgery (P<0.01 and P=0.049 for BCVA after CNV closure and BCVA after cataract development respectively, Student's t test for paired data). Mean follow-up after cataract surgery was 11.8 months (SD 6.1, range 3 to 22 months). CNV reactivation or appearance of new CNV lesions was not observed in any case during follow-up. CONCLUSION: Intravitreal bevacizumab immediately after cataract surgery may prevent CNV reactivation in patients previously treated from CNV secondary to AMD.