Pannexin-1 expression in tumor cells correlates with colon cancer progression and survival.

AIMS: Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study. MAIN METHODS: PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid. KEY FINDINGS: PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stage-dependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth. SIGNIFICANCE: PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.

Correlation of Diagnostic Components of Metabolic Syndrome with Electrocardiographic and Echocardiographic Alterations in Patients with Obesity

Abstract Introduction: Metabolic syndrome (MS) and obesity are risk factors for cardiovascular diseases (CVD). However, the development of cardiovascular pathologies in obese individuals without MS is being investigated. Objective: To investigate whether there are similar electrocardiographic (ECG) and echocardiographic changes in individuals with obesity with and without MS. Methodology: A retrospective, descriptive cross-sectional study was carried out with obese patients at a university hospital in Belém, Pará, Brazil. Anthropometric, laboratory, ECG and echocardiographic data were evaluated in both populations. The chi-square test was used to describe the relationship between variables among groups; hypothesis tests with p < 0.05 were considered statistically significant values. Results: The study evaluated 100 individuals with obesity, 60 of whom had MS. The average age was 54 years, and the female sex was prevalent. Systolic blood pressure, HDL, and waist circumference were altered in both groups. Systemic arterial hypertension and low HDL demonstrated 4.27 times and 3.32 times greater likelihood of presenting changes in the ECG and echocardiogram for both groups. On the ECG, diffuse changes in ventricular repolarization were observed in both groups. On echocardiography, left ventricular diastolic dysfunction and left ventricular hypertrophy were present in both populations studied. Conclusion: Obese individuals without MS present a similar risk, requiring adequate attention to their cardiac health.

Impact of MICA 3'UTR allelic variability on miRNA binding prediction, a bioinformatic approach.

MicroRNAs (miRNAs) are small non-coding RNAs that participate as powerful genetic regulators. MiRNAs can interfere with cellular processes by interacting with a broad spectrum of target genes under physiological and pathological states, including cancer development and progression. Major histocompatibility complex major histocompatibility complex class I-related chain A (MICA) belongs to a family of proteins that bind the natural-killer group 2, member D (NKG2D) receptor on Natural Killer cells and other cytotoxic lymphocytes. MICA plays a crucial role in the host's innate immune response to several disease settings, including cancer. MICA harbors various single nucleotide polymorphisms (SNPs) located in its 3'-untranslated region (3'UTR), a characteristic that increases the complexity of MICA regulation, favoring its post-transcriptional modulation by miRNAs under physiological and pathological conditions. Here, we conducted an in-depth analysis of MICA 3'UTR sequences according to each MICA allele described to date using NCBI database. We also systematically evaluated interactions between miRNAs and their putative targets on MICA 3'UTR containing SNPs using in silico analysis. Our in silico results showed that MICA SNPs rs9266829, rs 1880, and rs9266825, located in the target sequence of miRNAs hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-93, hsa-miR-1207.5p, and hsa-miR-711 could modify the binding free energy between -8.62 and -18.14 kcal/mol, which may affect the regulation of MICA expression. We believe that our results may provide a starting point for further exploration of miRNA regulatory effects depending on MICA allelic variability; they may also be a guide to conduct miRNA in silico analysis for other highly polymorphic genes.

The effect of long-term exposure to nonylphenol at environmentally relevant levels on mouse liver and adipose tissue.

Exposure to the xenoestrogen nonylphenol (NP) during critical windows of development leads to metabolic abnormalities in adult life. However, less is known about NP exposure outside the developmental period on metabolic outcomes. We investigated the effect of prolonged exposure to NP after sexual maturity and at environmentally relevant concentrations below the 'no observable adverse effects level' (0.5 and 2.5 mg/kg/d). Male Swiss mice fed a normal-fat diet exposed to 2.5 mg/kg/d NP showed reduced weight gain and hepatic fat content. In male and female C57BL/6 mice fed a high-fat diet, NP exposure modified the mRNA levels of estrogen receptor α (Esr1) and adipose lineage markers in a sexually dimorphic and adipose depot-dependent pattern. Moreover, in primary female but not male stromal vascular cells from C57BL/6 mouse inguinal WAT induced to differentiate into adipocytes, NP upregulated Fabp4 expression. Low-level exposure to NP outside critical developmental windows may affect the metabolic phenotype distinctly. DATA AVAILABILITY STATEMENT: All data not included in the manuscript, such as raw results, are available upon request and should be addressed to AAA.

Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition

Abstract Background Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. Methods Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. Results ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. Conclusion We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

Is there an association between family structure and the oral health of socially vulnerable children?

Abstract The aim of this study was to evaluate the impact of the family structure on the oral health status of socially vulnerable children in the Federal District of Brazil. A total of 471 schoolchildren with a mean age of 8.12 (± 0.90) years were examined for dental caries using the CAST instrument. Dental biofilm and oral pain were also registered. Children's guardians were interviewed about socioeconomic variables and oral hygiene habits. The association between oral pain in the previous 30 days and the child's maximum CAST score were analyzed using the Pearson chi-squared test. Multivariate Poisson regression models with robust variance were used to determine the predictors of presence of biofilm, oral pain, and caries severity. The prevalence of cavitated dentin lesions was 43.74% and, both dentin and enamel lesions, 52.87%; for both dentitions. An association between pain and severe nontreated carious lesions was found (p < 0.0001). The family structure was not related to the presence of dental caries, but a significant association was found between low maternal education and severe carious lesions (PR = 1.41; p = 0.0077) and oral pain (PR = 1.47; p = 0. 0335); not owning a residence and frequency of toothbrushing were also associated with the substantial presence of biofilm (PR = 1.13, p = 0.0493 and PR = 1.18, p = 0.0470; respectively). For socially vulnerable children, variables related to the socioeconomic status of the families were more relevant than the family structure in relation to their oral health status.

BmooMPα-I, a Metalloproteinase Isolated from Bothrops moojeni Venom, Reduces Blood Pressure, Reverses Left Ventricular Remodeling and Improves Cardiac Electrical Conduction in Rats with Renovascular Hypertension.

BmooMPα-I has kininogenase activity, cleaving kininogen releasing bradykinin and can hydrolyze angiotensin I at post-proline and aspartic acid positions, generating an inactive peptide. We evaluated the antihypertensive activity of BmooMPα-I in a model of two-kidney, one-clip (2K1C). Wistar rats were divided into groups: Sham, who underwent sham surgery, and 2K1C, who suffered stenosis of the right renal artery. In the second week of hypertension, we started treatment (Vehicle, BmooMPα-I and Losartan) for two weeks. We performed an electrocardiogram and blood and heart collection in the fourth week of hypertension. The 2K1C BmooMPα-I showed a reduction in blood pressure (systolic pressure: 131 ± 2 mmHg; diastolic pressure: 84 ± 2 mmHg versus 174 ± 3 mmHg; 97 ± 4 mmHg, 2K1C Vehicle, p < 0.05), improvement in electrocardiographic parameters (Heart Rate: 297 ± 4 bpm; QRS: 42 ± 0.1 ms; QT: 92 ± 1 ms versus 332 ± 6 bpm; 48 ± 0.2 ms; 122 ± 1 ms, 2K1C Vehicle, p < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, p > 0.05), with reversal of hypertrophy (left ventricular area: 12.1 ± 0.3; left ventricle wall thickness: 2.5 ± 0.2; septum wall thickness: 2.3 ± 0.06 versus 10.5 ± 0.3; 2.7 ± 0.2; 2.5 ± 0.04, 2K1C Vehicle, p < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, p < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect.

TNF-α Affects Signature Cytokines of Th1 and Th17 T Cell Subsets through Differential Actions on TNFR1 and TNFR2.

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine implicated in the etiology of several autoimmune diseases, including rheumatoid arthritis (RA). TNF-α regulates diverse effector functions through the activation of TNF-α receptor (TNFR)1 and TNFR2. Although the detrimental role of this cytokine has been addressed in distinct disease settings, the effects of TNF-α on cytokine production by isolated CD4+ T helper type 1 (Th1) and Th17 cells, two T cell subpopulations that contribute to the pathogenesis of RA, have not been completely elucidated. Here, we show that TNF-α promotes a reduction and expansion in the frequency of both T cell subsets producing IFN-γ and IL-17, respectively. Selective blockade of TNFR1 or TNFR2 on Th1 and Th17 cells revealed that TNFR2 mediates the decrease in IFN-γ production, while signaling through both receptors augments IL-17 production. We also demonstrate that Th1, but not Th17 cells from RA patients present lower levels of TNFR1 compared to healthy controls, whereas TNFR2 expression on both T cell types is similar between patients and controls. Since TNF-α receptors levels in RA patients are not significantly changed by the therapeutic blockade of TNF-α, we propose that targeting TNFR2 may represent an alternative strategy to normalize the levels of key cytokines that contribute to RA pathogenesis.

Nutraceutical Eriocitrin (Eriomin) Reduces Hyperglycemia by Increasing Glucagon-Like Peptide 1 and Downregulates Systemic Inflammation: A Crossover-Randomized Clinical Trial.

This double-blind, randomized, placebo/controlled, crossover study evaluated the efficacy of Eriomin® in reducing hyperglycemia and improving diabetes-related biomarkers in individuals with hyperglycemia above 110 mg/dL (mean 123 ± 18 mg/dL). Subjects (n = 30), divided into two groups (Eriomin or Placebo), who received a dose of 200 mg/d of the designated supplement for 12 weeks and, after a washout period of 2 weeks, switched to the other supplement in the following 12 weeks. Assessments of biochemical, metabolic, inflammatory, blood pressure, anthropometry, and dietary parameters were performed at the beginning and end of each intervention. Treatment with 200 mg/d of Eriomin significantly decreased blood glucose (-5%), homeostasis model assessment of insulin resistance (-11%), glucagon (-13%), interleukin-6 (-14%), tumor necrosis factor alpha (-20%), and alkaline phosphatase (-13%); but increased glucagon-like peptide 1 (GLP-1) by (17%) (P ≤ .05). At the end of the placebo period, there was a 13% increase in triglycerides (P ≤ .05). Other parameters evaluated did not change with Eriomin or placebo. In conclusion, intervention with Eriomin benefited the glycemic control of prediabetic and diabetic patients, with higher blood glucose levels, by increasing GLP-1 and decreasing systemic inflammation.

Immunogenicity, safety, and antiphospholipid antibodies after SARS-CoV-2 vaccine in patients with primary antiphospholipid syndrome.

OBJECTIVE: Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). Recent reports of thrombosis associated with adenovirus-based vaccines raised concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger clotting complications. Our objectives were to assess immunogenicity, safety, and aPL production in PAPS patients, after vaccinating with Sinovac-CoronaVac, an inactivated virus vaccine against COVID-19. METHODS: This prospective controlled phase-4 study of PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69 in naïve participants. Safety and aPL production were also assessed. RESULTS: We included 44 PAPS patients (31 naïve) and 132 CG (108 naïve) with comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092), as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity (64.3% vs. 60.9%, p=0.689). Thrombotic events up to 6 months or other moderate/severe side effects were not observed. PAPS patients remained with stable aPL levels throughout the study at D0 vs. D28 vs. D69: anticardiolipin (aCL) IgG (p=0.058) and IgM (p=0.091); anti-beta-2 glycoprotein I (aß2GPI) IgG (p=0.513) and IgM (p=0.468). CONCLUSION: We provided novel evidence that Sinovac-CoronaVac has high immunogenicity and safety profile in PAPS. Furthermore, Sinovac-CoronaVac did not trigger thrombosis nor induced changes in aPL production.

The association between excess body weight at diagnosis and pediatric leukemia prognosis: A systematic review and meta-analysis.

Obesity affects the prognosis of several types of cancer. However, whether excess body weight is independently associated with adverse outcomes following initial pediatric acute leukemia (AL) treatment is still unclear. We conducted a systematic review and meta-analysis to investigate the impact of overweight/obesity at diagnosis on pediatric AL prognosis following initial treatment by performing an extensive database search up to January 22, 2021. Twenty-three studies were included, providing data for 15689 children with acute lymphoblastic leukemia (ALL) and 2506 children with acute myeloid leukemia (AML). Data from 12 studies were pooled in the meta-analysis. Children with overweight/obesity at diagnosis of ALL had poorer event free-survival (random-effects hazard ratio of 1.44, 95%CI 1.16-1.79, p = 0.0008), but no difference in overall survival (random-effects hazard ratio 1.33, 95%CI 0.77-2.29, p = 0.31) when compared with healthy-weight children. Children with overweight/obesity at diagnosis of AML had no difference in event-free survival (random-effects hazard ratio of 0.88, 95%CI 0.48-1.59, p = 0.66) or overall survival (random-effects hazard ratio 1.40, 95%CI 0.78-2.49, p = 0.26), when compared with healthy-weight children. This systematic review and meta-analysis indicates that overweight/obesity negatively affects the prognosis of children with ALL. Future studies should address the best approach to consider nutritional status in their management.

Ameliorating effects of metabolic syndrome with the consumption of rich-bioactive compounds fruits from Brazilian Cerrado: a narrative review.

Evidence suggests that bioactive compounds present in fruits and vegetables, including carotenoids, polyphenols, and phytosterols, may have beneficial effects against the development of obesity and other diseases. The fruits of the Brazilian Cerrado are rich in biologically active compounds but are underexplored by the population being used only locally dietary consumption. The objective of this review is to direct attention to the bioactive compounds already elucidated for the fruits of "Cerrado" cashew (Anacadium othanianum Rizz.), baru almond (Dipteryx alata Vogel), cagaita (Eugenia dysenterica DC.), "Cerrado" pear (Eugenia klotzschiana Berg), mangaba (Hancornia speciosa), and pequi (Caryocar brasiliense Camb), demonstrating possible metabolic effects of the consumption of these fruits on the metabolic syndrome and its risk factors. Studies have shown that Cerrado native fruits have a high content of bioactive compounds such as phenolic compounds, which also demonstrate high antioxidant capacity and may be related to the protective effect in metabolic syndrome-related diseases by act as inhibitors in various processes in lipid metabolism and glucose transport. Although more scientific evidence is still needed, the consumption of native fruits from the Cerrado seems to be a promising strategy which -along with other strategies such as nutritional therapy- can ameliorate the effects of the metabolic syndrome.

Problemas internalizantes em adultos / Internalizing problems in adults

RESUMO são escassas as investigações sobre problemas internalizantes em adultos brasileiros. Estudos epidemiológicos apontam que ansiedade e depressão são mais comuns em mulheres. Este estudo apresenta uma investigação com 240 adultos de diferentes municípios da Região Metropolitana da Baixada Santista, com uso do Adult Self Report . Dados foram analisados por estatística descritiva e inferencial, considerando a variável sexo. Não foram encontradas diferenças significativas entre homens e mulheres da amostra em termos de problemas internalizantes, ansiedade/depressão, retraimento e queixas somáticas. Resultados são discutidos à luz de dados epidemiológicos sobre transtornos mentais em outros recortes populacionais brasileiros. Ficam sugeridos novos estudos com ampliação de amostra.

ABSTRACT investigations on internalizing problems in Brazilian adults are scarce. Epidemiological studies indicate that anxiety and depression are more common among women. This study presents an investigation with 240 adults from different municipalities in the Baixada Santista Metropolitan Region, using the Adult Self Report. The data was analyzed using descriptive and inferential statistics, considering as variable the gender. No significant differences were found between men and women in the sample in terms of internalizing problems, anxiety/depression, withdrawal and somatic complaints. Results are discussed in the light of epidemiological data on mental disorders in other Brazilian population segments. New studies with sample expansion are suggested.

A new application to one-step nucleic acid amplification-discarded sample in breast cancer: Preliminary results.

The one-step nucleic acid amplification (OSNA) assay is a molecular method used for detecting breast cancer (BC) metastasis in sentinel lymph nodes (SLNs). However, this method has a major disadvantage, since it prevents tissue structure analysis, while only one molecular marker can be evaluated, namely cytokeratin 19 mRNA. The aim of the present study was to evaluate whether an OSNA-discarded sample could be suitable for the gene expression analysis of the SLN microenvironment. The remaining intermediate phase of the centrifuged SLN homogenate obtained from the OSNA assay of samples from two patients with BC was used for mRNA extraction. Subsequently, the expression of five genes, namely forkhead box, cluster of differentiation 4 and three control genes, was determined by reverse transcription-quantitative PCR analysis. The results demonstrated that high-quality RNA was extracted. Therefore, this RNA may be used for gene expression analyses to predict novel molecular biomarkers associated with immuno-inflammatory microenvironment.

A Study on the Pathological Effects of Trypanorhyncha Cestodes in Dusky Groupers Epinephelus marginatus from the Canary Islands.

Trypanorhyncha are cestodes commonly infecting marine fish. Numerous studies have detailed the biology of Trypanorhyncha species, but information on the pathological changes produced by these parasites is limited. Dusky groupers are keystone species necessary for the preservation of several marine ecosystems. Considering their vulnerable state of conservation and the efforts being made to culture them, identification of the effects caused by Trypanorhyncha is vital. Here, we aimed to determine the prevalence and pathological changes produced by Trypanorhyncha in dusky groupers from the Canary Islands. The prevalence of trypanorhynch plerocerci was 96%. Grossly, in the abdominal cavity, there were numerous larvae-filled cysts and nodules. These were embedded in abundant fibrosis, producing visceral adhesions. Histologically, affecting the peritoneum, stomach, and intestine there were numerous degenerated encysted plerocerci and extensive deposition of mature connective tissue. These findings indicate that Trypanorhyncha is highly prevalent in adult dusky groupers from the Canary Islands, producing a progressive and chronic response. Furthermore, fish immune system appears to attempt to eliminate the parasites through fibrous encapsulation. Nonetheless, extensive fibrosis may have a detrimental impact on fish health when adjacent cells or tissues are compressed and their functions impaired.

Heat-killed Helicobacter pylori upregulates NKG2D ligands expression on gastric adenocarcinoma cells via Toll-like receptor 4.

BACKGROUND: Natural killer (NK) cells are paramount for immunity against infectious agents and tumors. Their cytokine and cytolytic responses can be mediated by natural killer group 2, member D (NKG2D), an activating receptor whose ligands (NKG2DL) expression is induced in conditions of cell stress and malignant transformation. Since sustained expression of NKG2DL MICA is related to lower survival rates in gastric adenocarcinoma patients, and Helicobacter pylori infection contributes to tumorigenesis; we asked whether H. pylori stimulus could promote NKG2DL expression on human gastric adenocarcinoma cells. METHODS: Heat-killed H. pylori (HKHP) was used to stimulate MKN45 cells before analysis of NKG2DL and Toll-like receptor 4 (TLR4) protein levels by flow cytometry and transcripts by real-time PCR. LPS from Rhodobacter sphaeroides and inhibitory peptide Pepinh MYD were used to inhibit TLR4/MyD88 signaling pathway to assess its participation on NKG2DL expression. NK cell-mediated cytotoxicity was measured by lactate dehydrogenase (LDH) and CD107a mobilization assays. RESULTS: Stimulation of MKN45 cells with HKHP increased MICA, ULBP4 (another NKG2DL), and TLR4 at the protein and transcriptional levels. MICA, but not ULBP4 expression, was upregulated in a TLR4/MyD88-dependent manner. Furthermore, the presence of NKG2DL on the surface of HKHP-stimulated MKN45 cells enabled NK cell cytotoxic activation. CONCLUSIONS: Our data indicate that induction of NKG2DL expression on gastric adenocarcinoma cells by H. pylori promotes an immune response that may ultimately contribute to either gastric tissue damage, as a consequence of persistent activation of immunity, or tumor immune evasion due to chronic NKG2DL expression.

Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer.

Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. MICA gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study MICA gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of MICA gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA*002 (*A9) as the most frequent allele in both, patients and controls, followed by MICA*008 allele (*A5.1). MICA*009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39-18.74], p = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA*A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12-0.98], p = 0.046). Survival analysis after gastrectomy showed that patients with MICA*002/002 or MICA*002/004 alleles had significantly higher survival rates than those patients bearing MICA*002/008 (p = 0.014) or MICA*002/009 (MICA*002/049) alleles (p = 0.040). The presence of threonine in the position MICA-181 (MICA*009/049 allele) was more frequent in GC patients than controls (p = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA*004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.

Is Diagnostic Hysteroscopy Safe for the Investigation of Type II Endometrial Cancer? A Retrospective Cohort Analysis.

STUDY OBJECTIVE: Although hysteroscopy (HSC) can be used for assessing the uterine cavity in women with suspected endometrial cancer (EC), it remains controversial as a procedure because it can potentially enhance the metastatic spread of cancer cells. Moreover, it is important to assess this hypothesis for type II EC, a more aggressive phenotype that usually presents with endometrial atrophy and has worse prognosis. Thus, we aimed to assess the prevalence of positive peritoneal cytology result in women with type II EC who underwent HSC as a diagnostic tool and to determine the factors associated with patient relapse/survival. DESIGN: Retrospective cohort analysis (2002-2017). SETTING: Tertiary, academic hospital. PATIENTS: One hundred twenty-seven women with type II EC. INTERVENTIONS: Diagnostic HSC (HSC) (n = 43) or dilation/curettage (D&C) (n = 84). MEASUREMENTS AND MAIN RESULTS: Primary end point was the frequency of positive peritoneal cytology result. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis with hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to assess the factors related with the disease-free survival (DFS) and the disease-specific survival (DSS). Advanced cancer stage and greater vascular invasion appeared more frequently in the D&C group (p = .008 and p = .04, respectively). Positive peritoneal cytology result was present in 2 of 43 (4.6%) women following HSC and in 9 of 84 (10.7%) following D&C (p = .22). DFS and DSS curves did not statistically differ between the groups. Multivariate analysis for DFS revealed that advanced cancer stage (III and IV) (HR = 4.67; 95% CI, 2.34-9.34; p <.001) and advanced age (HR = 1.08; 95% CI, 1.04-1.13]; p <.001) were the factors associated with relapse. For DSS, advanced age (HR = 1.08; 95% CI, 1.05-1.12; p <.001), cancer stage III/IV (HR = 3.95; 95% CI, 2.18-7.15; p <.001), and vascular invasion (HR = 2.47; 95% CI, 1.34-4.54; p = .004) increased the risk of mortality. CONCLUSION: Diagnostic HSC did not increase the rate of positive peritoneal cytology result at the time of surgical staging in this cohort of women with type II EC and is probably as safe as D&C.

Antioxidant, antibacterial and antitumoural activities of kraft lignin from hardwood fractionated by acid precipitation.

Kraft lignin, so far useful for energy generation, has been gathering considerable attention as an alternative material to replace fossil-based resources mainly due to its high phenolic content. However, the wide molecular weight distribution and chemical composition heterogeneity led to the development of fractionation methods. Herein, to narrow such characteristics we used eucalypt kraft lignin fractionated at pH's 9, 7, 5 and 3 by sequential acid precipitation. These lignin fractions were first characterised by simultaneous pyrolysis and trimethylsilylation (SPyT) with N-Methyl-N-(trimethylsilyl) trifluoroacetamide with posterior tests of antioxidant, antibacterial, and antitumour activities. We observed higher ratio of syringyl/guaiacyl groups and increase in antioxidant activity in those fractions with lower molecular weight (precipitated at lower pH's). Fractions precipitated at pH's 9 and 7 have shown an outstanding antibacterial activity against five bacteria. Moreover, fractions 7 and 5 presented at cytotoxicity tests higher ability to inhibit the growth of U87MG and T98G glioma cells, while only a slight inhibition of adult human fibroblasts (non-tumour cells) was detected.

An exploratory study using the network approach for quality of life and blood markers in a Brazilian population / Um estudo exploratório utilizando a aplicação da abordagem de rede à qualidade de vida e marcadores sanguíneos em uma população brasileira / Un estudio exploratorio utilizando la aplicación del enfoque de red a la calidad de vida y los marcadores sanguíneos en una población brasileña

Although it is generally considered that quality of life (QoL) is related to blood markers, there are different approaches to the relation between these variables. We proposed here a dynamic interaction test. The aim was to ascertain which blood indicators relate to QoL through a network perspective in a common population. Answered a questionnaire and conducted blood exams 108 Brazilians. Of these, 84 were female, with a mean age of 43.85 years old (SD = 16.20). Data analysis indicated that CRP, T4 (FT4), Thyroid-stimulating hormone, and Cortisol bridges with QoL dimensions. The data suggest that QoL is related to blood markers, but some trends were less than the literature has indicated. This present study is exploratory. The relations are complex, and our findings suggest that the dynamic network structure expands the range of QoL and blood markers research, making it possible to investigate a new range of questions and analyses.

Embora se considere geralmente que a qualidade de vida (QV) está relacionada a marcadores sanguíneos, existem diferentes abordagens para a relação entre essas variáveis. Propomos aqui um teste de interação dinâmica. O objetivo foi verificar quais indicadores de sangue se relacionam com a QV através de uma perspectiva de rede em uma população comum. Respondeu a um questionário e realizou exames de sangue 108 brasileiros. Desses, 84 eram do sexo feminino, com média de idade de 43,85 anos (DP = 16,20). A análise dos dados indicou que a PCR, T4 (FT4), hormônio estimulante da tireoide e cortisol fazem pontes com dimensões de QV. Os dados sugerem que a QV está relacionada a determinados marcadores sanguíneos, mas algumas tendências foram inferiores às indicadas pela literatura. O presente trabalho é exploratório. As relações são complexas e nossos achados sugerem que a estrutura dinâmica da rede expande a gama de pesquisas sobre QV e marcadores sanguíneos, possibilitando a investigação de um novo espectro de perguntas e análises.

Aunque generalmente se considera que la calidad de vida (QoL) esté relacionada con los marcadores sanguíneos, existen diferentes enfoques para la relación entre estas variables. Propusimos aquí una prueba de interacción dinámica. El objetivo era determinar qué indicadores sanguíneos se relacionan con la calidad de vida a través de una perspectiva de red en una población común. Respondieron a un cuestionario y realizaron exámenes de sangre a 108 brasileños. De estos, 84 eran mujeres, con una edad media de 43,85 años (DE = 16,20). El análisis de datos indicó que CRP, T4 (FT4), hormona estimulante de la tiroides y cortisol hacen puentes con dimensiones de calidad de vida. Los datos sugieren que la calidad de vida está relacionada con ciertos marcadores sanguíneos, pero algunas tendencias fueron menores de lo que la literatura ha indicado. El presente trabajo es exploratorio. Las relaciones son complejas, y nuestros hallazgos sugieren que la estructura dinámica de la red amplía el rango de QoL y las investigaciones de marcadores sanguíneos, lo que permite investigar un nuevo rango de preguntas y análisis.