Career Length After Surgically Treated ACL Plus Collateral Ligament Injury in Elite Athletes.

BACKGROUND: Limited data are available regarding career length and competition level after combined anterior cruciate ligament (ACL) and medial- or lateral-sided surgeries in elite athletes. PURPOSE: To evaluate career length after surgical treatment of combined ACL plus medial collateral ligament (MCL) and ACL plus posterolateral corner (PLC) injuries in elite athletes and, in a subgroup analysis of male professional soccer players, to compare career length and competition level after combined ACL+MCL or ACL+PLC surgeries with a cohort who underwent isolated ACL reconstruction (ACLR). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A consecutive cohort of elite athletes undergoing combined ACL+MCL and ACL+PLC surgery was analyzed between February 2001 and October 2019. A subgroup of male elite soccer players from this population was compared with a previously identified cohort having had isolated primary ACLR without other ligament surgery. A minimum 2-year follow-up was required. Outcome measures were career length and competition level. RESULTS: A total of 98 elite athletes met the inclusion criteria, comprising 50 ACL+PLC and 48 ACL+MCL surgeries. The mean career length after surgical treatment of combined ACL+MCL and ACL+PLC injuries was 4.5 years. Return-to-play (RTP) time was significantly longer for ACL+PLC injuries (12.8 months; P = .019) than for ACL+MCL injuries (10.9 months). In the subgroup analysis of soccer players, a significantly lower number of players with combined ACL+PLC surgery were able to RTP (88%; P = .003) compared with 100% for ACL+MCL surgery and 97% for isolated ACLR, as well as requiring an almost 3 months longer RTP timeline (12.9 months; P = .002) when compared with the isolated ACL (10.2 months) and combined ACL+MCL (10.0 months) groups. However, career length and competition level were not significantly different between groups. CONCLUSION: Among elite athletes, the mean career length after surgical treatment of combined ACL+MCL and ACL+PLC injuries was 4.5 years. Professional soccer players with combined ACL+PLC surgery returned at a lower rate and required a longer RTP time when compared with the players with isolated ACL or combined ACL+MCL injuries. However, those who did RTP had the same career longevity and competition level.

Region-Specific Gene Expression Changes Associated with Oleoylethanolamide-Induced Attenuation of Alcohol Self-Administration.

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have not been widely explored. Here, we tested the effects of OEA treatment during alcohol SA, extinction or previous to cue-induced reinstatement of alcohol seeking. In addition, we measured gene expression changes in the striatum and hippocampus of relevant receptors for alcohol consumption (Drd1, Drd2, Cnr1, Oprm) as well as immune-related proteins (Il-6, Il-1ß, Tlr4) and the brain-derived neurotrophic factor (Bdnf). Our results confirmed that when administered contingently, systemic OEA administration reduced alcohol SA and attenuated cue-induced reinstatement. Interestingly, we also observed that OEA treatment reduced the number of sessions needed for the extinction of alcohol seeking. Biochemical analyses showed that OEA induced gene expression changes in dopamine and cannabinoid receptors in the striatum and hippocampus. In addition, OEA treatment modulated the long-term immune response and increased Bdnf expression. These results suggest that boosting OEA levels may be an effective strategy for reducing alcohol SA and preventing relapse.

Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice

INTRODUCTION: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. OBJECTIVE: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. METHODS: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-ß, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student's t-test. RESULTS: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-ß transcripts were less expressed in the UT-treated. CONCLUSION: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.

Measuring cfDNA integrity as a biomarker for predicting neoadjuvant chemotherapy response in breast cancer patients: a pilot study.

PURPOSE: Circulating cell-free DNA (cfDNA) is a promising biomarker for predicting treatment response and disease outcomes in Breast Cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). To determine if cfDNA originates from tumors, matching tumor and cfDNA gene mutations are necessary, often requiring tumor DNA sequencing. We assessed plasma cfDNA integrity by measuring concentrations and ratios of larger-to-smaller Alu DNA fractions as a potential biomarker, eliminating the need for prior tumor sequencing. METHODS: We included patients with localized and/or locally advanced BC receiving standard NAC alone or in combination with immunotherapy and/or anti-HER2 targeted therapy. Blood samples were collected before treatment, every 2 weeks during treatment, and before surgery. RESULTS: Of the 38 evaluated patients, only 28 completed the protocol and underwent surgery after NAC. Seven patients (25%) achieved a pathologic complete response (pCR). We found that cfDNA integrity (cfDNAI) levels at 15 days after starting NAC were significantly higher in patients who achieved pCR (p = 0.045) and correlated significantly with Disease-Free Survival (DFS) in univariate analysis (p = 0.0371). CONCLUSIONS: Evaluation of cfDNAI 2 weeks after NAC initiation appears to be an early biomarker for tumor pCR and DFS. Measuring Alu fragments of different lengths may replace techniques requiring prior tumor sequencing to measure ctDNA, reducing costs and complexity of cfDNA serial measurements in BC patients undergoing NAC.

In vitro results with minimal blood toxicity of a combretastatin A4 analogue.

Cancer is a disease caused by uncontrolled cell growth that is responsible for several deaths worldwide. Breast cancer is the most common type of cancer among women and is the leading cause of death. Chemotherapy is the most commonly used treatment for cancer; however, it often causes various side effects in patients. In this study, we evaluate the antineoplastic activity of a parent compound based on a combretastatin A4 analogue. We test the compound at 0.01 mg mL- 1, 0.1 mg mL- 1, 1.0 mg mL- 1, 10.0 mg mL- 1, 100.0 mg mL- 1, and 1,000.0 mg mL- 1. To assess molecular antineoplastic activity, we conduct in vitro tests to determine the viability of Ehrlich cells and the blood mononuclear fraction. We also analyze the cytotoxic behavior of the compound in the blood and blood smear. The results show that the molecule has a promising antineoplastic effect and crucial anticarcinogenic action. The toxicity of blood cells does not show statistically significant changes.

Hydroxytyrosol Linoleoyl Ether Ameliorates Metabolic-Associated Fatty Liver Disease Symptoms in Obese Zucker Rats.

A main hepatic consequence of obesity is metabolic-associated fatty liver disease (MAFLD), currently treated by improving eating habits and administrating fibrates yet often yielding suboptimal outcomes. Searching for a new therapeutic approach, we aimed to evaluate the efficacy of hydroxytyrosol linoleoyl ether (HTLE), a dual Ppar-α agonist/Cb1 antagonist with inherent antioxidant properties, as an antisteatotic agent. Using lean and obese Zucker rats, they were administrated daily doses of HTLE (3 mg/kg) over a 15-day period, evaluating its safety profile, pharmacokinetics, impact on body weight, hepatic fat content, expression of key enzymes involved in lipogenesis/fatty acid oxidation, and antioxidant capacity. HTLE decreased the body weight and food intake in both rat genotypes. Biochemical analysis demonstrated a favorable safety profile for HTLE along with decreased concentrations of urea, total cholesterol, and aspartate aminotransferase AST transaminases in plasma. Notably, HTLE exhibited potent antisteatotic effects in obese rats, evidenced by a decrease in liver fat content and downregulation of lipogenesis-related enzymes, alongside increased expression of proteins controlling lipid oxidation. Moreover, HTLE successfully counteracted the redox imbalance associated with MAFLD in obese rats, attenuating lipid peroxidation and replenishing both glutathione levels and the overall antioxidant. Our findings highlight the effectiveness of triple-action strategies in managing MAFLD effectively. Based on our results in the Zucker rat model, HTLE emerges as a promising candidate with triple functionality as an anorexigenic, antisteatotic, and antioxidant agent, offering potential relief from MAFLD symptoms associated with obesity while exhibiting minimal side effects. In conclusion, our study positions HTLE as a highly promising compound for therapeutic intervention in MAFLD treatment, warranting further exploration in clinical trials.

Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

INTRODUCTION: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD). METHODS: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis. RESULTS: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis. CONCLUSIONS: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments.

BACKGROUND: Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. METHODS: Plasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed. RESULTS: Reduced body and femur length of Pappa2ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3ß, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2ko/ko females. CONCLUSIONS: Sex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

Understanding the physiological role of pregnancy-associated plasma protein-A2 (PAPP-A2), a proteinase involved in the insulin-like growth factor-1 (IGF1) availability to regulate growth, could provide insight into new treatments for patients with short stature and skeletal abnormalities. Although progressive postnatal growth retardation in patients with PAPP-A2 mutations can differ between males and females, we do not know the underlying differences in IGF1 system and signaling, and their response to treatment that contribute to growth improvement. The present study examines whether Pappa2 deficiency and pharmacological administration of rhGH, rhIGF1 and rhPAPP-A2 are associated with sex-specific differences in IGF1 ternary complexes and IGF1 signaling pathways. Reduced body and femur length of Pappa2-deficient mice was associated with sex- and tissue-specific alteration of IGF ternary/binary complexes and IGF1 signaling pathways. rhPAPP-A2 treatment induced female-specific increase in body and femur length and reduction in IGF ternary/binary complexes through STAT5-AKT-ERK2-AMPK signaling pathways in liver. The involvement of PAPP-A2 in sex-based growth physiology supports the use of promising drugs to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

Trilobatin contributes to the improvement of myopathy in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti-inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse. Eight-week-old male animals were treated with 160 mg/kg/day of trilobatin for 8 weeks. Control animals were treated with saline. Following treatment, muscle strength, serum creatine kinase (CK) levels, histopathology (necrotic myofibres, regenerated fibres/central nuclei, Feret's diameter and inflammatory area) and the levels of catalase and NF-κB (western blotting) of the quadriceps (QUA), diaphragm (DIA) and tibialis anterior (TA) muscles were measured. TLB was able to significantly increase muscle strength and reduce serum CK levels in dystrophic animals. The QUA of mdx mice showed a reduction in catalase and the number of fibres with a centralized nucleus after treatment with TLB. In the DIA of dystrophic animals, TLB reduced the necrotic myofibres, inflammatory area and NF-κB and increased the number of regenerated fibres and the total fibre diameter. In TA, TLB increased the number of regenerated fibres and reduced catalase levels in these animals. It is concluded that in the mdx experimental model, treatment with TLB was beneficial in the treatment of DMD.

Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks.

Aging populations worldwide are placing age-related diseases at the forefront of the research agenda. The therapeutic potential of natural substances, especially propolis and its components, has led to these products being promising agents for alleviating several cellular and molecular-level changes associated with age-related diseases. With this in mind, scientists have introduced a contextual framework to guide future aging research, called the hallmarks of aging. This framework encompasses various mechanisms including genomic instability, epigenetic changes, mitochondrial dysfunction, inflammation, impaired nutrient sensing, and altered intercellular communication. Propolis, with its rich array of bioactive compounds, functions as a potent functional food, modulating metabolism, gut microbiota, inflammation, and immune response, offering significant health benefits. Studies emphasize propolis' properties, such as antitumor, cardioprotective, and neuroprotective effects, as well as its ability to mitigate inflammation, oxidative stress, DNA damage, and pathogenic gut bacteria growth. This article underscores current scientific evidence supporting propolis' role in controlling molecular and cellular characteristics linked to aging and its hallmarks, hypothesizing its potential in geroscience research. The aim is to discover novel therapeutic strategies to improve health and quality of life in older individuals, addressing existing deficits and perspectives in this research area.

Bitter ginger (Zingiber zerumbet) for patients with solid tumors with no treatment options: A pilot clinical study.

INTRODUCTION: Zerumbone is a natural compound found in bitter ginger plants (Zingiber zerumbet) that shows antiproliferative, antioxidant, anti-inflammatory, and analgesic properties. We aimed to investigate the role of zerumbone in improving the quality of life and symptom control in cancer patients with no treatment options. METHODS: We conducted a pilot, non-randomized, single-center, open prospective, and systematic study on the use of 400 mg of zerumbone twice a day. RESULTS: The study included 35 patients (mean age, 68 years; 64% men), of which 16 completed the eight-week study. The intention-to-treat population showed no significant changes in weight or sleep quality over the eight-week study. Assessments performed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) showed significant improvements in the quality of life in the global (p = 0.072), activity (p = 0.0393), social (p = 0.0001), and emotional (p = 0.0023) dimensions. The Hospital Anxiety and Depression Scale (HADS) questionnaire scores showed significant improvement in anxiety (p = 0.032) and depression (p = 0.021), while the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire scores also indicated a significant improvement (p = 0.001). Bitter ginger showed low toxicity. CONCLUSIONS: Bitter ginger showed promising results in improving the quality of life and reducing symptoms of anxiety and depression in the study population. A randomized placebo-controlled study is necessary to confirm these results. This trial was registered under the number FMABC: CAAE - 93459418.00000082, at ISRCTN (BIOMED CENTRAL) NUMBER 4388 (03/07/23) and at Plataforma Brasil (https://plataformabrasil.saude.gov.br/login.jsf).

Effect of Brazilian green propolis in chronic ulcer treatment: a randomized clinical trial / Efecto delpropóleo verde brasileño en el tratamiento de úlceras crónicas: ensayo clínico aleatorizado / Efeito da própolis verde brasileira no tratamento de úlceras crônicas: ensaio clínico randomizado

ABSTRACT Objective: to assess the effectiveness of 5% Brazilian green propolis (ointment) in individuals with chronic ulcers. Methods: a randomized clinical trial, developed with 40 patients randomized equally to control group (treated with essential fatty acid) and experimental group (treated with 5% green propolis) for 30 days. The outcomes of interest were sociodemographic, clinical and laboratory characteristics, lesion characteristics, such as type of tissue in the bed, presence of exudate, edge characteristics, microbial content and pain. Results: regarding sociodemographic, clinical and laboratory characteristics, the two groups did not show statistically significant differences. After assessment in 30 days, an effect was observed for both treated groups, but for the experimental group, greater effectiveness in terms of the type of tissue in the bed, type of exudate, edge characteristics, microbial content and pain. Conclusion: propolis-based ointment showed a healing effect, presenting itself as a potential tool in healing chronic ulcers.

RESUMEN Objetivo: evaluar la eficacia del propóleo (ungüento) verde brasileño al 5% en personas con úlceras crónicas. Métodos: ensayo clínico aleatorizado, desarrollado con 40 pacientes aleatorizados por igual al grupo control (tratados con ácidos grasos esenciales) y al grupo experimental (tratados con 5% de propóleo verde) durante 30 días. Los resultados de interés fueron características sociodemográficas, clínicas y de laboratorio, características de la lesión, tales como tipo de tejido en el lecho, presencia de exudado, características del borde, contenido microbiano y dolor. Resultados: en cuanto a las características sociodemográficas, clínicas y de laboratorio, los dos grupos no mostraron diferencias estadísticamente significativas. Luego de la evaluación en 30 días, se observó efecto para ambos grupos tratados, pero para el grupo experimental mayor efectividad en cuanto al tipo de tejido del lecho, tipo de exudado, características de los bordes, contenido microbiano y dolor. Conclusion: la pomada a base de propóleo mostró un efecto curativo, presentándose como una herramienta potencial en la curación de úlceras crónicas.

RESUMO Objetivo: avaliar a eficácia da própolis verde brasileira a 5% (pomada) em indivíduos com úlceras crônicas. Métodos: ensaio clínico randomizado, desenvolvido com 40 pacientes aleatorizados igualmente para grupo controle (tratado com ácido graxo essencial) e grupo experimental (tratado com própolis verde a 5%) por 30 dias. Os desfechos de interesse foram características sociodemográficas, clínicas e laboratoriais, características das lesões, como tipo de tecido no leito, presença de exsudato, características da borda, conteúdo microbiano e dor. Resultados: quanto às características sociodemográficas, clínicas e laboratoriais, os dois grupos não apresentaram diferença estatisticamente significativas. Após avaliação em 30 dias, observou-se efeito para os dois grupos tratados, porém, para o grupo experimental, maior eficácia quanto ao tipo de tecido no leito, tipo de exsudato, característica da borda, conteúdo microbiano e dor. Conclusão: a pomada a base de própolis mostrou efeito cicatrizante, apresentando-se como potencial instrumento na cicatrização de úlceras crônicas.

Fracture of the fabella with radiologic and MRI.

The fabella is an inconstant sesamoid bone. A handful of cases have been reported so far describing fabella fracture, usually involving high energy mechanism or stress fractures after total knee arthroplasty. This paper presents a fabella fracture in a man in his 40s after suffering a car crash, the clinical and radiographic presentation, treatment and complete recovery at 4-months follow-up.

Relationship of irisin expression with metabolic alterations and cardiovascular risk in type 2 diabetes mellitus: a preliminary study.

OBJECTIVE: The aim of this study was to investigate the role of irisin in type 2 diabetes mellitus and its association with metabolic alterations and obesity. METHODS: A cross-sectional case-control study was conducted on participants treated at Centro Universitário FMABC between August 2018 and July 2019, by comparing a control group (n=14) with type 2 diabetes mellitus patients (n=16). The control group consisted of participants aged above 21 years with no chronic diseases, diabetes, smoking, or illicit drug use. The type 2 diabetes mellitus group included patients aged above 21 years, who were diagnosed with type 2 diabetes for at least 5 years (glycated hemoglobin>7%). Exclusion criteria were not willing to continue, recent hospitalization, and failure to meet inclusion criteria. Biochemical parameters included blood glucose, glycated hemoglobin, plasma irisin levels, and irisin gene expression in peripheral blood. RESULTS: Type 2 diabetes mellitus patients exhibited significantly higher plasma glucose levels [143 (40) vs. 92 (13) mg/dL, *p<0.05] and glycated hemoglobin levels [7.1% (1.6) vs. 5.6% (0.5), *p<0.05] compared to the control group. Irisin gene expression in type 2 diabetes mellitus patients was lower 0.02288 (0.08050) than the control group 8.506e-006 (1.412e-005) (p=0.06). Correlation analysis revealed a positive association between irisin expression and body mass index in type 2 diabetes mellitus (Rho=0.5221, 95%CI -0.058 to 0.838, p=0.06), while plasma irisin showed a negative correlation with body mass index (Rho=-0.656, 95%CI -0.836 to 0.215, p=0.03). No significant correlations were found between plasma glucose or glycated hemoglobin levels and irisin expression. CONCLUSION: The data suggests that body mass index directly influences plasma irisin levels and the regulation of irisin gene expression, possibly linking irisin to adiposity changes observed in obesity-related type 2 diabetes mellitus.

Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile.

Hyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy-DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult-DMA-or elderly-DME and control sham adult-CSA-or control sham elderly-CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1, MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies.

Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report.

BACKGROUND: The BRCA2 gene is a well-known tumor suppressor gene implicated in breast and ovarian cancers. BRCA1/2 mutations can be sensitive to poly ADP-ribose polymerase (PARP) inhibitors such as olaparib. However, some of these patients develop resistance to this treatment and an essential factor contributing to acquired insensitivity is the occurrence of reversion mutations in the BRCA1/2 genes. CASE PRESENTATION: We report the case of a 65-year-old Brazilian female patient who had previously been diagnosed with metastatic lung carcinoma carrying a BRCA2 mutation that had extended to the central nervous system. Following disease progression, olaparib was administered, resulting in a stabilizing effect on her condition for ~ 30 months. During a routine follow-up, a new triple-negative breast tumor was found. Genetic testing revealed the presence of two distinct BRCA2 gene mutations in the breast tumor. The original mutation (p.Val220Ilefs4) led to a frameshift, culminating in the production of a truncated and non-functional BRCA2 protein; the second mutation, K437fs22, rectified the reading frame of exon 11. Consequently, Rad51 could properly bind to BRCA2-an essential protein crucial for DNA repair. This restoration resulted in a functional BRCA2 protein, effectively elucidating the clinical resistance observed in the new breast tumor in this case. CONCLUSIONS: This case report highlights the clinical significance of comprehensive next-generation sequencing analyses for lung adenocarcinomas, both at diagnosis and upon progression. Such analyses enable informed decisions regarding targeted therapies and facilitate a deeper comprehension of resistance mechanisms.

Survivin expression as a prognostic marker for breast cancer.

OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Detection of Water Contaminants by Organic Transistors as Gas Sensors in a Bottom-Gate/Bottom-Contact Cross-Linked Structure.

Detecting volatile organic compounds is a fundamental step in water quality analysis. Methylisoborneol (MIB) provides a lousy odor to water, whereas geosmin (GEO) is responsible for its sour taste. A widely-used technique for their detection is gas-phase chromatography. On the other hand, an electronic nose from organic thin-film transistors is a cheaper and faster alternative. Poly(2,5-bis(3-tetradecyl-thiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT-C14) features semiconducting properties suitable for organic electronics. However, in order to expose the active layer in a bottom-gate transistor structure with photolithographically patterned electrodes, a cross-linked dielectric such as poly(4-vinyl phenol) (PVP) is necessary. In this work, the cross-linking was demonstrated using FTIR and Raman spectroscopies, as well as high-k capacitors with a dielectric constant of 5.3. The presence of enhanced crystallinity with terrace formation in the semiconducting film was confirmed with UV-visible spectrophotometry, atomic force microscopy, and X-ray diffraction. Finally, for the first time, a PBTTT-C14 transistor on cross-linked PVP was shown to respond to isoborneol with a sensitivity of up to 6% change in mobility per ppm. Due to its similarity to MIB, a system comprising these sensors must be investigated in the future as a tool for sanitation companies in real-time water quality monitoring.

Survivin expression as a prognostic marker for breast cancer

SUMMARY OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Oleoylethanolamide restores stress-induced prepulse inhibition deficits and modulates inflammatory signaling in a sex-dependent manner.

RATIONALE: Social stress contributes to the development of depressive and anxiety symptomatology and promotes pro-inflammatory signaling in the central nervous system. In this study, we explored the effects of a lipid messenger with anti-inflammatory properties - oleoylethanolamide (OEA) - on the behavioral deficits caused by social stress in both male and female mice. METHODS: Adult mice were assigned to an experimental group according to the stress condition (control or stress) and treatment (vehicle or OEA, 10 mg/kg, i.p.). Male mice in the stress condition underwent a protocol consisting of four social defeat (SD) encounters. In the case of female mice, we employed a procedure of vicarious SD. After the stress protocol resumed, anxiety, depressive-like behavior, social interaction, and prepulse inhibition (PPI) were assessed. In addition, we characterized the stress-induced inflammatory profile by measuring IL-6 and CX3CL1 levels in the striatum and hippocampus. RESULTS: Our results showed that both SD and VSD induced behavioral alterations. We found that OEA treatment restored PPI deficits in socially defeated mice. Also, OEA affected differently stress-induced anxiety and depressive-like behavior in male and female mice. Biochemical analyses showed that both male and female stressed mice showed increased levels of IL-6 in the striatum compared to control mice. Similarly, VSD female mice exhibited increased striatal CX3CL1 levels. These neuroinflammation-associated signals were not affected by OEA treatment. CONCLUSIONS: In summary, our results confirm that SD and VSD induced behavioral deficits together with inflammatory signaling in the striatum and hippocampus. We observed that OEA treatment reverses stress-induced PPI alterations in male and female mice. These data suggest that OEA can exert a buffering effect on stress-related sensorimotor gating behavioral processing.