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Heart failure (HF) is the leading cause of morbidity and mortality in cardiovascular diseases, being responsible for many hospitalizations annually. HF is considered a public health problem with significant economic and social impact, which makes searches essential for strategies that improve the ability to predict and diagnose HF. In this way, biomarkers can help in risk stratification for a more personalized approach to patients with HF. Preclinical and clinical evidence shows the participation of matrix metalloproteinase 9 (MMP-9) in the HF process. In this review, we will demonstrate the critical role that MMP-9 plays in cardiac remodeling and dysfunction. We will also show its importance as a blood biomarker in acute and chronic HF patients.

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Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent's total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications.

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BACKGROUND: Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. MATERIAL AND METHODS: From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5-60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. RESULTS: All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1-2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1-40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). CONCLUSIONS: Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes.

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Hypertension is one of the leading risk factors for the development of heart failure. Despite being a multifactorial disease, in recent years, preclinical and clinical studies suggest strong evidence of the pivotal role of inflammatory cells and cytokines in the remodeling process and cardiac dysfunction. During the heart remodeling, activation of extracellular matrix metalloproteinases (MMPs) occurs, with MMP-2 being one of the main proteases secreted by cardiomyocytes, fibroblasts, endothelial and inflammatory cells in cardiac tissue. In this review, we will address the process of cardiac remodeling and injury induced by the increase in MMP-2 and the main signaling pathways involving cytokines and inflammatory cells in the process of transcriptional, secretion and activation of MMP-2. In addition, an interaction and coordinated action between MMP-2 and inflammation are explored and significant in maintaining the cardiac cycle. These observations suggest that new therapeutic opportunities targeting MMP-2 could be used to reduce inflammatory biomarkers and reduce cardiac damage in hypertension.

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OBJECTIVE: To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. MATERIALS AND METHODS: Patients with spine metastases treated with SBRT (1 fraction/18 Gy or 5 fractions/7 Gy) during the last 12 years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. RESULTS: From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18 Gy (75%) or 5 fractions/7 Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2 months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3 years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). CONCLUSIONS: According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.

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Drug abuse is a global public health problem among adolescents, with alcohol often used in association with other psychotropic drugs, such as ketamine. Considering the scarcity of evidence, this study aimed to investigate emotional behavioral effects induced by ethanol plus ketamine co-abuse, as well as oxidative biochemistry, and neurotrophic mediator in the prefrontal cortex and hippocampus in the early withdrawal of adolescent female rats. Animals were divided into control, ethanol, ketamine, and ethanol plus ketamine groups. The protocol administration was performed for 3 consecutive days (binge-like pattern). Behavioral assays of open field, elevated plus maze, and forced swim test were performed. After that, the prefrontal cortex and hippocampus were collected to evaluate oxidative biochemistry (reactive oxygen species-ROS; Antioxidant capacity against peroxyl radicals-ACAP; and lipid peroxidation). We found that isolated or combined ethanol and ketamine exposure displayed anxiety- and depressive-like profile, in a non-synergistically manner during early withdrawal. However, oxidative damage was aggravated in the co-administered animals than in isolated exposed subjects. We concluded that ethanol plus ketamine co-abuse may intensify oxidative damage in the hippocampus and prefrontal cortex in the early withdrawal of adolescent female rats, which was not reflected in the emotional behavioral phenotype. DATA AVAILABILITY STATEMENT: The datasets used and/or analyzed during the current investigation are available upon reasonable request from the corresponding author.

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Ketamine, also called 'K-powder' by abusers, an analog of phencyclidine, primarily acts as an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, therapeutically used as an anesthetic agent. Ketamine also stimulates the limbic system, inducing hallucinations and dissociative effects. At sub-anesthetic doses, ketamine also displays hallucinatory and dissociative properties, but not loss of consciousness. These behavioral consequences have elicited its recreational use worldwide, mainly at rave parties. Ketamine is generally a drug of choice among teenagers and young adults; however, the harmful consequences of its recreational use on adolescent central nervous systems are poorly explored. Thus, the aim of the present study was to characterize the behavioral and biochemical consequences induced by one binge-like cycle of ketamine during the early withdrawal period in adolescent female rats. Adolescent female Wistar rats (n = 20) received intraperitoneally administered ketamine (10 mg/kg/day) for 3 consecutive days. Twenty-four hours after the last administration of ketamine, animals were submitted to behavioral tests in an open field, elevated plus-maze, and forced swimming test. Then, animals were intranasally anesthetized with 2% isoflurane and euthanized to collect prefrontal cortex and hippocampus to assess lipid peroxidation, antioxidant capacity against peroxyl radicals, reactive oxygen species, reduced glutathione, and brain-derived neurotrophic factor (BDNF) levels. Our results found that 24 h after recreational ketamine use, emotional behavior disabilities, such as anxiety- and depression-like profiles, were detected. In addition, spontaneous ambulation was reduced. These negative behavioral phenotypes were associated with evidence of oxidative stress on the prefrontal cortex and hippocampus.

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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.

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Aedes aegypti L. (Diptera: Culicidae) is an important transmitter of diseases in tropical countries and controlling the larvae of this mosquito helps to reduce cases of diseases such as dengue, zika and chikungunya. Thus, the present study aimed to evaluate the larvicidal potential of the essential oil (EO) of Ocimum basilicum var. minimum (L.) Alef. The EO was extracted by stem distillation and the chemical composition was characterized by gas chromatography coupled with mass spectrometry (GC/MS and GC-FID). The larvicidal activity of EO was evaluated against third instar Ae. aegypti following World Health Organization (WHO) standard protocol and the interaction of the major compounds with the acetylcholinesterase (AChE) was evaluated by molecular docking. The predominant class was oxygenated monoterpenes with a concentration of 81.69% and the major compounds were limonene (9.5%), 1,8-cineole (14.23%), linalool (24.51%) and methyl chavicol (37.41%). The O. basilicum var. minimum EO showed unprecedented activity against third instar Ae. aegypti larvae at a dose-dependent relationship with LC50 of 69.91 (µg/mL) and LC90 of 200.62 (µg/mL), and the major compounds were able to interact with AChE in the Molecular Docking assay, indicating an ecological alternative for mosquito larvae control.

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Methylmercury (MeHg) is the most common organic form of mercury (Hg) that humans are exposed and is considered an environmental pollutant. Several populations that live in endemic regions of MeHg exposure are subject to the toxicant for long periods, including pregnant women and children, causing damage to several organs during early periods of development. Alveolar bone is an essential structure for the oral cavity, responsible for supporting teeth and masticatory forces. However, evidence on the effects of MeHg on alveolar bone and the intrauterine and lactation period is lacking. Thus, this study aimed to investigate the effects of MeHg exposure during gestation and lactation on the developing alveolar bone of offspring rats after maternal exposure. Dams were exposed during 41 days of pregnancy and lactation, and the mandibles of the offspring were collected. The alveolar bone was analyzed by Fourier Transform Infrared Spectroscopy to evaluate the physicochemical composition; by Scanning Electron Microscopy for ultrastructural evaluation; by histopathological, histochemical, and morphometric for tissue analyses. In addition, bone quality was assessed by X-ray microtomography. MeHg exposure altered the mineral composition and caused histological damage associated with a lower quantity and thickness of bone trabeculae, as well as reduced osteocyte density and collagen fiber content. A reduction in trabecular thickness and bone volume and an increase in trabecular spaces were observed and were associated with anatomical compromise of the vertical bone dimensions. Thus, the results suggest that the developing alveolar bone is susceptible to the toxic effects of MeHg when organisms are exposed during intrauterine and lactation periods. From a translational perspective, these changes in the alveolar bone can help us understand possible abnormalities induced by toxic metals and highlight the need for care for structures other than those already seen as targets for damage triggered by environmental MeHg exposure.

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