ABSTRACT
The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.
Subject(s)
Alzheimer Disease , Cognition Disorders , Mice , Animals , Acetylcholinesterase/metabolism , Streptozocin/toxicity , Cognition Disorders/chemically induced , Cognition Disorders/drug therapy , Oxidative Stress , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Hippocampus , Disease Models, AnimalABSTRACT
Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy. We previously uncovered that acetate-induced mitochondrial-mediated apoptosis in CRC cells is significantly enhanced by the inhibition of the lysosomal protease cathepsin D (CatD), which indicates both mitochondria and the lysosome are involved in the regulation of acetate-induced apoptosis. Herein, we sought to determine whether mitochondrial function affects CatD apoptotic function. We found that enhancement of acetate-induced apoptosis by CatD inhibition depends on oligomycin A-sensitive respiration. Mechanistically, the potentiating effect is associated with an increase in cellular and mitochondrial superoxide anion accumulation and mitochondrial mass. Our results provide novel clues into the regulation of CatD function and the effect of tumor heterogeneity in the outcome of combined treatment using acetate and CatD inhibitors.
Subject(s)
Apoptosis , Cathepsin D , Colorectal Neoplasms , Mitochondria , Oligomycins , Humans , Acetates/pharmacology , Apoptosis/drug effects , Cathepsin D/metabolism , Cathepsin D/antagonists & inhibitors , Cell Line, Tumor , Cell Respiration/drug effects , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Mitochondria/metabolism , Mitochondria/drug effects , Oligomycins/pharmacologyABSTRACT
Background: Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex and cerebellum is gaining prominence in the literature due to its potential to favor learning and motor performance. If administered during motor training, tDCS is capable of increasing the effect of training. Considering the motor impairment presented by children with Autism Spectrum Disorders (ASD), atDCS applied during motor training may contribute to the rehabilitation of these children. However, it is necessary to examine and compare the effects of atDCS over the motor cortex and the cerebellum on the motor skills of children with ASD. This information may benefit future clinical indications of tDCS for rehabilitation of children with ASD. The aim of the proposed study is to determine whether anodal tDCS over the primary motor cortex and cerebellum can enhance the effects of gait training and postural control on motor skills, mobility, functional balance, cortical excitability, cognitive aspects and behavioral aspects in children with ASD. Our hypothesis is the active tDCS combined with motor training will enhance the performance of the participants in comparison to sham tDCS. Methods and design: A randomized, sham-controlled, double-blind clinical trial will be conducted involving 30 children with ASD that will be recruited to receive ten sessions of sham or ten sessions of active anodal tDCS (1 mA, 20 min) over the primary motor cortex or cerebellun combined with motor training. The participants will be assessed before as well as one, four and eight weeks after the interventions. The primary outcome will be gross and fine motor skills. The secondary outcomes will be mobility, functional balance, motor cortical excitability, cognitive aspects and behavioral aspects. Discussion: Although abnormalities in gait and balance are not primary characteristics of ASD, such abnormalities compromise independence and global functioning during the execution of routine activities of childhood. If demonstrated that anodal tDCS administered over areas of the brain involved in motor control, such as the primary motor cortex and cerebellum, can enhance the effects of gait and balance training in only ten sessions in two consecutive weeks, the clinical applicability of this stimulation modality will be expanded as well as more scientifically founded.Clinical trial registration February 16, 2023 (https://ensaiosclinicos.gov.br/rg/RBR-3bskhwf).
ABSTRACT
Chronic skin wounds, namely diabetic/non-diabetic ulcers and post-surgical wounds, present key obstacles to achieve anatomic and functional regeneration within approximately 3 months [...].
ABSTRACT
Oral diseases affect over three billion people worldwide, making it one of the most common infections. Recent studies show that one approach to reducing the risk of chronic infections, such as caries, gingivitis, periodontitis, and halitosis, is to control the ecology of the oral microbiome instead of completely removing both the harmful and beneficial microorganisms. This is based on the knowledge that oral diseases are not caused by a single pathogen but rather by a shift in the homeostasis of the entire microbiota, a process known as dysbiosis. Consequently, it is of the utmost importance to implement strategies that are able to prevent and control oral dysbiosis to avoid serious complications, including heart, lung, and other systemic diseases. Conventional treatments include the use of antibiotics, which further disrupt the equilibrium in the oral microbiota, together with the mechanical removal of the decayed cavity area following its formation. Therefore, it is imperative to implement alternative strategies with the potential to overcome the disadvantages of the current therapy, namely, the use of broad-spectrum antibiotics. In this sense, probiotics and postbiotics have received particular attention since they can modulate the oral microbiota and decrease the dysbiotic rate in the oral cavity. However, their mechanisms of action need to be addressed to clarify and drive their possible applications as preventive strategies. In this sense, this review provides an overview of the potential of probiotics and postbiotics, focusing on their antimicrobial and antibiofilm activities as well as their ability to modulate the inflammatory response. Finally, it also showcases the main advantages and disadvantages of orodispersible films-a promising delivery mechanism for both probiotics and postbiotics to target oral dysbiosis.
Subject(s)
Microbiota , Periodontitis , Humans , Dysbiosis/prevention & control , Microbiota/physiology , Anti-Bacterial Agents/therapeutic useABSTRACT
The aim of this study was to investigate the effects of inorganic mercury (Hg2+) exposure on biochemical parameters of dams and their offspring exposed to metal in drinking water. Female Wistar rats were exposed to 0, 10, and 50 µg Hg2+/mL (as HgCl2) for 42 days corresponding to gestational (21 days) and lactational (21 days) periods. The offspring were sacrificed on postnatal days 10, 20, 30, and 40. Dams exposed to Hg2+ presented a decrease in water intake in gestation [total: F(2,19) = 15.84; p ≤ 0.0001; daily: F(2,21) = 12.71; p = 0.0002] and lactation [total: F(2,19) = 4.619; p = 0.024; daily: F(2,21) = 5.309; p = 0.0136] without alteration in food intake. Dams exposed to 50 µg Hg2+/mL had an increase in kidney total [F(2,21) = 8.081; p = 0.0025] and relative [F(2,21) = 14.11; p = 0.0001] weight without changes in biochemical markers of nephrotoxicity. Moreover, dams had an increase in hepatic [F(2,10) = 3.847; p = 0.0577] and renal [F(2,11) = 6.267; p = 0.0152] metallothionein content concomitantly with an increase in renal Hg levels after Hg2+ exposure. Regarding offspring, the exposure to Hg2+in utero and breast milk increased the relative liver [F(2,18) = 5.33; p = 0.0152] and kidney [F(2,18) = 3.819; p = 0.0415] weight only on the postnatal day 40. In conclusion, dams were able to handle the Hg2+ avoiding the classic Hg2+ toxic effects as well as protecting the offspring. We suggest that this protection is related to the hepatic and renal metallothionein content increase.
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Pesticide exposure has deleterious effects on human health and development; however, no review has been conducted on human exposure to pesticides and the risk of congenital malformations and cancer in the same cohort. We systematically reviewed the evidence for this relationship following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases, namely, PubMed, Scopus, Cochrane Library, and BVS, were searched for studies deposited till July 2020 that examined the influence of pesticide exposure on congenital malformations and cancer outcomes in the same cohort. Seven studies were systematically included in this review. Among these, four were case-control studies, two were cross-sectional studies, and one was a longitudinal cohort study. The sources of contamination were food, water, or exposure during agricultural work. A link between the occurrence of cancer, congenital malformations, and exposure to pesticides was observed in most studies.
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OBJECTIVE: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. METHODS: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. RESULTS: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. CONCLUSIONS: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. SIGNIFICANCE: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.
Subject(s)
Telemedicine , Transcranial Direct Current Stimulation , Consensus , Electric Stimulation , Humans , Transcranial Direct Current Stimulation/methodsABSTRACT
Recreating the biological complexity of living bone marrow (BM) in a single in vitro strategy has faced many challenges. Most bioengineered strategies propose the co-culture of BM cellular components entrapped in different matrices limiting their migration and self-organization capacity or in open scaffolds enabling their escaping. We propose a methodology for fabricating a "human bone marrow-in-a-liquefied-capsule" to overcome these challenges, embracing the most important BM components in a single platform. Since free dispersion of the cells within the BM is an essential feature to maintain their in vivo properties, this platform provides a liquefied environment for the encapsulated cells to move freely and self-organize. Inside liquefied capsules, an engineered endosteal niche (eEN) is co-cultured with human umbilical cord cells, including endothelial cells and hematopoietic stem and progenitor cells (HSPCs). Two different human-like BM niches were recreated under static and dynamic systems. Although the culture of the engineered BM capsules (eBMC) in these different environments did not change the structural and compositional features of the BM niches, the biophysical stimulation potentiated the cellular intercommunication and the biomolecules secretion, demonstrating an enhanced in vitro bio performance. Moreover, while the eBMC without HSPCs provided the secretion of hematopoietic supportive factors, the presence of these cells recapitulated more closely the biological complexity of the native BM niches. This functional eBMC approach is an innovative platform capable of investigating several components and interactions of BM niches and how they regulate BM homeostasis and hematopoiesis. STATEMENT OF SIGNIFICANCE: The recapitulation of the multifaceted bone marrow (BM) microenvironment under in vitro conditions has gained intensive recognition to understand the intrinsic complexity of the native BM. While conventional strategies do not recapitulate the BM osteovascular niches nor give the cellular components a free movement, we report for the first time the development of human bone marrow-in-a-liquefied-capsule to overcome such limitations. Our engineered BM capsules (eBMC) partially mimic the complex structure, composition, and spatial organization of the native osteovascular niches present in the BM. This strategy offers a platform with physiological relevance to exploit the niches' components/networks and how they regulate the hematopoiesis and the initiation/progression of various BM-related pathologies.
Subject(s)
Bone Marrow , Stem Cell Niche , Bioengineering , Bone Marrow Cells , Endothelial Cells , Hematopoietic Stem Cells , HumansABSTRACT
Bone presents an intrinsic ability for self-regeneration and repair, however critical defects and large fractures require invasive and time-consuming clinical interventions. As an alternative to current therapy, bone tissue engineering (BTE) has primarily aimed to recreate the bone microenvironment by delivering key biomolecules and/or by modification of scaffolds to guide cell fate towards the osteogenic lineage or other phenotypes that may benefit the bone regeneration mechanism. Considering that bone cells communicate, in their native microenvironment, through biochemical and physical signals, most strategies fail when considering only chemical, geometrical or mechanical cues. This is not representative of the physiological conditions, where the cells are simultaneously in contact and stimulated by several cues. Therefore, this review explores the synergistic effect of biochemical/physical cues in regulating cellular events, namely cell adhesion, proliferation, osteogenic differentiation, and mineralization, highlighting the importance of the combined modifications for the development of innovative bone regenerative therapies.
Subject(s)
Osteogenesis , Tissue Scaffolds , Bone Regeneration , Cell Differentiation , Cues , Osteogenesis/genetics , Tissue Engineering , Tissue Scaffolds/chemistryABSTRACT
Toxic metals, such as mercury (Hg), lead (Pb), cadmium (Cd), and copper (Cu), are widespread in the biosphere, and human activities have contributed to their continuous release into the ecosystems. Metal-induced toxicity has been extensively studied in mammals; however, the effects of these metals on insects' behavior have been explored to far lesser degree. As the main mechanism of toxicity, the cationic metals, explored in this review, have high affinity for thiol-containing molecules, disrupting the function of several proteins and low-molecular-weight thiol-containing molecules. Existing literature has corroborated that Hg, Pb, Cd, and Cu can disrupt locomotor and mating behaviors, but their effects on insects' memory and learning have yet to be fully characterized. Though field studies on metal-induced toxicity in insects are limited, results from Drosophila melanogaster as an experimental model suggest that insects living in contaminated environments can have behavioral foraging and reproductive deficits, which may cause population decline. In this review, we address the interaction between metals and endogenous thiol groups, with emphasis on alterations in insect behavior.
Subject(s)
Cadmium , Mercury , Animals , Drosophila melanogaster , Ecosystem , Humans , Lead , Mammals , Sulfhydryl CompoundsABSTRACT
The aim of this study was to evaluate the effects of Pb exposure on full-scale IQ score in pediatric subjects. Following PRISMA guidelines, the data from January 2010 to April 2020 were systematically searched and collected on electronic databases (PubMed, Scopus, and Embase). The eligibility criteria included cross-sectional, cohort, and case-control studies that were published in English, from 2010 to 2020, that analyzed the blood Pb levels of pediatric subjects (0-19 years) and possible changes in the full-scale IQ score. In this study, 2174 scientific papers were collected from three electronic databases. From those, 726 were duplicates and 1421 were excluded because they did not meet the eligibility criteria, resulting in a total of 27 papers, from which, seven were used to perform the meta-analysis. The 27 scientific papers systematically selected for this study were separated by the country where the study was realized in developed and underdeveloped/developing countries. In the underdeveloped/developing countries the blood Pb levels are higher and showed a greater variation (1.30-11.66 µgPb/dL of blood) than in countries with higher development index (0.57-4.80 µgPb/dL of blood). The full-scale IQ score are inversely proportional to the blood Pb values, and it is possible to see that in the underdeveloped/developing countries the full-scale IQ score showed lower values and greater variation (59.2-111) compared to the individuals from developed countries (91.9-114.5). In conclusion, it was observed that blood Pb levels alter the full-scale IQ score. Thus, policies for the prevention of environmental contamination and the reduction of Pb exposure must be taken, mainly, in underdeveloped/developing countries.
Subject(s)
Developing Countries , Intelligence , Child , Cohort Studies , Cross-Sectional Studies , Environmental Pollution , HumansABSTRACT
The repair process of bone fractures is a complex biological mechanism requiring the recruitment and in situ functionality of stem/stromal cells from the bone marrow (BM). BM mesenchymal stem/stromal cells have been widely explored in multiple bone tissue engineering applications, whereas the use of hematopoietic stem cells (HSCs) has been poorly investigated in this context. A reasonable explanation is the fact that the role of HSCs and their combined effect with other elements of the hematopoietic niches in the bone-healing process is still elusive. Therefore, in this review we intend to highlight the influence of HSCs in the bone repair process, mainly through the promotion of osteogenesis and angiogenesis at the bone injury site. For that, we briefly describe the main biological characteristics of HSCs, as well as their hematopoietic niches, while reviewing the biomimetic engineered BM niche models. Moreover, we also highlighted the role of HSCs in translational in vivo transplantation or implantation as promoters of bone tissue repair. Impact statement The ability of bone to natural self-heal depends on the size and stabilization level of the tissue fracture, and it is impaired in several pathophysiological conditions. Considering that the available treatment options have demonstrated limited regenerative performance, the hematopoietic stem cells (HSCs) co-cultured in different tissue engineering strategies have emerged as a powerful tool to promote effective bone regeneration and healing. Here, we reviewed the most important biomimetic bone-marrow hematopoietic niches and showed the regenerative potential of these cells, both in vitro and in translational in vivo transplantation/implantation approaches. This knowledge encourages the development of new HSC-related bone regenerative therapies.
Subject(s)
Hematopoietic Stem Cells , Mesenchymal Stem Cells , Bone Marrow , Bone Marrow Cells , Bone Regeneration , HumansABSTRACT
The bone microenvironment is characterized by an intricate interplay between cellular and noncellular components, which controls bone remodeling and repair. Its highly hierarchical architecture and dynamic composition provide a unique microenvironment as source of inspiration for the design of a wide variety of bone tissue engineering strategies. To overcome current limitations associated with the gold standard for the treatment of bone fractures and defects, bioengineered bone microenvironments have the potential to orchestrate the process of bone regeneration in a self-regulated manner. However, successful approaches require a strategic combination of osteogenic, vasculogenic, and immunomodulatory factors through a synergic coordination between bone cells, bone-forming factors, and biomaterials. Herein, we provide an overview of (i) current three-dimensional strategies that mimic the bone microenvironment and (ii) potential applications of bioengineered microenvironments. These strategies range from simple to highly complex, aiming to recreate the architecture and spatial organization of cell-cell, cell-matrix, and cell-soluble factor interactions resembling the in vivo microenvironment. While several bone microenvironment-mimicking strategies with biophysical and biochemical cues have been proposed, approaches that exploit the ability of the cells to self-organize into microenvironments with a high regenerative capacity should become a top priority in the design of strategies toward bone regeneration. These miniaturized bone platforms may recapitulate key characteristics of the bone regenerative process and hold great promise to provide new treatment concepts for the next generation of bone implants.
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Platforms with liquid cores are extensively explored as cell delivery vehicles for cell-based therapies and tissue engineering. However, the recurrence of synthetic materials can impair its translation into the clinic. Inspired by the adhesive proteins secreted by mussels, liquefied capsule is developed using gelatin modified with hydroxypyridinones (Gel-HOPO), a catechol analogue with oxidant-resistant properties. The protein-based liquefied macrocapsule permitted the compartmentalization of living cells by an approachable and non-time-consuming methodology resorting to i) superhydrophobic surfaces as a processing platform of hydrogel beads, ii) gelation of gelatin at temperatures < 25 °C, iii) iron coordination of the hydroxypyridinone (HOPO) moieties at physiological pH, and iv) core liquefaction at 37 °C. With the design of a proteolytically degradable shell, the possibility of encapsulating human adipose-derived mesenchymal stem cells (hASC) with and without the presence of polycaprolactone microparticles (µPCL) is evaluated. Showing prevalence toward adhesion to the inner shell wall, hASC formed a monolayer evidencing the biocompatibility and adequate mechanical properties of these platforms for proliferation, diminishing the need for µPCL as a supporting substrate. This new protein-based liquefied platform can provide biofactories devices of both fundamental and practical importance for tissue engineering and regenerative medicine or in other biotechnology fields.
Subject(s)
Mesenchymal Stem Cells , Tissue Engineering , Capsules , Gelatin , Humans , HydrogelsABSTRACT
The Alzheimer's disease is a neurodegenerative condition with severe consequences interfering with patient quality of life. It is characterized as a progressive and irreversible brain disorder hampering memory and thinking, affecting the capacity to perform daily tasks leading to physical and cognitive incapacitation. The conventional treatment occurs by the oral route, but it presents relevant drawbacks such as low bioavailability, fast metabolism, limited brain exposure, and undesirable side effects. The intranasal route has been proposed as a promising alternative to deliver drugs and improve the Alzheimer's disease treatment. Still, there is not a clear alternative delivery system available in the market with advantageous bioavailability and safety. The aim of this review is to perform an overview on the strategies for drug intranasal delivery for Alzheimer's disease treatment. The advantages and disadvantages of this delivery route and the delivery systems developed so far are discussed. A special focus is given on the use of permeation enhancers, the types of intranasal drug delivery devices, as well as possible toxicity concerns.
Subject(s)
Alzheimer Disease , Pharmaceutical Preparations , Administration, Intranasal , Alzheimer Disease/drug therapy , Blood-Brain Barrier , Brain , Drug Delivery Systems , Humans , Quality of LifeABSTRACT
AIM: This study evaluated medication poisoning in paediatric patients through a systematic review and a retrospective documentary analysis in a Brazilian toxicological centre. METHODS: The data were systematically collected on PubMed, Scopus and SciELO databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We included epidemiologic and prevalence studies that were published in English or Portuguese from 2013 to 2017 and covered paediatric patients. The retrospective incidence study was carried out in a Brazilian toxicological centre and was a documentary analysis of paediatric medication poisoning cases from 2005 to 2015. RESULTS: The systematic review comprised 13 papers covering 895 206 poisoning cases from six different countries. The main agents of intoxication were analgesics and antihistamines. The eight papers that explored the reasons for the poisonings showed that 93% of those 762 863 cases were accidental. The Brazilian toxicological centre recorded 443 paediatric patients poisoned by medication such as benzodiazepines, analgesics and antibiotics and found that 63.2% were accidental. However, it agreed with the global findings in many other aspects. CONCLUSION: The systematic review showed a sustained number of paediatric medication toxicity cases worldwide and the key findings were broadly reflected by the retrospective study carried out in the Brazilian toxicological centre.
Subject(s)
Benzodiazepines , Poisoning , Analgesics , Brazil , Child , Humans , Incidence , Poisoning/epidemiology , Retrospective StudiesABSTRACT
Snakes of the genus Lachesis, commonly known as bushmasters, are the largest venomous snakes in the Americas. Because these snakes have their habitats in areas of remote forests they are difficult to find, and consequently there are few studies of Lachesis taxa in their natural ecosystems. Bushmasters are distributed in tropical forest areas of South and Central America. In Brazil they can be found in the Amazon Rainforest and the Atlantic Forest. Despite the low incidence of cases, laquetic envenoming causes severe permanent sequelae due to the high amount of inoculated venom. These accidents are characterized by local pain, hemorrhage and myonecrosis that can be confused with bothropic envenomings. However, victims of Lachesis bites develop symptoms characteristic of Lachesis envenoming, known as vagal syndrome. An important message of this bibliographic synthesis exercise is that, despite having the proteomic profiles of all the taxa of the genus available, very few structure-function correlation studies have been carried out. Therefore the motivation for this review was to fill a gap in the literature on the genus Lachesis, about which there is no recent review. Here we discuss data scattered in a number of original articles published in specialized journals, spanning the evolutionary history and extant phylogeographic distribution of the bushmasters, their venom composition and diet, as well as the pathophysiology of their bites to humans and the biological activities and possible biotechnological applicability of their venom toxins.
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Mercury is a hazardous substance that has unique neurodevelopmental toxic effects in humans. However, the precise sequence of molecular events that culminate in Hg-induced neuropathology is still unknown. Though the omics studies have been generating an enormous amount of new data about Hg toxicity, our ability to interpret such a large quantity of information is still limited. In this opinion article, we will reinforce the necessity of new high throughput and accurate analytical proteomic methodologies, especially, thiol and selenol-proteome. Overall, we posit that improvements in thiol- and selenol-proteomic analyses will be pivotal in identifying the primary cellular targets of Hg. However, a better understanding of the complex cascades and molecular pathways involved in its toxicity will require extensive complementary studies in more complex systems.
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Approximately 90% of bladder carcinomas are of the urothelial carcinoma type, which are characterized by high rates of recurrence and predisposition to progress to invasive tumors, representing one of the most costly neoplasms for health systems. Intravesical chemotherapy is a standard for the treatment of non-invasive bladder cancer. However, chemotherapy is usually aggressive and cytotoxic, which increases the death rates caused by cancer. Heterocyclic compounds which exhibit favorable pharmacokinetic and pharmacodynamic properties may enhance drug affinity for a target protein by targeting the treatment. Thus, this work presents the synthesis, characterization, and in vitro biological evaluation of new antioxidant (inhibition of lipid peroxidation, scavenging of free radical DPPH, and thiol peroxidase-like activity) and antiproliferative chalcogenobiotin derivatives and tests them against bladder carcinoma 5637 cells. A prominent response was obtained for the selected compounds, with tellurium biotin derivatives displaying effective antioxidant and antiproliferative activity. The effective compounds also demonstrated no toxicity in in vitro or in vivo studies.