Myeloid­derived suppressor cells as targets of emerging therapies and nanotherapies (Review).

Breast cancer (BC) is the leading cause of cancer-related mortality among women worldwide. Immunotherapies are a promising approach in cancer treatment, particularly for aggressive forms of BC with high mortality rates. However, the current eligibility for immunotherapy remains limited to a limited fraction of patients with BC. Myeloid-derived suppressor cells (MDSCs), originating from myeloid cells, are known for their dual role in immunosuppression and tumor promotion, significantly affecting patient outcomes by fostering the formation of premetastatic niches. Consequently, targeting MDSCs has emerged as a promising avenue for further exploration in therapeutic interventions. Leveraging nanotechnology-based drug delivery systems, which excel in accumulating drugs within tumors via passive or active targeting mechanisms, are a promising strategy for the use of MDSCs in the treatment of BC. The present review discusses the immunosuppressive functions of MDSCs, their role in BC, and the diverse strategies for targeting them in cancer therapy. Additionally, the present review discusses future advancements in BC treatments focusing on MDSCs. Furthermore, it elucidates the mechanisms underlying MDSC activation, recruitment and differentiation in BC progression, highlighting the clinical characteristics that render MDSCs suitable candidates for the therapy and targeted nanotherapy of BC.

Long-term disability after cerebral ischemic stroke following a Bothrops atrox snakebite in the Brazilian Amazon.

Bothrops atrox envenomations in the Brazilian Amazon are responsible for a number of local and systemic effects. Among these, stroke presents the worst prognosis for the patient since it may evolve into disabilities and/or premature death. This complication is caused by coagulation disorders and generates hemorrhagic and thrombotic conditions. This study presents a case report of a 54-year-old female patient who presented extensive cerebral ischemia after a B. atrox envenomation that occurred in the state of Amazonas, Brazil. The patient was hospitalized for 102 days, which included a stay in the intensive care unit. Clinical and laboratory findings indicated a thrombogenic coagulopathy. On discharge, the patient had no verbal response, partial motor response, and right hemiplegia. The assessment carried out four years after discharge evidenced incapacitation, global aphasia and bilateral lower and upper limbs showed hypotrophy with a global decrease in strength. Ischemic stroke is a possible complication of B. atrox snakebites even after antivenom treatment, with the potential to cause debilitating long-term consequences.

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction.

Mood disorders and substance use disorder (SUD) are of immense medical and social concern. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, it is only relatively recently that the role of glia in these disorders has attracted attention. Detailed understanding of the glial functions in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, the specific contributions of neurotrophic factors, neuroinflammation, and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes, and synantocytes) on phenotypic manifestation of mood disorders or SUD are emphasized. In addition, use of this knowledge in the potential development of novel therapeutics is touched upon.

Niobic acid as a support for microheterogeneous nanocatalysis of sodium borohydride hydrolysis under mild conditions.

This study explores the stabilization by niobic acid, of Pt, Ni, Pd, and Au nanoparticles (NPs) for the efficient microheterogeneous catalysis of NaBH4 hydrolysis for hydrogen production. Niobic acid is the most widely studied Nb2O5 polymorph, and it is employed here for the first time for this key reaction relevant to green energy. Structural insights from XRD, Raman, and FTIR spectroscopies, combined with hydrogen production data, reveal the role of niobic acid's Brønsted acidity in its catalytic activity. The supported NPs showed significantly higher efficiency than the non-supported counterparts regarding turnover frequency, average hydrogen production rate, and cost. Among the tested NPs, PtNPs and NiNPs demonstrate the most favorable results. The data imply mechanism changes during the reaction, and the kinetic isotope assay indicates a primary isotope effect. Reusability assays demonstrate consistent yields over five cycles for PtNPs, although catalytic efficiency decreases, likely due to the formation of reaction byproducts.

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies identified nAChRs in nonneuronal cell types, including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in the prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and, specifically, their nAChRs in PD pathology and/or treatment.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up.

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

The Phytochemical Agathisflavone Modulates miR146a and miR155 in Activated Microglia Involving STAT3 Signaling.

MicroRNAs (miRs) act as important post-transcriptional regulators of gene expression in glial cells and have been shown to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigated the effects of agathisflavone, a biflavonoid purified from the leaves of Cenostigma pyramidale (Tul.), on modulating the expression of miRs and inflammatory mediators in activated microglia. C20 human microglia were exposed to oligomers of the ß-amyloid peptide (Aß, 500 nM) for 4 h or to lipopolysaccharide (LPS, 1 µg/mL) for 24 h and then treated or not with agathisflavone (1 µM) for 24 h. We observed that ß-amyloid and LPS activated microglia to an inflammatory state, with increased expression of miR-146a, miR-155, IL1-ß, IL-6, and NOS2. Treatment with agathisflavone resulted in a significant reduction in miR146a and miR-155 induced by LPS or Aß, as well as inflammatory cytokines IL1-ß, IL-6, and NOS2. In cells stimulated with Aß, there was an increase in p-STAT3 expression that was reduced by agathisflavone treatment. These data identify a role for miRs in the anti-inflammatory effect of agathisflavone on microglia in models of neuroinflammation and AD.

Beyond land use planning and ecosystem services assessment with the conservation use potential framework: A study in the Upper Rio das Velhas basin, Brazil.

Human actions can damage the ecosystems and affect the services depending on them, with ample detrimental consequences. In earlier studies, the Conservation Use Potential (PCU) framework proved useful in assessing the capacity for aquifer recharge, suitable land uses and resistance to erosion at the river basin scale. On the other hand, the joint analysis of PCU and land uses allowed identifying the adequacy of current uses in relation to suitability (natural uses) in various basins. This was especially useful from the management perspective in basins with environmental conflicts, where current uses differed from suitability, because the PCU indicated how and where the conflicts should be mitigated. Besides the use as management tool, the PCU has potential to shed light over environmental issues such as ecosystem services, but that was not tempted so far. The aim of this work was therefore to bridge that knowledge gap and frame the PCU's application from the standpoint of Ecosystem Services (ES) assessment. We demonstrated how the PCU could be used to improve provision (recharge), support (sustainable agriculture) and regulation (resistance to erosion) services in a specific basin with land use conflicts (the Upper Rio das Velhas basin, located in Minas Gerais, Brazil), through the planning of suitable uses. It was noted that the studied basin is mostly composed of Very Low, Low and Medium potentials. These classes occur because steep slopes, fragile soils and lithologies with high denudation potential and low nutrient supply dominate in the basin. On the other hand, urban sprawl has a negative impact on all ES, while maintaining agricultural areas with appropriate management can effectively regulate erosion. As per the current results, the premise of using the PCU as joint management-environmental tool was fully accomplished, and is recommended a basis for public policy design and implementation in Brazil and elsewhere.

Effect of the Flavonoid Rutin on the Modulation of the Myenteric Plexuses in an Experimental Model of Parkinson's Disease.

Recent discoveries have shown that enteric glial cells play an important role in different neurodegenerative disorders, such as Parkinson's disease (PD), which is characterized by motor dysfunctions caused by the progressive loss of dopaminergic neurons in the substance nigra pars compacta and non-motor symptoms including gastrointestinal dysfunction. In this study, we investigated the modulatory effects of the flavonoid rutin on the behavior and myenteric plexuses in a PD animal model and the response of enteric glia. Adult male Wistar rats were submitted to stereotaxic injection with 6-hydroxydopamine or saline, and they were untreated or treated with rutin (10 mg/kg) for 14 days. The ileum was collected to analyze tissue reactivity and immunohistochemistry for neurons (HuC/HuD) and enteric glial cells (S100ß) in the myenteric plexuses. Behavioral tests demonstrated that treatment with rutin improved the motor capacity of parkinsonian animals and improved intestinal transit without interfering with the cell population; rutin treatment modulated the reactivity of the ileal musculature through muscarinic activation, reducing relaxation through the signaling pathway of nitric oxide donors, and increased the longitudinal contractility of the colon musculature in parkinsonian animals. Rutin revealed modulatory activities on the myenteric plexus, bringing relevant answers regarding the effect of the flavonoid in this system and the potential application of PD adjuvant treatment.

Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Mediastinal T-cell lymphoma in a free-ranging brown howler monkey (Alouatta guariba clamitans).

A free-ranging brown howler monkey (Atelidae: Alouatta guariba clamitans) was necropsied and a mediastinal T-cell lymphoma and esophageal dilation were diagnosed. The case report may contribute to the differential diagnosis of neoplastic and esophageal lesions in non-human primates and highlighted the importance of surveillance of cancer in wildlife.

Heterologous expression and biochemical characterization of the recombinant nucleoside triphosphate diphosphohydrolase 2 (LbNTPDase2) from Leishmania (Viannia) braziliensis.

Leishmania braziliensis is a pathogenic protozoan parasite that causes American Tegumentary Leishmaniasis (ATL), an important tropical neglected disease. ENTPDases are nucleotidases that hydrolyze intracellular and/or extracellular nucleotides. ENTPDases are known as regulators of purinergic signalling induced by extracellular nucleotides. Leishmania species have two isoforms of ENTPDase, and, particularly, ENTPDase2 seems to be involved in infectivity and virulence. In this study, we conducted the heterologous expression and biochemical characterization of the recombinant ENTPDase2 of L. braziliensis (rLbNTPDase2). Our results show that this enzyme is a canonical ENTPDase with apyrase activity, capable of hydrolysing triphosphate and diphosphate nucleotides, and it is dependent on divalent cations (calcium or magnesium). Substrate specificity was characterized as UDP>GDP>ADP>GTP>ATP=UTP. The enzyme showed optimal activity at a neutral to basic pH and was partially inhibited by suramin and DIDS. Furthermore, the low apparent Km for ADP suggests that the enzyme may play a role in adenosine-mediated signalling. The biochemical characterization of this enzyme can open new avenues for using LbNTPDase2 as a drug target.

The Impact of Biomaterial Surface Properties on Engineering Neural Tissue for Spinal Cord Regeneration.

Tissue engineering for spinal cord injury (SCI) remains a complex and challenging task. Biomaterial scaffolds have been suggested as a potential solution for supporting cell survival and differentiation at the injury site. However, different biomaterials display multiple properties that significantly impact neural tissue at a cellular level. Here, we evaluated the behavior of different cell lines seeded on chitosan (CHI), poly (ε-caprolactone) (PCL), and poly (L-lactic acid) (PLLA) scaffolds. We demonstrated that the surface properties of a material play a crucial role in cell morphology and differentiation. While the direct contact of a polymer with the cells did not cause cytotoxicity or inhibit the spread of neural progenitor cells derived from neurospheres (NPCdn), neonatal rat spinal cord cells (SCC) and NPCdn only attached and matured on PCL and PLLA surfaces. Scanning electron microscopy and computational analysis suggested that cells attached to the material's surface emerged into distinct morphological populations. Flow cytometry revealed a higher differentiation of neural progenitor cells derived from human induced pluripotent stem cells (hiPSC-NPC) into glial cells on all biomaterials. Immunofluorescence assays demonstrated that PCL and PLLA guided neuronal differentiation and network development in SCC. Our data emphasize the importance of selecting appropriate biomaterials for tissue engineering in SCI treatment.

Nature Photographs as Complementary Care in Chemotherapy: A Randomized Clinical Trial.

The incidence of cancer cases is increasing worldwide, and chemotherapy is often necessary as part of the treatment for many of these cases. Nature-based interventions have been shown to offer potential benefits for human well-being. OBJECTIVE: This study aims to investigate the outcome of nature images on clinical symptom management related to chemotherapy. METHODS: A randomized clinical trial was conducted in an outpatient cancer unit of a private hospital in Brazil, with 173 participants over the age of 18 who were undergoing chemotherapy and had signed an informed consent form. The intervention consisted of the presentation of a 12-min video featuring nature images categorized under the themes of Tranquility, Beauty, Emotions Up, or Miscellany. Images were sourced from the e-Nature Positive Emotions Photography Database (e-NatPOEM), a publicly available collection of affectively rated images. Sociodemographic and clinical data, as well as the participants' connection to nature, were investigated. The Positive Affect/Negative Affect Scale (PANAS) and the Edmonton Symptom Assessment System (ESAS) were applied pre- and post-intervention. RESULTS: Data showed very strong evidence of a reduction in negative affect for the intervention group (p < 0.001) and moderate evidence for the control group (p = 0.034). There was also a significant reduction in the intervention group for pain (p < 0.001), tiredness (p = 0.002), sadness (p < 0.001), anxiety (p < 0.001), and appetite (p = 0.001). The Beauty video had the best performance, while the Tranquility video showed no significant improvement in any of the symptoms evaluated. These findings suggest that images of nature may be a valuable tool to help control clinical and psychological symptoms in cancer patients undergoing chemotherapy.

3D bioprinting for organ and organoid models and disease modeling.

INTRODUCTION: 3D printing, a versatile additive manufacturing technique, has diverse applications ranging from transportation, rapid prototyping, clean energy, and medical devices. AREAS COVERED: The authors focus on how 3D printing technology can enhance the drug discovery process through automating tissue production that enables high-throughput screening of potential drug candidates. They also discuss how the 3D bioprinting process works and what considerations to address when using this technology to generate cell laden constructs for drug screening as well as the outputs from such assays necessary for determining the efficacy of potential drug candidates. They focus on how bioprinting how has been used to generate cardiac, neural, and testis tissue models, focusing on bio-printed 3D organoids. EXPERT OPINION: The next generation of 3D bioprinted organ model holds great promises for the field of medicine. In terms of drug discovery, the incorporation of smart cell culture systems and biosensors into 3D bioprinted models could provide highly detailed and functional organ models for drug screening. By addressing current challenges of vascularization, electrophysiological control, and scalability, researchers can obtain more reliable and accurate data for drug development, reducing the risk of drug failures during clinical trials.

The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome.

Agathisflavone, purified from Cenostigma pyramidale (Tul.) has been shown to be neuroprotective in in vitro models of glutamate-induced excitotoxicity and inflammatory damage. However, the potential role of microglial regulation by agathisflavone in these neuroprotective effects is unclear. Here we investigated the effects of agathisflavone in microglia submitted to inflammatory stimulus in view of elucidating mechanisms of neuroprotection. Microglia isolated from cortices of newborn Wistar rats were exposed to Escherichia coli lipopolysaccharide (LPS, 1 µg/mL) and treated or not with agathisflavone (1 µM). Neuronal PC12 cells were exposed to a conditioned medium from microglia (MCM) treated or not with agathisflavone. We observed that LPS induced microglia to assume an activated inflammatory state (increased CD68, more rounded/amoeboid phenotype). However, most microglia exposed to LPS and agathisflavone, presented an anti-inflammatory profile (increased CD206 and branched-phenotype), associated with the reduction in NO, GSH mRNA for NRLP3 inflammasome, IL1-ß, IL-6, IL-18, TNF, CCL5, and CCL2. Molecular docking also showed that agathisflavone bound at the NLRP3 NACTH inhibitory domain. Moreover, in PC12 cell cultures exposed to the MCM previously treated with the flavonoid most cells preserved neurites and increased expression of ß-tubulin III. Thus, these data reinforce the anti-inflammatory activity and the neuroprotective effect of agathisflavone, effects associated with the control of NLRP3 inflammasome, standing out it as a promising molecule for the treatment or prevention of neurodegenerative diseases.

Amburana cearensis seed extract stimulates astrocyte glutamate homeostatic mechanisms in hippocampal brain slices and protects oligodendrocytes against ischemia.

BACKGROUND: Stroke is a leading cause of death and disability worldwide. A major factor in brain damage following ischemia is excitotoxicity caused by elevated levels of the neurotransmitter glutamate. In the brain, glutamate homeostasis is a primary function of astrocytes. Amburana cearensis has long been used in folk medicine and seed extract obtained with dichloromethane (EDAC) have previously been shown to exhibit cytoprotective activity in vitro. The aim of the present study was to analyse the activity of EDAC in hippocampal brain slices. METHODS: We prepared a dichloromethane extract (EDAC) from A. cearensis seeds and characterized the chemical constituents by 1H and 13C-NMR. Hippocampal slices from P6-8 or P90 Wistar rats were used for cell viability assay or glutamate uptake test. Hippocampal slices from P10-12 transgenic mice SOX10-EGFP and GFAP-EGFP and immunofluorescence for GS, GLAST and GLT1 were used to study oligodendrocytes and astrocytes. RESULTS: Astrocytes play a critical role in glutamate homeostasis and we provide immunohistochemical evidence that in excitotoxicity EDAC increased expression of glutamate transporters and glutamine synthetase, which is essential for detoxifying glutamate. Next, we directly examined astrocytes using transgenic mice in which glial fibrillary acidic protein (GFAP) drives expression of enhanced green fluorescence protein (EGFP) and show that glutamate excitotoxicity caused a decrease in GFAP-EGFP and that EDAC protected against this loss. This was examined further in the oxygen-glucose deprivation (OGD) model of ischemia, where EDAC caused an increase in astrocytic process branching, resulting in an increase in GFAP-EGFP. Using SOX10-EGFP reporter mice, we show that the acute response of oligodendrocytes to OGD in hippocampal slices is a marked loss of their processes and EDAC protected oligodendrocytes against this damage. CONCLUSION: This study provides evidence that EDAC is cytoprotective against ischemia and glutamate excitotoxicity by modulating astrocyte responses and stimulating their glutamate homeostatic mechanisms.

Synthesis, solid state characterization, theoretical and experimental spectroscopic studies of the new lanthanide complexes.

Three new complexes Na[Ln(pic)4]ּ⋅2.5H2O (Ln = Tb, Eu or Gd; pic = picolinate) were synthesized and characterized by infrared spectroscopy, powder X-ray diffraction and thermogravimetric analyses. The molecular structures of the complexes have been determined by single-crystal X-ray diffraction. The three isostructural lanthanide complexes crystalize in the hexagonal system with space group P6122 to Eu complex and Gd complex and space group P6522 to Tb complex. In each of the complexes, the picolinate ligands are bonded to Ln3+ and Na+ ions by different coordination modes promoting polymeric structures. The photoluminescent properties of complexes were studied and combined with theoretical studies using the density functional theory (DFT: B3LYP, PBE1PBE) and the semiempirical method AM1/Sparkle from the single crystal X-ray diffraction structures to assign a suitable model for describing the system. The B3LYP DFT functional was considered the most adequate for providing structural properties of the compounds and for describing luminescence properties. The excited triplet states (T1) and excited singlet states (S1) of the ligand were determined theoretically using Time-dependent DFT calculations (TD-DFT: B3LYP, CAM-B3LYP and LC-wPBE) and INDO/S-CIS, with the best agreement with experimental values obtained from the LC-wPBE DFT functional. The photoluminescent spectra of the complexes and their lifetime measurements were determined indicating that the Eu complex and Tb complex display different intramolecular energy transfer mechanisms with higher efficiency to ligand-to-terbium energy transfer. In addition, the experimental and theorical Judd-Ofelt intensity parameters and quantum yields of the complexes were also determined and discussed besides to a proposed 9-state diagram to describe the luminescence properties of the Eu complex. The low value of emission quantum efficiency of 5D0 emitting level of Eu(III) ion was explained by the presence of the ligand-to-metal charge transfer state (LMCT) evidenced experimentally and theoretically. A good agreement was obtained between the proposed kinetic model and experimental results showing the consistency of the set of rate equations assumed and the intramolecular pathways proposed.

3D bioprinting complex models of cancer.

Cancer is characterized by the uncontrolled division of cells, resulting in the formation of tumors. The tumor microenvironment (TME) consists of a variety of cell types present within a heterogeneous extracellular matrix (ECM). Current 2D culture methods for mimicking this microenvironment remain limited due to spatial constraints. Many different types of 3D cancer models have been developed in recent years using spheroids/organoids, biomaterial scaffolds, and cancer-on-chip systems. However, these models cannot precisely control the organization of multiple cell types inside of complex architectures. Bioprinted cancer models can incorporate both stromal and cancer cells inside of 3D constructs to generate custom models of this complex disease. 3D bioprinting can generate complex, multicellular, and reproducible constructs where the matrix composition and rigidity are tailored locally to the tumor. These capabilities make 3D bioprinting an attractive method for reproducing the tumor TME found in vivo. Recent advancements in biomaterial-based bioinks enable the generation of 3D bioprinted cancer models that accurately mimic the TM. Here we discuss recent examples of such 3D-bioprinted cancer models, including those of the lungs, prostate, skin, brain, and colon. We then highlight the advantages of using 3D bioprinting compared to other in vitro modeling techniques and detail its limitations.

Impact of Plant-Derived Compounds on Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by progressive motor neuron degeneration. Conventional therapies for ALS are based on treatment of symptoms, and the disease remains incurable. Molecular mechanisms are unclear, but studies have been pointing to involvement of glia, neuroinflammation, oxidative stress, and glutamate excitotoxicity as a key factor. Nowadays, we have few treatments for this disease that only delays death, but also does not stop the neurodegenerative process. These treatments are based on glutamate blockage (riluzole), tyrosine kinase inhibition (masitinib), and antioxidant activity (edaravone). In the past few years, plant-derived compounds have been studied for neurodegenerative disorder therapies based on neuroprotection and glial cell response. In this review, we describe mechanisms of action of natural compounds associated with neuroprotective effects, and the possibilities for new therapeutic strategies in ALS.