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Augmenting adaptive immunity is a critical goal for developing next-generation cancer therapies. T and B cells infiltrating the tumor dramatically influence cancer progression through complex interactions with the local microenvironment. Cancer cells evade and limit these immune responses by hijacking normal immunologic pathways. Current experimental models using conventional primary cells, cell lines, or animals have limitations for studying cancer-immune interactions directly relevant to human biology and clinical translation. Therefore, engineering methods to emulate such interplay at local and systemic levels are crucial to expedite the development of better therapies and diagnostic tools. In this review, we discuss the challenges, recent advances, and future directions toward engineering the tumor-immune microenvironment (TME), including key elements of adaptive immunity. We first offer an overview of the recent research that has advanced our understanding of the role of the adaptive immune system in the tumor microenvironment. Next, we discuss recent developments in 3D in-vitro models and engineering approaches that have been used to study the interaction of cancer and stromal cells with B and T lymphocytes. We summarize recent advancement in 3D bioengineering and discuss the need for 3D tumor models that better incorporate elements of the complex interplay of adaptive immunity and the tumor microenvironment. Finally, we provide a perspective on current challenges and future directions for modeling cancer-immune interactions aimed at identifying new biological targets for diagnostics and therapeutics.

The tumor microbiota has emerged as a pivotal contributor to a variety of cancers, impacting disease development, progression, and therapeutic resistance. Due to the complexity of the tumor microenvironment, reproducing the interactions between the microbes, tumor cells, and the immune system remains a great challenge for both in vitro and in vivo studies. To this end, significant progress has been made toward leveraging tumor-on-a-chip model systems to replicate critical hallmarks of the native disease in vitro . These microfluidic platforms offer the ability to mimic essential components of the tumor microenvironment, including controllable fluid flow conditions, manipulable extracellular matrix dynamics, and intricate 3D multi-cellular communication. The primary objective of this review is to discuss recent challenges and advances in engineering host-microbiota and tumor interactions on-a-chip. Ultimately, overcoming these obstacles will help us gain deeper insights into tumor-microbe interactions and enhance avenues for developing more effective cancer therapies.

Bone homeostasis depends on spatially orchestrated interactions among osteoclasts, osteoblasts, and osteocytes that are embedded within a unique extracellular matrix that is mineralized on the nanoscale to define the structure and function of bone. Reconstructing these interactions to enable autonomous cell differentiation and tissue remodeling has remained a significant challenge towards mimicking adequate bone physiology in-vitro. Here, we present an engineered model that spatially defines the paracrine communication of heterogeneous cell populations within bone tissue that support the rapid maturation of primary osteoblasts into osteocytes, the differentiation of macrophages into osteoclasts, and calcified tissue resorption within a mineralized cell-laden bone-like tissue. We demonstrate that nanoscale mineralization of cell-laden collagen hydrogels on-a-chip enhances osteoblast to osteocyte differentiation, whereas osteocytes in the matrix accelerate osteoclastogenesis and remodeling in a spatially defined manner without the need for exogenous growth factors. Osteocyte-dependent osteoclastogenesis on-a-chip outperformed conventional stimulation with RANKL and M-CSF, reproduced the clinical response of anti-resorptive drugs, and mimicked established tumor-bone interactions observed in invasive oral cancer. By replicating essential aspects of bone composition and function, this system provides a robust, self-regulated microphysiologic model to investigate bone remodeling, cancer-bone crosstalk, and therapeutic interventions.

Ornithodoros rostratus is a South American argasid tick which importance relies on its itchy bite and potential as disease vector. They feed on a wide variety of hosts and secrete different molecules in their saliva and intestinal content that counteract host defences and help to accommodate and metabolize the relatively large quantity of blood upon feeding. The present work describes the transcriptome profile of salivary gland (SG) and midgut (MG) of O. rostratus using Illumina sequencing. A total of 8,031 contigs were assembled and assigned to different functional classes. Secreted proteins were the most abundant in the SG and accounted for ~67% of all expressed transcripts with contigs with identity to lipocalins and acid tail proteins being the most representative. On the other hand, immunity genes were upregulated in MG with a predominance of defensins and lysozymes. Only 10 transcripts in SG and 8 in MG represented ~30% of all RNA expressed in each tissue and one single contig (the acid tail protein ORN-9707) represented ~7% of all expressed contigs in SG. Results highlight the functional difference of each organ and identified the most expressed classes and contigs of O. rostratus SG and MG.

Acanthophis antarcticus, commonly known as the death adder, is a venomous Australian snake and a member of the Elapidae family. Due to its robust body and triangular head, it was historically misclassified as a viper. Its venom is known for neurotoxic, hemorrhagic, and hemolytic effects but displays low anticoagulant activity. Although key toxins such as three-finger toxins (3FTxs) and phospholipase A2 (PLA2) have been previously described, no study has integrated proteomic and functional analyses to date. In this study, we conducted a comprehensive characterization of A. antarcticus venom. Reverse-phase high-performance liquid chromatography (RP-HPLC) followed by LC-MS/MS enabled the identification of nine toxin families, with 3FTxs and PLA2 as the most abundant. Less abundant but functionally relevant toxins included Kunitz-type inhibitors, CRISP, SVMP, LAAO, NGF, natriuretic peptides, and nucleotidases, the latter being reported here for the first time based on proteomic evidence. Hydrophilic interaction chromatography (HILIC) coupled with MALDI-TOF was used to analyze polar, non-retained venom components, revealing the presence of low-molecular-weight peptides (2–4 kDa). Functional assays confirmed the enzymatic activity of HYAL, PLA2, and LAAO and, for the first time, demonstrated inhibitory activity on serine peptidases and fibrinogenolytic activity in the venom of this species. These findings expand our understanding of the biochemical and functional diversity of this venom.

In a cohort of patients with Chagas' heart disease, multivariate analysis was used to identify six risk factors for death: New York Heart Association class III or IV, cardiomegaly, left ventricular systolic dysfunction, nonsustained ventricular tachycardia, low QRS voltage, and male sex. These variables were incorporated into a risk score that was validated in a second cohort of patients. In patients with Chagas' heart disease, multivariate analysis was used to identify six risk factors for death: New York Heart Association class III or IV, cardiomegaly, left ventricular systolic dysfunction, nonsustained ventricular tachycardia, low QRS voltage, and male sex. Chagas' disease is due to a parasitic infection with Trypanosoma cruzi . It is transmitted to humans through the feces of infected bloodsucking insects in areas in which the disease is endemic and, occasionally, by nonvectorial mechanisms such as blood transfusion. Chagas' disease is a serious problem in most Latin American countries, with 18 million persons chronically infected and approximately 200,000 new cases each year. 1 Cardiac involvement is the main cause of death. 2 The clinical course of Chagas' heart disease is variable, and the identification of patients at risk for death remains a challenge. Previous reports 3 – 13 demonstrated that many . . .

Carbon-based nanomaterials (CBNs) are a category of nanomaterials with various systems based on combinations of sp2 and sp3 hybridized carbon bonds, morphologies, and functional groups. CBNs can exhibit distinguished properties such as high mechanical strength, chemical stability, high electrical conductivity, and biocompatibility. These desirable physicochemical properties have triggered their uses in many fields, including biomedical applications. In this review, we specifically focus on applying CBNs as scaffolds in tissue engineering, a therapeutic approach whereby CBNs can act for the regeneration or replacement of damaged tissue. Here, an overview of the structures and properties of different CBNs will first be provided. We will then discuss state-of-the-art advancements of CBNs and hydrogels as scaffolds for regenerating various types of human tissues. Finally, a perspective of future potentials and challenges in this field will be presented. Since this is a very rapidly growing field, we expect that this review will promote interdisciplinary efforts in developing effective tissue regeneration scaffolds for clinical applications. Keywords: carbon, biomaterial, nanotechnology, tissue engineering, scaffold

Green harvest sugarcane management has increased soil organic C and N stocks over time. However, emerging sugarcane straw removal to meet increasing bioenergy demands has raised concerns about soil C and N depletions. Thus, we conducted a field study in southeast Brazil over nearly three years (1100 days) for assessing soil C and N responses to increasing sugarcane straw removal rates. In order to detect the C input as a function of the different amounts of straw over three years, a field simulation was performed, where the original soil layer (0–0.30 m) was replaced by another from an adjacent area with low total C and δ13C. The treatments tested were as follows: (i) 0 Mg ha−1 year−1 (i.e., 100% removal), (ii) 3.5 Mg ha−1 year−1 (i.e., 75% removal), (iii) 7.0 Mg ha−1 year−1 (i.e., 50% removal), (iv) 14.0 Mg ha−1 year−1 (i.e., no removal), and (v) 21.0 Mg ha−1 year−1 (i.e., no removal + extra 50% of the straw left on the field). The results showed that sugarcane straw removal affected the soil C and total N pools. In the first 45 days of straw decomposition, a small but important straw-derived C portion enters into the soil as dissolved organic carbon (DOC). The lower the straw removal rate, the higher was straw-derived DOC content found into the soil, down to 0.50 m depth. After 3 years of management, keeping sugarcane straw on soil surface significantly increased C and N stocks within surface soil layer (0–0.025 m). Our findings suggest that under no straw removal management (i.e., 14 Mg ha−1), approximately 364 kg ha−1 of C and 23 kg ha−1 of N are annually stored into this low-C soil. The contribution of the straw-derived C (C-C4) to the total soil C increases over time, which accounted for about 60% under no straw removal rate. The greatest contribution of the C storage preferentially occurs into the fraction of organic matter (< 0.53 μm) associated with soil clay minerals. We concluded that indiscriminate sugarcane straw removal to produce cellulosic ethanol or bioelectricity depletes soil C stocks and reduces N cycling in sugarcane fields, impairing environmental gains associated with bioenergy production. Therefore, this information, linked with other agronomic and environmental issues, should be taken into account towards a more sustainable straw removal management for bioenergy production in Brazil.

Background The clinical management of leprosy Type 1 (T1R) and Type 2 (T2R) reactions pose challenges mainly because they can cause severe nerve injury and disability. No laboratory test or marker is available for the diagnosis or prognosis of leprosy reactions. This study simultaneously screened plasma factors to identify circulating biomarkers associated with leprosy T1R and T2R among patients recruited in Goiania, Central Brazil. Methods A nested case-control study evaluated T1R (n = 10) and TR2 (n = 10) compared to leprosy patients without reactions (n = 29), matched by sex and age-group (+/- 5 years) and histopathological classification. Multiplex bead based technique provided profiles of 27 plasma factors including 16 pro inflammatory cytokines: tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), interleukin (IL)- IL12p70, IL2, IL17, IL1 β, IL6, IL15, IL5, IL8, macrophage inflammatory protein (MIP)-1 alpha (MIP1α), 1 beta (MIP1β), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractrant protein 1 (MCP1), CC-chemokine 11 (CCL11/Eotaxin), CXC-chemokine 10 (CXCL10/IP10); 4 anti inflammatory interleukins: IL4, IL10, IL13, IL1Rα and 7 growth factors: IL7, IL9, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF). Results Elevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction. IL6 (p = 0.05), IL7 (p = 0.039), and PDGF-BB (p = 0.041) were elevated in T2R. RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples. Conclusion Potential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2. Additional studies on these biomarkers may help understand the immunopathologic mechanisms of leprosy reactions and indicate their usefulness for the diagnosis and for the clinical management of these events.

Saliva of the blood feeding sand fly was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system.