Emergence of Quantum Dots as Innovative Tools for Early Diagnosis and Advanced Treatment of Breast Cancer.

Quantum dots (QDs) semiconducting nanomaterials, have garnered attention due to their distinctive properties, including small size, high luminescence, and biocompatibility. In the context of triple-negative breast cancer (TNBC), notorious for its resistance to conventional treatments, QDs exhibit promising potential for enhancing diagnostic imaging and providing targeted therapies. This review underscores recent advancements in the utilization of QDs in imaging techniques, such as fluorescence tomography and magnetic resonance imaging, aiming at the early and precise detection of tumors. Emphasis is placed on the significance of QD design, synthesis and functionalization processes as well as their use in innovative strategies for targeted drug delivery, capitalizing on their ability to selectively deliver therapeutic agents to cancer cells. As the research in this field advances rapidly, this review covers a classification of QDs according to their composition, the characterization techniques than can be used to determine their properties and, subsequently, emphasizes recent findings in the field of TNBC-targeting, highlighting the imperative need to address challenges, like potential toxicity or methodologies standardization. Collectively, the findings explored thus far suggest that QDs could pave the way for early diagnosis and effective therapy of TNBC, representing a significant stride toward precise and personalized strategies in treating TNBC.

Vanadocene-functionalized mesoporous silica nanoparticles: platforms for the development of theranostic materials against breast cancer.

Nanoscale materials have demonstrated a very high potential in anticancer therapy by properly adjusting their functionalization and physicochemical properties. Herein, we report the synthesis of some novel vanadocene-loaded silica-based nanomaterials incorporating four different S-containing amino acids (penicillamine, methionine, captopril, and cysteine) and different fluorophores (rhodamine B, coumarin 343 or Alexa Fluor™ 647), which have been characterized by diverse solid-state spectroscopic techniques viz; FTIR, diffuse reflectance spectroscopies,13C and51V solid-state NMR spectroscopy, thermogravimetry and TEM. The analysis of the biological activity of the novel vanadocene-based nanostructured silicas showed that the materials containing cysteine and captopril aminoacids demonstrated high cytotoxicity and selectivity against triple negative breast cancer cells, making them very promising antineoplastic drug candidates. According to the biological results it seems that vanadium activity is connected to its incorporation through the amino acid, resulting in synergy that increases the cytotoxic activity against cancer cells of the studied materials presumably by increasing cell internalization. The results presented herein hold significant potential for future developments in mesoporous silica-supported metallodrugs, which exhibit strong cytotoxicity while maintaining low metal loading. They also show potential for theranostic applications highlighted by the analysis of the optical properties of the studied systems after incorporating rhodamine B, coumarin 343 (possible)in vitroanticancer analysis, or Alexa Fluor™ 647 (in vivostudies of cancer models).

Donor-Acceptor-Donor 1H-Benzo[d]imidazole Derivatives as Optical Waveguides.

A new series of donor-acceptor-donor (D-A-D) structures derived from arylethynyl 1H-benzo[d]imidazole was synthesized and processed into single crystals with the goal of testing such crystals' ability to act as optical waveguides. Some crystals displayed luminescence in the 550-600 nm range and optical waveguiding behavior with optical loss coefficients around 10-2 dB/µm, which indicated a notable light transport. The crystalline structure, confirmed by X-ray diffraction, contains internal channels that are important for light propagation, as we previously reported. The combination of a 1D assembly, a single crystal structure, and notable light emission properties with low losses from self-absorption made 1H-benzo[d]imidazole derivatives appealing compounds for optical waveguide applications.

Toward Prediction of Financial Crashes with a D-Wave Quantum Annealer.

The prediction of financial crashes in a complex financial network is known to be an NP-hard problem, which means that no known algorithm can efficiently find optimal solutions. We experimentally explore a novel approach to this problem by using a D-Wave quantum annealer, benchmarking its performance for attaining a financial equilibrium. To be specific, the equilibrium condition of a nonlinear financial model is embedded into a higher-order unconstrained binary optimization (HUBO) problem, which is then transformed into a spin-1/2 Hamiltonian with at most, two-qubit interactions. The problem is thus equivalent to finding the ground state of an interacting spin Hamiltonian, which can be approximated with a quantum annealer. The size of the simulation is mainly constrained by the necessity of a large number of physical qubits representing a logical qubit with the correct connectivity. Our experiment paves the way for the codification of this quantitative macroeconomics problem in quantum annealers.

Dissecting operant alcohol self-administration using saccharin-fading procedure.

BACKGROUND: Although alcohol use disorder is a complex human pathology, the use of animal models represents an opportunity to study some aspects of this pathology. One of the most used paradigms to study the voluntary alcohol consumption in rodents is operant self-administration (OSA). AIMS: In order to facilitate the performance of this paradigm, we aim to describe some critical steps of OSA under a saccharin-fading procedure. MATERIAL & METHODS: We used 40 male Wistar rats to study the process of acquiring the operant response through a saccharin-fading procedure under a fixed ratio (FR1) schedule of reinforcement. Next, we analyze the alcohol introduction and concentration increase, the effect of an alcohol deprivation, and the analogy between this paradigm with the Drinking in the Dark-Multiple Scheduled Access paradigm. RESULTS: During alcohol concentration increase, animals reduced their lever presses in accordance with the increase in alcohol concentration. On the contrary, the consumption measured in g·kg-1 BW showed a great stability. The lever presses pattern within operant session changes with the introduction of different alcohol concentrations: at higher alcohol concentrations, animals tended to accumulate most of their presses in the initial period of the session. DISCUSSION: We show the utility of fading with low concentrations of saccharin and the evolution of the operant response through the different concentrations of alcohol. CONCLUSION: Taken together, our results aimed to dissect the acquisition and maintenance of OSA behavior as well as other related variables, to facilitate the understanding and performance of this paradigm.

Azaindole grafted titanium dioxide for the photodegradation of pharmaceuticals under solar irradiation.

The application of metal-free organic molecules grafted titanium dioxide (TiO2) as photocatalysts for the degradation of pharmaceuticals under solar light has been scarcely studied. Herein, a novel photocatalyst was synthesized anchoring a bipolar electron-donor and -acceptor molecule based on azaindole derivative (AZA4) onto TiO2 aiming to improve the photoactivity under simulated solar irradiation. The TiO2-azaindole (TiO2-AZA4) was fully characterized, confirming that AZA4 was successfully grafted onto TiO2 and improving the light absorption. The grafted TiO2 was applied in the photodegradation of acetaminophen in water, showing a significantly better photocatalytic performance compared to that of pure TiO2 under both solar and visible irradiations. AZA4 grafting leads to the TiO2 band gap narrowing and favors the charge separation, thus improving the TiO2 photoactivity. The photocatalytic performance of TiO2-AZA4 was evaluated using different conditions such as photocatalyst dose or initial pH of the solution, and the radical species involved in the process were investigated. The high activity of TiO2-AZA4 was confirmed in the photodegradation of a mixture of pharmaceuticals, namely acetaminophen, ibuprofen, and antipyrine, further demonstrating its stability and catalytic performance in a novel continuous flow test under simulated solar irradiation, thus finding a new strategy to design solar-light driven photocatalysts for the degradation of pollutants in water.

Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies.

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5-HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies: relationship with COVID-19 diagnosis, symptoms, smoking, and method of transmission.

Aims: The study of SARS-CoV-2 antibodies in the population is a crucial step towards overcoming the COVID-19 pandemic. Seroepidemiological studies allow an estimation of the number of people who have been exposed to the virus, as well as the number of people who are still susceptible to infection. Methods: In total, 13 560 people from Arganda del Rey, Madrid (Spain) were assessed between January and March 2021 for the presence of IgG antibodies, using rapid tests and histories of symptoms compatible with COVID-19. Results: 24.2% of the participants had IgG antibodies and 9% had a positive COVID-19 diagnosis. Loss of smell/taste was the most discriminating symptom of the disease. The main transmitters of infection were found to be household members. Unexpectedly, in smokers, the incidence of positive COVID-19 diagnoses was significantly lower. Additionally, it was found that there was a discrepancy between COVID-19 diagnosis and the presence of IgG antibodies. Conclusions: Rapid anti-IgG tests are less reliable in detecting SARS-CoV-2 infection at an individual level, but are functional in estimating SARS-CoV-2 infection rates at an epidemiological level. The loss of smell/taste is a potential indicator for establishing COVID-19 infection.

Enabling Context-Aware Data Analytics in Smart Environments: An Open Source Reference Implementation.

In recent years, many proposals of context-aware systems applied to IoT-based smart environments have been presented in the literature. Most previous works provide a generic high-level structure of how a context-aware system can be operationalized, but do not offer clues on how to implement it. On the other hand, there are many implementations of context-aware systems applied to specific IoT-based smart environments that are context-specific: it is not clear how they can be extended to other use cases. In this article, we aim to provide an open-source reference implementation for providing context-aware data analytics capabilities to IoT-based smart environments. We rely on the building blocks of the FIWARE ecosystem and the NGSI data standard, providing an agnostic end-to-end solution that considers the complete data lifecycle, covering from data acquisition and modeling, to data reasoning and dissemination. In other words, our reference implementation can be readily operationalized in any IoT-based smart environment regardless of its field of application, providing a context-aware solution that is not context-specific. Furthermore, we provide two example use cases that showcase how our reference implementation can be used in a variety of fields.

The Immune System through the Lens of Alcohol Intake and Gut Microbiota.

The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted mucosal immunity. This damage to the permeability of the intestinal membrane allows bacteria and their components to enter the blood tissue, reaching other organs such as the liver or the brain. Although chronic heavy drinking has harmful effects on the immune system cells at the systemic level, this review focuses on the effect produced on gut, brain and liver, because of their significance in the link between alcohol consumption, gut microbiota and the immune system.

Distinct Roles of Vav Family Members in Adaptive and Innate Immune Models of Arthritis.

Genetic evidence suggests that three members of the VAV family (VAV1, VAV2 and VAV3) of signal transduction proteins could play important roles in rheumatoid arthritis. However, it is not known currently whether the inhibition of these proteins protects against this disease and, if so, the number of family members that must be eliminated to get a therapeutic impact. To address this issue, we have used a collection of single and compound Vav family knockout mice in experimental models for antigen-dependent (methylated bovine serum albumin injections) and neutrophil-dependent (Zymosan A injections) rheumatoid arthritis in mice. We show here that the specific elimination of Vav1 is sufficient to block the development of antigen-induced arthritis. This protection is likely associated with the roles of this Vav family member in the development and selection of immature T cells within the thymus as well as in the subsequent proliferation and differentiation of effector T cells. By contrast, we have found that depletion of Vav2 reduces the number of neutrophils present in the joints of Zymosan A-treated mice. Despite this, the elimination of Vav2 does not protect against the joint degeneration triggered by this experimental model. These findings indicate that Vav1 is the most important pharmacological target within this family, although its main role is limited to the protection against antigen-induced rheumatoid arthritis. They also indicate that the three Vav family proteins do not play redundant roles in these pathobiological processes.

An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage.

Since its discovery in 1994, leptin has been considered as an adipokine with pleiotropic effects. In this review, we summarize the actual information about the impact of this hormone on cartilage metabolism and pathology. Leptin signalling depends on the interaction with leptin receptor LEPR, being the long isoform of the receptor (LEPRb) the one with more efficient intracellular signalling. Chondrocytes express the long isoform of the leptin receptor and in these cells, leptin signalling, alone or in combination with other molecules, induces the expression of pro-inflammatory molecules and cartilage degenerative enzymes. Leptin has been shown to increase the proliferation and activation of immune cells, increasing the severity of immune degenerative cartilage diseases. Leptin expression in serum and synovial fluid are related to degenerative diseases such as osteoarthritis (OA), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Inhibition of leptin signalling showed to have protective effects in these diseases showing the key role of leptin in cartilage degeneration.

Monomeric C reactive protein (mCRP) regulates inflammatory responses in human and mouse chondrocytes.

C-reactive protein (CRP) is an acute-phase protein that is used as an established biomarker to follow disease severity and progression in a plethora of inflammatory diseases. However, its pathophysiologic mechanisms of action are still poorly defined and remain elusive. CRP, in its pentameric form, exhibits weak anti-inflammatory activity. On the contrary, the monomeric isoform (mCRP) exhibits potent pro-inflammatory properties in endothelial cells, leukocytes, and platelets. So far, no data exists regarding mCRP effects in human or mouse chondrocytes. This work aimed to verify the pathophysiological relevance of mCRP in the etiology and/or progression of osteoarthritis (OA). We investigated the effects of mCRP in cultured human primary chondrocytes and in the chondrogenic ATDC5 mouse cell line. We determined mRNA and protein levels of relevant factors involved in inflammatory responses and the modulation of nitric oxide synthase type II (NOS2), an early inflammatory molecular target. We demonstrate, for the first time, that monomeric C reactive protein increases NOS2, COX2, MMP13, VCAM1, IL-6, IL-8, and LCN2 expression in human and murine chondrocytes. We also demonstrated that NF-kB is a key factor in the intracellular signaling of mCRP-driven induction of pro-inflammatory and catabolic mediators in chondrocytes. We concluded that mCRP exerts a sustained catabolic effect on human and murine chondrocytes, increasing the expression of inflammatory mediators and proteolytic enzymes, which can promote extracellular matrix (ECM) breakdown in healthy and OA cartilage. In addition, our results implicate the NF-kB signaling pathway in catabolic effects mediated by mCRP.

Organic Semiconductor Micro/Nanocrystals for Laser Applications.

Organic semiconductor micro/nanocrystals (OSMCs) have attracted great attention due to their numerous advantages such us free grain boundaries, minimal defects and traps, molecular diversity, low cost, flexibility and solution processability. Due to all these characteristics, they are strong candidates for the next generation of electronic and optoelectronic devices. In this review, we present a comprehensive overview of these OSMCs, discussing molecular packing, the methods to control crystallization and their applications to the area of organic solid-state lasers. Special emphasis is given to OSMC lasers which self-assemble into geometrically defined optical resonators owing to their attractive prospects for tuning/control of light emission properties through geometrical resonator design. The most recent developments together with novel strategies for light emission tuning and effective light extraction are presented.

Evaluation of Virola oleifera activity in musculoskeletal pathologies: Inhibition of human multiple myeloma cells proliferation and combination therapy with dexamethasone or bortezomib.

ETHNOPHARMACOLOGICAL RELEVANCE: Virola oleifera (Schott) A.C. Smith, Myristicaceae, has been widely used in traditional medicine in Brazil to treat rheumatic pain, joint tumours, skin diseases, halitosis, bronchial asthma, haemorrhoids, and intestinal worms. Recently, research data showed the antioxidant properties in several oxidative stress-related models. However, there is no experimental evidence supporting its potential use in managing rheumatic diseases and bone malignancies. AIMS OF THE STUDY: To evaluate the therapeutic potential of the resin from Virola oleifera in joint and bone diseases, namely arthritis, osteosarcoma, chondrosarcoma, and multiple myeloma. MATERIALS AND METHODS: To determine Virola oleifera resin (VO) effects on arthritis-associated inflammation and cartilage degradation, the LPS-induced NO production, and mRNA and protein expression of ADAMTS5, MMP13, COL2, and ACAN, were evaluated in chondrocytes (ATDC5 and TC28 cell lines). The cytotoxic effects of VO (0.05-50 µg/ml) on multiple myeloma (ARH-77), osteosarcoma (SAOS-2), and chondrosarcoma (SW-1353) cell lines were analysed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The VO effects, combined with dexamethasone or bortezomib, were evaluated in a multiple myeloma cell line. The mechanisms of VO, alone or in combination with bortezomib, were determined by cell cycle analysis through flow cytometry, while expression levels of p-Akt/Akt, p-ERK/ERK, p-p38/p38 MAPK, Bax, Bcl-2, and cleaved-caspase-3/caspase-3 proteins by Western blot. RESULTS: VO had no significant effect on LPS-induced NO production in chondrocytes at non-cytotoxic concentrations. VO treatment diminished the mRNA levels of metalloproteinases and ECM components; however, any significant effect was observed on the protein expression levels. The cell viability of a multiple myeloma cell line was strongly reduced by VO treatment in a dose- and time-dependent manner, while osteosarcoma and chondrosarcoma cell lines viability was significantly affected only by the highest dose assessed. In multiple myeloma cells, VO leads to G2/M cell cycle arrest. Furthermore, it synergizes with dexamethasone by increasing cell toxicity. Finally, VO reverts bortezomib activity by counteracting ERK1/2, Bax, and caspase-3 activation. CONCLUSIONS: The current work supports the ethnopharmacological use of Virola oleifera (Schott) A.C. Smith in bone and joint diseases, but there is no evidence for the amelioration of arthritis-associated inflammatory or catabolic processes. Our data also supports the potential use of Virola oleifera as adjuvant therapy to optimize the pharmacologic effects of current chemotherapeutic drugs. However, possible herb-drug interactions should be considered before clinical application.

Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells.

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1ß and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 was able to induce the secretion of IL-1ß via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO2 in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk.

Dickkopf-3 (DKK3) Signaling in IL-1α-Challenged Chondrocytes: Involvement of the NF-κB Pathway.

OBJECTIVE: Osteoarthritis (OA) is an age-related biomechanical and low-grade inflammometabolic disease of the joints and one of the costliest and disabling forms of arthritis. Studies on matrix-degrading enzymes such as metalloproteases, which are implicated in the increased catabolism of extracellular matrix, are of paramount relevance. DKK3 is a member of DKK family and is best known for its role in cancer. Although there is some information about the participation of DKK3 in cartilage pathophysiology and on metalloproteases regulation, in particular, little is known about DKK3 signaling mechanisms. Thus, the aim of this study is to explore how DKK3 regulates matrix metalloproteinase-13 (MMP-13) expression. DESIGN: Gene, protein expression and protein phosphorylation in primary human chondrocytes and ATDC5 mouse cells were assessed by RT-qPCR and Western blot analysis. Further studies on DKK3 activity were performed by targeting DKK3 gene with a specific siRNA. RESULTS: DKK3 expression was found to be higher in OA human chondrocytes than healthy cells, being its expression decreased in interleukin-1α (IL-1α)-stimulated cells. DKK3 knockdown increased the induction of MMP-13 elicited by IL-1α in human and mouse chondrocytes and after the analysis of different signalling pathways, we observed that NF-κB pathway was involved in the regulation of MMP-13 expression by DKK3. CONCLUSIONS: Herein we have demonstrated, for the first time, that DKK3 gene silencing exacerbated NF-κB activation, resulting in an increased IL-1α-driven induction of MMP-13. Our results further confirm that DKK3 may play a protective role in OA by attenuating NF-κB activation and the subsequent production of metalloproteases.

Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) recently emerged as a promising cancer immunotherapy target. We set out to investigate the functional role of PTPN2 in the pathogenesis of human colorectal carcinoma (CRC), as its role in immune-silent solid tumors is poorly understood. We demonstrate that in human CRC, increased PTPN2 expression and activity correlated with disease progression and decreased immune responses in tumor tissues. In particular, stage II and III tumors displayed enhanced PTPN2 protein expression in tumor-infiltrating T cells, and increased PTPN2 levels negatively correlated with expression of PD-1, CTLA4, STAT1, and granzyme A. In vivo, T cell- and DC-specific PTPN2 deletion reduced tumor burden in several CRC models by promoting CD44+ effector/memory T cells, as well as CD8+ T cell infiltration and cytotoxicity in the tumor. In direct relevance to CRC treatment, T cell-specific PTPN2 deletion potentiated anti-PD-1 efficacy and induced antitumor memory formation upon tumor rechallenge in vivo. Our data suggest a role for PTPN2 in suppressing antitumor immunity and promoting tumor development in patients with CRC. Our in vivo results identify PTPN2 as a key player in controlling the immunogenicity of CRC, with the strong potential to be exploited for cancer immunotherapy.

N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo.

N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.

Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a debilitating, chronic, inflammatory, autoimmune disease associated with cachexia. The substitutive therapy of gut hormone ghrelin has been pointed at as a potential countermeasure for the management of metabolic and inflammatory complications in RA. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inverse agonist/antagonist of the ghrelin receptor makes feasible the development of a more rational pharmacological approach. This work aimed to assess the serum LEAP2 levels, in a cohort of RA patients, in comparison with healthy individuals and determine its correlation with inflammatory parameters. LEAP2 levels were determined by a commercial ELISA kit, plasma C-reactive protein (CRP) levels were evaluated using immunoturbidimetry, and serum levels of inflammatory mediators, namely IL-6, IL-8, IL-1ß, MIP1α, MCP1, and LCN2, were measured by XMap multiplex assay. LEAP2 serum levels were significantly increased in RA patients (n = 101) compared with control subjects (n = 26). Furthermore, the LEAP2 levels significantly correlated with CRP and inflammatory cytokines, but not with BMI. These data reveal LEAP2 as a new potential RA biomarker and indicated the pharmacological control of LEAP2 levels as a novel approach for the treatment of diseases with alterations on the ghrelin levels, such as rheumatoid cachexia.