Protective Effects of Annona Atemoya Extracts on Inflammation, Oxidative Stress, and Renal Function in Cadmium-Induced Nephrotoxicity in Wistar Rats.

BACKGROUND: Cadmium (Cd), a highly toxic heavy metal from agricultural activities, and its exposure can lead to impaired renal function by increasing reactive oxygen species. The atemoya fruit is known for its high phenolic and antioxidant compounds. This study aimed to evaluate the effects of atemoya extracts on renal function, oxidative stress parameters, and inflammatory biomarkers in a cadmium-induced nephrotoxicity model. METHODS: Three aqueous extracts were prepared from different parts of the atemoya fruit: seeds, peel, and pulp. Twenty-five male Wistar rats were allocated into four groups: control, seed, peel, and pulp extracts at 2 g/kg for 25 days. All treatment groups administered intraperitoneal injections of cadmium chloride (CdCl2) (2 mg/kg) to induce renal damage. RESULTS: The cadmium-treated groups showed decreased creatinine clearance, SOD, CAT, and GPx activities (p < 0.05) and increased serum levels of TNF-α and IL-6 compared to the control group (p < 0.05). The treatment with seed, peel, and pulp extracts increased creatinine clearance (p < 0.05), increased SOD, CAT, and GPx activities (p < 0.05), and reduced serum levels of TNF-α and IL-6 compared to the Cd group (p < 0.05). CONCLUSIONS: This study supports the use of atemoya as a promising candidate for mitigating nephrotoxicity and highlights the importance of its antioxidant and anti-inflammatory properties in renal health.

Bioeconomy in the Amazon: Lessons and gaps from thirty years of non-timber forest products research.

Non-timber forest products (NTFPs) play an essential role in the Amazon region, contributing to the integration between biodiversity conservation and the enhancement of the bioeconomy. This study has examined the scope of NTFP research in the Amazon and pinpointed areas lacking scientific insight. From the 219 publications initially identified, 146 satisfied established inclusion criteria based on the methodology employed and the results achieved. It was found that the inaugural publication indexed by Scopus on Amazonian NTFPs dates to 1992. It was found that the inaugural publication indexed by Scopus on Amazonian NTFPs dates to 1992. Despite the extensive body of research, there is a noticeable deficit in studies addressing legal and regulatory frameworks within the NTFP production chain and public policy development. Research has predominantly concentrated on production, distribution, management, and economic aspects, often neglecting the social, normative, and political dimensions. Advancing the bioeconomy value chains in the Amazon necessitates empowering local communities to derive economic benefits from biodiversity. However, recognizing the complexity of these communities' relationships with the forest is important. Their interaction with the forest extends beyond economic considerations, embracing cultural, subsistence, and spiritual connections. These insights underscore the necessity for a comprehensive and sustainable approach to NTFP management in the Amazon, ensuring that biodiversity conservation and local community empowerment are integrally pursued. This holistic perspective is vital for fostering a resilient bioeconomy in the region.

Sialyl-Tn glycan epitope as a target for pancreatic cancer therapies.

Pancreatic cancer (PC) is the sixth leading cause of cancer-related deaths worldwide, primarily due to late-stage diagnosis and limited treatment options. While novel biomarkers and immunotherapies are promising, further research into specific molecular targets is needed. Glycans, which are carbohydrate structures mainly found on cell surfaces, play crucial roles in health and disease. The Thomsen-Friedenreich-related carbohydrate antigen Sialyl-Tn (STn), a truncated O-glycan structure, is selectively expressed in epithelial tumors, including PC. In this study, we performed a comprehensive analysis of STn expression patterns in normal, premalignant, and malignant pancreatic lesions. Additionally, we analyzed the association between STn expression and various clinicopathological features. STn expression was statistically associated with pathological diagnosis; it was absent in normal pancreatic tissue but prevalent in pancreatic carcinoma lesions, including pancreatic ductal adenocarcinoma (PDAC), pancreatic acinar cell carcinoma, and pancreatic adenosquamous carcinoma. Moreover, we found a significant association between STn expression and tumor stage, with higher STn levels observed in stage II tumors compared to stage I. However, STn expression did not correlate with patient survival or outcomes. Furthermore, STn expression was assessed in PDAC patient-derived xenograft (PDX) models, revealing consistent STn levels throughout engraftment and tumor growth cycles. This finding supports the PDX model as a valuable tool for testing new anti-STn therapeutic strategies for PC in clinical setting.

The association between anxiety and depression symptoms and clinical and pain characteristics in patients with hip and knee osteoarthritis.

OBJECTIVES: This study aimed to estimate the prevalence of anxiety and depression symptoms and explore the association between these symptoms and clinical and pain characteristics in patients with chronic pain (CP) due to hip and knee osteoarthritis (OA). METHODS: In this cross-sectional study, adult patients with CP and knee and/or hip OA were included. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Visual analogue scale, Western Ontario and McMaster Universities Arthritis Index (WOMAC) and PainDetect Questionnaire assessed pain characteristics and Health Assessment Questionnaire (HAQ) evaluated functional disability. Correlation coefficients were used to explore the associations between anxiety and depression symptoms and clinical and pain characteristics. RESULTS: A total of 61 patients (age 66.2±9.4 years, 67.2% female) were included. Most patients (70.5%) had clinically significant anxiety and/or depression symptoms. Patients with anxiety and/or depression symptoms had higher pain severity (p=0.032) and disability (p=0.014). Depression symptoms had a moderate positive correlation with WOMAC physical function subscale (r=0.520), WOMAC total (r=0.511) and HAQ (r=0.405). CONCLUSIONS: Anxiety and depression symptoms are prevalent in knee or hip OA patients with CP and were associated with higher pain severity and functional disability. These findings support the screening of anxiety and depression symptoms in OA patients, in order to develop more effective multidisciplinary treatments.

Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function.

Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.

Long-term blood-free rearing of Anopheles mosquitoes with no effect on fitness, Plasmodium infectivity nor microbiota composition.

Mosquito-borne diseases kill millions of people each year. Therefore, many innovative research and population control strategies are being implemented but, most of them require large-scale production of mosquitoes. Mosquito rearing depends on fresh blood from human donors, experimentation animals or slaughterhouses, which constitutes a strong drawback since high blood quantities are needed, raising ethical and financial constraints. To eliminate blood dependency and the use of experimentation animals, we previously developed BLOODless, a patented diet that represents an important advance towards sustainable mosquito breeding in captivity. BLOODless diet was used to maintain a colony of Anopheles stephensi for 40 generations. Bloodmeal appetite, fitness, Plasmodium berghei infectivity, whole genome sequencing and microbiota were evaluated over time. Here we show that BLOODless can be implemented in Anopheles insectaries since it allows long-term rearing of mosquitoes in captivity, without a detectable effect on their fitness, infectivity, nor on their midgut and salivary microbiota composition.

Can Breastfeeding Prevent Long-Term Overweight and Obesity in Children? A Population-Based Cohort Study.

The aims of this study were to assess the impact of exclusive breastfeeding up to 6 months of age on reducing the incidence of overweight and obesity in children up to 10 years of age and to estimate the annual incidence of obesity and overweight in the study population. Our retrospective cohort analysis using electronic health records included children from zero to ten years old, born between 1 January 2006 and 31 December 2022, followed up at the Unidade Local de Saúde de Matosinhos (ULSM). Information on their comorbidity history was collected, and positive or negative control results were defined. In the first year of life, around 29% of the children on exclusive breastfeeding were obese and 20% were overweight. This trend was reversed by the age of 9. Asthma and allergic rhinitis were used as positive control outcomes and allergic dermatitis as a negative control outcome. There seems to be no relationship between exclusive and non-exclusive breastfeeding and the development of overweight or obesity at the age of 10. The results showed that breastfeeding is associated with a lower risk of asthma in the future.

Symptom flares in women with chronic pelvic pain: Questionnaire study within a cohort study (translational research in pelvic pain (TRiPP)).

OBJECTIVE: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). DESIGN: Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. SETTING: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). POPULATION OR SAMPLE: A total of 100 participants. METHODS: Descriptive and comparative analysis from flares questionnaire. MAIN OUTCOME MEASURES: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. RESULTS: We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. CONCLUSIONS: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.

Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis.

Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.

Emotion dysregulation and depressive symptoms mediate the association between inhibitory control difficulties and aggressive behaviour in children with ADHD.

Background/objectives: Impulsive aggressive behaviour, although not a core symptom, is often part of the clinical presentation of attention-deficit/hyperactivity disorder (ADHD). Recently, impulsive aggression has been attributed to emotion dysregulation, which is currently conceptualised as a transdiagnostic factor and seems to contribute to the co-occurrence of other problems in ADHD. Thus, this study investigated the presence of impulsive aggressive behaviour and explored whether emotion dysregulation mediates the relationship between inhibitory control difficulties and aggressive behaviour in children with ADHD. Because ADHD may act as a risk factor for the development of other conditions, such as internalising problems, we aimed to understand whether depressive symptoms contribute to this relationship. Methods: Seventy-two children were recruited from a hospital and the community, 38 of whom had ADHD and 34 were typically developing (TD). Parents completed the Child Behaviour Checklist, the Behaviour Rating Inventory of Executive Function, and the Emotion Regulation Checklist. Simple mediation and serial mediation models were performed to test our hypotheses. Results: Aggressive behaviour was significantly higher in ADHD children compared to TD children. Emotion dysregulation fully mediated the relationship between inhibitory control difficulties and aggressive behaviour in ADHD children. Adding depressive symptoms to the model increased the explained variance in aggressive behaviour. Conclusion: The main result of our study supports the role of emotion dysregulation and depressive symptoms in mediating the relationship between inhibitory control difficulties and impulsive aggressive behaviour in children with ADHD. This highlights that aggressive behaviour is, in part, a result of the inability of the child to appropriately regulate their emotions. Future interventions may be tailored to improve emotion regulation skills to address aggressive behaviour.

Heterologous expression and structure prediction of a xylanase identified from a compost metagenomic library.

Xylanases are key biocatalysts in the degradation of the ß-1,4-glycosidic linkages in the xylan backbone of hemicellulose. These enzymes are potentially applied in a wide range of bioprocessing industries under harsh conditions. Metagenomics has emerged as powerful tools for the bioprospection and discovery of interesting bioactive molecules from extreme ecosystems with unique features, such as high temperatures. In this study, an innovative combination of function-driven screening of a compost metagenomic library and automatic extraction of halo areas with in-house MATLAB functions resulted in the identification of a promising clone with xylanase activity (LP4). The LP4 clone proved to be an effective xylanase producer under submerged fermentation conditions. Sequence and phylogenetic analyses revealed that the xylanase, Xyl4, corresponded to an endo-1,4-ß-xylanase belonging to glycosyl hydrolase family 10 (GH10). When xyl4 was expressed in Escherichia coli BL21(DE3), the enzyme activity increased about 2-fold compared to the LP4 clone. To get insight on the interaction of the enzyme with the substrate and establish possible strategies to improve its activity, the structure of Xyl4 was predicted, refined, and docked with xylohexaose. Our data unveiled, for the first time, the relevance of the amino acids Glu133 and Glu238 for catalysis, and a close inspection of the catalytic site suggested that the replacement of Phe316 by a bulkier Trp may improve Xyl4 activity. Our current findings contribute to enhancing the catalytic performance of Xyl4 towards industrial applications. KEY POINTS: • A GH10 endo-1,4-ß-xylanase (Xyl4) was isolated from a compost metagenomic library • MATLAB's in-house functions were developed to identify the xylanase-producing clones • Computational analysis showed that Glu133 and Glu238 are crucial residues for catalysis.

Predicting Exacerbations in Alpha-1 Antitrypsin Deficiency Using Clinical and Pulmonary Function Tests: Portuguese EARCO Registry.

INTRODUCTION: Exacerbations are common in individuals with alpha-1 antitrypsin deficiency (AATD)-related lung disease. This study intended to identify independent predictive factors for exacerbations in AATD using the Portuguese European Alpha-1 Research Collaboration (EARCO) registry. METHODS: This study includes patients from the Portuguese EARCO registry, a prospective multicenter cohort (NCT04180319). From October 2020 to April 2023, this registry enrolled 137 patients, 14 of whom were excluded for analysis for either missing 12 months of follow-up or baseline pulmonary function. RESULTS: Among the 123 AATD patients, 27 (22.0%) had at least one exacerbation in the last 12 months of follow-up. Patients with Pi*ZZ phenotype were three times more likely than the rest of the population to experience any exacerbation (32.7 vs. 14.1%, p = 0.014; OR 3.0). BODE index was significantly higher in exacerbators than in non-exacerbators (3.9 ± 2.4 vs. 1.3 ± 1.2; p < 0.001), including on multivariate analysis (p = 0.002). Similar results were found for BODEx (multivariate p < 0.001). DLCO was the only functional parameter independently associated with exacerbations (p = 0.024). CONCLUSIONS: DLCO, BODE, and BODEx were independent predictors of exacerbations at 12 months in AATD patients. Understanding these risk factors can aid decision-making on AATD-related lung disease management and improve patient outcomes.

Adenosine receptors are the on-and-off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex.

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R-A2AR or CB1R-A1R heteromers that ultimately impact mPFC synaptic plasticity. CB1R-mediated Ca2+ transients increased and decreased when A1R and A2AR were activated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long-term potentiation (LTP) in the mPFC, under the control of A1R but not of A2AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca2+ level elevations, CB1R activation decreases LTP, which is not modified by A1R or A2AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of A1R, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca2+ signaling.

HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches.

Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

Topical capsaicin 8% patch in peripheral neuropathic pain: Efficacy and quality of life.

Introduction: Peripheral neuropathic pain (PNP) is one of the most challenging diseases to treat with a significant negative impact on the patients' health-related quality of life (HRQoL). Capsaicin 8% patch has arisen in the last decades as an alternative to oral drugs in the treatment of PNP with fewer side effects and promising results in efficacy. Objectives: This work aims to evaluate the effectiveness of the topical application of capsaicin in PNP and its impact on patients' HRQoL based on the use of capsaicin in a tertiary hospital of Oporto. Methods: This study included 100 patients with localized PNP with poor pain control and without improvement with previous treatments that were treated at least once with an 8% capsaicin patch. Effectiveness on pain relief, number of treatments needed, safety and impact on HRQoL were assessed through a set of questionnaires. Results: Regarding the aetiology of PNP, 67.6% (N = 46) have post-surgery or trauma induced PNP with 64.7% (N = 44) of patients reporting pain in the lower limb. After the treatment, 30.9% (N = 21) felt minimally improved, 22.1 (N = 15) felt much improved and 13.2 (N = 9) felt very much improved. On a scale from 1 to 10, in the week prior to the survey, the median intensity of pain was 6 and the median interference in quality of life was 7. The majority of patients still report limitations in mobility and daily activities and moderate pain. Conclusion: Capsaicin 8% patch is effective in PNP treatment at least in the short term. Repeated applications may be important for long-term analgesia. The low systemic dose and few side effects mean that the treatment is generally well tolerated by patients. Due to the analgesic effect, capsaicin can improve the HRQoL of patients with PNP.

Plant-derived Durvalumab variants show efficient PD-1/PD-L1 blockade and therapeutically favourable FcR binding.

Immune checkpoint blocking therapy targeting the PD-1/PD-L1 inhibitory signalling pathway has produced encouraging results in the treatment of a variety of cancers. Durvalumab (Imfinzi®) targeting PD-L1 is currently used for immunotherapy of several tumour malignancies. The Fc region of this IgG1 antibody has been engineered to reduce FcγR interactions with the aim of enhancing blockade of PD-1/PD-L1 interactions without the depletion of PD-L1-expressing immune cells. Here, we used Nicotiana benthamiana to produce four variants of Durvalumab (DL): wild-type IgG1 and its 'Fc-effector-silent' variant (LALAPG) carrying further modifications to increase antibody half-life (YTE); IgG4S228P and its variant (PVA) with Fc mutations to decrease binding to FcγRI. In addition, DL variants were produced with two distinct glycosylation profiles: afucosylated and decorated with α1,6-core fucose. Plant-derived DL variants were compared to the therapeutic antibody regarding their ability to (i) bind to PD-L1, (ii) block PD-1/PD-L1 inhibitory signalling and (iii) engage with the neonatal Fc receptor (FcRn) and various Fcγ receptors. It was found that plant-derived DL variants bind to recombinant PD-L1 and to PD-L1 expressed in gastrointestinal cancer cells and are able to effectively block its interaction with PD-1 on T cells, thereby enhancing their activation. Furthermore, we show a positive impact of Fc amino acid mutations and core fucosylation on DL's therapeutic potential. Compared to Imfinzi®, DL-IgG1 (LALAPG) and DL-IgG4 (PVA)S228P show lower affinity to CD32B inhibitory receptor which can be therapeutically favourable. Importantly, DL-IgG1 (LALAPG) also shows enhanced binding to FcRn, a key determinant of serum half-life of IgGs.

3D bioactive ionic liquid-based architectures: An anti-inflammatory approach for early-stage osteoarthritis.

3D bioprinting enables the fabrication of biomimetic cell-laden constructs for cartilage regeneration, offering exclusive strategies for precise pharmacological screenings in osteoarthritis (OA). Synovial inflammation plays a crucial role in OA's early stage and progression, characterized by the increased of the synovial pro-inflammatory mediators and cytokines and chondrocyte apoptosis. Therefore, there is an urgent need to develop solutions for effectively managing the primary events associated with OA. To address these issues, a phenolic-based biocompatible ionic liquid approach, combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), was used to produce easily printable bioinks. Through the use of this strategy 3D constructs with good printing resolution and high structural integrity were obtained. The encapsulation of chondrocytes like ATDC5 cells provided structures with good cell distribution, viability, and growth, for up to 14 days. The co-culture of the constructs with THP-1 macrophages proved their ability to block pro-inflammatory cytokines (TNF-α and IL-6) and mediators (GM-CSF), released by the cultured cells. Moreover, incorporating the biocompatible ionic liquid into the system significantly improved its bioactive performance without compromising its physicochemical features. These findings demonstrate that ALG/ACE/Ch[Caffeate] bioinks have great potential for bioengineering cartilage tissue analogs. Besides, the developed ALG/ACE/Ch[Caffeate] bioinks protected encapsulated chondrocyte-like cells from the effect of the inflammation, assessed by a co-culture system with THP-1 macrophages. These results support the increasing use of Bio-ILs in the biomedical field, particularly for developing 3D bioprinting-based constructs to manage inflammatory-based changes in OA. STATEMENT OF SIGNIFICANCE: Combining natural resources with active biocompatible ionic liquids (Bio-IL) for 3D printing is herein presented as an approach for the development of tools to manage inflammatory osteoarthritis (OA). We propose combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), a phenolic-based Bio-IL with anti-inflammatory and antioxidant features, to produce bioinks that allow to obtain 3D constructs with good printing resolution, structural integrity, and that provide encapsulated chondrocyte-like cells good viability. The establishment of a co-culture system using the printed constructs and THP-1-activated macrophages allowed us to study the encapsulated chondrocyte-like cells behaviour within an inflammatory scenario, a typical event in early-stage OA. The obtained outcomes support the beneficial use of Bio-ILs in the biomedical field, particularly for the development of 3D bioprinting-based models that allow the monitoring of inflammatory-based events in OA.

Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine.

Astrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic plasticity. However, the precise impact of astrocyte-released D-serine on neuronal modulation remains insufficiently characterized. To address this, we have used the dominant negative SNARE (dnSNARE) mouse model, which selectively inhibits SNARE-dependent exocytosis from astrocytes. We recorded field excitatory postsynaptic potentials (fEPSPs) in CA3-CA1 synapses within hippocampal slices obtained from dnSNARE mice and wild-type (Wt) littermates. Our results demonstrate that hippocampal θ-burst long-term potentiation (LTP), a critical form of synaptic plasticity, is impaired in hippocampal slices from dnSNARE mice. Notably, this LTP impairment was rescued upon incubation with D-serine. To further investigate the involvement of astrocytes in D-serine-mediated mechanisms of LTP maintenance, we perfused hippocampal slices with L-serine - a substrate used by both neurons and astrocytes for D-serine production. The enhancement in LTP observed in dnSNARE mice was exclusively associated with D-serine presence, with no effects evident in the presence of L-serine. Additionally, both D- and L-serine reduced basal synaptic strength in the hippocampal slices of both Wt and dnSNARE mice. These results provide compelling evidence that distinct processes underlie the modulation of basal synaptic transmission and LTP through D-serine. Our findings underscore the pivotal contribution of astrocytes in D-serine-mediated processes that govern LTP establishment and basal transmission. This study not only provides essential insights into the intricate interplay between neurons and astrocytes but also emphasizes their collective role in shaping hippocampal synaptic function.