Zinc and selenium supplementation on treated HIV-infected individuals induces changes in body composition and on the expression of genes responsible of naïve CD8+ T cells function.

Background and aim: Deficiency of zinc and selenium is common in persons living with human immunodeficiency virus (PLWHIV) and has been associated with the development of non-AIDS related comorbidities, impaired immune system function and mortality. Micronutrient supplementation on long-term-treated PLWHIV could bring potential clinical and immunological benefits improving their health status and quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density, CD4+ T-cell counts, metabolic profile and immune system status on clinical stable PLWHIV on long-term antiretroviral therapy (ART). Methods: This is a randomized pilot clinical trial in which we recruited 60 PLWHIV on ART who were assigned to the intervention groups: zinc (30 mg of zinc gluconate), selenium (200 µg of selenium yeast), zinc + selenium (same doses and presentations) or to a control group (without nutritional supplementation) who received supplementation during 6 months. Primary outcome was defined as changes in body composition (weight, muscle and fat mass and bone mineral density) and secondary outcomes as changes in biochemical and immunological parameters (CD4+ T-cell count, cholesterol, glucose, triglycerides and seric zinc and selenium seric concentrations) before and after supplementation. Peripheral blood mononuclear cells (PBMCs) of one individual of each intervention group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p = 0.03), fat mass (p = 0.03), and trunk fat (p = 0.01) decreased after 6 months of selenium supplementation. No changes were observed for cholesterol, glucose or triglycerides after supplementation (p > 0.05 in all cases). CD4+ T cells percentage increased after 6 months of selenium supplementation (p = 0.03). On the transcriptome analysis, zinc and selenium supplementation induced changes on de expression of genes associated with the function of naive and memory CD8+ T-cells (p < 0.05 in all cases). Conclusion: Zinc and selenium supplementation could represent a complementary intervention that may improve the health status and immune response of treated PLWHIV.

Involvement of extracellular vesicles in the interaction of hosts and Toxoplasma gondii.

Toxoplasma gondii, the causative agent of toxoplasmosis, is widely distributed. This protozoan parasite is one of the best adapted, being able to infect innumerous species of animals and different types of cells. This chapter reviews current literature on extracellular vesicles secreted by T. gondii and by its hosts. The topics describe the life cycle and transmission (1); toxoplasmosis epidemiology (2); laboratorial diagnosis approach (3); The T. gondii interaction with extracellular vesicles and miRNAs (4); and the perspectives on T. gondii infection. Each topic emphases the host immune responses to the parasite antigens and the interaction with the extracellular vesicles and miRNAs.

Dendritic cell-based immunotherapy in non-small cell lung cancer: a comprehensive critical review.

Despite treatment advances through immunotherapies, including anti-PD-1/PD-L1 therapies, the overall prognosis of non-small cell lung cancer (NSCLC) patients remains poor, underscoring the need for novel approaches that offer long-term clinical benefit. This review examined the literature on the subject over the past 20 years to provide an update on the evolving landscape of dendritic cell-based immunotherapy to treat NSCLC, highlighting the crucial role of dendritic cells (DCs) in immune response initiation and regulation. These cells encompass heterogeneous subsets like cDC1s, cDC2s, and pDCs, capable of shaping antigen presentation and influencing T cell activation through the balance between the Th1, Th2, and Th17 profiles and the activation of regulatory T lymphocytes (Treg). The intricate interaction between DC subsets and the high density of intratumoral mature DCs shapes tumor-specific immune responses and impacts therapeutic outcomes. DC-based immunotherapy shows promise in overcoming immune resistance in NSCLC treatment. This article review provides an update on key clinical trial results, forming the basis for future studies to characterize the role of different types of DCs in situ and in combination with different therapies, including DC vaccines.

Prenatal Stress and Ethanol Exposure: Microbiota-Induced Immune Dysregulation and Psychiatric Risks.

Changes in maternal gut microbiota due to stress and/or ethanol exposure can have lasting effects on offspring's health, particularly regarding immunity, inflammation response, and susceptibility to psychiatric disorders. The literature search for this review was conducted using PubMed and Scopus, employing keywords and phrases related to maternal stress, ethanol exposure, gut microbiota, microbiome, gut-brain axis, diet, dysbiosis, progesterone, placenta, prenatal development, immunity, inflammation, and depression to identify relevant studies in both preclinical and human research. Only a limited number of reviews were included to support the arguments. The search encompassed studies from the 1990s to the present. This review begins by exploring the role of microbiota in modulating host health and disease. It then examines how disturbances in maternal microbiota can affect the offspring's immune system. The analysis continues by investigating the interplay between stress and dysbiosis, focusing on how prenatal maternal stress influences both maternal and offspring microbiota and its implications for susceptibility to depression. The review also considers the impact of ethanol consumption on gut dysbiosis, with an emphasis on the effects of prenatal ethanol exposure on both maternal and offspring microbiota. Finally, it is suggested that maternal gut microbiota dysbiosis may be significantly exacerbated by the combined effects of stress and ethanol exposure, leading to immune system dysfunction and chronic inflammation, which could increase the risk of depression in the offspring. These interactions underscore the potential for novel mental health interventions that address the gut-brain axis, especially in relation to maternal and offspring health.

Direct and Abscopal Antitumor Responses Elicited by AlPcNE-Mediated Photodynamic Therapy in a Murine Melanoma Model.

Melanoma, the most aggressive form of skin cancer, presents a major clinical challenge due to its tendency to metastasize and recalcitrance to traditional therapies. Despite advances in surgery, chemotherapy, and radiotherapy, the outlook for advanced melanoma remains bleak, reinforcing the urgent need for more effective treatments. Photodynamic therapy (PDT) has emerged as a promising alternative, leading to targeted tumor destruction with minimal harm to surrounding tissues. In this study, the direct and abscopal antitumor effects of PDT in a bilateral murine melanoma model were evaluated. Although only one of the two tumors was treated, effects were observed in both. Our findings revealed significant changes in systemic inflammation and alterations in CD4+ and CD8+ T cell populations in treated groups, as evidenced by blood analyses and flow cytometry. High-throughput RNA sequencing (RNA-Seq) further unveiled shifts in gene expression profiles in both treated and untreated tumors. This research sheds light on the novel antitumor and abscopal effects of nanoemulsion of aluminum chloride phthalocyanine (AlPcNE)-mediated PDT in melanoma, highlighting the potential of different PDT protocols to modulate immune responses and to achieve more effective and targeted cancer treatments.

Lysosomal Activation Mediated by Endocytosis in J774 Cell Culture Treated with N-Trimethyl Chitosan Nanoparticles.

Safety and effectiveness are the cornerstone objectives of nanomedicine in developing nanotherapies. It is crucial to understand the biological interactions between nanoparticles and immune cells. This study focuses on the manufacture by the microfluidic technique of N-trimethyl chitosan/protein nanocarriers and their interaction with J774 cells to elucidate the cellular processes involved in absorption and their impact on the immune system, mainly through endocytosis, activation of lysosomes and intracellular degradation. TEM of the manufactured nanoparticles showed spherical morphology with an average diameter ranging from 36 ± 16 nm to 179 ± 92 nm, depending on the concentration of the cargo protein (0, 12, 55 µg/mL). FTIR showed the crosslinking between N-trimethyl chitosan and the sodium tripolyphosphate and the α-helix binding loss of BSA. TGA revealed an increase in the thermal stability of N-trimethyl chitosan/protein nanoparticles compared with the powder. The encapsulation of the cargo protein used was demonstrated using XPS. Their potential to improve cell permeability and use as nanocarriers in future vaccine formulations was demonstrated. The toxicity of the nanoparticles in HaCaT and J774 cells was studied, as well as the importance of evaluating the differentiation status of J774 cells. Thus, possible endocytosis pathways and their impact on the immune response were discussed. This allowed us to conclude that N-trimethyl chitosan nanoparticles show potential as carriers for the immune system. Still, more studies are required to understand their effectiveness and possible use in therapies.

Analysis of the expression of cytokines and chemokines, platelet-leukocyte aggregates, sCD40L and sCD62P in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is a malignancy with a variable incidence worldwide and a poor advanced-stage prognosis. Melanoma growth is closely associated with the immune system. METHODS: A cross-sectional study was performed on CM patients admitted at the Hospital de Cancer de Pernambuco (HCP) between 2015 and 2018. Fifty-one CM patients were included, and 30 healthy individuals. The study aimed to evaluate the association of platelet activation mechanisms and inflammatory response in patients with cutaneous melanoma. RESULTS: Elevated serum IL10 and low serum TNF levels in CM patients compared to controls (p < 0.05). High IL6 levels in patients with negative lymph nodes LN (-) compared to positive lymph nodes group (LN +, p = 0.0005). Low RANTES levels in patients compared to controls (p < 0.05). Elevated levels of platelet-lymphocyte (PLA), platelet-monocytes (PMA), and platelet-neutrophils (PNA) aggregates were observed in patients compared to controls (p < 0.05). CM patients with stage II had lower PMA levels than stages I and III (p < 0.05). High PMA levels were observed in patients with LN (+) compared to the LN (-) group (p < 0.0001). Patients with SSM had high levels of sCD40L and sCD62P compared to controls (p < 0.05)). High sCD40L levels in stage II compared to the stage III group, and sCD62P in stages I and II compared to the stage III group (p < 0.05). High sCD62P levels in patients with LN (-) compared to the group LN (+) (p < 0.05). CONCLUSION: It was observed the immunosuppressive profile in CM may favor tumor progression. High levels of platelet-leukocyte aggregates, sCD40L, and sCD62P may be associated with the worst prognosis.

Antimicrobial peptides (AMPs) from microalgae as an alternative to conventional antibiotics in aquaculture.

The excessive use of conventional antibiotics has resulted in significant aquatic pollution and a concerning surge in drug-resistant bacteria. Efforts have been consolidated to explore and develop environmentally friendly antimicrobial alternatives to mitigate the imminent threat posed by multi-resistant pathogens. Antimicrobial peptides (AMPs) have gained prominence due to their low propensity to induce bacterial resistance, attributed to their multiple mechanisms of action and synergistic effects. Microalgae, particularly cyanobacteria, have emerged as promising alternatives with antibiotic potential to address these challenges. The aim of this review is to present some AMPs extracted from microalgae, emphasizing their activity against common pathogens and elucidating their mechanisms of action, as well as their potential application in the aquaculture industry. Likewise, the biosynthesis, advantages and disadvantages of the use of AMPs are described. Currently, biotechnology tolls are used to enhance the action of these peptides, such as genetically modified microalgae and recombinant proteins. Cyanobacteria are also mentioned as major producers of peptides, among them, the genus Lyngbya is described as the most important producer of bioactive peptides with potential therapeutic use. The majority of cyanobacterial AMPs are of the cyclic type, meaning that they have cysteine and disulfide bridges, thanks to this, their greater antimicrobial activity and selectivity. Likewise, we found that large hydrophobic aromatic amino acid residues increase specificity, and improve antibacterial efficacy. However, based on the results of this review, it is possible to highlight that while microalgae show potential as a source of AMPs, further research in this field is necessary to achieve safe and competitive production. Therefore, the data presented here can aid in the selection of microalgal species, peptide structures, and target bacteria, with the goal of establishing biotechnological platforms for aquaculture applications.

Hematoimmunological responses of juvenile Nile tilapia (Oreochromis niloticus) receiving the dietary supplementation of immunomodulators and different levels of vitamins after challenge with physical stress.

In this study, we analyzed the hematoimmunological effects of dietary supplementation with immunomodulators (ß-glucans + nucleotides) and different levels of vitamins on Nile tilapia (Oreochromis niloticus) after exposure to physical stress. The following four diet treatments were used: diets with indicated vitamin levels (Vitind), diets with Vitind + immunomodulator (Vitind + Immune), diets with high vitamin content (Vithigh), and those with Vithigh + immunomodulator (Vithigh + Immune). The experiment included 560 fish in 28 tanks (20 fish tank-1), with seven replicates per treatment. After 60 days of supplementation, the water temperature was set at 20 °C, and complete biometrics were performed. The animals were then subjected to physical stress with temperature oscillations of 20 ºC to 30 ºC/30 ºC to 20 ºC/20 ºC to 30 ºC. Hematoimmunological data from 140 animals were collected post-stress. Antimicrobial titer and total plasma protein levels were significantly higher in fish not receiving immunomodulator-supplemented diets (2.88 ± 0.43 log2 and 26.81 ± 4.01 mg∙mL-1, respectively) than in those that did. Conversely, the agglutination titer increased in fish fed with lower vitamin levels (3.33 ± 0.66 log2) compared to those with higher vitamin levels. Increased immunoglobulin levels were observed in fish fed diets co-supplemented with vitamins and immunomodulators, revealing an interaction between immunomodulators and dietary vitamin levels. In summary, the inclusion of immunomodulators in the diet enhanced the animals' resistance to physical stress and improved hematoimmunological parameters. Additionally, a high vitamin content in the diet did not modulate the immune responses in the animals.

Neste estudo analisamos os efeitos hematoimunológicos da suplementação dietética com imunomoduladores (ß-glucanos+nucleotídeos) e diferentes níveis de vitaminas na tilápia do Nilo (Oreochromis niloticus) após exposição ao estresse físico. Foram utilizados quatro tratamentos: dietas com níveis indicados de vitaminas (Vitind), dietas com Vitind + imunomodulador (Vitind+Immune), dietas com alto teor de vitaminas (Vithigh) e dietas com Vithigh + imunomodulador (Vithigh+Immune). O experimento incluiu 560 peixes em 28 tanques (20 peixes tanques-1), com sete repetições por tratamento. Após 60 dias de suplementação, a temperatura da água foi fixada em 20 °C e realizada biometria completa. Os animais foram submetidos a estresse físico com oscilações de temperatura de 20 ºC a 30 ºC/30 ºC a 20 ºC/20 ºC a 30 ºC. Dados hematoimunológicos de 140 animais foram coletados pós-estresse. O título antimicrobiano e os níveis de proteína plasmática total foram significativamente maiores em peixes que não receberam dietas com imunomodulador (2,88±0,43 log2 e 26,81±4,01 mg∙mL−1) do que naqueles que receberam. Por outro lado, o título de aglutinação aumentou em peixes alimentados com níveis mais baixos de vitaminas (3,33±0,66 log2) comparado àqueles com níveis mais elevados. Níveis aumentados de imunoglobulinas foram observados em peixes alimentados com dietas co-suplementadas com vitaminas e imunomoduladores, revelando interação entre imunomoduladores e níveis de vitaminas na dieta. Em resumo, a inclusão de imunomoduladores na dieta aumentou a resistência dos animais ao estresse físico e melhorou os parâmetros hematoimunológicos. Além disso, o alto teor de vitaminas na dieta não modulou as respostas imunológicas dos animais.

Association between Physical Activity and Dengue and Its Repercussions for Public Health: New Insights.

Dengue is an endemic disease in tropical countries, mainly in South America, Southwest Asia, and Africa, which, despite having a low lethality rate, can overwhelm health systems. Strengthening the immune system through regular physical activity can be an important tool to prevent contagion, worsening, hospitalizations, and deaths caused by the disease, as seen in the COVID-19 pandemic. Therefore, this point of view aims to analyze the possible association between physical activity and dengue and its repercussions on public health. Comments were made on the main characteristics of dengue as well as on the main vaccines available to date. It was also discussed the impacts of dengue on health systems, in addition to the main repercussions for public health when a very large number of people are infected. It was also commented on the main factors that contribute to the worsening of the clinical stage of dengue, in addition to discussions and reflections on physical activity, strengthening the immune system, and dengue. There are assumptions that regular physical activity can be an important public health strategy to prevent contagion, severity, and hospitalizations caused by dengue and that it needs to be promoted by governments around the world as a tool for preventing and treating not only chronic communicable diseases but also infectious diseases.

Biological Significance of Probiotic Microorganisms from Kefir and Kombucha: A Review.

(1) Background: The human microbiota is essential for maintaining a healthy body. The gut microbiota plays a protective role against pathogenic bacteria. Probiotics are live microorganisms capable of preventing and controlling gastrointestinal and balancing the immune system. They also aid in better nutrients and vitamins absorption. Examples of natural probiotic cultures are kefir and kombucha. (2) Methods: Therefore, the aim of this review was to address the beneficial properties of probiotic kefir and kombucha using a Boxplot analysis to search for scientific data in the online literature up to January 2024: (Latin American and Caribbean Health Sciences (LILACS), PubMed, Medical Literature Analysis (MED-LINE), Science Direct, Google Scholar/Google Academic, Bioline Inter-national and Springer Link). Boxplots showed the summary of a set of data "Index Terms-Keywords" on kefir and kombucha in three languages (English, Portuguese and Spanish). (3) Results: Google Scholar was the database with the highest number of articles found, when the search for the keywords used in the study (containing ~4 × 106-~4 million articles available). This was Followed by the Science Direct database, containing ~3 × 106-~3 million articles available, and the BVS databases-Biblioteca Virtual de Saúde (Virtual Health Library) e Lilacs, both containing a value of ~2 × 106-~2 million articles available. The databases containing the smallest number of articles found were Nutrients and Medline, both containing a value of ≤0.1 × 106-≤100 thousand articles. (4) Conclusions: Scientific studies indicate that kefir and kombucha certainly contain various functional properties, such as antimicrobial, antitumor, anticarcinogenic and immunomodulatory activity, in addition to having a microbiological composition of probiotic bacteria and yeasts. Kefir and kombucha represent key opportunities in the food and clinic/medical fields.

A cross sectional study assessing steatotic liver disease in patients with systemic lupus erythematosus.

Patients with immune-mediated inflammatory diseases are prone to steatotic liver disease (SLD), which has been observed in patients with psoriasis and hidradenitis suppurativa. We aimed to assess whether systemic lupus erythematosus (SLE) was associated with SLD and to define factors associated with SLD in SLE. This was a cross-sectional study, we included 106 consecutive patients with SLE who were seen in the rheumatology clinic between June 2021 and March 2022 and we chose two sex-paired controls for each SLE. All the participants underwent FibroScan and anthropometric assessments. SLD was defined as a controlled attenuation parameter ≥ 275dB/m. Prevalence of SLD was lower in patients with SLE (21.7% vs 41.5%, p < 0.001). Patients with SLE and SLD had a lower frequency of hydroxychloroquine use (65% vs 84%, p = 0.04), and higher C3 levels [123mg/dl (IQR 102-136) vs 99mg/dl (IQR 78-121), p = 0.004]. Factors associated with SLD in SLE were body mass index (BMI), waist circumference, glucose, and C3; hydroxychloroquine use was a protective factor. On univariate analysis, SLE was associated with a reduced risk of SLD (OR 0.39, 95%CI 0.23-0.67); however, after adjusting for age, BMI, waist, glucose, triglycerides, high-density cholesterol, low-density cholesterol, leukocytes, and hydroxychloroquine, it was no longer associated (OR 0.43, 95%CI 0.10-1.91). In conclusion, the prevalence of SLD in patients with SLE was not higher than that in the general population, and SLE was not associated with SLD. The factors associated with SLD were anthropometric data, glucose, hydroxychloroquine, and C3 levels.

Expression of CD28, FAS, PD1, and CTLA4 molecules in the blood of women with triple-negative breast cancer.

BACKGROUND: Locally advanced triple-negative breast cancer (TNBC) represents a public health problem in Brazil. Its standard treatment consists of neoadjuvant chemotherapy (NAC). METHODS: This was a longitudinal study with follow-up performed between the years 2015 and 2017. Thirty women with locally advanced TNBC submitted to NAC, and 30 healthy were included. Peripheral blood samples were collected before NAC (Pre-NAC) and after NAC (Post-NAC). RESULTS: Patients with TNBC had elevated levels of CD28+ T, FAS+ T, CTLA4+ T, PD1+ T, CD28+CD4+ T, PD1+CD4+ T and CD8+ T and PD1+ CD8+ T cells compared to controls (p < 0.05). Patients with pathological complete response (pCR) had low FAS+ T cells, FAS+CD4+ T cells, and PD1+CD8+ T cells compared to the non-pCR (p < 0.05). Significant differences were observed in the levels of CD28+ T cells, FAS+ T and PD1+ T, CD4+ T, CD28+CD4+ T, FAS+CD4+ T, PD1+CD4+ T, CD8+ T, and PD1+CD8+ T cells between Pre-NAC and Post-NAC groups (p < 0.05). CONCLUSION: Alterations in the circulating FAS+CD4+ T and PD1+CD8+ T cell levels Pre-NAC are associated with pCR, suggesting potential predictive biomarkers of NAC response in TNBC. The largest changes in the cellular immune response profile Post-NAC showed that chemotherapy treatment can modulate the immune response and that it is associated with prognosis in TNBC.

Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos / Immune compromise in patients with Down syndrome. A case series

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer.

BACKGROUND: In prostate cancer (PCa), well-established biomarkers such as MSI status, TMB high, and PDL1 expression serve as reliable indicators for favorable responses to immunotherapy. Recent studies have suggested a potential association between CDK12 mutations and immunotherapy response; however, the precise mechanisms through which CDK12 mutation may influence immune response remain unclear. A plausible explanation for immune evasion in this subset of CDK12-mutated PCa may be reduced MHC expression. RESULTS: Using genomic data of CDK12-mutated PCa from 48 primary and 10 metastatic public domain samples and a retrospective cohort of 53 low-intermediate risk primary PCa, we investigated how variation in the expression of the MHC genes affected associated downstream pathways. We classified the patients based on gene expression quartiles of MHC-related genes and categorized the tumors into "High" and "Low" expression levels. CDK12-mutated tumors with higher MHC-expressed pathways were associated with the immune system and elevated PD-L1, IDO1, and TIM3 expression. Consistent with an inflamed tumor microenvironment (TME) phenotype, digital cytometric analyses identified increased CD8 + T cells, B cells, γδ T cells, and M1 Macrophages in this group. In contrast, CDK12-mutated tumors with lower MHC expression exhibited features consistent with an immune cold TME phenotype and immunoediting. Significantly, low MHC expression was also associated with chromosome 6 loss of heterozygosity (LOH) affecting the entire HLA gene cluster. These LOH events were observed in both major clonal and minor subclonal populations of tumor cells. In our retrospective study of 53 primary PCa cases from this Institute, we found a 4% (2/53) prevalence of CDK12 mutations, with the confirmation of this defect in one tumor through Sanger sequencing. In keeping with our analysis of public domain data this tumor exhibited low MHC expression at the RNA level. More extensive studies will be required to determine whether reduced HLA expression is generally associated with primary tumors or is a specific feature of CDK12 mutated PCa. CONCLUSIONS: These data show that analysis of CDK12 alteration, in the context of MHC expression levels, and LOH status may offer improved predictive value for outcomes in this potentially actionable genomic subgroup of PCa. In addition, these findings highlight the need to explore novel therapeutic strategies to enhance MHC expression in CDK12-defective PCa to improve immunotherapy responses.

Immunological alterations in patients with current and lifetime suicide ideation and attempts: Examining the relationship with depressive symptoms.

Background: Suicidal ideation and attempt (SI/SA) have been associated with dysregulation of the immune response and inflammation. However, few studies have explored how innate and acquired cellular immunity impact on the peripheral immune response. Our study addresses this gap by examining the composition of peripheral immune cells and humoral markers among individuals with current SI/SA, individuals with a history of SI/SA, and healthy controls (HC). Additionally, we aim to explore whether depressive symptoms settle the relationship between inflammation and SI/SA. Methods: This is a multicenter case-control study that included 105 participants. Clinical and demographic characterists together with hemogram parameters, soluble pro and anti-inflamatory factors, and specific innate and adaptive immune cell populations were compared among patients with current SI/SA (n = 21), a history of lifetime SI/SA (n = 42), and HC (n = 42). Results: Patients with both current and lifetime SI/SA had a significant increase in the absolute count of monocytes and in the monocyte/lymphocyte ratio (MLR). Additionally, patients with current and lifetime SI/SA showed a significant increase in high-sensitivity C- reactive protein (hs-CRP), and patients with lifetime SI/SA also showed higher levels of Erythrocyte Sedimentation Rate (ESR). The cellular inflammatory status of patients with SI/SA was characterized by altered proportions of monocytes with higher levels of nonclassical and intermediate monocytes. No differences were observed in the number of lymphocytes and the proportion of CD4 and CD8 between patients and HC, but we found differences in markers of exhaustion of CD4 lymphocytes, with increased levels of Programmed cell death protein 1 (PD1) in Current SI/SA and Lymphocyte activation gene 3 (LAG3) in Current SI/SA and Lifetime SI/SA compared to HC. The plasmainflammatory status was marked by higher levels of soluble Triggering receptor expressed on myeloid cells 2 (sTREM2) in patients with lifetime SI/SA compared to HC. Finally, the multinomial analysis indicates that inflammation and depressive symptoms are independently associated with SI/SA. Conclusion: This study highlights the association of immunological alterations with SI/SA. Furthremore, SI/SA is independently influenced by depressive symptoms and inflammation. This may have important therapeutic implications, as in these patients, it may be necessary to treat the inflammatory process beyond treating the depressive symptoms.

The association of blood biomarkers with cerebral white matter and myelin content in bipolar disorder: a systematic review.

OBJECTIVES: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. METHODS: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. RESULTS: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). CONCLUSION: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.

The Impact of Exercise on Interleukin-6 to Counteract Immunosenescence: Methodological Quality and Overview of Systematic Reviews.

OBJECTIVE: This study evaluated the methodological quality of published systematic reviews on randomized and non-randomized clinical trials to synthesize evidence on the association between IL-6, immunosenescence, and aerobic and/or resistance exercise. METHOD: The Preferred Reporting Items for Overviews of Systematic Reviews (PRIO-harms) guideline was used, with registration number CRD42022346142-PROSPERO. Relevant databases such as Cochrane Library, PubMed, Web of Science, Scopus, and Google Scholar were searched using English Medical Subject Headings terms. Inclusion criteria were systematic reviews analyzing aerobic exercise, resistance exercise, or a combination of both and assessing IL-6 as a biomarker of cellular immunosenescence in humans. The Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) was employed. RESULTS: Out of 742 identified articles, 18 were eligible, and 13 were selected for analysis. Sample sizes ranged from 249 to 1421 participants, mostly female, with ages ranging from 17 to 95 years. Aerobic exercise was the most studied type (46.15%), followed by combined exercise (38.46%) and resistance exercise (15.38%). Aerobic exercise showed a statistically significant reduction in IL-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) levels. Among the 13 reviews analyzed using AMSTAR-2, 8 were rated as critically low quality, and 5 were classified as low quality. CONCLUSION: Aerobic exercise has anti-inflammatory properties and the potential to modulate IL-6, CRP, and TNF-α levels in immunosenescence. However, the limited methodological quality of the analyzed systematic reviews highlights the urgent need for robust, high-quality studies to improve access to information and facilitate evidence-based decision-making in healthcare.

Oral administration of a new copper (I) complex with coumarin as ligand: modulation of the immune response and the composition of the intestinal microbiota in Onchorhynchus mykiss.

[Cu(NN1)2]ClO4 is a copper (I) complex, where NN1 is an imine ligand 6-((quinolin-2-ylmethylene) amino)-2H-chromen-2-one obtained by derivatization of natural compound coumarin, developed for the treatment of infectious diseases that affect salmonids. In previous research, we showed that the Cu(I) coordination complex possesses antibacterial activity against Flavobacterium psychrophilum, providing protection against this pathogen in rainbow trout during challenge assays (with an RPS of 50%). In the present study, the effects of administering [Cu(NN1)2]ClO4 to Oncorhynchus mykiss over a 60-days period were evaluated with regard to systemic immune response and its potential to alter intestinal microbiota composition. In O. mykiss, an immunostimulatory effect was evident at days 30 and 45 after administration, resulting in an increment of transcript levels of IFN-γ, IL-12, TNF-α, lysozyme and perforin. To determine whether these immunomodulatory effects correlated with changes in the intestinal microbiota, we analyzed the metagenome diversity by V4 16S rRNA sequencing. In O. mykiss, both [Cu(NN1)2]ClO4 and commercial antibiotic florfenicol had comparable effects at the phylum level, resulting in a predominance of proteobacteria and firmicutes. Nonetheless, at the genus level, florfenicol and [Cu(NN1)2]ClO4 complex exhibited distinct effects on the intestinal microbiota of O. mykiss. In conclusion, our findings demonstrate that [Cu(NN1)2]ClO4 is capable of stimulating the immune system at a systemic level, while inducing alterations in the composition of the intestinal microbiota in O. mykiss.