HERV-W upregulation expression in bipolar disorder and schizophrenia: unraveling potential links to systemic immune/inflammation status.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SZ) are the two main mental disorders with unknown etiology that significantly impact individuals' quality of life. The potential pro-inflammatory role in their pathogenesis is postulated and Human Endogenous Retrovirus W (HERV-W) is an emerging candidate to modulate this pathogenic finding. HERVs, ancient retroviruses in the human genome, may play roles in inflammation and disease pathogenesis. Despite HERVs' involvement in autoimmune diseases, their influence on mental disorders remains underexplored. Therefore, the aim of this study was to assess the level of HERV-W-env expression and the systemic inflammatory profile through the concentration of IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ cytokines in BD and SZ patients. RESULTS: All participants showed HERV-W-env expression, but its expression was higher in mental disorder patients (p < 0.01) than in control. When separated, SZ individuals exhibited higher HERV-W expression than the control group (p < 0.01). Higher serum levels of TNF-α and IL-10 were found in BD (p = 0.0001 and p = 0.001, respectively) and SZ (p = 0.01) and p = 0.01, respectively) than in the control group, while SZ showed decreased levels IFN-γ and IL-2 as compared to controls (p = 0.05) and BD patients (p = 0.05), respectively. Higher TNF-α/IL-4 and TNF-α/IL-10 ratios, and lower IFN-γ/IL-10 were observed in BD and SZ patients than controls. Significant negative correlation between HERV-W-env expression and IL-10 (r=-0.47 p < 0.05), as well as positive correlations between HERV-W-env expression and TNF-α/IL-10 or IFN-γ/IL-10 ratios (r = 0.48 p < 0.05 and r = 0.46 p < 0.05, respectively) were found in BD patients. CONCLUSION: These findings suggest not only a potential link between HERV-W-env expression both in BD and SZ, but also a possible involvement of systemic inflammatory status in BD patients.

Expression of monocyte chemokine receptors in diabetes after non-surgical periodontal treatment: A pilot study.

The aim of this study was to evaluate the effect of non-surgical periodontal treatment in the expression of chemokine receptors, in individuals with Periodontitis, associated or not with Diabetes. Pilot study, which included patients (n = 45) with Periodontitis, associated (n = 25) or not (n = 20) with Diabetes, submitted to the non-surgical periodontal treatment for one month. The expression of chemokine receptors CCR2, CCR5, and CX3CR1 at the mRNA level was evaluated in the peripheral mononuclear cells, as well as the expression of these receptors at the protein level was verified in monocyte subtypes (classical, intermediate, and non-classical monocytes). There was higher expression of CCR2 and CCR5 receptors at the initial visit in the group with Diabetes, with no differences for CX3CR1 (p = 0.002; p = 0.018, and p = 0.896, respectively), without differences after treatment. There was higher expression of CCR2 and CCR5 proteins in the group with Diabetes at the initial visit for classical, intermediate, and nonclassical monocytes, with no differences for CX3CR1 (CCR2: p = 0.004; p = 0.026; p = 0.024; CCR5: 0.045; p = 0.045; p = 0.013; CX3CR1: p = 0.424; p = 0.944; p = 0.392, respectively), without differences after the end of treatment. Concerning each group separately, there were reductions in the expression of CCR2 as well as CCR5 in classical, intermediate, and nonclassical monocytes, and reduction of CX3CR1 in classical monocytes after treatment in the group with Diabetes (p = 0.003; p = 0.006; p = 0.039; p = 0.007; p = 0.006; p = 0.004; p = 0.019, respectively), without differences in the group without Diabetes. The expression of the chemokine receptors CCR2 and CCR5, in patients with Periodontitis associated with Diabetes, is favorably modified after the end of the non-surgical periodontal treatment.

BMP-7, MMP-9, and TGF-ß tissue remodeling proteins and their correlations with interleukins 6 and 10 in chronic rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis without nasal polyposis (CRSsNP) and Chronic rhinosinusitis with nasal polyposis (CRSwNP) present distinct tissue remodeling processes. The proteins involved in the process of tissue remodeling have their production and activity related to the inflammatory environment they are. This study aimed to evaluate the protein expression of BMP-7, MMP-9, TGF-ß in chronic sinusitis with and without nasal polyposis and their relations with IL-6 and IL-10. METHODS: Cross-sectional observational study with 86 participants was divided into three groups: patients with CRSwNP (n = 34), patients with CRSsNP (n = 26), and a control group (CG) without inflammatory disease of the nasal mucosa (n = 26). The primary outcomes were the concentrations of BMP-7, MMP-9, TGF-ß, IL-6, and IL-10. Secondary outcomes were the correlations of these markers. RESULTS: The TGF-ß dosage was elevated in the CRSsNP group and reduced in the CSwNP group. The dosage of IL-6 was higher in the CSwNP group, and the IL-10 dosage lower in the groups with sinusitis, and IL-10 was positively correlated with BMP-7 in all groups. There was a negative correlation between IL-6 and IL-10 in all groups observed. The correlation between MMP-9 and interleukins was lost in the CRSsNP group. There was a positive correlation between TGF-ß and IL-6 in the CG, and negative in the CRSsNP group. CONCLUSION: An inflammation shown in rhinosinusitis with an increase in IL-6 and decrease in IL-10 when compared with the control group; only TGF-ß was altered in the tissue remodeling process when compared with BMP-7 and MMP-9 in rhinosinusitis. There is a loss of correlation between tissue remodeling proteins and interleukins studied in CRSsNP.

Collagen peptides modulate the metabolism of extracellular matrix by human dermal fibroblasts derived from sun-protected and sun-exposed body sites.

Clinical data published in recent years have demonstrated positive effects of collagen hydrolysate (CH) on skin aging clinical signs. CH use as food supplement has a long history; however, few studies have addressed the underlying purpose of CH on the cellular and molecular biology of skin cells that could elucidate clinical improvement findings. Wide diversity of characteristics has been reported for dermal fibroblasts derived from different body sites and it is unknown whether collagen peptides could modulate differently cells from chronological aged and photoaged skin areas. This study investigated the influence of CH on the extracellular matrix metabolism and proliferation of human dermal fibroblasts (HDFs) derived from chronological aged (sun-protected) and photoaged (sun-exposed) body sites. CH treatment did not affect cellular proliferation of either cell cultures, but notably modulated cell metabolism in monolayer model, increasing the content of dermal matrix precursor and main protein, procollagen I and collagen I, respectively. These effects were confirmed in the human dermal equivalent model. The increase in collagen content in the cultures was attributed to stimulation of biosynthesis and decreased collagen I metabolism through inhibition of metalloproteinase activity (MMP) 1 and 2. Modulation of CH in dermal metabolism did not differ between cells derived from sun-protected and sun-exposed areas, although lower concentrations of CH seemed to be enough to stimulate sun-exposed-derived HDFs, suggesting more pronounced effect in these cells. This study contributes to understanding the biological effects of CH on skin cells and viability of its use as a functional ingredient in food supplements.

Sudden sensorineural hearing loss: audiological profile during the COVID-19 pandemic.

Introduction: Sudden sensorineural hearing loss (SSNHL) is an otological emergency that requires prompt recognition and intervention to prevent devastating impacts on people's lives. During the COVID-19 pandemic, sensory deprivations have been reported in patients positive for SARS-CoV-2 virus, including deleterious effects on the auditory pathway. This study aims to describe the audiological profile of individuals with SSNHL during the COVID-19 pandemic and to correlate hearing recovery in subgroups of individuals with or without COVID-19. Methods: Prospective cohort including patients diagnosed with SSNHL evaluated in a tertiary care center between March 2020 and September 2022. Hearing loss was confirmed with pure-tone and speech audiometry, with Speech Recognition Threshold (SRT) and word recognition score (WRS). Audiometric testing was performed at the moment of diagnosis, then 7, 30 and 120 days after diagnosis. The average degree of hearing loss was assessed by calculating the 4-frequency pure tone average (4fPTA). The investigation of COVID-19 included RT-PCR technique for the SARS-CoV-2 virus and collection of information regarding disease severity. A statistical analysis was performed using an analysis of covariance (ANCOVA) model to compare the 4fPTA between the four groups (with and without a history of COVID-19, unilateral and bilateral cases) at the end of the follow-up period. Results: Fifty-two patients with SSNHL were assessed, 40 (76.9%) with unilateral and 12 (23.1%) with bilateral hearing loss, totaling 64 ears included. Of those, 15 (28.8%) patients tested positive for SARS-CoV-2 and were symptomatic for COVID-19. Of all unilateral cases, 22.5% were seropositive and showed symptoms of COVID-19, a number that increased to 50% for bilateral cases. Comparing the COVID-19 positive groups, individuals with unilateral SSNHL went from 40 dB as their average 4fPTA at onset to 20 dB as their average 4fPTA after 120 days, whereas those with bilateral SSNHL went from an initial average of 60 dB to a final average of 66 dB. Although the 4fPTA value of individuals with unilateral SSNHL improved in 7 days, the mean values showed no significant difference between positive and negative groups. There was a higher incidence of bilateral simultaneous SSNHL in patients who had not been vaccinated against COVID-19 and who presented with symptoms of severe COVID-19. Conclusion: Infection with SARS-CoV-2 resulted in more severe SSNHL, in bilateral SSNHL, and in poorer recovery from SSNHL in bilateral cases. Bilateral SSNHL was seen more frequently in patients who had not received vaccination against COVID-19.

Acute and chronic response of supervised band-elastic resistance exercise in systemic cytokines levels of bipolar disorders and schizophrenia individuals: a pilot study.

Despite earlier research demonstrating the immunomodulatory effects of acute and chronic exercise in many medical illnesses, there is a lack of literature evaluating the acute and chronic effects of exercise on the cytokine levels in individuals with bipolar disorder (BD) or schizophrenia (SCH). This study aims to examine the acute effects of resistance exercise on cytokines and the chronic effects of resistance exercise by 10 weeks on cytokine levels, symptoms of disease, and muscular strength in individuals with BD and SCH. The included individuals (N=10) performed a single session of band-elastic resistance exercises (six exercises, 3 sets of 12 to 15 repetitions, 60seconds of interval between sets). A sub-sample (N=6) of individuals performed a supervised band-elastic resistance exercise program (2 times a week, for 10 weeks, 6 exercises, 3 sets of 12 to 15 repetitions, 60seconds of interval). We verified for acute effects: IL-2 (P=0.0085) and IL-4 (P=0.0253) levels increased, while IL-6 decreased (P=0.0435), and for chronic effects: increased IL-2 and IL-4 levels (significant effect size - Pre vs Post), a decrease in disease symptoms, and an increase in muscular strength. This study adds to what is already known about how resistance exercises affect people with BD and SCH in both short-term (systemic cytokines levels) and long-term (symptoms of disease, muscular strength, and systemic cytokines levels).

Synthetic hemozoin as a nanocarrier for cross-presentation.

It is known that conventional antigen presentation involves phagocytosis of antigens followed by its internalization in endocytic compartments and presentation of epitopes through MHC class II molecules for CD4 T cells. However, since 1976 a cross-presentation pathway has been studied, in which CD8 T cells are activated via MHC class I with antigens acquired through phagocytosis or endocytosis by dendritic cells (DCs). Among some important molecules involved in the cross-presentation, the C-type lectin receptor of the Dectin-1 cluster (CLECs), particularly the CLEC9A receptor, not only is expressed in dendritic cells but also presents a pivotal role in this context. In special, CLEC12A has been highlighted as a malaria pigment hemozoin (HZ) receptor. During Plasmodium infection, hemozoin crystals defend the parasite against heme toxicity within erythrocytes, as well as the released native HZ elicits pro-inflammatory responses and can induce cross-presentation. Particularly, this crystal can be synthesized from hematin anhydride and mimics the native form, and the gaps generated between the nanocrystal domains during its synthesis allow for substance coupling followed by its coating. Therefore, this study aimed to assess whether synthetic hemozoin (sHz) or hematin anhydride could be a nanocarrier and promote cross-presentation in dendritic cells. Firstly, it was verified that sHz can carry coated and coupled antigens, the compounds can associate to LAMP1-positive vesicles and decrease overall intracellular pH, which can potentially enhance the cross-presentation of ovalbumin and Leishmania infantum antigens. Thus, this study adds important data in the molecular intricacies of antigen presentation by showing not only the sHz immunomodulatory properties but also its potential applications as an antigen carrier.

The inflammatory and metabolic status of patients with sudden-onset sensorineural hearing loss.

Introduction: Sudden sensorineural hearing loss (SSNHL) is a common emergency symptom in otolaryngology that requires immediate diagnosis and treatment. SSNHL has a multifactorial etiology, and its pathophysiologic mechanisms may be associated with inflammatory and metabolic changes that may affect the cochlear microenvironment or its nervous component, thus triggering the process or hindering hearing recovery. Therefore, the aim of this study was to assess metabolic and inflammatory changes to identify systemic parameters that could serve as prognostic factors for hearing recovery in patients with SSNHL. Materials and methods: Thirty patients with a sudden hearing loss of at least 30 dB in three contiguous frequencies were enrolled in this study. Patients were followed up for 4 months and peripheral blood samples were collected at 7 days (V1), 30 days (V2) and 120 days (V3). Interleukins (IL)-1F7, IL-2, IL-4, IL-5, IL-6, IL-10, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and adiponectin were quantified in serum. In addition, lipid and glycemic profiles as well as concentration of creatinine, uric acid, fructosamine, peroxide, total proteins and albumin were analyzed. Patients underwent weekly ear-specific hearing tests with standard pure tone thresholds for frequencies of 250-8,000 Hz, speech recognition threshold and word recognition score. Results: Patients with SSNHL were divided into a group of patients who did not achieve hearing recovery (n = 14) and another group who achieved complete and significant recovery (n = 16). Most serologic parameters showed no significant changes or values indicating clinical changes. However, IFN-γ levels decreased by 36.3% between V1 and V2. The cytokine TNF-α showed a statistically significant decrease from V1 to V3 (from 22.91 to 10.34 pg./mL). Adiponectin showed a decrease from 553.7 ng/mL in V1 to 454.4 ng/mL in V3. Discussion: Our results show that serologic cytokine levels change in the acute phase of manifestation of SSNHL and establish a parallel between systemic changes and improvements in hearing, especially TNF-α, which showed differences in hearing recovery. The use of IFN-γ, TNF-α and adiponectin may elucidate the clinical improvement in these patients.

Role of circulating microparticles and cytokines in periodontitis associated with diabetes.

Background: Periodontitis is a chronic inflammatory condition that affects the supporting tissues of the teeth, and can lead to serious complications such as tooth loss and systemic health problems, including diabetes, which have a bidirectional relationship with periodontitis. Circulating microparticles originate from different cell types after stimuli such as activation or apoptosis. Interleukins are related to processes in the regulation of the immune response, inflammation, and cell growth. This study aimed to evaluate circulating microparticles as well as interleukins in the plasma, at baseline and 1 month after the end of the non-surgical periodontal treatment. Methods: Samples were collected from 45 patients, with moderate to severe periodontitis with diabetes (N = 25) and without diabetes (N = 20). Microparticles were evaluated in the platelet-poor plasma by flow cytometer. Cytokine levels were evaluated by the enzyme immunoabsorption assay (ELISA). Results: Higher levels of the pro-inflammatory cytokines were found in the group with diabetes compared to the non-diabetic group both at baseline and 1 month after the end of the treatment. A higher IL-6/IL-10 ratio was found in patients with diabetes compared to the group without diabetes at T0 and T1, whereas an increased IFN-γ/IL-10 ratio was only found at T1 in patients with diabetes in comparison to the group without diabetes. In the group with diabetes, it was verified positive correlations between IL-10 and IL-6 or IFN-γ and a negative correlation between IL-6 and PMP, at T0; in contrast, in the T1, negative correlations were found between TNF-α and IL-10 or PMP. Besides, at T0, it was evidenced positive correlations both between circulating TNF-α and IL-6, and IL-10 and EMP, as well as a negative correlation between IL-10 and PMP in the group with diabetes. In addition, it was observed in T1 positive correlations between levels of TNF-α and IL-6, IFN-γ, or IL-10, and between PMP and IFN-γ, and between EMP and IL-6, TNF-α and IFN-γ in this group. Conclusion: The results suggest a modulatory effect of the periodontitis associated with diabetes, as well as the periodontal treatment, in the systemic inflammatory status of the participants of the study.

Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion.

BACKGROUND: ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. RESULTS: In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. CONCLUSIONS: ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells.

Differential Angiogenic Induction Impacts Nasal Polyp Tissue Growth.

In chronic rhinosinusitis with nasal polyps, inflammatory edema drives tissue remodeling favoring anomalous growth of the nasal mucosa, but a proangiogenic contribution of nasal polyp in support of tissue growth is still controversial. The chorioallantoic membrane of chicken embryo model was employed to address the potentiality of nasal tissue fragments to modulate angiogenesis. Fifty-seven fertilized eggs were implanted with polyp or healthy nasal mucosa tissue or were kept as non-implanted controls. The embryos' size, length, and development stage, and chorioallantoic membrane vasculature morphology were evaluated after 48 h. Quantitative computer vision techniques applied to digital chorioallantoic membrane images automatically calculated the branching index as the ratio between the areas of the convex polygon surrounding the vascular tree and the vessels' area. Ethics approval and consent to participate: the study was approved by the Human Research Ethics Committee of the Federal University of São Paulo (CAAE number: 80763117.1.0000.5505) and by the Animal Research Ethics Committee of University of São Paulo (nº CEUA 602-2019). Mucosal, but not polyp tissue implants, hampered embryo development and induced underdeveloped chorioallantoic membranes with anastomosed, interrupted, and regressive vessels. Vessels' areas and branching indexes were higher among the chorioallantoic membranes with polyp implants and controls than among those with healthy mucosa implants. Nasal polyp presents differential angiogenic induction that impacts tissue growth.

Persistence of a proinflammatory status after treatment of the acute myocardial infarction.

AIM: To evaluate the lipid-lowering and antiplatelet combined strategies on the expression of the receptors CCR2, CCR5, and CX3CR1 and the percentage of CCR2, CCR5, and CX3CR1 cells in monocyte subtypes after acute myocardial infarction. METHODS: Prospective, randomized, open-label study, with blinded analyses of endpoints (PROBE, ClinicalTrials.gov Identifier: NCT02428374, registration date: April 28, 2015). Participants were treated with rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg. The chemokine receptors CCR2, CCR5, and CX3CR1 were analyzed by real-time polymerase chain reaction as well as the percentages of CCR2, CCR5, and CX3CR1 cells in the monocyte subtypes (classical, intermediate, and non-classical), which were quantified by flow cytometry, at baseline, and after 1 and 6 months of treatment. RESULTS: After comparisons between the three visits, regardless of the treatment arm, there was an increase in CCR2 expression after treatment, as well as an increase in intermediate monocytes CCR2+ and a reduction in non-classical monocytes CCR2+ at the end of treatment. There was also a lower expression of CCR5 after treatment and an increase in classical and non-classical monocytes CCR5+. Concerning CX3CR1, there were no differences in the expression after treatment; however, there were reductions in the percentage of intermediate and non-classical monocytes CX3CR1+ at the end of treatment. CONCLUSIONS: The results suggest the persistence of the inflammatory phenotype, known as trained immunity, even with the highly-effective lipid-lowering and antiplatelet therapies. Geriatr Gerontol Int 2023; 23: 700-707.

Association among inflammaging, body composition, physical activity, and physical function tests in physically active women.

Background: Inflammaging is a phenomenon that has been associated with the development and progression of sarcopenia and frailty syndrome. According to the literature, on the one side, the increase in body fat is associated with a systemic pro-inflammatory status, which consequently favors inflammaging, and on the other side, the regular practice of physical exercise can mitigate the development of this scenario. Therefore, here, we aimed to evaluate the association between inflammaging and physical factors, both body and functional, in a group of physically active older women. Methods: Seventy older women (mean age 72.66 ± 6.17 years) participated in this observational cross-sectional and were separated into the eutrophic, overweight, and obese groups. It was assessed: by bioimpedance-body fat percentage (Fat%) and total (Fat kg), skeletal muscle mass (muscle), and free fat mass both in percentage (FFM%) and total (FFMkg); by the International Physical Activity Questionnaire (IPAQ)-the time of moderate-intensity physical activity per week; by physical tests-handgrip (HG), sit-up-stand-on-the-chair in 5 repetitions (Sit-up) and vertical squat jump test (SJ); in addition to the determination of serum cytokine concentration (IL-6, TNF-α, IL-10, and IL-8), and also body mass index (BMI) and calf circumference (Calf). Results: Higher FFM% and lower body fat (both kg and %) were found in the eutrophic group than in the other groups. The eutrophic group also performed more weekly physical activity, jumped higher, and presented not only higher serum IL-6 concentration but also an increased ratio of IL-10/IL-6, IL-10/TNF-α, IL-10/IL-8 as compared to the values found in the overweight group. The obese group presented higher body fat (kg and %) and lower FFM% than the other groups and also higher serum IL-6 concentration than the overweight group. Interestingly, several significant negative and positive correlations between body composition, physical tests, and serum cytokine concentrations were found in the eutrophic and obese groups. Conclusion: While the eutrophic older women group showed a remarkable regulation of the systemic inflammatory status with positive associations in the physical parameters assessed, the overweight and obese groups presented impairment regulations of the inflammaging, which could be related to less weekly physical activity and higher body fat.

Cellular and Humoral Immune Responses to Vaccination for COVID-19 Are Negatively Impacted by Senescent T Cells: A Case Report.

BACKGROUND: Herein, we aimed to follow up on the cellular and humoral immune responses of a group of individuals who initially received the CoronaVac vaccine, followed by a booster with the Pfizer vaccine. METHODS: Blood samples were collected: before and 30 days after the first CoronaVac dose; 30, 90, and 180 days after the second CoronaVac dose, and also 20 days after the booster with the Pfizer vaccine. RESULTS: Whilst the positivity to gamma interferon-type cellular response increased after the first CoronaVac dose, neutralizing and IgG antibody levels only raised 30 days after the second dose, followed by a drop in these responses after 90 and 180 days. The booster with the Pfizer vaccine elicited a robust cellular and humoral response. A higher number of double-negative and senescent T cells, as well as increased pro-inflammatory cytokines levels were found in the participants with lower humoral immune responses. CONCLUSION: CoronaVac elicited an early cellular response, followed by a humoral response, which dropped 90 days after the second dose. The booster with the Pfizer vaccine significantly enhanced these responses. Furthermore, a pro-inflammatory systemic status was found in volunteers who presented senescent T cells, which could putatively impair the immune response to vaccination.

Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction.

Introduction: Although it is broadly known that monocyte recruitment is involved in atherosclerosis development and that, in accordance with the microenvironment, these cells can be modulated into three well-known subpopulations: Classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++), the effects of treatment with different pharmacological strategies (based on lipid-lowering and antiplatelets) after acute myocardial infarction upon the monocytes modulation and the role of the chemokine receptors CCR2, CCR5 and CX3CR1 in this context, are poorly understood. Methods: In this study, patients [n = 148, both men (n = 105, 71%) and women (n = 43, 29%)] submitted to treatment with a 2×2 factorial design, in which they received rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg were enrolled. Monocyte subsets were analyzed by flow cytometry at baseline (BL), and after one (1-M) and 6 months (6-M) of treatment. Results: Firstly, our results showed that, regardless of the treatment received, higher percentages of classical monocytes and lower of non-classical monocytes were found at the 6-M time point than BL values, whilst the percentage of intermediate monocytes was higher in all time points assessed than the other subsets. There were reductions in the CCR2 expression by non-classical and intermediate monocytes, without differences for the classical subtype. Concerning the CCR5 expression, there were reductions in the three monocyte subtypes, whereas the CX3CR1 expression increased both in intermediate and classical monocytes, without differences for non-classical monocytes. In relation to the treatment received, a higher percentage of intermediate monocytes at the 6-M time point than the values BL was observed in the group treated with simvastatin + ezetimibe + clopidogrel. No significant differences were found concerning non-classical, intermediate, and classical monocytes, for CCR2, CCR5, and CX3CR1 in the four treatment arms. Conclusion: Taken together, our results demonstrated that even under lipid-lowering and antiplatelet therapy for 6 months, the inflammatory phenotype of monocytes still persisted in the patients enrolled in this study.

Distinct Immunological Profiles Help in the Maintenance of Salivary Secretory IgA Production in Mild Symptoms COVID-19 Patients.

Background: Relevant aspects regarding the SARS-CoV-2 pathogenesis and the systemic immune response to this infection have been reported. However, the mucosal immune response of the upper airways two months after SARS-CoV-2 infection in patients with mild/moderate symptoms is still not completely described. Therefore, we investigated the immune/inflammatory responses of the mucosa of the upper airways of mild/moderate symptom COVID-19 patients two months after the SARS-CoV-2 infection in comparison to a control group composed of non-COVID-19 healthy individuals. Methods: A cohort of 80 volunteers (age 37.2 ± 8.2), including non-COVID-19 healthy individuals (n=24) and COVID-19 patients (n=56) who presented mild/moderate symptoms during a COVID-19 outbreak in Brazil in November and December of 2020. Saliva samples were obtained two months after the COVID-19 diagnosis to assess the levels of SIgA by ELISA and the cytokines by multiplex analysis. Results: Salivary levels of SIgA were detected in 39 volunteers into the COVID-19 group and, unexpectedly, in 14 volunteers in the control group. Based on this observation, we distributed the volunteers of the control group into without SIgA or with SIgA sub-groups, and COVID-19 group into without SIgA or with SIgA sub-groups. Individuals with SIgA showed higher levels of IL-10, IL-17A, IFN-γ, IL-12p70, IL-13, and IFN-α than those without SIgA. In intergroup analysis, the COVID-19 groups showed higher salivary levels of IL-10, IL-13, IL-17A, and IFN-α than the control group. No statistical differences were verified in the salivary levels of IL-6 and IFN-ß. Lower IL-12p70/IL-10 and IFN-γ/IL-10 ratios were found in the control group without SIgA than the control group with SIgA and the COVID-19 group with SIgA. Conclusion: We were able to present, for the first time, that associations between distinct immunological profiles can help the mucosal immunity to maintain the salivary levels of SIgA in COVID-19 patients two months after the SARS-CoV-2 infection.

Effects of physical distancing by COVID-19 pandemic on diet quality, neurological and immunological markers, and fecal microbiota of Brazilian older women.

Physical distancing was used to prevent transmission of COVID-19, however there are concerns that this may promote harmful impacts on health, such as reduced levels of physical practice and changes in food intake and gut microbiota composition. This study evaluated the impacts of 6 months physical distancing on Brazilian older women upon body mass index (BMI), strength, physical activity level (IPAQ), eating habits, neurological markers (brain-derived neurotrophic factor-BDNF and cortisol), cytokines (IL-2, IL-5, IL-6, IL-10, interferon-IFN-γ, tumor necrosis factor-TNF-α), aging-associated markers (vascular endothelial growth factor-VEGF, insulin-like growth factor-IGF-1, klotho and thymic stromal lymphopoietin-TSLP), besides specific groups of fecal microbiota. Fifteen women, over 60 years old, residents of São Paulo state (Brazil), were evaluated in March and in September 2020. The older adult women, with a mean age 66 ± 6.2 years presented significantly increased BMI and high effect size for non-protective foods consumption, reduced light physical activity and strength 6 months following the physical distancing. Furthermore, the serum concentration of IFN-γ, IGF-1, and IFN-γ/IL-5 were significantly higher, while lower concentration of IL-2 and IL-5 were observed 6 months after the physical distancing. Significant increase was noted only to Blautia spp. abundance after 6 months of physical distancing. Several correlations were observed at both before and after physical distancing, however, interestingly, many of them were lost or inverted 6 months following, while new ones emerged. Taken together, these results showed that lifestyle changes and stress conditions addressed by physical distancing from the COVID-19 pandemic impacted the health of older women included in the present study. Therefore, future follow-up studies are essential to propose interventions in order to restore the health conditions observed before the pandemic period, and thus to maintain the quality of life of older adults in different socioeconomic contexts.

Evaluation of Oxidative-Stress Pathway and Recovery of Sudden Sensorineural Hearing Loss.

Introduction Although the pathogenesis of sudden sensorineural hearing loss (SSNHL) has been discussed in the literature, many unclear points remain. Several authors have hypothesized that oxidative stress plays a role in the pathogenesis of noise-related hearing loss, as well as in drug- and aging-related hearing loss. Reactive oxygen species (ROS) may contribute to the pathogenesis of SSNHL in a similar way as in cases of ototoxicity, noise-induced hearing loss and presbyacusis. Objective The aim of the present study was to find potential peripheral biomarkers to show the levels of oxidative stress in samples of peripheral blood collected from SSNHL patients with and withouth metabolic disease. Methods In total, 80 consecutive patients with SSNHL were evaluated in the otolaryngology emergency room and outpatient clinic of a tertiary hospital between May 2017 and May 2019. All patients underwent detailed anamnesis, physical examination, audiometry, magnetic resonance imaging (MRI) of the inner ears, and blood tests for serum lipids and plasma activity of thiobarbituric acid reactive species (TBARS). Results No significant effect of malondialdehyde (MDA) activity was observed regarding the hearing recovery of patients who developed SSNHL. Conclusion We did not observe a significant correlation between the concentration of TBARs in the peripheral blood or the presence of arterial hypertension and the severity of the initial hearing loss or the prognosis of hearing recovery in patients with SSNHL. The concentration of TBARs in the peripheral blood may not adequately represent the abnormalities that occur in the intracoclear environment.

In Nasal Mucosal Secretions, Distinct IFN and IgA Responses Are Found in Severe and Mild SARS-CoV-2 Infection.

Likely as in other viral respiratory diseases, SARS-CoV-2 elicit a local immune response, which includes production and releasing of both cytokines and secretory immunoglobulin (SIgA). Therefore, in this study, we investigated the levels of specific-SIgA for SARS-CoV-2 and cytokines in the airways mucosa 37 patients who were suspected of COVID-19. According to the RT-PCR results, the patients were separated into three groups: negative for COVID-19 and other viruses (NEGS, n = 5); negative for COVID-19 but positive for the presence of other viruses (OTHERS, n = 5); and the positive for COVID-19 (COVID-19, n = 27). Higher specific-SIgA for SARS-CoV-2, IFN-ß, and IFN-γ were found in the COVID-19 group than in the other groups. Increased IL-12p70 levels were observed in OTHERS group as compared to COVID-19 group. When the COVID-19 group was sub stratified according to the illness severity, significant differences and correlations were found for the same parameters described above comparing severe COVID-19 to the mild COVID-19 group and other non-COVID-19 groups. For the first time, significant differences are shown in the airway's mucosa immune responses in different groups of patients with or without respiratory SARS-CoV-2 infection.

Cell death and lumen formation in spheroids of MCF-7 cells.

3D (three-dimensional) cell culture permits a more integrated analysis of the relationship between cells, inserting them into a structure more closely resembling the cellular microenvironment in vivo. The development of in vitro parameters to approximate in vivo 3D cellular environments makes a less reductionist interpretation of cell biology possible. For breast cells, in vitro 3D culture has proven to be an important tool for the analysis of luminal morphogenesis. A greater understanding of this process is necessary because alterations in the lumen arrangement are associated with carcinogenesis. Following lumen formation in 3D cell culture using laser scanning confocal microscopy, we observed alterations in the arrangement of cytoskeletal components (F-actin and microtubules) and increasing levels of cell death associated with lumen formation. The formation of a polarized monolayer facing the lumen was characterized through 3D reconstructions and the use of TEM (transmission electron microscopy), and this process was found to occur through the gradual clearing of cells from the medullary region of the spheroids. This process was associated with different types of cell death, such as apoptosis, autophagy and entosis. The present study showed that changes in the extracellular matrix associated with long periods of time in 3D cell culture lead to the formation of a lumen in MCF-7 cell spheroids and that features of differentiation such as lumen and budding formation occur after long periods in 3D culture, even in the absence of exogenous extracellular compounds.