Human leukocyte antigen-G polymorphisms in periodontitis.

Objective: This study evaluated human leucocyte antigen-G gene polymorphisms in patients with periodontitis and healthy controls.Material and methods: The insertion/deletion polymorphism of 14 bp and a single nucleotide polymorphism (SNP) C > G on the position +3142 of the 3' untranslated region of the gene were analyzed in chronic periodontitis (n = 62), aggressive periodontitis (n = 24) patients and healthy individuals (n = 47).Results: Considering the 14 bp insertion/deletion, a significant deviation from Hardy-Weinberg expectations in the chronic periodontitis group was observed, but not in the other groups. No significant deviations were observed in patients and control groups considering the +3142 C > G SNP. A significant increased frequency of homozygotes for the 14 bp deletion allele was observed in the chronic periodontitis group as compared to controls. This group also presented a higher frequency of the deletion allele, which was marginally not significant. Concerning this polymorphism, no significant differences were observed between the aggressive periodontitis and healthy control groups. In addition, no significant differences were seen amongst patients and controls when considering the +3142 C > G frequencies.Conclusion: No differences were found amongst patients and controls when considering the +3142 C > G SNP haplotypes frequencies, but a significant increased frequency of homozygotes for the 14 bp deletion allele was observed in chronic periodontitis patients compared to healthy controls, suggesting a susceptibility role of this polymorphism in the pathogenesis of this condition.

Experimental Post-traumatic Stress Disorder Decreases Astrocyte Density and Changes Astrocytic Polarity in the CA1 Hippocampus of Male Rats.

Post-traumatic stress disorder (PTSD) is a psychiatric condition resulting from exposure to a traumatic event. It is characterized by several debilitating symptoms including re-experiencing the past trauma, avoidance behavior, increased fear, and hyperarousal. Key roles in the neuropathology of PTSD and its symptomatology have been attributed to the hippocampus and amygdala. These regions are involved in explicit memory processes and context encoding during fear conditioning. The aim of our study was to investigate whether PTSD is capable of altering the morphology, density and expression of glial fibrillary acidic protein (GFAP) in astrocytes from the CA1 region of the hippocampus and the medial amygdala and correlate the data obtained with the orientation index of the polarity of astrocytes. Thirty male rats were divided in two groups: control (n = 15) and PTSD (n = 15). The inescapable shock protocol, in which the animals are exposed to a single episode of footshock, was used to induce PTSD. Our results show that, in the hippocampus, PTSD is capable of decreasing the density of GFAP+ astrocytes as well as altering astrocytic morphology, as shown by the reductions observed in the total number of primary processes, in the number of primary processes in the lateral quadrants, and the degree of branching in the lateral quadrants. The analysis of the orientation index indicates that PTSD alters the polarity of hippocampal astrocytes. No alterations were observed in the amygdala astrocytes. Therefore, this study demonstrates notable changes in hippocampal astrocytes, supporting the concept that these cells play an important role in PTSD symptomatology.

Antidepressant Effects of Ketamine Are Not Related to ¹8F-FDG Metabolism or Tyrosine Hydroxylase Immunoreactivity in the Ventral Tegmental Area of Wistar Rats.

Major depressive disorder (MDD) is an important health problem that is often associated to stress. One of the main brain regions related to MDD is the ventral tegmental area (VTA), a dopaminergic center, part of the reward and motivation circuitry. Recent studies show that changes to VTA dopaminergic neurons are associated with depression and treatment. Ketamine has recently shown a fast, potent antidepressant effect in acute, sub-anesthetic doses. Thus, our aims were to elucidate if ketamine would be able to revert depression-like behaviors induced by a chronic unpredictable stress (CUS) protocol and if it could cause alterations to metabolism and tyrosine hydroxylase (TH)-immunoreactivity in VTA. For this, 48 Wistar rats were divided into four groups: control + saline (CTRL + SAL), control + ketamine (CTRL + KET), CUS + saline (CUS + SAL), CUS + ketamine (CUS + KET). The CUS groups underwent 28 days of CUS protocol. Saline or ketamine (10 mg/kg) was administered intraperitonially once on day 28. The behavior was assessed by the sucrose preference test, the open field test, and the forced swim test. Glucose brain metabolism was assessed and quantified with microPET. TH-immunoreactivity was assessed by estimating neuronal density and regional and cellular optical densities. A decrease in sucrose intake in the CUS groups and an increase in immobility was rapidly reverted by ketamine (p < 0.05). No difference was observed in the open field test. There was no alteration to VTA metabolism and TH-immunoreaction. These results suggest that the depressive-like behavior induced by CUS and the antidepressant effects of ketamine are unrelated to changes in neuronal metabolism or dopamine production in VTA.

Degree of myelination (g-ratio) of the human recurrent laryngeal nerve.

The g-ratio (estimated by dividing the axon diameter by the myelinated fiber diameter) can be useful to the evaluation of the relationship between nerve conduction velocity and fiber morphology during peripheral nerve regeneration. However, there is little detailed information about the g-ratio of the human recurrent laryngeal nerve (RLN), especially between men and women. The objective of this study was to investigate the g-ratio of the RLN by quantifying histomorphometric data (axon diameter and myelinated fiber diameter) in the RLN of men and women. The RLN was bilaterally studied in human specimens obtained from necropsies (seven men and seven women). The nerves were analyzed using histology, and the morphometric parameters were measured using Image Pro-Plus Software (Image Pro-Plus 6.0; Media Cybernetics, Silver Spring, MD, USA). When compared with the RLN of the women, the parameters of the RLN of the men are significantly larger, as shown by the axon diameter (19.0%) (P = 0.0001), myelinated fiber diameter (7.1%) (P = 0.0497), and g-ratio (12.5%) (P = 0.0005). Our findings demonstrated that there are morphological asymmetries between the g-ratio (degree of the myelination) of the masculine and feminine RLN. These morphological findings are probably related to physiological differences.

Neural underpinnings of fine motor skills under stress and anxiety: A review.

This review offers a comprehensive examination of how stress and anxiety affect motor behavior, particularly focusing on fine motor skills and gait adaptability. We explore the role of several neurochemicals, including brain-derived neurotrophic factor (BDNF) and dopamine, in modulating neural plasticity and motor control under these affective states. The review highlights the importance of developing therapeutic strategies that enhance motor performance by leveraging the interactions between key neurochemicals. Additionally, we investigate the complex interplay between emotional-cognitive states and sensorimotor behaviors, showing how stress and anxiety disrupt neural integration, leading to impairments in skilled movements and negatively impacting quality of life. Synthesizing evidence from human and rodent studies, we provide a detailed understanding of the relationships among stress, anxiety, and motor behavior. Our findings reveal neurophysiological pathways, behavioral outcomes, and potential therapeutic targets, emphasizing the intricate connections between neurobiological mechanisms, environmental factors, and motor performance.

Environmental Enrichment in Stroke Research: an Update.

Environmental enrichment (EE) refers to different forms of stimulation, where the environment is designed to improve the levels of sensory, cognitive, and motor stimuli, inducing stroke recovery in animal models. Stroke is a leading cause of mortality and neurological disability among older adults, hence the importance of developing strategies to improve recovery for such patients. This review provides an update on recent findings, compiling information regarding the parameters affected by EE exposure in both preclinical and clinical studies. During stroke recovery, EE exposure has been shown to improve both the cognitive and locomotor aspects, inducing important neuroplastic alterations, increased angiogenesis and neurogenesis, and modified gene expression, among other effects. There is a need for further research in this field, particularly in those aspects where the evidence is inconclusive. Moreover, it is necessary refine and adapt the EE paradigms for application in human patients.

Plasma cytokines levels in aggressive and chronic periodontitis.

OBJECTIVE: The present study evaluated the Th1/Th2 cytokine profile in plasma from healthy controls and different types of periodontitis patients. MATERIALS AND METHODS: The concentration of IL-2, IL-4, IL-5, IL-10, TNF-α and IFN-γ was determined in healthy controls (n = 18) and patients with chronic (n = 19) and aggressive periodontitis (n = 19) using a flow cytometric multiplex immunoassay. Means and standard deviations were calculated and compared using Kruskal-Wallis test. Spearman rho coefficient was used to correlate cytokines in the studied groups. RESULTS: Although there was no significant difference in the concentration of cytokines between groups, there was a tendency to lower levels of IL-5 and IL-10 in the aggressive periodontitis group. Stronger correlations were observed between IL-2/IL-4 and IL-2/IL-10 in healthy controls (0.938 and 0.669, respectively) compared with chronic (0.746 and 0.532) and aggressive periodontitis groups (0.395 and 0.266). When compared to healthy (0.812) and chronic periodontitis (0.845) groups, the correlation of IL-4/IL-5 was weaker in the aggressive group (0.459). CONCLUSION: No difference between systemic levels of Th1/Th2 was observed. In aggressive periodontitis patients, nevertheless, a trend towards low levels of Th2 cytokines could suggest a contribution to the development of such an exacerbated manifestation of this disease.

Can anxiety-like behavior and spatial memory predict the extremes of skilled walking performance in mice? An exploratory, preliminary study.

Introduction: Skilled walking is influenced by memory, stress, and anxiety. While this is evident in cases of neurological disorders, memory, and anxiety traits may predict skilled walking performance even in normal functioning. Here, we address whether spatial memory and anxiety-like behavior can predict skilled walking performance in mice. Methods: A cohort of 60 adult mice underwent a behavioral assessment including general exploration (open field), anxiety-like behavior (elevated plus maze), working and spatial memory (Y-maze and Barnes maze), and skilled walking performance (ladder walking test). Three groups were established based on their skilled walking performance: superior (SP, percentiles ≥75), regular (RP, percentiles 74-26), and inferior (IP, percentiles ≤25) performers. Results: Animals from the SP and IP groups spent more time in the elevated plus maze closed arms compared to the RP group. With every second spent in the elevated plus maze closed arms, the probability of the animal exhibiting extreme percentiles in the ladder walking test increased by 1.4%. Moreover, animals that spent 219 s (73% of the total time of the test) or more in those arms were 4.67 times more likely to exhibit either higher or lower percentiles of skilled walking performance. Discussion: We discuss and conclude anxiety traits may influence skilled walking performance in facility-reared mice.

Conventional Mirror Therapy versus Immersive Virtual Reality Mirror Therapy: The Perceived Usability after Stroke.

Background: Stroke is a widespread and complex health issue, with many survivors requiring long-term rehabilitation due to upper-limb impairment. This study is aimed at comparing the perceived usability of two feedback-based stroke therapies: conventional mirror therapy (MT) and immersive virtual reality mirror therapy (VR). Methods: The study involved 45 participants, divided into three groups: the stroke survivors (n = 15), stroke-free older adults (n = 15), and young controls (n = 15). Participants performed two tasks using both MT and VR in a semirandom sequence. Usability instruments (SUS and NASA-TLX) were applied at the end of the activities, along with two experience-related questions. Results: The results indicated that both MT and VR had similar levels of perceived usability, with MT being more adaptable and causing less overall discomfort. Conversely, VR increased the perception of task difficulty and prevented participants from diverting their attention from the mirror-based feedback. Conclusion: While VR was found to be less comfortable than MT, both systems exhibited similar perceived usability. The comfort levels of the goggles may play a crucial role in determining the usability of VR for upper limb rehabilitation after stroke.

Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide.

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H2O2) to induce oxidative stress activation and BZF treatment was administered at the same moment as H2O2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H2O2-induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H2O2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H2O2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis.

The Foot Fault Scoring System to Assess Skilled Walking in Rodents: A Reliability Study.

The foot fault scoring system of the ladder rung walking test (LRWT) is used to assess skilled walking in rodents. However, the reliability of the LRWT foot fault score has not been properly addressed. This study was designed to address this issue. Two independent and blinded raters analyzed 20 rats and 20 mice videos. Each video was analyzed twice by the same rater (80 analyses per rater). The intraclass correlation coefficient (ICC) and the Kappa coefficient were employed to check the accuracy of agreement and reliability in the intra- and inter-rater analyses of the LRWT outcomes. Excellent intra- and inter-rater agreements were found for the forelimb, hindlimb, and both limbs combined in rats and mice. The agreement level was also excellent for total crossing time, total time stopped, and the number of stops during the walking path. Rating individual scores in the foot fault score system (0-6) ranged from satisfactory to excellent, in terms of the intraclass correlation indexes. Moreover, we showed that experienced and inexperienced raters can obtain reliable results if supervised training is provided. We concluded that the LRWT is a reliable and useful tool to study skilled walking in rodents and can help researchers address walking-related neurobiological questions.

Contagious depression: Automatic mimicry and the mirror neuron system - A review.

Contagious depression is a theory proposing that depression can be induced or triggered by our social environment. This theory is based on emotional contagion, the idea that affective states can be transferred during social interaction, since humans can use emotional contagion to communicate feelings and emotions in conscious and unconscious ways. This review presents behavioral, physiological, and neuroanatomical aspects of two essential contagious depression mechanisms, automatic mimicry and the mirror neuron system.

Rat Adipose-Derived Stromal Cells (ADSCs) Increases the Glioblastoma Growth and Decreases the Animal Survival.

Many studies have shown that mesenchymal stromal cells (MSCs) and their secreted factors may modulate the biology of tumor cells. However, how these interactions happen in vivo remains unclear. In the present study, we investigated the effects of rat adipose-derived stromal cells (ADSCs) and their conditioned medium (ADSC-CM) in glioma tumor growth and malignancy in vivo. Our results showed that when we co-injected C6 cells plus ADSCs into the rat brains, the tumors generated were larger and the animals exhibited shorter survival, when compared with tumors of the animals that received only C6 cells or C6 cells pre-treated with ADSC-CM. We further showed that the animals that received C6 plus ADSC did not present enhanced expression of CD73 (a gene highly expressed in ADSCs), indicating that the tumor volume observed in these animals was not a mere consequence of the higher density of cells administered in this group. Finally, we showed that the animals that received C6 + ADSC presented tumors with larger necrosis areas and greater infiltration of immune cells. These results indicate that the immunoregulatory properties of ADSCs and its contribution to tumor stroma can support tumor growth leading to larger zones of necrosis, recruitment of immune cells, thus facilitating tumor progression. Our data provide new insights into the way by which ADSCs and tumor cells interact and highlight the importance of understanding the fate and roles of MSCs in tumor sites in vivo, as well as their intricate crosstalk with cancer cells.

Age-related tolerance to paraquat-induced parkinsonism in Drosophila melanogaster.

Paraquat (PQ) is a widely used herbicide that can cross the dopaminergic neuronal membrane, accumulate in mitochondria and damage complex I of the electron transport chain, leading to neuronal death. In Drosophila melanogaster, PQ exposure leads to the development of parkinsonism and is a classical model for studying Parkinson's Disease (PD). Muscle mitochondrial dysfunction, affecting survival and locomotion, is described in familial PD in D. melanogaster mutants. However, no study has shown the effects of PQ-induced parkinsonism in D. melanogaster regarding muscle ultrastructure and locomotor behavior at different ages. Thus, we evaluated survival, locomotion, and morphological parameters of mitochondria and myofibrils using transmission electron microscopy in 2 and 15-day-old D. melanogaster, treated with different PQ doses: control, 10, 50, 100, 150, and 200 mM. PQ100mM presented 100% lethality in 15-day-old D. melanogaster, while in 2-day-old animals PQ150mM produced 20% lethality. Bradykinesia was only observed in 15-day-old D. melanogaster treated with PQ10 mM and PQ50 mM. However, these results are unlikely to be associated with changes to morphology. Taken together, our data indicate pathophysiological differences between PQ-induced parkinsonism and familial parkinsonism in D. melanogaster (resultant from gene mutations), demonstrating for the first time a differential susceptibility to PQ in two developmental stages.

Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats.

Type 1 diabetes mellitus (T1DM) is associated with neurocognitive dysfunction and astrogliosis. Physical exercise prevents cognitive impairments and induces important brain modifications. The aim of our study was to investigate the effect of treadmill exercise on spatial memory and astrocytic function in the hippocampus of a T1DM model. Fifty-seven Wistar rats were divided into four groups: trained control (TC) (n = 15), non-trained control (NTC) (n = 13), trained diabetic (TD) (n = 14) and non-trained diabetic (NTD) (n = 15). One month after streptozotocin-induced diabetes, exercise groups were submitted to 5 weeks of physical training, and then, all groups were assessed in the novel object-placement recognition task. Locomotor activity was analyzed in the open field apparatus using Any-maze software. The expression of glial fibrillary acidic protein (GFAP) and S100B in hippocampus and cerebrospinal fluid were measured using ELISA assay, and hippocampal GFAP immunoreactivity was evaluated by means of immunohistochemistry and optical densitometry. The results showed that physical exercise prevents and/or reverts spatial memory impairments observed in NTD animals (P < 0.01). Decreased locomotor activity was observed in both the NTD and TD groups when compared with controls (P < 0.05). ELISA and immunohistochemistry analyzes showed there was a reduction in GFAP levels in the hippocampus of NTD animals, which was not found in TD group. ELISA also showed an increase in S100B levels in the cerebrospinal fluid from the NTD group (P < 0.01) and no such increase was found in the TD group. Our findings indicate that physical exercise prevents and/or reverts the cognitive deficits and astroglial alterations induced by T1DM.

Morphological and mechanical changes induced by quercetin in human T24 bladder cancer cells.

Quercetin is a flavonoid found in a great variety of foods such as vegetables and fruits. This compound has been shown to inhibit the proliferation of various types of cancer cells, as well as the growth of tumors in animal models. In the present study, we analyze morphological and mechanical changes produced by quercetin in T24 bladder cancer cells. Decreased cell viability and cell number were observed following quercetin treatment at 40 µM and 60 µM, respectively, as observed by the MTT assay and trypan blue exclusion test, supporting the hypothesis of quercetin anticancer effect. These assays also allowed us to determine the 40, 60, and 80 µM quercetin concentrations for the following analyses, Lactate Dehydrogenase assay (LDH); Nuclear Morphometric Analysis (NMA); and atomic force microscopy (AFM). The LDH assay showed no cytotoxic effect of quercetin on T24 cancer cells. The AFM showed morphological changes following quercetin treatment, namely decreased cell body, cytoplasmic retraction, and membrane condensation. Following quercetin treatment, the NMA evidenced an increased percentage of nuclei characteristic to the apoptotic and senescence processes. Cells also presented biophysical alterations consistent with cell death by apoptosis, as increased roughness and aggregation of membrane proteins, in a dose-dependent manner. Cellular elasticity, obtained through force curves, showed increased stiffness after quercetin treatment. Data presented herein demonstrate, for the first time, in a quantitative and qualitative form, the morphological and mechanical alterations induced by quercetin on bladder cancer cells.

SARS-CoV-2 mutations in Brazil: from genomics to putative clinical conditions.

Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, contributing towards studies of selective structure-based drug discovery and vaccine development.

Does Angiotensin II Peak in Response to SARS-CoV-2?

Human infection by the SARS-CoV-2 is causing the current COVID-19 pandemic. With the growing numbers of cases and deaths, there is an urgent need to explore pathophysiological hypotheses in an attempt to better understand the factors determining the course of the disease. Here, we hypothesize that COVID-19 severity and its symptoms could be related to transmembrane and soluble Angiotensin-converting enzyme 2 (tACE2 and sACE2); Angiotensin II (ANG II); Angiotensin 1-7 (ANG 1-7) and angiotensin receptor 1 (AT1R) activation levels. Additionally, we hypothesize that an early peak in ANG II and ADAM-17 might represent a physiological attempt to reduce viral infection via tACE2. This viewpoint presents: (1) a brief introduction regarding the renin-angiotensin-aldosterone system (RAAS), detailing its receptors, molecular synthesis, and degradation routes; (2) a description of the proposed early changes in the RAAS in response to SARS-CoV-2 infection, including biological scenarios for the best and worst prognoses; and (3) the physiological pathways and reasoning for changes in the RAAS following SARS-CoV-2 infection.

Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats.

Peri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH1-24 on a collagenase-induced lesion of the germinal matrix (GM) in newborn male rats. Animals received microinjection of the vehicle (PBS, 2 µl) or collagenase type VII (0.3 IU) into the GM/periventricular tissue on postnatal day (PN) 2. Twelve hours later pups received microinjection of either the agonist ACTH1-24 (0.048 mg/kg), or the antagonist SHU9119 (antagonist of MCR3/MCR4 receptors, 0.01 mg/kg), or their combination. Morphological outcomes included striatal injury extension, neuronal and glial cells counting, and immunohistochemical expression of brain lesion biomarkers ipsilateral and contralateral to the hemorrhagic site. Data were evaluated on PN 8. Collagenase induced PIVH and severe ipsilateral striatal lesion. ACTH1-24 dampened the deleterious effects of collagenase-induced hemorrhage in significantly reducing the extension of the damaged area, the striatal neuronal and glial losses, and the immunoreactive expression of the GFAP, S100ß, and NG2-glia biomarkers in the affected periventricular area. SHU9119 blocked the glial density rescuing effect of ACTH1-24. ACTH1-24 could be further evaluated to determine its suitability for preclinical models of PVH in premature infants.

Hemispheric brain injury and behavioral deficits induced by severe neonatal hypoxia-ischemia in rats are not attenuated by intravenous administration of human umbilical cord blood cells.

Neonatal hypoxia-ischemia (HI) is an important cause of mortality and morbidity in infants. Human umbilical cord blood (HUCB) is a potential source of cellular therapy in perinatology. We investigated the effects of HUCB cells on spatial memory, motor performance, and brain morphologic changes in neonate rats submitted to HI. Seven-day-old rats underwent right carotid artery occlusion followed by exposure to 8% O(2) inhalation for 2 h. Twenty-four hours after HI, rats received either saline solution or HUCB cells i.v. After 3 wk, rats were assessed using a Morris Water Maze and four motor tests. Subsequently, rats were killed for histologic, immunohistochemical, and polymerase chain reaction (PCR) analyses. HI rats showed significant spatial memory deficits and a volumetric decrease in the hemisphere ipsilateral to arterial occlusion. These deficits and decreases were not significantly attenuated by the injection of HUCB cells. Moreover, immunofluorescence and PCR analysis revealed few HUCB cells located in rat brain. Intravenous administration of HUCB cells requires optimization to achieve improved therapeutic outcomes in neonatal hypoxic-ischemic injury.