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Existing literature suggests that infection-specific mechanisms may play a significant role in the onset and progression of dementia, as opposed to the broader phenomenon of systemic inflammation. In addition, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors have been proposed as a potential therapeutic approach for sepsis, given their anti-inflammatory and antioxidant properties. We investigated the neuroprotective effect of an HMG-CoA reductase inhibitor (simvastatin) by analyzing neurodegenerative markers, mitochondrial respiration, and neuronal tracing in the prefrontal cortex (PFC) and thalamic nucleus reuniens (RE) of sepsis survivor animals. Adult Wistar rats were subjected to sepsis by cecal ligation and puncture or left non-manipulated. The animals were treated with simvastatin or vehicle for 4 days before and 10 days after surgery. The treatment preserved the non-associative memory (P < 0.05), recovered expression of Smad-3 in the hippocampus (P < 0.05), and prevented increased expression of calpain-1 (hippocampus: P < 0.0001; PFC: P < 0.05) and GSKβ (hippocampus: P < 0.0001; PFC: P < 0.0001) in the brain structures of the sepsis survivor animals. These animals also showed mitochondrial dysfunction and decreased axon terminals in the RE. Simvastatin seems to restore energy metabolism by improving the electron transfer system (ETS) values in the hippocampus (P < 0.01) and the oxidative phosphorylation/ETS (P/E) ratio in the PFC (P < 0.05), in addition to preventing the reduction of axon terminals in survivor animals. These results suggest a potential neuroprotective effect and the importance of considering HMG-CoA reductase inhibitors as a possible adjuvant therapy in sepsis., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Childhood maltreatment may be linked to epigenetics and brain-derived neurotrophic factor (BDNF) changes, which are mechanisms altered in several psychiatric conditions, including bipolar disorder (BD). However, the specific mechanisms connecting childhood maltreatment to the pathophysiology of BD remain unclear. The present study aims to examine the effects of childhood maltreatment on epigenetic and neurotrophic outcomes in BD patients and health controls. History of childhood maltreatment was obtained using the Childhood Trauma Questionnaire (CTQ) from 36 BD outpatients and 46 healthy subjects. DNA methyltransferase (DNMT) activity, HMTH3K9 activity, histone 3 lysine 9 tri-methylation (H3K9me3) levels, histone deacetylase (HDAC)1 levels, HDAC2 levels, histone 3 lysine 14 acetylation (H3K14ac) levels, and mRNA of BDNF were evaluated in peripheral blood mononuclear cells. Plasma BDNF levels were also measured. Total scores of CTQ, as well as the subscale scores of emotional abuse, sexual abuse, and emotional neglect, were predictive of changes in DNMT and HMTh3k9 activity, H3K9m3 levels, BDNF mRNA expression, and BDNF levels. These findings were observed in all our samples and, in some cases, among BD patients. Emotional abuse was the main childhood maltreatment subtype associated with epigenetic alterations in BD. Our results elucidate some mechanisms by which childhood maltreatment can alter epigenetic and neurotrophic markers. Especially in BD subjects, our results suggest childhood maltreatment per se is not a direct cause for epigenetic alterations. In another way, we suppose that the effect of childhood maltreatment could be cumulative and interact with other factors associated with the pathophysiology of BD., Competing Interests: Declarations Ethical statement The Regional Ethics Committee for Research on Humans of the University of Southern Santa Catarina approved the present study under protocol number 2,928,502. Competing interests JQ has a clinical research support relationship with LivaNova; is a member of the speaker bureau with Myriad Neuroscience and AbbVie; is a consultant for EMS, Libbs, and Eurofarma; is a stockholder at Instituto de Neurociencias Dr. Joao Quevedo; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. MF Juruena is funded by the NIHR Biomedical Research Centre (BRC) at the South London and Maudsley (SLaM) NHS Foundation Trust and King’s College London. Received honoraria for lectures and advisory boards from most of the major pharmaceutical companies with drugs used in affective and related disorders, in the last year advisory board for Janssen (J&J), Daiichi Sankyo, Lundbeck, honoraria from Janssen, Abbott, EMS, Libbs, Eurofarma and Livanova. In addition, receives copyrights Nature/Springer Books, Cambridge Press and Elsevier Press. All other authors have no conflicts of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Postoperative cognitive dysfunction (POCD), a complication following procedures such as orthopedic surgery, is associated with a worsened prognosis, especially in the elderly population. Several mechanisms have been proposed for communication between the immune system and the brain after surgery. In an experimental tibial fracture (TF) model, we aimed to understand the role of the NLR family pyrin domain containing 3 (NLRP3) on oxidative stress and mitochondrial dysfunction as mechanisms underlying POCD in aged and adult rats. Adult or aged male Wistar rats were subjected to the TF model and received intracerebroventricular saline or MCC950 (140 ng/kg), a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome. We followed the control (sham) and TF groups treated with MCC950 or saline for seven days to determine cognitive function and survival. The prefrontal cortex and hippocampus were isolated for NLRP3 evaluation, cytokine analysis, oxidative stress measurements, myeloperoxidase activity, nitric oxide formation, mitochondrial respiratory chain enzymes, and succinate dehydrogenase (SDH) activity. Seven days after TF induction, NLRP3 levels increased in the hippocampus and prefrontal cortex in both ages, showed an enhancement in aged rats compared to adults, and experienced a reversal with MCC950 administration. The administration of MCC950 restored memory, IL-1β and IL-10 levels, nitrite/nitrate, lipid peroxidation in the hippocampus and prefrontal cortex, and preserved catalase activity in the prefrontal cortex in aged rats. At the same age, the complex I activity alteration in both regions and complex II, IV, and SDH in the prefrontal cortex were reversed. In conclusion, NLRP3 activation contributes to POCD development because it is intrinsically involved in mitochondrial dysfunction and oxidative stress after orthopedic surgery in aged rats., Competing Interests: Declarations Ethics approval This study was approved by the Animal Research Ethic Committee of the University of Southern Santa Catarina (protocol 19.034.4.01.IV). The “Principles of Laboratory Animal Care” (NIH publication n° 80–23, revised 1996) and the “EC Directive 86/609/EEC” were followed in all experiments. Consent to participate Not applicable. Consent for publication All authors gave their consent for publication. Conflicts of interest The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Obesity is a complex multifactorial disease in which excess body fat triggers negative health effects. Systemically, obesity causes several changes, such as inflammation, oxidative stress, mitochondrial dysfunction and apoptosis; factors linked to the slow and incomplete epithelial regenerative process. Specifically, in the integumentary system, obesity causes an expansion of the skin's surface area and changes in collagen deposition. Molecular underpinnings of why obesity delays wound healing are still poorly understood. In addition to the primary role of dermal adipocytes in lipid storage and heat insulation, they also promote skin immunity, wound healing and hair follicle cycling. As a consequence of the cellular and dysfunctional adaptations of adipocytes, inflammatory immune alterations, alteration in the expression of proteins genes associated with the blood supply, altered collagen formation through fibroblast senescence and excessive degradation of extracellular matrix proteins are metabolic characteristics of the system in obesity that contribute to sustained inflammation and decreased mechanical resistance of the skin., (© 2024 The Wound Healing Society.)

Background: Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects. The present study evaluated the genotoxic and mutagenic effects of moderate chronic consumption of India Pale Ale (IPA) craft beer. Sixty-four adult male Swiss mice were used and divided into control and treatment groups receiving water, IPA beer with 55.23 g of ethanol per liter of beer, aqueous solution with 55.23 g of ethanol per liter, and hop infusion ad libitum for 30 days. After this period, the animals were genetically evaluated with a comet assay. For the ex vivo comet assay, blood was collected and exposed to hydrogen peroxide (H 2 O 2 ). For the in vivo assay, the alkylating agent cyclophosphamide (CP) was administered to the groups after blood collection and sacrificed after 24 h. Brain, liver, and heart tissues were analyzed. Bone marrow was collected and submitted to the micronucleus test., Results: The groups treated with IPA beer, ethanol, and hops did not show genotoxic and mutagenic action in the blood, brain, heart, or liver. The antigenotoxic action of IPA beer and hops was observed in both in vivo and ex vivo models, showing a similar reduction in DNA damage caused by CP. There was no significant difference between the groups with regard to the formation of micronuclei by CP., Conclusion: Moderate chronic consumption of IPA beer and hops infusion showed antigenotoxic effects in mice but no antimutagenic action. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The purpose of this review was to evaluate the effect of Photobiomodulation (PBM) in managing shoulder and neck pain and disability. A literature search was conducted using the PubMed and ScienceDirect/EMBASE databases. The keywords used were "Low-level laser therapy", "photobiomodulation", "LASER", combined with "shoulder" or "neck". Only clinical studies written in English, Portuguese, Spanish, Italian, French, and German, were included. The review included 36 studies applying PBM therapy to alleviate pain or disability in patients with shoulder and neck conditions. Of these, 12 studies focused on neck conditions, and 24 studies addressed shoulder conditions, with one study concurrently examining both areas. This review on PBM therapy for shoulder and neck conditions shows promising results, particularly in pain relief and functional improvements, with infrared wavelengths being the most commonly used. Subacromial Impingement Syndrome (SAIS) and Myofascial Pain Syndrome (MPS) were the most frequently studied conditions. However, chronic and complex conditions like cervical osteoarthritis and post-stroke shoulder pain were less frequently represented, indicating a research gap. PBM was found to be a safe and non-invasive therapeutic option. Despite positive outcomes, variability in PBM protocols remains a challenge. Further standardized trials are needed to confirm its effectiveness across diverse conditions. This review updates current knowledge, highlights key findings, and provides direction for future research and clinical applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The innate immune system consists of a diverse set of immune cells, including innate lymphoid cells (ILCs), which are grouped into subsets based on their transcription factors and cytokine profiles. Among these are natural killer (NK) cells, group 1 ILCs, group 2 ILCs, group 3 ILCs, and lymphoid tissue inducers (LTi). Unlike T and B cells, ILCs do not express the diverse antigen receptors typically found on those cells. Although ILCs function in various systems, further research is needed to understand their role in the brain and their involvement in neurological diseases such as stroke. This review explores the general immunological aspects of ILCs, with a particular focus on their role in the central nervous system and the pathophysiology of ischemic stroke., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Inc.)

The reproducibility crisis in bioscience, characterized by inconsistent study results, impedes our understanding of biological processes and global collaborative studies offer a unique solution. This study is the first global collaboration using the zebrafish ( Danio rerio ) novel tank test, a behavioral assay for anxiety-like responses. We analyzed data from 20 laboratories worldwide, focusing on housing conditions and experimental setups. Our study included 488 adult zebrafish, tested for 5 min, focusing on a variety of variables. Key findings show females exhibit more anxiety-like behavior than males, underscoring sex as a critical variable. Housing conditions, including higher stocking densities and specific feed types, influenced anxiety levels. Optimal conditions (5 fish/L) and nutritionally rich feeds (e.g., rotifers), mitigated anxiety-like behaviors. Environmental stressors, like noise and transportation, significantly impacted behavior. We recommend standardizing protocols to account for sex differences, optimal stocking densities, nutritionally rich feeds, and minimizing stressors to improve zebrafish behavioral study reliability., Competing Interests: Competing Interest Statement: The authors declare no competing interests.

Objective: An eucalyptus essential oil-based nanoemulsion was produced and evaluated for its antimicrobial properties against Streptococcus mutans and its cytotoxicity in the surface mucous cells of rabbits. Methods: The essential oil-based nanoemulsion was synthesized with two species of eucalyptus- Eucalyptus citriodora and Eucalyptus globulus -followed by physicochemical characterization and the determination of antimicrobial activity and cell viability. Subsequently, the mouthwash formulations (fluoride and fluoride-free) were functionalized with the nanoemulsion, and their in vitro antimicrobial actions were evaluated against S. mutans . Results: The nanoemulsion presented an average particle size of around 100 nm, a polydispersity index close to 0.3, a zeta potential between -19 and -30 mV, a pH close to 7, a spherical shape, and a cell viability above 50%. The antimicrobial activity analysis showed that the nanoemulsion was effective in the control of S. mutans. The mouthwashes functionalized with the nanoemulsion also presented bacteriostatic and bactericidal properties. Conclusions: The bio-based material produced with eucalyptus essential oil presented adequate physicochemical characteristics, with the potential to be used as an innovative material in preventive dentistry, contributing to the maintenance of oral and systemic health.

Alcohol is the most consumed addictive substance worldwide that elicits multiple health problems. Consumption of alcoholic beverages by pregnant women is of great concern because pre-natal exposure can trigger fetal alcohol spectrum disorder (FASD). This disorder can significantly change the embryo's normal development, mainly by affecting the central nervous system (CNS), leading to neurobehavioral consequences that persist until adulthood. Among the harmful effects of FASD, the most reported consequences are cognitive and behavioral impairments. Alcohol interferes with multiple pathways in the brain, affecting memory by impairing neurotransmitter systems, increasing the rate of oxidative stress, or even activating neuroinflammation. Here, we aimed to evaluate the deleterious effects of alcohol on the cholinergic signaling and memory in a FASD zebrafish model, using inhibitory avoidance and novel object recognition tests. Four months after the embryonic exposure to ethanol, the behavioral tests indicated that ethanol impairs memory. While both ethanol concentrations tested (0.5 % and 1 %) disrupted memory acquisition in the inhibitory avoidance test, 1 % ethanol impaired memory in the object recognition test. Regarding the cholinergic system, 0.5 % ethanol decreased ChAT and AChE activities, but the relative gene expression did not change. Overall, we demonstrated that FASD model in zebrafish impairs memory in adult individuals, corroborating the memory impairment associated with embryonic exposure to ethanol. In addition, the cholinergic system was also affected, possibly showing a relation with the cognitive impairment observed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Stroke is the second most common cause of death and one of the most common causes of disability worldwide. The intestine is home to several microorganisms that fulfill essential functions for the natural and physiological functioning of the human body. There is an interaction between the central nervous system (CNS) and the gastrointestinal system that enables bidirectional communication between them, the so-called gut-brain axis. Based on the gut-brain axis, there is evidence of a link between the gut microbiota and the regulation of microglial functions through glial activation. This interaction is partly due to the immunological properties of the microbiota and its connection with the CNS, such that metabolites produced by the microbiota can cross the gut barrier, enter the bloodstream and reach the CNS and significantly affect microglia, astrocytes and other cells of the immune system. Studies addressing the effects of short-chain fatty acids (SCFAs) on glial function and the BBB in ischemic stroke are still scarce. Therefore, this review aims to stimulate the investigation of these associations, as well as to generate new studies on this topic that can clarify the role of SCFAs after stroke in a more robust manner., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.

Major depressive disorder (MDD) has demonstrated its negative impact on various aspects of the lives of those affected. Although several therapies have been developed over the years, it remains a challenge for mental health professionals. Thus, understanding the pathophysiology of MDD is necessary to improve existing treatment options or seek new therapeutic alternatives. Clinical and preclinical studies in animal models of depression have shown the involvement of synaptic plasticity in both the development of MDD and the response to available drugs. However, synaptic plasticity involves a cascade of events, including the action of presynaptic proteins such as synaptophysin and synapsins and postsynaptic proteins such as postsynaptic density-95 (PSD-95). Additionally, several factors can negatively impact the process of spinogenesis/neurogenesis, which are related to many outcomes, including MDD. Thus, this narrative review aims to deepen the understanding of the involvement of synaptic formations and their components in the pathophysiology and treatment of MDD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: Gestational diabetes mellitus (GDM) is the main cause of hyperglycemia in pregnancy and is related to complications throughout the gestational and post-partum period., Objectives: To analyze the pregnancy outcomes related to the occurrence of GDM in women and their offspring., Methods: Third-trimester pregnant women were interviewed and monitored until childbirth. The diagnosis of GDM, blood glucose ≥ 92 mg/dL, was defined by the criteria of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)., Results: A total of 138 women participated, and there were 136 births (due to 2 fetal losses); 23 (16.7%) were diagnosed with GDM. The risk of complications during childbirth was higher among pregnant women with GDM (RR 3.40; 95%CI 1.65-7.00), as was the occurrence of cesarean birth (RR 1.9; 95%CI 1.46-2.59). The occurrence of preterm birth did not show a significant difference between GDM/non-GDM groups. There was a non-significant association in adjusted analyses of macrosomia (birth weight ≥ 4000 g) among newborns born to mothers with GDM (RR 1.27; 95%CI 0.67-2.38). For newborns born to pregnant women with GDM, there was a higher risk for the following outcomes: large for gestational age (LGA) (3.29 95%CI 1.62-6.64), low Apgar (4.98 95%CI 2.32-10.69), and birth asphyxia (9.51 95%CI 3.42-26.48)., Conclusions: The findings reinforce that GDM is an important risk factor for adverse pregnancy outcomes for women and their offspring.

Autism spectrum disorder (ASD) etiology probably involves a complex interplay of both genetic and environmental risk factors, which includes pre- and perinatal exposure to environmental stressors. Thus, this study evaluated the effects of prenatal exposure to valproic acid (VPA) combined with maternal deprivation (MD) on behavior, oxidative stress parameters, and inflammatory state at a central and systemic level in male and female rats. Pregnant Wistar rats were exposed to VPA during gestation, and the offspring were submitted to MD. Offspring were tested for locomotor and social behavior; rats were euthanized, where the cerebellum, posterior cortex, prefrontal cortex, and peripheric blood were collected for oxidative stress and inflammatory analysis. It was observed that young rats (25-30 days old) exposed only to VPA presented a lower social approach when compared to the control group. VPA + MD rats did not present the same deficit. Female rats exposed to VPA + MD presented oxidative stress in all brain areas analyzed. Male rats in the VPA and VPA + MD groups presented oxidative stress only in the cerebellum. Regarding inflammatory parameters, male rats exposed only to MD exhibited an increase in pro-inflammatory cytokines in the blood and in the cortex total. The same was observed in females exposed only to VPA. Animals exposed to VPA + MD showed no alterations in the cytokines analyzed. In summary, gestational (VPA) and perinatal (MD) insults can affect molecular mechanisms such as oxidative stress and inflammation differently depending on the sex and brain area analyzed. Combined exposition to VPA and MD triggers oxidative stress especially in female brains without evoking an inflammatory response., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cerebrovascular disease is the second-leading cause of death and disability worldwide, with stroke being the most common cause. In ischemic stroke, several processes combine to produce immunosuppression, leaving the post-stroke body susceptible to infection, which in turn affects neuroinflammation. Interleukin-33 (IL-33), a member of the interleukin-1 family (IL-1), functions as a modulator of immune responses and inflammation, playing a crucial role in the establishment of immunologic responses. IL-33 has been shown to have a protective effect on brain injury and represents a potential target by modulating inflammatory cytokines and stimulating immune regulatory cells. With an emphasis on preclinical and clinical studies, this review covers the impact of IL-33 on immune system mechanisms following ischemic stroke., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ischemic stroke (IS) results in the interruption of blood flow to the brain, which can cause significant damage. The pathophysiological mechanisms of IS include ionic imbalances, oxidative stress, neuroinflammation, and impairment of brain barriers. Brain barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (B-CSF), protect the brain from harmful substances by regulating the neurochemical environment. Although the BBB is widely recognized for its crucial role in protecting the brain and its involvement in conditions such as stroke, the B-CSF requires further study. The B-CSF plays a fundamental role in regulating the CSF environment and maintaining the homeostasis of the central nervous system (CNS). However, the impact of B-CSF impairment during pathological events such as IS is not yet fully understood. In conditions like IS and other neurological disorders, the B-CSF can become compromised, allowing the entry of inflammatory substances and increasing neuronal damage. Understanding and preserving the integrity of the B-CSF are crucial for mitigating damage and facilitating recovery after ischemic stroke, highlighting its fundamental role in regulating the CNS during adverse neurological conditions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The role of adenosine receptors in fascial manipulation-induced analgesia has not yet been investigated. The purpose of this study was to evaluate the involvement of the adenosine A 1 receptor (A 1 R) in the antihyperalgesic effect of plantar fascia manipulation (PFM), specifically in mice with peripheral inflammation. Mice injected with Complete Freund's Adjuvant (CFA) underwent behavioral, i.e. mechanical hyperalgesia and edema. The mice underwent PFM for either 3, 9 or 15 min. Response frequency to mechanical stimuli was then assessed at 24 and 96 h after plantar CFA injection. The adenosinergic receptors were assessed by systemic (intraperitoneal, i.p.), central (intrathecal, i.t.), and peripheral (intraplantar, i.pl.) administration of caffeine. The participation of the A 1 R was investigated using the 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A 1 R subtype antagonist. PFM inhibited mechanical hyperalgesia induced by CFA injection and did not reduce paw edema. Furthermore, the antihyperalgesic effect of PFM was prevented by pretreatment of the animals with caffeine given by i.p., i.pl., and i.t. routes. In addition, i.pl. and i.t. administrations of DPCPX blocked the antihyperalgesia caused by PFM. These observations indicate that adenosine receptors mediate the antihyperalgesic effect of PFM. Caffeine's inhibition of PFM-induced antihyperalgesia suggests that a more precise understanding of how fascia-manipulation and caffeine interact is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: Gut dysbiosis may play a role in immune-mediated diseases, such as psoriasis. There is a growing interest in understanding microbiome influence, with speculations around the importance of an altered gut microbiome linked to the progression to psoriatic arthritis in psoriasis. The objective of this study is to study the gut microbiome in patients with severe psoriatic disease with or without psoriatic arthritis., Methods: V3/V4 16S rRNA gene sequencing and bioinformatics analyses were performed with the total DNA extracted from the stool samples of 30 patients with psoriatic disease, 15 of whom had documented psoriatic arthritis., Results: We found differences in gut microbiome composition in psoriatic arthritis patients when looking for relative and especially differential abundances. Bacteroidaceae family (P = .02), Bacteroides genus (P=.02), and Bacteroides uniformis (P=.03) were more abundant in psoriatic arthritis patients on differential abundance, adjusted for each taxonomic level. However, the present study did not show significant differences in alpha or beta diversity., Conclusion: This study shows different patterns of gut microbiome composition in patients with psoriatic arthritis, with significant overexpression of the Bacteroides genus. This reinforces the microbiome as a field of interest in psoriasis. Nevertheless, it should be noted that some previously described findings related to lower diversity and different clustering between groups could not be demonstrated, probably due to the small number of patients. Additionally, it remains difficult to understand the magnitude of the gut microbiome influence. Is dysbiosis a cause or consequence of the disease? However, the microbiome deserves our attention, especially since it brings different opportunities for intervention through diet, prebiotics and probiotics, pretreatment analysis, prognosis, and even microbiome modulation and transplantation.

Depression affects several aspects of life, including socioeconomic status, relationships, behavior, emotions, and overall health. The etiology of depression is complex and influenced by various factors, with obesity emerging as a significant contributor. This narrative review aims to investigate the factors associated with the development of depression, with a particular focus on the role of obesity. The literature search was conducted on PubMed, Embase, and PsycINFO from May to July 2024. The review highlights the impact of environmental and socioeconomic conditions; lifestyle choices, including physical activity and dietary habits; stress; traumatic experiences; neurotransmitter imbalances; medical and psychological conditions; hormone fluctuations; and epigenetic factors on depression. A key emphasis is placed on the inflammatory processes linked to obesity, which may drive the bidirectional relationship between obesity and depression. The findings suggest that obesity is associated with an increased risk of depression, potentially due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management. Understanding these interconnected factors is important for developing targeted interventions to address both obesity and depression, leading to improved quality of life for those affected.

Autism spectrum disorder (ASD) is characterized by repetitive behaviors and deficits in social interaction. Its etiology is not completely clear, but both genetic and environmental factors contribute to and influence its development and course. The increased number of autism cases in recent years has been strongly associated with increased exposure to heavy metals. Mercury (Hg) has gained prominence in the scientific literature as a result of its presence as an urban pollutant and well-described neurotoxicity. This review assessed the relationship between Hg exposure in the pre- and post-natal period and ASD. The systematic review identified observational clinical studies and pre-clinical trials in journals indexed in the PubMed, Embase, ProQuest, and LILACS databases. The aim of this study was to investigate the association between exposure to Hg and ASD and to define the critical period of exposure. A total of 57 articles were selected for this review, with 35 articles (61.40%) identifying a positive association between ASD and Hg, while 22 articles (38.60%) did not find the same outcome. The biological samples most used to analyze Hg body burdens were hair (36.84%) and blood (36.84%). Most case-control studies found an increase in Hg levels in individuals with ASD who were exposed to a polluted environment in the post-natal period. Taken together, the studies suggest that these patients have a deficient detoxification system, and this could worsen the symptoms of the disorder. However, new studies addressing the influence of Hg on the post-natal nervous system and its relationship with ASD should be carried out., (© 2024 International Society for Neurochemistry.)

Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include post-stroke infection, as sepsis. Additionally, oxidative stress is recognized for inducing functional deficits in peripheral organs during sepsis. Therefore, sex differences in stroke exist and we aimed to investigate the peripheral oxidative stress caused by sepsis after stroke in male and female rats. Wistar rats (male and female) were divided into sham+sham, middle cerebral artery occlusion (MCAO) + sham, sham+ cecal ligation and perforation (CLP) and MCAO+CLP groups to males and female rats. Animals were subjected to MCAO or sham and after 7 days, were subjected to sepsis by CLP or sham. After 24 h, serum, total brain, lung, liver, heart, and spleen were collected. Brain edema, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, oxidative damage to lipids and proteins, and catalase activity were evaluated. Brain edema was observed only in male rats in MCAO+CLP group compared to MCAO+sham. Regarding MPO activity, an increase was verified in male in different organs and serum in MCAO+CLP group. For N/N levels, the increase was more pronounced in females submitted to MCAO+CLP. In general, to oxidative stress, an increase was only observed in animals exposed to MCAO+CLP, or with a greater increase in this group compared to the others. The findings provided the first indication that animals exposed to MCAO exhibit a heightened vulnerability to the harmful impacts of sepsis, as evidenced by brain edema and peripheral oxidative stress, and this susceptibility is dependent of sex., Competing Interests: Declaration of competing interest None of the authors or funding sources has conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The field of psychoneuroimmunology has significantly expanded in the last few decades and so has our understanding of the bidirectional communications between the immune and central nervous systems (CNS). There is a preponderance of evidence supporting the fact that immunological pathways and neuroinflammation are involved in the pathophysiology of multiple neurological and mental health conditions. In this chapter, we have explored various neuroimmunological biomarkers involved in these pathways, responsible for developing and perpetuating different neuropsychiatric disorders. This chapter will examine inflammatory biomarkers and those associated with intestinal homeostasis, blood-brain barrier (BBB) permeability, glial cells, and neuronal injury. A range of tests has been developed to evaluate these markers, and we will also explore the existing methods currently employed for these techniques. Further studies of these inflammatory and neurological markers are needed to support their utility as biomarkers for diagnosis and prognosis and to inform treatment strategies for various neuropsychiatric disorders., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Alcohol is a harmful drug, and reducing its consumption is a significant challenge for users. Furthermore, alcohol dependence is often treatment-resistant, and no completely effective treatment model is available for chemical dependence. Classic psychedelics, such as LSD, psilocybin, and ayahuasca have been used in different clinical and pre-clinical trials, demonstrating promising pharmacotherapeutic effects in the treatment of treatment-resistant psychopathological conditions, such as addiction, especially related to alcohol dependence. In this work, we conducted a narrative review of the emerging research regarding the potential of psychedelics for alcohol use disorder treatment. Psychedelic substances have demonstrated potential for treating drug addiction, especially AUD, mostly by modulating neuroplasticity in the brain. Given that serotonergic psychedelics do not produce physical dependence or withdrawal symptoms with repeated use, they may be considered promising treatment options for managing drug use disorders. However, certain limitations could be found. Although many participants achieve positive results with only one treatment dose in clinical studies, great inter-individual variability exists in the duration of these effects. Therefore, further studies using different doses and experimental protocols should be conducted to enhance evidence about psychedelic substances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical Statement for Progress in Neuro-Psychopharmacology Biological Psychiatry. I testify on behalf of all co-authors that our article submitted to Progress in Neuro-Psychopharmacology Biological Psychiatry., (Copyright © 2024. Published by Elsevier Inc.)

Although many efforts have been made to understand the pathophysiological mechanisms of COVID-19, critical gaps remain to be explored. This study aimed to investigate potential alterations in adipokine levels (specifically adiponectin, leptin, and resistin) among individuals with COVID-19. Within this population, we further assessed the association between these markers with both, body mass index (BMI) and psychiatric symptoms. This cross-sectional study included an age- and sex-matched sample of adults with COVID-19 (cases) and without COVID-19 (controls). We evaluated the severity of psychiatric symptoms, BMI, and adipokines. Individuals with COVID-19 presented greater BMI, stress levels, and leptin levels when compared to controls. Leptin levels were greater in individuals with moderate/severe COVID-19 as compared to individuals with COVID-19 who were asymptomatic or having mild symptoms. Leptin levels were positively correlated with BMI, severity of depressive and anxiety symptoms, and stress levels in the total sample. Leptin levels were also positively correlated with BMI, severity of anxiety symptoms, and stress levels in controls. In cases, there was a positive correlation between adiponectin and the severity of depressive symptoms and stress levels and leptin/resistin with BMI. A linear regression model revealed that BMI, severity of anxiety symptoms, and the diagnosis of COVID-19 are independently associated with increased leptin levels. Thus, leptin levels seem to be impacted by the COVID-19 infection, anxiety, and BMI., Competing Interests: Declarations. Ethics Approval: This study was approved by the ethics committee under protocol numbers 4.172.382 and 4.298.662. Consent to Participate: All participants signed an informed consent form before participating in the study. Consent for Publication: Not applicable. Competing Interests: Dr. de Azevedo Cardoso is a scientific editor at JMIR Publications. Other authors report no biomedical financial interests or potential conflicts of interest., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic hyperglycemia caused by diabetes mellitus (DM) slows down the healing process due to prolonged inflammation which impedes the regeneration progression. Photobiomodulation (PBM) is considered a non-pharmacological intervention and has anti-inflammatory and biostimulatory effects that accelerate the healing process. Currently found IL-1β inhibitors are difficult to implement due to their cytotoxic potential, excessive amounts, and invasive administration, and therefore, the application of this peptide in diabetic wounds represents a promising intervention to help resolve the inflammatory response. This study aimed to investigate the effect of an IL-1β inhibitor molecule associated with PBM irradiation in a model of epithelial injury in diabetic mice. After the induction of the DM model with streptozotocin (STZ), the skin lesion model was implemented through surgical excision. Sixty C57BL/6 mice divided into five experimental groups (n = 12) were used: excisional wound (EW), DM + EW, DM + EW + DAP 1-2 (inhibitor peptide), DM + EW + PBM, and DM + EW + PBM + DAP 1-2. Treatment started 12 h after wound induction and was performed daily for 5 days. Twenty-four hours after the last application, the animals were euthanized and the outer edge of the wound was removed. The results obtained demonstrate that the DM + EW + PBM + DAP 1-2 group caused a reduction in the levels of pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, and an increase in TGF-β and maintenance of the cellular redox state with a consequent reduction in levels of inflammatory infiltrate and concomitant stimulation of type III collagen gene expression, as well as a decrease in the size of the wound in square centimeter 6 days after the injury. Only the combination of therapies was able to favor the process of tissue regeneration due to the development of an approach capable of acting at different stages of the regenerative process, through the mechanisms of action of interventions on the inflammatory process by avoiding its stagnation and stimulating progression of regeneration., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Material and method: Male Wistar rats (250-350g) were submitted to CLP, or sham as control, and divided into the sham + water, sham + MD (300 mg/kg), CLP + water, and CLP + MD (300 mg/kg) groups. Ten days after the administration of MD and CLP, the rats were submitted to a memory test by passive avoidance apparatus being sacrificed. The nitrite and nitrate (N/N) concentration, myeloperoxidase (MPO) and catalase (CAT) activity, lipid and protein oxidative damage, and brain-derived neurotrophic factor (BDNF) levels were measured in the prefrontal cortex and hippocampus., Results: The passive avoidance test verified an increase in the latency time compared training and test section in the groups sham + water and CLP + MD. Decreased N/N concentration and MPO activity were verified in the prefrontal cortex of rats submitted to CLP and MD treatment, as well as reduced protein and lipid oxidative damage in the hippocampus, which was accompanied by increased CAT activity and BDNF levels. Conclusion: Our data indicate the role of MD in attenuating oxidative stress parameters, the alteration of BDNF, and an improvement in memory impairment in rats ten days after induction of sepsis.

We evaluated glycemia and triglyceride, hepatic, muscular, and renal damage markers, redox profile, and leptin and ghrelin hormone levels in COVID-19 patients. We also conducted statistical analysis to verify the potential of biomarkers to predict poor prognosis and the correlation between them in severe cases. We assessed glycemia and the levels of triglycerides, hepatic, muscular, and renal markers in automatized biochemical analyzer. The leptin and ghrelin hormones were assessed by the ELISA assay. Severe cases presented high glycemia and triglyceride levels. Hepatic, muscular, and renal biomarkers were altered in severe patients. Oxidative stress status was found in severe COVID-19 patients. Severe cases also had increased levels of leptin. The ROC curves indicated many biomarkers as poor prognosis predictors in severe cases. The Spearman analysis showed that biomarkers correlate between themselves. Patients with COVID-19 showed significant dysregulation in the levels of several peripheral biomarkers. We bring to light that a robust panel of peripheral biomarkers and hormones predict poor prognosis in severe cases of COVID-19 and biomarkers correlate with each other. Early monitoring of these biomarkers may lead to appropriate clinical interventions in patients infected by SARS-CoV2., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Aims: Infection is a complication after stroke and outcomes vary by sex. Thus, we investigated if sepsis affects brain from ischemic stroke and sex involvement., Main Methods: Male and female Wistar rats, were submitted to middle cerebral artery occlusion (MCAO) and after 7 days sepsis to cecal ligation and perforation (CLP). Infarct size, neuroinflammation, oxidative stress, and mitochondrial activity were quantified 24 h after CLP in the prefrontal cortex and hippocampus. Survival and neurological score were assessed up to 15 days after MCAO or 8 days after CLP (starting at 2 h after MCAO) and memory at the end., Key Findings: CLP decreased survival, increased neurological impairments in MCAO females. Early, in male sepsis following MCAO led to increased glial activation in the brain structures, and increased TNF-α and IL-1β in the hippocampus. All groups had higher IL-6 in both tissues, but the hippocampus had lower IL-10. CLP potentiated myeloperoxidase (MPO) in the prefrontal cortex of MCAO male and female. In MCAO+CLP, only male increased MPO and nitrite/nitrate in hippocampus. Males in all groups had protein oxidation in the prefrontal cortex, but only MCAO+CLP in the hippocampus. Catalase decreased in the prefrontal cortex and hippocampus of all males and females, and MCAO+CLP only increased this activity in males. Female MCAO+CLP had higher prefrontal cortex complex activity than males. In MCAO+CLP-induced long-term memory impairment only in females., Significance: The parameters evaluated for early sepsis after ischemic stroke show a worse outcome for males, while females are affected during long-term follow-up., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) and depression are inflammatory pathologies, leading to increased inflammatory response and neurotoxicity. Therefore, this study aimed to evaluate the effect of the treatment with fluoxetine and/or galantamine and/or donepezil on the levels of proinflammatory and anti-inflammatory cytokines in a mixed animal model of depression and dementia. Adult male Wistar rats underwent chronic mild stress (CMS) protocol for 40 days and were subjected to stereotaxic surgery for intra-hippocampal administration of amyloid-beta (Aꞵ) peptide or artificial cerebrospinal fluid (ACSF) to mimic the dementia animal model. On the 42nd day, animals were treated with water, galantamine, donepezil, and/or fluoxetine, orally for 17 days. On the 57th and 58th days, the Splash and Y-maze tests for behavior analysis were performed. The frontal cortex and hippocampus were used to analyze the tumor necrosis factor alfa (TNF-α), interleukin 1 beta (IL-1ꞵ), IL-6, and IL-10 levels. The results of this study show that animals subjected to CMS and administration of Aꞵ had anhedonia, cognitive impairment, increased TNF-α and IL-1ꞵ levels in the frontal cortex, and reduced IL-10 levels in the hippocampus. All treatment groups were able to reverse the cognitive impairment. Only donepezil did not decrease the TNF-α levels in the hippocampus. Fluoxetine + galantamine and fluoxetine + donepezil reversed the anhedonia. Fluoxetine reversed the anhedonia and IL-1ꞵ levels in the frontal cortex. In addition, fluoxetine + donepezil reversed the reduction of IL-10 levels in the hippocampus. The results indicate a pathophysiological interaction between AD and depression, and the association of medications in the future may be a possible therapeutic strategy to reduce inflammation, especially the fluoxetine-associated treatments., Competing Interests: Declaration of competing interest Meaning all authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Aim: To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM)., Materials and Methods: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I 2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software., Results: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01)., Conclusion: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk., (© 2024 John Wiley & Sons Ltd.)

Background: Older people are the fastest-growing age group, with the highest risk of cognitive impairment. This study assessed the prevalence and associated factors with cognitive impairment in community-dwelling older people., Methods: Older people were interviewed and accomplished through sociodemographic and health questionnaires. The quantitative variables were described by mean and standard deviation or median and interquartile range. The significance level adopted was 5 % (p < 0.05). The association between the quantitative variables was evaluated using the Pearson or Spearman correlation coefficients., Results: The research population comprised 165 long-lived adults aged ≥80. The youngest one was 80, and the oldest one was 94 years old. The participants were 84.8 ± 3.6 years old, female (63 %) with a mean of education of 2.9 ± 1.8 years. A poor performance in the Mini-Mental State Examination (MMSE) was found in 58 (35.2 %) individuals when adjusted for educational level. After adjustment for confounding factors, body mass index (BMI) (p = 0.09), total older adults' income (up to 1 minimum wage [mw], p = 0.023; over 1 to 2 mw, p = 0.023), functional disability (Moderate dependence 75 %, p = 0.038; Moderate dependence 50 %, p = 0.081; Moderate dependence 25 %, p = 0.054), and the anxiety scale (p = 0.032), remained associated with cognitive impairment., Conclusions: This study showed that BMI, total older adults' income, functional disability, and anxiety are related to cognitive impairment in long-lived adults. This study has some limitations, such as the fact that it is a cross-sectional study, the reduced number of individuals, and the fact that there were no comparisons among different ages and populations., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)