Curcumin attenuates neuroinflammatory damage induced by LPS: implications for the role of S100B.

Brain disease results in inflammatory damage that alters cell function in microglia and astrocytes as well as other neuronal cell types. Astrocytes modulate blood flow, regulate glutamate metabolism, and exert antioxidant protection. When responding to inflammatory damage, astrocytes enhance immune cell infiltration and amplify inflammatory responses via the upregulation of cytokine production. Several molecules have been proposed to attenuate neuroinflammation and control neurological diseases. Curcumin gained attention due to its capacity to cross the blood-brain barrier and its well-described anti-inflammatory and antioxidant activities. Our study aimed to understand if oral curcumin administration could protect against central nervous system inflammatory damage induced by intracerebroventricular injection of LPS while focusing on astrocyte function. Despite its poor bioavailability, we found that curcumin reaches the central nervous system, prevents the locomotory damage caused by LPS, and reduces inflammatory signaling via IL-1ß and COX-2. Furthermore, we observed that curcumin was protective against LPS-induced S100B secretion in the cerebrospinal fluid and GSH reduction in the hippocampal tissue. However, curcumin could not protect the animals from anhedonia, assessed by the sucrose preference test, and weight loss induced by LPS. Our results indicate that oral curcumin administration exerts a protective anti-inflammatory action in the central nervous system, attenuating the sickness behavior induced by ICV LPS. This work demonstrates that curcumin has an important modulative effect on astrocytes, thus suggesting that astrocytes are critical to the anti-inflammatory effects of curcumin.

Physiology and Execution of Swallowing Maneuvers in 3D Videos: Integrating the Technology into Patient Care.

Educational technologies have proven to be an effective way to guide and educate patients, allowing them to increase awareness of their dysphagia condition and how treatment will help them. In this sense, this study aimed to develop and validate the content and appearance of 3D iconographic videos, which addressed the physiological demonstration and execution of protective and facilitating swallowing maneuvers, as well as verifying the feasibility of its use in teleconsultation, having adults and elderly people with oropharyngeal dysphagia as the main target audience. The development of the 3D videos was elaborated based on a guiding scientific script, constructed from an integrative literature review. After the development of the 3D videos by the digital designer, a committee of 12 expert judges evaluated the material produced to validate the content and appearance where a minimum agreement index of 0.8 among the judges was considered satisfactory. Subsequently with the validated material, the proof of concept was conducted together with the target population of 10 dysphagic patients through individual teleconsultation via Google Meet platform. After the teleconsultation, patients responded to a Google Forms questionnaire, analyzing the videos presented. From the integrative literature review, 29 studies that contained relevant information about the physiological effects caused by swallowing maneuvers were selected. Based on this information, the scientific script was created, allowing a detailed description of the physiological events that occurred during swallowing while executing the maneuvers. With the finished script, 3D videos of swallowing maneuvers were produced. After developing the material, the committee of expert judges validated the content and appearance. The twelve items that had an agreement index below 0.8 were adjusted. Once the adjustments were completed, the videos were analyzed again, obtaining approval from the judges, and ensuring the validation of content and appearance of the material developed. A proof of concept was conducted on ten dysphagic patients. The maneuver applied was chosen according to the patient's physiological changes, causing only 4 of the 9 maneuvers to be tested, as the patients did not demonstrate changes in swallowing that would justify the use of the other maneuvers. After this, patients answered a form in which all items covered received positive evaluations, related to both ease of understanding and learning. This study allowed the development of the 3D videos with a didactic demonstration of the physiology and execution of protective and facilitating swallowing maneuvers, in addition to having its content and appearance validity assured through analysis by the committee of expert judges.

Calorie Restriction Attenuates Memory Impairment and Reduces Neuroinflammation in Obese Aged Rats.

Obesity and aging collectively potentiate inflammatory responses, particularly within the central nervous system. Managing obesity presents a significant challenge, even more so considering the context of aging. Caloric restriction (CR) has been extensively documented in the literature for its multiple health benefits. Motivated by these findings, we hypothesized that CR could serve as a valuable intervention to address the brain alterations and cognitive decline associated with obesity in aged rats. Our investigation revealed that cafeteria diet increased hippocampal and hypothalamic transcripts related to neuroinflammation, along with cognitive deficits determined in the object recognition test in 18-month-old male rats. Western blot data indicate that the obesogenic diet may disrupt the blood-brain barrier and lead to an increase in Toll-like receptor 4 in the hippocampus, events that could contribute to the cognitive deficits observed. Implementing CR after the onset of obesity mitigated neuroinflammatory changes and cognitive impairments. We found that CR increases GABA levels in the hippocampus of aged animals, as demonstrated by liquid chromatography coupled with mass spectrometry analysis. These findings underscore the potential of CR as a therapeutic opportunity to ameliorate the neuroinflammatory and cognitive alterations of obesity, especially in the context of aging.

Omega-3 Attenuates Disrupted Neurotransmission and Partially Protects Metabolic Dysfunction Caused by Obesity in Wistar Rats.

Omega-3 (n3) is a polyunsaturated fatty acid well known for its anti-inflammatory and neuroprotective properties. Obesity is linked to chronic inflammation that disrupts metabolism, the intestine physiology and the central nervous system functioning. This study aims to determine if n3 supplementation can interfere with the effects of obesity on the mitochondrial activity, intestinal barrier, and neurotransmitter levels in the brain of Wistar rats that received cafeteria diet (CAF). We examined adipose tissue, skeletal muscle, plasma, intestine, and the cerebral cortex of four groups: CT (control diet), CTn3 (control diet with n3 supplementation), CAF, and CAFn3 (CAF and n3). Diets were offered for 13 weeks, with n3 supplementation in the final 5 weeks. Adipose tissue Electron Transport Chain complexes I, II, and III showed higher activity in CAF groups, as did complexes III and IV in skeletal muscle. Acetate levels in plasma were reduced in CAF groups, and Lipopolysaccharide (LPS) was higher in the CAF group but reduced in CAFn3 group. Claudin-5 in the intestine was lower in CAF groups, with no n3 supplementation effect. In the cerebral cortex, dopamine levels were decreased with CAF, which was reversed by n3. DOPAC, a dopamine metabolite, also showed a supplementation effect, and HVA, a diet effect. Serotonin levels increased in the CAF group that received supplementation. Therefore, we demonstrate disturbances in mitochondria, plasma, intestine and brain of rats submitted to CAF and the potential benefit of n3 supplementation in endotoxemia and neurotransmitter levels.

Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ.

Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1ß (IL-1ß), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1ß concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.

Cannabidiol improves maternal obesity-induced behavioral, neuroinflammatory and neurochemical dysfunctions in the juvenile offspring.

Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established. We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams. Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus. CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes. Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.

Effect of Probiotic Lacticaseibacillus rhamnosus LB1.5 on Anxiety-like Behavior, Neuroprotection and Neuroinflammation Markers of Male Mice Fed a High-Fat Diet.

Probiotic supplementation has been identified as a potential target to reduce inflammatory mediators associated with obesity. Therefore, this study assessed the effect of probiotic Lacticaseibacillus rhamnosus LB1.5 on anxiety-like behavior, gene expression in the prefrontal cortex, and neuroinflammation in the cerebral cortex and hippocampus of male mice fed a high-fat diet. Mice aged 21 days were divided into four groups: control (CONT), control plus probiotic (CONT + PROB), high-fat diet (HFD), and high-fat diet plus probiotic (HFD + PROB), and fed for 13 weeks. The probiotic Lact. rhamnosus 1.5 (3.1 × 108 CFU/mL, derived from raw buffalo milk) was administered by gavage three times a week. Probiotic supplementation provided an anxiolytic effect in CONT and HFD. The IL-6 showed lower levels after probiotic supplementation in the HFD. Regarding immunoreactivity for GFAP in the cerebral cortex, we demonstrated that animals HFD-fed had a reduction in cells number compared to CONT. In the hippocampus, we found an interaction between diet and supplementation, as well as an effect of probiotic supplementation. A higher number of Th positive cells was observed in the cerebral cortex in mice fed HFD. Lact. rhamnosus LB1.5 supplementation decreased serum IL-6 levels in HFD-fed mice and promoted a reduction in anxiety-like behavior.

Lactate Protects Microglia and Neurons from Oxygen-Glucose Deprivation/Reoxygenation.

Lactate has received attention as a potential therapeutic intervention for brain diseases, particularly those including energy deficit, exacerbated inflammation, and disrupted redox status, such as cerebral ischemia. However, lactate roles in metabolic or signaling pathways in neural cells remain elusive in the hypoxic and ischemic contexts. Here, we tested the effects of lactate on the survival of a microglial (BV-2) and a neuronal (SH-SY5Y) cell lines during oxygen and glucose deprivation (OGD) or OGD followed by reoxygenation (OGD/R). Lactate signaling was studied by using 3,5-DHBA, an exogenous agonist of lactate receptor GPR81. Inhibition of lactate dehydrogenase (LDH) or monocarboxylate transporters (MCT), using oxamate or 4-CIN, respectively, was performed to evaluate the impact of lactate metabolization and transport on cell viability. The OGD lasted 6 h and the reoxygenation lasted 24 h following OGD (OGD/R). Cell viability, extracellular lactate concentrations, microglial intracellular pH and TNF-ɑ release, and neurite elongation were evaluated. Lactate or 3,5-DHBA treatment during OGD increased microglial survival during reoxygenation. Inhibition of lactate metabolism and transport impaired microglial and neuronal viability. OGD led to intracellular acidification in BV-2 cells, and reoxygenation increased the release of TNF-ɑ, which was reverted by lactate and 3,5-DHBA treatment. Our results suggest that lactate plays a dual role in OGD, acting as a metabolic and a signaling molecule in BV-2 and SH-SY5Y cells. Lactate metabolism and transport are vital for cell survival during OGD. Moreover, lactate treatment and GPR81 activation during OGD promote long-term adaptations that potentially protect cells against secondary cell death during reoxygenation.

Effects of omega-3 supplementation on anxiety-like behaviors and neuroinflammation in Wistar rats following cafeteria diet-induced obesity.

ABSTRACTObjetives: Omega-3 (n3) fatty acids have been studied as an option to alleviate the harmful effects of obesity. However, its role in obesity-related behavioral changes is still controversial. This study aimed to evaluate the effects of n3 on behavior and neuroinflammation in obese animals. Methods: Male Wistar rats were divided into four groups: control diet (CT), CT+n3, cafeteria diet (CAF), and CAF+n3. Diet was administered for 13 weeks, and n3 was supplemented during the last 5 weeks. Metabolic and biochemical parameters were evaluated, as well as anxiety-like behaviors. Immunoblots were conducted in the animals' cerebral cortex and hippocampus to assess changes in neuroinflammatory markers.Results: CAF-fed animals showed higher weight gain, visceral adiposity, fasting glucose, total cholesterol, triglycerides, and insulin levels, and n3 improved the lipid profile and restored insulin sensitivity. CAF-fed rats showed anxiety-like behaviors in the open field and light-dark box tasks but not in the contextual aversive conditioning. Omega-3 did not exert any effect on these behaviors. Regarding neuroinflammation, diet and supplementation acted in a region-specific manner. In the hippocampus, CAF reduced claudin-5 expression with no effect of n3, indicating a brain-blood barrier disruption following CAF. Furthermore, in the hippocampus, the glial fibrillary acidic protein (GFAP) and toll-like receptor 4 (TLR-4) were reduced in treated obese animals. However, n3 could not reverse the TLR-4 expression increase in the cerebral cortex.Discussion: Although n3 may protect against some neuroinflammatory manifestations in the hippocampus, it does not seem sufficient to reverse the increase in anxiolytic manifestations caused by CAF.

Symptoms of oropharyngeal dysphagia, efficiency, and safety of swallowing in patients after treatment for head and neck cancer.

PURPOSE: The aim of this study is to investigate the relation between symptoms and signs of oropharyngeal dysphagia after treatment for head and neck cancer. METHODS: An observational analytical study with retrospective and prospective components was carried out including 25 adult and elderly patients with head and neck cancer who had completed the treatment at least 3 months before data collection. Data from the Eating Assessment Tool (EAT-10) protocol were analyzed, as well as from the videofluoroscopic swallowing exams. Based on videofluoroscopy, the degree of oropharyngeal dysphagia was classified, as well as the safety and efficiency grade using the DIGEST (Dynamic Imaging Grade of Swallowing Toxicity) scale. Pearson's correlation test was applied, adopting a significance level of 5%. RESULTS: There was a significant correlation between question 4 of the EAT-10 (swallowing solids takes extra effort) and the efficiency profile (p = 0.004), as well as between question 4 and the DIGEST score (p = 0.002). No significant relation was found between the DIGEST score and EAT-10 total score (p = 0.180) and not even between EAT-10 total score and efficiency (p = 0.129) or safety grade (p = 0.878). CONCLUSION: In conclusion, no relation was found between most of the dysphagia signs and symptoms investigated, demonstrating that the individual's perception of the swallowing function may not be consistent with the findings of the instrumental evaluation after long-term treatment for head and neck cancer.

Effects of Zinc Supplementation on Inflammatory and Cognitive Parameters in Middle-Aged Women with Overweight or Obesity.

Obesity has been linked to cognitive decline and adverse effects on brain health. Zinc (Zn) is a mineral with important metabolic functions that can modulate obesity-related neurological impairment. Thus, the present study aimed to evaluate the effects of 12 weeks of Zn supplementation on the inflammatory profile, cognitive function, and mood of overweight or obese women through a double-blind, placebo-controlled study. The study included 42 women aged between 40 and 60, randomly divided into two groups: Zn supplementation (30 mg/day) or placebo for 12 weeks. Data regarding sociodemographic, anthropometric, dietary, and physical activity were collected. Mini-mental state examination (MMSE), verbal fluency test, clock drawing test, and Stroop test were performed. Anxiety and depression symptoms were assessed using the Beck anxiety inventory and the BDI-II, respectively. Saliva samples were collected to evaluate IL-1ß, IL-6, TNF-α, insulin, nitrite, and Zn levels. Of the 42 participants (mean age 49.58 ± 6.46 years), 32 were included in the study analyses. Changes in body weight and macronutrient consumption were not different between placebo and Zn supplementation groups. Cognitive scores on the MMSE and Stroop tests were higher in the Zn supplementation group than in the placebo group. Salivary levels of IL-1b and Zn increased in the Zn group compared to placebo. There was no significant change in the adjusted means of the BDI-II and BECK scores between the zinc vs. placebo groups. Twelve weeks of Zn supplementation was able to partially improve the cognitive scores assessed in overweight or obese women, regardless of weight loss. These findings suggest that Zn supplementation can be considered an adjunct strategy to enhance cognitive health in overweight or obese women.

Oral-health-related quality of life in adolescents: umbrella review.

BACKGROUND: To evaluate oral conditions, demographic and socioeconomic characteristics of oral health-related quality of life (OHRQoL) in adolescents. METHODS: Umbrella review, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta Analyzes (PRISMA) checklist. The search strategy used a combination of words, applied in the electronic databases PubMed, WebScience, Embase, Lilacs, Scopus and Cochrane. Included publications until January 2022, without restrictions. Data collection took place with systematized practices and the eligibility criteria were studies focusing on OHRQoL; teenagers; adolescentes; present the term "systematic review" and/or "meta-analysis" in the title or abstract. The quality assessment followed the Assessment of Multiple Systematic Reviews (AMSTAR 2) and the adherence of the article to the PRISMA was verified. RESULTS: Three hundred sixty-two articles were identified, and 22 were included, published between 2009 and 2022. 21 Systematic reviews focused on the English language. Most studies showed heterogeneity in the methodological structuring process: 10 articles were considered of low and 10 critically low quality. Clinical conditions associated with worsening in quality of life were dental caries, malocclusion, dental trauma, toothache, edentulism, need for orthodontic treatment, irregular brushing, and periodontal disease. Socioeconomic factors related to housing, parental education, access to health care, absence of siblings and nuclear family influence OHRQoL. Completion of orthodontic treatment, health promotion programs, dental care and safe housing all have a positive impact. CONCLUSION: Worse oral health status, older age, female sex and worse socioeconomic status were significantly associated with worse OHRQoL. TRIAL REGISTRATION: PROSPERO CRD4202129352.

Consecutive Liver and Bone Marrow Transplantation for Erythropoietic Protoporphyria: Case Report and Literature Review.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disease of heme biosynthesis resulting in the accumulation of protoporphyrin, characterized by liver failure in a minority of cases. Although liver transplant (LT) is the therapeutic strategy for advanced hepatic disease, it does not correct the primary defect, which leads to recurrence in liver graft. Thus, hematopoietic stem cell transplantation (HSCT) is an approach for treating EPP. METHODS: We aim to describe the first sequential LT and HSCT for EPP performed in Latin America, besides reviewing the present-day literature. RESULTS: The patient, a 13-year-old female with a history of photosensitivity, presented with symptoms of cholestatic and hepatopulmonary syndrome and was diagnosed with EPP. Liver biopsy demonstrated cirrhosis. She was submitted to a successful LT and showed improvement of respiratory symptoms. However, she had disease recurrence on the liver graft. She underwent a myeloablative HSCT using a matched unrelated donor, conditioning with BuCy (busulfan and cyclophosphamide), and GvHD (graft vs. host disease) prophylaxis with ATG (thymoglobulin), tacrolimus and methotrexate. Neutrophil engraftment occurred on D+18. She has presented mixed chimerism, but normalization of PP levels, being 300 days after HSCT, in good state of health and normal liver function. CONCLUSIONS: Consecutive LT and HSCT for EPP is a procedure that has been described in 10 cases in the literature and, even though these patients are a highly diversified population, studies have shown favorable results. This concept of treatment should be considered in patients with established liver disease.

Effects of different maternal diets on adipose tissue inflammation and liver tissue oxidative stress in dams and their female offspring.

Pregnancy and lactation are important stages of fetal development. Therefore, this study investigated how different maternal diets offered during gestation and lactation periods affect adipose tissue inflammation and liver tissue oxidative stress of dams and their female offspring. Female BALB/c albino mice (60 days old) were randomized into three groups receiving a standard (CONT), hypercaloric (HD), or restricted (RD) diet during the pregnancy. After birth, female offspring weaned at 21 days were divided into two groups that received a standard or restricted diet (CONT/CONT, CONT/RD, RD/CONT, RD/RD, HD/CONT, and HD/RD) until 100 days old. Histological, oxidative parameters and inflammatory infiltrate of dams' and offspring's liver and adipose tissue were evaluated. HD dams presented non-alcoholic steatohepatitis (NASH) diagnosis and an increase in tumor necrosis factor-alpha (TNF-α) concentrations when compared to the RD and CONT dams, indicating a pro-inflammatory state. High concentrations of malondialdehyde (MDA) formation and catalase (CAT) activity in HD when compared to the CONT in the liver. SOD activity decreased in RD mice compared to CONT, and the SOD/CAT ratio was decreased in the RD and HD in comparison to the CONT. The maternal diet leads to an increase in SOD in RD/RD compared to HD/RD. RD-fed dams showed an increase in inflammatory infiltrates compared to CONT, evidencing changes caused by a restrictive diet. In the HD/CONT offspring, we verified an increase in inflammatory infiltrates in relation to the offspring fed a standard diet. In conclusion, HD, and RD, during pregnancy and lactation, altered the liver and adipose tissues of mothers. Furthermore, the maternal diet negatively impacts the offspring's adipose tissue but does not cause liver damage in these animals in adult life.

Weight Gain, Lifestyle, and Cognition During the COVID-19 Pandemic in Southern Brazil.

BACKGROUND: During the COVID-19 pandemic, the world experienced social distancing that resulted in changes in habits and lifestyle. Such changes can compromise healthy eating habits and the practice of physical activities, known risk factors for developing weight gain and obesity. OBJECTIVE: The main objective of this study was to describe the change in eating habits, lifestyle, and cognition of the population of Rio Grande do Sul, a state in Southern Brazil, during social distancing due to COVID-19. METHODS: The study was conducted from July 21 to August 10, 2020, through a structured online questionnaire that asked for sociodemographic information (age, gender, and education), anthropometric (reported weight and height), change in eating habits, lifestyle (sleep quality and physical activity), and cognition. Chi-square, McNemar tests, and univariate and multivariate analysis were used to evaluate the variables. Confidence intervals were calculated with a significance level of 5%. RESULTS: Of a total of 1072 participants, 57.3% of respondents reported weight gain, and an increased percentage of people were classified as obese. Nearly half of the participants (46%) reported changes in their eating habits for the worse. Body mass index (BMI) was significantly associated with increased consumption of unhealthy foods. Our results identified high physical inactivity (46.9%) and obesity (19%) during social distancing. The changes in eating habits and lifestyle also increased the risk for decreased cognition. CONCLUSIONS: These findings highlighted that social distancing impacted eating habits and lifestyle, which increased obesity rates and might predispose to decreased cognition.

Calorie restriction mitigates metabolic, behavioral and neurochemical effects of cafeteria diet in aged male rats.

Besides metabolic dysfunctions, elderly individuals with obesity are at special risk of developing cognitive decline and psychiatric disturbances. Restricted calorie consumption could be an efficient strategy to improve metabolic function after obesity. However, its effects on anxiety-like behaviors in aged rats submitted to an obesogenic diet are unknown. For this purpose, 42 Wistar rats (18-months old) were divided into four groups: Control (CT), calorie restriction (CR), cafeteria diet (CAF), and CAF+CR (CAF/CR). CT, CR, and CAF groups received the diets for 8 weeks. CAF/CR group was submitted to the CAF menu for 7 weeks and then switched to a standard diet on a CR regimen, receiving 30% lower calories than consumed by the CT, for another 5 weeks. CAF's menu consisted of ultra-processed foods such as cookies, chocolate, sausage, and bologna. Body weight, visceral adiposity, and biochemical blood analysis were evaluated for obesity diagnosis. The profile of gut microbiota was investigated, along with circulating levels of LPS. Neurochemical parameters, such as neurotransmitter levels, were dosed. Anxiety-like behaviors were accessed using open field (OF) and elevated plus maze (EPM) tests. As expected, CR reduced weight gain and improved glucose homeostasis. Gut microbiome disturbance was found in CAF-fed animals accompanied by increased levels of LPS. However, CR after CAF mitigated several harmful responses. The obesogenic diet triggered anxiety-like manifestations in the OF and EPM tests that were not evidenced in the CAF/CR group. These findings indicate that CR can be a promising strategy for the neurological effects of obesity in aged rats.

Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity.

Introduction: The implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed. Methods: Here we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats. Results: We have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1ß in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to in utero neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes. Discussion: Together, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.

Daily Vitamin D Supplementation Improves Vitamin D Deficiency in Patients With Chronic Liver Disease.

OBJECTIVE: The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency. METHODS: This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders. RESULTS: We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment. CONCLUSION: Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.

A high-fat diet changes placental morphology but does not change biochemical parameters, placental oxidative stress or cytokine levels.

INTRODUCTION: The placenta is an organ that forms the bridge between mother and fetus during pregnancy. Changes in the intrauterine environment directly impact the fetus' health, with maternal nutrition determining its development. This study analyzed the effects of different diets and probiotic supplementation during pregnancy on the biochemical parameters of maternal serum and placental morphology, oxidative stress, and cytokine levels in mice. METHODS: Female mice were fed standard (CONT), restrictive (RD), or high-fat (HFD) diets before and during pregnancy. During pregnancy, the CONT and HFD groups were divided into two groups that received the Lactobacillus rhamnosus LB1.5 three times per week (CONT + PROB and HFD + PROB). The RD, CONT, or HFD groups received vehicle control. Maternal serum biochemical parameters (glucose, cholesterol, and triglycerides) were evaluated. The morphology, redox profile (thiobarbituric acid reactive substances, sulfhydryls, catalase, and superoxide dismutase enzyme activity), and inflammatory cytokines (interleukins 1α, 1ß, IL-6, and tumor necrosis factor-alpha) were evaluated in the placenta. RESULTS: The serum biochemical parameters presented no differences between the groups. Regarding placental morphology, the HFD group showed an increased thickness of the labyrinth zone compared to the CONT + PROB group. However, no significant difference was found in the analysis of the placental redox profile and cytokine levels. DISCUSSION: RD and HFD, for 16 weeks before and during pregnancy, as well as probiotic supplementation during pregnancy, caused no change in serum biochemical parameters nor the gestational viability rate, placental redox state, and cytokine levels. However, HFD increased the thickness of the placental labyrinth zone.

Impact of cafeteria diet and n3 supplementation on the intestinal microbiota, fatty acids levels, neuroinflammatory markers and social memory in male rats.

OBJECTIVE: To assess the effects of omega-3 (n3) supplementation on intestinal microbiota, fatty acids profile, neuroinflammation, and social memory of cafeteria diet (CAF)-fed rats. METHODS: Male Wistar rats were fed with CAF for 20 weeks. Omega-3 (500 mg/kg/day) was supplemented between the 16th and 20th week. Colon morphology, intestinal microbiota composition, short-chain fatty acids (SCFA) and lipopolysaccharide (LPS) in the plasma, fatty acids profile, TLR-4 and claudin-5 expressions in the brain, and social memory were investigated. RESULTS: CAF reduced colon length, crypts' depth, and microbiota diversity, while n3 increased the Firmicutes/Bacteroidetes ratio. CAF increased SCFA plasma levels, but n3 reduced butyrate and isobutyrate in obese rats. LPS was increased in CAF-fed rats, and n3 decreased its levels. In the cerebral cortex, n3 increased caprylic, palmitic, stearic, tricosanoic, lignoceric, myristoleic, and linoleic acids. CAF increased palmitic acid and TLR-4 expression in the cerebral cortex while decreasing claudin-5 in the hippocampus. In the social memory test, CAF-fed animals showed greater social interaction with no effect of n3. CONCLUSIONS: The lack of n3 effect in some of the evaluated parameters may be due to the severity of the obesity caused by CAF. However, n3 reduced LPS levels, suggesting its ability to reverse endotoxemia.