Is the enteric nervous system a lost piece of the gut-kidney axis puzzle linked to chronic kidney disease?

The enteric nervous system (ENS) regulates numerous functional and immunological attributes of the gastrointestinal tract. Alterations in ENS cell function have been linked to intestinal outcomes in various metabolic, intestinal, and neurological disorders. Chronic kidney disease (CKD) is associated with a challenging intestinal environment due to gut dysbiosis, which further affects patient quality of life. Although the gut-related repercussions of CKD have been thoroughly investigated, the involvement of the ENS in this puzzle remains unclear. ENS cell dysfunction, such as glial reactivity and alterations in cholinergic signaling in the small intestine and colon, in CKD are associated with a wide range of intestinal pathways and responses in affected patients. This review discusses how the ENS is affected in CKD and how it is involved in gut-related outcomes, including intestinal permeability, inflammation, oxidative stress, and dysmotility.

Child health nursing consultation and competencies for Advanced Practice Nurses.

OBJECTIVE: To analyze nurses' practice in child health nursing consultations and the presence of care management competencies proposed for Advanced Practice Nurses (APN). METHOD: Multicenter, exploratory sequential mixed methods research, carried out in 17 Basic Health Units in four Brazilian cities. Collection was carried out from May to July 2022 through filming of consultation and analysis of medical records. Consultations with compliance with the Nursing Process ≥50% were analyzed to identify the competencies proposed for APN. RESULTS: 24 child consultations carried out by 12 nurses were filmed. In the quantitative analysis, 11 nursing consultations, carried out by seven nurses, achieved ≥50% Nursing Process compliance. In the qualitative analysis of these consultations, some APN competencies in care management were identified, but incomplete. CONCLUSION: child health nursing consultations present weaknesses in carrying out the Nursing Process, and nurses demonstrated a partial and superficial application of the care management competencies proposed for APN.

Lipid Metabolism Modulation during SARS-CoV-2 Infection: A Spotlight on Extracellular Vesicles and Therapeutic Prospects.

Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged as potential therapeutic targets against the SARS-CoV-2 infection. Studies on COVID-19 patients have shown that they frequently have dysregulated lipid profiles, which are associated with an increased risk of severe repercussions. Lipid droplets (LDs) serve as organelles with significant roles in lipid metabolism and energy homeostasis as well as having a wide range of functions in infections. The down-modulation of lipids, such as sphingolipid ceramide and eicosanoids, or of the transcriptional factors involved in lipogenesis seem to inhibit the viral multiplication, suggesting their involvement in the virus replication and pathogenesis as well as highlighting their potential as targets for drug development. Hence, this review focuses on the role of modulation of lipid metabolism and EVs in the mechanism of immune system evasion during SARS-CoV-2 infection and explores the therapeutic potential of EVs as well as application for delivering therapeutic substances to mitigate viral infections.

Brazil Nut-Enriched Diet Modulates Enteric Glial Cells and Gut Microbiota in an Experimental Model of Chronic Kidney Disease.

Introduction: Chronic kidney disease (CKD) promotes gut dysbiosis, and enteric glial reactivity, a feature of intestinal inflammation. Brazil nut modulated enteric glial profile in healthy animals and could modulate these cells in 5/6 nephrectomized rats.Methods: A 5/6 nephrectomy-induced CKD and Sham-operated rats were divided as follows: CKD and Sham received a standard diet and CKD-BN and Sham-BN received a 5% Brazil nut enriched-diet. The protein content of glial fibrillary acid protein (GFAP), enteric glial marker, and GPx protein content and activity were assessed in the colon. The major phyla of gut microbiota were assessed.Results: CKD-BN group presented a decrease in GFAP content (p = 0.0001). The CKD-BN group modulated the abundance of Firmicutes, increasing its proportion compared to the CKD group. The CKD-BN group showed increased GPx activity in the colon (p = 0.0192), despite no significant difference in protein content.Conclusion: Brazil nut-enriched diet consumption decreased enteric glial reactivity and modulated gut microbiota in the CKD experimental model.

Effects of Probiotic-Enriched Minas Cheese (Lactobacillus acidophilus La-05) on Cardiovascular Parameters in 5/6 Nephrectomized Rats.

Dairy foods have become an interest in chronic kidney disease (CKD) due to their nutritional profile, which makes them a good substrate for probiotics incorporation. This study evaluated the effect of probiotic-enriched Minas cheese with Lactobacillus acidophilus La-05 in an experimental rat model for CKD on cardiac, inflammatory, and oxidative stress parameters. Male Wistar rats were divided into 4 groups (n = 7/group): 5/6 nephrectomy + conventional Minas cheese (NxC); 5/6 nephrectomy + probiotic Minas cheese (NxPC); Sham + conventional Minas cheese (ShamC); Sham + probiotic Minas cheese (ShamPC). Offering 20 g/day of Minas cheese with Lact. acidophilus La-05 (108-109 log CFU/g) for 6 weeks. The cardiomyocyte diameter was determined. Superoxide dismutase (SOD) activity in plasma, heart, kidney, and colon tissue was performed. At the end of supplementation, no significant changes in lipid profile and renal parameters were found. The NxPC group showed a decrease in cardiomyocyte diameter compared to the NxC group (16.99 ± 0.85 vs. 19.05 ± 0.56 µm, p = 0.0162); also they showed reduced plasmatic SOD activity (502.8 ± 49.12 vs. 599.4 ± 94.69 U/mL, p < 0.0001). In summary, probiotic-enriched Minas cheese (Lact. acidophilus La-05) consumption suggests a promisor cardioprotective effect and was able to downregulate SOD activity in a rat model of CKD.

COVID-19 and Adrenal Insufficiency: Unmasking the Link.

We describe a case of a 28-year-old male who presented with general malaise, fatigue, anorexia, occasional epigastric pain, and vomiting a few days after a mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clinical evolution led to weight loss (6 kg in six months) and craving for salty foods. Physical examination revealed dehydration, hypotension, and hyperpigmentation of the skin and mucosal surfaces. Laboratory tests demonstrated normocytic normochromic anemia, acute kidney injury, hyperkalemia, hyponatremia, and compensated metabolic acidosis. Adrenal workup allowed us to establish a diagnosis of adrenal insufficiency (AI) due to autoimmune adrenalitis, considering findings of a low cortisol and positive 21-hydroxylase antibodies (21OH-Abs), as well as high serum renin and adrenocorticotropic hormone (ACTH). Atypical presentations and comorbidities may appear regarding coronavirus disease 2019 (COVID-19), such as the association between COVID-19 and the hypothalamic-pituitary-adrenal (HPA) axis, which may be affected in any patient with SARS-CoV-2 infection, thus making adrenal insufficiency a diagnosis to consider.

Lipid droplets as multifunctional organelles related to the mechanism of evasion during mycobacterial infection.

Tuberculosis (TB) is an infectious disease caused by the bacteria of the Mycobaterium tuberculosis (Mtb) complex. The modulation of the lipid metabolism has been implicated in the immune response regulation, including the formation of lipid droplets (LD)s, LD-phagosome association and eicosanoid synthesis. Mtb, M. bovis BCG and other pathogenic mycobacteria, as well as wall components, such as LAM, can induce LDs formation in a mechanism involving surface receptors, for instance TLRs, CD36, CD14, CD11b/CD18 and others. In addition, the activation of the lipid-activated nuclear receptor PPARγ is involved in the mechanisms of LD biogenesis, as well as in the modulation of the synthesis of lipid mediators. In infected cells, LDs are sites of compartmentalized prostaglandin E2 synthesis involved in macrophage deactivation, bacterial replication and regulation of the host cytokine profile. LDs also have a function in vesicle traffic during infection. Rab7 and RILP, but not Rab5, are located on LDs of infected macrophages, suggesting that LDs and phagosomes could exchange essential proteins for phagosomal maturation, interfering in mycobacterial survival. The pharmacological inhibition of LDs biogenesis affects the bacterial replication and the synthesis of lipid mediators and cytokines, suggesting that LDs may be new targets for antimicrobial therapies. However, it is still controversial if the accumulation of LDs favors the mycobacterial survival acting as an escape mechanism, or promotes the host resistance to infection. Thus, in this mini-review we discuss recent advances in understanding the important role of LDs in the course of infections and the implications for the pathophysiology of mycobacteriosis.

Heat-resistant and biofilm-forming Escherichia coli in pasteurized milk from Brazil.

Escherichia coli harboring a transmissible locus of stress tolerance (tLST) and the ability to form biofilms represent a serious risk in dairy production. Thus, we aimed to evaluate the microbiological quality of pasteurized milk from two dairy producers in Mato Grosso, Brazil, with a focus on determining the possible presence of E. coli with heat resistance (60 °C/6 min), biofilm-forming potential phenotypes and genotypes, and antimicrobial susceptibility. For this, fifty pasteurized milk samples from producers named A and B were obtained for 5 weeks to investigate the presence of Enterobacteriaceae members, coliforms, and E. coli. For heat resistance, E. coli isolates were exposed to a water bath at 60 °C for 0 and 6 min. In antibiogram analysis, eight antibiotics belonging to six antimicrobial classes were analyzed. The potential to form biofilms was quantified at 570 nm, and curli expression by Congo Red was analyzed. To determine the genotypic profile, we performed PCR for the tLST and rpoS genes, and pulsed-field gel electrophoresis (PFGE) was used to investigate the clonal profile of the isolates. Thus, producer A presented unsatisfactory microbiological conditions regarding Enterobacteriaceae and coliforms for weeks 4 and 5, while all samples analyzed for producer B were contaminated at above-the-limit levels established by national and international legislation. These unsatisfactory conditions enabled us to isolate 31 E. coli from both producers (7 isolates from producer A and 24 isolates from producer B). In this way, 6 E. coli isolates (5 from producer A and 1 from producer B) were highly heat resistant. However, although only 6 E. coli showed a highly heat-resistant profile, 97% (30/31) of all E. coli were tLST-positive. In contrast, all isolates were sensitive to all antimicrobials tested. In addition, moderate or weak biofilm potential was verified in 51.6% (16/31), and the expression of curli and presence of rpoS was not always related to this biofilm potential. Therefore, the results emphasize the spreading of heat-resistant E. coli with tLST in both producers and indicate the biofilm as a possible source of contamination during milk pasteurization. However, the possibility of E. coli producing biofilm and surviving pasteurization temperatures cannot be ruled out, and this should be investigated.

Early Infliximab Clearance Predicts Remission in Children with Crohn's Disease.

BACKGROUND AND AIMS: Children with Crohn's disease have lower response rates to infliximab, lower infliximab levels, and higher infliximab clearance on weight-based dosing than adults. We hypothesize infliximab clearance is a predictive of later outcomes on infliximab in children with Crohn's disease. METHODS: In this single-center retrospective study, data were collected from charts on diagnosis, anthropometry, routine labs, infliximab therapeutic drug monitoring, infliximab dosing, disease activity, and other treatments. With these data we generated a population pharmacokinetic model using non-linear mixed effects modeling and calculated infliximab clearance for each patient over time. Patients were classified as in remission, responder-only or non-responder at 5, 10 and 16 months. Regression and ROC analyses were used to assess for early predictors of remission and response to infliximab. RESULTS: Eighty-five subjects were included, with a median follow-up of 22.3 months (IQR 10.1-36.8). Our pharmacokinetic model showed infliximab clearance was positively associated with CRP and weight, while negatively associated with albumin. In regression analyses, early infliximab clearance was the only significant, consistent predictor of remission. A 0.1 L/day increase in infliximab clearance predicted remission with an OR between 0.179 and 0.426. Differences in dosing did not account for differences in outcome. Infliximab clearance alone had moderate predictive accuracy of remission, with an AUC between 0.682 and 0.738. CONCLUSIONS: Early infliximab clearance is strongly associated with remission in children with Crohn's disease. It may be useful as a marker of response in proactive therapeutic drug monitoring to guide early dose optimization and/or changes in treatment for betterment of long-term outcomes.

Intestinal parasite infections associated with sociodemographic and seasonal factors in the Western Amazon.

Intestinal parasites are a constant public health problem in the Amazon region, with a high prevalence of cases related to poor sanitary conditions. We investigated the sociodemographic and seasonal factors associated with human intestinal parasite infections in an area of the Western Amazon, Brazil, from September 2017 to August 2019. Data were collected using a database available at the Diagnostic Support Centre (Centro de Apoio ao Diagnóstico, CAD) of the Municipality of Rio Branco, on positive diagnoses for intestinal parasites. Among the 53,200 samples analysed, 18.3% (n = 9712) were positive. Of these, 96.4% (n = 9363) and 3.6% (n = 349) were protozoan and helminthic infections, respectively. Males showed higher odds ratio (OR) for Enterobius vermicularis infection (OR: 2.3) and giardiasis (OR: 1.9) and lower OR for Endolimax nana (OR: 0.9) and Entamoeba coli (OR: 0.9) infections. Individuals aged ≥ 15 presented higher OR for Strongyloides stercoralis (OR: 3.4), hookworms (OR: 2.3), and almost all protozoan infections than younger individuals. In the dry season, the OR for hookworms (OR: 1.5), Iodamoeba butschlii (OR: 1.4), and Endolimax nana (OR: 1.3) infections was higher than that in the rainy season, including a high chance of polyparasitism (OR: 1.6). We concluded that there was a significant difference between the different types of intestinal parasites, particularly protozoa, with high OR in the dry season and for certain groups.

Pediatric Patient and Caregiver Satisfaction With the Use of Transabdominal Bowel Ultrasound in the Assessment of Inflammatory Bowel Diseases.

OBJECTIVES: Transabdominal bowel ultrasound (TABUS) is emerging as an attractive, noninvasive tool in inflammatory bowel disease (IBD). Patient and caregiver experience with TABUS is not well described. We aimed to determine pediatric patient and caregiver satisfaction with TABUS and the impact of IBD severity, gender, age, and a history of anxiety on satisfaction. METHODS: Pediatric patients (0-18 years old) with suspected IBD prospectively underwent baseline TABUS, magnetic resonance enterography (MRE), blood work, stool studies, and endoscopy. Patients and their caregiver each completed a cross-sectional satisfaction questionnaire (5-point Likert scale) after the baseline investigations. RESULTS: There were 54 patients included (67% male). The majority were completely satisfied and strongly agree TABUS was better tolerated than other investigations, regardless of disease severity ( P > 0.05). Patients with higher Simple Endoscopic Score for Crohn Disease (SES-CD) scores felt that TABUS increased their understanding of their IBD ( P < 0.05) and disease location ( P < 0.05). Patients with Crohn disease had similar responses to those with ulcerative colitis, but more strongly agreed that TABUS was better than MRE and endoscopy ( P < 0.05). Those with anxiety did not have an increased level of worry about potential ultrasound findings ( P > 0.05). CONCLUSIONS: Pediatric patients and their caregivers were highly satisfied with TABUS, preferring it to other modalities. It did not lead to increased worry, and was particularly important in those with severe IBD. These findings support wider implementation of this well tolerated and preferred monitoring tool in pediatrics.

Far from being a simple question: The complexity between in vitro and in vivo responses from nutrients and bioactive compounds with antioxidant potential.

Food nutrients and bioactive compounds have been widely explored due to the increased prevalence of chronic non-communicable diseases. Antioxidant supplementation might be a crucial non-pharmacological strategy against oxidative stress. However, although some assays evaluate the antioxidant potential of a particular food or food compound, in vivo responses related to oxidative stress in the body may not be reproduced or directly correlated with in vitro values. Therefore, this review aims to discuss the relationship between data obtained in vitro for the antioxidant potential of food/food compounds and the effects observed in vivo. More specifically, we examined in vitro methods for evaluating antioxidant potential, their limitations, and the effects of consuming food rich in antioxidants on oxidative stress biomarkers. This review will help to understand the effects of antioxidant compounds on oxidative stress biomarkers (usually measured in vivo) and their use as health parameters to explain the effects of dietary antioxidants.

Osteoblastic Lesions as the First Presentation of a Gastric Mixed-Type Adenocarcinoma: A Case Report.

Bone metastasis might be associated with several tumors; however, the association between gastric malignant neoplasms and bone secondary lesions is very rare, with the osteoblastic form having the rarest presentation. In fact, osteoblastic lesions, as the first presentation of gastric adenocarcinomas, are even rarer and known to have a very poor prognosis associated with them. Therefore, we present a clinical case of a patient with lower back pain as the first symptom, which led to the diagnosis of osteoblastic lesions of the spine and iliac bones, suggested as secondary lesions. Later, the investigation of the primary tumor led to the diagnosis of a gastric adenocarcinoma (stage IV disease). In this report, we highlight the steps taken for the etiological study course and the challenges associated with them from the beginning. We also emphasize the very unfavorable evolution of our patient, with the inability to carry out targeted treatment, neither curative nor palliative, due to the advanced stage of the disease and the very poor survival time associated with it.

An Atypical Presentation of Non-Hodgkin's Lymphoma.

Lymphomas result from the proliferation of malignant lymphocytes, which can affect lymph nodes, blood, and other organs. Primary involvement of the spine by haematological diseases is rare. Non-Hodgkin's lymphoma with an extranodal location most frequently involves the gastrointestinal tract and airways, affecting the bone, muscle, and nervous system. We present a clinical case of an atypical form of non-Hodgkin's lymphoma. A 78-year-old woman was admitted to the hospital with complaints of pain in the lumbar region, hip, and left leg for the last month. Computed tomography of the lumbar spine revealed a mass of left paravertebral tissue with involvement from L3 to L5. Thoraco-abdominal CT-guided biopsy revealed diffuse large-cell non-Hodgkin B lymphoma. The remainder of the study did not show lymphatic involvement, so a diagnosis of primary extranodal large cell non-Hodgkin B lymphoma was made.

Bioactive compounds modulating Toll-like 4 receptor (TLR4)-mediated inflammation: pathways involved and future perspectives.

Chronic inflammation is associated with the development and progression of several noncommunicable diseases, such as diabetes, cardiovascular disease, chronic kidney disease, cancer, and nonalcoholic fatty liver disease. Evidence suggests that pattern recognition receptors that identify pathogen-associated molecular patterns and danger-associated molecular patterns are crucial in chronic inflammation. Among the pattern recognition receptors, Toll-like receptor 4 (TLR4) stimulates several inflammatory pathway agonists, such as nuclear factor-κB, interferon regulator factor 3, and nod-like receptor pyrin domain containing 3 pathways, which consequently trigger the expression of pro-inflammatory biomarkers, increasing the risk of noncommunicable disease development and progression. Studies have focused on the antagonistic potential of bioactive compounds, following the concept of food as a medicine, in which nutritional strategies may mitigate inflammation via TLR4 modulation. Thus, this review discusses preclinical evidence concerning bioactive compounds from fruit, vegetable, spice, and herb extracts (curcumin, resveratrol, catechin, cinnamaldehyde, emodin, ginsenosides, quercetin, allicin, and caffeine) that may regulate the TLR4 pathway and reduce the inflammatory response. Bioactive compounds can inhibit TLR4-mediated inflammation through gut microbiota modulation, improvement of intestinal permeability, inhibition of lipopolysaccharide-TLR4 binding, and decreasing TLR4 expression by modulation of microRNAs and antioxidant pathways. The responses directly mitigated inflammation, especially nuclear factor-κB activation and inflammatory cytokines release. These findings should be considered for further clinical studies on inflammation-mediated diseases.

Cell-Fibronectin Interactions and Actomyosin Contractility Regulate the Segmentation Clock and Spatio-Temporal Somite Cleft Formation during Chick Embryo Somitogenesis.

Fibronectin is essential for somite formation in the vertebrate embryo. Fibronectin matrix assembly starts as cells emerge from the primitive streak and ingress in the unsegmented presomitic mesoderm (PSM). PSM cells undergo cyclic waves of segmentation clock gene expression, followed by Notch-dependent upregulation of meso1 in the rostral PSM which induces somite cleft formation. However, the relevance of the fibronectin matrix for these molecular processes remains unknown. Here, we assessed the role of the PSM fibronectin matrix in the spatio-temporal regulation of chick embryo somitogenesis by perturbing (1) extracellular fibronectin matrix assembly, (2) integrin-fibronectin binding, (3) Rho-associated protein kinase (ROCK) activity and (4) non-muscle myosin II (NM II) function. We found that integrin-fibronectin engagement and NM II activity are required for cell polarization in the nascent somite. All treatments resulted in defective somitic clefts and significantly perturbed meso1 and segmentation clock gene expression in the PSM. Importantly, inhibition of actomyosin-mediated contractility increased the period of hairy1/hes4 oscillations from 90 to 120 min. Together, our work strongly suggests that the fibronectin-integrin-ROCK-NM II axis regulates segmentation clock dynamics and dictates the spatio-temporal localization of somitic clefts.

Supplementation of diet with Brazil nut modulates body composition, bone parameters, and lipid peroxidation in Wistar rats.

Oxidative stress, adipose tissue, and bone compartments can be disturbed in chronic diseases. Non-pharmacological strategies, such as Brazil nuts (BNs), can improve these parameters. This study evaluated the effects of BN supplementation at different concentrations on body composition, lipid profile, and peroxidation in healthy rats. Male Wistar rats were divided into three groups: control (CT), Brazil nut 5% (BN5), and Brazil nut 10% (BN10) groups. Body composition, brown adipose tissue (BAT), plasma lipid peroxidation, and lipid profile were evaluated in the three groups. The BN5 group showed an improvement in all bone parameters compared with that of the CT group (p  < .0001). The BN5 and BN10 groups showed reduced plasma lipid peroxidation compared with that of the CT group (p = .0009), whereas the BN10 group presented lower BAT lipid peroxidation than that of the other groups (p = .01). High-density lipoprotein-cholesterol (HDL-c) levels were higher in the BN5 group than in the CT group (p = .01). Conclusively, the use of BNs in a controlled manner promoted improvement in bone parameters, HDL-c levels, and lipid peroxidation in healthy rats. PRACTICAL APPLICATIONS: Nuts has been included in the diet because of their versatility, acceptance, and easy access. Among them, Brazil nut (BN) is considered one of the major known food sources of selenium as well as a source of fibers, unsaturated fatty acids, and phenolic compounds. Studies have shown that BN supplementation is effective in reducing oxidative stress, inflammation, lipid peroxidation, and selenium deficiency when used as a non-pharmacological strategy in experimental models of chronic diseases and in clinical trials. The present study showed that controlled administration of BN improved bone parameters, high-density lipoprotein-cholesterol levels, and lipid peroxidation in healthy rats. Therefore, BN is a promising non-pharmacological agent for the prevention of the onset of chronic non-communicable diseases.

Relaxing the "second brain": nutrients and bioactive compounds as a therapeutic and preventive strategy to alleviate oxidative stress in the enteric nervous system.

The enteric nervous system (ENS) regulates several functional and immunological processes in the gastrointestinal tract. However, some diseases can disrupt the ENS functionality, impacting the behavior of enteric neurons and enteric glial cells by increasing the accumulation of reactive oxygen species. Oxidative stress is considered to be a trigger for alterations in these cells' morphology, density, and neurochemical patterns. In light of this, nutritional strategies are a growing field of investigation regarding their potential to modulate enteric neurons and enteric glial cells through reduced reactive oxygen species production. Moreover, several lines of evidence show that nutrients are related to counteracting oxidative stress. Some studies have evaluated the potential of nutrients with antioxidant roles (such as amino acids, polyphenols, prebiotics, vitamins, and specific extracts obtained from foods) to modulate the ENS. Thus, this review discusses how bioactive compounds and nutrients can impact the ENS by alleviating oxidative stress.

5/6 nephrectomy affects enteric glial cells and promotes impaired antioxidant defense in the colonic neuromuscular layer.

AIMS: Chronic kidney disease (CKD) produces multiple repercussions in the gastrointestinal tract (GIT), such as alterations in motility, gut microbiota, intestinal permeability, and increased oxidative stress. However, despite enteric glial cells (EGC) having important neural and immune features in GIT physiology, their function in CKD remains unknown. The present study investigates colonic glial markers, inflammation, and antioxidant parameters in a CKD model. MAIN METHODS: A 5/6 nephrectomized rat model was used to induce CKD in rats and Sham-operated animals as a control to suppress. Biochemical measures in plasma and neuromuscular layer such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were carried out. Kidney histopathology was evaluated. Colon morphology analysis and glial fibrillary acid protein (GFAP), connexin-43 (Cx43), nuclear factor-kappa B (NF-κB) p65, and GPx protein expression were performed. KEY FINDINGS: The CKD group exhibited dilated tubules and tubulointerstitial fibrosis in the reminiscent kidney (p = 0.0002). CKD rats showed higher SOD activity (p = 0.004) in plasma, with no differences in neuromuscular layer (p = 0.9833). However, GPx activity was decreased in the CKD group in plasma (p = 0.013) and neuromuscular layer (p = 0.0338). Morphological analysis revealed alterations in colonic morphometry with inflammatory foci in the submucosal layer and neuromuscular layer straightness in CKD rats (p = 0.0291). In addition, GFAP, Cx43, NF-κBp65 protein expression were increased, and GPx decreased in the neuromuscular layer of the CKD group (p < 0.05). SIGNIFICANCE: CKD animals present alterations in colonic cytoarchitecture and decreased layer thickness. Moreover, CKD affects the enteric glial network of the neuromuscular layer, associated with decreased antioxidant activity and inflammation.

Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer.

Inhibitors of the programmed cell death-1 (PD-1/PD-L1) signaling axis are approved to treat non-small cell lung cancer (NSCLC) patients, based on their significant overall survival (OS) benefit. Using transcriptomic analysis of 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy from two large randomized clinical trials, we find a significant B cell association with extended OS with PD-L1 blockade, independent of CD8+ T cell signals. We then derive gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA sequencing (RNA-seq) data. Importantly, we find increased plasma cell signatures to be predictive of OS in patients treated with atezolizumab, but not chemotherapy. B and plasma cells are also associated with the presence of tertiary lymphoid structures and organized lymphoid aggregates. Our results suggest an important contribution of B and plasma cells to the efficacy of PD-L1 blockade in NSCLC.