Longitudinal markers of cerebral amyloid angiopathy and related inflammation in rTg-DI rats.

Cerebral amyloid angiopathy (CAA) is a prevalent vascular dementia and common comorbidity of Alzheimer's disease (AD). While it is known that vascular fibrillar amyloid ß (Aß) deposits leads to vascular deterioration and can drive parenchymal CAA related inflammation (CAA-ri), underlying mechanisms of CAA pathology remain poorly understood. Here, we conducted brain regional proteomic analysis of early and late disease stages in the rTg-DI CAA rat model to gain molecular insight to mechanisms of CAA/CAA-ri progression and identify potential brain protein markers of CAA/CAA-ri. Longitudinal brain regional proteomic analysis revealed increased differentially expressed proteins (DEP) including ANXA3, HTRA1, APOE, CST3, and CLU, shared between the cortex, hippocampus, and thalamus, at both stages of disease in rTg-DI rats. Subsequent pathway analysis indicated pathway enrichment and predicted activation of TGF-ß1, which was confirmed by immunolabeling and ELISA. Further, we identified numerous CAA related DEPs associate with astrocytes (HSPB1 and MLC1) and microglia (ANXA3, SPARC, TGF-ß1) not previously associated with astrocytes or microglia in other AD models, possibly indicating that they are specific to CAA-ri. Thus, the data presented here identify several potential brain protein biomarkers of CAA/CAA-ri while providing novel molecular and mechanistic insight to mechanisms of CAA and CAA-ri pathological progression and glial cell mediated responses.

Biomaterial-based combinatorial approach of aescin-comprised zein-coated gelatin nanoparticles alleviates synovial inflammation in experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mostly affects joints. Although RA therapy has made significant progress, difficulties including extensive medication metabolism and its quick clearance result in its inadequate bioavailability. The anti-inflammatory effect of zein was reported with other medications, but it has certain limitations. There are reports on the anti-oxidant and anti-inflammatory effect of aescin, which exhibits low bioavailability for the treatment of rheumatoid arthritis. Also, the combinatorial effect of zein with other effective drug delivery systems is still under investigation for the treatment of experimental collagen-induced rheumatoid arthritis. The focus of this study was to formulate and define the characteristics of zein-coated gelatin nanoparticles encapsulated with aescin (Ze@Aes-GNPs) and to assess and contrast the therapeutic effectiveness of Ze@Aes-GNPs towards collagen-induced RA in Wistar rats. Nanoprecipitation and the layer-by-layer coating process were used to fabricate Ze@Aes-GNPs and their hydrodynamic diameter was determined to be 182 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to further validate the size, shape, and surface morphology of Ze@Aes-GNPs. When tested against foreskin fibroblasts (BJ), these nanoparticles demonstrated significantly high cytocompatibility. Both Aes and Ze@Aes-GNPs were effective in treating arthritis, as shown by the decreased edoema, erythema, and swelling of the joints, between which Ze@Aes-GNPs were more effective. Further, it was demonstrated that Aes and Ze@Aes-GNPs reduced the levels of oxidative stress (articular elastase, lipid peroxidation, catalase, superoxide dismutase and nitric oxide) and inflammatory indicators (TNF-α, IL-1ß and myeloperoxidase). The histopathology findings further demonstrated that Ze@Aes-GNPs considerably reduced the infiltration of inflammatory cells at the ankle joint cartilage compared to Aes. Additionally, immunohistochemistry examination showed that treatment with Ze@Aes-GNPs suppressed the expression of pro-inflammatory markers (COX-2 and IL-6) while increasing the expression of SOD1. In summary, the experiments indicated that Aes and Ze@Aes-GNPs lowered the severity of arthritis, and critically, Ze@Aes-GNPs showed better effectiveness in comparison to Aes. This suppression of oxidative stress and inflammation was likely driven by Aes and Ze@Aes-GNPs.

Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling.

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations, charted their spatial organization, and revealed their polarization or recruitment in inflammation. We found a staged progression of inflammation-associated tissue neighborhoods defined, in part, by multiple inflammation-associated fibroblasts, with unique expression profiles, spatial localization, cell-cell interactions, and healthy fibroblast origins. Similar signatures in ulcerative colitis suggest conserved human processes. Broadly, we provide a framework for understanding inflammation-induced remodeling in the gut and other tissues.

Prognostic significance of systemic inflammatory parameters in high-grade glial tumor patients: Two center experience.

We aimed to determine the prognostic values of the neutrophil-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, body mass index, and prognostic nutritional index scores in patients with high-grade glioma. This was a retrospective observational case series. Between 2015 and 2020, 79 patients with high-grade gliomas 2 oncology centers were included in our study. All patients (n = 79) had high-grade glial tumors and were treated with RT. Sixty-nine (87.3%) patients died, and the median 2 years overall survival was 12.7 months. Recurrence was observed in 25 (31.6%) patients at the end of the treatment. The median recurrence free survival was 24.4 months. There was no significant correlation between systemic inflammation indicators and survival parameters for OS and RFS. Only a marginally significant association between the neutrophil-lymphocyte ratio and RFS was found. Systemic inflammatory parameters and outcomes were not significantly correlated in patients with high-grade gliomas.

Effect of epicatechin consumption on the inflammatory pathway and mitochondria morphology in PBMC from a R350P desminopathy patient: A case report.

Desminopathy R350P is a human myopathy that is characterized by the progressive loss of muscle fiber organization. This results in the loss of muscle size, mobility, and strength. In desminopathy, inflammation affects muscle homeostasis and repair, and contributes to progressive muscle deterioration. Mitochondria morphology was also suggested to affect desminopathy progression. Epicatechin (Epi)-a natural compound found in cacao-has been proposed to regulate inflammatory signaling and mitochondria morphology in human and animal models. Hence, we hypothesize chronic Epi consumption to improve inflammatory pathway and mitochondria morphology in the peripheral blood mononuclear cells (PBMCs) of a desminopathy R350P patient. We found that 12 weeks of Epi consumption partially restored TRL4 signaling, indicative of inflammatory signaling and mitochondria morphology in the desminopathy patient. Moreover, Epi consumption improved blood health parameters, including reduced HOMA-IR and IL-6 levels in the desminopathy patient. This indicates that Epi consumption could be a useful tool to slow disease progression in desminopathy patients.

Association of the systemic immuno-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio with diabetic microvascular complications.

Background: The systemic immuno-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are widely used and have been shown to be predictive indicators of various diseases. Diabetic nephropathy (DN), retinopathy (DR), and peripheral neuropathy (DPN) are the most prominent and common microvascular complications, which have seriously negative impacts on patients, families, and society. Exploring the associations with these three indicators and diabetic microvascular complications are the main purpose. Methods: There were 1058 individuals with type 2 diabetes mellitus (T2DM) in this retrospective cross-sectional study. SII, NLR, and PLR were calculated. The diseases were diagnosed by endocrinologists. Logistic regression and subgroup analysis were applied to evaluate the association between SII, NLP, and PLR and diabetic microvascular complications. Results: SII, NLR, and PLR were significantly associated with the risk of DN [odds ratios (ORs): 1.52, 1.71, and 1.60, respectively] and DR [ORs: 1.57, 1.79, and 1.55, respectively] by multivariate logistic regression. When NLR ≥2.66, the OR was significantly higher for the risk of DPN (OR: 1.985, 95% confidence interval: 1.29-3.05). Subgroup analysis showed no significant positive associations across different demographics and comorbidities, including sex, age, hypertension, HbA1c (glycated hemoglobin), and dyslipidemia. Conclusion: This study found a positive relationship between NLR and DN, DR, and DPN. In contrast, SII and PLR were found to be only associated with DN and DR. Therefore, for the diagnosis of diabetic microvascular complications, SII, NLR and PLR are highly valuable.

Dynamics of CD44+ bovine nucleus pulposus cells with inflammation.

Intervertebral Disc (IVD) degeneration has been associated with a chronic inflammatory response, but knowledge on the contribution of distinct IVD cells, namely CD44, to the progression of IVD degeneration remains elusive. Here, bovine nucleus pulposus (NP) CD44 cells were sorted and compared by gene expression and proteomics with the negative counterpart. NP cells were then stimulated with IL-1b (10 ng/ml) and dynamics of CD44 gene and protein expression was analyzed upon pro-inflammatory treatment. The results emphasize that CD44 has a multidimensional functional role in IVD metabolism, ECM synthesis and production of neuropermissive factors. CD44 widespread expression in NP was partially associated with CD14 and CD45, resulting in the identification of distinct cell subsets. In conclusion, this study points out CD44 and CD44-based cell subsets as relevant targets in the modulation of the IVD pro-inflammatory/degenerative cascade.

Oxidative stress, inflammation, and steatosis elucidate the complex dynamics of HgCl2 induced liver damage in Channa punctata.

Water bodies are highly pollution-prone areas in which mercury (Hg) is considered as a major menace to aquatic organisms. However, the information about the toxicity of mercuric chloride (HgCl2) in a vital organ such as the liver of fish is still inadequate. This study aimed to assess the impact of mercuric chloride (HgCl2) exposure on the liver of Channa punctata fish over 15, 30, and 45 days, at two different concentrations (0.039 mg/L and 0.078 mg/L). Mercury is known to be a significant threat to aquatic life, and yet, information regarding its effects on fish liver remains limited. The results of this study demonstrate that exposure to HgCl2 significantly increases oxidative stress markers, such as lipid peroxidation (LPO) and protein carbonyls (PC), as well as the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in the fish. Additionally, the transcriptional and protein analysis of specific genes and molecules associated with necroptosis and inflammation, such as ABCG2, TNF α, Caspase 3, RIPK 3, IL-1ß, Caspase-1, IL-18, and RIPK1, confirm the occurrence of necroptosis and inflammation in the liver. Histopathological and ultrastructural examinations of the liver tissue further reveal a significant presence of liver steatosis. Interestingly, the upregulation of PPARα suggests that the fish's body is actively responding to counteract the effects of liver steatosis. This study provides a comprehensive analysis of oxidative stress, biochemical changes, gene expression, protein profiles, and histological findings in the liver tissue of fish exposed to mercury pollution in freshwater environments.

Microenvironment, systemic inflammatory response and tumor markers considering consensus molecular subtypes of colorectal cancer.

Introduction: Colorectal carcinomas (CRC) are one of the most frequent malignancies worldwide. Based on gene expression profile analysis, CRCs can be classified into four distinct subtypes also known as the consensus molecular subtypes (CMS), which predict biological behaviour. Besides CMS, several other aspects of tumor microenvironment (TME) and systemic inflammatory response (SIR) influence the outcome of CRC patients. TME and inflammation have important role in the immune (CMS1) and mesenchymal (CMS4) subtypes, however, the relationship between these and systemic inflammation has not been assessed yet. Our objective was to evaluate the connection between CMS, TME and SIR, and to analyze the correlation between these markers and routinely used tumor markers, such as CEA (Carcinoembryonic Antigen) and CA19-9 (Carbohydrate Antigen 19-9). Methods: FFPE (Formalin Fixed Paraffin Embedded) samples of 185 CRC patients were collected. TME was described using tumor-stroma ratio (TSR), Klintrup-Makinen (KM) grade, and Glasgow Microenvironment Score (GMS). CMS classification was performed on tissue microarray using MLH1, PMS2, MSH2 and MSH6, and pan-cytokeratin, CDX2, FRMD6, HTR2B and ZEB1 immunohistochemical stains. Pre-operative tumor marker levels and inflammatory markers [C-reactive protein - CRP, albumin, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute platelet count (APC)] and patient history were retrieved using MedSolution database. Results: Amongst TME-markers, TSR correlated most consistently with adverse clinicopathological features (p < 0.001) and overall survival (p < 0.001). Elevated CRP and modified Glasgow Prognostic Score (mGPS) were associated with worse outcome and aggressive phenotype, similarly to tumor markers CEA and CA19-9. Stroma-Tumor Marker score (STM score), a new combined score of CA19-9 and TSR delivered the second best prognostication after mGPS. Furthermore, CMS4 showed association with TSR and several laboratory markers (albumin and platelet derived factors), but not with other SIR descriptors. CMS did not show any association with CEA and CA19-9 tumor markers. Conclusion: More routinely available TME, SIR and tumor markers alone and in combination deliver reliable prognostic data for choosing the patients with higher risk for propagation. CMS4 is linked with high TSR and poor prognosis, but in overall, CMS-classification showed only limited effect on SIR- and tumor-markers.

TP53INP2 knockdown inhibits inflammatory response and apoptosis after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a traumatic neurological disorder with limited therapeutic options. Tumor protein p53-inducible nuclear protein 2 (TP53INP2) is involved in the occurrence and development of various diseases, and it may play a role during SCI via affecting inflammation and neuronal apoptosis. This study investigated the associated roles and mechanisms of TP53INP2 in SCI. METHODS: Mouse and lipopolysaccharide (LPS)-induced SCI BV-2 cell models were constructed to explore the role of TP53INP2 in SCI and the associated mechanisms. Histopathological evaluation of spinal cord tissue was detected by hematoxylin and eosin staining. The Basso, Beattie, and Bresnahan score was used to measure the motor function of the mice, while the spinal cord water content was used to assess spinal cord edema. The expression of TP53INP2 was measured using RT-qPCR. In addition, inflammatory factors in the spinal cord tissue of SCI mice and LPS-treated BV-2 cells were measured using enzyme-linked immunosorbent assay. Apoptosis and related protein expression levels were detected by flow cytometry and western blot analysis, respectively. RESULTS: TP53INP2 levels increased in SCI mice and LPS-treated BV-2 cells. The results of in vivo and in vitro experiments showed that TP53INP2 knockdown inhibited the inflammatory response and neuronal apoptosis in mouse spinal cord tissue or LPS-induced BV-2 cells. CONCLUSIONS: After spinal cord injury, TP53INP2 was upregulated, and TP53INP2 knockdown inhibited the inflammatory response and apoptosis.

Inflammation and Exosomes in Fabry Disease Pathogenesis.

Fabry Disease (FD) is one of the most prevalent lysosomal storage disorders, resulting from mutations in the GLA gene located on the X chromosome. This genetic mutation triggers glo-botriaosylceramide (Gb-3) buildup within lysosomes, ultimately impairing cellular functions. Given the role of lysosomes in immune cell physiology, FD has been suggested to have a profound impact on immunological responses. During the past years, research has been focusing on this topic, and pooled evidence strengthens the hypothesis that Gb-3 accumulation potentiates the production of pro-inflammatory mediators, revealing the existence of an acute inflammatory process in FD that possibly develops to a chronic state due to stimulus persistency. In parallel, extracellular vesicles (EVs) have gained attention due to their function as intercellular communicators. Considering EVs' capacity to convey cargo from parent to distant cells, they emerge as potential inflammatory intermediaries capable of transporting cytokines and other immunomodulatory molecules. In this review, we revisit the evidence underlying the association between FD and altered immune responses and explore the potential of EVs to function as inflammatory vehicles.

Recently Updated Role of Chitinase 3-like 1 on Various Cell Types as a Major Influencer of Chronic Inflammation.

Chitinase 3-like 1 (also known as CHI3L1 or YKL-40) is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but it is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce mammalian chitinases, such as CHI3L1, to protect the body from exogenous pathogens as well as hostile environments, and it was thought that it had a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pathophysiological role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we summarize the expression of CHI3L1 under chronic inflammatory conditions in various disorders and discuss the potential roles of CHI3L1 in those disorders on various cell types.

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning.

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-ß, TGF-ß1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-ß induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-ß1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

Immune microniches shape intestinal Treg function.

The intestinal immune system is highly adapted to maintaining tolerance to the commensal microbiota and self-antigens while defending against invading pathogens1,2. Recognizing how the diverse network of local cells establish homeostasis and maintains it in the complex immune environment of the gut is critical to understanding how tolerance can be re-established following dysfunction, such as in inflammatory disorders. Although cell and molecular interactions that control T regulatory (Treg) cell development and function have been identified3,4, less is known about the cellular neighbourhoods and spatial compartmentalization that shapes microorganism-reactive Treg cell function. Here we used in vivo live imaging, photo-activation-guided single-cell RNA sequencing5-7 and spatial transcriptomics to follow the natural history of T cells that are reactive towards Helicobacter hepaticus through space and time in the settings of tolerance and inflammation. Although antigen stimulation can occur anywhere in the tissue, the lamina propria-but not embedded lymphoid aggregates-is the key microniche that supports effector Treg (eTreg) cell function. eTreg cells are stable once their niche is established; however, unleashing inflammation breaks down compartmentalization, leading to dominance of CD103+SIRPα+ dendritic cells in the lamina propria. We identify and validate the putative tolerogenic interaction between CD206+ macrophages and eTreg cells in the lamina propria and identify receptor-ligand pairs that are likely to govern the interaction. Our results reveal a spatial mechanism of tolerance in the lamina propria and demonstrate how knowledge of local interactions may contribute to the next generation of tolerance-inducing therapies.

Immune Homeostasis Maintenance Through Advanced Immune Therapeutics to Target Atherosclerosis.

Atherosclerosis remains the leading cause of coronary heart disease (CHD) with enormous health and societal tolls. Traditional drug development approaches have been focused on small molecule-based compounds that aim to lower plasma lipids and reduce systemic inflammation, two primary causes of atherosclerosis. However, despite the widely available lipid-lowering and anti-inflammatory small compounds and biologic agents, CHD prevalence still remains high. Based on recent advances revealing disrupted immune homeostasis during atherosclerosis pathogenesis, novel strategies aimed at rejuvenating immune homeostasis with engineered immune leukocytes are being developed. This chapter aims to assess basic and translational efforts on these emerging strategies for the effective development of atherosclerosis treatment, as well as key challenges in this important translational field.

Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats.

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation. This study aimed to investigate the anti-OA effect of scutellarein (SCU), a single-unit flavonoid compound obtained from Scutellaria barbata D. Don, in rats. METHODS: The extracted rat chondrocytes were treated with SCU and IL-1ß. The chondrocytes were divided into control group, IL-1ß group, IL-1ß+SCU 50 µmol/L group, and IL-1ß+SCU 100 µmol/L group. Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining. CCK-8 method was used to detect the cytotoxicity of SCU. ELISA, qRT-PCR, Western blotting, immunofluorescence, SAß-gal staining, flow cytometry, and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1ß intervention. Additionally, anterior cruciate ligament transection (ACL-T) was used to establish a rat OA model. Histological changes were detected by safranin O/fast green, hematoxylin-eosin (HE) staining, and immunohistochemistry. RESULTS: SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms. Specifically, it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation. In addition, SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase (NF-κB/MAPK) pathway, thereby reducing inflammatory cytokine production in the joint cartilage. Furthermore, SCU significantly reduced IL-1ß-induced apoptosis and senescence in rat chondrocytes, further highlighting its potential role in OA treatment. In vivo experiments revealed that SCU (at a dose of 50 mg/kg) administered for 2 months could significantly delay the progression of cartilage damage, which was reflected in a lower Osteoarthritis Research Society International (OARSI) score, and reduced expression of matrix metalloproteinase 13 (MMP13) in cartilage. CONCLUSION: SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.

Neutrophil extracellular traps as a unique target in the treatment of inflammatory pain.

Pain is a widespread motivation for seeking healthcare and stands as a substantial global public health concern. Despite comprehensive investigations into the mechanisms of pain sensitization induced by inflammation, efficacious treatments options remain scarce. Neutrophil extracellular traps (NETs) have been associated with the progression and tissue damage of diverse inflammatory diseases. This study aims to explore the impact of NETs on the progression of inflammatory pain and explore potential therapeutic approaches. Initially, we observed neutrophil infiltration and the formation of NETs in the left hind paw of mice with inflammatory pain induced by complete Freund's adjuvant (CFA). Furthermore, we employed the peptidyl arginine deiminase 4 (PAD4) inhibitor Cl-amidine (diluted at 50 mg/kg in saline, administered via tail vein injection once daily for three days) to impede NETs formation and administered DNase1 (diluted at 10 mg/kg in saline, once daily for three days) to break down NETs. We investigated the pathological importance of peripheral NETs formation in inflammatory pain and its influence on the activation of spinal dorsal horn microglia. The findings indicate that neutrophils infiltrating locally generate NETs, leading to an increased release of inflammatory mediators that worsen peripheral inflammatory reactions. Consequently, this results in the transmission of more harmful peripheral stimuli to the spinal cord, triggering microglial activation and NF-κB phosphorylation, thereby escalating neuroinflammation and fostering pain sensitization. Suppression of peripheral NETs can mitigate peripheral inflammation in mice with inflammatory pain, reverse mechanical and thermal hypersensitivity by suppressing microglial activation in the spinal cord, ultimately diminishing inflammatory pain. In conclusion, these discoveries propose that obstructing or intervening with NETs introduces a novel therapeutic avenue for addressing inflammatory pain.

Bronchoconstriction damages airway epithelia by crowding-induced excess cell extrusion.

Asthma is deemed an inflammatory disease, yet the defining diagnostic feature is mechanical bronchoconstriction. We previously discovered a conserved process called cell extrusion that drives homeostatic epithelial cell death when cells become too crowded. In this work, we show that the pathological crowding of a bronchoconstrictive attack causes so much epithelial cell extrusion that it damages the airways, resulting in inflammation and mucus secretion in both mice and humans. Although relaxing the airways with the rescue treatment albuterol did not affect these responses, inhibiting live cell extrusion signaling during bronchoconstriction prevented all these features. Our findings show that bronchoconstriction causes epithelial damage and inflammation by excess crowding-induced cell extrusion and suggest that blocking epithelial extrusion, instead of the ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.

Kidney damage associated with COVID-19: from the acute to the chronic phase.

Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) infection is well established as a systemic disease including kidney damage. The entry point into the renal cell remains the angiotensin-converting enzyme 2 (ACE-2) receptor and the spectrum of renal lesions is broad, with a clear predominance of structural and functional tubular lesions. The most common form of glomerular injury is collapsing glomerulopathy (CG), which is strongly associated with apolipoprotein L1(APOL-1) risk variants. These acute lesions, which are secondary to the direct or indirect effects of SARS-CoV-2, can progress to chronicity and are specific to long COVID-19 in the absence of any other cause. Residual inflammation associated with SARS-CoV-2 infection, in addition to acute kidney injury (AKI) as a transitional state with or without severe histological lesions, may be responsible for greater kidney function decline in mild-to-moderate COVID-19. This review discusses the evidence for renal histological markers of chronicity in COVID-19 patients and triggers of low-grade inflammation that may explain the decline in kidney function in the post-COVID-19 period.