Inflammatory Cell Infiltration Research Articles

TNBS colitis induces architectural changes and alpha-synuclein overexpression in mouse distal colon: A morphological study.

Alpha-synuclein (α-syn) is widely expressed in presynaptic neuron terminals, and its structural alterations play an important role in the pathogenesis of Parkinson's disease (PD). Aggregated α-syn has been found in brain, in the peripheral nerves of the enteric nervous system (ENS) and in the intestinal neuroendocrine cells during synucleinopathies and inflammatory bowel disorders. In the present study, we evaluated the histomorphological features of murine colon with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, a common model of colitis. Thereafter, we investigated the expression of α-syn, Toll-like receptor 4 (TLR4), choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), and calcitonin-like receptor (CALCR). Finally, we investigated the presence of phosphorylated α-syn (pS129 α-syn) aggregates and their relationship with inflammatory cells. Colon from TNBS mice showed an increase in inflammatory cells infiltrate and significative changes in the architecture of the intestinal mucosa. α-Syn expression was significantly higher in inflamed colon. VIP was increased in both the mucosa and muscularis externa of TNBS mice, while TH, CGRP, and CALCR were significantly reduced in TNBS mice. Amyloid aggregates of pS129 α-syn were detectable in the ENS, as in the macrophages around the glands of the mucosa correlating with the markers of inflammation. This study describes - for the first time - the altered expression of α-syn and the occurrence of amyloid α-syn aggregates in the inflammatory cells under colitis, supporting the critical role of bowel inflammation in synucleinopathies and the involvement of α-syn in IBD.

Generation of a SARS-CoV-2-susceptible mouse model using adenovirus vector expressing human angiotensin-converting enzyme 2 driven by an elongation factor 1α promoter with leftward orientation

IntroductionTo analyze the molecular pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a small animal model such as mice is needed: human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice.MethodsWe conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an elongation factor 1α (EF1α) promoter with a leftward orientation.ResultsIn this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication. An early circulating strain of SARS-CoV-2 caused the most severe weight loss when compared to SARS-CoV-2 variants such as Alpha, Beta and Gamma, although histopathological findings, viral replication, and cytokine expression characteristics were comparableDiscussionWe found that a distinct proteome of an early circulating strain infected lung characterized by elevated complement activation and blood coagulation, which were mild in other variants, can contribute to disease severity. Unraveling the specificity of early circulating SARS-CoV-2 strains is important in elucidating the origin of the pandemic.

Quercetin alleviates ulcerative colitis through inhibiting CXCL8-CXCR1/2 axis: a network and transcriptome analysis

IntroductionUlcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract in which mucosal healing is a crucial measure of therapeutic efficacy. Quercetin, a flavonoid prevalent in various foods and traditional Chinese medicines, exhibits notable pharmacological properties, including antioxidant and anti-inflammatory activities. Consequently, it warrants investigation to determine its potential therapeutic effects on UC. The objective of this study was to investigate the effects and underlying mechanisms of quercetin in a murine model of UC.MethodsA comprehensive approach integrating network predictions with transcriptomic analyses was employed to identify the potential targets and enriched pathways associated with quercetin in UC. Subsequently, the effects of quercetin on pathological morphology, inflammatory mediators, and mucosal barrier-associated proteins, as well as the identified potential targets and enriched pathways, were systematically investigated in a murine model of dextran sulfate sodium (DSS)-induced UC.ResultsNetwork analyses identified CXCL8 and its receptors, CXCR1 and CXCR2, as primary target genes for therapeutic intervention in UC. Further validation through transcriptomic analysis and immunofluorescence staining demonstrated significant upregulation of the CXCL8-CXCR1/2 axis in the intestinal tissues of patients with UC. Experimental investigations in animal models have shown that quercetin markedly alleviates DSS-induced symptoms in mice. This effect includes the restoration of colonic crypt architecture, normalization of goblet cell structure and density, reduction of inflammatory cell infiltration, and decreased concentrations of inflammatory mediators. Quercetin enhanced the expression of tight junction (TJ) proteins, including ZO-1, MUC2 (Mucin 2), and occludin, thereby preserving the integrity of the intestinal mucosal barrier. Additionally, it significantly diminished the levels of IL-17A, NF-κB, CXCL8, CXCR1, and CXCR2 in the colonic tissues of mice with UC.DiscussionThe ameliorative effects of quercetin on colon tissue damage in DSS-induced UC mice were significant, possibly due to its ability to inhibit the CXCL8-CXCR1/2 signaling axis. These findings provide a solid foundation for the clinical application and pharmaceutical advancement of quercetin.

Chronic Cannabis Extract Modulates Anxiety Behavior in Wistar Rats: VTA Histology and Catecholamine Analysis

Cannabis, derived from the Cannabis sativa plant, has seen a surge in global use, particularly in medicinal and recreational contexts, over the past decade. The VTA, a critical component of the brain’s reward system, plays a pivotal role in motivation and addiction through its dopaminergic pathways. While research has examined the behavioral and neurochemical effects of cannabis, there is limited exploration of cannabis-induced histological changes in the VTA, thus, this study investigated the effects of chronic cannabis ethanol extract exposure on anxiety behavior, ventral tegmental area (VTA) histology, and catecholamine levels in Wistar rats. Using the Elevated Plus Maze (EPM) test, anxiety behavior was assessed across four groups exposed to varying doses (0, 50, 100, and 150 mg/kg) of cannabis extract. Histological analysis of the VTA and catecholamine quantification were conducted to evaluate structural and biochemical changes. Behavioral results indicated dose-dependent increases in anxiety, with Group 3 (100 mg/kg) showing the highest anxiety-related behaviors, evidenced by reduced open-arm exploration and increased closed-arm preference (p < 0.05). Histological analysis revealed fatty changes and inflammatory cell infiltration in the VTA, with severity increasing at higher doses. Catecholamine levels declined dose-dependent (p < 0.05), suggesting suppressed neurotransmitter synthesis or metabolism. These findings align with previous reports of cannabis-induced neurotoxicity and its biphasic effects on anxiety, extending understanding of its behavioral, structural, and biochemical impacts. The results highlight the potential risks of chronic cannabis use, particularly at higher doses, on anxiety regulation and neural integrity in the VTA.

Effects of PGK1 on immunoinfiltration by integrated single-cell and bulk RNA-sequencing analysis in sepsis

BackgroundSepsis, a life-threatening organ dysfunction caused by a dysregulated immune response to infection, remains a significant global health challenge. Phosphoglycerate kinase 1 (PGK1) has been implicated in regulating inflammation and immune cell infiltration in inflammatory conditions. However, the role of PGK1 in sepsis remains largely unexplored.MethodsFour microarray datasets and a high throughput sequencing dataset were acquired from GEO database to reveal the PGK1 expression in patients of sepsis. Quantitative real-time PCR and western blotting was then used to validate the PGK1 level. Additionally, microarray and single-cell RNA sequencing data integration, including gene set enrichment analysis (GSEA), KEGG and GO functional enrichment analysis, immune infiltration analysis, and single-cell sequencing analysis, were performed to elucidate the role of PGK1 in sepsis.ResultsOur results revealed a significant upregulation of PGK1 in sepsis patients, with the area under the ROC curve (AUC) exceeding 0.9 across multiple datasets, indicating PGK1’s strong potential as a diagnostic biomarker. Notably, PGK1 was enriched in key immune-related pathways, including the TNF signaling pathways, and leukocyte transendothelial migration, suggesting its involvement in immune regulation. Furthermore, PGK1 expression showed a positive correlation with the levels of inflammatory mediators CXCL1, CXCL16, and the chemokine receptor CCR1. In terms of immune cell infiltration, PGK1 was positively correlated with naive B cells, resting memory CD4 T cell, gamma delta T cells, M0 macrophages, eosinophils and negatively correlated with plasma cells, CD8 T cells, activated memory CD4 T cell, Tregs, activated dendritic cells.ConclusionsThis study concluded that PGK1 served as a novel diagnostic biomarker for sepsis, with potential implications for prognosis and immune regulation. The significant upregulation of PGK1 in sepsis patients and its association with immune-related pathways and cell types highlight its potential role in the pathogenesis of sepsis.

Impact of Glyphosate herbicide on blood parameters and selected tissues organs of rabbits (oryctolagus cuniculus)

Numerous studies have demonstrated that pesticides are toxic and harmful to human, animal, and environmental health. Glyphosate is the most widely used herbicide globally. This research aimed to assess the impacts of various dosages of glyphosate on rabbits. A total of 30 rabbits were divided into four groups: one control group and three treatment groups, with three concentrations of glyphosate selected as D1 (200 mg/kg/bw). The treatment groups were administered glyphosate at a dosage of 1 mL/day for 6 days per week over 4 weeks. The findings substantially reduced several hematological parameters, including hemoglobin, erythrocytes, leukocytes, hematocrit, and platelets. At the same time, the levels of white blood cells and lymphocytes increased significantly in all glyphosate-treated groups compared to the control group. Additionally, changes were observed in the liver, thymus, and kidney tissues, including alterations in hepatocyte cells, portal blood vessel congestion, inflammatory cell infiltration, and necrosis of sporadic hepatocytes.

The effect of remdesivir on heart in pregnant female rats

Remdesivir is the first medication that the FDA has authorized for use in treating COVID-19 pandemic. To evaluate the effect of remdesivir on level of sodium and potassium in blood and its effect on heart tissue in pregnant female rats. 10 pregnant female rats were used and split into two groups. 1ST group was a control group that was treated with distilled water every 48 hours, starting from 5th day of pregnancy until 19th day. 2nd group was treated with remdesivir at a concentration of 5 mg/kg body weight, every 48 hours, beginning on the 5th day of pregnancy and ending on the 19th day. On day 20, the animals were sacrificed and blood samples were taken to conduct the required tests, then an autopsy was performed to remove heart and make histological sections. Giving remdesivir was administered to the 2nd group, the blood serum potassium level significantly decreased and the sodium level significantly increased , additionally, blood congestion and hemorrhage occurred, some blood cells lysed, and there were severe cases of inflammatory cell infiltration in the heart sections compared to the 1st group. The use of remdesivir caused an imbalance in the level of electrolytes in blood and tissue damage to the heart muscle.

Can aged Camellia oleifera Abel oil truly be used to treat atopic dermatitis?

Atopic dermatitis is an inflammatory skin condition characterized by erythema, eruption, lichenification, and pruritus. Aged Camellia oleifera Abel oil, an effective empirical plant oil utilized by the Gannan Hakka people in China to alleviate the symptoms of atopic dermatitis. However, no scientific studies have been reported to prove whether this oil is truly effective. We conducted this study to confirm whether aged C. oleifera oil could alleviate the symptoms of 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Differences in the thickness and weight of the right and left ears were measured. ELISA was used to determine the serum levels of the inflammatory factors IL-4, IgE, IFN-γ, and TNF-α. HE staining was performed to observe inflammatory cell infiltration in the mouse skin lesions. In addition, the metabolites of aged C. oleifera oils were analyzed, and molecular docking was used to assess the binding affinity of the major metabolites to filaggrin, a protein involved in skin barrier function. Animal studies showed that aged C. oleifera oil significantly improved the symptoms of atopic dermatitis. HE staining and measurement of inflammatory factor levels revealed similar results. A total of 41 metabolites were tentatively identified in the oil, with fatty acids emerging as the major metabolites. Molecular docking confirmed that the three most abundant fatty acids, i.e., oleic acid, n-hexadecanoic acid, and octadecanoic acid, bind well to filaggrin. Our results suggest that aged C. oleifera oils can be used to ameliorate the symptoms of atopic dermatitis. Fatty acids may be the major active metabolites responsible for the observed therapeutic effects by reducing transdermal water loss, increasing skin hydration, alleviating DNCB-induced skin barrier alterations, and eliminating itchy scratching caused by dry skin.

Urinary presepsin is a novel biomarker capable of directly assessing monocyte/macrophage infiltration in kidney diseases

Serum presepsin levels are elevated during sepsis and are widely employed in clinical practice. However, the association between urinary presepsin and kidney diseases remains elusive. Given that monocytes/macrophages, primary presepsin producers, are closely associated with the pathophysiology of nephritis, we explored the potential of urinary presepsin as a kidney disease biomarker. In a cross-sectional study involving patients who underwent kidney biopsy (n = 463 patients; 43% female, median age 58 years), the median urinary presepsin/creatinine levels were 590 (interquartile range [IQR], 244–1276), 1023 (IQR, 491–2749), 1429 (IQR, 644–2725), and 3518 (IQR, 2084–6321) ng/g creatinine, indicating minimal (< 5%), mild (5–25%), moderate (26–50%), and severe (> 50%) interstitial inflammatory cell infiltration in biopsy samples, respectively. The area under the curve of urinary presepsin/creatinine (0.81) had a higher accuracy for distinguishing severe interstitial inflammatory cell infiltration than that of the N-acetyl-β-D-glucosaminidase/creatinine (0.70) (P = 0.003). The tubulointerstitial nephritis group had the highest urinary presepsin/creatinine level. Immunofluorescence staining revealed that monocytes and macrophages predominantly expressed presepsin in the kidney interstitium, with the stained area positively and significantly correlated with presepsin/creatinine values (r = 0.57, P = 0.02). Urinary presepsin could be a biomarker for directly assessing monocyte/macrophage infiltration in kidney disease.

(−)-Epigallocatechin-3-gallate (EGCG) ameliorates ovalbumin-induced asthma by inhibiting inflammation via the TNF-α/TNF-R1/NLRP3 signaling pathway

(−)-Epigallocatechin-3-gallate (EGCG) is a polyphenol in green tea with potential lung-protective effects. However, the effects of EGCG on airway inflammation in asthma remain unclear. The aim of this study was to investigate the effect and mechanism of EGCG on asthmatic airway inflammation. In this study, the therapeutic effects of EGCG on ovalbumin (OVA)-induced asthmatic mice were tested first. Second, the effects of EGCG on airway inflammation, airway hyperresponsiveness (AHR), airway mucus hypersecretion, cell apoptosis and differential genes were investigated. Finally, the relationships between the effects of EGCG on airway inflammation and the TNF-α/TNF-R1/NLRP3 signaling pathway in asthmatic mice were explored. The results showed that EGCG could attenuate AHR, alleviate the symptoms of alveolar wall thickening and inflammatory cell infiltration, decrease the levels of inflammatory cytokines and airway mucus markers, reduce apoptosis and reactive oxygen species (ROS) and increase the mitochondrial membrane potential (MMP) in primary lung cells in asthmatic mice. Additionally, EGCG significantly inhibited the activation of the TNF-α/TNF-R1/NLRP3 signaling pathway in the lung tissues of asthmatic mice. The lowest binding free energies of EGCG with TNF-α, TNF-R1 and NLRP3 were −11.6, −11.6 and −8.2 kcal/mol, respectively. Moreover, the equilibrium dissociation constant (KD) of EGCG and TNF-R1was 26.05 μmol/L. EGCG-mediated inhibition of TNF-α/TNF-R1/NLRP3 signaling pathway activation was blocked in LPS-induced BEAS-2B and RAW264.7 cells overexpressing TNF-α. Consequently, EGCG effectively attenuated AHR and inhibited airway inflammation and airway mucus hypersecretion in asthmatic mice, and these effects may be closely related to the TNF-α/TNF-R1/NLRP3 signaling pathway.

Ultrasound-targeted sirolimus-loaded microbubbles improves acute rejection of heart transplantation in rats by inhibiting TGF-β1-Smad signaling pathway, promoting autophagy and reducing inflammation

Acute rejection (AR) remains a pivotal complication and leading cause of mortality within the first year following heart transplantation (HT). In this study, we assessed the impact of ultrasound-targeted microbubbles loaded with sirolimus (SIR-MBs) on AR in a rat HT model and delved into the underlying mechanisms. We established a rat abdominal ectopic HT model, which was stratified into three groups receiveing the PBS, SIR-MBs + ultrasound-targeted microbubble destruction (UTMD), and sirolimus, respectively. The protective effects of each treatments on survival rate, inflammatory response, autophagy and TGF-β1-Smad signaling pathway-related proteins were evaluted. Additionally, rescue experiment was performed via adding the autophagy inhibitor or TGF-β1 agonist in combination therapy. UTMD combined SIR-MBs mediated 15-fold higher local drug concentration compared to direct sirolimus administration. The infiltration of inflammatory cells in the transplanted hearts indicated that SIR-MBs combined with UTMD were effective in mitigating the inflammatory response, achieving levels significantly lower than those observed in the sirolimus group. Furthermore, after SIR-MBs combined with UTMD treatment, the expression levels of TGF-β1-Smad signaling pathway-related proteins in heart tissues also showed a significant decrease compared to the model control group. Conversely, the expressions of autophagy proteins LC3-II, Beclin-1 and β-arrestin showed an up-regulated trend. Rescue experiments also revealed that the enhancement in survival trends was markedly suppressed following the administration of CsA or SRI-011381, respectively. Collectively, our findings suggest that SIR-MBs combined with UTMD augment the local treatment efficacy for AR in rat HT models by inhibiting the TGF-β1-Smad signaling pathway, promoting autophagy, and alleviating inflammation.

"Polyethylene Terephthalate Nanoplastics Caused Hepatotoxicity in Mice Can be Prevented by Betaine: Molecular and Immunohistochemical Insights".

Polyethylene terephthalate nanoplastics (PET-NPs) are one of the most frequently distributed nanoplastics in daily life. Betaine is thought to be a promising hepatoprotective agent. The current investigation focused on whether orally administered PET-NPs caused hepatotoxicity and ameliorative effect of betaine. Forty adult male Swiss albino mice were randomly split into four groups: group I control, group II betaine (1000 mg/kg I/P), group III PET-NPs (200 mg/kg orally), and group IV betaine plus PET-NPs at doses similar to group II& III respectively. After 30 days, blood sample were collected then animals were euthanized and liver specimens were dissected out for biochemical and histopathological examination. PET-NPs induced a significant elevation in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA), as well as an increase in the inflammatory genes a proto-oncogene (c-FOS) and cyclooxygenase 2 (COX2) (p ≤ 0.05), with a substantial decrease in glutathione (GSH) (p ≤ 0.05). Furthermore, on the level of histopathological analysis PET-NPs caused alterations in hepatic tissue architecture as vascular dilatation and congestion with hepatocytes degeneration, bile duct epithelial hyperplasia and inflammatory cell infiltrations While on the level of immunohistochemistry, PET-NPs trigger positive tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-ҠB) expression in comparison to control. Meanwhile, betaine treatment reduced the deleterious effects of PET-NPs. To summarize, PET-NPs may cause hepatotoxicity in mice, with a belief that betaine could mitigate the detrimental impact.

Levistolide a Attenuates Acute Kidney Injury in Mice by Inhibiting the TLR-4/NF-κB Pathway.

Acute kidney injury (AKI) is characterized by a significant reduction in kidney function and the accumulation of metabolites such as Creatinine (CRE) and Blood Urea Nitrogen (BUN). Levistolide A (LA), an active component of Ligusticum chuanxiong, offers multiple therapeutic benefits, including cardiovascular and neuroprotection, antitumor and analgesic effects, as well as anti-inflammatory, antioxidant, antifibrotic, and proapoptotic actions. However, the underlying mechanism of LA in treating AKI has not been fully elucidated. In this study, we established a glycerol-induced AKI model in mice to evaluate the protective effects of LA. Renal function was assessed by measuring levels of CRE and BUN. Histological analyses were performed to evaluate kidney tissue damage. Additionally, oxidative stress markers, apoptosis indicators, inflammatory cell infiltration, and inflammatory mediator levels were assessed. The involvement of the TLR-4/NF-κB signaling pathway was investigated through molecular assays. LA treatment significantly ameliorated glycerol-induced AKI in mice, evidenced by reduced levels of CRE and BUN. Histological examination revealed decreased renal tissue damage in LA-treated groups. LA exerted antioxidant effects by increasing the levels of Glutathione (GSH) and Superoxide Dismutase (SOD), while reducing Reactive Oxygen Species (ROS) accumulation. Apoptosis in renal tissues was attenuated, as indicated by decreased caspase-3 activation. Furthermore, LA reduced the infiltration of inflammatory cells and the release of inflammatory mediators such as TNF-α and IL-6. Mechanistically, LA suppressed the inflammatory response by inhibiting the TLR-4/NF-κB signaling pathway, as demonstrated by reduced NF-κB activation and decreased expression of TLR-4. Levistolide A mitigates acute kidney injury through its antioxidative properties and modulation of the TLR-4/NF-κB signaling pathway. These findings provide valuable insights into the therapeutic potential of LA for AKI treatment and lay the groundwork for further mechanistic studies.

First molecular report of the Chelonid alphaherpesvirus 5 (ChHV5 Scutavirus chelonidalpha5) in a green turtle (Chelonia mydas) with fibropapillomatosis in the southwest Gulf of Mexico

Fibropapillomatosis (FP) is an emerging neoplastic disease associated with chelonid herpesvirus 5 (ChHV5; Scutavirus chelonidalpha 5) that affects all species of marine turtles worldwide, mainly green turtles (Chelonia mydas) at coastal feeding sites. This report describes the case of a juvenile green turtle stranded alive on the coast of Veracruz, Mexico that presented 41 lesions suggestive of FP distributed on the eyes, neck, front flippers, axillary/inguinal regions and plastron. Morphologically, the lesions varied in size, shape and appearance of the surface. A tumour was collected and analysed by histopathology revealing a benign neoplasm with fibropapilloma characteristics (dermal and epidermal proliferation) and cytopathic effects consistent with herpesvirus infection, such as ballooning, reticular, and vacuolar degeneration, cell necrosis, eosinophilic intranuclear inclusion bodies, and inflammatory cell infiltration. The tumour tested positive for ChHV5 through conventional PCR targeting the UL30, UL18, UL22, and UL27 genes. Phylogenetic analysis of the DNA Polymerase (UL30) placed the Veracruz variant in the Western Atlantic/Eastern Caribbean cluster along with sequences from Florida, Colombia, Barbados, and Brazil. Additional identification of the CMA1.1 DNA mitochondrial haplotype for this individual supports the connectivity between green turtles from the northern and southern regions of the Gulf of Mexico (GoM) and the Caribbean. It also suggests a potential risk route for ChHV5 infection. This report details the first case of FP linked to ChHV5 in Veracruz and the southwestern GoM. Further research on FP and ChHV5 in these areas is crucial due to their role as habitats for five sea turtle species across various life stages.

Effect of the arabinogalactan from Ixeris chinensis (Thunb.) Nakai. attenuates DSS-induced colitis and accompanying depression-like behavior.

An arabinogalactan (ICPA) was extracted from the medicinal and edible plant Ixeris chinensis (Thunb.) Nakai., and ICPA exhibited excellent immunomodulatory activity. In this research, the impact of ICPA on DSS-induced ulcerative colitis was investigated. The results indicated that ICPA ameliorated the symptoms of colitis mice including loss of body weight, decrease of disease activity index, shortness of colon length and reduction of spleen index that caused by DSS. After treatment with ICPA, inflammatory cell infiltration and crypt loss were alleviated, and the number of goblet epithelial cells was enriched. ICPA inhibited the overproduction of TNF-α, IL-1β, and NLRP3, and promoted the secretion of IL-10 in colon tissues. Meanwhile, the intestinal barrier integrity was restored through increasing the expression of ZO-1 and occludin. ICPA could also regulate the structure of gut microbiota through elevating the abundance of Turicibacter and Bifidobacterium, and decreasing the ratio of Bacteroidetes/Firmicutes. In addition, ICPA improved the depression-like behavior of UC mice, and reduced the expression of proteins NLRP3, GFAP, and Iba-1 in brain tissues. These results suggested ICPA had an alleviative effect on UC and accompanied depression-like behavior, and could be developed as a dietary supplement for the prevention and treatment of UC.

Clear cell stromal tumor of the lung: Report of 3 cases with emphasis on multifocal tumors.

We describe 3 patients with clear cell stromal tumor (CCST) of the lung, all of whom presented with multifocal disease. The patients were 2 men and 1 woman aged 47-58 years (mean, 54 years). Two patients had evidence of autoimmune disease and their pulmonary disease was an incidental finding; one patient presented with non-specific respiratory symptoms. Radiologic imaging revealed multiple pulmonary nodules in all patients. Histologically, the tumors were solid-cystic and composed of cytologically bland, medium-sized ovoid to spindle cells with eosinophilic to clear cytoplasm arranged in a subtle nested pattern. These tumor cells were set in a highly vascularized stroma. Occasional cytologic atypia with multinucleated tumor cells was noted but mitotic activity was low. An infiltrate of mixed inflammatory cells was apparent in all tumors. Immunohistochemical analysis demonstrated diffuse expression of vimentin and TFE3 in all cases. Next generation sequencing revealed the presence of YAP1::TFE3 fusion in 1/1 case. All patients have remained alive albeit with stable or progressive disease, 24-66 months after diagnosis. These cases highlight the existence of multifocal pulmonary CCST and seem to support the notion that multifocality in CCST may be associated with more protracted clinical course. Awareness of the existence of multifocal pattern is important for patient management and prognosis.

The oxidized hyaluronic acid hydrogels containing paeoniflorin microspheres regulates the polarization of M1/M2 macrophages to promote wound healing

Controlling excessive inflammation of acute wound is an effective means to shorten the healing time. Therefore, targeted control of the inflammatory response of the wound is a promising therapeutic strategy. In this study, paeoniflorin (Pae) was encapsulated in microspheres and combined with oxidized hyaluronic acid hydrogels to prepare the hydrogel loaded with Pae microspheres (Pae-MPs@OHA) to promote the healing of acute wounds in rats. The results demonstrated that the particle size of the Pae-MPs was 6.84 ± 0.51 μm, and the positive charge was 26.87 ± 1.51 mV. The uniform spherical structure of the Pae-MPs was observed by TEM. The Pae-MPs@OHA can maintain colloidal state in the range of 0.1–3.16 Hz. FTIR suggested that Pae could be effectively wrapped in MPs, and SEM indicated that the Pae-MPs@OHA had a uniform network pore structure. The Pae-MPs@OHA can realize the sustained release of Pae for 96 h. Biocompatibility experiments showed that the Pae-MPs@OHA hydrogels were safe and available. The Pae-MPs@OHA hydrogels can accelerate wound healing in rats. HE and masson staining suggested that the Pae-MPs@OHA could reduce inflammatory cell infiltration, promote re-epithelialization and collagen formation. The Pae-MPs@OHA could decrease the number of M1 and increase the number of M2 in macrophages, thus regulating the release of inflammatory factor TNF-α and IL-1β. The results of molecular docking and western blot results also confirmed that the Pae-MPs@OHA could reduce the expression of NF-κB, pNF-κB, NLRP3, ASC and pro-caspase-1. These findings suggest that the Pae-MPs@OHA has great potential for application in the treatment of inflammatory wound.

Untargeted serum metabonomic reveals alleviated ovalbumin-induced asthma by Baijin Pingchuan through primary bile acid biosynthesis.

To investigate the effect of baijinpingchuan (, BJPC) on the asthma rat model and identify differential metabolites and disturbed metabolic pathways. The rats were categorized into six groups: control, dexamethasone (DEX), ovalbumin (OVA), and low-, median-, and high-dose BJPC. The rats, except for the control group, were initially treated with OVA to develop the asthma model, which was then activated using DEX, OVA, and low-, median-, and high-dose BJPC. Enzyme-linked immunosorbent assay kit was used to detect the expression of interleukin (IL)-33, IL-25, thymic stromal lymphopoietin (TSLP), and transforming growth factor-beta 1 (TGF-β1). Hematoxylin and eosin staining were performed to observe the pathological condition of the lung. Untargeted serum metabonomic analysis was conducted to identify differential metabolites and disturbed metabolic pathways. High-dose BJPC significantly inhibited the expression of IL-33, IL-25, TSLP, and TGF-β1 (P < 0.0001). Further, high-dose BJPC improved inflammatory cell infiltration, which plays a similar role in asthma as DEX. OVA-induced and BJPC-treated rats were identified through 17 differential metabolites, especially cholic acid. Furthermore, primary bile acid biosynthesis was a significantly differential pathway in the mechanism of BJPC for treating asthma. BJPC plays an anti-inflammation role in asthma, which might be a promising therapy through mediating primary bile acid biosynthesis.

Saikosaponin inhibits Eimeria tenella infection by modifying the NF-κB pathway and regulating cytokines and the intestinal microbial community

Eimeria tenella (E. tenella) is an intestinal parasite that not only endangers the health of broiler chickens but may also cause death in severe cases. However, the growing critical problem of drug resistance in E. tenella complicates therapy. Consequently, a more natural and safer technique for treating E. tenella is urgently warranted. Saikosaponin (SS) is a saponin component extracted from the traditional Chinese herb Chaihu that has been demonstrated to treat various diseases. However, little is known regarding the function of SS in E. tenella treatment. In the present investigation, SS lowered the weight loss rate and increased the survival rate of broiler chickens infected with E. tenella. SS inhibited the NF-κB pathway and regulated the gut microbiota structure to inhibit E. tenella-induced inflammatory damage in broiler chickens. In addition, 16S high-throughput sequencing results demonstrated that SS reconstructed the gut microbiota of E. tenella infected broilers, preserving gut microbial balance, increasing the production of total short-chain fatty acids (SCFAs), repairing intestinal villi and intestinal wall integrity, and decreasing inflammatory cell infiltration in the cecum. Overall, these findings show that SS could prevent E. tenella-induced inflammatory damage in broiler chickens by blocking the NF-κ B pathway and regulating the gut microbiota composition.

Prognostic value of neurotensin in experimental terminal ileitis

Background Terminal ileitis (TI) is an inflammatory condition of the distal portion of the ileum. Objective To investigate the changes and significance of neurotensin (NT) in the course of experimental terminal ileitis (ETI). Methods A total of 90 Sprague Dawley (SD) rats were randomly divided into the control, model, and suture groups (30 rats in each group). After 2, 4, and 8 weeks of surgery, 10 TI tissues were taken for endoscopic observation in each group. Hematoxylin-eosin (HE) staining was used to detect the pathological changes. The NT levels in serum and terminal ileum mucosa were detected by Enzyme-linked immunosorbent assay (ELISA). Results Acute inflammatory changes were observed in the suture and the model groups after 2-week of operation. At 4 weeks, compared to the control group, the inflammatory damage in the model group became heavier, but it was reduced in the suture group. At 8 weeks, the model group showed chronic inflammation. However, there was no obvious inflammatory cell infiltration in both the suture group and control group. NT levels were increased in the suture and model groups at 2 weeks, particularly in the model group, and they were significantly higher in the suture and model groups than those in the control group ( P &lt; 0.05). At 4 weeks, the NT levels in the model group continued to rise, while they decreased in the suture group ( P &lt; 0.05). After 8 weeks, NT levels in the model group were significantly higher than those in the suture and control groups ( P &lt; 0.05). Furthermore, from 2 weeks to 8 weeks, the NT concentration in the model group gradually increased, and the suture group increased for 2 weeks, followed by a downward trend. Conclusions In the ETI, the changes in NT concentration in serum and TI mucosa were positively correlated with the degree of inflammation.