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Highlights LPS-induced ARDS rats and PMVECs have low Fcgr2b level and high Elk1 level; Fcgr2b overexpression mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 knockdown mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 represses Fcgr2b transcription by recruiting H3K9me3; Elk1/Fcgr2b axis aggravates LPS-induced ALI/ARDS in rats and PMVECs.

Highlights: LPS-induced ARDS rats and PMVECs have low Fcgr2b level and high Elk1 level; Fcgr2b overexpression mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 knockdown mitigates LPS-induced ALI/ARDS in rats and PMVECs; Elk1 represses Fcgr2b transcription by recruiting H3K9me3; Elk1/Fcgr2b axis aggravates LPS-induced ALI/ARDS in rats and PMVECs. Objective: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with significant mortality rates. The role of Fcgr2b in the pathogenesis of ALI/ARDS is not fully elucidated. This study aimed to investigate the functions of Fcgr2b in ALI/ARDS and explore its underlying mechanisms. Methods: Methods: In this study, rat models of ARDS and pulmonary microvascular endothelial cell (PMVEC) injury models were established through the administration of lipopolysaccharide (LPS). The expression levels of Fcgr2b and Elk1 were quantified in both LPS-induced ARDS rats and PMVECs. Subsequent gain- and loss-of-function experiments were conducted, followed by comprehensive assessments of lung tissue for pathomorphological changes, edema, glycogen storage, fibrosis, and infiltration of inflammatory cells. Additionally, bronchoalveolar lavage fluid was analyzed for T-helper 17 (Th17) cell infiltration, inflammatory response, and microvascular permeability to evaluate lung injury severity in ARDS models. Furthermore, the activity, cytotoxicity, apoptosis, and angiogenic potential of PMVECs were assessed to gauge cell injury. The interaction between Elk1 and Fcgr2b was also examined to confirm their regulatory relationship. Results: In the context of LPS-induced ARDS and PMVEC injury, Fcgr2b expression was markedly reduced, whereas Elk1 expression was elevated. Overexpression of Fcgr2b led to a decrease in Th17 cell infiltration and mitigated lung tissue damage in ARDS models, in addition to reducing LPS-induced injury in PMVECs. Elk1 was found to suppress Fcgr2b transcription through the recruitment of histone 3 lysine 9 trimethylation (H3K9me3). Knockdown of Elk1 diminished Th17 cell infiltration and lung tissue damage in ARDS models, and alleviated LPS-induced injury in PMVECs, effects that were reversed upon Fcgr2b upregulation. Conclusion: Elk1 negatively regulates Fcgr2b transcription, thereby augmenting the inflammatory response and exacerbating lung injury in LPS-induced ALI/ARDS. [ABSTRACT FROM AUTHOR]

Cigarette smoke contains toxic compounds that can initiate an inflammatory reaction and infiltrate inf lammatory cells. The nasal mucosa is the initial part of the respiratory system that comes into contact with irritating chemicals such as cigarettes. Prior studies indicated that Nigella sativa extract (NS) has thymoquinone, a bioactive compound with anti-inflammatory properties. Our study aims to determine the effect of different doses of NS on inflammation of the nasal mucosa in Wistar rats exposed to cigarette smoke. The study employed an experimental post-test-only control group design. Twenty-five Wistar rats were randomly assigned to one of the five groups: negative control (K-), positive control (K+), and three treatment groups of P1, P2, and P3 receiving NS at the dose of 0.5, 1, and 1.5 g/kg bw/day, respectively. All treatment groups and the positive control group were exposed to smoke from 4 cigarettes/day for 28 days. The degree of inflammatory cell infiltration was evaluated using a histological scoring : 0 if normal; 1 if infiltration was less than 1/3; 2 if infiltration was between 1/2 and 2/3, 3 if infiltration of more than 2/3 indicating normal, less than 1/3, 1/3 to 2/3, and more than 2/3, respectively. The degree of inflammatory cell infiltration in group: K(-): 1.00±0.00, K(+): 1.00±0.00, P1: 1.00±0.00, P2: 1.00±0.37, and P3: 1.00±0.33. The Kruskal-Wallis test showed a p-value of 0.001, indicating a significant difference. The Mann-Whitney test revealed significant differences between the K+ and P2 groups (p=0.032), K+ and P3 groups (p=0.013), and P1 and P3 groups (p=0.049). In conclusion, NS can decrease the presence of inflammatory cells in the nasal mucosa in Wistar rats exposed to cigarette smoke. [ABSTRACT FROM AUTHOR]

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable.Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days.Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells.Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.

Early diagnosis of acute rejection is of significance for the protection of renal allograft function. Pathological puncture biopsy is the gold standard for the diagnosis of acute rejection of renal allografts. Nevertheless, it may provoke multiple complications, such as bleeding, infection and renal parenchymal injury, which limit its widespread application. In recent years, the sensitivity of contrast-enhanced ultrasound in the diagnosis of acute rejection has been constantly improved. Ultrasound-targeted microbubble technique has further enhanced the diagnostic specificity of contrast-enhanced ultrasound, making it possible to replace pathological puncture biopsy. Besides, in the field of acute rejection treatment, microbubble ultrasonic cavitation may promote local delivery of immunosuppressants by inducing sonoporation and exhibit anti-rejection effect. In this article, the application of contrast-enhanced ultrasound in the diagnosis and treatment of acute rejection after kidney transplantation was reviewed, aiming to provide reference for widespread application of contrast-enhanced ultrasound in kidney transplantation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of Gonadotropin releasing hormone (GnRH) analogues on blood viscosity, uterine coefficient and inflammatory cell infiltration in rat models of uterine fibroids. Methods: Rat models of uterine fibroids (n=36) were equally randomly divided into three groups-model group, mifepristone group and GnRH analogue group. The three groups were given intraperitoneal injection of 0.15 mL of normal saline, 2 mg/kg of mifepristone, 2 mg/kg GnRH analogue, once a week for 8 weeks. Results: The values of whole blood specific viscosity, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the 4th and 8th weeks of treatment in the mifepristone group and GnRH analog group were lower than those of the model group (P<0.05), the GnRH analog group were lower than mifepristone group (P<0.05). Uterine coefficient, uterine interleukin (IL)-10 and tumor necrosis factor (TNF)-α expression levels in the mifepristone group and GnRH analog group at the 8th week of treatment were lower than those in the model group (P<0.05), GnRH analog The group were lower than the mifepristone group (P<0.05). The endometrial thickness, gland-to- interstitial area ratio, gland area and gland cavity area of the mifepristone group and the GnRH analog group were higher than the model group at the 8th week of treatment (P<0.05), and the GnRH analog group were higher than that in the GnRH analog group Mifepristone group (P<0.05). The relative expression levels of Wnt5b and β-catenin protein in the uterine tissue of the mifepristone group and the GnRH analog group were lower than the model group at the 8th week of treatment (P<0.05), and the GnRH analog group were lower than the mifepristone group (P< 0.05). Conclusion: The application of GnRH analogues in rat models of uterine fibroids can reduce blood viscosity, inhibit the secretion of serum sex hormones, increase uterine coefficient, and inhibit the expression of Wnt5b and β-catenin proteins, thereby improving morphology of the endometrium uterine fibroids and the infiltration state of inflammatory cells in rats. [ABSTRACT FROM AUTHOR]

Paeoniflorin (PF) is a monoterpene glucoside with various biological properties, and it suppresses allergic and inflammatory responses in a rat model of urticaria-like lesions (UL). In the present study, we treated OVA-induced mice presenting UL with PF at four circadian time points (ZT22, ZT04, ZT10, and ZT16) to determine the optimal administration time of PF. The pharmacological effects of PF were assessed by analyzing the scratching behavior; histopathological features; allergic responses such as immunoglobulin E (IgE), leukotriene B4 (LTB4), and histamine (HIS) release; inflammatory cell infiltration [mast cell tryptase (MCT) and eosinophil protein X (EPX)]; and mRNA levels of inflammatory cytokines such as interleukin (IL)-12, IL-6, interferon-γ (IFN-γ), and IL-4. It was demonstrated that PF significantly alleviated scratching behavior and histopathological features, and ZT10 dosing was the most effective time point in remission of the condition among the four circadian time points. Moreover, PF decreased the serum levels of IgE, LTB4, and HIS, and PF administration at ZT10 produced relatively superior effectiveness. PF treatment, especially dosing at ZT10, significantly reduced the number of mast cells and granules and diminished the infiltration of MCT and EPX in the skin tissues of mice with UL. Furthermore, the oral administration of PF effectively decreased the inflammatory cytokine levels of IL-12 mRNA. In conclusion, different administration times of PF affected its efficacy in mice with UL. ZT10 administration demonstrated relatively superior effectiveness, and it might be the optimal administration time for the treatment of urticaria. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Disease (IBD) is a well known reported gastrointestinal tract disease, which the prevalence continous to increase in Southeast Asia and other developing countries. Animal model have already been widely used for gut inflammation study. Lambda (λ) carrageenan is a chemical substance which commonly used to induced inflammation in IBD animal models. Physical exercise is a non-pharmacological therapy recommended for IBD. However, further study is needed to determine the effects of this therapy. This study was aimed to determine the physical exercise effect on colon inflammation in mice induced λ-carrageenan. Thirty-eight mice were divided into 2 groups. Control group (C) which induced with λ-carrageenan and treatment group (T) which induced by λ-carrageenan and treadmill exercise. The degree of colon inflammation was obtained by histopathological examination using Hematoxylin-Eosin (HE) staining and inflammation scoring system, which include inflammatory cell infiltration and intestinal architecture. All mice colon samples in both group were inflamed with varying degrees. The treatment group had a higher Inflammatory degree score than control group (p

Objective: to study the relationship between metalloproteinases and expression TIMP1 expression and intensity of inflammatory response in the cervical stroma of women with cervical intraepithelial neoplasia and microinvasive carcinoma. Material and methods. Morphological, morphometric and immunohistochemical examination of cervical biopsies in patients with cervical epithelial neoplasia (cINI–III) and microinvasive carcinoma was carried out. all patients were divided into two age groups: group 1 consisted of 95 patients of early reproductive age ranged from 18 to 35 years (mean age 28.5 ± 0.58 years) and group 2 consisted of 85 perimenopausal and menopausal patients aged 49 to 65 (mean age 55.4 ± 0.98 years). Results. In women of both age groups, the density of inflammatory cell infiltrate was shown to increase, being significantly higher in women of group 1 than in women of group 2. the increase in the expression level of metalloproteinases-2, -3, -7, and -9 with dysplasia progression was observed in women of both age groups, being also higher in group 1 women. the tIMP1 expression level was higher in group 2 women and increased with disease progression. Conclusion. In young women, pronounced and active inflammation in the cervical stroma contributes to a high potential for metalloproteinase synthesis. a higher level of tIMP1 expression in perimenopausal and menopausal women may be one of the factors contributing to a decrease in the metalloproteinase synthesis in these women.

Paeoniflorin (PF) is a monoterpene glucoside with various biological properties, and it suppresses allergic and inflammatory responses in a rat model of urticaria-like lesions (UL). In the present study, we treated OVA-induced mice presenting UL with PF at four circadian time points (ZT22, ZT04, ZT10, and ZT16) to determine the optimal administration time of PF. The pharmacological effects of PF were assessed by analyzing the scratching behavior; histopathological features; allergic responses such as immunoglobulin E (IgE), leukotriene B4 (LTB4), and histamine (HIS) release; inflammatory cell infiltration [mast cell tryptase (MCT) and eosinophil protein X (EPX)]; and mRNA levels of inflammatory cytokines such as interleukin (IL)-12, IL-6, interferon-γ (IFN-γ), and IL-4. It was demonstrated that PF significantly alleviated scratching behavior and histopathological features, and ZT10 dosing was the most effective time point in remission of the condition among the four circadian time points. Moreover, PF decreased the serum levels of IgE, LTB4, and HIS, and PF administration at ZT10 produced relatively superior effectiveness. PF treatment, especially dosing at ZT10, significantly reduced the number of mast cells and granules and diminished the infiltration of MCT and EPX in the skin tissues of mice with UL. Furthermore, the oral administration of PF effectively decreased the inflammatory cytokine levels of IL-12 mRNA. In conclusion, different administration times of PF affected its efficacy in mice with UL. ZT10 administration demonstrated relatively superior effectiveness, and it might be the optimal administration time for the treatment of urticaria.

Isolated spinal demyelinating lesions are rare and often associated with multiple sclerosis. While initial radiological findings may suggest a tumor, a definitive diagnosis requires a histological diagnosis. A 45-year-old woman presented with progressive spastic tetraparesis for 1 week. She had no prior history of neurological or systemic illness. Brain and thoracic magnetic resonance imaging (MRI) were normal, but cervical MRI revealed an intramedullary tumor extending from C3 to C4. Surgery was performed. Histopathological examination revealed an inflammatory demyelinating plaque, not a tumor. The patient experienced significant improvement in her clinical condition postsurgery and remains under neurological follow-up. We discuss this case alongside a review of similar cases reported in the literature, focusing on clinical presentation, laboratory findings, MRI features, and follow-up of patients with tumor-like inflammatory demyelinating diseases of the spinal cord initially diagnosed as intramedullary tumors., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days. Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells. Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry., Competing Interests: Author KS was employed by Biotronik SE & Co. KG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Woitschach, Kloss, Kischkel, Macháček, Reinholdt, Senz, Schlodder, Löbermann, Grabow, Reisinger and Sombetzki.)

Pulpitis is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps. A GEO dataset GSE16134 comprising data of inflamed dental pulp tissues was used for bioinformatics analyses. A protein-protein interaction (PPI) analysis suggested that chemokine receptor 4 (CXCR4) owned a high correlation with platelet endothelial cell adhesion molecule-1 (PECAM1). A rat model with pulpitis was established, and lipopolysaccharide (LPS)-induced human dental pulp fibroblasts (HDPFs) were used for in vitro experiments. Then, high expression of PECAM1 and CXCR4 was validated in the inflamed dental pulp tissues in rats and in LPS-induced HDPFs. Either downregulation of PECAM1 or CXCR4 suppressed inflammatory cell infiltration in inflamed tissues as well as the inflammation and apoptosis of HDPFs. A transcription factor myocyte-enhancer factor 2 (MEF2C) was predicted and validated as a positive regulator of either PECAM1 or CXCR4, which activated the NF-κB signaling pathway and promoted pulpitis progression. To sum up, this study suggested that MEF2C transcriptionally activates PECAM1 and CXCR4 to activate the B-cell and NF-κB signaling pathways, leading to inflammatory cell infiltration and pulpitis progression.

A 45-year-old woman presented with upper abdominal and back pain. A cystic lesion in the pancreas and inflammation around the splenic artery were detected by computed tomography. Although imaging studies were difficult to exclude malignancy, pathological and cytological findings of a fine-needle aspiration showed no signs of malignancy. The patient was, therefore, followed-up for 3 months, during which time the cyst increased in size and developed a cyst-in-cyst structure. She was diagnosed with mucinous cyst neoplasm and underwent distal pancreatectomy. Histologically, the patient was diagnosed as low-grade mucinous cystic adenoma. Soft tissue shadows around the splenic artery were considered to indicate fibrosis and infiltration of inflammatory cells. After distal pancreatectomy, the patient has been uneventful with symptom resolution. This case highlights the potentially atypical presentation of mucinous cystic neoplasms with inflammatory cell infiltration around the splenic artery. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of interleukin (IL)-17C in mice undergoing kidney transplantation. Methods The life-supporting kidney transplantation mice models were established using Balb/c (H-2Kd ) mice as the donors, IL-17C gene knock out (IL-17CKO) mice (knockout group) and C57BL/6J(H-2Kb ) mice (wild group) were chosen as the recipients. The postoperative body mass and survival time of mice were statistically compared between two groups. Pathological examination of the kidney graft was performed by using hematoxylineosin (HE) staining and periodic acid-Schiff (PAS) staining. The expression levels of granzyme B, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 and IL-1β messenger ribonucleic acid (mRNA) in the kidney graft tissue were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). The proportion of inflammatory cell infiltration in the kidney graft tissue was detected by flow cytometry. Results In the knockout group, the survival time of mice after kidney transplantation was significantly shorter than that of the wild mice (P=0.031). The body mass was more evidently decreased in the knockout group with no statistical significance from that in the wild group. Pathological examination demonstrated that the kidney graft injury in the knockout group was significantly worse than that in the wild group. The mRNA expression levels of granzyme B, IFN-γ, TNF-α, IL-6 mRNA in the knockout group were significantly up-regulated compared with those in the wild group (all P<0.01). The mRNA expression level of IL-1β showed a decreasing trend with no statistical significance (P=0.16). Flow cytometry analysis revealed that the infiltration of CD45+ CD11b+ Ly6G+ neutrophil and CD45+ CD11b+ Ly6Chi monocyte in the kidney graft of knockout mice was significantly higher compared with that of the wild mice (P<0.05, P<0.01), whereas the infiltration of CD45+ Ly6ChiF4/80+ macrophage did not significantly differ between two groups (P>0.05). Conclusions IL-17C participates in the regulation of inflammatory response after kidney transplantation. It can alleviate acute rejection and improve the survival of kidney graft by down-regulating the expression of pro-inflammatory cytokines and infiltration of inflammatory cells. [ABSTRACT FROM AUTHOR]

Background: In this study, we examined whether RORA (retinoic acid receptor-related orphan receptor alpha) was capable of alleviating the progression of allergic rhinitis (AR). Methods: In order to elucidate the possible effects of RORA and the regulatory mechanism between RORA and the Wnt/β-catenin signaling pathway, mouse AR models were established and treated with RORA vector, siRNA against RORA, or the Wnt/β-catenin pathway inhibitor WIF-1. Subsequently, the serum levels of inflammatory cytokines (IgE, INF-γ, IL-1β, IL-4, and IL-17), red blood cell (RBC) immune adhesion function, the levels of RORA, β-catenin, and GSK3β, as well as the extent of β-catenin and GSK-3β phosphorylation were evaluated and measured. Results: The OVA-induced AR mouse model exhibited obvious nasal mucosal injury and inflammatory cell infiltration. RORA overexpression or the inactivation of the Wnt/β-catenin signaling pathway was uncovered as a way to ameliorate nasal mucosal injury and eosinophil infiltration of the OVA-induced AR mouse model. On the other hand, it reduced the number of eosinophils and mast cells, which also resulted in downregulated expression of IgE, INF-γ, IL-1β, IL-4, IL-17, β-catenin, and GSK-3β. Moreover, this led to a decreased extent of β-catenin and GSK-3β phosphorylation, while the rates of C3b receptor rosette and Ic rosette were elevated. Conclusion: Taken together, the key findings provided evidence suggesting that the elevated RORA could potentially alleviate nasal mucosal injury and simultaneously enhance RBC immune adhesion function through the inhibition of the Wnt/β-catenin signaling pathway activation in an OVA-induced AR mouse model. This emphasizes a novel therapeutic target for the treatment of AR. [ABSTRACT FROM AUTHOR]

Objective: Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a recently described, rare gastric polyposis syndrome. It is characterized by extensive involvement of the fundus and body of the stomach with fundic gland polyps sparing the antrum and lesser curvature, an autosomal dominant inheritance pattern with incomplete penetrance, and a significant predisposition for the development of gastric adenocarcinoma. Due to the recent discovery of APC promotor IB mutations (c.-191T>C, c.-192A>G, and c.-195A>C), which reduce binding of the transcription factor Yin Yang 1 (YY1) and transcriptional activity of the promotor, as its underlying genetic perturbation, GAPPS has been added to the growing molecular class of APC-associated disorders. Recent reports on family members afflicted by gastric polyposis due to GAPPS have described the development of metastatic cancer or the presence of invasive gastric adenocarcinoma in total gastrectomy specimens after variable periods of endoscopic surveillance emphasizing the need for an improved understanding of the to-date poorly characterized natural history of the syndrome. There are, however, currently no guidelines on screening, timing of prophylactic gastrectomy, or endoscopic surveillance for GAPPS available. In this review, we summarize the clinical, pathological, and genetic aspects of GAPPS as well as management approaches to this rare cancer predisposition syndrome, highlighting the need for early recognition, a multidisciplinary approach, and the creation of prospective family registries and consensus guidelines in the near future. [ABSTRACT FROM AUTHOR]

Sclerosing mucoepidermoid carcinoma (SMEC) is extremely rare variant of the mucoepidermoid carcinoma, which is the most common primary malignancy of the salivary glands. As its name suggests, SMEC is characterized by an intense central sclerosis that occupies the entirety of an otherwise typical tumor, frequently with an inflammatory infiltrate of plasma cells, eosinophils, and/or lymphocytes at its peripheral regions, but its uncompanionship with inflammatory cell infiltration might explain its progressive stage of the sclerosis. The sclerosis associated with these tumors may obscure their typical morphologic features and result in diagnostic difficulties. Tumor infarction and extravasation of mucin eventuating in reactive fibrosis are two mechanisms of formation that have been suggested as underlying this morphologic variant. Morphologic evidence in support of the mucin extravasation hypothesis was identified, as small pools of mucin were present throughout the tumor.

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. It is characterized by mononuclear cell infiltration around the small blood vessels in the central nervous system (CNS). Previous investigations have found that apoptosis is associated with the occurrence and development of autoimmune disease, and that mononuclear cell apoptosis and clearance from the CNS is one of the repair mechanisms of EAE. Tripterygium wilfordii glycoside (TWP) is an organic matter isolated from Tripterygium wilfordii, which has anti-inflammatory and immunosuppressive effects. In the present study, male Lewis rats were randomly divided into a normal control, EAE and TWP groups. Rats in EAE and TWP groups received injections of emulsified EAE antigen (myelin protein) at two points on the footpad while control group received PBS. The TWP group was then treated with TWP daily for 21 days. Symptoms and nerve function scores were observed and evaluated. Specimens of blood, brain and spinal cord were collected for further pathological examination, Tunel assay, ELISA and immunohistochemistry were performed to examine the effect of TWP on the onset of EAE, and changes in CNS inflammatory infiltration, cell apoptosis, and the expression of nuclear factor (NF)-κB P65 and interleukin (IL)-2. The results showed that the TWP treatment group exhibited decreased EAE and delayed onset, compared with the control. The clinical symptoms were significantly reduced and alleviation of inflammatory cell infiltration was observed. Compared with the EAE group, a higher inflammatory cell apoptotic rate, and reduced serum levels of IL-2 and NF-κB p65-positive cells were observed in the TWP treatment group. Therefore, TWP effectively inhibited EAE via the inhibition of CNS inflammatory cell infiltration, enhancement of inflammatory cell apoptosis, and downregulation of the expression of NF-κB and IL-2. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of the epidermis, and dermal infiltration of inflammatory cells. Appropriate animal models that recapitulate human AD and allow the analysis of disease processes in a reliable manner are essential to the study of AD. In this study, we established two AD models in rabbits by applying an allergen, Dermatophagoides farinae (Der f), or a hapten, oxazolone (OXZ). Application of the allergen or hapten induced a rapid onset and a chronically sustained AD-like skin lesion. The clinical symptoms, which include skin erythema, scaling, papula and edema, of AD-like rabbit skin were similar to those in human AD. Histological analysis showed that allergen- or hapten-treated rabbit skin showed increased epidermal thickening and inflammatory cell infiltration. Furthermore, PCNA and keratin 10 (K10) staining revealed excessive proliferation and insufficient differentiation of the epidermis in the rabbit AD-like skin. Western blot analysis showed decreased expression of thymic stromal lymphopoietin (TSLP), an AD cytokine, in the rabbit AD-like skin. Our results suggest that the allergen- or hapten-induced rabbit AD models have pathological features of human AD-like symptoms and will be useful for evaluating both pathogenic mechanisms and potential therapeutic agents for human AD. [ABSTRACT FROM AUTHOR]

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P<0.001) of the tumor, fibrosis (P<0.001), and the degree of desmoplasmic stroma (P=0.004). In contrast, inflammatory infiltration in the center of the tumor was associated with the tumor node metastasis stage (P=0.012), Dukes' stage (P=0.009), primary tumor stage (P=0.036), lymph node status (P=0.005), number of lymph nodes (P=0.006), invasion of lymph node pouches (P=0.021), size of lymph node metastasis (P=0.025) and the degree of desmoplasmic stroma (P=0.002). The low-group, who demonstrated an absent or weak inflammatory cell infiltrate in the invasive front of the tumor, had a statistically significant shorter disease-free survival (DFS) time (P=0.004). Inflammatory cell infiltrate in the invasive front was identified as an independent predictive factor in CRC (P=0.041). In conclusion, the degree of inflammatory cell infiltration in the invasive front of the primary tumor significantly affects various variables that determine disease progression and DFS rates of patients with CRC. Furthermore, the routine histopathological assessment of this parameter in tissue stained with H&E may have potential prognostic value. [ABSTRACT FROM AUTHOR]

This article is devoted to the study of the prognostic value of immunohistochemical markers of local immune homeostasis of parodontal with definition of CD3+, CD4+, CD8+, CD20+, CD68+, CD138+ cells of the immune series and S100 + dendritic cells, angiogenesis CD34 and VEGF, reparative proliferation Ki-67, stromal degradation MMP-1 and inducible nitric oxide synthase iNOS in inflammatory processes periodontal definition of morphological relations between the values of immunohistochemical indices and aggressiveness of generalized parodontitis.

Publisher's Note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Keywords: urticaria-like lesion; paeoniflorin; allergic response; inflammatory cell infiltration; inflammatory cytokine; chronotherapeutic EN urticaria-like lesion paeoniflorin allergic response inflammatory cell infiltration inflammatory cytokine chronotherapeutic 1 2 2 05/23/22 20220519 NES 220519 In the original article, there was a mistake in "Figure 6" as published. Urticaria-like lesion, paeoniflorin, allergic response, inflammatory cell infiltration, inflammatory cytokine, chronotherapeutic. [Extracted from the article]