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Peroxisome proliferator-activated receptors γ (PPARγ) is a master regulator that controls energy metabolism and cell fate. PPARγ2, a PPARγ isoform, is highly expressed in the normal prostate but expressed at lower levels in prostate cancer tissues. In the present study, PC3 and LNCaP cells were used to examine the benefits of restoring PPARγ2 activity. PPARγ2 was overexpressed in PC3 and LNCaP cells, and cell proliferation and migration were detected. Hematoxylin and eosin (H&E) staining was used to detect pathological changes. The genes regulated by PPARγ2 overexpression were detected by microarray analysis. The restoration of PPARγ2 in PC3 and LNCaP cells inhibited cell proliferation and migration. PC3-PPARγ2 tissue recombinants showed necrosis in cancerous regions and leukocyte infiltration in the surrounding stroma by H&E staining. We found higher mixed lineage kinase domain-like (MLKL) and lower microtubule-associated protein 1 light chain 3 (LC3) expression in cancer tissues compared to controls by immunohistochemistry (IHC) staining. Microarray analysis showed that PPARγ2 gain of function in PC3 cells resulted in the reprogramming of lipid- and energy metabolism-associated signaling pathways. These data indicate that PPARγ2 exerts a crucial tumor-suppressive effect by triggering necrosis and an inflammatory reaction in human prostate cancer.

Shao-Chun Wu,1,* Cheng-Shyuan Rau,2,* Pao-Jen Kuo,3 Fu-Yuan Shih,2 Hui-Ping Lin,3 Yi-Chan Wu,3 Ting-Min Hsieh,4 Hang-Tsung Liu,4 Ching-Hua Hsieh3 1Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Department of Trauma Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Ching-Hua HsiehDepartment of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung, 833, TaiwanTel +886-7-7327476Fax +886-7-3450431Email m93chinghua@gmail.comPurpose: Severe trauma may lead to the systemic release of inflammatory mediators into the circulation with profound acute-phase responses; however, the understanding of the expression of these mediators remains limited. This study aimed to characterize the alterations in the expression of circulating acute-phase proteins, cytokines, and checkpoint proteins in patients with severe trauma injuries.Patients and Methods: The study population included trauma patients in the intensive care unit (ICU) with an injury severity score equal to or greater than 16 and who had used a ventilator for 48 hours. A total of 12 female and 28 male patients were recruited for the study; six patients died and 34 survived. Blood samples collected at acute stages were compared with those drawn at the subacute stage, the time when the patients were discharged from the ICU, or before the discharge of the patients from the hospital.Results: The study identified that the expression of acute-phase proteins, such as alpha-1-acid glycoprotein and C-reactive protein, and cytokines, including granulocyte colony-stimulating factor, interleukin-6, and interleukin-1 receptor antagonist, was elevated in the circulation after severe trauma. In contrast, the levels of acute-phase proteins, such as alpha-2-macroglobulin, serum amyloid P, and von Willebrand factor, and cytokines, including interleukin-4 and interferon gamma-induced protein 10, were reduced. However, there were no significant differences in the expression of checkpoint proteins in the circulation.Conclusion: The dysregulated proteins identified in this study may serve as potential therapeutic targets or biomarkers for treating patients with severe trauma. However, the related biological functions of these dysregulated factors require further investigation to validate their functions.Keywords: circulation, inflammatory reaction, biomarkers, severe trauma, critical illness

Background/aim: This study aimed to assess the inflammatory adverse reactions of vocal fold injection laryngoplasty with hyaluronic acid. Materials and methods: This study was a retrospective chart review of patients who underwent vocal fold injection augmentation with HA injection from January 2005 to September 2016 in nine different institutions. Demographic data, indication for injection, injection techniques, types of injection material, settings of procedure, and complications were reviewed. The types of complication, onset time, and management of complications were also noted. Results: In all, 467 patients were identified. The majority of patients had been injected under general anesthesia (n = 382, 84.7%). For injection material, two different types of hyaluronic acid were used: hyaluronic acid alone or hyaluronic acid with dextranomer. Complications occurred in nine patients (1.9%). The majority of complications were inflammatory reactions (n = 7, 1.47%). Main symptoms were dysphonia and/or dyspnea with an onset of 0 h to 3 weeks after the hyaluronic acid injection. Three patients were hospitalized, one of which was also intubated and observed in the intensive care unit for 24 h. Systemic steroids and antibiotics were the main medical treatment in the majority of cases. There was no statistical difference in complication rates between patients who received hyaluronic acid and those who received hyaluronic acid with dextranomer (P = 0.220). Conclusion: Hyaluronic acid can be considered as a safe substance for the injection of vocal folds with a low risk of inflammatory reaction.

BACKGROUND Sulongga-4 (SL-4) is a herbal formula used in traditional Mongolian medical clinics for the treatment of peptic ulcers and gastroenteritis, even though its pharmacological mechanism has not been well characterized. AIM To evaluate the protective effect and identify the mechanisms of action of SL-4 on gastroduodenal ulcer induced by pyloric ligation (PL) in rats. METHODS PL was performed to induce gastric and duodenal ulcers in rats, which were then treated with oral SL-4 (1.3, 2.6, or 3.9 g/kg per day) for 15 d. PL-induced gastroduodenal ulceration. Therapeutic effects were characterized by pathological and histological evaluations and inflammatory indicators were analyzed by enzyme-linked immunosorbent assay. Microarray analyses were conducted to identify gene expression profiles of gastroduodenal tissue in PL rats with or without SL-4 treatment. The candidate target genes were selected and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS SL-4 decreased histopathological features in the PL-induced ulcerated rats. SL-4 significantly (P < 0.05) decreased expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, endotoxin, platelet-activating factor, and increased prostaglandin E2 and epidermal growth factor in ulcer tissue. Microarray analysis was used to identify a panel of candidate target genes for SL-4 acting on PL-induced ulceration. Genes included some complement and coagulation cascade and retinol metabolism pathways that are closely associated with inflammatory responses and gastric mucosal protective mechanisms. qRT-PCR showed that altered expression of the selected genes, such as CYP2b2, UGT2b1, A2m, and MASP1 was consistent with the microarray results. CONCLUSION SL-4 exerts protective effects against PL-induced gastroduodenal ulcers via reducing inflammatory cytokines and elevating expression of gastric acid inhibitory factors. Downregulation of CYP2b2 and UGT2b1 genes in retinol metabolism and upregulation of A2m and MASP1 genes in the complement and coagulation cascades pathways are possibly involved in SL-4-mediated protection against gastroduodenal ulcer.

Septic shock is one of the most significant health concerns across the world, involving hypo-perfusion and defects in tissue energy. The current study investigates the role of NLR family CARD domain containing protein 4 (NLRC4) in septic shock-induced inflammatory reactions, lung tissue injuries, and dendritic cell (DC) apoptosis. Septic shock mice models were established by modified cecal ligation and puncture and injected with retroviral vector expressing siRNA-NLRC4. DCs were then isolated and transfected with siRNA-NLRC4. The degree of lung tissue injury, cell cycle distribution, cell apoptosis and cell viability of DCs were assessed. NLRC4 was found to be expressed at high levels in mice with septic shock. NLRC4 silencing inhibited the activation of the NOD-like receptor (NLR) pathway as evidenced by the decreased levels of NOD1, NOD2, RIP2, and NF-κB. In addition, NLRC4 silencing reduced the inflammatory reaction as attributed by reduced levels of IL-1β, TNF-α and IL-6. Suppressed NLRC4 levels inhibited cell viability and promoted cell apoptosis evidenced by inhibited induction of DC surface markers (CD80, CD86, and MHC II), along with alleviated lung tissue injury. In conclusion, NLRC4 silencing ameliorates lung injury and inflammation induced by septic shock by negatively regulating the NLR pathway.

The present study aimed to investigate the effect of probiotic Lactobacilli addition on Listeria monocytogenes load, inflammatory reaction, and virulence properties in broilers from 1 to 14 D of age. A total of 480 broiler chicks were randomly allocated to 4 treatments of 6 replicates each. All birds were infected with L. monocytogenes on the first day and supplemented an equal amount mixture of Lactobacillus acidophilus and Lactobacillus plantarum at doses of 0 (control), 106, 108, 1010 cfu/kg of diet. The results showed that on 7 and 14 D after administration, Lactobacilli addition at the 3 doses decreased (P

Lower extremity arterial disease (LEAD) is considered as a common cause resulting the narrowing in the vessels of the lower limbs. This study investigated effect of drug-eluting stent (DES) implantation after percutaneous transluminal angioplasty (PTA) on restenosis incidence in patients with LEAD.The patients with LEAD in control group received PTA alone, and the patients in intervention group received PTA and DES implantation. Skin temperature, transcutaneous oxygen tension (TcPO2), ankle brachial index (ABI), recurrence rate, total response rate, ulcer cure and improvement rates and restenosis incidence 6 months and 12 months after treatment were compared. Clinical symptoms, signs, and foot ulcer condition before and after treatment were compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of like interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) andC-reactive protein (CRP) 3 d and 6 months. Six months after treatment, the patients in intervention group showed increased TcPO2 and ABI and ulcer cure rate but decreased restenosis incidence, and 12 months after treatment, the patients in intervention group exhibited increased skin temperature, TcPO2 and ABI but decreased recurrence rate and restenosis incidence. Moreover, compared with the control group, total response rate, symptoms, signs and foot ulcer condition were increased, but the levels of IL-6, TNF-α and CRP decreased 3 d and 6 months in the intervention group. The total effective rate of restenosis after LEAD intervention was associated with treatment regimen, Fontaine staging, and Hb A1c. Collectively, DES implantation after PTA decreases restenosis incidence and inflammatory reaction in LEAD patients compared with PTA alone.

The aim of the present study was to investigate the new silicate cement mineral trioxide aggregate (MTA Repair HP) with respect to its effect on the inflammation process involving the tooth and periodontal tissues. The composition of MTA Repair HP was supplemented with plasticizer agents which can have a negative effect on the modulation of tooth inflammation. The silicate-based material in question is widely used in regeneration of the pulp-dentin complex, treatment of perforations of various locations in the tooth, as well as in surgical treatment of the complications of periapical tissue. The improved bioceramic restorative cement can affect the expression of metalloproteinases MMP-2 and MMP-9 in monocytes/macrophages involved in modulation of inflammation and regenerative processes of the tooth and periodontal tissues. The novel aspect of the present study lies in the application of the model of THP-1 monocyte/macrophage and applying the biomaterial in direct contact with the cells. Hence, it provides a representation of clinical conditions with respect to regenerative pulp and periodontal treatment with the use of MTA Repair HP. A lack of macrophage activation (as measured with flow cytometry) was found. Moreover, the study identified a lack of expression stimulation of the studied metalloproteinases (with the use of Western blotting and fluorescent microscopy). Similarly, no increase in MMP-2 and MMP-9 concentration was found (measured by ELISA method) in vitro when incubated with MTA Repair HP. Based on the results it can be concluded that new MTA Repair HP does not increase the inflammatory response in monocytes/macrophages associated with the activity of the described enzymes. It can also be speculated that they do not affect the process of dentin regeneration in which MMP-2 and MMP-9 play significant roles.

Made available in DSpace on 2022-04-28T19:45:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) This study aims to demonstrate the applicability and importance of zebrafish (Danio rerio) model to study acute and chronic inflammatory responses induced by different stimuli: carrageenan phlogogen (nonimmune); acute infection by bacteria (immune); foreign body reaction (chronic inflammation by round glass coverslip implantation); reaction induced by xenotransplantation. In addition to the advantages of presenting low breeding cost, high prolificity, transparent embryos, high number of individuals belonging to the same spawning and high genetic similarity that favor translational responses to vertebrate organisms like humans, zebrafish proved to be an excellent tool, allowing the evaluation of edema formation, accumulation of inflammatory cells in the exudate, mediators, signaling pathways, gene expression and production of specific proteins. Our studies demonstrated the versatility of fish models to investigate the inflammatory response and its pathophysiology, essential for the successful development of studies to discover innovative pharmacological strategies. Laboratory of Animal Pharmacology and Toxicology Brazil University (UB) Department of Preventive Veterinary Medicine São Paulo State University (UNESP) Department of Morphology Federal University of Minas Gerais (UFMG) Department of Physiology and Pharmacology Federal University of Minas Gerais (UFMG) Department of Biochemistry and Immunology Federal University of Minas Gerais (UFMG) Department of zootechnics at the Veterinary School Federal University of Minas Gerais (UFMG) Postgraduate Program in Health Sciences - PROCISA Federal University of Roraima Immunochemistry Laboratory Butantan Institute Department of Clinical and Toxicological Analyses Federal University of Minas Gerais (UFMG) Department of Pharmacology University of São Paulo (ICB-USP) Department of Preventive Veterinary Medicine São Paulo State University (UNESP) FAPESP: 2013/25971-9 FAPESP: 2018/07098-0 FAPESP: 2019/19939-1 CNPq: 301473 / 2016-1 CNPq: 307526/2018-6 CNPq: 477816/2013-4

Background Activating transcription factor 3 (ATF3) is an early response gene that is activated in response to atherosclerotic stimulation and may be an important factor in inhibiting the progression of atherosclerosis. In this study, we directly measured the expression of ATF3 and inflammatory factors in human coronary atherosclerotic plaques to examine the relationship between ATF3 expression, inflammation and structural stability in human coronary atherosclerotic plaques. Methods A total of 68 coronary artery specimens were collected from the autopsy group, including 36 cases of sudden death from coronary heart disease (SCD group) and 32 cases of acute death caused by mechanical injury with coronary atherosclerosis (CHD group). Twenty-two patients who had no coronary heart disease were collected as the control group (Con group). The histological structure of the coronary artery was observed under a light microscope after routine HE staining, and the intimal and lesion thicknesses, thickness of the fibrous cap, thickness of necrosis core, degree of lumen stenosis were assessed by image analysis software. Western blotting and immunohistochemistry were used to measure the expression and distribution of ATF3, inflammatory factors (CD45, IL-1β, TNF-α) and matrix metalloproteinase-9 (MMP-9) and vascular cell adhesion molecule 1 (VCAM1) in the coronary artery. The Pearson correlation coefficient was used to analyse the correlation between ATF3 protein expression and inflammatory factors and between ATF3 protein expression and structure-related indexes in the lesion group. Results Compared with those in the control group, the intima and necrotic core in the coronary artery were thickened, the fibrous cap became thin and the degree of vascular stenosis was increased in the lesion group, while the intima and necrotic core became thicker and the fibrous cap became thinner in the SCD group than in the CHD group (P P P P Conclusions The expression of ATF3 may be related to the progression and stability of atherosclerotic plaques, and may affect the structural stability of atherosclerotic plaques by regulating the inflammatory response, thus participating in the regulation of atherosclerotic progression.

Background and aim Recent clinical trials have confirmed that Helicobacter pylori infection is positively associated with nonalcoholic fatty liver disease (NAFLD), although some research has shown a negative association. Therefore, to confirm whether H. pylori eradication treatment is feasible for NAFLD patients in our hospital, we aimed to establish the association between H. pylori infection and NAFLD. Methods We enrolled 91 patients with NAFLD diagnosed by abdominal B-mode ultrasonography between January and December 2018. H. pylori infection was confirmed by C13 urea breath test, and liver function, glycometabolism, insulin sensitivity, lipid metabolism, as well as inflammatory reaction were assessed through blood biochemical analyses. Results A minority of NAFLD patients had liver dysfunction, increased fasting glucose and insulin levels, a score of insulin-resistance (HOMA-Ir), lipid metabolism, slight inflammatory response, fasting hyperglycemia and hypertension. Most patients were complicated with overweight/visceral obesity and dyslipidemia. Moreover, these abnormal indicators were closely associated with the severity of NAFLD and H. pylori infection. Notably, the prevalence of H. pylori infection showed a significant difference between mild, moderate and severe NAFLD, and hepatic steatosis with coexistent NAFLD also revealed a striking difference between H. pylori-positive and H. pylori-negative patients (P

OBJECTIVETo investigate the roles and underlying mechanism of exogenous H2S (hydrogen sulfide) in attenuating the myocardial fibrosis in diabetic rats. Methods A total of 40 SD rats were randomly divided into 4 groups: control group, STZ group, STZ + H2S group and H2S group. To build the DM rat model , the rats in the STZ group and STZ + H2S group were injected streptozotocin (STZ) intraperitoneally, While the rats in the STZ + H2S group and the H2S group received sodium hydrosulfide (NaHS), which provides exogenous H2S. Eight weeks later, the myocardial tissues of rats were used to detecting the collagen deposition through Masson staining, as well as some protein expressions related to myocardial fibrosis and signaling pathway by western blotting. Results Comparing to control group, the collagen deposition of myocardial matrix remarkably increased in the STZ group, and almost all the proteins that are relative to myocardial fibrosis, inflammatory and signaling pathway show an overexpression, except for PPARG and NF-κBp65. When Compared with the STZ group, the collagen deposition was obviously attenuated in STZ + H2S group, as well as the protein expressions above-mentioned, While PPARG was up-regulated. Conclusion The myocardial fibrosis in DM rats can be attenuated effectively by exogenous H2S, and the underlying mechanism is likely to regulating PKC-ERK1/2MAPK signaling pathway, improving the MMPs/TIMPs expression dysregulation and inhibiting inflammatory reaction.

Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on 18F-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.

While artificial insemination (AI) with frozen-thawed sperm results in low fertility rates in donkeys, the addition of seminal plasma, removed during cryopreservation, partially counteracts that reduction. Related to this, an apparent inflammatory reaction in jennies is induced following AI with frozen-thawed sperm, as a high amount of polymorphonuclear neutrophils (PMN) are observed within the donkey uterus six hours after AI. While PMN appear to select the sperm that ultimately reach the oviduct, two mechanisms, phagocytosis and NETosis, have been purported to be involved in that clearance. Remarkably, sperm interacts with PMN, but the presence of seminal plasma reduces that binding. As seminal plasma is a complex fluid made up of different molecules, including proteins, this study aimed to evaluate how different seminal plasma fractions, separated by molecular weight (&lt, 3, 3–10, 10–30, 30–50, 50–100, and &gt, 100 kDa), affect sperm–PMN binding. Sperm motility, viability, and sperm–PMN binding were evaluated after 0 h, 1 h, 2 h, 3 h, and 4 h of co-incubation at 38 °C. Two seminal plasma fractions, including 30–50 kDa or 50–100 kDa proteins, showed the highest sperm motility and viability. As viability of sperm not bound to PMN after 3 h of incubation was the highest in the presence of 30–50 and 50–100 kDa proteins, we suggest that both fractions are involved in the control of the jenny’s post-breeding inflammatory response. In conclusion, this study has shown for the first time that specific fractions rather than the entire seminal plasma modulate sperm–PMN binding within the donkey uterus. As several proteins suggested to be involved in the control of post-AI endometritis have a molecular weight between 30 and 100 kDa, further studies aimed at determining the identity of these molecules and evaluating their potential effect in vivo are much warranted.

Weaning of piglets is accompanied by intestinal inflammation, impaired intestinal barrier function, and intestinal microflora disorder. Regulating intestinal microflora structure can directly or indirectly affect intestinal health and host growth and development. However, whether dietary fiber (DF) affects the inflammatory response and barrier function by affecting the intestinal microflora and its metabolites is unclear. In this study, we investigated the role of intestinal microflora in relieving immune stress and maintaining homeostasis using piglets with lipopolysaccharide (LPS)-induced intestinal injury as a model. DF improved intestinal morphology and barrier function, inhibited the expression of inflammatory signal pathways (Toll-like receptor 2 [TLR2], TLR4, and NF-κB) and proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, and tumor necrosis factor alpha [TNF-α]), and upregulated the expression of barrier-related genes (encoding claudin-1, occludin, and ZO-1). The contents of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and the activity of diamine oxidase in plasma were decreased. Meanwhile, DF had a strong effect on the composition and function of intestinal microflora at different taxonomic levels, the relative abundances of cellulolytic bacteria and anti-inflammatory bacteria were increased, and the concentrations of propionate, butyrate, and total short-chain fatty acids (SCFAs) in intestinal contents were increased. In addition, the correlation analysis also revealed the potential relationship between metabolites and certain intestinal microflora, as well as the relationship between metabolites and intestinal morphology, intestinal gene expression, and plasma cytokine levels. These results indicate that DF improves intestinal barrier function, in part, by altering intestinal microbiota composition and increasing the synthesis of SCFAs, which subsequently alleviate local and systemic inflammation. IMPORTANCE Adding DF to the diet of LPS-challenged piglets alleviated intestinal and systemic inflammation, improved intestinal barrier function, and ultimately alleviated the growth retardation of piglets. In addition, the addition of DF significantly increased the relative abundance of SCFA-producing bacteria and the production of SCFAs. We believe that the improvement of growth performance of piglets with LPS-induced injury can be attributed to the beneficial effects of DF on intestinal microflora and SCFAs, which reduced the inflammatory response in piglets, improving intestinal barrier function and enhancing body health. These research results provide a theoretical basis and guidance for the use of specific fiber sources in the diet to improve intestinal health and growth performance of piglets and thus alleviate weaning stress. Our data also provide insights for studying the role of DF in regulating gastrointestinal function in human infants.

Abstract Cigarette smoke has been identified as a major risk factor for the development of age-related macular degeneration (AMD). As an alternative to conventional cigarettes (C-cigarette), electronic cigarettes (E-cigarette) have been globally promoted and are currently widely used. The increasing usage of E-cigarettes raises concerns with regard to short- (2 weeks), medium- (3 months), and long- (8 months) term consequences related to retinal tissue. In this report, a controlled study in mouse models was conducted to probe the comprehensive effects of E-cigarette vapor on retina, retinal pigmented epithelium (RPE), and choroidal tissues by (1) comparing the effects of C-cigarette smoke and E-cigarette vapor on retina separately and (2) determining the effects of E-cigarette vapor on the RPE and analyzing the changes with regard to inflammatory (IL-1β, TNFα, iNOS) and angiogenic (VEGF, PEDF) mediators in retina/RPE/choroid by ELISA assays. The data showed that C-cigarette smoke exposure promoted an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor developed inflammatory and angiogenic reactions more pronounced in RPE and choroid as compared to retinal tissue, while nicotine-containing E-cigarette vapor caused even a more serious reaction. Both inflammatory and pro-angiogenic reactions increased with the extension of exposure time. These results demonstrate that exposure to C-cigarette smoke is harmful to the retina. Likewise, the exposure to E-cigarette vapor (with or without nicotine) increases the occurrence and progression of inflammatory and angiogenic stimuli in the retina, which might also be related to the onset of wet AMD in humans. Key messages C-cigarette smoke exposure promotes an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor develop inflammatory and angiogenic reactions more pronounced in RPE and choroid compared to retinal tissue, while nicotine-containing E-cigarette vapor causes even a more serious reaction. Both inflammatory and pro-angiogenic reactions increase with the extension of E-cigarette vapor exposure time.

The inflammatory response and apoptosis are key factors in cerebral ischemia-reperfusion injury. The severity of the inflammatory reaction and apoptosis has an important impact on the prognosis of stroke. The ultrasmall superparamagnetic iron oxide particle has provided an effective magnetic resonance molecular imaging method for dynamic observation of the cell infiltration process in vivo. The aims of the present study were to investigate the inflammatory response of cerebral ischemia-reperfusion injury in mice using ferumoxytol-enhanced magnetic resonance imaging, and to observe the dynamic changes of inflammatory response and apoptosis. In the present study a C57BL/6n mouse cerebral ischemia-reperfusion model was established by blocking the right middle cerebral artery with an occluding suture. Subsequently, the mice were injected with ferumoxytol via the tail vein, and magnetic resonance scanning was performed at corresponding time points to observe the signal changes. Furthermore, blood samples were used to measure the level of serum inflammatory factors, and histological staining was performed to assess the number of iron-swallowing microglial cells and apoptotic cells. The present results suggested that there was no significant difference in the serum inflammatory factors tumor necrosis factor-α and interleukin 1β between the middle cerebral artery occlusion (MCAO) and MCAO + ferumoxytol groups injected with ferumoxytol and physiological saline. The lowest signal ratio in the negative enhancement region was decreased 24 h after reperfusion in mice injected with ferumoxytol. The proportion of iron-swallowing microglial cells and TUNEL-positive cells were the highest at 24 h after reperfusion, and decreased gradually at 48 and 72 h after reperfusion. Therefore, the present results indicated that ferumoxytol injection of 18 mg Fe/kg does not affect the inflammatory response in the acute phase of cerebral ischemia and reperfusion. Ferumoxytol-enhanced magnetic resonance imaging can be used as an effective means to monitor the inflammatory response in the acute phase of cerebral ischemia-reperfusion injury. Furthermore, it was found that activation of the inflammatory response and apoptosis in the acute stage of cerebral ischemia-reperfusion injury is consistent.

Atopic dermatitis (AD) is considered a great challenge for human communities and imposes both physiological and mental burdens on patients. Natural products have widely been used to treat a wide range of diseases, including cancer, gastrointestinal diseases, asthma, neurological disorders, and infections. To seek potential natural products against AD, in the current review, we searched the terms “atopic dermatitis” and “natural product” in Pubmed, Medline, Web of Science，Science Direct, Embase, EBSCO, CINAHL, ACS. The results show that many natural products, especially puerarin, ferulic acid and ginsenosides, cound protect against AD. Meanwhile, we discussed the therapeutic mechanisms and showed that the natural products exert their anti-inflammatory effects by suppressing the quantity and activity of many inflammatory cell types and cytokines, including neutrophils, monocytes, lymphocytes, Langerhans cells, interleukins (ILs, including IL-1α, IL-1β, IL-4), TNF-α, and TSLP, IgE. via inhibition of JAK/STAT, MAPKs and NF-κB signaling pathways, thereby, halting the inflammatory cascade. Future investigations should focus on studies with more reflective of the clinical characteristics and demographics, so as to develop natural products that will be hopefully available for the treatment of human AD disease.

This article belongs to the Special Issue West Nile Virus Infection., West Nile virus (WNV) is the most widespread flavivirus in the world with a wide vertebrate host range. Its geographic expansion and activity continue to increase with important human and equine outbreaks and local bird mortality. In a previous experiment, we demonstrated the susceptibility of 7-week-old red-legged partridges (Alectoris rufa) to Mediterranean WNV isolates Morocco/2003 and Spain/2007, which varied in virulence for this gallinaceous species. Here we study the pathogenesis of the infection with these two strains to explain the different course of infection and mortality. Day six post-inoculation was critical in the course of infection, with the highest viral load in tissues, the most widespread virus antigen, and more severe lesions. The most affected organs were the heart, liver, and spleen. Comparing infections with Morocco/2003 and Spain/2007, differences were observed in the viral load, virus antigen distribution, and lesion nature and severity. A more acute and marked inflammatory reaction (characterized by participation of microglia and CD3+ T cells) as well as neuronal necrosis in the brain were observed in partridges infected with Morocco/2003 as compared to those infected with Spain/2007. This suggests a higher neurovirulence of Morocco/2003, probably related to one or more specific molecular determinants of virulence different from Spain/2007., This study has been supported by the project PAC08-0296-7771 (JCCM), and from INIA-MARM funds (INIA CC08-020). Elena Sotelo was a fellow from INIA. Elisa Perez Ramirez was a fellow of the National Research Council (CSIC) and Ana Valeria Gutierrez was a fellow of the JCCM.

Objectives This study evaluated the biocompatibility and bioactive potential of NeoMTA Plus mixed as a root canal sealer in comparison with MTA Fillapex. Materials and methods Polyethylene tubes filled with NeoMTA Plus (n = 20), MTA Fillapex (n = 20), or nothing (control group, CG; n = 20) were inserted into the connective tissue in the dorsal subcutaneous layer of rats. After 7, 15, 30 and 60 days, the specimens were processed for paraffin embedding. The capsule thickness, collagen content, and number of inflammatory cells (ICs) and interleukin-6 (IL-6) immunolabeled cells were measured. von Kossa-positive structures were evaluated and unstained sections were analyzed under polarized light. Two-way analysis of variance was performed, followed by the post hoc Tukey test (p ≤ 0.05). Results At 7 days, the capsules around NeoMTA Plus and MTA Fillapex had more ICs and IL-6-immunostained cells than the CG. However, at 60 days, there was no significant difference in the IC number between NeoMTA Plus and the CG (p = 0.1137) or the MTA Fillapex group (p = 0.4062), although a greater number of IL-6-immunostained cells was observed in the MTA Fillapex group (p = 0.0353). From 7 to 60 days, the capsule thickness of the NeoMTA Plus and MTA Fillapex specimens significantly decreased, concomitantly with an increase in the collagen content. The capsules around root canal sealers showed positivity to the von Kossa stain and birefringent structures. Conclusions The NeoMTA Plus root canal sealer is biocompatible and exhibits bioactive potential.

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Made available in DSpace on 2021-06-25T10:19:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Aim: To evaluate the periodontium response to tricalcium silicate (TCS) with zirconium oxide (ZrO2) or niobium oxide (Nb2O5) used in the sealing of perforated pulp chamber floors in rat maxillary molars. Methodology: In eighty rats, the perforations in right maxillary molars were filled with either TCS + ZrO2, TCS + Nb2O5, White MTA (used as a gold standard material) or no repair material was placed (Sham Group, SG); the left molars of SG, were used as controls (CG). Sections of maxillary fragments following 7, 15, 30 and 60 days were used to evaluate the volume densities of inflammatory cells (VvIC) and fibroblasts (VvFb), width of the periodontal space, amount of collagen, number of osteoclasts and number of IL-6-immunostained cells. The data were subjected to two-way ANOVA followed by Tukey’s test (P ≤ 0.05). Results: At all periods, significant differences in VvIC were not detected among TCS + ZrO2, TCS + Nb2O5 and MTA groups, which had values significantly lower (P 0.05) at 15, 30 and 60 days. At 7, 15 and 30 days, the number of osteoclast was significantly greater in TCS + ZrO2, TCS + Nb2O5 and MTA (P 0.05). The width of the periodontal space and amount of collagen in TCS + ZrO2 and TCS + Nb2O5 groups were similar to the CG at 30 and 60 days while SG specimens had a significant reduction (P

Objectives This study explored the effects of the timing of laparoscopic cholecystectomy (LC) after endoscopic retrograde cholangiopancreatography (ERCP) on liver function, bile biochemical indices, inflammatory reactions, and cholecysto-choledocholithiasis patient prognoses. Methods A total of 103 cholecysto-choledocholithiasis patients were stratified into control (CG; n=51; LC at 4-7 d after ERCP) and observation groups (OG; n=52; LC at 1-3 d after ERCP) using a random number table. Results The surgical time was shorter and intraoperative blood loss was less in OG than in CG, and the two groups were not statistically different in terms of time to the first passage of gas through anus, length of postoperative hospital stay, conversion rate to laparotomy, and stone-free rate. Four weeks after LC, alanine aminotransferase (ALT), total bilirubin (TBil), albumin (ALB), and glutamyl transpeptidase (GGT) levels declined in both groups, but the difference was not statistically significant. Three days after LC, total bile acid (TBA) levels increased, and cholesterol (CHO), unconjugated bilirubin (UCB), and TBiL levels were reduced in both groups, but were not statistically different (p>0.05). Three days after LC, interleukin (IL)-6, procalcitonin (PCT), and high-sensitivity C-reactive protein (hs-CRP) levels in the serum and bile increased in both groups and were lower in OG. The total incidence of perioperative complications was 1.92% in OG, which was lower than 15.69% in the CG. Conclusion For cholecysto-choledocholithiasis patients, LC at 1-3 d after ERCP can shorten surgical times, reduce intraoperative blood loss, improve liver function and bile biochemistry, relieve inflammatory reactions, reduce complications, and improve prognoses.

Curcumin exhibits anti‐inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry‐heat conditions. We divided Sprague‐Dawley rats into four groups: dry‐heat 0‐ (normal temperature control group), 50‐, 100‐, and 150‐minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high‐dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule‐1, and neutrophil gelatinase‐associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry‐heat environment group (P

Fine particulate matter (PM2.5) has been verified to augmented the incidence of pneumonia, asthma, pulmonary fibrosis, and other pulmonary diseases. Airway inflammation is the pathological basis of the respiratory system, and understanding the molecular mechanisms responsible for airway inflammation may thus support the diagnosis and treatment of respiratory diseases. In our study, human bronchial epithelial cells (BEAS-2B) were exposed to various concentrations of PM2.5 for 48 h. PM2.5 entered the cells, resulting in increased production of interleukin 6 (IL-6) and interleukin 8 (IL-8) and decreased the expression of circular RNA 406961 (circ_406961). Further, PM2.5 with a concentration of 75 μg/mL was applied to mechanism study. Functional experiments further confirmed that circ_406961 inhibited PM2.5-induced BEAS-2B cell inflammation. RNA pull-down and mass spectrometry showed that circ_406961 interacted with interleukin enhancer-binding factor 2 (ILF2), which could regulate phosphorylation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase 8 (MAPK8, JNK). Our studies showed that circ_406961 inhibited activation of STAT3/JNK pathways via interacting with ILF2 protein, thereby inhibiting the PM2.5-induced inflammatory reaction.

Stroke is one of the major devastating diseases with no effective medical therapeutics. Because of the high rate of disability and mortality among stroke patients, new treatments are urgently required to decrease brain damage following a stroke. In recent years, the inflammasome is a novel breakthrough point that plays an important role in the stroke, and the inhibition of inflammasome may be an effective method for stroke treatment. Briefly, inflammasome is a multi-protein complex that causes activation of caspase-1 and subsequent production of pro-inflammatory factors including interleukin (IL)-18 and IL-1β. Among them, the NLRP3 inflammasome is the most typical inflammasome, which can detect cell damage and mediate inflammatory response to tissue damage in ischemic stroke. The NLRP3 inflammasome has become a key mediator of post-ischemic inflammation, leading to a cascade of inflammatory reactions and cell death eventually. Thus, NLRP3 inflammasome is an ideal therapeutic target due to its important role in the inflammatory response after ischemic stroke. In this mini review article, we will summarize the structure, assembly, and regulation of NLRP3 inflammasome, the role of NLRP3 inflammasome in ischemic stroke, and several treatments targeting NLRP3 inflammasome in ischemic stroke. The further understanding of the mechanism of NLRP3 inflammasome in patients with ischemic stroke will provide novel targets for the treatment of cerebral ischemic stroke patients.

This study is to explore the neuroprotective effects and involved glial scar of saffron (Crocus sativus L.) on the late cerebral ischemia in rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats that were randomly divided into sham group, MCAO group, edaravone group (as a positive control) and saffron groups (saffron extract 30, 100, 300 mg/kg). Saffron was administered orally at 2 h at the first day and once daily from day 2 to 42 after ischemia. Behavioral changes were detected from day 43 to 46 after ischemia to evaluate the effects of saffron. Infarct volume, survival neuron density, activated astrocyte, and the thickness of glial scar were also detected. GFAP, neurocan, phosphocan, neurofilament expressions and inflammatory cytokine contents were detected by Western-blotting and ELISA methods, respectively. Saffron improved the body weight loss, neurological deficit and spontaneous activity. It also ameliorated anxiety-like state and cognitive dysfunction, which were detected by elevated plus maze (EPM), marble burying test (MBT) and novel object recognition test (NORT). Toluidine blue staining found that saffron treatment decreased the infarct volume and increased the neuron density in cortex in the ischemic boundary zone. The activated astrocyte number and the thickness of glial scar in the penumbra zone reduced after saffron treatment. Additionally, saffron decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in the ischemic boundary zone. GFAP, neurocan, and phosphocan expressions in ischemic boundary zone and ischemic core zone all decreased after saffron treatment. Saffron exerted neuroprotective effects on late cerebral ischemia, associating with attenuating astrogliosis and glial scar formation after ischemic injury.

Objective: To investigate the protective effect of repaglinide on rat with atherosclerosis. Methods: Sprague Dawley (SD) rats were divided into control, model, repaglinide, and metformin groups. In addition to the normal group, rats were given intraperitoneal injection of streptozotocin and high-fat diet (HFD). Meanwhile, repaglinide or metformin was administrated to the treatment rats, respectively, for 4 weeks. Serum, plasma, liver, epididymal fat, and aorta thoracica were obtained to observe the protective effect of repaglinide on rat with atherosclerosis. Results: Compared to the control group, blood glucose was increased in the model group ( P < .05), while it was decreased in the drug-administered groups. In addition, the levels of endothelin 1, TG, TC, low-density lipoprotein cholesterol, atherogenic index, liver index, and epididymal fat index were significantly increased, but the levels of high-density lipoprotein cholesterol, plasminogen activator inhibitor 1, and antiatherogenic index were decreased significantly in the model group compared to the control group ( P < .05, respectively). And these effects were reversed by treatment with repaglinide ( P < .05, respectively). Conclusion: Our results suggested that repaglinide may regulate the formation of early atherosclerosis through the abovementioned mechanisms.

BiodentineTM is a material based on hydrated calcium silicate with odontotropic properties. However, from the clinician&rsquo, s perspective, every material used to fill a tooth&mdash, even those showing the optimal biochemical parameters&mdash, is in fact a foreign body introduced to the organism of the host. Therefore, apart from the chemical parameters of such materials, equally important is the so-called biocompatibility of such materials. The aim of the study was to investigate whether BiodentineTM, used in the regeneration of the pulp-dentine complex, may affect the expression of the enzymes cyclooxygenase 1 (COX1) and cyclooxygenase 2 (COX2) in THP-1 monocytes/macrophages and the amount of prostanoids synthesized by these enzymes-precursors of biologically active prostanoids such as prostaglandin E2 (PGE2) and thromboxane (TXB2) which are mediators of inflammation. An original aspect of this research is the use of the THP-1 monocyte/macrophage cell model and the use of biomaterial in direct contact with cells. In this way we tried to reflect the clinical conditions of regenerative pulp and periodontal tissue treatment using BiodentineTM. The results of our study showed a lack of macrophage activation (measured by flow cytometry) and a lack of stimulation of the expression of the studied cyclooxygenase enzymes (measured by Western blotting and fluorescent microscopy), as well as a lack of increase in the concentration (measured by ELISA method) of their inflammatory mediators (PGE2 and TXB2) in vitro incubated with BiodentineTM.

The prevention and treatment of cerebral ischemia/reperfusion injury has become a key link in the treatment of ischemic cerebrovascular diseases. In this study, Wistar rats were randomly divided into Sham, low-dose ginsenoside (L-CK), high-dose ginsenoside (H-CK) and nimodipine groups, and the rats in the L-CK, H-CK, and nimodipine groups were intragastrically given the corresponding agents successively once a day for 15 days before surgery. At 1 h after the last administration, a rat cerebral ischemia/reperfusion model was established by suture-occluded method and the effects of ginsenoside CK on the neurological scores, brain tissue water content, brain infarct volume, oxidative stress and inflammation were investigated. The results showed that, compared with those in the model group, the neurological behaviour scores in the L- and H-CK groups, the brain tissue water content in the H-CK group, and the brain infarct volume ratios in the L- and H-CK groups were significantly reduced. Compared with those in the model group, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities increased, whereas the malondialdehyde (MDA) content decreased significantly in the brain tissue of the rats in the L- and H-CK groups. Compared with that in the model group, the content of TNF-α in the H-CK group, the content of IL-1β and the expression of HMGB1 protein in the L- and H-CK groups were significantly reduced. These results suggest that ginsenoside CK can protect against cerebral ischemia reperfusion injury in rats, which may be related to its anti-oxidative, anti-inflammatory and HMGB1-expression inhibitory activity.