Continuous renal replacement therapy with vitamin E-coated polysulfone hemofilter reduces inflammatory responses in a porcine lipopolysaccharide-treated model.

INTRODUCTION: Biological invasions may promote the onset of systemic inflammatory response syndrome in patients eligible for continuous renal replacement therapy (CRRT), leading to poor prognosis. Hence, we aimed to examine the inflammatory reactions in circulation using vitamin E-coated polysulfone hollow fiber membrane (ViLIFE). METHODS: Lipopolysaccharides were intravenously administered to pigs (2 µg/kg/30 min) to establish an acute inflammation model. Extracorporeal circulation was performed for 6 h in continuous venovenous hemodiafiltration mode using a hemofilter for CRRT filled with a polysulfone hollow fiber membrane or ViLIFE, and the differences in inflammatory reactions were evaluated. RESULTS: The ViLIFE group exhibited low platelet and cytokine levels (p < 0.05 vs. sham-CRRT group). Additionally, the ViLIFE group had lower lactate and high mobility group box 1 levels than the other groups. CONCLUSION: ViLIFE represents a promising CRRT modality that can inhibit the inflammatory response in circulation and inhibit further biological invasions.

Postpartum acute myometritis suppresses expression of contraction-associated proteins in the gravid uterus.

Uterine atony is a major contributor to postpartum hemorrhage. We previously proposed the novel histological concept of postpartum acute myometritis (PAM) to elucidate the pathophysiology of uterine atony. This concept involves the infiltration of macrophages and neutrophils, as well as mast cell and complement activation in the myometrium. However, the pathological mechanism underlying uterine atony in the context of PAM remains unclear. Herein, we focused on uterine contraction-associated proteins (CAPs) including connexin 43 (Cx43), oxytocin receptors (OXR), prostaglandin receptors EP1, EP3, FP, and protease-activated receptor (PAR)-1. This follow-up study aimed to compare CAP expression between PAM and control groups. We selected 38 PAM subjects from the cases enrolled in our amniotic fluid embolism registry between 2011 and 2018. Control tissues from 10 parturients were collected during cesarean section. We stained the myometrial tissues with the following CAP markers, inflammatory cell markers, and other markers: Cx43, OXR, EP1, EP3, FP, PAR-1, C5a receptor, tryptase, neutrophil elastase, CD68, ß-actin, and Na+/K+-ATPase. The immunostaining-positive areas of Cx43, OXR, EP1, EP3, and FP standardized by ß-actin in the PAM tissue were significantly smaller than in the control group, whereas those of PAR-1 and Na+/K+-ATPase increased significantly in the PAM group. The Cx43- and OXR-positive areas correlated negatively with the immunostaining-positive cell numbers of CD68 and tryptase with halo, respectively. PAM may impair individual and synchronized myocyte contraction, leading to uterine atony refractory to uterotonics. Further cell-based studies are needed to elucidate the molecular mechanism by which inflammatory cells suppress CAP expression.

Role of Oxidative Stress in Periodontal Diseases.

Periodontal disease, a significant worldwide health burden, is characterized by chronic inflammation and destruction of periodontal tissues, including the cementum, periodontal ligament (PDL), alveolar bone, and gingival tissue. Recent research has linked the development and progression of periodontal disease to oxidative stress. This study provides comprehensive explanations of the mechanisms behind oxidative stress in periodontal disease, with a focus on the generation of reactive oxygen species (ROS) and their effects on periodontal tissues. Oxidative stress triggers a number of detrimental reactions, including lipid peroxidation, protein oxidation, and damage to deoxyribonucleic acid (DNA). Alveolar bone resorption, connective tissue degradation, and periodontal inflammation are further conditions exacerbated by these processes. In addition, the delicate balance between antioxidants and oxidants is upset by oxidative stress, which impairs antioxidant defense systems and exacerbates periodontal tissue damage. This review highlights the negative effects of oxidative stress and enhances periodontal health outcomes.

Assessment of acute toxicity, genotoxicity, and anti-inflammatory activity of SteLL, a lectin from Schinus terebinthifolia Raddi. Leaves, in mice.

ETHNOPHARMACOLOGY RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae), known as Brazilian pepper tree, stands out as a medicinal plant widely used in traditional medicine. The leaves are popularly used as anti-inflammatory agent and to relieve inflammatory conditions such as bronchitis, ulcers, and wounds, for example. AIM OF THE STUDY: The present study evaluated the acute toxicity, genotoxicity, and anti-inflammatory activity of S. terebinthifolia leaf lectin (SteLL) in mice (Mus musculus). MATERIALS AND METHODS: In the acute toxicity assay, the animals were treated intraperitoneally (i.p.) or orally (per os) with a single dose of 100 mg/kg. Genotoxicity was assessed by the comet and micronucleus assays. Carrageenan-induced peritonitis and paw edema models were used to evaluate the anti-inflammatory effects of SteLL (1, 5 and 10 mg/kg, i.p.). RESULTS: No animal died and no signs of intoxication or histopathological damage were observed in the acute toxicity assay. Genotoxic effect was not detected. In peritonitis assay, SteLL reduced in 56-69% leukocyte migration to the peritoneal cavity; neutrophil count decreased by 25-32%, while mononuclear cell count increased by 67-74%. SteLL promoted a notable reduction of paw edema after 4 h (61.1-63.4%). Morphometric analysis showed that SteLL also decreased the thickness of epidermal edema (30.2-40.7%). Furthermore, SteLL decreased MPO activity, plasma leakage, NO release, and modulated cytokines in both peritoneal fluid and paw homogenate. CONCLUSION: SteLL did not induce acute toxicity or genotoxicity in mice and stands out as a promising candidate in the development of new phytopharmaceuticals with anti-inflammatory action.

Characteristics of Neutrophil Migration and Function in Acute Inflammation Induced by Zymosan and Carrageenan in the Mice Air Pouch Model.

Deciphering the complex and redundant process of acute inflammation remains challenging. The failure of numerous clinical trials assessing anti-inflammation agents which had promising preclinical effects inevitably questions the validity of current animal models of inflammation. This study aimed to better understand the process of immune inflammatory response and to select more suitable models to evaluate the effect of potential anti-inflammatory drugs. Zymosan and λ-carrageenan are the most used representatives of particulate and soluble irritants that trigger acute inflammation in the air pouch inflammation model. When zymosan was used, the number of exudate cells first increased at 4 h-8 h, followed by a drop at 12 h-24 h. While, the changes in number of leukocytes in peripheral blood and proportion of neutrophils in bone marrow have the opposite trend. Meanwhile, neutrophils released neutrophil extracellular traps (NETs) to clean zymosan particles. In contrast, the cell migration response to carrageenan increased during 4 h to 24 h, no obvious NETs were observed, and the number of leukocytes in peripheral blood increased and the proportion of neutrophils in bone marrow decreased slightly. This study indicated that although both zymosan and carrageenan are sterile irritants, the characteristics of the inflammatory response induced by each other were different. In the acute phase of inflammation, zymosan-stimulated neutrophils were mobilized, recruited, and engulfed, and then died by NETs. Carrageenan stimulated the production of cytokines/chemokines by neutrophils or macrophages, but did not lead to an obvious death by releasing NETs.

A nox2/cybb zebrafish mutant with defective myeloid cell reactive oxygen species production displays normal initial neutrophil recruitment to sterile tail injuries.

Reactive oxygen species are important effectors and modifiers of the acute inflammatory response, recruiting phagocytes including neutrophils to sites of tissue injury. In turn, phagocytes such as neutrophils are both consumers and producers of reactive oxygen species. Phagocytes including neutrophils generate reactive oxygen species in an oxidative burst through the activity of a multimeric phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex. Mutations in the NOX2/CYBB (previously gp91phox) nicotinamide adenine dinucleotide phosphate oxidase subunit are the commonest cause of chronic granulomatous disease, a disease characterized by infection susceptibility and an inflammatory phenotype. To model chronic granulomatous disease, we made a nox2/cybb zebrafish (Danio rerio) mutant and demonstrated it to have severely impaired myeloid cell reactive oxygen species production. Reduced early survival of nox2 mutant embryos indicated an essential requirement for nox2 during early development. In nox2/cybb zebrafish mutants, the dynamics of initial neutrophil recruitment to both mild and severe surgical tailfin wounds was normal, suggesting that excessive neutrophil recruitment at the initiation of inflammation is not the primary cause of the "sterile" inflammatory phenotype of chronic granulomatous disease patients. This nox2 zebrafish mutant adds to existing in vivo models for studying reactive oxygen species function in myeloid cells including neutrophils in development and disease.

Preparation and anti-inflammatory effect of mercury sulphide nanoparticle-loaded hydrogels.

We successfully prepared mercury sulphide nanoparticle hydrogels by physical encapsulation method. The successfully prepared mercuric sulphide nanoparticle hydrogel was a zinc folate hydrogel, which showed an obvious porous structure with interconnected and uniformly distributed pores and a pore size range of about 20 µm. The maximum drug loading of the hydrogels was 3%, and the in vitro cumulative release degree was in accordance with the first-order kinetic equation Mt = 149.529 (1 - e-0.026t). The particles in mercuric sulphide nanoparticle hydrogels significantly down-regulated the expression of the cell surface co-stimulatory molecule CD86 (p < .0001). Meanwhile, the inflammatory response was regulated through the NF-κB pathway in LPS-induced inflammatory cells. Later, it was observed that mercuric sulphide nanoparticle hydrogels could significantly counteract the inflammatory and immune models through a mouse ear swelling model, a rat foot-plantar swelling model and a rheumatoid arthritis model. This design targets the immunomodulatory, and anti-inflammatory effects through nanocomposite hydrogel technology. It reduces the drawbacks of low mercury utilisation and susceptibility to accumulation of toxicity. It aims to provide an experimental basis for the development of mercuric sulphide and the treatment of inflammatory and immune-related diseases.HighlightsMercury sulphide nanoparticle hydrogel has an optimal mercury sulphide nanoparticle content of 2%, is structurally homogeneous and stable, and does not exhibit significant liver or kidney toxicity.Mercuric sulphide nanoparticle hydrogel exerts anti-inflammatory effects in cells and rats, and regulates the expression of macrophage surface molecules and factors related to the NF-κB pathway.Mercuric sulphide nanoparticle hydrogel improves the condition of ankle synovial joints in a rat model of rheumatoid arthritis.

Effects of the immune system on muscle regeneration.

Muscle regeneration is a complex process orchestrated by multiple steps. Recent findings indicate that inflammatory responses could play central roles in bridging initial muscle injury responses and timely muscle injury reparation. The various types of immune cells and cytokines have crucial roles in muscle regeneration process. In this review, we provide an overview of the functions of acute inflammation in muscle regeneration.

Nerve Growth Factor Shows Biphasic Expression during Adjuvant-Induced Neurogenic Inflammation.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression patterns of NGF in rat skin (epidermis) during adjuvant-induced arthritis (AIA). Sprague Dawley rats were randomly divided into control and complete Freund's adjuvant (CFA)-treated groups. Levels of NGF were evaluated following unilateral AIA at different time points, and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

Ginseng Berry Juice (GBJ) Regulates the Inflammation in Acute Ulcerative Mouse Models and the Major Bioactive Substances Are Ginsenosides Rb3, Rc, Rd, and Re.

Panax ginseng fruit is known to have various biological effects owing to its large amount of saponins such as ginsenosides. In the present study, ginseng berry juice was confirmed to be effective against acute inflammation. Ginseng berry juice was used for analysis of active constituents, antioxidant efficacy, and in vivo inflammation. A high-performance liquid chromatography method was used for analysis of ginsenosides. In an HCl/ethanol-induced acute gastric injury model, microscopic, immunofluorescent, and immunohistochemical techniques were used for analysis of inhibition of gastric injury and mechanism study. In a mouse model of acute gastritis induced with HCl/ethanol, ginseng berry juice (GBJ, 250 mg/kg) showed similar gastric injury inhibitory effects as cabbage water extract (CB, 500 mg/kg, P.O). GBJ dose-dependently modulated the pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-13 (IL-13). GBJ inhibited the activation of Nuclear Factor kappa bB (NF-κB) and suppressed the expressions of cyclooxigenase-2 (COX-2) and prostaglandin 2 (PGE2). The anti-inflammatory effect of GBJ is attributed to ginsenosides which have anti-inflammatory effects. Productivity as an effective food source for acute gastritis was analyzed and showed that GBJ was superior to CB. In addition, as a functional food for suppressing acute ulcerative symptoms, it was thought that the efficacy of gastric protection products would be higher if GBJ were produced in the form of juice rather than through various extraction methods.

Harnessing Extracellular microRNAs for Diagnostics and Therapeutics in Acute Systemic Inflammation.

Micro-ribonucleic acids (miRNAs) are small sequences of genetic materials that are primarily transcribed from the intronic regions of deoxyribonucleic acid (DNAs), and they are pivotal in regulating messenger RNA (mRNA) expression. miRNAs were first discovered to regulate mRNAs of the same cell in which they were transcribed. Recent studies have unveiled their ability to traverse cells, either encapsulated in vesicles or freely bound to proteins, influencing distant recipient cells. Activities of extracellular miRNAs have been observed during acute inflammation in clinically relevant pathologies, such as sepsis, shock, trauma, and ischemia/reperfusion (I/R) injuries. This review comprehensively explores the activity of miRNAs during acute inflammation as well as the mechanisms of their extracellular transport and activity. Evaluating the potential of extracellular miRNAs as diagnostic biomarkers and therapeutic targets in acute inflammation represents a critical aspect of this review. Finally, this review concludes with novel concepts of miRNA activity in the context of alleviating inflammation, delivering potential future directions to advance the field of miRNA therapeutics.

Safe Induction of Acute Inflammation with Enhanced Antitumor Immunity by Hydrogel-Mediated Outer Membrane Vesicle Delivery.

Acute inflammation has the potential for the recruitment of immune cells, inhibiting tumor angiogenesis, metastasis, and drug resistance thereby overcoming the tumor immunosuppressive microenvironment caused by chronic inflammation. Here, an acute inflammation inducer using bacteria outer membrane vesicles (OMVs) loaded in thermal-sensitive hydrogel (named OMVs-gel) for localized and controlled release of OMVs in tumor sites is proposed. OMVs trigger neutrophil recruitment and amplify acute inflammation inside tumor tissues. The hydrogel ensures drastic inflammation is confined within the tumor, addressing biosafety concerns that the direct administration of free OMVs may cause fatal effects. This strategy eradicated solid tumors safely and rapidly. The study further elucidates one of the possible immune mechanisms of OMVs-gel therapy, which involves the assembly of antitumor neutrophils and elastase release for selective tumor killing. Additionally, tumor vascular destruction induced by OMVs-gel results in tumor darkening, allowing for combinational photothermal therapy. The findings suggest that the use of OMVs-gel can safely induce acute inflammation and enhance antitumor immunity, representing a promising strategy to promote acute inflammation application in tumor immunotherapy.

Delayed-Onset Muscle Soreness Alters Mechanical Sensitivity, but Not Thermal Sensitivity or Pain Modulatory Function.

Introduction: Many clinical musculoskeletal pain conditions are characterized by chronic inflammation that sensitizes nociceptors. An unresolved issue is whether inflammation affects all nociceptors in a similar manner. Exercise-induced muscle damage (EIMD) has been proposed as a model for simulating clinical inflammatory pain in healthy samples. We sought to test the effect of EIMD on various painful stimuli (pressure and thermal), central pain processing (via the nociceptive flexion reflex) and endogenous pain modulation via conditioned pain modulation and exercise-induced hypoalgesia. Methods: Eighteen participants (9F, age: 24.6 ± 3.3) were recruited for repeated measures testing and each completed pain sensitivity testing prior to and 48 hours after an eccentric exercise protocol. The participants performed a minimum of 6 rounds of 10 eccentric knee extension exercises to induce muscle damage and localized inflammation in the right quadriceps. Force decrements, knee range-of-motion, and delayed onset muscle soreness (DOMS) were used to quantify EIMD. Results: There was a significant main effect of time for pressure pain (%diff; -58.9 ± 23.1; p = 0.02, ηp2 = 0.28) but no significant main effect was observed for limb (%diff; -15.5 ± 23.9; p = 0.53, ηp2 = 0.02). In contrast, there was a significant interaction between time and limb (p < 0.001, ηp2 = 0.47) whereby participants had lower pressure pain sensitivity in the right leg only after the damage protocol (%diff; -105.9 ± 29.2; p = 0.002). Discussion: Individuals with chronic inflammatory pain usually have an increased sensitivity to pressure, thermal, and electrical stimuli, however, our sample, following muscle damage to induce acute inflammation only had sensitivity to mechanical pain. Exercise induced inflammation may reflect a peripheral sensitivity localized to the damaged muscle rather than a global sensitivity like those with chronic pain display.

Blocking cerebral lymphatic system reduces central and peripheral inflammatory response in ischemic stroke.

Reduced blood supply to the brain activates the intracranial inflammatory response, a key contributor to secondary brain damage in ischemic stroke. Post-stroke, activation of peripheral immune cells leads to systemic inflammatory responses. Usingin vivo approaches, we investigated meningeal lymphatics' role in central immune cell infiltration and peripheral immune cell activation. The bilateral deep cervical lymph nodes (dCLNs) were removed 7 days before right middle cerebral artery occlusion in Sprague Dawley (SD) rats. At 3, 24, and 72 h post-intervention, brain immune cell infiltration and microglial and astrocyte activation were measured, while immune cells were classified in the spleen and blood. Inflammatory factor levels in peripheral blood were analyzed. Simultaneously, reverse verification was conducted by injecting AAV-vascular endothelial growth factor C (AAV-VEGFC) adenovirus into the lateral ventricle 14 days before middle cerebral artery occlusion (MCAO) induction to enhance meningeal lymph function. Blocking meningeal LVs in MCAO rats significantly reduced infarct area and infiltration, and inhibited microglia and pro-inflammatory astrocytes activation. After removing dCLNs, CD4+ T lymphocytes, CD8+ T lymphocytes, B lymphocytes, macrophages, and neutrophils in the spleen and blood of MCAO rats decreased significantly at different time points. The levels of inflammatory factors IL-6, IL-10, IL-1ß, and TNF-α in plasma decreased significantly. Tests confirmed the results, and AAV-VEGFC-induced MCAO rats provided reverse validation.

Evaluation of Iris Kashmiriana Baker plant extracts against nociception and rheumatoid arthritis in experimental rats: A concept proof by In-silico model.

ETHNOPHARMACOLOGICAL RELEVANCE: Iris Kashmiriana Baker, a traditional medicinal plant, is native to Asia, found in India, Nepal, Afghanistan, Pakistan, as name indicates majorly it's found in Kashmir region of India. Ethnopharmacologically this plant has been used there for the management of joint pain, but there was no scientific literature available. This species also comes under critically endangered species. AIM OF THE STUDY: The current study aims to evaluate the effect of Iris kashmiriana Baker against nociception and rheumatoid arthritis in experimental rats with In-silico model. MATERIAL AND METHODS: Various extracts of the plant were investigated for their in-vitro antioxidant activity. Acute inflammation and FCA induced in rat model, then acetic acid-induced writhing in mice were used. These anti-rheumatic results were justified by the computational method. RESULTS: The total phenolic and flavonoid concentration of HE extracts were found to be 95.30 ± 2.80 mg/g and 18.18 ± 5.88 mg/g respectively. IC50 and maximum inhibition of HE extracts against DPPH and H2O2 were also effective. Among different doses, 400 mg/kg of HE extracts showed significant (p<0.001) reduction in acute inflammation (16.42 %), in analgesic activity, the HE extract was found statistically (p<0.001) reduced (60.15 %) and in arthritis model, maximum inflammation reduced (25.9%) was found with hydro ethanol extract and statistical significant (p<0.001). and the paw thickness was reduced (27.4 %). Antioxidant activity of HE extract was found to be optimum (37.01%, p<0.001), Superoxide dismutase concentration was found to be optimum (65.12%, p<0.001). In Histopathology, HE 400 mg/kg showed mild inflammation only. The weight of the thymus and spleen were also determined and the HE 400 mg/kg extract inhibited the increase in weight of these organs compared with positive group (28.26 %, and 25.11 %), respectively. CONCLUSION: Among all the different extracts and various doses, the iris kashmiriana Baker hydro-ethanolic (60:40) 400 mg/kg extract showed the best response among all different extracts.

Bivalent inhibitors of the BTB E3 ligase KEAP1 enable instant NRF2 activation to suppress acute inflammatory response.

Most BTB-containing E3 ligases homodimerize to recognize a single substrate by engaging multiple degrons, represented by E3 ligase KEAP1 dimer and its substrate NRF2. Inactivating KEAP1 to hinder ubiquitination-dependent NRF2 degradation activates NRF2. While various KEAP1 inhibitors have been reported, all reported inhibitors bind to KEAP1 in a monovalent fashion and activate NRF2 in a lagging manner. Herein, we report a unique bivalent KEAP1 inhibitor, biKEAP1 (3), that engages cellular KEAP1 dimer to directly release sequestered NRF2 protein, leading to an instant NRF2 activation. 3 promotes the nuclear translocation of NRF2, directly suppressing proinflammatory cytokine transcription. Data from in vivo experiments showed that 3, with unprecedented potency, reduced acute inflammatory burden in several acute inflammation models in a timely manner. Our findings demonstrate that the bivalent KEAP1 inhibitor can directly enable sequestered substrate NRF2 to suppress inflammatory transcription response and dampen various acute inflammation injuries.

Anti-inflammatory potential of a Thai traditional remedy called Prabchompoothaweep in an animal model of acute and sub-acute inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Prabchompoothaweep (PCT) is a Thai remedy which is composed of 23 herbs and has been added onto the National List of Essential Medicines (NLEM) of Thailand. This remedy has been used to treat allergic rhinitis and asthma in Thai traditional medicine for many years. Furthermore, a few studies have reported anti-allergic, anti-malarial, anti-inflammatory and antioxidant activities. AIM OF THE STUDY: This study aims to evaluate anti-inflammatory activity of PCT extract in an animal model. MATERIALS AND METHODS: The animal model of acute inflammation was studied over a 24-h period, utilizing the method of carrageenan-induced paw oedema. In addition, sub-acute inflammation was examined over 7 days, using the formalin-induced paw oedema method. The treatment groups received PCT extracts, via the oral route, at 1-h prior to injection and then the sub plantar of the rat right paw was injected with the named substances to generate paw oedema. The paw thickness was measured by vernier caliper at regular intervals after injection. At the end of experiment, the blood and paw tissues were collected for measurement of pro-inflammatory cytokines and histological examination respectively. RESULTS: In acute inflammation, all doses of PCT extract (250, 500 and 1000 mg/kg p.o.) significantly reduced paw thickness after the first 3 h in a dose-dependent manner and the percentage of inhibition was 38.7%, 47.8% and 49.5% respectively. The pro-inflammatory cytokines, including TNF-α and IL-1ß, statistically decreased with all doses of the extracts. However, the histological examination did not reveal significant results due to the short time duration. As regards to sub-acute inflammation, all doses of PCT extract significantly reduced paw thickness with 12.78%, 23.64% and 35.78%, in a dose dependent manner. Also, the pro-inflammatory cytokines (TNF-α and IL-1ß) significantly decreased at day 7. Interestingly, the histological examination of paw tissue demonstrated reductions of mononuclear infiltrations of inflammatory cells, this was observed in the group receiving PCT extracts, also in a dose-dependent manner. CONCLUSION: Therefore, PCT exerted anti-inflammatory activity in an animal model of acute and sub-acute inflammation, suggesting that it could be used as a new source for treatment of inflammatory diseases.

Construction of a super large Stokes shift near-infrared fluorescent probe for detection and imaging of superoxide anion in living cells, zebrafish and mice.

As one of the major reactive oxygen species (ROS), superoxide anion (O2•-) is engaged in maintaining redox homeostasis in the cell microenvironment. To identify the pathological roles in related disorders caused by abnormal expression of O2•-, it is of great significance to monitor and track the fluctuation of O2•- concentration in vivo. However, the low concentration of O2•- and the interference caused by tissue autofluorescence make the development of an ideal detection methodology full of challenges. Herein, a "Turn-On" chemical response near-infrared (NIR) fluorescence probe Dcm-Cu-OTf for O2•- detection in inflamed models, was constructed by conjugating the NIR fluorophore (dicyanisophorone derivative) with an O2•- sensing moiety (trifluoromethanesulfonate). Dcm-Cu-OTf exerted about 140-fold fluorescence enhancement after reacting 200 µM O2•- with an excellent limited of detection (LOD) as low as 149 nM. Additionally, Dcm-Cu-OTf exhibited a super large Stokes shift (260 nm) and high selectivity over other bio-analytes in stimulated conditions. Importantly, Dcm-Cu-OTf showed low toxicity and enabled imaging of the generation of O2•- in the Lipopolysaccharide (LPS)-stimulated HeLa cells, zebrafish, and LPS-induced inflamed mice. The present study provided a potential and reliable detection tool to inspect the physiological and pathological progress of O2•- in living biosystems.

Roles of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor 2 in Endotoxin-Induced Acute Retinal Inflammation.

PURPOSE: To investigate the roles of sphingosine kinases (SphKs) and sphingosine-1-phosphate receptors (S1PRs) in endotoxin-induced uveitis (EIU) mice. METHODS: EIU model was induced using an intraperitoneal injection of lipopolysaccharide (LPS). The expression of SphKs and S1PRs in the retina was assessed using quantitative polymerase chain reaction (qPCR) and immunofluorescence. The effects of S1PR antagonists on the expression of inflammatory cytokines in the retina were evaluated using qPCR and western blotting. Effects of leukocyte infiltration of the retinal vessels were evaluated to determine the effects of the S1PR2 antagonist and genetic deletion of S1PR2 on retinal inflammation. RESULTS: Retinal SphK1 expression was significantly upregulated in EIU. SphK1 was expressed in the GCL, IPL, and OPL and S1PR2 was expressed in the GCL, INL, and OPL. Positive cells in IPL and OPL of EIU retina were identified as endothelial cells. S1PR2 antagonist and genetic deletion of S1PR2 significantly suppressed the expression of IL-1α, IL-6, TNF-α, and ICAM-1, whereas S1PR1/3 antagonist did not. Use of S1PR2 antagonist and S1PR2 knockout in mice significantly ameliorated leukocyte adhesion induced by LPS. CONCLUSION: SphK1/S1P/S1PR2 signaling was upregulated in EIU and S1PR2 inhibition suppressed inflammatory response. Targeting this signaling pathway has potential for treating retinal inflammatory diseases.

A Case of Atraumatic Acute Carpal Tunnel Syndrome Requiring Emergency Surgery.

Acute carpal tunnel syndrome (ACTS) is an urgent condition in which symptoms progress rapidly on an hourly basis, and emergency surgery may be required to treat it. ACTS often occurs after a traumatic event such as a fracture of the distal radius, and rarely occurs non-traumatically. We present a case of a 60-year-old male with ACTS secondary to acute synovitis due to rheumatoid arthritis. The patient complained of strong numbness from the thumb to the ring finger and pain in the palm, and he was unable to actively flex or extend his fingers. In addition, severe tenderness was observed in the palm; on the contralateral side, no obvious tenderness of the forearm and wrist joint was observed. Due to the intolerable pain and numbness, ACTS was suspected. Internal pressure from the forearm to the palm was measured, and it was found that the internal pressure of the carpal tunnel was elevated at 150 mmHg. Based on these findings, non-traumatic ACTS was diagnosed, and emergency surgery was performed. The transverse carpal ligament was exposed, an incision was made from the distal end, and the proximal part was fully incised to the forearm fascia so that the carpal tunnel was completely released. The synovial membranes around the median nerve were peeled off, confirming that the nerve had been loosened sufficiently. After the operation, finger pain and numbness improved dramatically from the day after surgery. Proper diagnosis and prompt treatment with surgical median nerve decompression are crucial for good functional recovery in these patients.