Inflammatory Reaction Research Articles

Yersinia ruckeri Infection and Enteric Redmouth Disease among Endangered Chinese Sturgeons, China, 2022.

During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.

Histology and transcriptomic analysis reveal effects of dietary fish oil and soybean oil on lipid absorption and immune inflammation in the foregut of adult female spotted scat (Scatophagus argus)

The foregut is the main site of lipid absorption in fish, but the effect of different lipid sources on the foregut lipid absorption and metabolism in adult female spotted scat is still unclear. In this experiment, adult female spotted scat (length = 19.48 ± 1.13cm, weight = 242.83 ± 50.90g) were fed two iso-nitrogenous (45% crude protein) and iso-lipidic (12.5% crude lipid) diets configured with either 8% fish oil (FO) or 8% soybean oil (SO) for 60 days. Histological observations, serum measurements and transcriptome sequencing were used to investigate the effects of the oil sources on the foregut. Histological observation showed that the foregut folds of the SO group were shorter and narrower than those of the FO group, and nuclear vacuolation and villous atrophy were observed in the intestinal cells of fish in the SO group, indicating an inflammatory reaction. Both serum triglyceride and total cholesterol levels were significantly higher in the FO group than in the SO group. Transcriptome analysis revealed 1355 differentially expressed genes between the FO and SO groups. Genes related to lipid metabolism (adipor2 and creb3l3) and cholesterol absorption and efflux (npc1l1 and sphk2) were up-regulated, whereas genes related to fatty acid synthesis and transport (fad1 and mfsd2ab) were down-regulated in the FO group. Circadian rhythm related genes ciart and nfil3, which are also involved in lipid metabolism, were up- and down-regulated, respectively in the FO group. The immune-related genes steap4, ddit4 and cldn6 which can inhibit inflammation, were up-regulated in the FO group, whereas pro-inflammation gene rnf225 was up-regulated in the SO group. In conclusion, compared with SO, FO may enhance the lipid absorption and reduce the inflammatory response in the foregut of the spotted scat. The results of this study provide a reference for the selection of dietary oil sources for adult female spotted scat.

Lecithin-complexed oregano essential oil-encapsulated fibrous barriers prevent postoperative adhesions by regulating Nrf2/NF-κB signaling pathways

Postoperative adhesions are prone to a variety of complications, which can adversely affect the quality of life (QOL) of patients. While anti-adhesion scaffolds rapidly degrade, foreign body reactions (FBR), exaggerated inflammatory reactions, and oxidative stress may increase tissue adhesions. This necessitates the development of anti-adhesion scaffolds with multifunctional anti-inflammatory, anti-bacterial, and anti-oxidative characteristics. The objective of this study was to simultaneously leverage natural antimicrobial and anti-oxidative bioactive molecules, such as lecithin (L) and Oregano essential oil (O) to afford poly(lactic-co-glycolic acid) (PLGA)-based electrospun membranes for postoperative anti-adhesion management. A series of assays revealed a beneficial effect of L and O co-loaded membranes (P@LO) to suppress bacterial growth, reduce the proliferation of fibroblasts, and confer anti-oxidative and anti-inflammatory functionalities to membranes than that of the control (P) or only a single cue-loaded groups (P@L and P@O). The underlying molecular mechanism of the anti-inflammatory effect may be an upregulation of the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation. An assessment of membranes in an abdominal and a tendon adhesion model showed a significant effect of P@LO membranes to prevent post-operative tissue adhesion. The P@LO membranes were found to up-regulate the phosphorylation of Nrf2 while down-regulate the phosphorylation of nuclear factor kappa-B (NF-κB) P65. This resulted in lower expression of collagen Ⅰ (Col-Ⅰ), collagen Ⅲ (Col-Ⅲ), and alpha-smooth muscle actin (α-SMA) alongside inflammation resolution and less transition of fibroblasts to myofibroblasts. Taken together, these multifunctional scaffolds may have broad implications for postoperative adhesion management.

Clinical efficacy of ganciclovir combined with transfer factor oral solution for pediatric infectious mononucleosis

This study investigates the clinical efficacy of ganciclovir combined with transfer factor oral solution in the treatment of patients with infectious mononucleosis (IM) to provide a reference for clinical application. A total of 150 children with IM who received treatment in our hospital from 2020 to 2022 were randomly selected as the research subjects. They were randomly divided into a control group receiving intravenous administration of ganciclovir (n = 75) and an observation group receiving transfer factor oral liquid in combination with intravenous administration of ganciclovir (n=75). The results showed that after treatment, the serum levels of CK-MB, CK, CRP, IL-6, and TNF-α were significantly reduced in both groups. The observation group showed lower levels than the control group. Additionally, peripheral blood CD4+ T cells, CD4+/CD8+ ratio, and Tfr expression were higher in the observation group compared to the control group, while the level of CD8+ T cells was lower than that of the control group. Furthermore, there were no significant changes in the levels of IgA, IgM, and IgG antibodies in the two groups before and after treatment. In conclusion, the combination therapy of transfer factor oral solution and ganciclovir demonstrates favorable clinical efficacy and safety in the treatment of children with IM, as it effectively reduces inflammatory reactions, regulates cellular immune function, promotes Tfr differentiation, and shortens recovery time.

Hydrogen sulfide: physiological roles and therapeutic implications against COVID-19.

The COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) poses a major menace to economic and public health worldwide. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are two host proteins that play an essential function in the entry of SARS-COV-2 into host cells. Hydrogen sulfide (H2S), a new gasotransmitter, has been shown to protect the lungs from potential damage through its anti-inflammatory, antioxidant, antiviral, and anti-aging effects. It is well known that H2S is crucial in controlling the inflammatory reaction and the pro-inflammatory cytokine storm. Therefore, it has been suggested that some H2S donors may help treat acute lung inflammation. Furthermore, recent research illuminates a number of mechanisms of action that may explain the antiviral properties of H2S. Some early clinical findings indicate a negative correlation between endogenous H2S concentrations and COVID-19 intensity. Therefore, reusing H2S-releasing drugs could represent a curative option for COVID-19 therapy.

Highly Effective Nobiletin-MPN in Yeast Microcapsules for Targeted Modulation of Oxidative Stress, NLRP3 Inflammasome Activation, and Immune Responses in Ulcerative Colitis.

Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.

SHARPIN contributes to sevoflurane-induced neonatal neurotoxicity through up-regulating HMGB1 to repress M2 like-macrophage polarization.

Sevoflurane exposure can result in neurotoxicity especially among children, which remains an important complication after surgery. However, its related mechanisms remain unclear. Here, we investigated the biological roles of SHARPIN in sevoflurane-induced neurotoxicity. As detected by qPCR, Western blotting and immunohistochemical staining, SHARPIN and HMGB1 expression was elevated in sevoflurane-stimulated mice as compared with the control mice. SHARPIN depletion attenuated hippocampus injury, repressed the expression of HMGB1 and M1-like macrophage markers (iNOS, TNF-α, IL-1β, IL-6), but enhanced the expression of M2-like macrophage markers (ARG-1, IL-10). GST pull-down and Co-IP assays demonstrated that SHARPIN directly interacted with HMGB1 to enhance HMGB1 expression in SH-SY5Y cells. The inhibitory effects of SHARPIN silencing on inflammatory reaction and M1-like macrophages were counteracted by HMGB1 overexpression. Finally, SHARPIN-HMGB1 pathway affected neuroinflammation triggered by sevoflurane via modulating macrophage polarization. Collectively, our data suggested that SHARPIN stimulated sevoflurane-induced neurotoxicity via converting M2-like macrophages to M1-like macrophages by enhancing HMGB1 expression. SHARPIN intervention may be a promising therapeutic method to relieve sevoflurane-induced neurotoxicity.

Coatings for Permanent Meshes Used to Enhance Healing in Abdominal Hernia Repair: A Scoping Review.

Hernia meshes are used to reduce recurrence and pain rates, but the rates are still high. This could be improved with coatings of the mesh. This scoping review aimed to provide an overview of mesh coatings used to promote healing in abdominal hernia repair and to report beneficial and unbeneficial effects. We included human and animal studies with abdominal hernias that were repaired with non-commercially coated meshes. We searched Pubmed, Embase, Cochrane Central, LILACS, and CNKI without language constraints. Of 2933 identified studies, 58 were included: six studies had a total of 408 humans and 52 studies had 2679 animals. The median follow-up was 12 months (range 1-156), and 95% of the hernias were incisional. There were 44 different coatings which included platelet-rich plasma, mesenchymal stem cells, growth factors, vitamin E, collagen-derived products, various polysaccharides, silk proteins, chitosan, gentamycin, doxycycline, nitrofurantoin, titanium, and diamond-like carbon. Mesenchymal stem cells and platelet-rich plasma were the most researched. Mesenchymal stem cells notably reduced inflammation and foreign body reactions but did not impact other healing metrics. In contrast, platelet-rich plasma positively influenced tissue ingrowth, collagen deposition, and neovascularization and had varying effects on inflammation and foreign body reactions. We identified 44 different mesh coatings and they showed varying results. Mesenchymal stem cells and platelet-rich plasma were the most studied, with the latter showing considerable promise in improving biomechanical properties in hernia repair. Further investigations are needed to ascertain their definitive use in humans.

Effect of saline irrigation temperature difference on postoperative acute pain and hypothermia during biportal endoscopic spine surgery.

Recently, enhanced recovery after surgery (ERAS) protocols have attracted attention; they emphasize on avoiding intraoperative hypothermia while performing lumbar fusion surgery. However, none of the studies have reported the protocol for determining the temperature of saline irrigation during biportal endoscopic spine surgery (BESS) procedure. This study evaluated the effectiveness of warm saline irrigation during BESS in acute postoperative pain and inflammatory reactions. Fifty-five patients who underwent BESS procedure were retrospectively analyzed for the incidence of perioperative hypothermia (< 36oC), postoperative inflammatory factors (white blood cells (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)), and clinical outcomes (back visual analog scale (VAS) score, postoperative shivering). The patients were divided into the warm and cold saline irrigation groups. Hemoglobin, WBC, ESR, creatine kinase, and creatine kinase-muscle brain levels did not significantly differ between the warm and cold saline groups. The mean CRP, IL-6, and SAA levels were significantly higher in the cold saline group than in the warm saline group (p = 0.0058, 0.0028, and 0.0246, respectively); back VAS scores were also higher with a statistically significant difference until two days postoperatively (p < 0.001). During the entire procedure, the body temperature was significantly lower in the cold saline irrigation group, but the hypothermia incidence rate significantly differed 30min after the operation was started. Using warm saline irrigation during BESS is beneficial for early recovery after surgery, as it is associated with reduced postoperative pain and complication rates.

Depression and type 2 diabetes: A causal relationship and mechanistic pathway.

Depression is a mood disorder that may increase risk for the development of insulin resistance (IR) and type 2 diabetes (T2D), and vice versa. However, the mechanistic pathway linking depression and T2D is not fully elucidated. The aim of this narrative review, therefore, was to discuss the possible link between depression and T2D. The coexistence of T2D and depression is twice as great compared to the occurrence of either condition independently. Hyperglycaemia and dyslipidaemia promote the incidence of depression by enhancing inflammation and reducing brain serotonin (5-hydroxytryptamine [5HT]). Dysregulation of insulin signalling in T2D impairs brain 5HT signalling, leading to the development of depression. Furthermore, depression is associated with the development of hyperglycaemia and poor glycaemic control. Psychological stress and depression promote the development of T2D. In conclusion, T2D could be a potential risk factor for the development of depression through the induction of inflammatory reactions and oxidative stress that affect brain neurotransmission. In addition, chronic stress in depression may induce the development of T2D through dysregulation of the hypothalamic-pituitary-adrenal axis and increase circulating cortisol levels, which triggers IR and T2D.

Exploring the lung-gut direction of the gut-lung axis in patients with ARDS.

Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements in treatment perspectives, ARDS still carries a high mortality rate, often due to systemic inflammatory responses leading to multiple organ dysfunction syndrome(MODS). Indeed, the deterioration and associated mortality in patients with acute lung injury (LI)/ARDS is believed to originate alongside respiratory failure mainly from the involvement of extrapulmonary organs, a consequence of the complex interaction between initial inflammatory cascades related to the primary event and ongoing mechanical ventilation-induced injury resulting in multiple organ failure (MOF)and potentially death. Even though recent research has increasingly highlighted the role of the gastrointestinal tract in this process, the pathophysiology of gut dysfunction in patients with ARDS remains mainly underexplored. This review aims to elucidate the complex interplay between lung and gut in patients with LI/ARDS. We will examine various factors, including systemic inflammation, epithelial barrier dysfunction, the effects of mechanical ventilation (MV), hypercapnia, and gut dysbiosis. Understanding these factors and their interaction may provide valuable insights into the pathophysiology of ARDS and potential therapeutic strategies to improve patient outcomes.

Oral administration of liposome-encapsulated thymol could alleviate the inflammatory parameters in serum and hippocampus in a rat model of Alzheimer's disease

BackgroundNeuroinflammation is closely related to Alzheimer's Disease (AD) pathology, hence supplements with anti-inflammatory property could help attenuate the progression of AD. This study was conducted to evaluate the potential anti-inflammatory effects of liposome encapsulated thymol (LET), administered orally, in prevention of Alzheimer in a rat model by anti-inflammatory mechanisms. MethodsThe rats were grouped into six groups (n = 10 animals per group), including Control healthy (Con), Alzheimer's disease (AD) model, AD model treated with free thymol in 40 and 80 mg/kg body weight (TH40 and TH80), AD model treated with LET in 40 and 80 mg/kg of body weight (LET40 and LET80). The behavioral response of step through latency (Passive Avoidance Test), concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) were assessed in serum and hippocampus. ResultsThe results showed that significant increase in concentrations of IL-1β (P = 0.001), IL-6 (P = 0.001), TNF-α (P = 0.001) and COX-2 (P = 0.001) in AD group compared with healthy control rats. AD induction significantly reduced step through latency and revealed deficits in passive avoidance performance. The results also showed the treatment with free thymol especially in higher concentrations and also LTE could decrease serum concentrations of IL-1β (P < 0.05), IL-6 (P < 0.05), TNF-α (P < 0.05), and COX-2 (P < 0.05) and increase BDNF (P < 0.05) compared with control Alzheimer rats in hippocampus and serum. There were also significant correlations between serum and hippocampus concentrations of IL-1β (r2 = 0.369, P = 0.001), IL-6 (r2 = 0.386, P = 0.001), TNF-α (r2 = 0.412, P = 0.001), and COX-2 (r2 = 0.357, P = 0.001). It means a closed and positive relation between serum and hippocampus concentrations of IL-1β, IL-6, TNF-α, and COX-2. ConclusionsLET demonstrates its ability to attenuate neuroinflammatory reaction in AD model through suppression of IL-1β, IL-6, and TNF-α and COX-2 indicators. Hence, it can ameliorate AD pathogenesis by declining inflammatory reaction.

Electro-scalp acupuncture regulates the expression of CYP27a1/b1, CYP24a and related inflammatory cytokines in ischemic cortex of rats with middle cerebral artery occlusion.

To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1β and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1β in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1β in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.

Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis.

To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Propolis Alleviates Acute Lung Injury Induced by Heat-Inactivated Methicillin-Resistant Staphylococcus aureus via Regulating Inflammatory Mediators, Gut Microbiota and Serum Metabolites

Propolis has potential anti-inflammatory properties, but little is known about its efficacy against inflammatory reactions caused by drug-resistant bacteria, and the difference in efficacy between propolis and tree gum is also unclear. Here, an in vivo study was performed to study the effects of ethanol extract from poplar propolis (EEP) and poplar tree gum (EEG) against heat-inactivated methicillin-resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI) in mice. Pre-treatment with EEP and EEG (100 mg/kg, p.o.) resulted in significant protective effects on ALI in mice, and EEP exerted stronger activity to alleviate lung tissue lesions and ALI scores compared with that of EEG. Furthermore, EEP significantly suppressed the levels of pro-inflammatory mediators in the lung, including TNF-α, IL-1β, IL-6, and IFN-γ. Gut microbiota analysis revealed that both EEP and EEG could modulate the composition of the gut microbiota, enhance the abundance of beneficial microbiota and reduce the harmful ones, and partly restore the levels of short-chain fatty acids. EEP could modulate more serum metabolites and showed a more robust correlation between serum metabolites and gut microbiota. Overall, these results support the anti-inflammatory effects of propolis in the treatment of ALI, and the necessity of the quality control of propolis.

Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study

Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-α, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-β, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (∼93%) was significantly greater than the control group (∼58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.

Exploration of Potential Targets and Molecular Mechanisms of the Yiqi Jianpi Tongqiao Formula in Treating Allergic Rhinitis Mouse Model based on Network Pharmacology and Molecular Docking.

To investigate the therapeutic effect of Yiqi Jianpi Tongqiao (YJT) formula (Hedysarum Multijugum Maxim, Magnoliae Flos, Xanthii Fructus, Notopterygii Rhizoma Et Radix, Kaempferiae Rhizoma, Acoritataninowii Rhizoma, Saposhnikoviae Radix) on an allergic rhinitis mouse model, and to explore the active ingredients, key targets, and molecular mechanisms of this formula using network pharmacology and molecular docking methods. An allergic rhinitis mouse model was established to observe changes in rhinitis symptoms, nasal mucosal morphology, and serum indicators after administering the YJT formula. The TCMSP, GeneCards, OMIM, and DisGeNET databases were used to screen for the active ingredients, action targets, and disease targets of the YJT formula. The Cytoscape software was used to construct a network of the active ingredients and action targets. The protein-protein interaction (PPI) network was used to predict hub genes. The corresponding active compounds with the hub genes' highest oral bioavailability (OB) values were identified, followed by molecular docking analysis. Animal experiments demonstrated that the YJT formula reduced rhinitis symptoms (nasal itching, runny nose, and face scratching) in allergic rhinitis mice, as well as decreased nasal mucosal inflammatory reactions and serum inflammatory indicators (histamine, OVAspecific IgE, IL-1β levels). Furthermore, 63 active components and 101 potential indicator targets of the YJT formula were identified, along with 5 hub genes (IL6, AKT1, IL1B, VEGFA, and PTGS2), and the corresponding active compounds with the highest OB values were quercetin, aloe-emodin, and denudanolide b. Molecular docking results revealed the binding energy between quercetin, aloe-emodin, denudanolide b and 5 hub genes (IL6, AKT1, IL1B, VEGFA, and PTGS2) were -5.78 to -10.22 kcal/mol, the binding energy between dexamethasone and 5 hub genes were -6.3 to -9.7 kcal/mol. In addition, GO and KEGG analysis suggested significant enrichment of these genes in biological processes such as response to lipopolysaccharide, response to molecule of bacterial origin, and response to reactive oxygen species, as well as signaling pathways like AGE-RAGE signaling pathway in diabetic complications, Lipid and atherosclerosis, and IL-17 signaling pathway. The YJT formula has therapeutic effects in an allergic rhinitis mouse model, with the main active components being quercetin, aloe-emodin, and denudanolide b, and the key targets being IL6, AKT1, IL1B, VEGFA, and PTGS2, involving multiple signaling pathways.

Lipopolysaccharide pretreatment increases the sensitivity of the TRPV1 channel and promotes an anti-inflammatory phenotype of capsaicin-activated macrophages

BackgroundThe transient receptor potential vanilloid 1 (TRPV1) is well-established in neuronal function, yet its role in immune reactions remains enigmatic. The conflicting data on its inflammatory role, suggesting both pro-inflammatory and anti-inflammatory effects upon TRPV1 stimulation in immune cells, adds complexity. To unravel TRPV1 immunomodulatory mechanisms, we investigated how the TRPV1 agonist capsaicin influences lipopolysaccharide (LPS)-induced pro-inflammatory macrophage phenotypes.ResultsChanges in the surface molecules, cytokine production, and signaling cascades linked to the phenotype of M1 or M2 macrophages of the J774 macrophage cell line and bone marrow-derived macrophages, treated with capsaicin before or after the LPS-induced inflammatory reaction were determined. The functional capacity of macrophages was also assessed by infecting the stimulated macrophages with the intracellular parasite Leishmania mexicana.ConclusionOur findings reveal that TRPV1 activation yields distinct macrophage responses influenced by the inflammatory context. LPS pre-treatment followed by capsaicin activation prompted increased calcium influx, accompanied by a shift toward an anti-inflammatory M2b-like polarization state.

Anti-Vasculogenic, Antioxidant, and Anti-Inflammatory Activities of Sulfated Polysaccharide Derived from Codium tomentosum: Pharmacokinetic Assay

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of sulfated polysaccharide from C. tomentosum (PCT) using carrageenan (CARR)-induced paw edema in a rat model and anti-vasculogenic activity on a chorioallantoic membrane assay (CAM) model. Based on in vitro tests of anti-radical, total antioxidant, and reducing power activities, PCT presents a real interest via its antioxidant activity and ability to scavenge radical species. The in vivo pharmacological tests suggest that PCT possesses anti-inflammatory action by reducing paw edema and leukocyte migration, maintaining the redox equilibrium, and stabilizing the cellular level of several pro-/antioxidant system markers. It could significantly decrease the malondialdehyde levels and increase superoxide dismutase, glutathione peroxidase, and glutathione activities in local paw edema and erythrocytes during the acute inflammatory reaction of CARR. PCT pretreatment was effective against DNA alterations in the blood lymphocytes of inflamed rats and reduced the hematological alteration by restoring blood parameters to normal levels. The anti-angiogenic activity results revealed that CAM neovascularization, defined as the formation of new vessel numbers and branching patterns, was decreased by PCT in a dose-dependent manner, which supported the in silico bioavailability and pharmacokinetic findings. These results indicated the therapeutic effects of polysaccharides from C. tomentosum and their possible use as anti-proliferative molecules based on their antioxidant, anti-inflammatory, and anti-angiogenic activities.

Analysis of Tissue Repair of a New Cement Based on Calcium and Strontium Aluminates: A Triple-Blinded, Randomized, Controlled Trial in an Animal Model.

The focus of this triple-blind randomized study was to evaluate the biocompatibility of a new root canal filling sealer (RCFS) based on tristrontium aluminate and dodecacalcium hepta-aluminate in living tissue. Forty-five Wistar rats (Rattus norvegicus) were divided into three groups: control (polyethylene), sealer (Bio-C Sealer, Londrina, PR, Brazil), and experimental (tristrontium aluminate and dodecacalcium hepta-aluminate). The tissues were analyzed under an optical microscope to assess different cellular events at different time intervals (7, 15, and 30 days). Data were analyzed using the Kruskal-Wallis and Dunn (p < 0.05) tests. In the initial period, a moderate inflammatory infiltrate was observed, similar between the endodontic cements groups (p = 0.725). The intensity of the infiltrate decreased with time, with no significant difference among the groups (p > 0.05). The number of young fibroblasts was elevated in all groups evaluated at 7 days. The experimental group showed the highest number of cells at all time intervals, but the difference with the sealer group at 7 (p = 0.001) and 15 days (p = 0.002) and the control group at 30 days was not significant (p = 0.001). Regarding tissue repair events, the amount of collagen fibers increased over the experimental intervals, with no significant difference between the sealer and control groups (p > 0.05). The experimental RCFS based on calcium and strontium aluminates proved to be biocompatible for use in close contact with periapical tissue, inducing a low inflammatory reaction and favoring rapid tissue repair.