Serum Levels Of Inflammatory Cytokines Research Articles

Intestinal alkaline phosphatase improves intestinal permeability and alleviates multiple organ dysfunction caused by heatstroke

ObjectiveHeatstroke (HS) is a severe acute disease related to gastrointestinal barrier dysfunction, systemic inflammation and multiple organ injury. Many of the functions of Intestinal alkaline phosphatase (IAP) have been linked to gut homeostasis, gut barrier function and inflammation. However, the protective effect of IAP on heatstroke is not fully elucidated. This study aims to explore the protective effect of IAP on heatstroke by maintaining intestinal barrier and improving permeability. MethodsMale C57BL/6 mice were placed in a controlled climate chamber (ambient temperature: 40.0 ± 0.5 °C; humidity: 60 ± 5 %) until the maximum core temperature (Tc, max) reached 42.7 °C (the received criterion of HS). Then heat exposed mice (n = 195) were divided into three groups: 0.2 mL of 0.9 % physiological saline (HS) or vehicle (HS + Vehicle) or 300 IU IAP (HS + IAP) by gavage at 0, 24, and 48 h after onset. Control group mice (Con) (n = 65) were not exposed to heat and were gavaged with 0.9 % physiological saline of the same volume at the same time. ResultsIAP treatment significantly reduced the levels of endotoxin, FD4, and D-lactate in the blood of heatstroke mice, reduced intestinal permeability and maintained the integrity of the intestinal barrier by increasing the expression of tight junction proteins. Meanwhile, IAP treatment alleviated liver and kidney damage caused by heatstroke, reduced serum levels of inflammatory cytokines, and thus improved survival rate of mice after heatstroke. ConclusionThis study indicates that IAP can improve the intestinal barrier function and intestinal permeability by increasing intestinal tight junctions, reduce systemic inflammation and multiple organ injury and improving the survival rate of heatstroke. Therefore, we consider IAP may be added to enteral nutrition formulas as a potential means for diseases characterized by intestinal permeability disorders, including heatstroke.

Microbial modifications with Lycium barbarum L. oligosaccharides decrease hepatic fibrosis and mitochondrial abnormalities in mice.

Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied. Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis. Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices). The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and β-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis. These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.

Bifidobacterium longum subsp. longum BL21 ameliorates alcoholic liver disease in mice through enhancement of the hepatic antioxidant capacity and modulation of the gut microbiota.

Alcoholic liver disease (ALD) is a chronic liver injury caused by excessive alcohol consumption, could be impacted by gut-liver axis dysfunction. The gut microbiota plays a crucial role in the development and progression of ALD. Given the role of gut-liver axis dysfunction in ALD, strategies targeting gut microbiota modulation have gained interest for therapeutic interventions. Bifidobacterium longum subsp. longum BL21 has shown promise in alleviating gut microbiota disturbances and metabolic regulation in high-fat diet-induced obesity and type 2 diabetes mellitus models. Thus, this study aimed to evaluate the therapeutic effect of BL21 on ALD mice and explore the potential mechanism by which the gut microbiota mediates the amelioration of ALD by BL21. A total of 30 mice were randomly assigned to three groups (n=10 mice/group): a healthy control (CTL) group, an ALD group, and a BL21 group. Each group was fed a Lieber-DeCarli liquid diet with (ALD and BL21) or without alcohol (CTL). The intervention period lasted 6 weeks, after which the effects of BL21 intervention (intragastric administration of 1 billion CFU of BL21 daily) on serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, hepatic oxidative stress, serum inflammatory cytokine levels, and gut microbiota composition in ALD mice were investigated. Dietary BL21 reduced the ethanol-induced abnormal elevation of serum AST and ALT levels in ALD mice (P<0.001 for both). BL21 treatment significantly attenuated alcohol-induced hepatic oxidative stress by decreasing malondialdehyde concentration and increasing superoxide dismutase, catalase, and glutathione concentrations in the livers of ALD mice. In addition, the serum levels of tumor necrosis factor-alpha, interleukin-1 beta (IL-1β), and IL-6 were significantly lower (P<0.001 for both), while that of IL-10 was significantly higher (P<0.05), in the BL21 group than in the ALD group. Intestinal microbiota analysis showed an increased relative abundance of Escherichia/Shigella, Enterococcus, and Alistipes in the ALD group compared with the CTL group. BL21 intervention increased the relative abundance of Bifidobacterium and Akkermansia compared with the ALD group. Dietary BL21 ameliorates ALD via enhancement of the hepatic antioxidant capacity and modulation of the gut microbiota and may therefore be a promising strategy to prevent or treat ALD.

The Protective Effect of Ramelteon and in combination with Dexamethasone on the Lipopolysaccharide-induced Cytokine Storm in mice

Cytokine Storm Syndrome (CSs) is a potentially life threatening condition, characterized by robust elevated; of circulating pro- inflammatory cytokines; occurring after a hyperactive immune system. Is a well-known as a worldwide health problem, leading to multi-organ failure and death. Objectives: This study was carried out to investigate the protective role and probability of additive or synergistic anti-inflammatory activity; of ramelteon and in combination with dexamethasone on the lipopolysaccharide (LPS) induced “Cytokine Storm” on mice model and its potential regulatory mechanism(s). Methods: Sixty Swiss albino male mice of ;( 25 ± 5 grams; 8-12 weeks) had free access to food and water. After 2weeks of adaptation, mice; randomly separated in five groups (n =12): Group I, mice received (0.9% N\S i.p.); Group II, mice received (5mg\kg i.p.) LPS only .Group III, mice received (2.5mg/kg, i.p.) dexamethasone, Group IV, mice received (100mg/kg i.p.) ramelteon, Group V, mice received half dose of dexamethasone+ ramelteon combination (1.25 mg\kg i.p +50mg\kg i.p). For systematic inflammatory stimulation mimicking “cytokine storm” LPS; E. coli O55:B5 (5mg\kg i.p.) was induced within one hr. After 48h the effects of interventional agents and vehicle or LPS challenge; on lung, heart, liver, kidney histopathological changes, and levels of inflammatory cytokines :( IL-6, IL8 IL-1β, and TNF-α) in the serum were detected. Results: IL-1β, IL-6, IL8 and TNF-α elevated serum levels significantly reduced (p&lt;0.001) in all treatment group. Additionally, they ameliorated the histopathological changes induced by (LPS) and improving macroscopic scores (p&lt;0.001). Conclusion: In conclusion, ramelteon treatment had a diverse protective effects against “Cytokine Storm” with a mechanism based on attenuation serum levels of inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α)and through reduction of histopathological damage during endotoxemia induced via LPS challenge on male mice model. RAM/DEX combination had superior advantage than an agent use alone probably via synergistic anti-inflammatory activity.

NLRP3-inflammasome inhibition by MCC950 attenuates cardiac and pulmonary artery remodelling in heart failure with preserved ejection fraction

AimsThe purpose of this study was to evaluate the role of the NLRP3-inflammasome in heart failure with preserved ejection fraction (HFpEF). Main methodsSerum inflammatory cytokines were detected in patients with heart failure. Correlation analysis was performed to investigate the relationship between serum inflammatory cytokines and left ventricular diastolic function. A ‘two-hit’ (metabolic stress and mechanical stress) mouse model of HFpEF was established. Furthermore, MCC950 was used to determine the role of NLRP3-inflammasome inhibition in cardiac and pulmonary artery remodelling in HFpEF mice. Key findingsCompared with heart failure patients with reduced ejection fraction, patients with HFpEF have significantly elevated serum inflammatory cytokine levels. Serum NLRP3 and interleukin-1β levels were positively correlated with the diastolic function of HFpEF. In the HFpEF mouse model, the inhibition of the NLRP3-inflammasome by MCC950 improved exercise intolerance, glucose intolerance, and left ventricular diastolic function, but had no significant effect on systolic function. Meanwhile, MCC950 attenuated the release of inflammatory cytokines, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, the potential protective effects of MCC950 are achieved by inhibiting activation of the NLRP3-IL-1β pathway and cascade expansion of downstream inflammatory cytokines. Additionally, the inhibition of NLRP3-inflammasome by MCC950 reduced pulmonary artery pressure and improved pulmonary artery remodelling in HFpEF. SignificanceThe NLRP3-inflammasome plays a considerable role in inflammation and cardiac and pulmonary artery remodelling in HFpEF by activating the cascade reaction of inflammatory cytokines. This study is the first to comprehensively elucidate the role of the NLRP3-inflammasome in HFpEF, and will provide reference for future study.

Nanobody-based pannexin1 channel inhibitors reduce inflammation in acute liver injury

BackgroundThe opening of pannexin1 channels is considered as a key event in inflammation. Pannexin1 channel-mediated release of adenosine triphosphate triggers inflammasome signaling and activation of immune cells. By doing so, pannexin1 channels play an important role in several inflammatory diseases. Although pannexin1 channel inhibition could represent a novel clinical strategy for treatment of inflammatory disorders, therapeutic pannexin1 channel targeting is impeded by the lack of specific, potent and/or in vivo-applicable inhibitors. The goal of this study is to generate nanobody-based inhibitors of pannexin1 channels.ResultsPannexin1-targeting nanobodies were developed as potential new pannexin1 channel inhibitors. We identified 3 cross-reactive nanobodies that showed affinity for both murine and human pannexin1 proteins. Flow cytometry experiments revealed binding capacities in the nanomolar range. Moreover, the pannexin1-targeting nanobodies were found to block pannexin1 channel-mediated release of adenosine triphosphate. The pannexin1-targeting nanobodies were also demonstrated to display anti-inflammatory effects in vitro through reduction of interleukin 1 beta amounts. This anti-inflammatory outcome was reproduced in vivo using a human-relevant mouse model of acute liver disease relying on acetaminophen overdosing. More specifically, the pannexin1-targeting nanobodies lowered serum levels of inflammatory cytokines and diminished liver damage. These effects were linked with alteration of the expression of several NLRP3 inflammasome components.ConclusionsThis study introduced for the first time specific, potent and in vivo-applicable nanobody-based inhibitors of pannexin1 channels. As demonstrated for the case of liver disease, the pannexin1-targeting nanobodies hold great promise as anti-inflammatory agents, yet this should be further tested for extrahepatic inflammatory disorders. Moreover, the pannexin1-targeting nanobodies represent novel tools for fundamental research regarding the role of pannexin1 channels in pathological and physiological processes.Graphical

Modulation of the Cardiovascular Effects of Polycyclic Aromatic Hydrocarbons: Physical Exercise as a Protective Strategy.

Exposure to polycyclic aromatic hydrocarbons (PAHs) present in air pollution increases cardiovascular risk. On the contrary, physical exercise is a widely used therapeutic approach to mitigate cardiovascular risk, but its efficacy in an environment of air pollution, particularly with PAHs, remains unclear. This study investigates the effects of exercise on inflammation, endothelial dysfunction, and REDOX imbalance due to PAH exposure using a mouse model. Twenty male BALB/c mice were subjected to a mixture of PAHs (phenanthrene, fluoranthene, pyrene) in conjunction with aerobic exercise. The investigation evaluated serum levels of inflammatory cytokines, gene expression linked to inflammatory markers, endothelial dysfunction, and REDOX imbalance in aortic tissues. Furthermore, the study evaluated the expression of the ICAM-1 and VCAM-1 proteins. Exercise led to notable changes in serum inflammatory cytokines, as well as the modulation of genes associated with endothelial dysfunction and REDOX imbalance in aortic tissue. In turn, exercise produced a modulation in the protein expression of ICAM-1 and VCAM-1. The findings implicate the potential of exercise to counter PAH-induced damage, as demonstrated by changes in markers. In conclusion, exercise could mitigate the adverse effects related to exposure to PAHs present in air pollution, as evidenced by changes in inflammatory markers, endothelial dysfunction, and REDOX imbalance.

Determinants of serum cytokines in a population sample of healthy subjects from Iran

IntroductionCytokines are synthesized and released by immune system cells and mediate critical immune responses. Aging is associated with increased serum levels of some pro-inflammatory cytokines . A positive correlation between the concentration of several cytokines and blood pressure has been reported; higher cytokine concentrations may be related to the underlying causes of hypertension through the effects of inflammatory responses or as an independent etiology for hypertension .To assess the relationship between the serum levels of inflammatory cytokines and growth factors, with biochemical and anthropometric characteristics in healthy Iranian subjects.Material and methodsAnthropometric measurements and blood sampling were performed in 103 healthy Iranian participants. Fasting blood glucose (FBG), hs-CRP and lipid profile were measured in these participants. 12 serum cytokines/growth factors (MCP-1, TNF-α, EGF, IFN-γ, VEGF, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8 and IL-10 were measured.ResultsFBG was positively associated with serum IL-2, IL-4 and IL-1α (P = 0.044, &lt; 0.001 and = 0.017, respectively). Serum EGF and IL-4 were positively associated with age (P &lt; 0.001). IL-8 was inversely associated with SBP (P = 0.002) and gender (P = 0.028). There was a positive association between VEGF and HDL (P = 0.007). The serum levels of IFN-γ and TNF-α were positively associated with serum TG (P = 0.018 and 0.006, respectively).ConclusionsThere are associations between various pro-and anti-inflammatory cytokines in serum and several anthropometric measurements.

Activation of AHR by ITE improves cardiac remodelling and function in rats after myocardial infarction.

Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay; F4/80+ iNOS+ M1 macrophages and F4/80+ CD206+ M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P-Akt, p70S6K, P-p70S6K, Bcl-2, Bax, caspase-3, and cleaved caspase-3 protein levels were determined via Western blotting. We found that therapy with the AHR agonist ITE rescued cardiac remodelling and dysfunction in rats with MI and attenuated myocardial fibrosis, inflammation, and mitochondrial damage. Further studies confirmed that ITE dose-dependently improved myocardial cell apoptosis after MI, as demonstrated by reduced levels of the apoptosis-related proteins cleaved caspase-3 and Bax but increased expression levels of Bcl-2. These effects were attributed to ITE-induced activation of AHR receptors, leading to the down-regulation of Akt and p70S6K phosphorylation. The AHR agonist ITE alleviates cardiomyocyte apoptosis through the Akt/p70S6K signalling pathway, thereby rescuing left ventricular adverse remodelling and cardiac dysfunction after MI.

LncRNA CASC9 enhances the stability of SOCS-1 by combining with FUS to alleviate sepsis-induced liver injury

BackgroundLiver injury plays a major role in the development of sepsis. Liver damage after sepsis is an independent risk factor for multiple organ failure and death. Cancer susceptibility candidate 9 (CASC9) exerts a protective effect on sepsis-induced acute lung injury (ALI). However, the role and underlying mechanism haven’t been fully evaluated. MethodsAnimal and cell models of sepsis were established in vivo and in vitro experiments. The histological and apoptosis analyses of liver tissues were tested by hematoxylin–eosin (HE) staining and terminal dUTP nick end labeling (TUNEL) assay, respectively. Serum levels of inflammatory cytokines were detected via using an enzyme-linked immunosorbent assay (ELISA). The expressions of CASC9, suppressor of cytokine signaling (SOCS)-1, Bcl-2, Bax, Bad, and caspase3 were measured by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to examine cell viability and apoptosis, respectively. RNA immunoprecipitation (RIP) and RNA-pull down assay were used to verify the binding relationships among CASC9, SOCS-1 and FUS. ResultsCASC9 and SOCS-1 were lowly expressed in animal and cell models of sepsis liver injury. CASC9 or SOCS-1 overexpression could inhibit cell apoptosis upon lipopolysaccharide (LPS) induction. Meanwhile, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-8 were reduced by CASC9 or SOCS-1 overexpression in LPS-induced LO2 cells. Mechanistically, CASC9 interacted with fused in sarcoma (FUS) to stabilize the mRNA of SOCS-1. SOCS-1 silencing antagonized the effects of CASC9 on improving sepsis liver injury. ConclusionCASC9 overexpression ameliorated the sepsis-induced liver injury, and the probable underlying mechanism may be that CASC9 stabilized the SOCS-1 mRNA by interacting with FUS.

Taify Pomegranate Juice Extract Abrogates Testicular Dysfunction Induced by Acrylamide: Role of Inflammatory, Antioxidants, and Oxidative Stress Biomarkers

High altitude (HA) poses various dangers to living organisms, the most serious of which are oxidative stress and its accompanying metabolic problems, as well as hypoxia and its associated metabolic abnormalities. Acrylamide is a poisonous chemical produced under the oxidative stress as a result of intracellular reactive oxygen species formation and toxicity. Heating carbohydrates-rich meals give acrylamide that is widely used in the industry. The precise mechanism of acrylamide toxicity is unknown. The current study aimed to examine the impacts of Taify pomegranate juice (TPJ) from Taif area (Punica granatum L.) on acrylamide-induced testicular stress and dysfunction. Twenty four male of adult Wistar rats, were divided into four groups: Group 1 was a negative-control received only saline; Group 2 was a positive-control that received orally acrylamide (20 mg/kg/bw) for consecutive 4 weeks; and Group 3 received TPJ; 2 mL/kg/bw, orally for 4 weeks. Rats in Group 4 received pomegranate juice and acrylamide as described in Groups 2 and 3, with the TPJ delivered 1 week before the acrylamide. Acrylamide elevated serum levels of inflammatory cytokines (interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α)). Moreover, acrylamide decreased concentrations of follicle stimulating hormone (FSH), leutinizing hormone (LH), and testosterone and altered semen characteristics (decreased sperm viability and concentration, and increased sperm abnormalities). Acrylamide increased malondialdehyde levels (MDA), while it decreased antioxidant activities (superoxide dismutase; SOD and reduced glutathione; GSH). The inflammation associated cytokines were restored by TPJ administration to acrylamide rats. GSH and SOD were significantly recovered to near control levels in TPJ plus acrylamide group compared to acrylamide-administered rats. TPJ preadministration to rats restored semen profiles, alteration in testis pathology, and normalized the changes on the male reproductive hormones affected by acrylamide. Furthermore, the TPJ reversed the upregulation in caspases-3 and the decrease in B-cell lymphoma-2 (Bcl-2) gene expressions affected by acrylamide, with significant upregulation of hemoxygenase-1 (HO-1) and nuclear factor erythroid-2 (Nrf2) mRNA expression. These findings collectively revealed that TPJ possesses anti-inflammatory, potent antioxidant, and antiapoptotic effect against acrylamide-induced testicular damage.

Serum Inflammatory Cytokine Levels in Herpes Zoster Patients and Their Association with Postherpetic Neuralgia: A Prospective Study.

BACKGROUND This study aimed to investigate the serum levels of inflammatory cytokines in patients with herpes zoster (HZ) and to assess their correlation with the development of postherpetic neuralgia (PHN). Understanding this relationship may offer insight into the mechanisms of PHN and provide avenues for targeted treatment. MATERIAL AND METHODS We selected 169 patients diagnosed with HZ and 43 healthy controls (HCs) for the study. Serum levels of inflammatory cytokines were measured in all participants. Pain severity was evaluated using the visual analog scale (VAS). Based on follow-up data, the 169 HZ patients were categorized into 2 groups: those who developed PHN (HZ-PHN) and those who did not (HZ-Con). We then analyzed the differences in cytokine levels and their correlation with PHN development. RESULTS Compared to the HCs group, HZ patients exhibited a significant decrease in TNF-a levels and an increase in IL-10 levels (P<0.05, P<0.01). The VAS score was negatively correlated with TNF-alpha levels and positively correlated with IL-10 levels in HZ patients (r=-0.3081, P<0.01; r=0.5619, P<0.01). Distinctive levels of TNF-alpha, IL-6, IL-8, and IL-10 were observed among different pain groups (P<0.05, P<0.01). The HZ-PHN group showed lower TNF-alpha and higher IL-10 levels compared to the HZ-Con group (P<0.05, P<0.01). IL-10 level was identified as an independent risk factor for PHN, with a sensitivity and specificity of 76.4% and 54.3%, respectively. CONCLUSIONS Abnormal levels of inflammatory cytokines are present in HZ patients, and the IL-10 level may serve as a valuable indicator for predicting the risk of developing PHN.

Febuxostat alleviates Arsenic Trioxide-Induced renal injury in Rats: Insights on the crosstalk between NLRP3/TLR4, Sirt-1/NF-κB/TGF-β signaling Pathways, and miR-23b-3p, miR-181a-5b expression

Febuxostat (FBX), a xanthine oxidase inhibitor, is known to improve renal function and can show promise as a therapeutic agent for preventing drug-induced nephrotoxicity. This study aimed to explore the protective effect of FBX in preventing renal damage caused by arsenic trioxide (ATO) toxicity and uncover the underlying mechanisms. The researchers examined how FBX (10 mg/kg, orally) affected ATO-induced kidney injury (5 mg/kg, intraperitoneally) in rats. Kidney function and toxicity parameters in serum and oxidative stress biomarkers and inflammatory cytokine levels in renal tissue were measured. H&E staining was used to detect histopathological changes in the kidney. Network the molecular mechanisms of FBX in improving kidney injury were investigated using Western blotting and PCR techniques. The findings showed that FBX improved kidney function by inhibiting the pathological changes seen in H&E staining, decreasing levels of probed kidney function and toxicity measures in serum and tissue, and exhibiting antioxidant and anti-inflammatory effects. FBX decreased MDA, MPO, TNF-α, IL-1β, IL-6, COX-II, and NADPH oxidase levels, while increased GSH, GPx, SOD, and IL-10 levels. FBX also reduced the expression of NLRP3, ASC, TLR4, and micro-RNA 181a-5b while increased the expression of IKBα, Sirt-1, and micro-RNA 23b-3p, according to Western blotting and PCR results. In conclusion, FBX can play a vital role in reducing kidney injury in cases of ATO-induced nephrotoxicity, though more clinical research needs to be conducted.

Anti-Inflammatory Effects and Macrophage Activation Induced by Bioavailable Cinnamon Polyphenols in Mice.

Cinnamon is a commonly used spice and herb that is rich in polyphenols. Due to the limited bioavailability of oral polyphenols, it remains unclear to which extent they can reach cells and exert a biological effect. This study aims to investigate the impact of bioavailable cinnamon polyphenols on lipopolysaccharide (LPS)-stimulated macrophages. A polyphenol fraction is prepared from cinnamon (Cinnamomi ramulus) (CRPF) by boiling cinnamon in water and adsorbing the extract onto a hydrophobic resin. Mice are orally administered CRPF for 7 days and then subjected to three independent experiments: endotoxemia, serum collection, and macrophage isolation. Upon intraperitoneal lipopolysaccharide challenge, CRPF decreases serum levels of inflammatory cytokines, involving suppression of liver and spleen macrophages. When normal macrophages are cultured in serum obtained from CRPF-treated mice, they exhibit an anti-inflammatory phenotype. However, macrophages from CRPF-treated mice show an increased production of inflammatory cytokines when cultured in fetal bovine serum and stimulated with LPS. The study provides evidence for the presence of bioavailable cinnamon polyphenols with anti-inflammatory properties and macrophage activation. These findings suggest that cinnamon polyphenols have the potential to modulate macrophage function, which could have implications for reducing inflammation and improving immune function.

Observation of the Curative Effect of Recombinant Human Interferon α2b Gel Combined with LEEP Knife in Cervicitis Caused by IUD and The Effect of Copper/Low-Density Polyethylene Nanocomposite IUD

In this study, we explored the curative effect of recombinant human interferon α2b gel combined with a loop electrosurgical excision procedure (LEEP) knife to treat cervicitis. We also analyzed the clinical applications of a copper/low-density polyethylene nanocomposite intrauterine device (IUD). We selected 62 patients with IUD-induced cervicitis admitted to our hospital from March 2020 to December 2022 and divided them into experimental and control groups according to the random number table method (n = 31/group). The control group was treated with recombinant human interferon α2b gel only, while the experimental group was treated using a combination of the gel and LEEP knife. We compared the total efficacy rate of both treatments by recording the serum inflammatory cytokines levels, hospitalization, and vaginal drainage times before and after three months of treatment. We selected 50 married women of childbearing age who came to our hospital voluntarily to receive IUDs during the same period and randomly divided them into two groups (n = 25/group). Each group was administered either a copper/low-density polyethylene (Cu/LDPE) nanocomposite intrauterine device (IUD) or a TCu220C IUD. We conducted follow-ups at three, six, and 12 months after the implantation and analyzed the clinical and side effects. We observed that the total efficacy rate of the cervicitis treatment in the experimental group was 93%, 72% higher than in the control group. After six months of treatment, the tumor necrosis factor-α (TNF-α), hypersensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) levels, and the leukocyte counts of both groups were lower than that before treatment, with the test group showing lower values than the control group. Simultaneously, the hospitalization and vaginal discharge times of the experimental group were lower than those of the control group. We also followed up on the two different IUD groups after three, six, and 12 months. Compared with TCu220C IUD, the Cu/LDPE nanocomposite IUD group showed lesser side effects, such as uterine bleeding and abdominal pain. There was no significant difference between the hemoglobin levels of both groups before and after IUD insertion. In conclusion, recombinant human interferon α2b gel combined with a LEEP knife is effective in treating cervicitis patients and can control the levels of inflammatory factors in the body. This treatment was safer and quicker and shortened the vaginal discharge time. Additionally, the clinical acceptance of Cu/LDPE nanocomposite IUD for human intrauterine contraception is good due to the low occurrence of adverse reactions, such as uterine bleeding and pain. Therefore, it should be promoted in clinical gynecological practice.

Serum Inflammatory Cytokines and Growth Factors in Patients with Sjögren’s Syndrome and Diabetes Mellitus

Abstract Background/ Aims: Sjögren’s syndrome (SS) and diabetes mellitus (DM) are common causes of dry eye disease (DED) and autologous serum is used when artificial tears are not sufficient. Our aim was to compare serum growth factor and inflammatory cytokine levels of SS and DM patients with the healthy individuals. Methods: Twenty-three SS patients (mean age 52.70±7.55 years), 25 DM patients (mean age 56.68±6.53 years), and 23 healthy subjects (mean age 51.70±9.14 years) were included in the study. After detailed ophthalmological examination, Schirmer test, tear break-up time (TBUT) and Ocular Surface Disease Index (OSDI) scores were measured. Serum levels of six different proinflammatory interleukins (IL), five growth factors, matrix metalloproteinase-9, and fibronectin were measured by immunoassay. One-way ANOVA or Kruskal-Wallis tests and Dunn-Bonferroni post hoc analysis were used for comparison and p&amp;lt;0.05 was considered significant. Results: Schirmer test and TBUT were significantly lower in the SS group (2.08±1.72 mm/5 min and 3.08±2.08 s) than in the DR (10.24±4.63 mm/5 min and 4.20±3.09 s) and control groups (13.30±5.95 mm/5 min and 9.00±1.75 s) (p&amp;lt;0.001). Among the parameters studied, mean serum IL-23 level was significantly higher in the SS group (156.66±207.94 pg/mL) than in the DM and control groups (73.48±95.91 and 69.59±105.39 pg/mL, respectively) (p&amp;lt;0.05). Serum insulin-like growth factor 1 (IGF-1) level was lowest in DM patients (DM: 12.89±21.09, SS: 30.77±19.85, and control: 27.08±21.93 ng/mL) (p&amp;lt;0.05). Sjögren’s syndrome disease activity index (ESSDAI) showed a negative correlation with TBUT and a positive correlation with IL-1, IL-2 and fibronectin (p&amp;lt;0.005). Conclusions: Except IL-23 and IGF-1, the contents of serum obtained from patients with SS and DM are similar with the healthy individuals. Therefore, autologous serum seems to be a good option to replace deficient tear fluid in these subjects.

Highly proliferative and hypodifferentiated CAR-T cells targeting B7–H3 enhance antitumor activity against ovarian and triple-negative breast cancers

Chimeric antigen receptor (CAR)-T cell immunotherapy is highly effective against hematological neoplasms. However, owing to tumor variability, low antigen specificity, and impermanent viability of CAR-T cells, their use in the treatment of solid tumors is limited. Here, a novel CAR-T cell targeting B7–H3 and incorporating a 4-1BB costimulatory molecule with STAT3-and STAT5-related activation motifs was constructed using lentivirus transduction. B7–H3, a tumor-associated antigen, and its scFv antibody endowed CAR-T cells with tumor-specific targeting capabilities. Moreover, the integration of the trIL2RB and YRHQ motifs stimulated STAT5 and STAT3 in an antigen-dependent manner, inducing a remarkable increase in the proliferation and survival of CAR-T cells via the activation of the JAK-STAT signaling pathway. Besides, the proportion of less-differentiated T cells increased among BB-trIL2RB-z(YRHQ) CAR-T cells. Moreover, BB-trIL2RB-z(YRHQ) effectively inhibited ovarian cancer (OC) and triple-negative breast cancer (TNBC) in vivo at low doses, without high serum levels of inflammatory cytokines and organ toxicity. Therefore, our study proposes a combination of elements for the construction of superior pluripotent CAR-T cells to provide an effective strategy for the treatment of intractable solid tumors.

Co-occurrence of non-alcoholic steatohepatitis exacerbates psoriasis associated with decreased adiponectin expression in a murine model.

Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity. Here, we explored bidirectional causal linkages between NASH and psoriasis using a murine model. NASH was induced in mice by streptozotocin injection at 2 days of age and by high-fat diet feeding (STAM™ model). Psoriasis was induced by topical application of imiquimod (IMQ) on the ear. The severities of liver damage and psoriatic skin changes were determined using histological analysis. Gene expression in the skin tissues was evaluated using quantitative PCR analysis. Serum cytokine levels were determined using enzyme-linked immunosorbent assay. To examine the innate immune responses of normal human epidermal keratinocytes (NHEKs), the cells were treated with interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and AdipoRon, an adiponectin receptor agonist. There were no differences in the degree of liver tissue damage (fat deposition, inflammation, and fibrosis) between NASH mice with and those without psoriasis. Conversely, the co-occurrence of NASH significantly augmented psoriatic skin changes, represented by epidermal hyperplasia, in psoriatic mice. Pro-inflammatory cytokines were expressed in the inflamed skin of psoriatic mice, and the expression of genes, especially Il23a, Il1b, Il36g, and Mip2, was significantly upregulated by the co-occurrence of NASH. The expression of keratinocyte activation marker genes Defb4b and Krt16 was also upregulated by the co-occurrence of NASH. The serum TNF-α and IL-17 levels were increased by the co-occurrence of NASH and psoriasis. The serum adiponectin levels decreased in NASH mice compared with that in non-NASH mice. In NHEK culture, TNF-α and IL-17A synergistically upregulated CXCL1, CXCL8, and IL1B expression. The upregulated pro-inflammatory gene expression was suppressed by AdipoRon treatment, reflecting the anti-inflammatory capacity of adiponectin. The co-occurrence of NASH exacerbated psoriatic skin changes associated with increased serum inflammatory cytokine levels and decreased serum adiponectin levels. Combined with in vitro findings, increased inflammatory cytokine levels and decreased adiponectin levels likely promote innate immune responses in epidermal keratinocytes in psoriatic skin lesions. Overall, therapeutic intervention for co-occurring NASH is essential to achieve a favorable prognosis of psoriasis in clinical practice.

Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease.

Chronic colitis was induced in male Sprague Dawley rats via weekly administration of 2,4,6-trinitrobenzenesulfonic acid over 21 days following BMP7 or corticosteroid treatment for five days. The levels of serum and colon tissue inflammatory cytokines, RANKL/OPG system, as well as markers of macrophage polarization, were detected using RT-PCR, ELISA, or immunohistochemistry. Long bone and spine analyses were performed using microcomputed tomography (micro-CT). The administration of BMP7 reduced the adverse effects of colitis and led to elevated OPG and RANK in the colon with a simultaneous decrease in TNF-α and an increase in IL-10 and TGF-β. Decreased expression of the M2 macrophage marker CD163 was found in the BMP7-treated rats compared with the colitis group, whereas the number of M1 marker iNOS-positive cells did not differ between the groups. As a result of the BMP7 treatment, morphometric parameters of trabecular bone increased, and increased trabecular separation noted in the colitis group did not appear. We showed that BMP7 suppressed the inflammatory response in chronic colitis, mainly by shifting the cytokine balance and by triggering alterations in the RANKL/OPG system rather than through a macrophage polarization imbalance. In addition, considering the demonstrated effect of BMP7 on bone morphology and structure, it can be suggested that BMP7 plays a role in the managing of osteoporosis in chronic colitis, and thus, its therapeutic potential in the treatment of IBD should be further evaluated.

Omega-3 Polyunsaturated Fatty Acids Alleviate Intestinal Barrier Dysfunction in Obstructive Jaundice Rats.

Obstructive jaundice (OJ) can cause multiple pathophysiological consequences including intestinal barrier dysfunction. Omega-3 has been indicated to have a promising therapeutic effect on OJ. This study aimed to further investigate the functions of omega-3 on OJ-induced intestinal injury.A rat OJ model was established by bile duct ligation with or without omega-3 administration. ELISA was utilized for measuring serum levels of inflammatory cytokines. Hematoxylin-eosin staining and TUNEL staining were employed for detecting the morphological changes and cell apoptosis in rat intestine. Western blotting was utilized for evaluating expression of tight junction proteins in the intestinal tissues.Omgea-3 offset the reduction in body weight of OJ rats. Omega-3 alleviated inflammatory response, pathological damages and cell apoptosis in the intestine of OJ rats. Additionally, omega-3 enhanced levels of tight junction proteins in the intestinal tissues of OJ rats.Omega-3 ameliorates OJ-triggered impairment of intestinal barrier function in rats.