Comparing the Effectiveness and Safety of Dexamethasone, Methylprednisolone and Betamethasone in Lumbar Transforaminal Epidural Steroid Injections.

BACKGROUND: Particulate steroids are thought to exert their effects for long durations at injection sites. However, these types of steroids carry higher risks when used in epidural steroid injections. Catastrophic spinal cord complications, including sudden-onset paraplegia, have been reported due to intravascular particulate steroid preparations that cause embolisms and occlusion of blood vessels, resulting in spinal cord infarctions. Clinicians, therefore, recommend nonparticulate steroids to mitigate these adverse events. To our knowledge, this is the first retrospective study that addresses the effectiveness and safety of methylprednisolone, dexamethasone, and betamethasone when used in transforaminal epidural steroid injections (TFESIs) for the treatment of lumbar radiculopathy. OBJECTIVES: The primary goal of this study was to compare the proportion of patients who received injections of particulate steroids and required zero repeat injections within 12 months of their initial injection to the proportion of patients who received injections of nonparticulate steroids and also required zero repeat injections, as well as to compare the number of patients in the particulate cohort who required one or more repeat injections within 12 months of their initial injection to the number of patients in the nonparticulate cohort who required the same. The secondary goal was to evaluate the proportion of patients ultimately requiring surgery. STUDY DESIGN: This is a single-center, IRB-approved, retrospective study evaluating the safety and effectiveness of nonparticulate as compared to particulate steroid medications when used in TFESIs as minimally invasive treatments for chronic lumbar radiculopathy. SETTING: This study captured data (n = 1717) over a 4-year time frame (01/15/2018 to 01/15/2022). METHODS: The following data were collected from each patient's chart: age, gender, BMI, race, date of initial injection, number of repeat injections at the same lumbosacral level and on the same side within 12 months of the initial injection, and lumbar surgery date (if applicable). Inclusion criteria included: 1) having chronic low back pain of radicular etiology; 2) being at least 18 years old; 3) having experienced the failure of conservative therapy after 12 weeks (including physical therapy and/or medications); 4) having positive physical exam findings supporting nerve impingement (straight leg raise, slump test); and 5) showing lumbar MRI evidence of nerve impingement from disc herniation. Exclusion criteria included: 1) having received prior lumbar surgery at any level (L1-S1); 2) having been given prior TFESIs fewer than 6 months prior to initial injection; 3) having contracted a systemic infection at the proposed injection site; 4) undergoing active cancer treatment; and 5) having gotten any other spine injections. RESULTS: A significantly greater proportion of patients in the nonparticulate steroid cohort received 0 repeat injections (87.5% vs 71.4%, P < 0.001). The particulate steroid cohort demonstrated a significantly greater proportion of patients who received repeat injections within 12 months after the initial injections (12.5% vs 29.6%, P < 0.001). There were no significant differences among patients requiring surgery between the 2 cohorts. Other outcome measures included the identification of risk factors significantly associated with repeat injections. There was a statistically significant weak positive correlation between age and repeat injections (Pearson corr = 0.102; P < 0.001) and a weak negative correlation between ethnicity/race and repeat injections (point-biserial corr = -0.093; P < 0.001).  No adverse events were reported. LIMITATIONS: Not all clinicians included in this study used each of the 3 steroid types, and all clinicians used either particulate or nonparticulate steroids exclusively. CONCLUSIONS: Our study demonstrates that the clinical outcomes associated with TFESIs of nonparticulate steroids are superior to those associated with TFESIs of particulate steroids when either variety of medication is used to treat lumbar radiculopathy. This is the first study to include a clinically useful predictive model using information on laterality, age, and steroid type.

Co-administration of either curcumin or resveratrol with cisplatin treatment decreases hepatotoxicity in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Background: Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol. Materials and Methods: Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done. Results: Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues. Conclusion: Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Brazilin cream from Caesalpinia sappan inhibit periodontal disease: in vivo study.

Background: Gingivitis is an inflammation of the gums that is the initial cause of the development of periodontal disease by the activity of Nuclear Factor-kappa B (NF-κB), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), p38, and Tumor Necrosis Factor-α (TNF-α). Unaddressed chronic inflammation can lead to persistent disturbances in other parts of the body. Brazilin is a naturally occurring plant chemical that may have antibacterial and anti-inflammatory effects. Treatment based on the natural plant compound, brazilin, is developed in the form of a topical cream for easy application. Objective: The aim is to develop the natural compound brazilin in the form of a topical cream as an anti-inflammatory agent to reduce NF-κB expression through Imunohistochemistry (IHC) methods, and the expression of pro-inflammatory genes IL-1ß, IL-6, p38, and TNF-α. Methods: Male Sprague-Dawley rats were induced with gingivitis using P. gingivalis bacteria. The observed groups included rats treated with a single application of brazilin cream and rats treated with two applications of brazilin cream. The treatment was administered for 15 days. On days 3, 6, 9, 12, and 15, anatomical wound observations and wound histology using hematoxylin-eosin and Masson's Trichrome staining were performed. NF-κB protein expression was analyzed using the IHC method. Gingival inflammation gene expression of NF-κB, IL-1ß, IL-6, p38, and TNF-α was measured using q-RTPCR. Results: Single and double applications of brazilin cream increased angiogenesis and decreased NF-κB protein expression, in addition to the IL-1ß, IL-6, p38, and TNF-α gene expressions. Conclusion: In a rat gingivitis model, Brazilin cream may function as an anti-inflammatory agent in the gingival tissue.

Neohesperidin Dihydrochalcone Ameliorates Experimental Colitis via Anti-Inflammatory, Antioxidative, and Antiapoptosis Effects.

Neohesperidin dihydrochalcone (NHDC) is a citrus-originated, seminatural sweetener. There is no investigation concerning the effect of NHDC on ulcerative colitis. The purpose of this study was to determine the therapeutic and protective effects of NHDC in Wistar Albino rats. NHDC was given for 7 days after or before colitis induction. The results showed that NHDC significantly reduced the interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels. Catalase levels did not show a significant difference between the groups. NHDC provided a remarkable decrease in the expression levels of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κB). Total antioxidant status (TAS) levels were significantly elevated in NHDC treatment groups, while total oxidant status (TOS) and oxidative stress index (OSI) levels were significantly decreased. NHDC provided remarkable improvement in histological symptoms such as epithelial erosion, edema, mucosal necrosis, inflammatory cell infiltration, and hemorrhage. Also, caspase-3 expression levels were statistically decreased in NHDC treatment groups. The results indicated that NHDC might be a protection or alternative treatment for ulcerative colitis.

Preoperative high dose of dexamethasone in emergency laparotomy: randomized clinical trial.

BACKGROUND: Patients undergoing emergency laparotomy present with a profound inflammatory response, which could be an independent pathophysiological component in prolonged recovery. The aim of this study was to investigate the effects of a single preoperative high dose of intravenous dexamethasone on the inflammatory response and recovery after emergency laparotomy. METHODS: In this double-blinded placebo-controlled trial, patients were prospectively stratified according to surgical pathology (intestinal obstruction and perforated viscus) and randomized to preoperative 1 mg/kg dexamethasone or placebo at a ratio of 1 : 1. The primary outcome was C-reactive protein on postoperative day 1. Secondary outcomes were postoperative recovery, morbidity, and mortality. RESULTS: A total of 120 patients were included in the trial. On postoperative day 1, the C-reactive protein response was significantly lower in the dexamethasone group (a median of 170 versus 220 mg/l for dexamethasone and for placebo respectively; P = 0.015; mean difference = 49 (95% c.i. 13 to 85) mg/l) and when stratified according to intestinal obstruction (a median of 60 versus 160 mg/l for dexamethasone and for placebo respectively; P = 0.002) and perforated viscus (a median of 230 versus 285 mg/l for dexamethasone and for placebo respectively; P = 0.035). Dexamethasone administration was associated with improved recovery (better haemodynamics, better pulmonary function, less fatigue, and earlier mobilization). Furthermore, the dexamethasone group had a lower 90-day mortality rate (7% versus 23% for dexamethasone and for placebo respectively; relative risk 0.33 (95% c.i. 0.11 to 0.93); P = 0.023) and a decreased incidence of postoperative major complications (27% versus 45% for dexamethasone and for placebo respectively; relative risk 0.62 (95% c.i. 0.37 to 1.00); P = 0.032). CONCLUSION: A single preoperative high dose of intravenous dexamethasone significantly reduces the inflammatory response after emergency laparotomy and is associated with enhanced recovery and improved outcome. REGISTRATION NUMBER: NCT04791566 (http://www.clinicaltrials.gov).

Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization.

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin ß1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

Unlocking the power of polyphenols: A promising biomarker of improved metabolic health and anti-inflammatory diet in adolescents.

BACKGROUND: Metabolic syndrome (MetS) in adolescence is a risk factor for future cardiovascular disease. The chronic inflammation associated with MetS can be attenuated by the anti-inflammatory effect of polyphenols. We aimed to evaluate total urinary polyphenols as a biomarker of anti-inflammatory diets and their effect on MetS in adolescents. METHODS: In this retrospective analysis of a longitudinal cohort study, the relationship between total polyphenol excretion (TPE) in urine, the inflammatory potential of the diet measured through the Children's Dietary Inflammatory Index (C-DII), and the presence of metabolic syndrome was evaluated. The study population consisted of adolescents enrolled in the SI! Program for Secondary Schools trial, who had completed all the study forms and provided urine samples at baseline and at the two-year follow-up. Multivariate linear regression and multinominal logistic regression models were generated to evaluate the relationship of changes in TPE with changes in the C-DII score and changes in MetS status, respectively. An analysis of the ROC curve was performed to assess the potential of TPE as a biomarker of an anti-inflammatory diet. RESULTS: This study included 662 adolescents, 51.2% were males, and 48.8% were females, with a mean age of 12 (0.38) years at baseline. The relationship between changes in TPE and changes in the C-DII score was stratified by sex with a p-value <0.001 for the interaction. TPE and C-DII were inversely associated in males (-0.13 mg GAE/g creatinine [-0.26; -0.01] per 1-SD increase, p-value = 0.037). In addition, an increase in changes in TPE levels were associated with a reversal in MetS status in all adolescents (1.30 [1.27; 1.34] per 1-SD increase, p-value<0.001). The ROC curve showed that urinary TPE levels can predict dietary inflammatory potential with an AUC = 0.793 (0.725; 0.863) in males. CONCLUSION: Polyphenols excreted in urine are a potential biomarker of anti-inflammatory diets in males and are associated with a reversal of MetS status in adolescents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03504059, https://clinicaltrials.gov/study/NCT03504059.

Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Nanogel in a Complete Freund's Adjuvant-Induced Rheumatoid Arthritis Rat Model: Anti-Arthritic, Anti-Inflammatory, and Antioxidative Activity.

Lingzhi or reishi mushroom, Ganoderma lucidum, is a medicinal mushroom quite widely developed as herbal medicine because it has acted as an anticancer, antitumor, antioxidant, and anti-inflammatory. The active mycochemical compounds of G. lucidum mushrooms, such as flavonoids and polysaccharides, can suppress the release of pro-inflammatory cytokines and prevent lipid peroxidation due to oxidative stress. Rheumatoid arthritis (RA) is an autoimmune disease where the exact cause is unknown, and RA prevalence continues to increase yearly. In patients with RA, joint damage and inflammation occur. This study aims to evaluate the effectiveness of G. lucidum nanogels as anti-arthritis, anti-inflammatory, and antioxidative. The research method was a true experiment using a control group and treatment group that randomly assigned, using 24 male Wistar rats (Rattus norvegicus) induced with complete Freund's adjuvant (CFA) 0.1 mL. The rats were divided into six groups; healthy control/HCt (did not receive the treatment), negative control/NCt (induced by CFA), and positive control/PCt (given 0.012 diclofenac sodium). TG1 (given 250 mg G. lucidum nanogels), TG2 (given 500 mg G. lucidum nanogels), TG3 (given 750 mg G. lucidum nanogels). IgG, eNOS, IL-1ß, COX-2, NOS, TNF-α, and IL-6 parameters were measured using ELISA, and the data obtained were analyzed by one-way ANOVA using SPSS (P < 0.05). The results showed that administering G. lucidum nanogels significantly reduced IgG, NOS, TNF-α, COX-2, IL-1ß, and IL-6 and increased eNOS levels. The anti-inflammatory and antioxidative activities in suppressing pro-inflammatory cytokines and increasing eNOS levels prove that the nanogel extract G. lucidum have the potential to be developed as anti-arthritis natural therapeutic.

Coordinating Macrophage Targeting and Antioxidation by Injectable Nanocomposite Hydrogel for Enhanced Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA), an immune-mediated inflammatory disease, is characterized by a large number of infiltrated immune cells and abnormally elevated reactive oxygen species (ROS) in the joint. Various proinflammatory factors secreted by macrophages and the elevated ROS by inflammatory cells are deeply intertwined and together contribute to joint damage. Targeted and sustained anti-inflammation and antioxidation strategies are needed for RA treatment. To alleviate the oxidative stress and target the source of inflammatory cytokines, we developed a thermosensitive injectable hydrogel, Dex-DSLip/Cro@Gel, to coordinate the targeted anti-inflammatory and antioxidation effects. Within the injectable gel, dexamethasone (Dex)-loaded liposomes (Dex-DSLip), modified with dextran sulfate (DS), target macrophages via interaction with scavenger receptor A (SR-A). Simultaneously, crocin I (Cro) is loaded in the gel with a high loading capacity. The porous structure of Dex-DSLip/Cro@Gel successfully prolongs the retention time of both drugs and sustains the release of Dex and Cro. After intra-articular injection of Dex-DSLip/Cro@Gel in RA rats, the expression of inflammatory factors in the ankle joints was significantly reduced. Joint erythema and bone erosion were markedly alleviated. Through the synergistic effects of Dex and Cro, Dex-DSLip/Cro@Gel demonstrates targeted anti-inflammatory and antioxidation effects as well as mitigated bone erosion and long-term therapeutic effects for RA. This thermosensitive injectable nanocomposite hydrogel synergizes anti-inflammatory and antioxidation effects and targets the microenvironment in the joint, offering a new approach for RA treatment.

Retroductal dexamethasone administration promotes the recovery from obstructive and inflammatory salivary gland dysfunction.

Introduction: Salivary gland dysfunction, often resulting from salivary gland obstruction-induced inflammation, is a prevalent condition. Corticosteroid, known for its anti-inflammatory and immunomodulatory properties, is commonly prescribed in clinics. This study investigates the therapeutic implications and potential side effects of dexamethasone on obstructive sialadenitis recovery using duct ligation mice and salivary gland organoid models. Methods: Functional and pathological changes were assessed after administering dexamethasone to the duct following deligation 2 weeks after maintaining ligation of the mouse submandibular duct. Additionally, lipopolysaccharide- and tumor necrosis factor-induced salivary gland organoid inflammation models were established to investigate the effects and underlying mechanisms of action of dexamethasone. Results: Dexamethasone administration facilitated SG function restoration, by increasing salivary gland weight and saliva volume while reducing saliva lag time. Histological evaluation revealed, reduced acinar cell atrophy and fibrosis with dexamethasone treatment. Additionally, dexamethasone suppressed pro-inflammatory cytokines IL-1ß and TNF expression. In a model of inflammation in salivary gland organoids induced by inflammatory substances, dexamethasone restored acinar markers such as AQP5 gene expression levels, while inhibiting pro-inflammatory cytokines TNF and IL6, as well as chemokines CCL2, CXCL5, and CXCL12 induction. Macrophages cultured in inflammatory substance-treated media from salivary gland organoid cultures exhibited pro-inflammatory polarization. However, treatment with dexamethasone shifted them towards an anti-inflammatory phenotype by reducing M1 markers (Tnf, Il6, Il1b, and Cd86) and elevating M2 markers (Ym1, Il10, Cd163, and Klf4). However, high-dose or prolonged dexamethasone treatment induced acino-ductal metaplasia and had side effects in both in vivo and in vitro models. Conclusions: Our findings suggest the effectiveness of corticosteroids in treating obstructive sialadenitis-induced salivary gland dysfunction by regulating pro-inflammatory cytokines.

Could Photobiomodulation help lactating women and their newborns?

During the first several weeks following lactation, nipple pain frequently prevents mothers from continuing breastfeeding. To evaluate the efficacy of using Photobiomodulation (PBM) versus anti-inflammatory topical cream, on inflamed nipple, and the effect on milk production. This study was carried-out on 50 breastfeeding women with nipple pain and fissure. Our patients were divided into two groups ; study group (Group I): 25 patients received 12 sessions of PBM using Diode laser for a period of 4 weeks, 3 sessions per week every alternative day, and controlled group (Group II): 25 patients used Anti-inflammatory topical cream. Regarding inflammatory signs in both groups, Group I showed a significant decrease in redness compared to Group II at the 3rd and 4th week, and a significant decrease in nipple fissure and pain at the 3rd week. There was a significant increase in milk amount reflected on the infant's weight. We concluded that PBM was more effective in decreasing nipple pain, inflammation and subsequently milk production and infant weight than topical anti-inflammatory creams.

Medicinal Anti-Inflammatory Patch Loaded with Lavender Essential Oil.

Transdermal drug delivery offers a promising alternative for administering medications like ibuprofen, known for its analgesic and anti-inflammatory properties, with reduced gastrointestinal side effects compared to oral administration. This study explored the potential synergistic effects of combining ibuprofen with lavender essential oil (LEO) in transdermal patches. The composition of LEO was analyzed, revealing predominant compounds such as linalyl acetate and linalool, which are known for their analgesic and anti-inflammatory properties. The physicochemical properties of the patches were investigated, indicating improved cohesion with the addition of LEO. Additionally, thermal stability assessments demonstrated enhanced stability with LEO incorporation with an increase in onset decomposition temperature from 49.0 to 67.9 °C. The antioxidant activity of patches containing LEO was significantly higher with a free radical scavenging ability of 79.13% RSA compared to 60% RSA in patches without LEO. Release and permeation studies showed that patches with LEO exhibited an increased permeation of ibuprofen through the skin with 74.40% of the drug released from LEO-containing patches compared to 36.29% from patches without LEO after 24 h. Moreover, the permeation rate was notably faster with LEO, indicating quicker therapeutic effects. The inclusion of LEO in transdermal patches containing ibuprofen holds promise for enhancing drug delivery efficiency and therapeutic effectiveness, offering a potential strategy for improved pain management with reduced side effects.

The hemostatic and anti-inflammatory effects of intravenous single-dose of tranexamic acid in double-segment posterior lumbar interbody fusion: a case control study.

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.

Lutein, zeaxanthin, and meso-zeaxanthin supplementation attenuates inflammatory cytokines and markers of oxidative cardiovascular processes in humans.

BACKGROUND AND AIMS: Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the vascular endothelium has been hypothesized to be an initial step in the formation of atherosclerotic plaques, with inflammatory cytokines serving as the signaling mechanism for concomitant macrophage activation. Supplementation with the antioxidative macular xanthophylls (lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]) has been shown to aid in the reduction of inflammatory physiologic responses; therefore, we hypothesized that in our study population, supplementation with these xanthophylls would facilitate a systemic reduction in markers of inflammation and cardiovascular lipid oxidation. METHODS AND RESULTS: In this double-blind placebo-controlled supplementation study, participants were randomly allocated to receive the active intervention containing L (10 mg) + MZ (10 mg) + Z (2 mg) or placebo (containing sunflower oil). Serum concentrations of carotenoids (assessed by HPLC), inflammatory cytokines (IL-6, IL-1ß, TNF-α) and oxidized LDL (OxLDL; by solid-phase sandwich ELISA) were measured at baseline and at 6-months. Results showed that over the supplementation period, compared to placebo, the active group demonstrated statistically significant increases in serum concentrations of L, Z, & MZ (p < 0.05), reductions in inflammatory cytokines IL-1ß (p < 0.001) and TNF-α (p = 0.003), as well as a corresponding reduction in serum OxLDL (p = 0.009). CONCLUSIONS: Our data show that L, Z, & MZ supplementation results in decreased serum IL-1ß, TNF-α, and OxLDL. This suggests that these carotenoids are acting systemically to attenuate oxidative lipid products and inflammation, thus reducing their contribution to atherosclerotic plaque formation.

LEKTI domain 6 displays anti-inflammatory action in vitro and in a murine atopic dermatitis model.

BACKGROUND: Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a serine protease inhibitor consisting of multiple domains. A loss of function mutation is described in Netherton patients that show severe symptoms of atopic lesions and itch. OBJECTIVES: LEKTI domain 6 (LD6) has shown strong serine protease-inhibitory action in in vitro assays and thus it was tested in vitro and in vivo for potential anti-inflammatory action in models of atopic skin disease. METHODS: Human skin equivalents were treated with LD6 and an inflammatory reaction was challenged by kallikrein-related endopeptidase 5 (KLK5). Furthermore, LD6 was tested on dorsal root ganglia cells stimulated with KLK5, SLIGRL and histamine by calcium imaging. The effect of topically administered LD6 (0.4-0.8%) in lipoderm was compared to a topical formulation of betamethasone-diproprionate (0.1%) in a therapeutic setting on atopic dermatitis-like lesions in NC/Nga mice sensitized to house dust mite antigen. Endpoints were clinical scoring of the mice as well as determination of scratching behaviour. RESULTS: KLK5 induced an upregulation of CXCL-8, CCL20 and IL-6 in skin equivalents. This upregulation was reduced by pre-incubation with LD6. KLK5 as well as histamine induced calcium influx in a population of neurons. LD6 significantly reduced the calcium response to both stimuli. When administered onto lesional skin of NC/Nga mice, both LD6 and betamethasone-dipropionate significantly reduced the inflammatory reaction. The effect on itch behaviour was less pronounced. CONCLUSION: Topical administration of LD6 might be a new therapeutic option for treatment of lesional atopic skin.

Topical application of Artemisia annua L. essential oil ameliorates 2,4-dintrochlorobenzene-induced atopic dermatitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Volatile oil is widely used in traditional Chinese medicine owing to its unique hydrophobic and lipophilic properties and rapid skin absorption. Artemisia annua L. (A.annua) essential oil (AAEO), a volatile oil extracted from A. annua, exhibits anti-inflammatory properties. However, few studies have investigated its effects on skin inflammation. AIM OF THE STUDY: To investigate and elucidate the mechanisms of action of AAEO in the treatment of atopic dermatitis (AD). MATERIALS AND METHODS: Network pharmacology was used to predict the targets and pathways of AAEO for the treatment of AD. The AD mouse model was established by topical application of 2,4-dintrochlorobenzene (DNCB), AAEO, and the positive control drug hydrocortisone butyrate cream (HBC). We evaluated the symptoms of AD, SCORAD scores, histological analysis, and serum IgE and TNF-α levels in mice. Immunofluorescence, western blotting, and qPCR were used to investigate the signaling pathways. RESULTS: Network pharmacology analysis indicated that AAEO may exert its effects via the MAPK/NF-κB signaling pathway. Animal experiments demonstrated that topical application of AAEO and HBC significantly ameliorated skin lesions, reduced dermatitis score, and decreased spleen weight compared to DNCB treatment. AAEO reduced skin epidermal thickness and mast cell infiltration. DNCB markedly reduced the protein levels of filaggrin (FLG) and loricrin (LOR), whereas AAEO reversed these changes. Notably, the 5% concentration of AAEO demonstrated substantial improvement in skin barrier function. Compared to the DNCB group, the levels of FLG and LOR remained almost unchanged following HBC treatment. DNCB markedly elevated IgE and TNF-α levels, which were reversed by AAEO and HBC treatment. Among the inflammatory cytokines, DNCB increased mRNA expression of TNF-α, IL-1ß, and IL-6, however, it reduced IL-10, with AAEO and HBC reversing these changes to various degrees. Additionally, DNCB-induced ERK, JNK, and P38 phosphorylation, associated with the upregulation of phosphorylation of NF-κB, whereas, AAEO and HBC exhibited potent inhibition of the MAPK/NF-κB signaling pathway. CONCLUSIONS: This study systematically demonstrated the possible therapeutic effects and mechanisms of AAEO in AD via network pharmacological analysis and experimental confirmation. These results revealed that topical application of AAEO can suppress skin inflammation and restore skin barrier function. These findings provide the potential application of AAEO in synthesizing external preparations for both pharmacological and cosmetic industries.

Local delivery of methotrexate/glycyrrhizin-loaded hyaluronic acid nanofiber for the management of oral cancer.

The challenges in treating oral cancer include the limited effectiveness and systemic side effects of conventional chemotherapy and radiation therapy. Hyaluronic acid (HA) based Glycyrrhizin (GL) and Methotrexate (MT) loaded localized delivery systems, specifically nanofiber (NF) based platforms, were developed to address these challenges. The electrospinning method was used for the successful fabrication of a homogenous NF membrane and characterized for morphology, drug entrapment efficiency, tensile strength, and ex-vivo mucoadhesive study. Also, it was evaluated for in-vitro drug release profile, ex-vivo drug permeability, in-vitro anti-inflammatory, apoptosis assay by MTT and flow, and against specific cell lines in order to determine their potential for therapeutic use. Superior tensile breaking force (50 g), mucoadhesive strength of 153 gm/cm2, drug permeability, and releasing properties of designed NF, making them perfect requirements for oral cavity delivery. The anticancer potential of MT in the MTT assay and flow cytometry analysis was significantly increased in oral epidermal carcinoma cell (KB cell) for drug-loaded NF with 63.97 ± 1.99 % apoptosis, at 24 h. With these incorporated, GL with MT in NF had an anti-inflammatory potential, also demonstrated in-vitro and in-vivo. In the Ehrlich Ascites Carcinoma (EAC) induced mice model, the optimal formulation's shows better potential for tumor regression when comparing the developed NF formulation to the drugs. Experimental results show that by lowering mucositis-related inflammation and enhancing the effectiveness of oral cancer treatment, a developed nanofiber-based local drug delivery system offers a feasible strategy for managing oral cancer.

Dexmedetomidine Attenuates Inflammation in Elderly Patients Following Major Hepatobiliary and Pancreatic Surgery: A Randomized Clinical Trial.

Background: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury. Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery. Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China. Patients: 86 patients aged 60-75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio. Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 µg kg-1 for 10 min, followed by 0.5 µg kg-1 hr-1 for maintenance until the end of surgery. Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes. Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P<0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups. Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs. Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.

The effect of a selenium-based anti-inflammatory strategy on postoperative functional recovery in high-risk cardiac surgery patients - A nested sub-study of the sustain CSX trial.

AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

Fabrication and characterization of thin self-rolling film for anti-inflammatory drug delivery.

Thin films have been identified as an alternative approach for targeting sensitive site as drug delivery tool. In this work, the preparation of self-rolling thin films to form tubes for wound healing and easy placement (e.g. in the colon via colonoscopy) have been studied. We explored the use of thin films as a protective dressing combined to local release of an anti-inflammatory in order to improve drug efficacy and limit the side effects of the oral route. Non-cytotoxic poly(ethylene) glycol and poly(lactic acid) photo-crosslinkable star copolymers were used for rapid UV crosslinking of bilayered films loaded with prednisolone. The films, crosslinked under UV lamp without the need of photoinitiator, are optimized and compared in terms of water uptake, swelling ratio, final tube diameter and morphology, anti-inflammatory drug loading and release. Our studies showed the spontaneous rolling of bilayer constructs directly after immersion in water. Tubular geometry allows application of the patch through minimally invasive procedures such as colonoscopy. Moreover, the rolled-up bilayers highlighted efficient release of encapsulated drug following Fickian diffusion mechanism. We also confirmed the anti-inflammatory activity of the released anti-inflammatory drug that inhibits the pro-inflammatory cytokine IL-1ß in RAW 264.7 macrophages stimulated by Escherichia coli (E. coli).