Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease), duration (transient versus chronic), and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to ad libitum access to food or fasted for 24 h prior to 0 (control), 10, or 100, 1.5 mA-5 s intermittent, inescapable tail shocks (IS). Glucose, nonesterified free fatty acids (NEFAs), insulin, leptin, and corticosterone were measured in plasma and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and IL-10 in plasma, and subcutaneous, intraperitoneal, and visceral compartments of white adipose tissue (WAT). In control rats, a 24 h fastreduced all measured basal cytokines in plasma and visceral WAT, IL-1β and IL-6 in subcutaneous WAT, and IL-6 in intraperitoneal WAT. In stressed rats (IS), fasting reduced visceral WAT TNF-α, subcutaneous WAT IL-1β, and plasma insulin and leptin. Short-term fasting may thus prove to be a usefuldietary strategy for reducing peripheral inflammatory states associated with visceral obesity and chronic stress.

BACKGROUND:It is important to manage inflammation after craniotomy. It may be prudent to reduce the excessive usage of antibiotics and to add supplementary treatments like acupuncture, which would be effective and safe. However, there are only a few studies available to date on the effects of acupuncture on anti-inflammatory response after craniotomy. The aim of this study was to explore the anti-inflammatory effects of acupuncture in patients after a craniotomy.

METHODS:This study was a single-center, prospective, open-label, controlled trial. Forty-four subjects who underwent craniotomy for an unruptured aneurysm, facial spasm, or brain tumor were allocated to either an acupuncture group or a control group. Both groups received postoperative routine care in the Department of Neurosurgery. The subjects in the acupuncture group also received a total of 6 acupuncture treatments sessions within 8 days after craniotomy. Acupuncture treatments included acupuncture, electroacupuncture, and intradermal acupuncture. The serum interleukin (IL)-1β and IL-6, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate levels were assessed four times within 7 days after surgery. The presence of fever, use of additional antibiotics, presence of infection including pneumonia or urinary tract infection, and safety were also reviewed.

RESULTS:The IL-1β levels of subjects who underwent aneurysmal clipping were significantly lower in the acupuncture group (P = .02). TNF-α levels of subjects who underwent aneurysmal clipping at the seventh postoperative day were also significantly lower in the acupuncture group (P = .03). Six cases of fever of unknown origin were observed in the control group, while none were seen in the acupuncture group, revealing that the incidence of fever was significantly lower in the acupuncture group (P = .02). No adverse events occurred during the trial.

CONCLUSION:Acupuncture showed a possibility of alleviating inflammation by attenuating the levels of proinflammatory cytokines and significantly reduced the incidence of fever of unknown origin in patients after craniotomy. Acupuncture would be suitable as an adjunctive therapy to alleviate inflammation after craniotomy.

AIM:Our main objective was to determine the effect of ascorbate supplementation in mice unable to synthesize ascorbic acid (gulo KO) when challenged with murine B16FO cancer cells.

METHODS:Gulo KO female mice 36-40 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to subcutaneous injection of 2.5×10(6) B16FO murine melanoma cells in the right flank of mice. A control group of wild type mice were also injected with the melanoma cells and maintained on a regular murine diet. Mice were continued on their respective diets for another 2 weeks after injection. The mice were then sacrificed, blood was drawn and their tumors were measured, excised and processed for histology.

RESULTS:Mean weight of animals decreased significantly (30%, p<0.0001) in the ascorbate-restricted group but increased slightly, but insignificantly, in the ascorbate-supplemented group. The mean tumor weight in ascorbate supplemented mice was significantly reduced (by 64%, p = 0.004) compared to tumor weight in ascorbate-deprived gulo mice. The mean tumor weight of wild type mice did not differ significantly from the ascorbate-supplemented mice. Gulo KO mice supplemented with ascorbate developed smaller tumors with more collagen encapsulation and fibrous capsule interdigitation, while gulo KO mice deprived of ascorbate hosted large tumors with poorly defined borders, showing more necrosis and mitosis. Ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine IL-6 (90% decrease, p = 0.04) and IL-1β (62% decrease) compared to the levels in gulo KO mice deprived of ascorbate.

CONCLUSION:Ascorbate supplementation modulated tumor growth and inflammatory cytokine secretion as well as enhanced encapsulation of tumors in scorbutic mice.

OBJECTIVE: To test whether breastfeeding's protection against anorectic responses to infection is mediated by n-3 fatty acids' attenuation of interleukin (IL)-1beta and tumor necrosis factor (TNF)alpha.

DESIGN: Experimental and observational studies.

SETTING: A hospital-based study was conducted. SUBJECTS: Five groups of infants were followed; three in the experimental and two in the observational study.

METHODS: Breast-fed- (BF-1), DHA-supplemented formula- (SFF-1), and non-DHA-supplemented formula-fed (FF-1) infants were studied before and after immunization against diphtheria, tetanus, pertussis and haemophilus influenzae type b. Pre- and post-immunization energy intakes (EI) and serum IL-1beta and TNFalpha were measured. The two other groups, breast-fed (BF-2) and formula-fed (FF-2) infants with pneumonia were followed throughout hospitalization. EI, IL-1beta and TNFalpha were measured at admission and discharge. Baseline erythrocyte fatty acid contents were determined.

RESULTS: Both cytokines increased following immunization in all feeding groups. Post-immunization reductions in EI of SFF-1 infants (-11.8+/-5%, CI(95)=-23.3, 1.4%, P=0.07) were intermediate to those observed in BF-1 (-5.2+/-4.2%, CI(95)=-15.2, 5.9%, P=0.27) and FF-1 infants (-18+/-4.4%, CI(95)=-29%, -5.4%, P=0.02). In the observational study, TNFalpha (17.2+/-8.3 vs 3.4+/-3.0 ng/l, P=0.001) and decreases in EI (-31+/-43 vs -15+/-31%, CI(95)=-34%, 0.001%, P=0.056) were greater in FF-2 than in BF-2 infants at admission. Breastfeeding duration was associated positively with docosahexaenoic acid (DHA) erythrocyte contents, and negatively with admission TNFalpha. Decreases in EIs were associated with IL-1beta and TNFalpha concentrations.

CONCLUSION: Reductions in EI following immunologic or infectious stimuli were associated with increases in IL-1beta and TNFalpha. Those reductions were attenuated by breastfeeding, and mediated in part by tissue DHA.

Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. However, the mechanisms of these effects are not completely understood. Using the BV-2 mouse microglial cell line and lipopolysaccharide (LPS) to induce an inflammatory response, we studied the signaling pathways engaged in the anti-inflammatory effects of cannabinoids as well as their influence on the expression of several genes known to be involved in inflammation. We found that the two major cannabinoids present in marijuana, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), decrease the production and release of proinflammatory cytokines, including interleukin-1beta, interleukin-6, and interferon (IFN)beta, from LPS-activated microglial cells. The cannabinoid anti-inflammatory action does not seem to involve the CB1 and CB2 cannabinoid receptors or the abn-CBD-sensitive receptors. In addition, we found that THC and CBD act through different, although partially overlapping, mechanisms. CBD, but not THC, reduces the activity of the NF-kappaB pathway, a primary pathway regulating the expression of proinflammatory genes. Moreover, CBD, but not THC, up-regulates the activation of the STAT3 transcription factor, an element of homeostatic mechanism(s) inducing anti-inflammatory events. Following CBD treatment, but less so with THC, we observed a decreased level of mRNA for the Socs3 gene, a main negative regulator of STATs and particularly of STAT3. However, both CBD and THC decreased the activation of the LPS-induced STAT1 transcription factor, a key player in IFNbeta-dependent proinflammatory processes. In summary, our observations show that CBD and THC vary in their effects on the anti-inflammatory pathways, including the NF-kappaB and IFNbeta-dependent pathways.

The purpose of the present study was to find out whether co-treatment of human neutrophils with high glucose and methylglyoxal (MGO) can alter the biochemical parameters of human neutrophils. We also examined if astaxanthin associated with vitamin C can improve those biochemical parameters. Neutrophils from healthy subjects were treated with 20 mM of glucose and 30μM MGO followed or not by the addition of the antioxidants astaxanthin (2 μM) and vitamin C (100 μM). MGO/high glucose treatment reduced the phagocytic capacity and the G6PDH, total/SOD and GR activities. Additionally, there was an increase in the activity of myeloperoxidase (MPO) with consequentincrease in the hypochlorous acid production, CAT activity and in the release of IL-6 cytokine without changes in intracellular calcium mobilization. Our study also shows that the association of astaxanthin with vitamin C greatly improved neutrophil phagocytic capacity, decreasing all reactive oxygen species measured, pro-inflammatory IL-1β and TNF-α release, MPO activity and HClO production. The combination of astaxanthin with vitamin C alone has more antioxidant and anti-inflammatory effects than when they were in the presence of MGO/high glucose. Injury to the function of neutrophils dueto high glucose and methylglyoxal appears not to involve oxidative stress or calcium release. The association of antioxidants astaxanthin and vitamin C promoted a significant improvement in the function of neutrophils and in the redox status.

Cinnamaldehyde, a bioactive component of cinnamon, is increasingly gaining interest for its preventive and therapeutic effects against metabolic complications like type-2 diabetes. This study is an attempt to understand the effect of cinnamaldehyde in high-fat diet (HFD)-associated increase in fasting-induced hyperphagia and related hormone levels, adipose tissue lipolysis and inflammation, and selected cecal microbial count in mice. Cinnamaldehyde, at 40µM dose, prevented lipid accumulation and altered gene expression toward lipolytic phenotype in 3T3-L1 preadipocyte cell lines. In vivo, cinnamaldehyde coadministration prevented HFD-induced body weight gain, decreased fasting-induced hyperphagia, as well as circulating leptin and leptin/ghrelin ratio. In addition to that, cinnamaldehyde altered serum biochemical parameters related to lipolysis, that is, glycerol and free fatty acid levels. At transcriptional level, cinnamaldehyde increased anorectic gene expression in hypothalamus and lipolytic gene expression in visceral white adipose tissue. Furthermore, cinnamaldehyde also decreased serum IL-1β and inflammatory gene expression in visceral white adipose tissue. However, cinnamaldehyde did not modulate the population of selected gut microbial (Lactobacillus, Bifidibaceria, and Roseburia) count in cecal content. In conclusion, cinnamaldehyde increased adipose tissue lipolysis, decreased fasting-induced hyperphagia, normalized circulating levels of leptin/ghrelin ratio, and reduced inflammation in HFD-fed mice, which augurs well for its antiobesity role.

Coriolus versicolor (CV) is a traditional medicine and food mushroom. Our previous study demonstrated that CV extract exhibited anti-hyperglycemia and anti-insulin resistance effects. However, the effect of CV on cardiac function in diabetic cardiomyopathy (DCM) remains unclear. Therefore, we aimed to investigate the effect of CV on cardiac function in diabetes mellitus (DM) rats. We found that the cardiac dysfunction of DM rats was markedly improved by CV extract treatment. CV extract administration significantly attenuated cardiac fibrosis in DM rats, which was accompanied by suppressed transforming growth factor beta 1 (TGF-β1)/Smad signaling as indicated by decreased levels of TGF-β1, p-Smad2, and p-Smad3 and increased Smad7 expression. Moreover, CV extract treatment significantly alleviated cardiac inflammation as shown by decreased levels of NLRP3 receptor, cleaved caspase-1, IL-1β, and IL-18 in DM rats at leastpartly due to the inhibition of the NF-κB. In addition, high-glucose treatment induced cardiac fibrosis and increased cardiac inflammation in cardiac fibroblast cells, but these effects were ameliorated by CV extract treatment. Therefore, we conclude that the protective effect of CV on DCM is associated with the suppression of TGF-β1/Smad signaling and attenuation of NLRP3 inflammasome activation, suggesting that CV extract may be a potential therapeutic agent for DCM.

BACKGROUND:Acupuncture has shown the capability of modulating the immuno-inflammatory response of the host. This study aims to evaluate the effects of electroacupuncture (EA) on ligature-induced periodontitis in rats.

METHODS:Thirty-two animals were divided into four groups: 1) control; 2) experimental periodontitis (EP); 3) sham-treated (EP/EA-sham); and 4) treated with EA (EP/EA). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. For EA treatment, large intestine meridian points LI4 and LI11 and stomach meridian points ST36 and ST44 were used. EA-sham was performed in off-meridian points. Animals were euthanized at day 11. Histomorphometric and microtomographic analyses were performed. Immunolabeling patterns for the receptor activator of nuclear factorκB ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) were assessed. Expressions of interleukin (IL)-1β, matrix metalloproteinase (MMP)-8, IL-6, and cyclooxygenase (COX)-2 messenger RNAs (mRNAs) were evaluated by quantitative reverse transcription-polymerase chain reaction. Data were analyzed statistically (P<0.05, analysis of variance).

RESULTS:Histomorphometric and microtomographic analyses demonstrated that group EP/EA presented reduced alveolar bone loss when compared to group EP (P<0.05). Reduced RANKL immunolabeling and fewer TRAP-positive multinucleated cells were observed in the EA-treated group in relation to group EP. No differences were observed in OPG expression among groups. EA treatment decreased the genic expression of IL-1β and MMP-8 (P<0.05), increased the mRNA expression of IL-6 (P<0.05), and did not modify the genic expression of COX-2 in animals with EP (P>0.05).

CONCLUSION:It can be concluded that EA reduced periodontal tissue breakdown and the expression of some proinflammatory mediators and a proresorptive factor in EP in rats.

BACKGROUND:Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Although several studies have demonstrated the anti-inflammatory activity of this fungus, its underlying mechanisms have not yet been clearly defined.

METHODS:In the present study, we have demonstrated the anti-inflammatory effects of ethanol extract of P. cocos (EEPC) in lipopolysaccaride (LPS)-stimulated RAW 264.7 macrophages. As inflammatory parameters, the productions of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were evaluated. We also examined the EEPC's effect on the nuclear factor-kappaB (NF-κB) signaling pathway.

RESULTS:Our results indicated that EEPC exhibits a potent inhibitory effect on NO production and inhibits PGE2 release in LPS-induced macrophages without affecting cell viability. EEPC also significantly attenuated LPS-induced secretion of inflammatory cytokines IL-1β and TNF-α. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1β, and TNF-α was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-κB, as well as the nuclear translocation of the NF-κB p65, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation.

CONCLUSIONS:Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.

Cytokine proteins may have important roles during different human physiological and pathological processes. In the oral cavity, the bone loss and periodontal tissue pathology was related to inflammatory process activation. The aim of the present study was to assess the effects of etiological periodontal therapy with and without the use of Low Level Laser Therapy (LLLT) on clinical periodontal parameters and interleukin (IL)-1β level in gingival crevicular fluid (GCF) from chronic periodontitis (CP) patients. Thirty non-smoker CP patients were selected from the Foggia University Dental Clinic and other 2 private dental clinics. All patients were divided into two homogeneous randomized groups: 15 patients were treated with only scaling and root planing (group 1) and 15 patients with scaling and root planing etiological treatment and LLLT (group 2). In all sites, at baseline before treatment, the periodontal pocket depth (PPD) and bleeding on probing (BOP) were measured. In the PPD sites, the GCF samples were collected from 30 deep (≥5 mm) and shallow (≤3 mm) sites and IL-1β were evaluated at baseline, after 10 days and 1 month. In all the samples at baseline, the IL-1β concentration in GCF and BOP rate were significantly higher at deep PPD sites than at the shallow ones. After 10 days in all samples noPPD improvement was observed in the BOP rate but the IL-1 β level was statistically significantly improved (p<0.005) in group 2 compared to group 1. At 10 days and 1 month, in all deep PPD sites, PPD and BOP improvements were observed. At same time, IL-1β levels were lower and statistically significantly (p<0.005) improved in group 2 compared to group 1. The results confirmed that the periodontal etiology treatment of deep PPD sites with or with-out associated LLLT promotes periodontal health. Etiological treatment associated with LLLT, improves BOP and inflammation in periodontal disease. Moreover, the IL-1β concentration changes in GCF suggest these cytokines as a predictable marker of gingival inflammation in chronic periodontitis patients.

Background:Grape seed proanthocyanidin extract (GSPE) has been extensively reported to possess a wide range of beneficial properties in multiple tissue damage. Previous studies have shown that exhaustive exercise-induced fatigue associates with oxidative stress injury, inflammatory response, and mitochondrial dysfunction.

Objective:The aim of this study is to investigate the anti-fatigue effects of GSPE in mice and explore its possible underlying mechanism.

Design:The mouse model of exhaustive exercise-induced fatigue was established by using the forced swimming test, and GSPE was orally treated for successive 28 days at 0, 1, 50 and 100 mg/kg/day of body weight, designated the control, GSPE-L, GSPE-M and GSPE-H groups, respectively.

Results:The presented results showed that treatment of GSPE at a dose of 50 and 100 mg/kg/day of body weight significantly relieved exhaustive exercise-induced fatigue, indicated by increasing the forced swimming time. In addition, treatment of GSPE significantly improved the creatine phosphokinase and lactic dehydrogenase, as well as lactic acid level in exhaustive swimming. For underlying mechanisms, treatment of GSPE had anti-fatigue effects by promoting antioxidant ability and resisting oxidative effect, as represented by increased total antioxidative capability levels, enhanced superoxide dismutase and catalase activities, and ameliorated malondialdehyde levels. Furthermore, treatment of GSPE significantly inhibited the activity of tumor necrosis factor-α and interleukin-1β, which suggested that its protective effects on exhaustive exercise-induced fatigue may be attributed to inhibition of inflammatory response. Last but not the least, treatment of GSPE significantly improved succinate dehydrogenase and Na+-K+-ATPase levels to enhance mitochondrial function during exhaustive swimming-induced fatigue.

Conclusions:These results proved that treatment of GSPE possessed the beneficial properties of anti-inflammatory, antioxidant, and mitochondrial protection to improve exhaustive exercise, which suggested that GSPE could be used as an effective functional food to delay fatigue.

Growing evidence has demonstrated that the nucleotide‑binding oligomerization domain‑like receptor family pyrin domain containing 3 (NLRP‑3) inflammasome‑mediated inflammatory pathways have been involved in the secondary injury of traumatic brain injury (TBI). In the present study, the authors investigated the effects of hyperbaric oxygen (HBO) therapy on the NLRP‑3 inflammasome pathway following TBI. Following the evaluation of motor deficits and brain edema, the therapeutic effects of HBO on interleukin (IL)‑1β and IL‑18 expression were assessed, as well as NLRP‑3 inflammasome activation following TBI. HBO may improve motor score and reduce brain edema, accompanied with the reduction of IL‑1β and IL‑18 during the 7‑day observation period. Furthermore, HBO suppressed mRNA and protein expression of NLRP‑3‑inflammasome components, especially reducing NLRP‑3 expression in microglia. Thus, these results suggestedthat HBO alleviates the inflammatory response in experimental TBI via modulating microglial NLRP‑3‑inflammasome signaling.

The aim of this study was to explore the mechanisms of Hyperbaric oxygen (HBO) protective on interleukin-1β (IL-1β) induced rat's mandibular condylar chondrocytes. Chondrocytes were exposure to Hyperbaric oxygen after induced inflammatory by IL-1β. After that, the expression of p-JNK and c-Jun was increased significantly, while the Sox-9 was decreased significantly, Immunofluorescence results showedthat the expression of p-JNK and p-c-Jun were decreased while the expression of Sox-9 and COL2 were increased in chondrocytes treated with IL-1β and selective JNK inhibitor. Hyperbaric oxygen might plays similar roles with the JNK-specific inhibitor SP600125, inducing the increase of Sox-9 and COL2expression. On the whole, IL-1β induced inflammatory in chondrocytes by activating the JNK/c-Jun signaling pathway and down-regulate the expression of Sox-9 and COL2. However, Hyperbaric oxygen can inhibits IL-1β induced inflammatory response in chondrocytes though block the JNK/c-Jun signaling pathway and up-regulate the expression of Sox-9 and COL2.

Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P < 0.05), 6.03 ± 1.47, 4.13 ± 1.82 (P < 0.05), 2.39 ± 0.25 (P < 0.05), and 1.43 ± 0.38 (P < 0.01), respectively. The expressions of TNF-α, MMP9, HIF-α, VEGF, NF-κB, and IL-1β were associated with the infiltration of inflammatory cells and the inhibition rate of tumor cells. Hyperbaric oxygen therapy (HBOT) could inhibit glioma cell proliferation and inflammatory cell infiltration, and exert a sensitizing effect on ACNU therapy partially through enhancing oxygen pressure (PO2 ) in tumor tissues and lower expression levels of HIF-1α, TNF-α, IL-1β, VEGF, MMP9, and NF-κB.

Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity.

Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

BACKGROUND:The aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human non-septic knee arthritis.

METHODS:In the phase I of the study, patients were randomized to receive either ice (30 min; N = 16) or cold CO(2 min; N = 16) applied twice during 1 day at an 8-h interval on the arthritic knee. In phase II, 16 other ice-treated arthritic knees according to the same protocol were compared to the contralateral non-treated arthritic knees (N = 16). The synovial fluid was analyzed just before the first cold application, then 24 h later. IL-6, IL-1β, TNF-α, IL-17A, VEGF, NF-kB-p65 protein, and PG-E2 levels were measured in the synovial fluid and compared before/after the two cold applications.

RESULTS:Forty-seven patients were included (17 gouts, 11 calcium pyrophosphate deposition diseases, 13 rheumatoid arthritides, 6 spondyloarthritides). Local ice cryotherapy significantly reduced the IL-6, IL-1β, VEGF, NF-kB-p65, and PG-E2 synovial levels, especially in the microcrystal-induced arthritis subgroup, while only phosphorylated NF-kB-p65 significantly decreased in rheumatoid arthritis and spondyloarthritis patients. Cold COonly reduced the synovial VEGF levels. In the phase II of the study, the synovial PG-E2 was significantly reduced in ice-treated knees, while it significantly increased in the corresponding contralateral non-treated arthritic knees, with a significant inter-class effect size (mean difference - 1329 [- 2232; - 426] pg/mL; N = 12).

CONCLUSIONS:These results suggest that local ice cryotherapy reduces IL-6, IL-1β, and VEGF synovial protein levels, mainly in microcrystal-induced arthritis, and potentially through NF-kB and PG-E2-dependent mechanisms.

TRIAL REGISTRATION:Clinicaltrials.gov, NCT03850392-registered February 20, 2019-retrospectively registered.

Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome,in accordance with down-regulation of pro-inflammatory cytokines IL-1β and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy canattenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diodetherapy (LED-T) on infarct reduction was mediated by inflammasome suppression.