This research aimed to compare anti-inflammatory effects of oligonol, acupuncture, and quantum light therapy in rat models of estrogen-induced prostatitis. Adult male Wistar albino rats were grouped as follows: Group I, control (n = 10); Group II, chronic prostatitis (n = 10); Group III, oligonol (n = 10); Group IV, acupuncture (n = 10); Group V, quantum (n = 10); Group VI, oligonol plus quantum (n = 10); Group VII, acupuncture plus oligonol (n = 10); Group VIII, quantum plus acupuncture (n = 10); and Group IX, acupuncture plus quantum plus oligonol (n = 10). Chronic prostatitis (CP) was induced by the administration of 17-beta-estradiol (E2) and dihydrotestosterone (DHT). Oligonol was given for 6 weeks at a dose of 60 mg/day. Acupuncture needles were inserted at CV 3/4 and bilaterally B 32/35 points with 1-hour manual stimulation. Quantum therapy was administered in 5-minute sessions three times weekly for 6 weeks. Lateral lobes of prostates were dissected for histopathologic evaluation. Although all of the treatment modalities tested in this study showed anti-inflammatory effects in the treatment of CP in male rats, a synergistic effect was observed for oligonol plus quantum light combination. Monotherapy with oligonol showed a superior anti-inflammatory efficacy as compared to quantum light and acupuncture monotherapies.

Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.

Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last few decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses. A plethora of scientific evidence showed that the activation of hypoxia inducible factor-1α (HIF-1a), nuclear factor of activated T-cells (NFAT), nuclear factor-erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE), and activated protein-1 (AP-1) pathways are the main molecular mechanisms underlying the therapeutic effects of ozone therapy. Activation of these molecular pathways leads to up-regulation of endogenous antioxidant systems, activation of immune functions as well as suppression of inflammatory processes, which is important for correcting oxidative stress in diabetes and spinal pain. The present study intended to review critically the available scientificevidence concerning the beneficial properties of ozone therapy for treatment of diabetic complications and spinal pain. It finds benefit for integrating the therapy with ozone into pharmacological procedures, instead of a substitutive or additional option to therapy.

The impact of ascorbate on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. Heatstroke is defined as a form of excessive hyperthermia associated with a systemic inflammatory response that results in multiple organ dysfunctions in which central nervous system disorders such as delirium, convulsions, and coma are predominant. The thermoregulatory, immune, coagulation and tissue injury responses of heatstroke closely resemble those observed during sepsis and are likely mediated by similar cellular mechanisms. This study was performed by using the characteristic high lethality rate and sepsis-mimic systemic inflammatory response of a murine model of heat stroke to test our hypothesis that supra-physiological doses of ascorbate may have therapeutic use in critical care. We demonstrated that parenteral administration of ascorbate abrogated the lethality and thermoregulatory dysfunction in murine model of heat stroke by attenuating heat stroke-induced accelerated systemic inflammatory, coagulation responses and the resultant multiple organ injury, especially in hypothalamus. Overall, our findings support the hypothesis and notion that supra-physiological doses of ascorbate may have therapeutic use in critical care.

Defect in gene transcription, excitotoxicity, neuroinflammation and oxidative stress are the dominant disease process that causes striatal cell loss with motor abnormalities in Huntington's disease (HD). Homogeneous pathological reminiscent of HD was extrapolated in the present study using a potent mitochondrial toxin, 3-Nitropropionic acid (3-NP). Administration of 3-NP for 14 days in the present study portends glial cell activation, N-methyl-D-aspartate (NMDA) receptor stimulation, neuroinflammation and motor deficits. The therapeutic strategy in the present study was improvised by formulating thymoquinone, a biologically active compound into a colloidal carrier namelysolid lipid nanoparticles. Treatment with 10 and 20 mg/kg b.w of thymoquinone loaded solid lipid nanoparticles (TQ-SLNs) and 80 mg/kg b.w of thymoquinone suspension (TQ-S) showed a significant (P < 0.01) improvement in ATPases function in 3-NP induced animals than TQ-S (40 mg/kg b.w) treated group. TQ-SLNs (10 and 20 mg/kg) treatment also attenuated the overexpression of glial fibrillary acidic protein (GFAP), pro-inflammatory cytokines and p-p65 NFκB nuclear translocation in 3-NP exposed animals. Further, TQ-SLNs treatment desensitizes NR2B-subtype NMDA receptor, improves tyrosine hydroxylase (TH) immune reactive neurons and ameliorated the motor abnormalities in 3-NP intoxicated animals than TQ-S treated group. Hence, the study signifies that the treatment with lower doses of nanoformulated thymoquinone than thymoquinone suspension can efficiently culminate 3-NP induced HD progression in the striatum of male wistar rats.

CONTEXT:Alternative medical and training approaches to accelerate recovery among athletes are growing in popularity. The potential benefits of acupressure massage on attenuating muscle soreness and promoting post-exercise recovery capacity are still unclear.

OBJECTIVE:This study compares the effects of traditional Chinese acupressure massage (TCAM) and active recovery, on subject recovery capacity after acute repeated jumping exercise.

DESIGN:Twenty healthy male athletes were randomly assigned to traditional Chinese acupressure massage (TCAM; N = 10) or active recovery (AR; performing low-intensity exercise during post-exercise recovery; N = 10) groups. TCAM and AR intervention were applied after repeated jumping exercise. Pain scale, knee active/passive range of motion (AROM/PROM), jumping performance, quadriceps maximum voluntary contraction force, creatine kinase, and leukocyte subpopulations were measured at baseline, after and 48 h after exercise.

RESULTS:No significant interaction effects were observed between the jumping performance, quadriceps maximum voluntary contraction (MVC) force, power-to-weight ratio for the two groups before the exercise, after the exercise, and 48 h post exercise. However, the knee flexion AROM/PROM was greater in the TCAM group than that for the AR group (p = 0.005). There were no differences in the VAS, MVC, and jumping performance between treatments. The white blood cell (p = 0.024), and monocytes (p = 0.023) responses were lower in the TCAM group.

CONCLUSIONS:We demonstrated that TCAM generates beneficial effects on attenuating joint mobility limitations and lowering systemic inflammatory responses after acute exercise in athletes. These findings suggest that TCAM may be a practical alternative approach for athletes participating in consecutive competitions containing eccentric elements.

Studies demonstrate that asthma, especially during childhood, affects the functions of the brain including learning and memory. Exercise is well known for its neuroprotective functions and for its beneficial effects on asthma. We aimed to assess the effects of exercise on cognitive function, synaptic plasticity, and hippocampal brain-derived neurotrophic factor (BDNF) levels in ovalbumin (OVA) sensitized juvenile rats. Rats were sensitized by intraperitoneal administration and inhaled OVA. Animals were subjected to treadmill running exercise during the OVA-challenged period. T-helper type 2 (Th2) cytokine [interleukin (IL)-4], Th1 cytokine (INF-γ) levels, and INF-γ/IL-4 (Th1/Th2) ratio in bronchoalveolar lavage fluid (BALF), and tracheal response to methacholine and OVA were measured. Further, memory behaviors and BDNF levels were measured in the hippocampus as well as long-term potentiation (LTP) was assessed by recording field excitatory postsynaptic potentials (fEPSPs) in the hippocampus. The levels of IL-4 and TGF-β were decreased but INF-γ level and INF-γ/IL-4 ratio increased in the BALF due to exercise in the OVA-sensitized animals. In addition, exercise improved OVA-sensitization induced cognitive impairments, increased BDNF levels, and enhanced hippocampal LTP in OVA-sensitized rats. Exercise is not only effective in the alleviation of airway inflammation by restoring Th1/Th2 cytokines balance, but also is a candidate for improvement of memory and synaptic plasticity deficits partially through increasing the levelsof hippocampal BDNF in OVA-sensitized rats.

Tendinopathy is a common and complex disorder. Once viewed as an inflammatory condition labeled tendinitis, it is now viewed along a continuum that can lead to tissue necrosis and risk of tendon rupture. Anti-inflammatory medications can alter symptoms but may also promote tissue degeneration. Loading of the tendon through exercise, especially exercise involving eccentric muscle contraction, has been shown to promote symptom resolution and functional recovery in many patients. This article reviews the pathoetiology of tendinopathy and the role anti-inflammatory interventions and therapeutic exercise in treatment of active patients.

Dopaminergic agonists, such as Parlodel((R)), are now widely used to inhibit lactation. However, some countries, such as the United States, no longer use these drugs in this indication because of their sometimes serious adverse effects. In this context, the authors tested a homeopathic treatment designed for parturients unable or not wanting to breastfeed. The APIS MELLIFICA 9 CH and BRYONIA 9 CH combination was chosen for its anti-inflammatory and analgesic effects. 71 patients were included in this double-blind placebo-controlled study. All received basic treatment comprising naproxen and fluid restriction. A significant improvement of lactation pain (main criterion of the study) was observed in parturients treated with homeopathy (p<0.02 on D2 and p<0.01 on D4). A similar effect (p<0.05 on D4) was observed for breast tension and spontaneous milk flow. No significant difference was observed for the other criteria of the study. The homeopathic combination studied was therefore effective on the pain of lactation and should be integrated into the therapeutic armamentarium.

OBJECTIVE:to evaluate changes in the expression of tumor necrosis factor-α in patients with rheumatoid arthritis submitted to phototherapy.

MATERIALS AND METHODS:This was an open label study, enrolling ten patients. The phototherapy scheme within a range of 425 to 650 nm, 11.33 Joules/cm2, 30 cm above the chest was as follows: a) 45-min daily sessions from Monday to Friday for 2 to 3 months; b) three, 45- min weekly sessions for 1 to 2 months; c) twice weekly 45-min sessions for 1 to 2 months, and d) one weekly session for 1 to 2 months until completion. Erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor were measured in peripheral blood and tumor necrosis factor-α, interleukin-1β, and interleukin-10 in leukocytes by quantitative real-time Reverse transcriptase-Polymerase chain reaction. In all the patients the next indexes: Karnofsky scale, Rheumatoid Arthritis-specific quality of life instrument, Steinbrocker Functional Capacity Rating and the Visual Analog Scale were evaluated.

RESULTS:Erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor declined notoriously after the indicated sessions. In gene expression, there was a tendency in tumor necrosis factor-α to decrease after 1 month, from 24.5±11.4 to 18±9.2 relative units, without reaching a significant statistical difference. The four tested indexes showed improvement.

CONCLUSION:Phototherapy appears to be a plausible complementary option to reduce the inflammatory component in rheumatoid arthritis.

Ganoderma lucidum, as food, tea, dietary supplement, and medicine, is widely used in China and Eastern Asian countries. In order to discover its anti-inflammatory constituents and provide some references for the usage of G. lucidum and G. sinense, two official species in China, the fruiting bodies of G. lucidum were studied, leading to the isolation of six new triterpenoids (1-6) and 27 known analogues (7-33). Compound 4 exhibited the most potent inhibition on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. The production of IL-6 and IL-1β, as well as the expression of iNOS, COX-2, and NF-κB were dose-dependently reduced by 4. The phosphorylations of IκBα and IKKβ in LPS-induced macrophage cells were blocked by 4. Therefore, 4 could be used as a potential anti-inflammatory candidate and the total triterpenoids might be developed as value-added functional food for the prevention of inflammation. In combination of previous studies, it should be cautious for the interchangeable usage of G. lucidum and G. sinense.

BACKGROUND:Zinc finger protein A20 (tumor necrosis factor alpha-induced protein 3) functions as a potent negative feedback inhibitor of the nuclear factor-kB (NF-kB) signaling. It exerts these effects by interrupting the activation of IkB kinase beta (IKKβ), the most critical kinase in upstream of NF-kB, and thereby controlling inflammatory homeostasis. We reported previously that electroacupuncture (EA) could effectively suppress IKKβ activation. However, the mechanism underlying these effects was unclear. Therefore, the current study further explored the effects of EA on A20 expression in rat brain and investigated the possible mechanism of A20 in anti-neuroinflammation mediated by EA using transient middle cerebral artery occlusion (MCAO) rats.

METHODS:Rats were treated with EA at the"Baihui (GV20),""Hegu (L14),"and"Taichong (Liv3)"acupoints once a day starting 2 h after focal cerebral ischemia. The spatiotemporal expression of A20, neurobehavioral scores, infarction volumes, cytokine levels, glial cell activation, and the NF-kB signaling were assessed at the indicated time points. A20 gene interference (overexpression and silencing) was used to investigate the role of A20 in mediating the neuroprotective effects of EA and in regulating the interaction between neuronal and glial cells by suppressing neuronal NF-kB signaling during cerebral ischemia/reperfusion-induced neuroinflammation.

RESULTS:EA treatment increased A20 expression with an earlier peak and longer lasting upregulation. The upregulated A20 protein was predominantly located in neurons in the cortical zone of the ischemia/reperfusion. Furthermore, neuronal A20 cell counts were positively correlated with neurobehavioral scores but negatively correlated with infarct volume, the accumulation of pro-inflammatory cytokines, and glial cell activation. Moreover, the effects of EA on improving the neurological outcome and suppressing neuroinflammation in the brain were reversed by A20 silencing. Finally, A20 silencing also suppressed the ability of EA to inhibit neuronal NF-kB signaling pathway.

CONCLUSIONS:Ischemia/reperfusion cortical neurons in MCAO rats are the main cell types that express A20, and there is a correlation between A20 expression and the suppression of neuroinflammation and the resulting neuroprotective effects. EA upregulated neuronal A20 expression, which played an essential role in the anti-inflammatory effects of EA by suppressing the neuronal NF-kB signaling pathway in the brains of MCAO rats.

OBJECTIVE:UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis.

APPROACH AND RESULTS:Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4forkhead box P3regulatory T cells and regulating proatherogenic T-cell responses. Experimental studies in Langerhans cell-depleted mice revealed that epidermal Langerhans cells play a critical role in UVB-dependent induction of CD4forkhead box P3regulatory T cells, suppression of proatherogenic T-cell responses, and prevention of atherosclerotic plaque development.

CONCLUSIONS:Our findings suggest the skin immune system as a novel therapeutic target for atherosclerosis and provide a novel strategy for the treatment and prevention of atherosclerosis.

This study was conducted to determine the effect of supplemental dietary vitamin C (VC) and vitamin E (VE) on improving semen quality and antioxidative status in breeder roosters challenged with dexamethasone (DEX). 120 45-week-old Lveyang black-boned breeder roosters were divided into 5 experimental treatments, including negative group, positive group, and three trial groups, which were fed basal diet supplemented with 300mg/kg VC, 200mg/kg VE, or 300mg/kg VC and 200mg/kg VE (VC+VE). At 49 weeks of age, the positive control and trial groups were subcutaneously injected 3 times every other day with DEX 4 mg/kg body weight, the negative control group was sham injected with saline. At 50 weeks of age, average daily feed intake of birds challenged with DEX significantly increased (P<0.05), however, serum testosterone significantly decreased (P<0.05). Dietary supplementation of VC+VE enhanced serum testosterone and sperm motility remarkably (P<0.05). There were no differences in sperm viability between the DEX-treated groups. During the post-stress recovery period (52 weeks of age), dietary supplementation of VE and VC+VE significantly increased the body weight of birds under oxidative stress (P<0.01). VC, VE, and VC+VE groups had greater sperm viability than control group (P<0.01). Additionally, there was a decrease in the semen plasma malondialdehyde content (P<0.05) of the VC and VC+VE groups, and in the testicular malondialdehyde content (P<0.01) of the VE and VC+VE groups. In summary, VC, VE, especially their combination alleviate the oxidative stress induced by DEX and are favorable for the fertility of breeder roosters.

Interactions of the cell adhesion molecules are known to play important roles in mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-α (TNF-α), activates the NF-kB signaling pathway, which induces the expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1). In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF-α in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment with vitamin C resulted in the downregulation of the TNF-α-induced surface expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover, a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF-kB activation and lkBα degradation induced by TNF-α. Taken together, these results suggest that vitamin C downregulates TNF-α-induced ICAM-1 expression via the inhibition of NF-kB activation.

Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation. Dox also caused an increase in the expression of proapoptotic proteins Bax, Bnip-3, Bak, and caspase-3. An increase in oxidative/nitrosative stress attributable to Dox was indicated by an increase in superoxide, protein carbonyl formation, lipid peroxidation, nitric oxide (NO), NO synthase (NOS) activity, protein nitrosylation, and inducible NOS protein expression. Dox increased the levels of cardiac proinflammatory cytokines TNF-α, IL-1β, and IL-6, whereas the expression of Vit C transporter proteins (sodium-ascorbate cotransporter 2 and glucose transporter 4) was reduced. Prophylactic and concurrent treatment with Vit C prevented all these changes and improved survival in the Vit C + Dox group. Vit C also improved Dox-mediated systolic and diastolic dysfunctions and structural damage. These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins.This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy by reducing oxidative/nitrosative stress, apoptosis, and inflammation along with upregulation of cardiac vitamin C transporter proteins. The latter may have a crucial role in improving antioxidant status in this cardiomyopathy.

Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by altering the inflammatory, proliferative and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo(-/-) ) were used in this study. VitC was provided in the water (sufficient), withheld from another group (deficient) and supplemented by daily intra-peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full thickness excisional wounds (6 mm) were created and tissue collected on days 7 and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects of In conclusion, VitC favorably on proliferation. Histological analysis showed improved wound matrix deposition and organisation in sufficient and deficient +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced expression of pro-inflammatory mediators and higher expression of woundhealing mediators. Supplementation of HnDF with AscA induced the expression of self-renewal genes and promoted fibroblast proliferation. VitC favourably impacts the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodelling.

There is anecdotal evidence that tocilizumab, an immunosuppressant drug, may be a potential therapeutic option for patients with severe manifestations of coronavirus disease 2019 (COVID-19). Like tocilizumab, Vitamin D appears to modulate the activity of an interleukin (IL-6), which may explain the seasonal variation in prevalence of influenza. While most cases of COVID-19 have, thus far, occurred in the Northern Hemisphere winter, limiting the ability to assess seasonal variation, there remains substantial variation in the severity of this condition that has yet to be explained. A retrospective comparison of Vitamin D levels in previously obtained blood samples between survivors and confirmed fatalities could establish a rationale for implementation of widespread Vitamin D supplementation. This would be far cheaper and simpler than tocilizumab as a therapeutic option to trial.