Treatment Of Chronic Inflammation Research Articles

Biomaterials-Based Antioxidant Strategies for the Treatment of Oxidative Stress Diseases.

Oxidative stress is characterized by an increase in reactive oxygen species or a decrease in antioxidants in the body. This imbalance leads to detrimental effects, including inflammation and multiple chronic diseases, ranging from impaired wound healing to highly impacting pathologies in the neural and cardiovascular systems, or the bone, amongst others. However, supplying compounds with antioxidant activity is hampered by their low bioavailability. The development of biomaterials with antioxidant capacity is poised to overcome this roadblock. Moreover, in the treatment of chronic inflammation, material-based strategies would allow the controlled and targeted release of antioxidants into the affected tissue. In this review, we revise the main causes and effects of oxidative stress, and survey antioxidant biomaterials used for the treatment of chronic wounds, neurodegenerative diseases, cardiovascular diseases (focusing on cardiac infarction, myocardial ischemia-reperfusion injury and atherosclerosis) and osteoporosis. We anticipate that these developments will lead to the emergence of new technologies for tissue engineering, control of oxidative stress and prevention of diseases associated with oxidative stress.

Alleviation of Splenic Injury by CB001 after Low-Dose Irradiation Mediated by NLRP3/Caspase-1-BAX/Caspase-3 Axis.

Low-dose radiation has been extensively employed in clinical practice, including tumor immunotherapy, chronic inflammation treatment and nidus screening. However, the damage on the spleen caused by low-dose radiation significantly increases the risk of late infection-related mortality, and there is currently no corresponding protective strategy. In the present study, a novel compound preparation named CB001 mainly constituted of Acanthopanax senticosus (AS) and Oldenlandia diffusa (OD) was developed to alleviate splenic injury caused by fractionated low-dose exposures. As our results show that, white pulp atrophy and the excessive apoptosis in spleen tissue induced by radiation exposure were significantly ameliorated by CB001. Mechanistically, BAX-caspase-3 signaling and nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) inflammasome signaling were demonstrated to be involved in the radio-protective activity of CB001 with the selective activators. Furthermore, the crosstalk between apoptosis signaling and NLRP3 inflammasome signaling in mediating the radio-protective activity of CB001 was clarified, in which the pro-apoptotic protein BAX but not the anti-apoptotic protein Bcl2 was found to be downstream of NLRP3. Our study demonstrated that the use of a novel drug product CB001 can potentially facilitate the alleviation of radiation-induced splenic injury for patients receiving medical imaging diagnosis or fractionated radiation therapy.

María Mittelbrunn: Science feeds my curiosity every day.

María Mittelbrunn leads the Immunometabolism and Inflammation Laboratory at the Severo Ochoa Molecular Biology Center. Her lab takes a multidisciplinary approach to explore immunometabolism as a therapeutic target in the treatment of chronic inflammation and aging. We recently spoke to María about the joy of discussing results with your team and how this can influence future projects, and optimism about the future of research.

The Role of VARVIMAX™ In the Treatment of Chronic Inflammation and Pain in Arthritis and Fibromyalgia

Background: Arthritis and fibromyalgia are chronic inflammatory conditions that cause significant pain and discomfort in affected individuals. Current treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are associated with adverse effects and do not always provide adequate relief. Therefore, there is a need for safe and effective treatments for chronic inflammation and pain in arthritis and fibromyalgia.
 Review of the Literature: This review aims to evaluate the safety and efficacy of VARVIMAX™, a dietary supplement derived from a plant extract, for managing chronic pain in arthritis and fibromyalgia. According to the literature, the prevalence of fibromyalgia and arthritis is still high and even these two conditions occur together. VARVIMAX™ is a dietary supplement derived from a plant extract. VARVIMAX™ contains high levels of anthocyanins, such as Astaxanthins have been shown to possess anti-inflammatory and antioxidant properties. The formulation includes amino acids and flavonoids such as choline L-bitartrate, GABA, L-arginine, black pepper (piperine), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), trans-resveratrol 98% (polygonum cuspidatum extract), which all have anti-inflammatory effects and play a significant role in pain management. Studies have shown that these ingredients have been effective in reducing pain, and inflammation, and improving joint function in patients with arthritis, fibromyalgia, and other inflammatory conditions. The most common side effects reported were gastrointestinal symptoms, such as nausea and diarrhea. 
 Conclusion: VARVIMAX™, a dietary supplement derived from a plant extract Ephedra, shows promise as a safe and effective treatment for chronic pain in arthritis and fibromyalgia. It is composed of several anthocyanins, amino acids, and flavonoids that impart it its characteristic anti-inflammatory and antioxidant properties. This results in reducing pain and inflammation, and improving joint function. Further research is needed to establish its long-term safety and efficacy in a wider range of inflammatory conditions.

Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase

The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site. In rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis, the fusion protein remained in the inflamed tissues and joints for about 1 week after injection, and the amelioration of local inflammation, disease progression and inflammatory pain in the animals were concomitant with homoeostatic preservation of the tissues and with the absence of global immune suppression. IDO-Gal3 may serve as an immunomodulatory enzyme for the control of focal inflammation in other inflammatory conditions.

Glomerella fusarioides-catalyzed structural transformation of steroidal drugs mesterolone and methasterone, and anti-inflammatory activity of resulting derivatives

Transformation of steroidal drug mesterolone (1) with Glomerella fusarioides yielded two new (17α-hydroxy-1α-methyl-5α-androstan-3-one-11α-yl acetate (2) and 15α-hydroxy-1-methyl-5α-androstan-1-en-3,17-dione (3)), and four known derivatives (15α,17β-dihydroxy-1α-methyl-5α-androstan-3-one (4), 15α-hydroxy-1α-methyl-5α-androstan-3,17-dione (5), 1α-methyl-androsta-4-en-3,17-dione (6) and 15α,17β-dihydroxy-1-methyl-5α-androstan-1-en-3-one (7). Similarly, G. fusarioides-catalyzed transformation of steroidal drug methasterone (8) afforded four new metabolites, 11α,17β-dihydroxy-2,17α-dimethylandrosta-1,4-diene-3-one (9), 3a,11α,17β-trihydroxy-2α,17α-dimethyl-5α-androstane (10), 1β,3β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane (11), and 11α,17β-dihydroxy-2,17α-dimethylandrosta-1,4-diene-3-one (12). Structures of new derivatives were determined by using 1D-, and 2D-NMR, HREI-MS, and IR spectroscopic data. New derivative 3 was identified as a potent inhibitor of NȮ production with the IC50 value of 29.9 ± 1.8 μM, in comparison to the standard l-NMMA (IC50 = 128.2 ± 0.8 µM) in vitro. In addition, methasterone (8) (IC50 = 83.6 ± 0.22 µM) also showed a significant activity comparable to new derivative 12 (IC50 = 89.8 ± 1.2 µM). New derivatives 2 (IC50 = 102.7 ± 0.5 µM), 9 (IC50 = 99.6 ± 5.7 µM), 10 (IC50 = 123.5 ± 5.7 µM), and 11 (IC50 = 170.5 ± 5.0 µM) showed a moderate activity. NG-MonomethylL-arginine acetate (IC50 = 128.2 ± 0.8 µM) was used as standared NO⋅- free radicals have an important role in the regulation of immune responses and cellular events. Their overproduction is associated with the pathogenesis of numerous ailments, such as Alzheimer’s cardiac disorders, cancer, diabetes, and degenerative diseases. Therefore, inhibition of NȮ production can help in the treatment of chronic inflammation and associated disorders. All derivatives were found to be non-cytotoxic to human fibroblast (BJ) cell line. The results presented here form the basis of further research for the development of new anti-inflammatory agents with improved efficacy through biotransformation approaches.

The anti-oxidative capacity of fermented lemon peel and its inhibitory effects on Lipopolysaccharide (LPS)-induced RAW 264.7 cell inflammatory response and cell apoptosis

Chronic inflammation plays a key role in the development and progression of several chronic diseases. Inhibiting the inflammatory cascade, thereby minimising the damage caused by the inflammatory mediators, can be one of the strategies in chronic disease management. In addition, inflammation is closely related to apoptosis, and inflammation can cause apoptosis. Lemon peel has been reported to have antioxidant and anti-inflammatory biological activities. This study aimed to investigate the antioxidant activity of fermented lemon peel (FLP) by Lactobacillus plantarum PNU and the effect of its extract (FLPE) on LPS-induced inflammatory response in RAW 264.7 cells. The results show that FLP has better antioxidant activity than unfermented lemon peel (UFLP). Compared with UFLP extract, FLPE more effectively inhibited the release of NO and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IFN-γ) and down-regulated pro-inflammatory genes (IL-1β, IL-6, NF-κB p65, COX-2, IFN-γ, iNOS, IL-5), and pro-apoptotic genes (caspase-3, caspase-9, p53, p21 and Bax), meanwhile, promoted the release of anti-inflammatory cytokine (IL-10) and up-regulated anti-inflammatory genes(IL-10 and IL-4), and anti-apoptotic gene (Bcl2) in LPS-induced RAW 264.7 cells. Therefore, this study elucidates the anti-inflammatory activity mechanism of fermented lemon peel by studying the balance of inflammatory response and the inhibition of apoptosis. It provides an important reference for the future research and treatment of chronic inflammation and related diseases, as well as the development of fermented foods with anti-inflammatory effects.

Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis.

Control of excessive mitochondrial oxidative stress could provide new targets for both preventive and therapeutic interventions in the treatment of chronic inflammation or any pathology that develops under an inflammatory scenario, such as rheumatoid arthritis (RA). Increasing evidence has demonstrated the role of mitochondrial alterations in autoimmune diseases mainly due to the interplay between metabolism and innate immunity, but also in the modulation of inflammatory response of resident cells, such as synoviocytes. Thus, mitochondrial dysfunction derived from several danger signals could activate tricarboxylic acid (TCA) disruption, thereby favoring a vicious cycle of oxidative/mitochondrial stress. Mitochondrial dysfunction can act through modulating innate immunity via redox-sensitive inflammatory pathways or direct activation of the inflammasome. Besides, mitochondria also have a central role in regulating cell death, which is deeply altered in RA. Additionally, multiple evidence suggests that pathological processes in RA can be shaped by epigenetic mechanisms and that in turn, mitochondria are involved in epigenetic regulation. Finally, we will discuss about the involvement of some dietary components in the onset and progression of RA.

Dextromethorphan Exhibits Anti-Inflammatory and Immunomodulatory Effects in a Murine Model: Therapeutic Implication in Psoriasis.

Psoriasis is an immune-mediated skin disease with a worldwide prevalence of 2–4% that causes scaling erythematous skin lesions. It is a chronic relapsing and complex multifactorial disease that often necessitates long-term therapy. Despite various novel therapies, psoriasis remains a treatable but non-curable disease. Because the antitussive medication dextromethorphan (DXM) can inhibit murine bone marrow and human monocytes and slow the progression of arthritis in mice with type II collagen-induced arthritis, we explored whether the oral administration of DXM to mice with imiquimod (IMQ)-induced psoriasis can effectively alleviate psoriasis symptoms and improve immune regulation. Herein, we examined the therapeutic effects of DXM on psoriasis and its potential mechanisms of action in an IMQ-induced psoriasis mice model. We found that an oral dose of DXM (10 mg/kg) could more significantly reduce psoriasis symptoms compared with intraperitoneal injection. Seven days after the oral administration of DXM, the Psoriasis Area and Severity Index (PASI) score was significantly decreased compared with that in the vehicle group. Furthermore, DXM treatment also significantly ameliorated the psoriasis symptoms and the histopathological features of psoriasis, including stratum corneum thickening, desquamation, and immune cell infiltration. Additionally, DXM reduced the mRNA levels of the cytokines TNF-α, IL-6, IL-17A, and IL-22 in skin and the percentage of IL-17A and IL-22 producing T cell receptor γδ T cells (TCRγδT). Taken together, our research demonstrated that DXM could inhibit keratinocyte proliferation and alleviate psoriasis symptoms, which suggests the potential application of DXM in the treatment of chronic inflammation and autoimmune diseases.

Primena mehaničkog udarnog talasa u lečenju kalcifikovanih tendinopatija

Tendons are the soft tissue that connects muscles to bones. They are made of collagen and elastin, they are strong and solid, and have no possibility of contraction. Their strength helps us to move. Recovery of tendon injuries is long-lasting and can take more than six months. If a tendon is shed during a time injury, calcification occurs at the site of the injury and the disease is called calcifying tendinopathy. The very existence of calcifications is an indication for treatment with a mechanical shock wave (Shock wave). Mechanical shock waves can act in focus or radially. The difference between focused and radial waves is primarily in their physical basis. Focused shock waves differ from radial shock waves in terms of therapeutic depth of penetration into the tissue. The basic biological effect of a mechanical shock wave is stimulating. The energy of the mechanical shock wave acts at the cellular level by stimulating the reduction of inflammation and pain in the tissue. Using mechanical shock wave in the treatment of calcified tendinopathies, a safe method for breaking calcifications was obtained. Shock wave can be applied to using: different frequency, different number of strokes, as well as different strength of strokes in their studies. The choice of parameters for the application depends on whether it is calcified or non-calcified tendinopathy. Indications for the use are: painful shoulder, heel spur, plantar fasciitis, tennis elbow, Achilles tendon tendinopathy, jumping knee, patellar tendinitis, myalgia, myogelosis and muscular tendon overstrain syndrome. Contraindications for the use are: the existence of prostheses, knees and hips, as well as various orthopedic material, pacemaker, as well as the presence of chronic diseases such as multiple sclerosis, amyotrophic lateral sclerosis or tumors. The application of a mechanical shock wave is new, non-invasive method, easy to apply, always reduces pain and practically without side effects. This method has a special role in the treatment of chronic inflammation of diseased tendons, with or without calcification. The only dilemma in the application of a mechanical shock wave can be in the number of applications as well as the time break between the applications of two consecutive mechanical shock waves therapy.

Exploring the Links between Diet and Inflammation: Dairy Foods as Case Studies

ABSTRACTSystemic chronic inflammation may be a contributing factor to many noncommunicable diseases, including diabetes, cardiovascular disease, and obesity. With the rapid rise of these conditions, identifying the causes of and treatment for chronic inflammation is an important research priority, especially with regard to modifiable lifestyle factors such as diet. An emerging body of evidence indicates that consuming certain foods, including dairy foods like milk, cheese, and yogurt, may be linked to a decreased risk for inflammation. To discuss both broader research on diet and inflammation as well as research on links between individual foods and inflammation, the National Dairy Council sponsored a satellite session entitled “Exploring the Links between Diet and Inflammation: Dairy Foods as Case Studies” at the American Society for Nutrition's 2020 LIVE ONLINE Conference. This article, a review based on the topics discussed during that session, explores the links between diet and inflammation, focusing most closely on the relations between intake of dairy fat and dairy foods like milk, cheese, and yogurt, and biomarkers of inflammation from clinical trials. While there is currently insufficient evidence to prove an “anti-inflammatory” effect of dairy foods, the substantial body of clinical research discussed in this review indicates that dairy foods do not increase concentrations of biomarkers of chronic systemic inflammation.

The remarkable characteristics of the children with colchicine-resistant familial Mediterranean fever in Turkey.

Colchicine is the fundamental treatment of familial Mediterranean fever (FMF). Still, 5-10% of patients are not in remission with colchicine treatment. A consensus could not be established for the definition of colchicine resistance in FMF. This study aimed to determine factors that help to predict colchicine resistance in pediatric FMF patients. Patients with FMF that age of diagnosis was under 18 years old were included in our study. Fifty colchicine responsive and 33 colchicine-resistant patients were stratified as groups 1 and 2, respectively. Patients' clinical and laboratory findings were evaluated. Logistic regression analysis was used to determine the risk factors of colchicine-resistant FMF. Receiver operating characteristic (ROC) curve analysis was used to identify and compare the predictive performances of colchicine-resistant FMF models. Homozygous exon 10 MEFV mutations were frequent in group 2 (Group 1: 34 (68%), group 2: 32 (97%), p = .013). Univariate analysis showed that the age of onset of symptoms, age of diagnosis, chronic arthritis, myalgia and diarrhea during attacks, and the number of attacks, high ISSF and Pras score, high C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values under colchicine treatment were risk factors for colchicine-resistant FMF. With multivariate analysis, the number of attacks (OR 1.418, CI (95%) 1.149-1.750, p = .001) and high ESR values (OR 1.129, CI (95%) 1.059-1.204, p<.001) were detected as independent risk factors for colchicine-resistant FMF. The predictive factors were determined for pediatric colchicine-resistant FMF in our study. The results will help to early diagnosis and treatment of chronic inflammation in FMF.

Production and Characterization of Anti-Inflammatory Monascus Pigment Derivatives.

The prevention and treatment of chronic inflammation using food-derived compounds are desirable from the perspectives of marketing and safety. Monascus pigments, widely used as food additives, can be used as a chronic inflammation treatment. Orange Monascus pigments were produced by submerged fermentation in a 5 L bioreactor, and multiple orange Monascus pigment derivatives with anti-inflammatory activities were synthesized using aminophilic reaction. A total of 41 types of pigment derivatives were produced by incorporating amines and amino acids into the orange pigments. One derivative candidate that inhibited nitric oxide (NO) production in Raw 264.7 cells and exhibited low cell cytotoxicity was identified via in vitro assay. The 2-amino-4 picoline derivative inhibited NO production of 48.4%, and exhibited cell viability of 90.6%. Expression of inducible NO synthase, an important enzyme in the NO synthesis pathway, was suppressed by such a derivative in a dose-dependent manner. Therefore, this derivative has potential as a functional food colorant with anti-inflammatory effects.

3PO inhibits inflammatory NFκB and stress-activated kinase signaling in primary human endothelial cells independently of its target PFKFB3.

Inhibition of the key glycolytic activator 6-phosphofructokinase 2/fructose-2,6-bisphosphatase-3 (PFKFB3) by 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) strongly attenuates pathological angiogenesis in cancer and inflammation. In addition to modulating endothelial proliferation and migration, 3PO also dampens proinflammatory activation of endothelial cells and experimental inflammation in vivo, suggesting a potential for 3PO in the treatment of chronic inflammation. The aim of our study was to explore if the anti-inflammatory action of 3PO in human endothelial cells was mediated by inhibition of PFKFB3 and glycolysis and assess if other means of PFKFB3 inhibition reduced inflammatory activation in a similar manner. We found that 3PO caused a rapid and transient reduction in IL-1β- and TNF-induced phosphorylation of both IKKα/β and JNK, thus inhibiting signaling through the NFκB and the stress-activated kinase pathways. However, in contrast to 3PO-treatment, neither shRNA-mediated silencing of PFKFB3 nor treatment with the alternative PFKFB3 inhibitor 7,8-dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (YN1) prevented cytokine-induced NFκB signaling and upregulation of the adhesion molecules VCAM-1 and E-selectin, implying off target effects of 3PO. Collectively, our results suggest that the anti-inflammatory action of 3PO in human endothelial cells is not limited to inhibition of PFKFB3 and cellular glycolysis.

Systemic ozone applications, Major autohemotherapy and Rectal Insufflation, evaluated according to the International classification of Evidence-Based Medicine. A new basis for reimbursement of medical expenses by private and social insurances [abstract

Now that indications are clearly defined, applications have mostly become standardized and the active mechanisms have been well confirmed, medical ozone application in the form of the low-dose concept, is established and proven as a complementary medical method in the treatment of chronic inflammations or diseases associated with chronic inflammatory conditions.&#x0D; More than 11,000 systemic ozone treatments in the form of Major Ozone Autohemotherapy (MAH) in 577 patients and ? 47,000 Rectal Insufflations (RI) in 716 patients in various clinical studies are subjected to critical clinical assessment and classification according to the criteria of evidence-based medicine (EBM).&#x0D; Statistically significant clinical and/or pharmacological improvements without side-effects or adverse reactions are found in all studies; special attention is drawn to maintaining hygiene when working with blood and to the use of ozone-resistent and biocompatible materials.&#x0D; On summarizing the evidence classification under RCT + CT (Randomized Controlled Trials + Controlled Trials), i.e. Levels Ib and IIa, 12 studies with 657 ozone-treated patients are obtained for MAH and 6 studies with 227 patients for RI.&#x0D; As a result of the evidence here assessed, the two systemic ozone applications, MAH and RI are part of evidence-based medicine. Both applications are effective, safe and economic.

Bacterial Manipulation of Autophagic Responses in Infection and Inflammation.

Eukaryotes have cell-autonomous defenses against environmental stress and pathogens. Autophagy is one of the main cellular defenses against intracellular bacteria. In turn, bacteria employ diverse mechanisms to interfere with autophagy initiation and progression to avoid elimination and even to subvert autophagy for their benefit. This review aims to discuss recent findings regarding the autophagic responses regulated by bacterial effectors. Effectors manipulate autophagy at different stages by using versatile strategies, such as interfering with autophagy-initiating signaling, preventing the recognition of autophagy-involved proteins, subverting autophagy component homeostasis, manipulating the autophagy process, and impacting other biological processes. We describe the barriers for intracellular bacteria in host cells and highlight the role of autophagy in the host-microbial interactions. Understanding the mechanisms through which bacterial effectors manipulate host responses will provide new insights into therapeutic approaches for prevention and treatment of chronic inflammation and infectious diseases.

THE ANALYSIS OF EFFICACY OF “CEFPOTEC” AND “CLABEL” PREPARATIONS IN TREATMENT OF SPECIFIC AND NONSPECIFIC PROSTATITIS

Objective: to establish the eff ectiveness of Сefpotek (cefpodoxime) and Сlabel (clarithromycin) drugs in the treatment of chronic prostate infl ammation in the stage of pronounced exacerbation caused by nonspecifi c infectious agents and infections of the mycoplasma and chlamydia groups.Materials and methods. The study was conducted in a prospective design on parallel groups. The study contingent consisted of 60 patients of the “Men’s Health Clinic”, suff ering from chronic prostatitis in state of pronounced exacerbation. The following research methods were used: sonographic examination of the prostate gland, bacteriological examination of the ejaculate, analysis of ejaculate and PCR diagnostics of specifi c infections.The results of the study. A diff erentiated course of etiotropic therapy was carried out. In case of non-specifi c prostatitis: oral administration of the drug “Cefpotek” (cefpodoxim) 1 tablet (200 mg) 2 times a day for a course of 14 days with the possibility of extending the course to 28 days. With specifi c prostatitis: oral administration of the drug “Clabel” (clarithromycin) 1 tablet (500 mg) 2 times a day for a course of 14 days.Conclusions. In the treatment of chronic infl ammation of the prostate gland in the stage of pronounced exacerbation caused by nonspecifi c infectious agents using oral administration of the drug “Сefpotek”, the full eff ectiveness was achieved in range from 83.3% to 96.6% of observations.In the treatment of chronic infl ammation of the prostate gland in the stage of pronounced exacerbation caused by infectious agents of the mycoplasma and chlamydia groups using oral administration of the drug “Clabel”, the full eff ectiveness was achieved in the range from 80.0% to 86.6% of observations (regardless of features of combinations of specifi c mixed infections).

11\u03b2-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy

BackgroundDespite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11β-HSD1 to GIOP.MethodsWild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR.ResultsWild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone.ConclusionsThis study demonstrates that 11β-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11β-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids.

DNA sensing by the cGAS-STING pathway in health and disease.

The detection of pathogens through nucleic acid sensors is a defining principle of innate immunity. RNA-sensing and DNA-sensing receptors sample subcellular compartments for foreign nucleic acids and, upon recognition, trigger immune signalling pathways for host defence. Over the past decade, our understanding of how the recognition of nucleic acids is coupled to immune gene expression has advanced considerably, particularly for the DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signalling effector stimulator of interferon genes (STING), as well as the molecular components and regulation of this pathway. Moreover, the ability of self-DNA to engage cGAS has emerged as an important mechanism fuelling the development of inflammation and implicating the cGAS-STING pathway in human inflammatory diseases and cancer. This detailed mechanistic and biological understanding is paving the way for the development and clinical application of pharmacological agonists and antagonists in the treatment of chronic inflammation and cancer.

The Use of Crude Extract of Alhagi graecorum and Urtica pilulifera in the Treatment of Chronic Inflammation of Seminal Fluid: A Case Study

The use of herbal products for therapeutic purposes has begun since prehistoric times [1,2].