Boswellic Acids: A Critical Appraisal of Their Therapeutic and Nutritional Benefits in Chronic Inflammatory Diseases.

BACKGROUND: In the last few decades, it has been largely perceived that the factors affecting the immune system and its varying pathways lead to the pathological progression of inflammation and inflammatory conditions. Chronic inflammation also contributes to common diseases, such as diabetes mellitus, ischemic heart disease, cancer, chronic renal inflammatory disease, non-alcoholic fatty hepat-ic disease, autoimmune diseases and neurodegenerative diseases. OBJECTIVE: Interestingly, plant sources and secondary metabolites from plants have been increasingly employed in managing acute and chronic inflammatory diseases for centuries. Boswellic acids are pentacyclic triterpenoidal moieties obtained from the oleo gum resin of different Boswellia species. METHODS: Detailed data was collected revealing the anti-inflammatory potential of Boswellic acids through various databases. RESULT: These are pharmacologically active agents that possess promising anti-inflammatory, anti-arthritic, antirheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, and anti-microbial effects. CONCLUSION: Boswellic acids have been in use since ancient times primarily to treat acute and chronic inflammatory diseases. This review discusses the various mechanisms underlying the inflammatory process and the necessity of such natural products as a medication to treat inflammatory diseases. In addition, a discussion has also been extended to understand the primary targets involved in inflammation. The review further explores the therapeutic potential of boswellic acids in.

Medicinal Herbs: Promising Immunomodulators for the Treatment of Infectious Diseases.

Humans are constantly at high risk of emerging pandemics caused by viral and bacterial infections. The emergence of new pandemics is mainly caused by evolved viruses and bacteria that are highly resistant to existing medications. The rapid evolution of infectious agents demands the urgent investigation of new therapeutic strategies to prevent and treat these infections at an early stage. One of these therapeutic strategies includes the use of medicinal herbs for their antibacterial and antiviral properties. The use of herbal medicines as remedies is very ancient and has been employed for centuries. Many studies have confirmed the antimicrobial activities of herbs against various pathogens in vitro and in vivo. The therapeutic effect of medicinal herbs is mainly attributed to the natural bioactive molecules present in these plants such as alkaloids, flavonoids, and terpenoids. Different mechanisms have been proposed for how medicinal herbs enhance the immune system and combat pathogens. Such mechanisms include the disruption of bacterial cell membranes, suppression of protein synthesis, and limitation of pathogen replication through the inhibition of nucleic acid synthesis. Medicinal herbs have been shown to treat a number of infectious diseases by modulating the immune system's components. For instance, many medicinal herbs alleviate inflammation by reducing pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha (TNF-α), interleukin-1, IL-6) while promoting the production of anti-inflammatory cytokines (e.g., IL-10). Medicinal herbs also play a role in defense against viral and intracellular infections by enhancing the proliferation and functions of natural killer cells, T-helper-1 cells, and macrophages. In this review, we will explore the use of the most common herbs in preventing and treating infectious and non-infectious diseases. Using current and recently published studies, we focus on the immunomodulatory and therapeutic effects induced by medicinal herbs to enhance immune responses during diseases.

Adjunctive use of omega-3 fatty acids in combination with low-dose aspirin in periodontitis: Systematic review and meta-analysis.

Periodontitis is one of the most common dental diseases with a range of treatment approaches, including pathogenetically reasonable use of various host immune modulators. One such approach is the use of omega-3 polyunsaturated fatty acids (PUFAs) in combination with low-dose aspirin. This systematic review and meta-analysis were performed to compare the standard treatment alone and adjunctive use of omega-3 PUFAs in combination with low-dose aspirin with or without standard treatment in patients with periodontitis. A systematic review of the literature was performed using MEDLINE/PubMed, Cochrane Central and Google Scholar databases. Selection criteria included the following: randomized controlled trials in subjects with periodontitis in the age group above 18 years old, with follow-up periods ranging from 6 weeks to 6 months. The meta-analysis was performed using standard methodological procedures according to Cochrane recommendations, including assessment of risk-of-bias and level of evidence (GRADE). Meta-analysis was performed for such clinical outcomes as plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP) and bleeding index (BI) based on data from seven randomized clinical trials conducted between 2010 and 2020. It was shown that adjunctive use of omega-3 PUFAs in combination with low-dose aspirin results in significant clinical improvement in PD, CAL and GI during both short and prolonged follow-up periods. The use of omega-3 PUFAs and low-dose aspirin in periodontitis patients may be promising as an adjunct therapy, however, due to a limited number of patients and significant heterogeneity, further studies need to be conducted.

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023.

On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.

New perspective on the immunomodulatory activity of ginsenosides: Focus on effective therapies for post-COVID-19.

More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10-60% of patients are expected to exhibit "post-COVID-19 symptoms," which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase blood oxygen saturation. Ginsenosides are the main active components of ginseng. In this review, we summarize the multiple ways in which ginsenosides affect post-COVID-19 symptoms, including inhibition of lipopolysaccharide, tumor necrosis factor signaling, modulation of chemokine receptors and inflammasome activation, induction of macrophage polarization, effects on Toll-like receptors, nuclear factor kappa-B, the mitogen-activated protein kinase pathway, lymphocytes, intestinal flora, and epigenetic regulation. Ginsenosides affect virus-mediated tissue damage, local or systemic inflammation, immune modulation, and other links, thus alleviating respiratory and pulmonary symptoms, reducing the cardiac burden, protecting the nervous system, and providing new ideas for the rehabilitation of patients with post-COVID-19 symptoms. Furthermore, we analyzed its role in strengthening body resistance to eliminate pathogenic factors from the perspective of ginseng-epidemic disease and highlighted the challenges in clinical applications. However, the benefit of ginsenosides in modulating organismal imbalance post-COVID-19 needs to be further evaluated to better validate the pharmacological mechanisms associated with their traditional efficacy and to determine their role in individualized therapy.

Plants and Plant-Derived Molecules as Natural Immunomodulators.

Background. Nowadays, the immunomodulatory properties of plants have been studied extensively with greater interest due to increasing awareness and combating the severity of immunomodulatory diseases. Scope and Approach. This paper highlights the efficacy of the available literature evidence on natural immunomodulators of plant origin and synthetic ones. In addition, several aspects of plants and their phytoconstituents responsible for immunomodulation have been discussed. Moreover, this review also discusses the mechanism involved in immunomodulation. Key Findings. One hundred fifty medicinal immunomodulatory plants are currently identified to find novel immunomodulatory drugs. Of these plants, the plant family Asteraceae also takes the first rank by offering 18 plant species (12%). Similarly of the plants studied so far, 40% belong to the Asteraceae family. Echinacea purpurea of this family is most known for its immunostimulating activity. The most prominent immune-active bioactive molecules are polyphenols, terpenoids, and alkaloids. Also, eight plant bioactive immunomodulators were checked for clinical trials and found in the market. These are six immunosuppressants, resveratrol, epigallocatechin-3-gallate, quercetin, colchicine, capsaicin, and andrographolide, and two immunostimulants, curcumin and genistein. Nowadays, there are a lot of polyherbal traditional medicinal products sold in the market and claimed to their immunomodulators. However, much work is still needed to find more active immunomodulatory agents. The mechanism by which immunomodulatory medicinal plant exert their effect is through the induction of cytokines and phagocyte cells and the inhibition of iNOS, PGE, and COX-2 synthesis.

Determination of immune factor levels in serum and local hematoma samples of osteoporotic fracture patients and clinical study of the effect of active vitamin D3 treatment on immune factor levels.

OBJECTIVE: The aim of this study was to investigate changes in systemic and local immune factors, namely, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, in patients with and without osteoporotic fractures and to explore the effects of active vitamin D3 treatment on immune function and fracture prognosis in patients with osteoporotic fractures. METHOD: The mRNA expression levels of IL-1ß, IL-6 and TNF-α were measured before the operation. After the operation, the patients in the control group were treated with conventional fracture treatment and calcium supplementation, and the patients in the treatment group were treated with calcium plus active vitamin D3 in addition to conventional fracture treatment. The serum of each patient was collected on the seventh day after the operation. RESULTS: The expression levels of the three immune factors (IL-1ß, IL-6 and TNF-α) in the fracture end hematoma samples were significantly positively correlated with those in the serum samples (P < 0.05). The mean values of the serums of IL-1ß, IL-6 and TNF-α in the osteoporosis group were significantly higher than those in the non-osteoporosis group (P < 0.05). The average number of hematomas in the osteoporosis group was significantly higher than that in the non-osteoporosis group (P < 0.05). The results for the active vitamin D3 treatment group were significantly lower than those for the control group (P < 0.05). The mean wrist function score of the active vitamin D3 treatment group was significantly better than that of the control group (P < 0.05). The average fracture healing time of the treatment group was significantly shorter than that of the control group (P < 0.05). CONCLUSION: The relative expression of IL-1ß, IL-6, and TNF-α in the fracture end hematoma samples was positively correlated with the corresponding levels of these immune factors in the serum samples. The levels of IL-1ß, IL-6 and TNF-α in the serum and fracture end hematoma samples of the osteoporotic fracture patients were higher than those of the non-osteoporotic fracture patients. Active vitamin D3 treatment promoted fracture healing by affecting the levels of these immune factors.

Sleep counts! Role and impact of sleep in the multimodal management of multiple sclerosis.

BACKGROUND: In the last years, research on pharmacotherapy and non-pharmacological approaches to Multiple Sclerosis (MS) has significantly increased, along with a greater attention to sleep as a clinical outcome measure. This review aims to update the state of the art on the effects of MS treatments on sleep, but above all to evaluate the role of sleep and its management within the current and future therapeutic perspectives for MS patients. METHOD: A comprehensive MEDLINE (PubMed)-based bibliographic search was conducted. This review includes the 34 papers that met the selection criteria. RESULTS: First-line disease modifying therapies (especially the interferon-beta) seem to have a negative impact on sleep, assessed subjectively or objectively, while second-line treatments (in particular, natalizumab) do not seem to lead to the onset of daytime sleepiness (also evaluated objectively) and, in some cases, an improvement in sleep quality has been observed as well. Management of sleep is considered a major factor in modifying disease progression in pediatric MS; however, probably because only fingolimod has recently been approved in children, information is still scarce in this group of patients. CONCLUSIONS: Studies on the effect of drugs and non-pharmacological treatments for MS on sleep are still insufficient and there is a lack of investigations on the most recent therapies. However, there is preliminary evidence that melatonin, chronotherapy, cognitive-behavioral therapy, and non-invasive brain stimulation techniques might be further assessed as adjuvant therapies, thus representing a promising field of research.

Overexpression of the key metabolic protein CPT1A defines mantle cell lymphoma patients with poor response to standard high-dose chemotherapy independent of MIPI and complement established highrisk factors.

The variable outcome to standard immunochemotherapy for mantle cell lymphoma (MCL) patients is a clinical challenge. Established risk factors, including high MCL International Prognostic Index (MIPI), high proliferation (Ki-67), non-classic (blastoid/pleomorphic) morphology, and mutated TP53, only partly identify patients in need of alternative treatment. Deepened understanding of biological factors that influence time to progression and relapse would allow for an improved stratification, and identification of novel targets for high-risk patients. We performed gene expression analyses to identify pathways and genes associated with outcome in a cohort of homogeneously treated patients. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry- based assessment of CPT1A can contribute to defining high-risk MCL.

Antitumoral effect of local injection of TLR-9 agonist emulsified in Lipiodol with systemic anti-PD-1 in a murine model of colorectal carcinoma.

Introduction: Local treatments of cancer, including transarterial chemoembolization, could enhance responses to systemic immune checkpoint inhibitors such as anti-PD-1 antibodies. Lipiodol, a radiopaque oil, is widely used for transarterial chemoembolization as a tumor-targeting drug carrier and could be used in emulsion with immunomodulators. This study aimed at evaluating the antitumoral effect of intra-tumoral injection of Lipiodol-immunomodulator emulsions combined with systemic anti-PD-1 therapy in a murine model of colorectal carcinoma. Method: Mice (male BALB/c) with anti-PD-1-resistant subcutaneous CT26 tumors were injected with immunomodulators, emulsified or not with Lipiodol (N=10-12/group). Results: The TLR-9 agonist CpG displayed antitumor effects, while Poly I:C and QS21 did not. The Lipiodol-CpG emulsion appeared to be stable and maintained CpG within tumors for a longer time. Repeated intra-tumoral injections, combined with anti-PD-1, induced responses towards the tumor as well as to a distant metastatic-like nodule. This treatment was associated with an increase in proliferative CD8+ T cells and of IFN-γ expression, a decrease in proliferative regulatory T cells but also, surprisingly, an increase in myeloid derived suppressor cells. Conclusions: Local administration of CpG emulsified with Lipiodol led to an effective antitumoral effect when combined to systemic anti-PD-1 therapy. Lipiodol, apart from its radiopaque properties, is an efficient drug-delivery system. The formulated oil-in-water emulsion allows efficient loading and control release of CpG, which induces favorable immune modifications in this murine tumor model.

Neem Leaf Glycoprotein in immunoregulation of cancer.

Cancer is a disease having global consequences. Though several new strategies and treatments have been developed so far, they often come with malicious side effects and this paved ways for demand of naturally extracted/driven product as potent anti-cancer agent owing to their reduced toxicity and side effects. One such common Indian household plant Neem (Azadirachta Indica) and its extract have variegated immunomodulatory effects as anti-cancer agent. Neem Leaf Glycoprotein (NLGP) modifies immune cells present in the tumor surroundings as well as in the peripheral system, rather than directly attacking the cancer cells. NLGP acts as a natural immunomodulator showing several functions like sustained tumor growth regulation by stimulating central and effector memory cells as a vaccination adjuvant, normalization of angiogenic activities, controls hypoxia, improves immune evasion techniques as well as suppresses the activity of several immunological cells (Tregs, myeloid-derived suppressor cells, and tumor-associated macrophages) which promote tumor growth and metastasis in the tumor microenvironment (TME). NLGP prioritises type1 immune-microenvironment which consists of T-bet+IFN-γ-producing group 1 innate lymphoid cell (ILC) (ILC1 and natural killer cells), CD8+ cytotoxic T cells (TC1), and CD4+ T helper1 (Th1) cells. In this review we aim to summarize detailed activity of NLGP in cancer immunoregulation.

Oral administration of Helianthus annuus leaf extract ameliorates atopic dermatitis by modulation of T cell activity in vivo.

BACKGROUND: Atopic dermatitis (AD) is multifactorial disease that is highly involved in the activity of T cells from the skin lesion. Seeds of Helianthus annuus extract have been traditionally used as anti-inflammatory reagent but few studies have been reported on leaf of H. annuus that are discarded uselessly as an immunomodulator. PURPOSE: Therefore, here, the regulatory effect of Helianthus annuus extract (HAE) on AD via suppression of T cell activity was investigated. METHODS: The efficacy of HAE was evaluated in T cells stimulated with CD3/CD28 antibody and PMA/A23187. And demonstration of the alleviating effect of HAE on AD in the ears of Balb/c female mice stimulated with mite extract and DNCB. RESULTS: Pre-treatment with HAE abrogates IL-2 production from activated T cells. It was also found that HAE suppresses the expression of surface molecules in activated T cells. Cell viability results demonstrated that HAE is not associated with cytotoxicity in resting and activated T cells. Besides, we exhibited that regulated phosphorylation of MAPK through TAK1-IKKα-NFκB by pre-treatment with HAE leads to the suppressive effect of HAE on T cell activation. Oral administration of HAE attenuates manifestations of AD including reduced thickness of dermis and epidermis, decreased IgE level in serum, and declined mRNA levels of atopic cytokines on ear tissues. The ameliorative effect of HAE on AD was found to be associated with suppressed activity of T cells from draining lymph nodes. CONCLUSION: Therefore, our results provide that HAE alleviates AD symptoms via modulation of T cell activity. In addition, these results suggest the immunomodulatory effect of HAE on T-cell mediated diseases.

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development.

Current chemotherapy strategies used in clinic appear with lots of disadvantages due to the low targeting effects of drugs and strong side effects, which significantly restricts the drug potency, causes multiple dysfunctions in the body, and even drives the emergence of diseases. Immunotherapy has been proved to boost the body's innate and adaptive defenses for more effective disease control and treatment. As a trace element, selenium plays vital roles in human health by regulating the antioxidant defense, enzyme activity, and immune response through various specific pathways. Profiting from novel nanotechnology, selenium nanoparticles have been widely developed to reveal great potential in anticancer, antibacterial, and anti-inflammation treatments. More interestingly, increasing evidence has also shown that functional selenium nanoparticles can be applied for potential immunotherapy, which would achieve more effective treatment efficiency as adjunctive therapy strategies for the current chemotherapy. By directly interacting with innate immune cells, such as macrophages, dendritic cells, and natural killer cells, selenium nanoparticles can regulate innate immunity to intervene disease developments, which were reported to boost the anticancer, anti-infection, and anti-inflammation treatments. Moreover, selenium nanoparticles can also activate and recover different T cells for adaptive immunity regulations to enhance their cytotoxic to combat cancer cells, indicating the potential of selenium nanoparticles for potential immunotherapy strategy development. Here, aiming to enhance our understanding of the potential immunotherapy strategy development based on Se NPs, this review will summarize the immunological regulation effects of selenium nanoparticles and the application of selenium nanoparticle-based immunotherapy strategies. Furthermore, we will discuss the advancing perspective of selenium nanoparticle-based potential immunotherapy as a kind of novel adjunctive therapy to enhance the efficiency of current chemotherapies and also introduce the current obstacles for the development of selenium nanoparticles for potential immunotherapy strategy development. This work is expected to promote the future research on selenium nanoparticle-assisted immunotherapy and finally benefit the more effective disease treatments against the threatening cancer and infectious and chronic diseases.

IL-38, a potential therapeutic agent for lupus, inhibits lupus progression.

BACKGROUND: Previous studies reported that IL-38 was abnormally expressed in patients with systemic lupus erythematosus (SLE). However, the involvement of IL-38 in the pathophysiology of SLE remains unknown. METHODS: The therapeutic potential of IL-38 was tested in pristane-treated wild-type (WT) and IL-38-/- mice. Thus, SLE was induced via pristane in WT and IL-38-/- mice. Afterwards, the liver, spleen, and kidney of each mouse were obtained. The flow cytometric analysis of the immune cells, serologic expression of inflammatory cytokines and autoantibodies, renal histopathology, and inflammatory signaling were evaluated. RESULTS: WT mice with pristane-induced lupus exhibited hepatomegaly, splenomegaly, severe kidney damages, increased lymphoproliferation, enhanced lymphoproliferation, and upregulated inflammatory cytokines, such as IL-6, IL-13, IL-17A, MIP-3α, IL-12p70, and IFNγ, and elevated levels of autoantibodies, such as ANA IgG, anti-dsDNA IgG, and total IgG. IL-38-/- mice whose lupus progressed, had elevated cells of CD14+, CD19+, CD3+, and Th1, upregulated inflammatory cytokines and autoantibodies, and severe pathological changes in kidney. Administration of recombinant murine IL-38 to pristane-treated IL-38-/- mice improved their renal histopathology, which depended on ERK1/2, JNK1/2, p38, NF-κB p65, and STAT5 signaling pathways. CONCLUSION: IL-38 regulates SLE pathogenesis. Furthermore, targeting IL-38 is critical in the treatment of SLE.

Use of an alfa-lipoic, Methylsulfonylmethane, Boswellia serrata and Bromelain dietary supplement (OPERA®) for aromatase inhibitors-related arthralgia management (AIA): a prospective phase II trial (NCT04161833).

Aromatase Inhibitors (AIs) are recommended for the adjuvant treatment of hormone receptor positive breast cancer in both high-risk pre-menopausal and post-menopausal population; arthralgia is the main cause of discontinuation of therapy and affects up to 25% of population on AI treatment. The objective of the study was to prospectively evaluate OPERA® (GAMFARMA srl, Milan, Italy), a new dietary supplement where α-Lipoic acid, Boswellia serrata, Methylsulfonylmethane and Bromelain are combined in a single hard-gelatin capsule to be taken once a day. Fifty-three patients with arthralgia (NCI-CTCAE v4.0 grade ≥ 1) occurring during AI therapy were enrolled. All patients received OPERA® from enrollment (T0) up to sixth months (T3). Patients' AI-related arthralgia was evaluated every two months with VAS Scale, PRAI questionnaire, and CTCAE scale. Primary endpoint was the number of patients with symptom resolution (G0) at T3 if compared to T0, according to CTCAE and VAS scale. Secondary endpoints were decrease in arthralgia intensity measured with PRAI score at T3 compared to baseline, safety of OPERA® and rate of AI interruption. Treatment with OPERA® supplement was overall well tolerated; no relevant toxicities related to OPERA® intake were reported. Seven subjects (13.2%) were not included in the final analysis because of consent withdrawal. 46 participants were eligible for final analysis. According to CTCAE scale, 10 out of 46 patients reported symptoms resolution at 6-month follow-up from the time of enrollment T0 (p = 0.0009). According to VAS score, 5 patients reported complete resolution of symptoms at T3 if compared to baseline starting situation T0 (p = 0.0222). Analysis of PRAI score showed a significant reduction in arthralgia-related pain perceived (p = 0.0001). OPERA® was able to reduce the intensity of arthralgia related to AI therapy. Randomized, double-blind studies are warranted to confirm the effectiveness of this dietary supplement.

Considering a Biologic: What's a Clinician to Do? Screening and Laboratory Monitoring for Biologic Therapies in the Treatment of Psoriasis.

Biologic therapies have revolutionized the treatment of psoriasis; however, these immunomodulatory therapies may increase the risk of reactivation of latent and chronic infections. Tumor necrosis factor alpha (TNF-α) inhibitors, in particular, have been associated with the increased risk of reactivation of tuberculosis (TB) in patients with latent TB, as well as hepatitis B virus (HBV), in patients with chronic HBV infections. Currently, baseline TB tests are the only screening tests supported with strong evidence. High-grade evidence for HBV screening tests is lacking; however, these tests are sometimes performed in clinical practice. We describe current recommendations for screening tests prior to the initiation of biologic therapy.

miRNA profiles change during grass pollen immunotherapy irrespective of clinical outcome.

Background: Subcutaneous immunotherapy (SCIT) is widely used in the treatment of allergic rhinitis (AR). This study aimed to determine the expression of 48 miRNAs in patients with AR undergoing grass pollen SCIT and investigate relations with clinical outcomes. Methodology: Expression of selected miRNAs was determined using RT-PCR in the full blood of 16 patients with AR and seven healthy controls. Results: miR-136, miR-208 and miR-190 were upregulated in the AR group. After 6 months of SCIT, significant downregulation of some proinflammatory miRNAs and upregulation of several miRNAs regulating Th1/Th2 balance were found. No differences were found between good and poor responders. Conclusion: miRNAs may play a regulatory role in SCIT, leading to tolerance induction.

Background: Subcutaneous immunotherapy is widely used in the treatment of allergic rhinitis (AR). MicroRNAs (miRNAs) are small molecules controlling gene expression. Their role in the process of immunotherapy is not yet well understood. This study aimed to investigate the expression of 48 miRNAs in patients with AR undergoing grass pollen immunotherapy and relations between miRNAs and clinical outcomes. Methodology: The expression of selected miRNAs was determined in the blood of 16 patients with AR and seven healthy people. Results: Three miRNAs were found to be overproduced in allergic patients. During immunotherapy, the production of several proinflammatory miRNAs was reduced while those responsible for allergen tolerance were produced in larger amounts. Conclusion: miRNAs may play an important role in immunotherapy, leading to better tolerance of allergens.

A systematic review on the treatment of pediatric severe alopecia areata by topical immunotherapy or Anthralin (contact sensitization) or low-level light/laser therapy (LLLT): focus on efficacy, safety, treatment duration, recurrence, and follow-up based on clinical studies.

INTRODUCTION: Alopecia areata (AA) in its extensive and severe forms is treatment-challenging, especially in pediatrics. METHOD: A PRISMA-compliant systematic review of seven electronic databases was searched by the terms "alopecia areata," "pediatric," "topical immunotherapy," "Anthralin," and "light therapy" from inception until March 2021. All the alternative names of the disease and therapies have been included in the search terms. 790 articles went to title abstract review by two independent reviewers. In the subsequent level, a review of the full text of studies was conducted. RESULTS: Finally, 10 relevant articles in terms of content structure, subject coverage, and purpose, were selected for further review. The highest percentages of complete hair regrowth were 79.6% and 63.61% by SADBE (topical immunotherapy) and laser therapy. By Anthralin (contact sensitization), the complete response rate was below 50% (between 30 and 35%). Regarding average response, the most effective methods were local immunotherapy (with an average effectiveness of 53.8%), laser therapy (52.55%), and the use of Anthralin-induced contact dermatitis (30.86%), respectively. However, recurrence rate-after treatment with induced contact dermatitis by topical medications like Anthralin (contact sensitization)-was lower (mean 43.53%) in comparison with local immunotherapy (57%). In topical immunotherapy, light base therapy, and contact sensitization, the highest percentage of complete hair regrowth and the average response rate were (63.61% and 52.55%), (79.6% and 53.8%) and (32% and 30.8%), respectively. These methods are considered safe in children. CONCLUSION: A high and more than 50% efficacy in hair regrowth could be expected by topical immunotherapy and light/laser therapy method. No serious side effects have been observed by these methods that are well tolerated in children. Therefore, a combination of local immunotherapy and light/laser therapy could be suggested for the treatment of extensive AA in children. The use of Anthralin could be associated with a lower but more durable response. These points are important for patient selection in individualized situations.