Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Background: Basic helix-loop-helix protein 40 (BHLHE40) can function as both a transcriptional activator and repressor. Recent studies have reported its regulatory functions in T helper (Th)1 and Th17 immune responses. Rheumatoid arthritis (RA) is an autoimmune inflammatory disease in which joints are involved. Both Th1 and Th17 contribute to the pathogenesis of the disease. In the present study, the levels of BHLHE40, interleukin 17 (IL-17), and interferon-gamma (IFN-γ) were assessed in the RA patients.

Methods: Two groups, including RA patients and healthy individuals, were included in the study. The relative expression levels of BHLHE40, IL-17, and IFN-γ were quantified in peripheral blood mononuclear cells (PBMCs) using real-time PCR.

Results: The results showed that the level of BHLHE40 was significantly higher in RA patients compared to the healthy control (P < 0.001) (11.1-fold increase). Accordingly, a significant increase in the levels of IL-17 (8.1 folds increase) (P < 0.021) and IFN-γ (12.7 folds) (P < 0.001) was observed.

Conclusion: Evaluation of the expression level of BHLHE40 in RA patients showed a significant increase. In line with the elevated level of BHLHE40, a significant increase in the expression level of IL-17 and IFN-γ was also detected. These findings point to the possible role of BHLHE40 in the disease course or severity by elevating the levels of inflammatory cytokines, including IL-17 and IFN-γ. Therefore, BHLHE40 might be considered either as a putative biomarker or as a candidate for therapy in a variety of human diseases.

Background: Toxoplasma gondii (T. gondii) is a widespread apicomplexan parasite that affects approximately one-third of the global population, posing particular risks to pregnant women and individuals with weakened immune systems. Despite its significant impact, there is currently no vaccine available for humans.

Objective: This study employs computational methods (in silico) to investigate the physicochemical, antigenic, and structural properties of Perforin-like proteins (PLPs) from T. gondii, as well as to identify immunogenic epitopes within these antigens.

Methods: For this aim, amino acid sequences of TgPLP1 and TgPLP2 were retrieved and submitted to the ProtParam (physicochemical), VaxiJen v2.0 (antigenicity), NetSurfP-6.0 (2D structure), Robetta (3D structure) web servers, along with the IEDB server to decipher the immunogenic epitopes. Subcellular characteristics such as signal peptide, transmembrane domain, post-translational modifications (PTMs), and cellular localization were also predicted.

Results: Both proteins had a high MW of 125.50 and 92.21, respectively, with an alkaline pI, a 30 hours half-life in mammalian reticulocytes, good thermotolerance (high aliphatic index), and hydrophilicity properties (negative GRAVY). They also showed good antigenicity (0.7021 [PLP1] vs 0.5701 [PLP2]), while they were non-allergenic. Both proteins were extracellular with numerous post-translational modification sites (phosphorylation, glycosylation, and acetylation), and a transmembrane domain was only present in TgPLP1, with no signal peptide in both. Furthermore, numerous immunogenic B- and T-cell epitopes were identified within the TgPLPs sequences, suggesting their potential for inclusion in multi-epitope vaccine designs.

Conclusion: Further studies are needed to confirm these findings and assess the efficacy of the proposed vaccine constructs.

The skin, as the body's largest organ, is crucial for maintaining homeostasis and providing protection, making it susceptible to wounds from various causes. Wound healing is a complex process involving numerous cellular activities. Any interruptions can lead to chronic, non-healing wounds, which present significant challenges in healthcare. Interleukin-24 (IL-24), a cytokine within the IL-10 family, has become recognized for its significant role in wound healing due to its diverse effects on cellular processes. IL-24 can inhibit keratinocyte migration, potentially leading to chronic wounds, and promote endothelial cell migration and angiogenesis, which are vital for tissue repair. This dual role highlights IL-24's intricate involvement in wound healing, as it can hinder and aid different aspects of the process. Research indicates that IL-24 expression increases in response to inflammatory mediators and is involved in various immune responses, emphasizing its regulatory function. Further research on IL-24's mechanisms and interactions is essential for developing new therapeutic strategies to enhance tissue regeneration and treat chronic wounds and skin disorders. A deeper understanding of IL-24's functions could transform wound care, providing new approaches for effectively managing and treating conditions involving impaired healing.

Background: Timolol is a beta-adrenergic blocker that has been shown to be effective in the healing of wounds. Oral mucositis (OM), an acute inflammation of the oral mucosa, is a bothersome side effect of some regimens of chemotherapy in which the oral mucosa becomes ulcerated. The current study aimed to evaluate the prophylactic effects of timolol mouthwash in preventing OM in adult patients receiving chemotherapy compared to the placebo.

Method: This randomized, double-blind trial was conducted on 30 adult patients receiving chemotherapy regimen, including doxorubicin or 5-fluorouracil (5-FU). The patients were randomized in a 1:1 ratio to receive either timolol 0.5% (w/v) (n = 15) or placebo (n = 15) mouthwash 5 ml three times per day. The outcomes of the study were the intensity of OM evaluated by the World Health Organization (WHO) mucositis scale and OM-related pain based on the Visual Analog Scale (VAS) weekly during the seven weeks of the study period.

Results: The results of the study showed that the scores of WHO mucositis scale significantly decreased in the timolol group compared to the control group during the study [week 1: mean (SD), 0.02 (0.41) in the timolol group, and 0.67 (0.48) in the control group; week 7: mean (SD), 0.33 (0.61) in the timolol group, and 0.87 (0.74) in the control group; P-value = 0.049]. Moreover, the mean pain scores significantly decreased in the first, second, and third weeks in the timolol group compared to the control group (P-value < 0.05).

Conclusion: The results of this preliminary clinical trial demonstrated that among the patients receiving doxorubicin or 5-FU chemotherapy regimens, the preventive use of timolol mouthwash significantly diminished the severity of OM compared to the control group during the seven weeks of follow-up. The severity of pain was also significantly lower during the first three weeks of the study; however, the effect size was less than the minimal clinically important difference. Further studies are required to assess both the long-term efficacy and safety of timolol mouthwash in preventing OM.

The Hibiscus sabdariffa plant is an herbaceous member of the Malvaceae family. It is a widely recognized herb with medicinal properties. It is utilized extensively in many traditional medical practices along with delicious food items, like jams, puddings, and cakes. The purpose of this review was to investigate and compile all of the available data and evidence about the calyxes of Hibiscus sabdariffa with a particular focus on their nutritional composition, bioactive components, and therapeutic benefits. This article provides a comprehensive overview of the plant's traditional usage, pharmacognostic characterization, nutritional and phytochemical composition, and pharmacological properties. This paper elucidates the mechanisms by which Hibiscus sabdariffa exerts neuroprotective and anti-inflammatory effects in managing neurological disorders. Additionally, Hibiscus sabdariffa has been shown to prevent memory impairment, which may be attributed to its effects on neuroinflammation and amyloidogenesis. Hibiscus sabdariffa has been reported to have anti-inflammatory effects due to the presence of polyphenol compounds that possess anti- inflammatory properties. Flavonoids are also commonly found in it, which inhibit the transcription factor nuclear factor kappa B. This plant has a variety of health benefits, including antioxidant, antidepressant, diuretic, antihyperlipidemic, anti-obesity, hepatoprotective, anti-inflammatory, anti-cancer, antimicrobial, and neuroprotective activities. Based on the literature, this review provides a thorough analysis of the pharmacological and phytochemical characteristics of Hibiscus sabdariffa.

The Toll-like Receptors (TLRs) family has significantly enhanced the understanding of innate immune responses by identifying and responding to various microbes or host-derived organisms. TLRs contribute to these responses by increasing the levels of cytokines, interleukins, and other inflammatory mediators through multiple pathways. Located both intracellularly and on the surface of various cells and tissues, including vascular smooth muscles (VSMs) and myocardium cells, TLRs play distinct roles in innate immune activation, such as recognizing pathogen-associated molecular patterns (PAMPs) and activating downstream signaling pathways. In the context of COVID-19, TLRs are critically involved in the pathophysiology by mediating excessive inflammatory responses that exacerbate disease severity, influencing both the acute phase and long-term outcomes. It has been observed that inflammatory diseases such as atherosclerosis, viral myocarditis, and other comorbidities associated with the spread of COVID-19 have increased, although the exact mechanisms remain not fully understood. Nonetheless, there is evidence of TLR-mediated increased pro-inflammatory signaling by different mechanisms in these diseases. This review explains the role of TLRs in various inflammatory diseases related to COVID-19, including viral myocarditis, acute lung infections, and atherosclerosis. Furthermore, the review discusses various herbal drugs, such as Platycodon grandiflorum, Acanthopanax senticosus, Scutellaria baicalensis Georgi, and Engelhardia roxburghiana, and their mechanisms of action on TLRs, including NF-κB, MyD88-dependent, MyD88-independent pathways, and Plasmacytoid DCs. Enhanced clarity on TLRs' specific contributions to COVID-19 pathophysiology and stronger evidence supporting herbal interventions targeting TLRs could improve the impact and applicability of these findings in clinical settings.

Background: Andrographolide (AP), a bioactive anti-inflammatory compound of Sambiloto, inhibits NF-κB, TNF-α, and interleukin IL-6. Nowadays, molecular docking simulation between AP and dexamethasone against NF-κB receptor presented the energy AP higher than dexamethasone. This becomes a potential treatment for psoriasis.

Objective: This manuscript reported the effectiveness of AP from Sambiloto in treating psoriasis compared to topical steroids.

Methods: This study conducted TLC analysis of AP content and its metabolite impurities, emulgel formulation, molecular docking, in-silico skin toxicity study, and in-vivo anti-psoriatic activity. This was a combination study of an in-silico study and an in-vivo study. This in-silico study was analyzed through multivariate statistical analysis (PCA) to elucidate the data constellation relationship of andrographolide derivatives with several target proteins. The intervention was performed in seven days. The PASI score, molecular parameters (IL-6, IL-17, VEGF, and TNF-a levels), and histopathological findings were assessed.

Results: Molecular docking results revealed andrographolide to exhibit a relatively high binding affinity towards IL-6, NF-kB, and TNF-α which is comparable to the corticosteroids, andrographolide also shares similar residue interaction profile with each of the respective protein's native ligand. In the in-vivo study, we found several parameters statistically significantly different regarding the intervention, including final PASI score (p = 0.017), redness (p = 0.017), scale (p = 0.040), thickness (p = 0.023), total histopathology of psoriasis score (p = 0.037), keratin layer score (p = 0.018).

Conclusion: Emulgel AP 0.1% could lower the anti-inflammatory agent, which is vital to psoriasis progression.

Background: It is well known that acute or chronic kidney injury could be due to free radicals and pro-oxidants. This investigation aimed to monitor tacrolimus or cyclosporine blood trough levels and anti-oxidant capacity after kidney transplantation.

Methods: There was no intervention in the routine management of transplant recipients. The sample size (n=70) included healthy individuals and kidney-transplanted recipients (n=25 on tacrolimus and n=10 on cyclosporine). The study population was matched for age. The attained information was examined by using the Statistical Package (SPSS Inc, Chicago, IL, USA). The significance level was considered as P ≤ 0.05.

Results: In healthy individuals, the mean ± SD for the capacity of antioxidants was 91.9 ± 16.6 (u/ml), which was significantly higher when compared to the mean value of 28.5 ± 22.6 (u/ml) versus 24.7 ± 25.5 (u/ml), kidney recipients with tacrolimus versus cyclosporine (P ≤ 0.04) as immunosuppressive drugs. The mean value of tacrolimus levels was 14.6 ± 6.4 (ng/ml). The correlation between tacrolimus and cyclosporine trough levels and anti-oxidant capacity was 0.19 (P ≤ 0.14). There were no significant differences regarding age in cases and controls (P ≤ 0.42).

Conclusion: This study showed that the capacity of anti-oxidants in kidney transplant recipients, those on tacrolimus or cyclosporine, might be lower than in healthy individuals. Subsequent investigations are recommended to delve into the therapeutic consequences of the influence of antioxidant therapies on the clinical outcomes of transplanted recipients.

Background: The Coronavirus disease 2019 (COVID-19) pandemic, prompted by SARS-CoV-2, has created complicated health crises. An excessive inflammatory response and cytokine storm characterize severe COVID-19. Corticosteroids like dexamethasone and methylprednisolone are used for their anti-inflammatory effects, but comparisons of their efficacy are lacking.

Objective: This study seeks to rigorously assess and contrast the effectiveness of dexamethasone and methylprednisolone in combating COVID-19 infections.

Methods: This retrospective clinical study evaluates the effects of these two corticosteroids by reviewing the files of 500 hospitalized COVID-19 patients. The baseline characteristics of the patients, chest CT severity score, type of steroid prescription, duration of hospitalization and steroid prescription, dosage of corticosteroid therapy, their recovery status, hospital mortality, and specific disease severity-associated markers, such as lactate dehydrogenase (LDH), complete blood count (CBC), C-reactive protein (CRP), and Erythrocyte sedimentation rate (ESR) were collected and compared.

Results: The study found no significant difference in most disease severity-associated markers between the two corticosteroid groups. However, lower mortality rates and shortened hospital stays were significantly associated with dexamethasone, especially in critical patient groups. A detailed analysis of inflammatory markers suggested minimal differences based on the type of corticosteroid used.

Conclusion: The study indicates that dexamethasone may have some advantages in specific clinical outcomes. Further research needs to explore the mechanisms involved despite similar anti-inflammatory profiles.

The study aims to investigate and assess the effectiveness of current novel techniques for the preparation of an efficient nanocarrier system in resolving the drawbacks associated with the delivery of herbal bioactives to treat rheumatoid arthritis. Systematic utilization of various search engines like Science Direct, Pubmed, Shodhganga, Google Scholar, and Google Patent databases based on various sets of key phrases has been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. The current study summarizes the existing research and development of new nano-formulations with a focus on herbal bioactive compounds for treating rheumatoid arthritis. Physicochemical properties of phytoconstituents, such as low aqueous solubility, low permeation coefficient, and chemical instability, poor bioavailability, short plasma half-life, and ultimately sub-therapeutic efficacy, limit their clinical translation despite their great potency. The utilization of Phytochemical-Based Nanocarrier Approaches for rheumatoid arthritis can be a milestone as a major population is affected by this disease worldwide. The intensive study recapitulates that novel drug delivery systems can provide new opportunities to efficiently deliver herbal bioactives with improved pharmacokinetic and pharmacodynamic properties. The exhaustive study concluded that transferosomes, ethosomes, transethosomes, niosomes, phytosomes, Solid Lipid Nanoparticles (SLN), Nano Lipid Carriers (NLC), bilosomes and hylurosomes are some of the efficient nanocarrier systems that may impart numerous benefits to the delivery of herbal bioactives for treatment of RA. These nanocarrier systems fabricated with phytoconstituents flaunt the evident promising benefits of improved aqueous solubility, low first-pass metabolism with upgraded bioavailability, sustained release action, resistance to enzymatic degradation etc., providing support in rheumatoid arthritis recovery. This review discusses that the upgradation of the pharmacological action and other relevant issues of herbal bioactives are possible by utilizing novel drug delivery systems, resulting in successful development of nano-loaded herbal bioactives. It also focuses on highlighting the pioneering progression in the field of herbal bioactives-loaded nanocarrier systems for rheumatoid arthritis both in vitro and in vivo along with their advanced preparation methods and applications and discussing the opportunities for further prospects. This compiled informative review will enlighten various researchers in the field of delivering herbal bioactives for rheumatoid arthritis.