Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Background: A literature survey revealed that many imidazo-thiadiazole molecules were used as key intermediates for the development of novel drugs. The synthesized imidazo-thiadiazole derivatives were tested for their in vitro antioxidant and anti-inflammatory properties. The purpose of this research paper is to provide readers with information regarding diseases caused by free radicals.

Objective: The objective of this study is to develop novel antioxidant and anti-inflammatory drugs.

Methods: Imidazo-thiadiazole derivatives 5a-f were synthesized through cyclo-condensation reactions in two steps. First, the synthesis of 2-amino-thiadiazole derivatives from substituted aromatic carboxylic acids and thiosemicarbazide by using POCl₃ as a solvent as well as a catalyst was performed. In the next step, imidazo-thiadiazoles were prepared from 2-amino-thiadiazole derivatives with appropriate α-haloketones in the presence of polyethylene glycol-300 (PEG-300) as a green solvent. These imidazo- thiadiazole derivatives were prepared by using a novel method. The synthesized compounds were in vitro tested for their antioxidant and anti-inflammatory activities.

Results: In vitro evaluation report showed that nearly all molecules possess potential antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR), and hydrogen peroxide (H₂O₂) radical scavenging activity. Most of the imidazo-thiadiazole derivatives have shown significant anti-inflammatory activity as compared to diclofenac sodium as a reference standard.

Conclusion: In the search for novel therapies to treat inflammation and oxidation, we have made efforts to develop anti-inflammatory and antioxidant agents with a preeminent activity. Imidazo-thiadiazoles 5a, 5e as well as 5f showed potential anti-inflammatory activity. All tested imidazo-thiadiazole deriv-atives (5a-f) showed potential antioxidant activity against one more radical scavenging species as com-pared to ascorbic acid as the reference standard. Thus, imidazo-thiadiazole derivatives constitute an interesting template for the design and development of new antioxidant as well as anti-inflammatory agents.

Background: Healthcare workers are at a high risk of developing Occupational Dermatitis (OD). Affected workers often experience severe impairment of their Quality of Life (QoL). This study aimed to assess the skin-related QoL of healthcare workers with OD and to explore its related factors.

Methods: A cross-sectional and exhaustive study was conducted among healthcare personnel of four public hospitals in the central region of Tunisia. All the cases of OD declared were included. Skin-related QoL was assessed using the validated Tunisian version of the "Dermatology Life Quality Index" (DLQI). Some related patents have also been discussed.

Results: A total of 37 cases of OD were collected with an annual incidence of 4.2 cases per 10000 workers. The population was predominantly female (73%) and the mean age was 44.7±9.4 years. Nurses were the most represented occupational category (38%). Allergic contact dermatitis was the most frequent diagnosis (96%). The use of gloves was the most frequently reported occupational hazard (86%). The most frequently affected sites were hands (97%). The median score of DLQI was five. Multivariate analysis showed an association between the impairment of skin-related QoL and female gender (p = 0.04; OR = 19.3,84), exposure to disinfecting chemicals in the workplace (p = 0.01; OR = 17,306) and the absence of occupational reclassification (p = 0.01; OR = 21,567).

Conclusion: About one-third of the population had an impaired quality of life. The score impairment was significantly related to the female gender, exposure to disinfecting chemicals and the absence of occupational reclassification.

Background: Many studies have used rotenone (ROT) to create an experimental animal model of Parkinson's disease (PD) because of its ability to induce similar behavioral and motor deficits. PD is the most common age-related motoric neurodegenerative disorder. Neuroinflammation and apoptosis play an important role in the pathogenesis of this disease.

Objective: This study investigated the effect of butanolic (n-BuOH) extract of Centaurea africana (200 mg/kg, 16 days) on a ROT-induced neurotoxicity model in male Wistar albino rats.

Methods: Estimation of Tumor Necrosis Factor (TNF-α) and Nitric Oxide (NO) levels along with the myeloperoxidase (MPO) activity in brains was carried out in order to evaluate neuro-inflammation. Oxidative stress, Caspase 3 activity (apoptosis), and behavioral alterations were also evaluated.

Results: In behavior assessment, using Ludolph Movement Analysis Scale, all ROT treated animals showed a decreased locomotor activity. The mitochondrial dysfunction induced by ROT was expressed by a decreased activity of complex I of the mitochondrial respiratory chain and increased lipid peroxidation and caspase 3. Co-treatment with the n-BuOH extract significantly restored the activity of complex I (65.41 %) compared to treatment with ROT alone. The n-BuOH extract also reduced the neuroinflammation in rat brains by reducing MPO activity (75.12 %), NO levels (77.43 %), and TNF-α (71.48 %) compared to the group treated with ROT.

Conclusion: The obtained results indicated that C. africana n-BuOH extract exhibited a protective effect in rats.

Breast cancer is a global issue, affecting greater than 1 million women per annum. Over the past two decades, there have been numerous clinical trials involving the use of various pharmacological substances as chemopreventive agents for breast cancer. Various pre-clinical as well as clinical studies have established numerous anti-inflammatory molecules, including nonsteroidal anti-inflammatory drugs (NSAIDs) and dietary phytochemicals as promising agents for chemoprevention of several cancers, including breast cancer. The overexpression of COX-2 has been detected in approximately 40% of human breast cancer cases and pre-invasive ductal carcinoma in-situ lesions, associated with aggressive elements of breast cancer such as large size of the tumour, ER/PR negative and HER-2 overexpression, among others. Anti-inflammatory molecules inhibit COX, thereby inhibiting the formation of prostaglandins and inhibiting nuclear factor-κBmediated signals (NF-kB). Another probable explanation entails inflammation-induced degranulation, with the production of angiogenesis-regulating factors, such as vascular endothelial growth factor, which can be possibly regulated by anti-inflammatory molecules. Apart from NSAIDS, many dietary phytochemicals have the ability to decrease, delay, or stop the progression and/or incidence of breast cancer by their antioxidant action, regulating inflammatory and proliferative cell signalling pathways as well as inducing apoptosis. The rapid progress in chemoprevention research has also established innovative strategies that can be implemented to prevent breast cancer. This article gives a comprehensive overview of the recent advancements in using antiinflammatory molecules in the chemoprevention of breast cancer along with their mechanism of action, supported by latest preclinical and clinical data. The merits of anti-inflammatory chemopreventive agents in the prevention of cardiotoxicity have been described. We have also highlighted the ongoing research and advancements in improving the efficacy of using antiinflammatory molecules as chemopreventive agents.

Background: Recently, researchers have worked on the development of new methods for the synthesis of bioactive heterocycles using polyethylene glycol as a green solvent. In this context, we report the synthesized 2-(2-hydrazinyl) thiazoles for their in vitro antioxidant, in vitro anti-inflammatory and in vitro anti-cancer activities.

Objective: The objective of the study was to develop novel antioxidant, anti-inflammatory and anti-cancer drugs.

Methods: At the outset, the condensation of substituted acetophenones 1, thiosemicarbazide 2, and α-haloketones 3 was carried out using PEG-400 (20 mL) in the presence of 5 mol% glacial acetic acid to afford thiosemicarbazones intermediate. Furthermore, these thiosemicarbazones were reacted with α-haloketones 3 to obtain appropriate 2-(2-hydrazinyl) thiazoles. The synthesized compounds were in vitro tested for their antioxidant, anti-inflammatory, and anti-cancer activity.

Results: In vitro evaluation report showed that nearly all molecules possessed potential antioxidant activity against 2,2-Diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR) and hydrogen peroxide (H₂O₂) radical scavenging activity. Most 2-(2-hydrazinyl) thiazoles derivatives have shown potential anti-inflammatory activity as compared to diclofenac sodium as a reference standard. 2-(2-Hydrazinyl) thiazoles derivatives showed significant anticancer activity for human leukemia cell line K-562 compared to adriamycin as a reference standard.

Conclusion: All tested compounds showed potential 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging activity. Among the tested series, 4b, 4d and 4e exhibited good hydrogen peroxide and 4b, 4e, 4f and 4g showed excellent superoxide radical scavenging activity. In addition, the 4b, 4e and 4g compounds revealed potent in vitro anti-inflammatory activity against standard diclofenac sodium drug. 2-(2-Hydrazinyl) thiazole derivatives, such as 4c and 4d, showed significant anticancer activity against human leukemia cell line K-562. Thus, these molecules provide an interesting template for the design and development of new antioxidant, anti-inflammatory, and anti-cancer agents.

Background: Hand, foot, and mouth disease is a common viral disease in childhood. Because the disease has the potential to reach epidemic levels and mortality is high in some countries, early recognition of this disease is of paramount importance.

Objective: This purpose of this article is to familiarize pediatricians with the clinical manifestations and management of hand, foot, and mouth disease.

Methods: A search was conducted in February 2022 in PubMed Clinical Queries using the key term "hand, foot, and mouth disease". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in English were included in this review.

Results: Hand, foot, and mouth disease is characterized by a painful oral enanthem and asymptomatic exanthem on the palms and soles. Children younger than 5 years are most commonly affected. Hand, foot, and mouth disease caused by enterovirus A71 is more severe and has a higher rate of complications than that attributed to other viruses such as coxsackievirus A16. Circulatory failure secondary to myocardial impairment and neurogenic pulmonary edema secondary to brainstem damage are the main causes of death. Fortunately, the disease is usually benign and resolves in 7 to10 days without sequelae. Given the self-limited nature of most cases, treatment is mainly symptomatic and supportive. Intravenous immunoglobulin should be considered for the treatment of severe/complicated hand, foot, and mouth disease and has been recommended by several national and international guideline committees. Currently, there are no specific antiviral agents approved for the treatment of the disease. Drugs such as ribavirin, suramin, mulberroside C, aminothiazole analogs, and sertraline have emerged as potential candidates for the treatment of hand, foot, and mouth disease. Vaccination of susceptible individuals in high-risk areas and good personal hygiene are important preventative measures to combat the disease.

Conclusion: Familiarity of the disease including its atypical manifestations is crucial so that a correct diagnosis can be made, and appropriate treatment initiated. A timely diagnosis can help avoid contact with the affected individual and decrease the risk of an outbreak.

Background: Psoriasis is a chronic inflammatory autoimmune disease that is considered linked to genetic and environmental factors such as stress. Since the neurotransmitter dopamine has a close association with stress configuration, it can be a candidate for relieving psoriasis representation. In addition to the CNS, immune cells can play a decisive role in regulating immune functions through dopamine synthesis and the expression of its receptors. Altered response of immune cells to dopamine as well as a distorted expression of dopamine receptors (DRs) in immune cells have been reported in some chronic inflammatory conditions.

Objective: This study aims the evaluation of dopamine receptor (DR1-DR5) gene expression in mononuclear blood cells of psoriatic patients in comparison with normal individuals.

Methods: We isolated peripheral mononuclear cells (PBMCs) from blood samples followed by total RNA extraction, cDNA synthesis, and real-time PCR using specific primer pairs.

Results: We found that all types of DRs are expressed in the PBMCs of normal and psoriatic individuals. We also concluded that compared to controls, DR2 and DR4 were overexpressed in psoriasis patients while DR3 was low-expressed.

Conclusion: Increased expression of DR2 and DR4 along with decreased expression of DR3 in PBMCs of psoriasis patients not only provide new insight into the pathogenesis of psoriasis but may also be effective in designing future therapeutic strategies attributable to psoriasis.