Therapeutic potential of limonene-based syringic acid nanoemulsion: Enhanced ex-vivo cutaneous deposition and clinical anti-psoriatic efficacy.

Nanoemulsions have carved their position in topical delivery owing to their peculiar features of forming a uniform film on the skin and conquering stratum corneum barrier and hence fostering dermal penetration and retention. The present work developed syringic acid nanoemulsion (SA-NE) by spontaneous emulsification as an anti-psoriatic remedy via the dermal route. SA-NE were prepared with either lauroglycol90, limonene or their combination (oil phase) and tween80 (surfactant) with variable concentrations. The physicochemical characteristics of SA-NE were assessed together with Ex-vivo skin deposition and dermal toxicity. The effectiveness of optimal formula in psoriatic animal model and psoriatic patients was investigated using PASI scoring and dermoscope examination. Results showed that, SA-NE containing mixture of lauroglycol 90, limonene and 10 % tween80 (F5), was selected as the optimal formula presenting stable nanoemulsion for 2-month period, showing droplet size of 177.6 ± 13.23 nm, polydispersity index of 0.16 ± 0.06, zeta potential of -21.23 ± 0.41 mV. High SA% in different skin strata and no dermal irritation was noticed with limonene-based SA-NE also it showed high in-vitro anti- inflammatory potential compared to the blank and control formulations. A preclinical study demonstrated that limonene-based SA-NE is effective in alleviating psoriasis-like skin lesions against imiquimod-induced psoriasis in rats. Clinically, promising anti-psoriatic potential was asserted as all patients receiving F5 experienced better clinical improvement and response to therapy, achieving ≥ 50 % reduction in PASI scores versus only 35 % responders in the Dermovate® cream group. Collectively, the practical feasibility of limonene-based SA-NE topical delivery can boost curative functionality in the treatment of psoriatic lesions.

Serum miRNA-21, miRNA-146a and plasma cell free DNA as novel biomarkers for assessing systemic lupus erythematosus activity.

BACKGROUND: MicroRNA and cell-free DNA have shown significant correlations with several autoimmune disorders including systemic lupus erythematosus (SLE). SLE has been associated with challenges in determining its activity, so that the need for biomarkers contributing to assessing its activity is emerging. The current study investigated miRNA-21, miRNA-146a and plasma cf-DNA in determination of SLE activity, in addition their association with clinical data including complement factor 3 (C3), complement factor(C4), anti-dsDNA, and other disease activity indices. METHODS AND RESULTS: Eighty subjects divided into; twenty active patients (with SLE-DAI2K score of 16-18) twenty inactive patients (with SLE-DAI2K score of 1-3), and forty healthy control participants) were included in this study. Serum miR-21, miR-146a, and plasma cf-DNA were quantified by real time PCR and their correlation with clinical data was statistically analyzed. The results demonstrated that active cases have significant upregulation of serum miRNA-21 and plasma cf-DNA. Moreover, miR-21 showed a negative, significant pertaining to C3, C4 and was positively related to Systemic Lupus Erythematosus Disease Activity Index 2 K score (SLE-DAI Index2K score) and Systemic-Lupus-Erythematosus-Disease Activity-Index 2 K activity (SLE-DAI 2 K activity). Also, Active group miRNA-146a was negatively, significantly correlated with C3, as well as a positive significant relationship with SLE-DAI2K score and SLEDAI 2 K activity, in addition to anti DNA Autoantibodies. Furthermore, miR-21 and cf-DNA demonstrated a differential value through Receiver Operating Characteristic (ROC) curve's study. CONCLUSIONS: the present study illustrated miR-21, miR-146a, and cf-DNA relationship with SLE clinical data. In addition to their potential value in SLE diagnosis, and activity determination.

A novel topical combination of minoxidil and spironolactone for androgenetic alopecia: Clinical, histopathological, and physicochemical study.

Topical minoxidil 5% are effective in androgenetic alopecia (AGA). Spironolactone acts as an androgen antagonist by competitively blocking androgen receptors. Studying the effect of topical minoxidil 5% gel and spironolactone gel 1% in management of AGA. The study includes 60 patients diagnosed as AGA; (group I): treated with topical minoxidil gel 5%, (group II): with topical spironolactone gel 1% and group (III) treated with combined minoxidil 5% and spironolactone 1% gel. All patients were followed up monthly throughout the treatment period. Scalp biopsy was taken before and after 12 months. In group I, the clinical response was in 90% of patients with variable degrees in improvement, in group II, the clinical response was in 80% of patients, meanwhile, in group III the clinical response was in all patients (100%). Histopathological examination of skin biopsy after treatment revealed significant increase in anagen hair on the other hand, both telogen and vellus hair was significantly decreased meanwhile, the T/V ratio was significantly increased. The results of this work revealed that topical minoxidil gel 5% and topical spironolactone gel 1% were effective in treatment of AGA, while the combination of two agents was better in treatment.

Receptor activator of nuclear factor kappa B ligand serum and synovial fluid level. A comparative study between rheumatoid arthritis and osteoarthritis.

To assess the levels of receptor activator of NF-κB ligand (RANKL) in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to correlate its levels with disease activity and severity. Serum and SF levels of RANKL were measured in 24 patients with RA (Group I) and 20 patients with OA (Group II); patients were selected according to the ACR criteria, and serum RANKL was measured in 13 healthy controls. All patients were subjected to full rheumatological assessment. In RA group, serum level of RANKL was significantly higher than control group (P = 0.01), but not correlated with disease activity and severity parameters apart from number of tender joints (P = 0.03). SF level of RANKL was significantly correlated with disease duration (P = 0.02), number of tender (P = 0.002) and swollen joints (P = 003), ESR (P = 0.01), CRP (P = 0.000), DAS-28 (P = 0.004), and SENS (P = 0.03). In patients with OA, serum level of RANKL was significantly higher than the control group (P < 0.001), and it was statistically insignificant with clinical, laboratory, or radiological data, while SF level of RANKL was statistically significantly higher in patients with Heberden and Bouchard nodes (P = 0.007), Kellgren-Lawrence score (P = 0.002), and with the erosive changes of hands (P = 0.006). The mean serum RANKL in RA group was insignificant with that of total OA group. SF level of RANKL was significantly higher in RA than erosive OA patients and in erosive than non-erosive OA with (P = 0.001, in each one). The SF level of RANKL is an important marker of both disease activity and severity in RA patients; while in OA patients, it is an important marker of disease severity especially in erosive than non-erosive types. Serum level of RANKL may be of low benefit in disease activity and severity of both rheumatoid arthritis and osteoarthritis.