© 2020 Elsevier B.V. The oral delivery of bile-based vesicles (BBVs) has been limited by their poor physical stability, low drug load and slow absorption rate. The novel consolidated bile-based vesicles/self-nanoemulsifying system (CBBVs/SNES) combines the advantages of vesicular and self-nanoemulsifying systems (SNES). This work aimed to prepare physically stable CBBVs/SNES loaded with the full dose of amlodipine besylate (AB) as model drug. AB-loaded BBVs dispersion was optimized using Box-Behnken design and evaluated for particle size distribution, encapsulation efficiency and solubilization efficiency. AB-loaded CBBVs/SNES was prepared by mixing the vesicles of the optimized BBV with Labrafil-based SNES that gave the highest drug solubility. AB-loaded CBBVs/SNES was evaluated for particle size, Polydispersity index (PDI) and in vitro release. When diluted in GIT fluids, consolidated system spontaneously emulsifies forming nanosized oil droplets and in-situ formed mixed micelles. The formation of nanosized mixed micelles (<100 nm) was confirmed by transmission electron microscopy and particle size analysis (PS; 106.8 ± 17.60 nm and PDI; 0.20 ± 0.01). The developed CBBVs/SNES showed enhanced physical stability when stored for 3 months at 2–8 °C. The ex-vivo transport study confirmed that the developed CBBVs/SNES improved the drug transport about 3.8 folds in comparison to the reconstituted vesicular dispersion through offering three pathways of transport (in-situ formed mixed micelles uptake, nanoemulsion droplet uptake and vesicular uptake). The various offered transport pathways and the improvement of drug load and physical stability propose that CBBVs/SNES administered via the oral route could therefore be promising in oral delivery of vesicular systems. In-vivo studies is presently investigated.

In the current investigation, a Parkinson's disease (PD) model was established by a single direct right intrastriatal injection of the 6-hydroxydopamine (OHDA) in male Wistar rats followed by 7 daily unilateral injection of angiotensin (Ang) 1-7 in the striatum. To confirm the putative role of Mas receptor (MasR), the selective antagonist A779 was also injected intrastriatally prior to Ang 1-7 injections and a correlation analysis was performed between MasR expression and the assessed parameters. Ang 1-7 upregulated MasR expression to correlate strongly with the improved rotarod (r = 0.95, p = 0.003) and spontaneous activity task (r = 0.99, p < 0.0001). This correlation extends to involve other effects of Ang 1-7, such as the increased striatal dopamine content (r = 0.98, p = 0.0005), substantia nigra pars compacta tyrosine hydroxylase immune-reactivity (r = 0.97, p = 0.001), active pY705-STAT3 (r = 0.99, p < 0.0001) and SOCS3 (r = 0.99, p < 0.0001). Conversely, Ang 1-7 inhibited inflammatory markers to correlate negatively with NF-κBp65 (r = -0.99, p < 0.0003) and its downstream targets, high mobility group box-1 (HMGB-1; r = -0.97, p = 0.002), receptor for advanced glycation end products (RAGE; r = -0.98, p = 0.0004), and TNF-α (r = -0.99, p < 0.0003), besides poly-ADP-ribose polymerase-1 (r = -0.99, p = 0.0002). In confirmation, the pre-administration of the selective MasR antagonist, A779, partially attenuated Ang 1-7-induced alterations towards 6-OHDA neurodegeneration. Collectively, our findings support a novel role for the anti-inflammatory capacity of the MasR axis to prove potential therapeutic relevance in PD via the upregulation/activation of MasR-dependent STAT3/SOCS3 cascade to negatively control the HMGB-1/RAGE/NF-κB axis hindering PD associated neuro-inflammation along with DA depletion and motor deficits.

Novel beta-coronavirus SARS-CoV-2 is the pathogenic agent responsible for coronavirus disease-2019 (COVID-19), a globally pandemic infectious disease. Due to its high virulence and the absence of immunity among the general population, SARS-CoV-2 has quickly spread to all countries. This pandemic highlights the urgent unmet need to expand and focus our research tools on what are considered "neglected infectious diseases" and to prepare for future inevitable pandemics. This global emergency has generated unprecedented momentum and scientific efforts around the globe unifying scientists from academia, government and the pharmaceutical industry to accelerate the discovery of vaccines and treatments. Herein, we shed light on the virus structure and life cycle and the potential therapeutic targets in SARS-CoV-2 and briefly refer to both active and passive immunization modalities, drug repurposing focused on speed to market, and novel agents against specific viral targets as therapeutic interventions for COVID-19.

Chronic ankle instability (CAI) is frequently developed due to failure of the functional rehabilitation after acute ankle sprain. So, there is a need for an alternative way by which we can begin neuro-muscular control retraining sooner.

PURPOSE: This study was conducted to examine the effect of 6-week Single-limb Balance Training Program of the non-affected side on the Overall Stability Index (OASI), Antero-Posterior Stability Index (APSI), and the Medio-Lateral Stability Index (MLSI) of the affected side in females with unilateral CAI.

METHODS: Thirty-two female patients with CAI with mean age 20.96 ± 1.69 years participated in this study. They were randomly assigned into three groups: experimental group A (Cross-Education) (n = 11) performed the exercises for the non-affected side, experimental group B (Traditional Training) (n = 11) performed the exercises for the affected side, and Control group C (n = 10) did not perform any exercises. The randomization was done using statistical random tables. Data were collected using the Biodex Balance system before and after training.

RESULTS: Two-way mixed design MANOVA revealed that there were significant improvements in the mean values of the OASI, APSI and MLSI after training (p < .05) in both the Cross-Education group (A) and Traditional Training group (B) with no significant difference in-between for the OASI, MLSI and APSI after training. There was no significant difference (p > .05) between the pre and post-training mean values of the OASI, MLSI and APSI in the Control group (C).

CONCLUSION: Single-limb balance training for the non-affected side is effective in improving the postural control of the affected side in patients with CAI.

BACKGROUND: Rosin (Colophony) is a natural resin derived from species of the pine family Pinaceae. It has wide industrial applications including printing inks, photocopying paper, adhesives and varnishes, soap and soda. Rosin and its derivatives are employed as ingredients in various pharmaceutical products such as ointments and plasters. Rosin-based products contain allergens that may exert some occupational health problems such as asthma and contact dermatitis.

OBJECTIVE: Our knowledge of the pharmaceutical and medicinal properties of rosin is limited. The current study aims at investigating the cytotoxic potential of Rosin-Derived Crude Methanolic Extract (RD-CME) and elucidation of its mode-of-action against breast cancer cells (MCF-7 and MDA-MB231).

METHODS: Crude methanol extract was prepared from rosin. Its phenolic contents were analyzed by Reversed- Phase High-Performance Liquid Chromatography (RP-HPLC). Antioxidant activity was evaluated by DPPH radical-scavenging assay. Antiproliferation activity against MCF-7 and MDA-MB231 cancerous cells was investigated by MTT assay; its potency compared with doxorubicin as positive control and specificity were assessed compared to two non-cancerous cell lines (BJ-1 and MCF-12F). Selected apoptosis protein markers were assayed by western blotting. Cell cycle analysis was performed by Annexin V-FITC/PI FACS assay.

RESULTS: RD-CME exhibited significant and selective cytotoxicity against the two tested breast cancer cells (MCF-7 and MDA-MB231) compared to normal cells as revealed by MTT assay. ELISA and western blotting indicated that the observed antiproliferative activity of RD-CME is mediated via the engagement of an intrinsic apoptosis signaling pathway, as judged by enhanced expression of key pro-apoptotic protein markers (p53, Bax and Casp 3) relative to vehicle solvent-treated MCF-7 control cells.

CONCLUSION: To our knowledge, this is the first report to investigate the medicinal anticancer and antioxidant potential of crude methanolic extract derived from colophony rosin. We provided evidence that RD-CME exhibits strong antioxidant and anticancer effects. The observed cytotoxic activity against MCF-7 is proposed to take place via G2/M cell cycle arrest and apoptosis. Colophony resin has a great potential to join the arsenal of plantderived natural anticancer drugs. Further thorough investigation of the potential cytotoxicity of RD-CME against various cancerous cell lines is required to assess the spectrum and potency of its novel activity.

Liver diseases are most commonly occurring nowadays, that’s why we are in argent need to develop new strategies in treatment. to evaluate the role of MSCs in regenerating liver cells and to clarify the anti-inflammatory role of HO-1 either alone or as a combined therapy with MSCs. 72 rats were divided into seven groups (n=10 rats/group) as follows, group1: control rats, group 2: CCL4, group 3: CCL4 that received MSCs group 4: CCL4 that received HO-1 inhibitor, group 5: CCL4 that received HO-1 inducer, group 6: CCL4 that received combined MSCs and HO-1 inhibitor , and group 7: CCL4 that received combined MSCs and HO-1 inducer. All groups were evaluated histopathologically with assessment of liver functions. The combined MSCs and HO-1 inducer group showed the highest significant results in ALT (p-value ˂0.05), albumin (p-value ˂0.05), HO-1 activity (p-value ˂0.0001), and genes expression compared to other groups. This is due to the cumulative anti-inflammatory role of both MSCs and HO-1 together with the ability of MSCs to increase the HO-1 expression with further reduction in inflammation and fibrosis. MSCs and HO-1 inducer provide promising tool in treatment of liver disease.
Key words: MSCs; liver fibrosis; HO-1 inducer; HO-1 inhibitor.

The discovery of >60 monogenic causes of nephrotic syndrome (NS) has revealed a central role for the actin regulators RhoA/Rac1/Cdc42 and their effectors, including the formin INF2. By whole-exome sequencing (WES), we here discovered bi-allelic variants in the formin DAAM2 in four unrelated families with steroid-resistant NS. We show that DAAM2 localizes to the cytoplasm in podocytes and in kidney sections. Further, the variants impair DAAM2-dependent actin remodeling processes: wild-type DAAM2 cDNA, but not cDNA representing missense variants found in individuals with NS, rescued reduced podocyte migration rate (PMR) and restored reduced filopodia formation in shRNA-induced DAAM2-knockdown podocytes. Filopodia restoration was also induced by the formin-activating molecule IMM-01. DAAM2 also co-localizes and co-immunoprecipitates with INF2, which is intriguing since variants in both formins cause NS. Using in vitro bulk and TIRF microscopy assays, we find that DAAM2 variants alter actin assembly activities of the formin. In a Xenopus daam2-CRISPR knockout model, we demonstrate actin dysregulation in vivo and glomerular maldevelopment that is rescued by WT-DAAM2 mRNA. We conclude that DAAM2 variants are a likely cause of monogenic human SRNS due to actin dysregulation in podocytes. Further, we provide evidence that DAAM2-associated SRNS may be amenable to treatment using actin regulating compounds.

BACKGROUND: Dermoscopy has been shown to be a useful supportive tool to assist the diagnosis of several non-neoplastic dermatoses (i.e. inflammatory, infiltrative and infectious skin diseases), yet data on skin of colour is still limited.

OBJECTIVES: To characterize dermoscopic features of non-neoplastic dermatoses in dark-skinned patients in order to identify possible clues that may facilitate the differential diagnosis of clinically similar conditions.

MATERIALS & METHODS: Members of the International Dermoscopy Society were invited to submit cases of any non-neoplastic dermatosis developing in patients with Fitzpatrick Phototypes V-VI whose diagnosis had been confirmed by the corresponding gold standard diagnostic test. A standardized assessment of the dermoscopic images and a comparative analysis according to clinical presentation were performed. Seven clinical categories were identified: (I) papulosquamous dermatoses; (II) facial hyperpigmented dermatoses; (III) extra-facial hyperpigmented dermatoses; (IV) hypopigmented dermatoses; (V) granulomatous dermatoses; (VI) sclerotic dermatoses; and (VII) facial inflammatory dermatoses.

RESULTS: A total of 653 patients (541 and 112 with Phototype V and VI, respectively) were recruited for the analysis. Thirty-six statistically significant dermoscopic features were identified for papulosquamous dermatoses, 24 for facial hyperpigmented disorders, 12 for extra-facial hyperpigmented disorders, 17 for hypopigmented disorders, eight for granulomatous dermatoses, four for sclerotic dermatoses and 17 for facial inflammatory diseases.

CONCLUSION: Our findings suggest that dermoscopy might be a useful tool in assisting the diagnosis of clinically similar non-neoplastic dermatoses in dark phototypes by revealing characteristic clues. Study limitations include the retrospective design, the lack of a direct dermoscopic-histological correlation analysis and the small sample size for less common diseases.