Hydroxyzine HCL (HHCL) is an antihistamine, used for the treatment of allergic skin conditions. The purpose of this study was to achieve a dual phase drug delivery rate across the intact skin, to enhance HHCL permeation through the stratum corneum, to assess the peripheral H₁-antihistaminic activity and the extent to which HHCL was systemically absorbed from transdermal gel loaded with solid lipid nanoparticles (SLNs), as well as to avoid its extreme bitterness. According to 2³ factorial design, eight formulations of HHCL-SLNs were prepared by the double emulsification method. Lipid type (X_A), surfactant concentration (X_B) and co-surfactant concentration (X_C) were the independent variables. All formulations were characterized for their surface morphology, particle size, entrapment efficiency and in-vitro drug release study. The optimized formula that provides greater desirability was then incorporated into the transdermal gel. In addition, the efficacy of the developed gel was tested in-vivo using 2,4-Dinitrochlorobenzene induced atopic dermatitis as lesion model in mice. F4 showed an average diameter 111 nm ± 0.03, zeta potential - 30 MV ± 2.4 and EE 75.2% ± 4.4. TEM images showed spherical, smooth morphology with uniform particles distribution. In-vivo study demonstrated potent antipruritic efficacy of transdermal gel in atopic dermatitis such as induced lesions compared to HHCL gel. Hence, HHCL solid lipid nanoparticles transdermal gel may be considered as potential for delivery of HHCL and alternatively to traditional oral use.

Benzyl isothiocyanate (BITC) is a member of the isothiocyanate compounds that found in cruciferous vegetables. BITC has a potential anticancer effect in different types of tumors. Few studies referred to the antineoplastic effect of BITC against HCC. The mechanism of BITC concerning retardation of HCC progression is incompletely understood. This study evaluated the role of HGF, pAkt and STAT3 in BITC induced HCC growth retardation. HCC was induced in mice using diethylnitrosamine (DEN) 75 mg/kg once a week for 4 weeks. BITC 10 and 20 mg/kg was given to mice orally each day for 10 weeks. The HCC cell lines HepG2 and Huh-7 were also used to evaluate the effect of BITC on tumor cells behavior. Immunoassay was used to detect expressions of caspase-3 activity, VEGF, MMP-2, TNF-α, HGF and pAkt. STAT3 expression was detected in liver tissues using immunohistochemical staining. BITC has a potential role in suppressing hepatic precancerous lesion progression in mice. The drug increased caspase-3 activity in tumor cells and inhibited the angiogenic marker VEGF. It also decreased the metastatic marker MMP-2. This anticancer effect of BITC was observed in DEN treated mice as well as in hepatoma cell lines. The reported antineoplastic activity was correlated with downregulation of HGF and its downstream molecules pAkt and STAT3. The effect of BITC on HGF /pAkt/ STAT3 axis has a potential role in both chemopreventive and chemotherapeutic effects of BITC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. The major challenge in managing HCC is the resistance to chemotherapy. Leptin hormone is associated with different oncogenic pathways implicated in drug resistance. Angiotensin II was found to decrease the production and secretion of leptin. This study investigated the potential role of an ACEI perindopril as a chemosensitizer agent to sorafenib. HCC was induced in mice using a single dose of diethylnitrosamine DENA (200 mg/kg) followed by phenobarbital 0.05% in drinking water for 16 weeks. Mice were then treated with perindopril (1 mg/kg/day), Sorafenib (30 mg/kg/day), or both of them for another four weeks. Leptin, VEGF, MMP-9, Cyclin D1, EpCAM, and β-catenin were measured using immunoassay while Wnt and ALDH1 were assayed using western blotting assay. Perindopril whether alone or in combination with sorafenib decrease liver enzymes and preserve the liver architecture. Our study revealed that perindopril significantly increased the antineoplastic, antiangiogenic as well as anti-metastatic effects of sorafenib. This effect was correlated with the downregulation of the leptin / Wnt / β-catenin pathway and overexpression of ALDH1 while downregulation of EpCAM This study presents perindopril as a potential chemosensitizer agent that works through decreased expression of the leptin / Wnt / β-catenin pathway.

Alzheimer’s disease (AD) is one of the major causes of dementia and its incidence represents approximately 60–70% of all dementia cases worldwide. Many theories have been proposed to describe the pathological events in AD, including deterioration in cognitive function, accumulation of β-amyloid, and tau protein hyperphosphorylation. Infection as well as various cellular molecules, such as apolipoprotein, micro-RNA, calcium, ghrelin receptor, and probiotics, are associated with the disruption of β-amyloid and tau protein hemostasis. This review gives an overview on the integrative cellular and signaling molecules that could play a complementary role in the dysregulation of β-amyloid and tau proteins.