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Gastric ulcer (GU) is a prevalent chronic digestive disease affecting about 10% of the world's population leading to gastrointestinal perforation and bleeding. Genistein is a legume flavonoid with antioxidants, anti-inflammatory and antibacterial activities. Therefore, we aimed to investigate the ability of genistein to reduce experimentally induced GU in rats by affecting gastric tissue fibrosis Wnt/β-catenin/TGF-β/SMAD4 pathway. Thirty rats were used. Ten rats served as control, and GU was induced in twenty rats using a single dose of indomethacin (80 mg/kg) orally. Following induction of GU, ten were treated with genistein 25 mg/kg orally. The gastric tissues were isolated to investigate markers of gastric fibrosis, Wnt, β-catenin, transforming growth factor (TGF)-β, SMAD4, and Protein kinase B (PKB). In addition, gastric sections were stained with PAS and anti-TGF-β antibodies. Investigation GU micro-images revealed degeneration in both surface cells and glandular epithelial cells, which was improved by genistein. In addition, treatment with genistein significantly reduced the expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB. Besides antioxidant activity, genistein improves experimentally induced GU in rats, at least in part, via reduction of gastric tissue fibrosis as indicated by reduction in expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB. [ABSTRACT FROM AUTHOR]

Patients with ulcerative colitis (UC) experience diarrhoea, hematochezia and abdominal pain. UC is a well‐known health challenge affecting 200–250 per 100 000 individuals worldwide, with a similar prevalence in both sexes and elevated upon activation of gut immune responses. We evaluated the potential therapeutic effects of cycloastragenol in experimentally induced UC rats and examined the modulation of sphingosine kinase (SphK), macrophage inflammatory protein (MIP)‐1α and miR‐143. We treated UC rats with 30 mg/kg cycloastragenol and assessed gene and protein expression levels of SphK, MIP‐1α, B‐cell lymphoma 2 (BCL2), BCL2‐associated X (BAX), miR‐143, NF‐κB, tumour necrosis factor (TNF)‐α and active caspase‐3. Colon sections were examined using electron microscopy; additional sections were stained with haematoxylin–eosin or immunostained with anti‐TNF‐α and anti‐caspase‐3 antibodies. Electron microscopy of UC specimens revealed dark distorted goblet cell nuclei with disarranged mucus granules and a nondistinct brush border with atypical microvilli. Haematoxylin–eosin staining showed damaged intestinal glands, severe haemorrhage and inflammatory cell infiltration. Cycloastragenol treatment improved the induced morphological changes. In UC rats, cycloastragenol significantly reduced expression levels of SphK, MIP‐1α, BAX, NF‐κB, TNF‐α and active caspase‐3, associated with BCL2 and miR‐143 overexpression. Therefore, cycloastragenol protects against UC by modulating SphK/MIP‐1α/miR‐143, subsequently deactivating inflammatory and apoptotic pathways. [ABSTRACT FROM AUTHOR]

The present study aimed to optimize luliconazole nanoemulsion using Box–Behnken statistical design, which was further incorporated into the polymeric gel of Carbopol 934. The formulation was characterized for its size, entrapment efficiency, ex vivo permeation, and mechanism of release. The size of the dispersed globules of the optimized drug-loaded nanoemulsion was found to be 17 ± 3.67 nm with a polydispersity index (PDI) less than 0.5. Although the surface charge was recorded at –9.53 ± 0.251, the stability was maintained by the polymeric matrix that prevented aggregation and coalescence of the dispersed globules. The luliconazole-nanoemulgel (LUL-NEG) was characterized for drug content analysis, viscosity, pH, and refractive index, where the results were found to be 99.06 ± 0.59%, 9.26 ± 0.08 Pa.s, 5.65 ± 0.17, and 1.31 ± 0.08, respectively. The permeation across the rat skin was found to be significantly higher with LUL-NEG when compared with LUL gel. Furthermore, the skin irritation test performed in experimental animals revealed that the blank NEG, as well as the LUL-NEG, did not produce any signs of erythema following 48 h exposure. In addition, the histopathological findings of the experimental skins reported no abnormal signs at the formulation application site. Finally, the NEG formulation was found to create a statistically significant zone of inhibition (P < 0.05) when compared to all other test groups. Overall, it could be summarized that the nanoemulgel approach of delivering luliconazole across the skin to treat skin fungal infections could be a promising strategy. [ABSTRACT FROM AUTHOR]

Objectives: Hepatocellular carcinoma (HCC) is characterized by elevated in oxidative stress and inflammatory cytokines, which enhance destructive effects of the tumor. Therefore, we conducted this study to investigate the protective effects of sodium ascorbate against thioacetamide-induced HCC in rats through studying its effect on the apoptotic pathway in rats. In addition, in vitro activity of sodium ascorbate was investigated on HepG2 and compared with cisplatin. Methods: HCC was experimentally induced by injecting rats with 200 mg/kg thioacetamide intraperitoneally twice weekly for 16 weeks. Part of HCC rats was concomitantly treated with 100 mg/kg sodium ascorbate intraperitoneally during the 16-week period. Hepatic tissues were used for the determination of NFκB, Nrf2, TNF-α, caspase-3, caspase-8 and caspase-9. Results: Sodium ascorbate significantly attenuated HCC-induced reduction in the expression of NrF2 associated with a reduction in concentrations of hydrogen peroxide and superoxide anion. In addition, sodium ascorbate blocked HCC-induced increase in the expression of NFκB and TNF-α. Sodium ascorbate slightly increased the activity of caspase-3, -8 and -9 in vitro but inhibited their activities in vivo. Conclusion: In spite of the antioxidant and anti-inflammatory activity of sodium ascorbate, it produced selective cytotoxic activity via direct activation of the apoptotic pathway in cancer cells without affecting the apoptotic pathway in normal hepatic cells. [ABSTRACT FROM AUTHOR]

As the world's population ages, global health care systems will face the burden of chronic diseases and polypharmacy use among older adults. The traditional tasks of medication dispensing and provision of basic education by pharmacists have evolved to active engagement in direct patient care and collaborative team-based care. The care of older patients is an especially fitting mission for pharmacists, since the key to geriatric care often lies with management of chronic diseases and polypharmacy use, and preventing harmful consequences of both. Because most chronic conditions are treated with medications, pharmacists, with their extensive training in pharmacotherapy and pharmacokinetics, are in a unique and critical position in the management of them. Pharmacists have the expertise to detect, resolve, and prevent medication errors and drug-related problems, such as overtreatment, undertreatment, adverse drug events, and nonadherence. Pharmacists are also competent in critically reviewing and applying clinical guidelines to the care of individual patients, and in some instances confront the lack of data (common in older adults) to provide the best possible patient-centered care. The current review aimed to depict the evidence of geriatric pharmacy care, demonstrate current impact of pharmacists' interventions on older patients, survey the tools used by pharmacists to provide effective care, and explore their role in pharmacotherapy optimization in elders. The findings of the current review strongly support previous studies that showed positive impact of pharmacists' interventions on older patients' health-related outcomes. There is a clear role for pharmacists working directly or collaboratively to improve medication use and management in older populations. Therefore, in global health care systems, teams caring for elders should involve pharmacists to optimize pharmacotherapy. [ABSTRACT FROM AUTHOR]

Various perspectives had been utilized to enhance the poor intestinal permeability and bioavailability of drugs with low water solubility. Berberine (Brb) is a unique molecule that possesses multiple therapeutic activities such as antimicrobial, anti-inflammatory, antioxidant and anti-hyperglycemic effects. To improve Brb permeability and bioavailability, this study presents a newly developed formulation, namely Brb hyaluronate-based liposomes, prepared by using film hydration method and characterized by dynamic light scattering measurements, entrapment efficiency percentage (EE%), transmission electron microscope (TEM), in vitro drug release and physical stability. The bioavailability of the selected formulations was assessed in vivo after oral administration to rats. The results revealed an enhanced effect of hyaluronic acid on the entrapment efficiency, reaching 78.1 ± 0.1% with mean size 520.7 ± 19.9 nm. Sustained release of Brb was recorded up to 24 h in comparison to Brb solution. Physical stability was maintained for three months at refrigeration temperature. Results of pharmacokinetics studies indicated the potential of the liposomal formulation to increase the oral bioavailability of Brb and to accelerate its entry into the bloodstream. The obtained results are accredited to the lipophilic nature of the prepared system, resembling the structural features of bio-membrane, in addition to their small size that enhances intestinal penetration. [ABSTRACT FROM AUTHOR]