Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection.

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.

Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis.

Most anti-angiogenic therapies currently being evaluated target the vascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here, we identified ferulic acid as a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor and a novel agent with potential anti-angiogenic and anti-cancer activities. Ferulic acid demonstrated inhibition of endothelial cell proliferation, migration and tube formation in response to basic fibroblast growth factor 1 (FGF1). In ex vivo and in vivo angiogenesis assays, ferulic acid suppressed FGF1-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of ferulic acid on different molecular components and found that ferulic acid suppressed FGF1-triggered activation of FGFR1 and phosphatidyl inositol 3-kinase (PI3K)-protein kinase B (Akt) signaling. Moreover, ferulic acid directly inhibited proliferation and blocked the PI3K-Akt pathway in melanoma cell. In vivo, using a melanoma xenograft model, ferulic acid showed growth-inhibitory activity associated with inhibition of angiogenesis. Taken together, our results indicate that ferulic acid targets the FGFR1-mediated PI3K-Akt signaling pathway, leading to the suppression of melanoma growth and angiogenesis.

[Expression of C-erb B-2 and its relation to angiogenesis in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the association of C-erb B-2 expression with angiogenesis in nasopharygeal carcinoma. METHODS: Seventy-seven specimens of nasopharygeal carcinoma were examined immunohistochemically for protein expressions of C-erb B-2 and vascular endothelial growth factor (VEGF), and the microvessel density (MVD) was determined by immunostaining of the endothelial cells for factor VIII-related antigen (F8). RESULTS: Positive C-erb B-2 immunostaining was observed in 36.36% (28/77) of the nasopharygeal carcinoma tissues, which had a VEGF positivity rate of 32.48% (25/77). High positivity rate of C-erg B-2 was associated with high positivity rate of VEGF and high MVD (P<0.05). CONCLUSION: The expression of C-erb B-2 may contribute to angiogenesis in nasopharygeal carcinoma.

[Short-term efficacy of combined chemotherapy of gemcitabine and cisplatin on advanced hormone refractory prostate cancer].

BACKGROUND & OBJECTIVE: Effective treatment for hormone refractory prostate cancer was required. This study was to evaluate efficacy of combined chemotherapy of gemcitabine and cisplatin on hormone refractory prostate cancer, and its toxicities. METHODS: Fifteen patients with advanced hormone refractory prostate cancer,who received castration and antiandrogen medicines,were conformed multiple bone metastatic carcinomas by emission computed tomography (ECT). One patient had hepatic metastasis, 1 had adrenal metastasis, and 1 had intracranial metastasis. The value of prostate special antigen (PSA) was in an ascending trend in all patients. Gemcitabine of 1 000 mg/m(2) and normal saline solution (NS) of 100 ml were administered by intravenous drip on day 1, and day 8, cisplatin of 100 mg/m(2) and NS of 500 ml were administered by intravenous drip on day 1, or cisplatin of 30 mg/m(2) and NS of 250 ml were administered by intravenous drip from day 1 to day 5 within each 28-day cycle. RESULTS: Values of PSA in 10 patients descended to normal level (< 4 ng/L), those in 4 patients descended by more than 50%, and that in 1 patient had no change. Before chemotherapy, 12 patients suffered from pain of bone metastasis with 4 cases of grade I, 5 cases of grade II, and 3 cases of grade III. After chemotherapy, 9 patients released from pain,only 2 suffered from pain of grade I, 1 suffered from pain of grade II. The maximal diameter of multiple intracranial metastatic lesions was reduced from 3.0 to 0.5 cm, and the symptoms of facial paralysis vanished. Diameter of hepatic metastatic tumor was reduced from 10.2 to 3.3 cm, that of adrenal metastatic tumor was reduced by more than 2/3. Patients were followed-up for 3-29 months with a mean of 15.2 months. Of 15 patients, 2 died of the disease,the median survival time was 14.7 months. Mean time of pain remission was 13.6 months, and the stable period of PSA value descent was 12.3 months. Toxicities of chemotherapy were tolerable, including nausea/vomiting,leukopenia,decreased hemoglobin,and thrombo- cytopenia. CONCLUSIONS: Combined chemotherapy of gemcitabine and cisplatin is effective in treating advanced hormone refractory prostate cancer with tolerable toxicities, and could be considered as an adjuvant therapy for advanced hormone refractory prostate cancer.