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.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion.

BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

Genome-wide identification and analysis of long noncoding RNAs in longissimus muscle tissue from Kazakh cattle and Xinjiang brown cattle.

OBJECTIVE: In recent years, long noncoding RNAs (lncRNAs) have been identified in many species, and some of them have been shown to play important roles in muscle development and myogenesis. However, the differences in lncRNAs between Kazakh cattle and Xinjiang brown cattle remain undefined; therefore, we aimed to confirm whether lncRNAs are differentially expressed in the longissimus dorsi between these two types of cattle and whether differentially expressed lncRNAs regulate muscle differentiation. METHODS: We used RNA-seq technology to identify lncRNAs in longissimus muscles from these cattle. The expression of lncRNAs were analyzed using StringTie (1.3.1) in terms of the fragments per kilobase of transcript per million mapped reads values of the encoding genes. The differential expression of the transcripts in the two samples were analyzed using the DESeq R software package. The resulting false discovery rate was controlled by the Benjamini and Hochberg's approach. KOBAS software was utilized to measure the expression of different genes in Kyoto encyclopedia of genes and genomes pathways. We randomly selected eight lncRNA genes and validated them by quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: We found that 182 lncRNA transcripts, including 102 upregulated and 80 downregulated transcripts, were differentially expressed between Kazakh cattle and Xinjiang brown cattle. The results of RT-qPCR were consistent with the sequencing results. Enrichment analysis and functional annotation of the target genes revealed that the differentially expressed lncRNAs were associated with the mitogen-activated protein kinase, Ras, and phosphatidylinositol 3-kinase (PI3k)/Akt signaling pathways. We also constructed a lncRNA/mRNA coexpression network for the PI3k/Akt signaling pathway. CONCLUSION: Our study provides insights into cattle muscle-associated lncRNAs and will contribute to a more thorough understanding of the molecular mechanism underlying muscle growth and development in cattle.

[Analysis on the inheritance of inhibition and anti-inhibition of coleoptile purple line in rice and the SSR location of Ai(t) gene].

The ratio of purple line: no-purple line(13:3) was observed in six different F2 populations produced by crossing between parents with purple line and no-purple line in coleoptile. The backcross of XNA//XNA/ 21A150 (XNA, no-purple line and CMS, as the recurrent parent) resulted in a ratio of 1:1 (purple line: no-purple line). Genetic analysis showed that the expression of rice coleoptile purple line was influenced by two genes, inhibiting gene I and anti-inhibiting gene Ai(t). I gene inhibits P gene of C_A_P_ system and Ai(t) inhibits / gene, respectively. The gene pools of Ai(t) ai(t) and ai(t) ai(t) were constructed with BF1 of XNA//XNA/21A150. SSR analysis indicated that Ai(t) gene was linked with the markers of RM335, RM295, RM287 and RM21 and the genetic distance from Ai(t) to these four markers were 2.8 cM, 10.2 cM, 13.9 cM, 26.1 cM, respectively.

The effect of simvastatin on the serum monocyte chemoattractant protein-1 and intracellular adhesion molecule-1 levels in diabetic rats.

OBJECTIVE: This study aimed to observe the effect of simvastatin on the serum monocyte chemoattractant protein-1 (MCP-1) and intracellular adhesion molecule-1 (ICAM-1) levels and to probe its protective mechanisms on macroangiopathy in diabetic rats. METHODS: Twenty-four Wistar rats were randomly assigned to a normal control group (Group A, n=8), and STZ-induced diabetic group (Group B, n=8), or a simvastatin-treated diabetic group (Group C, n=8). Rats in Group C were treated with simvastatin (20 mg kg(-1) day(-1)) 1 week after the establishment of the diabetic model. Groups A and B were treated with corresponding sodium chloride. Peripheral blood glucose was tested weekly; serum MCP-1, ICAM-1, and HbA1c levels were tested at the eighth week. RESULTS: At the second, fourth, and eighth week, peripheral blood glucose levels in Group B were similar to those of Group C, which were much higher than those of Group A. Serum MCP-1 and ICAM-1 levels in Groups B and C were higher than those of Group A (P<.01), and serum MCP-1 and ICAM-1 levels in Group C were lower than those of Group B (P<.01); HbA1c was not significantly different between Group C and Group B. CONCLUSION: Simvastatin has the effect of anti-inflammation, which may play some protection against the progress of atherosclerosis in diabetic rats.

[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.