Apoptotic effects of protocatechuic acid (PCA) at 1, 2, 4, 8 micromol/L on human breast cancer MCF7 cell, lung cancer A549 cell, HepG2 cell, cervix HeLa cell, and prostate cancer LNCaP cell were examined. Results showed that PCA concentration-dependently decreased cell viability, increased lactate dehydrogenase leakage, enhanced DNA fragmentation, reduced mitochondrial membrane potential, and lowered Na(+)-K(+)-ATPase activity for these cancer cells (P < 0.05). PCA also concentration-dependently elevated caspase-3 activity in five cancer cells (P < 0.05), but this agent at 2-8 micromol/L significantly increased caspase-8 activity (P < 0.05). PCA concentration-dependently decreased intercellular adhesion molecule level in test cancer cells (P < 0.05) but significantly inhibited cell adhesion at 2-8 micromol/L (P < 0.05). PCA also concentration-dependently lowered the levels of interleukin (IL)-6 and IL-8 in five cancer cells (P < 0.05), but this agent at 2-8 micromol/L significantly suppressed vascular endothelial growth factor production (P < 0.05). These findings suggest that PCA is a potent anticancer agent to cause apoptosis or retard invasion and metastasis in these five cancer cells.
Osteoporotic hip fractures cause high mortality in the elderly population. However, few population studies reported the long-term mortality of hip fracture among the elderly in Asian population. This study assessed the incidence, excess mortality, and risk factors after osteoporotic hip fractures through inpatients aged 60 years or older. A total of 143,595 patients with hip fracture were selected from Taiwan National Health Insurance database in the years 1999 to 2009 and followed up until the end of 2010. Annual incidence, mortality and SMR, and mortality and SMR at different periods after fracture were measured. From 1999 to 2005, hip fracture incidence gradually increased and then fluctuated after 2006. From 1999 to 2009, the male-to-female ratio of annual incidence increased from 0.60 to 0.66, annual mortality for hip fracture decreased from 18.10% to 13.98%, male-to-female ratio of annual mortality increased from 1.38 to 1.64, and annual SMR decreased from 13.80 to 2.98. Follow-up SMR at one, two, five, and ten years post-fracture was 9.67, 5.28, 3.31, and 2.89, respectively. Females had higher follow-up SMR in the younger age groups (60-69 yr of age) but lower follow-up SMR in the older age groups (over 80 yr of age) compared with males. Among the studied patients, incidence is gradually decreasing along with annual mortality and SMR. Hip fracture affects short-term but not long-term mortality.
The production of chemokine stromal cell-derived factor (SDF)-1 is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinase (MMP)-13 may contribute to the breakdown of articular cartilage during arthritis. Here, we found that SDF-1␣ increased the secretion of MMP-13 in cultured human chondrocytes, as shown by reverse transcriptase-polymerase chain reaction, Western blot, and zymographic analysis. SDF-1␣ also increased the surface expression of CXCR4 receptor in human chondrocytes. CXCR4-neutralizing antibody, CXCR4-specific inhibitor [1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)
What's known on the subject? and What does the study add?Silodosin administered by 4 mg twice daily is as effective as tamsulosin 0.2 mg daily in treating patients with LUTS associated with BPH.Relative to tamsulosin, silodosin has less cardiovascular side effects as judged by the minimal changes of blood pressure and pulse rats after treatment.
OBJECTIVE• To test the hypothesis that the efficacy of silodosin would not be inferior to tamsulosin in treating patients with lower urinary tract symptoms associated with benign prostate hyperplasia (BPH).
PATIENTS AND METHODS• At nine medical centres, 209 patients with an International Prostate Symptom Score (IPSS) of ≥ 13 were randomized to silodosin (4 mg twice daily) or tamsulosin (0.2 mg once daily) for 12 weeks.• The primary efficacy measure was the mean change from baseline to endpoint in IPSS.• The non-inferiority margin of the IPSS change was set at 1.0.• Secondary efficacy measures included change in maximal urinary flow rate (Q max ) and health-related quality of life (HRQL) score.
RESULTS• Of the 170 (81.3%) patients who completed the study, 86.2% in the silodosin group vs 81.9% in the tamsulosin group achieved a ≥ 25% decrease in IPSS ( P = 0.53).• The mean difference (silodosin minus tamsulosin) in IPSS change from baseline was − 0.60 (95% confidence interval − 2.15, 0.95), inferring the non-inferiority of silodosin to tamsulosin.• The mean changes in the Q max and HRQL score from baseline were comparable between the groups (both, P > 0.05). Although patients receiving silodosin had a significantly higher incidence of abnormal ejaculation (9.7% vs tamsulosin 1.0%, P = 0.009), only 1.9% discontinued treatment.• Tamsulosin treatment resulted in a significant reduction in mean systolic blood pressure ( − 4.2 mmHg, within-group P = 0.004) relative to the negligible change of silodosin ( − 0.1 mmHg, within-group P = 0.96)
CONCLUSION• The trial shows the non-inferiority of silodosin 4 mg twice daily to tamsulosin 0.2 mg once daily in patients with symptoms of BPH.
Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multichanneled (MC) scaffolds, cross-linked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts.
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