Preparation and characterization of genipin-crosslinked rat acellular spinal cord scaffolds.

The feasibility of rat acellular spinal cord scaffolds for tissue engineering applications was investigated. Fresh rat spinal cords were decellularized and crosslinked with genipin (GP) to improve their structural stability and mechanical properties. The GP-crosslinked spinal cord scaffolds possessed a porous structure with an average pore diameter of 31.1 µm and a porosity of 81.5%. The resultant scaffolds exhibited a water uptake ratio of 229%, and moderate in vitro degradation rates of less than 5% in phosphate-buffered saline (PBS) and slightly more than 20% in trypsin-containing buffer, within 14 days. The ultimate tensile strength and elastic modulus of GP-crosslinked spinal cord scaffolds were determined to be 0.193±0.064 MPa and 1.541±0.082 MPa, respectively. Compared with glutaraldehyde (GA)-crosslinked acellular spinal cord scaffolds, GP-crosslinked scaffolds demonstrated similar microstructure and mechanical properties but superior biocompatibility as indicated by cytotoxicity evaluation and rat mesenchymal stem cell (MSC) adhesion behavior. Cells were able to penetrate throughout the crosslinked scaffold due to the presence of an interconnected porous structure. The low cytotoxicity of GP facilitated cell proliferation and extracellular matrix (ECM) secretion in vitro on the crosslinked scaffolds over 7 days. Thus, these GP-crosslinked spinal cord scaffolds show great promise for tissue engineering applications.

Pulsed reduced dose-rate radiotherapy as re-irradiation for brain metastasis in a patient with lung squamous-celled carcinoma.

The recurrence and progression of brain metastases after brain irradiation are a major cause of mortality and morbidity in patients with cancer. The risk of radiation-induced neurotoxicity and efficacy probably leads oncologists to not consider re-irradiation. We report the case of a 48-year-old Asian male diagnosed with squamous cell lung cancer and multiple brain metastases initially treated with 40 Gy whole-brain radiotherapy and 20 Gy partial brain boost. Fourteen gray stereotactic radiosurgery as salvage for brain metastases in the left occipital lobe was performed after initial irradiation. The recurrence of brain metastases in the left occipital lobe was demonstrated on magnetic resonance imaging at 9 months after initial radiotherapy. He received the second course of 28 Gy stereotactic radiosurgery for the recurrent brain metastases in the left occipital lobe. The third relapse of brain metastases was demonstrated by a magnetic resonance imaging scan at 7 months after the second radiotherapy. The third course of irradiation was performed because he refused to undergo surgical resection of the recurrent brain metastases. The third course of irradiation used a pulsed reduced dose-rate radiotherapy technique. It was delivered in a series of 0.2 Gy pulses separated by 3-min intervals. The recurrent brain metastases were treated with a dose of 60 Gy using 30 daily fractions of 2 Gy. Despite the brain metastases receiving 162 Gy irradiation, this patient had no apparent acute or late neurologic toxicities and showed clinical improvement. This is the first report of the pulsed reduced dose-rate radiotherapy technique being used as the third course of radiotherapy for recurrent brain metastases.

LBP and CD14 polymorphisms correlate with increased colorectal carcinoma risk in Han Chinese.

AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs2232596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy controls of Han Chinese in a case-control study. Single-nucleotide polymorphisms (SNPs) between cases and controls were analyzed by unconditional logistic regression. RESULTS: GA and GG genotypes of LBP rs2232596 were associated with a significantly increased risk of CRC [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.15-1.99, P = 0.003; OR = 2.49, 95% CI 1.16-5.38, P = 0.016, respectively]. A similar association was also observed for the CG genotype of CD14 rs4914 (OR= 1.69, 95% CI 1.20-2.36, P = 0.002). In addition, a combination of polymorphisms in LBP rs2232596 and CD14 rs4914 led to a 3.4-fold increased risk of CRC (OR = 3.44, 95% CI 1.94-6.10, P = 0.000). CONCLUSION: This study highlights the LBP rs2232596 and CD14 rs4914 polymorphisms as biomarkers for elevated CRC susceptibility in the Chinese Han population.

Effects of berberine against radiation-induced intestinal injury in mice.

PURPOSE: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. METHODS AND MATERIALS: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-alpha, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. RESULTS: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-alpha, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonaldehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). CONCLUSION: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.