A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways.

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes.

The mechanism of curcumin post-treatment relieving lung injuries by regulating miR-21/TLR4/NF-κB signalling pathway.

OBJECTIVE: To investigate the mechanism by which curcumin prevents lung injury in a rat model of limb ischaemia-reperfusion injury. METHODS: Rats were randomized into four groups (n = 20): control group (sham group); ischaemia-reperfusion group (I/R group); curcumin group (I/R+Cur group); and inhibitor of agomir-21 group (I/R+Cur+antagomir-21 group). At 3 h after reperfusion, lung tissues were collected for histopathology and immunohistochemistry to determine the apoptosis index (AI). Lung injury score (LIS) and lung wet/dry (W/D) ratio were determined. Lung microRNA-21 (miR-21) mRNA levels were measured using reverse transcription-polymerase chain reaction. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) protein levels were measured by Western blot analysis. Tumour necrosis factor (TNF)-α and interleukin (IL)-1ß levels were determined by enzyme-linked immunosorbent assays. RESULTS: In the I/R group, the W/D, LIS, AI, miR-21 mRNA, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased and the PaO2 was decreased compared with the sham group. Evidence of lung injury was observed in the I/R group and this was alleviated in the I/R+Cur group. An inhibitor of miR-21 (antagomir-21) reversed the protective effects of curcumin. CONCLUSION: Curcumin post-treatment can alleviate the lung injuries induced by limb ischaemia-reperfusion via downregulating the levels of miR-21 mRNA.

Insights into the Roles of Midazolam in Cancer Therapy.

With its high worldwide mortality and morbidity, cancer has gained increasing attention and novel anticancer drugs have become the focus for cancer research. Recently, studies have shown that most anesthetic agents can influence the activity of tumor cells. Midazolam is a γ-aminobutyric acid A (GABAA) receptor agonist, used widely for preoperative sedation and as an adjuvant during neuraxial blockade. Some studies have indicated the potential for midazolam as a novel therapeutic cancer drug; however, the mechanism by which midazolam affects cancer cells needs to be clarified. This systematic review aims to summarize the progress in assessing the molecular mechanism of midazolam as an anticancer agent.

From palliative to curative treatment - stage IV mucinous adenocarcinoma, successfully treated with metronomic capecitabine in combination with Bevacizumab and surgery- a case report.

BACKGROUND: Mucinous adenocarcinoma (MAC) represents 6-19 % of all colorectal carcinoma. It is associated with poorer response to chemotherapy and chemoradiotherapy. CASE PRESENTATION: A 27-year-old Swedish woman presented with stomach pain and weight loss, and was diagnosed with locally advanced MAC in the transverse colon as well as 3 liver metastases. Neoadjuvant treatment with fluorouracil, folinic acid and oxaliplatin (FLOX) failed due to several infections, pulmonary embolism and deteriorated performance status. The patient was therefore considered palliative. Palliative treatment with metronomic capecitabine 500 mg × 2 daily and bevacizumab every other week were initiated. After 4 months of treatment the tumors had regressed and the patient was able to undergo radical surgery, thereby changing the treatment intention from palliative to curative. No adjuvant chemotherapy was given. There were no signs of recurrence 9 months later. CONCLUSIONS: The role of the combination of metronomic capecitabine and bevacizumab in patients with MAC merits further investigation.

Magnesium Lithospermate B Protects Neurons Against Amyloid ß (1-42)-Induced Neurotoxicity Through the NF-κB Pathway.

Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, a Chinese traditional herbal medicine colloquially known as Dan Shen. In this study, we investigated the neuroprotective effect of MLB against oligomeric amyloid ß (Aß) (1-42)-induced neurotoxicity in cultured FVB mouse hippocampal neurons. We found that pretreatment with MLB not only prevents a loss in neuronal cell viability following exposure to Aß (1-42), but also attenuates Aß (1-42)-induced release of pro-inflammatory cytokines and neuronal apoptosis in a dose-dependent manner. Mechanistic studies show that MLB counteracts Aß (1-42)-induced activation of the nuclear factor kappa B (NF-κB) pathway, evidenced by the suppression of NF-κB luciferase reporters, decreased expression of phosphorylated Inhibitor κB α and IκB kinase α, and reduced nuclear translocation of p65 in response to pre-treatment with 50 µg/ml MLB prior to Aß (1-42) exposure. MLB was able to reverse the increase in phosphorylated c-Jun N-terminal kinase (JNK) levels as well as the decrease in phosphorylated Akt levels that are induced by Aß (1-42), although this finding did not extend to extracellular signal-regulated kinase or p38 kinases. Furthermore, combining MLB with the JNK inhibitor SP600125 synergistically counteracts the Aß (1-42)-induced reduction in cell viability and neurite growth, and the neuroprotective effects of MLB could be attenuated by the Akt inhibitor triciribine. In conclusion, these results suggest that MLB can protect against Aß (1-42)-induced neuronal damage, which is most likely to be mediated by the NK-κB pathway.

Selenium geochemical distribution in the environment and predicted human daily dietary intake in northeastern Qinghai, China.

Ping'an is a selenium (Se)-rich region located in northeastern Qinghai Province of China. To better understand the selenium geochemical distribution and its potential ecological effects, this field study investigated the Se distribution in the local environment, soil Se bioavailability, and the daily dietary Se intake of Ping'an residents. Concentrations of total Se were determined in soil, plant, water, and food samples. Results showed that Ping'an is generally a Se-rich region in China. High-Se soil mainly distributes in the north of Hongshuiquan Town in the study region. Se concentration in 43 plant samples varied significantly from not detected (nd) to 904 µg/kg, following a descending order of pasture > grain > vegetable > fruit, which was much lower than other regions in China. The drinking water Se concentrations were also significantly lower than the European and Chinese surface water Se standards of 10 and 50 µg/L. The predicted daily dietary Se intake (48 ± 20 µg per person) in Ping'an met the demand of the WHO-recommended Se amount of 55 µg per person. The Se content is high in soil, but low in different kinds of plants and Se intake, indicating that Se that can be taken up by plants was very low. The K2HPO4-KH2PO4-extractable Se in the soil accounted for only 3% of the total soil Se, indicating that a low soil bioavailable Se might result in low Se accumulation in plant tissues in Ping'an. This might be due to the influences of geochemistry and the inherent properties of the parent materials of these soils. Therefore, further studies need to focus on better understanding the process and influential factors to soil Se bioavailability to successfully utilize the soil Se resource in low-Se-availability areas.

Cloning and in vitro function analysis of codon-optimized FatI gene.

Currently, n-3 polyunsaturated fatty acids (n-3 PUFAs) have attracted great attention because of their biological significance to organisms. In addition, PUFAs show an obvious impact on prevention and treatment of various diseases. Because n-3 PUFAs cannot be endogenously synthesized by mammals, mammals have to rely on a dietary supplement for sufficient supply. The finding and application of the fatty acid dehydrogenase I (FatI) gene are expected to change the current situation because it can convert n-6 polyunsaturated fatty acids (n-6 PUFAs) to n-3 PUFAs. Meanwhile, the gradual maturation of transgenic technology makes it possible to produce transgenic animals that can synthesize n-3 PUFAs by themselves. In this study, the DNA coding sequence of FatI was synthesized by a chemical method after codon optimization according to the mammal's codon bias. The synthesized DNA sequence was introduced into Boer goat fetal fibroblasts by the constructed recombinant eukaryotic expression vector pcDNA3.1(+)-FatI. Boer goat fetal fibroblasts were transfected by electroporation, and the stable transfected cell lines were obtained by G418 selection. Genomic DNA PCR and Southern blot were applied to verify that the foreign gene FatI was integrated into the genome of the Boer goat fibroblasts. RT-PCR results showed the expression of FatI gene at the mRNA level. The fatty acid profile of cells carrying the FatI gene revealed an increase in total n-3 PUFAs (from 0.61 to 0.95), but a decrease in n-6 PUFAs (from 10.34 to 9.85), resulting in a remarkable increase in the n-3:n-6 ratio (from 0.059 to 0.096). The n-3:n-6 ratio had a 63.49 percent increase, which is a precursor of the response of n-3 desaturase activity of the FatI gene. The study may provide a practical tool for producing transgenic animals that can produce n-3 PUFAs by themselves, and we hope that the application will lay the foundation for animals producing n-3 PUFAs, which will benefit human nutrition and wellness.

[Controlled observation on acupuncture at Fengchi (GB 20) and Tianzhu (BL 10) for treatment of vertebrobasilar insufficiency].

OBJECTIVE: To evaluate clinical therapeutic effect of acupuncture at Fengchi (GB 20) and Tianzhu (BL 10) on vertebrobasilar insufficiency (VBI). METHODS: One hundred and sixteen cases of VBI were randomly divided into 2 groups, 58 cases in each group. The treatment group were treated with acupuncture at Fengchi (GB 20) and Tianzhu (BL 10), and the control group with oral administration of Nimodipine. Clinical symptoms, and the average blood flow rates of left vertebral artery (LVA), right vertebral artery (RVA) and basilar artery (BA) detected by transcranial Doppler's method (TCD) before and after treatment were investigated. RESULTS: The total effective rate was 89.66% in the treatment group and 86.21% in the control group. Acupuncture had significantly therapeutic effect in improvement of clinical symptoms and the average blood flow rate of BA, better than Nimodipine. CONCLUSION: Acupuncture at Fengch; (GB 20) and Tianzhu (BL 10) has obvious therapeutic effect on vertebrobasilar insufficiency.

[Biweekly regimen of high dose of leucovorin, 5-fluorouracil, and paclitaxel for patients with advanced gastric cancer].

BACKGROUND & OBJECTIVE: Clinical study showed that paclitaxel (PTX) may be used to treat gastric cancer. The combination of PTX and 5-fluorouracil (5-FU) is effective, and safe in treating advanced gastric cancer. This study was to investigate efficacy of biweekly regimen of high dose of leucovorin (CF), 5-FU, and PTX on advanced gastric cancer, and its toxicities. METHODS: Twenty patients with advanced gastric cancer received biweekly regimen of CF/5-FU/PTX (200 mg/m(2) of CF, intravenous infusion for 2 h, day 1; 500 mg/m(2) of 5-FU, intravenous injection, day 1; 1 500 mg/m(2) of 5-FU, intravenous infusion for 46 h, day 1, 2; 90 mg/m(2) of PTX, intravenous infusion for 3 h,day 1). Efficacy, and toxicities were evaluated after 4 cycles. RESULTS: Total response rate was 65.0% (13/20) with 2 (10.0%) cases of complete remission (CR), and 11 (55.0%) cases of partial remission (PR). No treatment- related death occurred. Stomatitis, hand-foot syndrome, and loss of hair were main toxicities. CONCLUSION: Biweekly regimen of high dose of CF, 5-FU, and PTX may achieve a high response rate with tolerable toxicities in patients with advanced gastric cancer.

[Relationship of methylenetetrahydrofolate reductase C677T polymorphism and chemosensitivity to 5-fluorouracil in gastric carcinoma].

BACKGROUND & OBJECTIVE: Methylenetrahydrofolate reductase (MTHFR) C677T polymorphism modifies enzyme activity and thus effects the level of 5, 10-methylenetetrahydrofolate (5,10-MTHR), which correlates with the tumor response to 5-fluorouracil (5-FU). This study was to evaluate the effect of MTHFR C677T polymorphism on chemosensitivity and toxicity to 5-FU in patients with gastric carcinoma. METHODS: A total of 75 patients with histologically confirmed advanced gastric carcinoma were included. All patients received 5-fluoropyrimidine-based chemotherapy. Two milliliters of peripheral blood was extracted from each patient before treatment. PCR-RFLP was used to determine the genotypes of MTHFR, including wild-type homozygotes (C/C), heterozygotes (C/T), and mutant homozygotes (T/T). RESULTS: C/C genotype presented in 24 patients (24/75, 32.0%), C/T genotype presented in 33 patients (33/75, 44.0%), and T/T genotype presented in 18 patients (18/75, 24.0%). Total response rate of chemotherapy was 29.3%, among which 22 with partial response, 29 with no change, and 24 with progressive disease. Response rate in patients with T/T genotype (20/24, 83.3%) was significantly greater than either that in patients with C/C genotype (2/24, 8.3%) (Chi2=24.01, P< 0.001), or that in patients with C/T genotype (5/33, 15.2%) (Chi2=22.7, P< 0.001). There was no difference of response rate between C/C and C/T genotypes (Chi2=0.6, P=0.439). Multiple variances logistic regression analysis (adjusted for gender, age, chemotherapy regimens, and adjuvant chemotherapy factors) showed that the probability of chemotherapy work on patients with combination of C/C and C/T genotypes was 0.017-fold to that in patients with T/T genotype (95% CI ranging from 0.003 to 0.102, P< 0.001); incidence of treatment-related side effects, vomiting and nausea, was significantly greater in latter patients than in former patients (Chi2=12.264, P=0.002). CONCLUSIONS: MTHFR C677T polymorphism can predict the effects and toxicity of 5-fluoropyrimidine-based chemotherapy in advanced gastric carcinoma.

Acetylation of rice straw with or without catalysts and its characterization as a natural sorbent in oil spill cleanup.

An investigation of the acetylation of rice straw with acetic anhydride at 100 and 120 degrees C for 1-4 h with four tertiary amine catalysts (pyridine, 4-dimethylaminopyridine, N-methylpyrrolidine, and N-methylpyrrolidinone) or without catalyst in a solvent-free system was undertaken, and the extent of acetylation was measured by weight percent gain, which increased with the extent of reaction time and temperature and the amounts of catalyst used. 4-Dimethylaminopyridine was found to be the most effective catalyst of those studied. At a concentration of 7% of the catalyst in acetic anhydride, a weight percent gain of 15.4% was realized, compared with 11.2% for the noncatalyst reaction, after 0.5 h of exposure to the system at 120 degrees C. Characterization of acetylated straw was performed by FT-IR, CP MAS (13)C NMR, and thermal studies. Interestingly, the acetylated straw is significantly hydrophobic and does not get wet with water, thereby offering potential for the better utilization of cheap waste materials as natural sorbents in oil cleanup.