Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-ß (Aß) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aß aggregation and attenuating Aß-induced oxidation in vitro. When given before or after the onset of Aß deposition via i.p. injection, Edaravone substantially reduces Aß deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

BDNF promotes human neural stem cell growth via GSK-3ß-mediated crosstalk with the wnt/ß-catenin signaling pathway.

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/ß-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3ß expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and ß-catenin components were all downregulated, whereas GSK-3ß was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3ß. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/ß-catenin signaling pathway, and that this interaction may be mediated by GSK-3ß.

[Suprapubis-assisted umbilical laparoendoscopic mini-dual-site surgery for varicocele: a report of 80 cases].

OBJECTIVE: To study the safety, effectiveness and feasibility of suprapubis-assisted umbilical laparoendoscopic mini-dual-site surgery (SAU-LEMDS) in the treatment of varicocele. METHODS: This study included 80 varicocele patients aged 24 - 44 (mean 28.5 +/- 2.6) years, 25 cases of grade I, 45 cases of grade II and 10 cases of grade III, 58 cases in the left side, 6 in the right and 16 in both sides, and all with asthenospermia. The patients were treated by SAU-LEMDS under subarachnoid anesthesia combined with general anesthesia in a supine position with a head-down-feet-up slope of 15 degrees. Two 5 mm trocars were inserted bilaterally at the umbilical edge, one with a 5 mm 30 degrees laparoscope placed in it, and another into the abdominal cavity below the pubic hairline with a 5 mm laparoendoscopic clipper placed in it. The operation procedure was similar to that of standard laparoscopic ligation of spermatic veins, with reservation of the spermatic artery and double-ligation of spermatic veins. And the procedure was repeated for the contralateral lesion in the bilateral cases. Postoperative follow-up was conducted for the incidences of orchiatrophy and testicular hydrocele and changes of seminal parameters. RESULTS: All the operations were successful, with the mean operation time of (10 +/- 5.0) min (range 8 to 25 min) for the unilateral cases and (18 +/- 6.5) min (range 15 to 30 min) for the bilateral cases, the mean blood loss of (1.5 +/- 0.5) ml (range 1 to 2 ml), and the mean postoperative hospital stay of (2 +/- 0.5) d (range 1.5 to 3 d). The patients were followed up for 6 -24 (12 +/- 2.5) months, which showed significant improvement in sperm motility as compared with the baseline ([28.53 +/- 5.21] vs [19.62 +/- 3.56]%, P < 0.05), with 28 cases (35.0%) restored to normal. Recurrence was found in 4 cases (5.0%). Testicular hydrocele occurred in 7 cases (8.75%), but orchiatrophy in none. The scars in the umbilicus and suprapubis were invisible because of the wrinkles and pubic hair. CONCLUSION: SAU-LEMDS is safe, effective and feasible for the treatment of varicocele. It is superior to umbilical laparoendoscopic single-site surgery (U-LESS) for its less invasiveness, simpler operation, and better cosmetic appearance.

p75NTR regulates Abeta deposition by increasing Abeta production but inhibiting Abeta aggregation with its extracellular domain.

Accumulation of toxic amyloid-ß (Aß) in the cerebral cortex and hippocampus is a major pathological feature of Alzheimer's disease (AD). The neurotrophin receptor p75NTR has been proposed to mediate Aß-induced neurotoxicity; however, its role in the development of AD remains to be clarified. The p75NTR/ExonIII-/- mice and APPSwe/PS1dE9 mice were crossed to generate transgenic AD mice with deletion of p75NTR gene. In APPSwe/PS1dE9 transgenic mice, p75NTR expression was localized in the basal forebrain neurons and degenerative neurites in neocortex, increased with aging, and further activated by Aß accumulation. Deletion of the p75NTR gene in APPSwe/PS1dE9 mice reduced soluble Aß levels in the brain and serum, but increased the accumulation of insoluble Aß and Aß plaque formation. There was no change in the levels of amyloid precursor protein (APP) and its proteolytic derivatives, or α-, ß-, and γ-secretase activities, or in levels of BACE1, neprilysin (NEP), and insulin-degrading enzyme (IDE) proteins. Aß production by cortical neurons of APPSwe/PS1dE9 mice was reduced by deletion of p75NTR gene in vitro. Recombinant extracellular domain of p75NTR attenuated the oligomerization and fibrillation of synthetic Aß(42) peptide in vitro, and reduced local Aß plaques after hippocampus injection in vivo. In addition, deletion of p75NTR attenuated microgliosis but increased the microhemorrhage profiles in the brain. The deletion of p75NTR did not significantly change the cognitive function of the mice up to the age of 9 months. Our data suggest that p75NTR plays a critical role in regulating Aß levels by both increasing Aß production and attenuating its aggregation, and they caution that a therapeutic intervention simply reducing p75NTR may exacerbate AD pathology.

Huntingtin associated protein 1 regulates trafficking of the amyloid precursor protein and modulates amyloid beta levels in neurons.

Amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease. It is axonally transported, endocytosed and sorted to different cellular compartments where amyloid beta (Aß) is produced. However, the mechanism of APP trafficking remains unclear. We present evidence that huntingtin associated protein 1 (HAP1) may reduce Aß production by regulating APP trafficking to the non-amyloidogenic pathway. HAP1 and APP are highly colocalized in a number of brain regions, with similar distribution patterns in both mouse and human brains. They are associated with each other, the interacting site is the 371-599 of HAP1. APP is more retained in cis-Golgi, trans-Golgi complex, early endosome and ER-Golgi intermediate compartment in HAP1-/- neurons. HAP1 deletion significantly alters APP endocytosis and reduces the re-insertion of APP into the cytoplasmic membrane. Amyloid precursor protein-YFP(APP-YFP) vesicles in HAP1-/- neurons reveal a decreased trafficking rate and an increased number of motionless vesicles. Knock-down of HAP1 protein in cultured cortical neurons of Alzheimer's disease mouse model increases Aß levels. Our data suggest that HAP1 regulates APP subcellular trafficking to the non-amyloidogenic pathway and may negatively regulate Aß production in neurons.

New screening approach to detecting congenital syphilis in China: a retrospective cohort study.

BACKGROUND: Diagnosis of congenital syphilis (CS) is not straightforward and can be challenging. This study aimed to evaluate the validity of an algorithm using timing of maternal antisyphilis treatment and titres of non-treponemal antibody as predictors of CS. METHODS: Confirmed CS cases and those where CS was excluded were obtained from the Guangzhou Prevention of Mother-to-Child Transmission of syphilis programme between 2011 and 2019. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using receiver operating characteristics (ROC) in two situations: (1) receiving antisyphilis treatment or no-treatment during pregnancy and (2) initiating treatment before 28 gestational weeks (GWs), initiating after 28 GWs or receiving no treatment for syphilis seropositive women. RESULTS: Among 1558 syphilis-exposed children, 39 had confirmed CS. Area under the curve, sensitivity and specificity of maternal non-treponemal titres before treatment and treatment during pregnancy were 0.80, 76.9%, 78.7% and 0.79, 69.2%, 88.7%, respectively, for children with CS. For the algorithm, ROC results showed that PPV and NPV for predicting CS were 37.3% and 96.4% (non-treponemal titres cut-off value 1:8 and no antisyphilis treatment), 9.4% and 100% (non-treponemal titres cut-off value 1:16 and treatment after 28 GWs), 4.2% and 99.5% (non-treponemal titres cut-off value 1:32 and treatment before 28 GWs), respectively. CONCLUSIONS: An algorithm using maternal non-treponemal titres and timing of treatment during pregnancy could be an effective strategy to diagnose or rule out CS, especially when the rate of loss to follow-up is high or there are no straightforward diagnostic tools.

The Effect of Different Treatment Regimens and Multiple Risk Factors on Adverse Pregnancy Outcomes among Syphilis-Seropositive Women in Guangzhou: A Retrospective Cohort Study.

BACKGROUND: To eliminate mother-to-child transmission of syphilis, the Chinese government recommends a treatment regimen that slightly differs from the World Health Organization- (WHO-) recommended treatment. However, little is known about their difference in efficacy. This study is aimed at comparing the effect of China-recommended and WHO-recommend treatment regimens on adverse pregnancy outcomes (APOs) and at examining associated risk factors of APOs among syphilis-seropositive women. METHODS: Using the syphilis registry data, we retrospectively collected data from 4488 syphilis-infected pregnant women in Guangzhou during 2011-2018. Multivariate analyses were used to investigate the association between treatment regimens and APOs (ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth or low birth weight, newborn smaller than gestational age, congenital syphilis, and infant death) and the association between risk factors and APOs. RESULTS: Of 3474 participants, 27.3% had at least one APO. Compared to those receiving WHO-recommended treatment, women who received China-recommended treatment were less likely to have APOs (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.38-0.57), whereas those who received no treatment had 1.6 times higher odds of experiencing APOs. One common risk factor across different APOs was high levels of log2-transformed toluidine red unheated serum test (TRUST) titers before treatment (OR 1.14, 95% CI 1.10-1.19). China-recommended treatment was effective in reducing APOs for those with TRUST ≥ 1 : 8 (OR 0.21, 95% CI 0.14-0.29) and those with TRUST < 1 : 8 (OR 0.62, 95% CI 0.50-0.77). CONCLUSIONS: Syphilis-seropositive women receiving China-recommended treatment had lower odds of APOs, especially when TRUST titers before treatment were high. Findings can be used to guide health professionals to reduce APOs among syphilis-infected mothers and promote nationwide use of China-recommended treatment.

[Serum proteomics profiling for diagnosis of myasthenia gravis].

OBJECTIVE: To identify the significant protein peaks and establish the diagnostic model of myasthenia gravis (MG) by serum proteomics profiling analysis. METHODS: The serum samples from 56 MG patients and 16 healthy controls were detected by the technology of surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). The differentially expressed protein peaks were identified to establish a MG diagnostic model. And preliminary validation was performed. RESULTS: Thirty-eight specific protein peaks with significant differences were found in the serum protein pattern of 56 MG patients and 16 healthy controls. Systemic optimization identified 2 protein peaks of M4168.94 and M1122.57. And they were used to build the MG diagnostic model of differentiating 56 cases from 16 controls. CONCLUSION: The serum protein profiling can be a novel, effective and sensitive tool to screen for MG-related protein peaks and establish a diagnostic model.

[Gastric cancer detection using kubelka-Munk spectral function of DNA and protein absorption bands].

Differential diagnosis for epithelial tissues of normal human gastric, undifferentiation gastric adenocarcinoma, gastric squamous cell carcinomas, and poorly differentiated gastric adenocarcinoma were studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 250 to 650 nm, pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the DNA absorption bands at 260 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 68.5% (p < 0.05), 146.5% (p < 0.05), 282.4% (p < 0.05), 32.4% (p < 0.05), 56.00 (p < 0.05) and 83.0% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the protein absorption bands at 280 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 86.8% (p < 0.05), 262.9% (p < 0.05), 660.1% (p < 0.05) and 34% (p < 0.05), 72. 2% (p < 0.05), 113.5% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the carotene absorption bands at 480 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 59.5% (p < 0.05), 73% (p < 0.05), 258.9% (p < 0.05), 118.7% (p < 0.05), 139.2% (p < 0.05), and 324. 6% (p < 0.05) respectively. It is obvious that pathological changes of gastric epithelial tissues induced that there were significant changes in the contents of the DNA, protein and beta-carotene of gastric epithelial tissues. The conclusion can be applied to rapid, low-cost and noninvasive the optical biopsy for gastric cancer and provides a useful reference.

[Colon adenoma detection using Kubelka-Munk spectral function of DNA and protein bands].

Differential diagnosis of human colon adenoma was studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 590 to 1 064 nm pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the DNA absorption bands at 260 nm between normal and adenomatous colon epithelial tissues, and the differences were 218% (p < 0.05) and 68.5% (p < 0.05) respectively. Pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the protein absorption bands at 280 nm between normal and adenomatous colon epithelial tissues, and the differences were 208% (p < 0.05) and 59.0% (p < 0.05) respectively. Pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the beta-carotene absorption bands at 480 nm between normal and adenomatous colon epithelial tissues, and the differences were 41.7% (p < 0.05) and 32.9% (p < 0.05) respectively. Obviously, pathological changes of colon epithelial tissues were induced so that there were significant changes in the contents of the DNA, protein and beta-carotene of colon epithelial tissues. The conclusion can be applied to rapid, low-cost and noninvasive optical biopsy of colon adenoma, and provides a useful reference.

Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway.

The present study aimed to investigate the role of semaphorin 4D (Sema4D) in bladder cancer cell proliferation and metastasis in vivo and in vitro. Effects of Sema4D modulation on cancer cell viability and clonogenic abilities were assessed by MTT assay and colony formation assay. Cell apoptosis, cell cycle analysis, transwell assays, and wound-healing assays were also assayed. A mouse model of bladder cancer was established to observe the tumorigenesis in vivo. Our data showed that Sema4D was 4-fold upregulated in clinical bladder cancer tissues relative to noncancerous ones and differentially expressed in bladder cancer cell lines. Knockdown of Sema4D in bladder cancer T24 and 5637 cells significantly decreased cell proliferation, clonogenic potential, and motility. On the contrary, overexpression of Sema4D in bladder cancer SV-HUC-1 cells significantly increased cell viability and motility. Concordantly, knockdown of Sema4D impaired while overexpression of Sema4D promoted bladder cancer cell growth rates in xenotransplanted mice. Cell cycle was arrested by modulation of Sema4D. Cell apoptotic rates and the mitochondrial membrane potentials were consistently increased upon knockdown of Sema4D in T24 cells and 5637 cells. Western blotting revealed that epithelial-mesenchymal transition was promoted by Sema4D. The PI3K/AKT pathway was activated upon Sema4D overexpression in SV-HUC-1 cells, while it was inactivated by knockdown of Sema4D in T24 cells. All these data suggest that Sema4D promotes cell proliferation and metastasis in bladder cancer in vivo and in vitro. The oncogenic behavior of Sema4D is achieved by activating the PI3K/AKT pathway.

Effects of Antiretroviral Therapy and HIV Exposure in Utero on Adverse Pregnancy and Infant Outcomes: A Prospective Cohort Study in Guangzhou, China.

OBJECTIVE: This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children. METHODS: This cohort study enrolled 802 HIV-infected pregnant women between October 2009 and May 2018 in Guangzhou, China. The women were assigned to receive combination ART (cART) or mono/dual ART or no treatment. The primary outcomes were the combined endpoints of any adverse pregnancy outcome [including ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth, small for gestational age (SGA)] and adverse early growth outcome (including infant death, HIV infection of mother-to-child transmission, and underweight, wasting and stunting of infants at 4 weeks of age). RESULTS: Adverse pregnancy outcomes occurred in 202 (35.1%) of all enrolled HIV-infected women, and 121 (31.3%) of all infants exhibited adverse effects on early growth at 4 weeks of age. The rates of adverse pregnancy outcomes, spontaneous abortion, ectopic pregnancy, stillbirth, infant death and perinatal HIV infection were higher among women not receiving ART, compared to those treated with cART or mono/dual ART (P < 0.05). However, women treated with cART had a higher rate of SGA, compared to untreated women (P < 0.05). No differences in early infant growth were observed among the different treatment regimens. CONCLUSION: Our findings underscore the essentiality of prioritizing HIV-positive pregnant women for ART, as even mono/dual ART available in resource-limited countries could improve pregnancy outcomes and infant survival..

[Superficial bladder cancer detection using diffuse reflectance spectral ratio R540/R575 of oxygenated hemoglobin bands].

A low-cost, fast, and noninvasive method for early diagnosis of malignant lesions of mucosa tissue based on diffuse reflectance spectra was applied in the study of the optical biopsy of superficial human bladder cancer. In the present paper, differential diagnosis of superficial human bladder cancer was studied using the diffuse reflectance spectral ratio (R540/R575) of the oxygenated hemoglobin absorption bands at 540 and 575 nm in vitro. Diffuse reflectance spectra for mucosa/submucosa tissues of normal bladder and superficial bladder cancer were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that there were three the diffuse reflectance spectral dips at 415, 542 and 577 nm respectively for mucosa/submucosa tissues of normal bladder and superficial bladder cancer in the spectral range from 400 to 600 nm. The mean diffuse reflectance spectral ratio (R540/R575) of normal bladder mucosa/submucosa tissue decreased slowly with time increase after surgical excision, and the mean diffuse reflectance spectral ratio (R540/R575) of superficial bladder cancer mucosa/ submucosa tissue also decreased slowly with time increasing after surgical excision. The mean diffuse reflectance spectral ratios (R540/R575) of normal bladder mucosa/submucosa tissue were 111%, 107%, 104% and 102% after 2, 3, 4 and 5 h after surgical excision respectively, and those of superficial bladder cancer mucosa/submucosa tissue were 98.4%, 95.5%, 93.1% and 91.6% after 2, 3, 4 and 5 h after surgical excision respectively. There were significant differences in mean diffuse reflectance spectral ratio (R540/R575) for mucosa/submucosa tissues between normal bladder and superficial bladder cancer after 2, 3, 4 and 5 h after surgical excision respectively (p < 0.05). Differences in mean diffuse reflectance spectral ratio (R540/R575) for mucosa/ submucosa tissues between normal bladder and superficial bladder cancer were 12.6%, 11.5%, 10.9% and 10.4% after 2, 3, 4 and 5 h after surgical excision respectively. It is obvious that pathological changes in bladder mucosa/submucosa tissues induced changes in the component and structure of the tissues, and especially quantitative changes in oxyhemoglobin and de-oxyhemoglobin of tissues obviously. Conclusion of the study provides a new method that can be applied to rapid, low-cost and noninvasive optical biopsy of superficial bladder cancer.

[Randomized Controlled Clinical Trials of Treatment of Knee Osteoarthritis of Yang-deficiency Pattern by Acupuncture Plus Moxibustion].

OBJECTIVE: To compare the therapeutic effect of acupuncture plus moxibustion and simple acupuncture in the treatment of patients with knee osteoarthritis (KOA) of yang-deficiency syndrome. METHODS: Fifty-eight KOA patients with yang-deficiency syndrome were chosen and randomly divided into acupuncture plus moxibustion group (n＝30) and acupuncture group (n＝28). Neixiyan (EX-LE 4), Dubi (ST 35), Liangqiu (ST 34), Heding (EX-LE 2), Xuehai (SP 10), Yanglingquan (GB 34) on the affected side of the body were punctured with filiform needles or/and stimulated with moxibustion using seed-sized moxa cones. The treatment was conducted once daily for 10 days, followed with another 10 days after 2 days interval. The pain severity was evaluated by using visual analogue scale (VAS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to measure the KOA pain, stiffness and function before and after the treatment, and 1 month after the treatment. The therapeutic effect was also evaluated according to the "Standards for Diagnosis and Therapeutic Effect Evaluation of Diseases/Syndromes of Traditional Chinese Medicine" (issued by the State Administration of Traditional Chinese Medicine of China in 1994). RESULTS: Twenty days and 1 month after the treatment, the scores of VAS, and KOA pain, stiffness and motor function of WOMAC were significantly decreased in both groups in comparison with their own pre-treatment (P<0.01), and were obviously lower in the acupuncture plus moxibustion group than in the acupuncture group (P<0.05, P<0.01). Of the 28 and 30 cases in the acupuncture and acupuncture plus moxibustion groups, 7 and 12 experienced marked improvement, 12 and 16 were effective, 9 and 2 ineffective, with the therapeutic effect being 67.86% and 93.33%, respectively. The therapeutic effect of acupuncture plus moxibustion was apparently superior to that of simple acupuncture (P<0.05). CONCLUSION: Acupuncture plus moxibustion is significantly superior to simple acupuncture therapy in relieving symptoms of KOA patients, and also has a better post-effect.

[Canceration and thermal coagulation of human liver induced changes in the absorption and scattering properties of liver-tissue at near infrared in vitro].

Canceration and thermal coagulation of human liver induced changes in the absorption and scattering properties of liver tissue at 710, 730, 750, 77, 790, 810, 830, 850, 870 and 890 nm of Ti: sapphire laser were studied in vitro. The measurements were performed using a double-integrating-sphere setup, and the absorption and scattering properties were assessed from these measurements using the inverse adding-doubling method. The results of measurement showed that canceration of liver induced significant decrease in the absorption coefficients of liver tissue, and the maximum change in the absorption coefficients is 86.12% at 850 nm, while the minimum change in the absorption coefficients is 82.65% at 750 nm. Thermal coagulation of normal liver induced obvious change in the absorption coefficients from 710 to 890 nm, and the maximum change in the absorption coefficients is 79.55% at 710 nm, while the minimum change in the absorption coefficients 0.72% at 790 nm. Thermal coagulation of carcinoma liver tissue induced significant increase in the absorption coefficients, the maximum change in the absorption coefficients of carcinoma liver tissue is 78.69% at 810 nm, in the minimum change in the absorption coefficients of carcinoma liver tissue 38.16% at 710 nm. Canceration of liver induced significant increase in the scattering coefficients of liver tissue, and the maximum change in the scattering coefficients is 158.37% at 710 nm, while the minimum change in the scattering coefficients is 136.03% at 890 nm. Thermal coagulation of normal liver induced significant increase in the scattering coefficients of liver tissue, and the maximum change in the scattering coefficients is 632.92% at 890 nm, while the minimum change for the scattering coefficients is 587.40% at 710 nm. Thermal coagulation of carcinoma liver tissue induced significant increase in the scattering coefficients, and the maximum change in the scattering coefficients of carcinoma liver tissue is 384. 25% at 810 nm, while the minimum change in the scattering coefficients of carcinoma liver tissue is 330. 86% at 710 nm. The change in the absorption and scattering properties also varies with the change of laser wavelength.

[The effect of CACNA1H gene G773D mutation on calcium channel function].

OBJECTIVE: To study the effect of CACNA1H gene mutation G773D on calcium channel function. METHODS: By the overlap extension PCR we introduced G773D mutation into a human Cav3.2acDNA for constructing the mutant. And then using whole cell clamp technique, we studied the alterations of channel behavior in transfected HEK-293 cells. RESULTS: There were no difference in kinetics of activation and inactivation of calcium channel between wild type and mutant. However comparing with the wild-type Cav3.2 channel, G773D mutant could increase the calcium current density significantly. CONCLUSION: CACNA1H gene G773D mutation is able to increase calcium current and neuronal excitability.

[Precipitation trapping with phenylfluorone and determination of trace gallium, germanium, molybdenum and indium by GFAAS].

The preconcentration of trace gallium, germanium, molybdenum and indium by trapping with precipitation of phenylfluorone (PF), and the determination of the elements by GFAAS were developed. The effects such as those of acidity, amounts of PF, aging time, volume of test solution, and the coexistent ions on the preconcentration of the trace elements were examined in detail. The optimum conditions of preconcentration for Ga(III) were pH approximately 2 test solution 500 mL with added 10.00 mg x mL(-1) PF (2.00 mL) and aging for 4 h, those for Ge(IV) were pH approximately 2 test solution 500 mL with added 10.00 mg x mL(-1) PF (4.00 mL) and aging for 10 h, those for Mo(V) were pH approximately 3 test solution 1 000 mL with added 10.00 mg x mL(-1) PF (3.00 mL) and aging for 6 h, and those for In(III) were pH approximately 5 test solution 100 mL with added 10.00 mg x mL(-1) PF (3.00 mL) and aging for 10 h. The experiment results showed that the main contribution to trapping trace gallium, germanium, molybdenum and indium with PF precipitation was post-precipitation instead of coprecipitation. The detection limits (3s) were 0.12 ng x mL(-1) for gallium, 0.30 ng x mL(-1) for germanium, 0.046 ng x mL(-1) for molybdenum and 2.7 ng x mL(-1) for indium. The developed methods were successfully applied to the determination of trace amount of the elements in water samples, geological standard reference materials, and zinc concentrate samples by graphite furnace atomic absorption spectrometry.

Midkine is a serum and urinary biomarker for the detection and prognosis of non-small cell lung cancer.

Midkine, a heparin-binding growth factor, has been identified as a promising cancer biomarker. In non-small cell lung cancer (NSCLC), the serum and urine midkine levels have not been intensively investigated. The aim of the present study was to investigate the diagnostic and prognostic potential of serum and urine midkine levels in patients with NSCLC. The serum midkine levels were measured in 153 patients with NSCLC, 23 patients with benign pulmonary disease and 95 healthy controls using ELISA. Urine midkine levels were examined in 20 controls and 45 patients with NSCLC. Midkine expression in tumor tissues from 72 patients with NSCLC who underwent definitive surgical resection without any pre-operative treatments was examined by immunohistochemistry. Serum levels were significantly higher in patients with NSCLC than in healthy controls (657.36±496.58 pg/ml vs. 194.49±122.57 pg/ml, P<0.001). As shown in the ROC curve analysis, the sensitivity and specificity of the cut-off serum midkine concentration of 400 pg/ml for predicting the presence of NSCLC were 71.2% and 88.1%, respectively. Positive correlations between the serum midkine levels and immunohistochemistry staining scores (r=0.315, P=0.007) and between the serum midkine levels and urine midkine levels (r=0.636, P<0.001) were observed using Spearman's bivariate correlations. The serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, and its overexpression yielded a relative risk of death of 2.072 (0.01.

Melatonin inhibits AP-2ß/hTERT, NF-κB/COX-2 and Akt/ERK and activates caspase/Cyto C signaling to enhance the antitumor activity of berberine in lung cancer cells.

Melatonin, a molecule produced throughout the animal and plant kingdoms, and berberine, a plant derived agent, both exhibit antitumor and multiple biological and pharmacological effects, but they have never been combined altogether for the inhibition of human lung cancers. In this study, we investigated the role and underlying mechanisms of melatonin in the regulation of antitumor activity of berberine in lung cancer cells. Treatment with melatonin effectively increased the berberine-mediated inhibitions of cell proliferation, colony formation and cell migration, thereby enhancing the sensitivities of lung cancer cells to berberine. Melatonin also markedly increased apoptosis induced by berberine. Further mechanism study showed that melatonin promoted the cleavage of caspse-9 and PARP, enhanced the inhibition of Bcl2, and triggered the releasing of cytochrome C (Cyto C), thereby increasing the berberine-induced apoptosis. Melatonin also enhanced the berberine-mediated inhibition of telomerase reverses transcriptase (hTERT) by down-regulating the expression of AP-2ß and its binding on hTERT promoter. Moreover, melatonin enhanced the berberine-mediated inhibition of cyclooxygenase 2 (COX-2) by inhibiting the nuclear translocation of NF-κB and its binding on COX-2 promoter. Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2ß/hTERT, NF-κB/COX-2 and Akt/ERK signaling pathways. Our findings provide new insights in exploring the potential therapeutic strategies and novel targets for lung cancer treatment.

hnRNPA2/B1 activates cyclooxygenase-2 and promotes tumor growth in human lung cancers.

Cyclooxygenase-2 (COX-2) is highly expressed in tumor cells and has been regarded as a hallmarker for cancers, but the excise regulatory mechanism of COX-2 in tumorigenesis remains largely unknown. Here, we pulled down and identified a novel COX-2 regulator, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), which could specifically bind to COX-2 core promoter and regulate tumor growth in non-small-cell lung cancers (NSCLCs). Knockdown of hnRNPA2/B1 by shRNA or siRNA downregulated COX-2 expression and prostaglandin E2 (PGE2) production, and suppressed tumor cell growth in NSCLC cells in vitro and in vivo. Conversely, overexpression of hnRNPA2/B1 up-regulated the levels of COX-2 and PGE2 and promoted tumor cell growth. We also showed that hnRNPA2/B1 expression was positively correlated with COX-2 expression in NSCLC cell lines and tumor tissues, and the up-regulated expression of hnRNPA2/B1 and COX-2 predicted worse prognosis in NSCLC patients. Furthermore, we demonstrated that the activation of COX-2 expression by hnRNPA2/B1 was mediated through the cooperation with p300, a transcriptional co-activator, in NSCLC cells. The hnRNPA2/B1 could interact with p300 directly and be acetylated by p300. Exogenous overexpression of p300, but not its histone acetyltransferase (HAT) domain deletion mutation, augmented the acetylation of hnRNPA2/B1 and enhanced its binding on COX-2 promoter, thereby promoted COX-2 expression and lung cancer cell growth. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth by activating COX-2 signaling in NSCLC cells and imply that the hnRNPA2/B1/COX-2 pathway may be a potential therapeutic target for human lung cancers.