[Jiangtang Sanhuang tablet inhibits endoplasmic reticulum stress and autophagy in diabetic mouse islet cells].

OBJECTIVE: To investigate effects of Jiangtang Sanhuang tablet (JTSHT) for regulating blood glucose and alleviating islet cell damage in db/db mice and its protective effects against endoplasmic reticulum stress (ERS) and autophagy induced by glycolipid toxicity. METHODS: Forty db/db mice were randomized into 4 groups for daily intragastric administration of saline, JTSHT of 2.64 and 1.32 g/kg, and metformin at 0.225g/kg for 8 weeks, using 10 C57BL/6J mice as the normal control. After the treatments, the metabolic indexes of the mice were measured, and morphological changes of the islet cells were observed. A mouse islet cell line (MIN6) was exposed to high glucose (22 mmol/L glucose) and 0.1 mmol/L palmitic acid, followed by treatment with the sera from JTSHT- or saline- treated SD rats, alone or in combination with SP600125, and the changes in cell apoptosis, ERS and autophagy were evaluated using flow cytometry, RT-qPCR and Western blotting. RESULTS: In db/db mice, treatment with JTSHT significantly improved glucose and lipid metabolism (P < 0.05) and suppressed progressive weight gain (P < 0.05) without significant effect on drinking water volume (P > 0.05). JTSHT was also found to promote repair of islet cell injuries. In the cell experiments, high glucose exposure significantly increased apoptosis rate of MIN6 cells (P < 0.05), which was obviously lowered by treatment with JTSHT-treated rat serum (P < 0.05). Western blotting showed that JTSHT significantly reduced the level of ERS and autophagy caused by glycolipid toxicity in MIN6 cells (P < 0.05). Interference with ERS using SP600125 significantly attenuated the protective effect of JTSHT against MIN6 cell injury, apoptosis and autophagy induced by glycolipid toxicity (P < 0.05). CONCLUSION: JTSHT has protective effects against glycolipid toxicity in MIN6 cells possibly by inhibiting ERS and autophagy.

Effects of rumen-protected methionine and other essential amino acid supplementation on milk and milk component yields in lactating Holstein cows.

Objectives of this study were to investigate the effects of supplementing rumen-protected methionine (RP-Met), threonine (RP-Thr), isoleucine (RP-Ile), and leucine (RP-Leu) individually or jointly to a low-protein diet, on the performance of lactating dairy cows, as well as to determine the effects of these amino acids (AA) on the mammalian target of rapamycin (mTOR) in vivo. Ten lactating Holstein cows were randomly allocated to a repeated 5 × 5 Latin square experiment with five 19-d periods. Treatments were high-protein diet (16% crude protein, positive control; HP), low-protein diet (12% crude protein, negative control; LP), LP plus RP-Met (LPM), LP plus RP-Met and RP-Thr (LPMT), and LP plus RP-Met, RP-Thr, RP-Ile, and RP-Leu (LPMTIL). The dry matter intakes (DMI) of the LP, LPM, and LPMT diets were lower than that of the HP diet, whereas the DMI of the LPMTIL diet was intermediate between the HP diet and the other LP diets. Supplementing RP-Met to the LP diet increased the yields of milk and milk protein, increased the content of milk urea N, and tended to increase milk N efficiency. Co-supplementation of RP-Thr with RP-Met resulted in no further milk production increase. Co-supplementation of all 4 rumen-protected amino acids (RP-AA) increased milk and lactose yields to the level of the HP diet and tended to increase milk protein yield compared with the LPMT diet. We found no significant differences in the contents and yields of milk components between the LPMTIL and HP diets except for a lower milk urea N content in the LPMTIL diet. Venous concentrations of the measured AA were similar across the LP and LP diets supplemented with RP-AA. Relative to levels of the HP diet, LP diets had higher venous concentrations of Met and Gly and tended to have higher Phe concentration and lower concentrations of Val and BCAA. The LPMTIL diet had higher venous concentrations of Arg, Lys, Met, Phe, and Glu, and a lower Val concentration. Phosphorylation status of the measured mTOR components in LPM and LPMT treatments were similar to those in the LP treatment but phosphorylation status of mTOR and eIF4E-binding protein 1 (4eBP1) in LPMTIL treatment were higher. The phosphorylation rates of eukaryotic elongation factor 2 (eEF2) in the 4 LP and LP plus RP-AA diets were higher than that of the HP diet. Overall, results of the present study supported the concept that under the relatively short time of this experiment, supplementing RP-AA, which are believed to stimulate the mTOR signal pathway, can lead to increased milk protein yield. This increase appears to be due to increased DMI, greater mTOR signaling, and greater eEF2 activity.

Effects of jugular infusions of isoleucine, leucine, methionine, threonine, and other amino acids on insulin and glucagon concentrations, mammalian target of rapamycin (mTOR) signaling, and lactational performance in goats.

The supply and profile of absorbed AA may affect milk protein synthesis through hormonal changes and mammalian target of rapamycin (mTOR) signaling pathways; and Ile, Leu, Met, and Thr (ILMT) are the 4 AA that have been reported to have the greatest effect on mammary mTOR signaling. The extent to which ILMT and the other remaining AA (RAA) differ in their effects on milk protein synthesis needs to be systematically investigated. In this study, 5 lactating goats, averaging 120 ± 10 d in milk, fitted with jugular vein and carotid artery catheters, were fasted for 24 h, followed by intravenous infusions of a mixture containing AA and glucose for 8 h in a 5 × 5 Latin square design. The AA mixtures were formulated according to the profile of casein. The amounts of AA infused were calculated based on supplies of AA when metabolizable protein (MP) was at requirement (MR). Treatments were an infusate containing glucose without AA (NTAA); an infusate containing 3 × the MR of Ile, Leu, Met and Thr (3F0R); and infusates containing 3F0R plus 1, 2, or 3 × MR of RAA (3F1R, 3F2R, and 3F3R, respectively) according to amounts provided when fed to meet MP requirements for maintenance and lactation for each goat. Milk, arterial blood, and mammary tissue samples were collected immediately after halting the infusion. Relative to NTAA, supplementation of ILMT tended to increase milk protein production and plasma glucose concentrations, and increased milk and lactose production, but had no effects on production or content of milk fat. Graded supplementation of RAA tended to quadratically affect production of milk and lactose. Arterial glucose and glucagon concentrations decreased linearly, and plasma insulin concentrations decreased quadratically with increased RAA. Mammary p70-S6K1 phosphorylation was decreased by addition of ILMT compared with NTAA but increased linearly with increased RAA infusion. Furthermore, EIF4EBP1 gene expression was much lower for 3F-treated goats than for the NTAA treatment. Both MTOR and RPS6KB1 gene expressions were decreased quadratically with increased RAA supply. These results suggested that short-term milk protein yield tended to be increased by elevated ILMT availability, and this trend was not explained by variations in mammary mTOR signaling or pancreatic hormone secretions, whereas graded increase of RAA in combination with ILMT appeared to regulate the efficiency of conversion of glucose to lactose in a manner not involving milk protein production.

[Effects of application of vancomycin in the early stage of patients with extremely severe burn].

Objective: To evaluate the effects of application of vancomycin in the early stage of patients with extremely severe burn, in order to provide reference to drug for anti-infection treatment in the early stage of patients with extremely severe burn. Methods: Data of 15 patients of Kunshan explosion on August 2nd, 2014, admitted to the Department of Intensive Care in our hospital were retrospectively analyzed. The clinical efficacy of continuously intravenous dripping of vancomycin (combined with imipenem) in the early stage of burns (before and on post burn day 14) was analyzed. (1) The steady state plasma concentration of vancomycin was monitored respectively 30 min before the third, sixth, and tenth medication with direct chemiluminescent imaging method. (2) The distribution of Gram-positive bacteria of patients during hospitalization and their drug resistance to 14 antibiotics commonly used in clinic were analyzed. (3) Serum level of procalcitonin (PCT), white blood cell count, percentage of neutrophils before and after treatment, and efficacy grade of anti-infection treatment in the early stage of burns were analyzed. (4) Serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine before and after treatment, and the adverse effects during medication were analyzed. The WHONET 5.5 statistical software was used to analyze the distribution of Gram-positive bacteria in all the pathogens, and the status of drug resistance of Gram-positive bacteria to 14 antibiotics. Data were processed with Wilcoxon rank sum test. Results: (1) Twenty-nine times of steady state plasma concentration monitoring were performed in the patients in total, with the steady state plasma concentration of vancomycin from 4.3 to 42.1 µg/mL. In the monitoring before third, sixth, and tenth medication, the percentages of result reaching the standard were respectively 1, 3/14, and 2/7. (2) A total of 79 Gram-positive bacteria were isolated, including 49 (62.03%) strains of Staphylococcus aureus, 9 (11.39%) strains of Staphylococcus haemolyticus, 7 (8.86%) strains of Staphylococcus epidermidis, 12 (15.19%) strains of Enterococcus faecium, and 2 (2.53%) strains of Enterococcus faecalis. The above-mentioned Staphylococcus strains were with high drug resistance to antibiotics including penicillins, erythromycin, ciprofloxacin, and low drug resistance to linezolid, teicoplanin, and nitrofurantoin. The above-mentioned Enterococcus strains were with high drug resistance to antibiotics including erythromycin, ciprofloxacin, gentamicin, and low drug resistance to linezolid and teicoplanin. The above-mentioned Staphylococcus strains were all sensitive to vancomycin. Two strains of vancomycin-resistant Enterococcus were detected in the above-mentioned Enterococcus strains. (3) Serum level of PCT, white blood cell count, percentage of neutrophils of patients were (8.1±7.5) ng/mL, (24±10)×10(9)/L, and 0.898±0.029 before treatment, which were significantly higher than (3.0±2.8) ng/mL, (12±5)×10(9)/L, and 0.867±0.016 after treatment (with Z values respectively -2.103, -3.237, and -3.068, P<0.05 or P<0.01). After the early treatment, excellence, progess, and invalid results were achieved in 7, 5, and 3 patients, with the effective percentage of 4/5 in clinic. (4) There were no statistically significant differences in serum levels of AST, ALT, and creatinine of patients between before and after treatment (with Z values respectively-0.057, -1.508, and -1.363, P values above 0.05). Only one patient had liver and renal dysfunction during treatment. Conclusions: The positive and reasonable use of vancomycin can remove most of the Gram-positive bacteria, and control the development of sepsis combined with imipenem in the early stage of patients with extremely severe burn. However, the dose of vancomycin should be individualized and the steady state plasma concentration should be monitored to maintain the blood concentration within the safe and effective range, so as to improve the rational use of vancomycin.

Icariin promotes mouse hair follicle growth by increasing insulin-like growth factor 1 expression in dermal papillary cells.

BACKGROUND: Icariin is a major flavonoid isolated from Epimedium spp. leaves (Epimedium Herba), and has multiple pharmacological functions, including anti-angiogenesis, anti-oxidant, anti-inflammatory and immunoprotective effects. AIM: To investigate whether icariin can stimulate growth of hair follicles in mice and the underlying mechanism. METHODS: In vitro, the effect of icariin on hair growth was assessed by using a vibrissae hair follicle (VHF) organ-culture model. The proliferation of hair matrix keratinocytes and the expression of insulin-like growth factor (IGF)-1 in follicles were examined by double immunostaining for 5-bromo-2'-deoxyuridine and IGF-1, in the presence or absence of icariin. Dermal papilla cells (DPCs) were cultured and IGF-1 level was measured by reverse transcription-PCR and ELISA after icariin treatment. In vivo, the effect of icariin on hair growth was examined by gavage feeding of icariin to mice whose backs had been depilated, and the conversion of telogen to anagen hair was observed. RESULTS: Treatment with icariin promoted hair shaft elongation, prolonged the hair cycle growth phase (anagen) in cultured VHFs, and accelerated transition of hair cycle from telogen to anagen phase in the dorsal skin of mice. There was significant proliferation of matrix keratinocytes and an increased level of IGF-1 in cultured VHFs. Moreover, icariin treatment upregulated IGF-1 mRNA expression in DPCs and increased IGF-1 protein content in the conditioned medium of DPCs. CONCLUSIONS: These results suggest that icariin can promote mouse hair follicle growth via stimulation of IGF-1 expression in DPCs.

Tea consumption and its interactions with tobacco smoking and alcohol drinking on oral cancer in southeast China.

BACKGROUND/OBJECTIVES: Epidemiological results on the association between tea consumption and oral cancer remain controversial. We aimed to evaluate the exact relationship between tea consumption and oral cancer in Chinese population. SUBJECTS/METHODS: A large-scale case-control study was conducted on 586 oral cancer patients and 1024 controls frequency-matched by age and gender. Epidemiological data were collected through face-to-face interviews with a structure questionnaire. Unconditional logistic regression model was used to assess the effect of tea consumption on oral cancer stratified by smoking, alcohol drinking and demographics. Quantity of tea consumed (ml/day) was categorized into five subgroups based on quartiles and then its interactions was evaluated with tobacco smoking and alcohol drinking at each subgroup. RESULTS: Tea consumption showed an inverse association with oral cancer for non-smokers or non-alcohol drinkers (the odds ratios (ORs) were 0.610 (95% confidence interval (CI): 0.425-0.876) and 0.686 (95% CI: 0.503-0.934), respectively). For smokers or alcohol drinkers, decreased risk was only observed in those who consumed >800 ml/day. Furthermore, oolong tea consumption was associated with decreased risk of oral cancer in smokers or alcohol drinkers but not in non-smokers or non-alcohol drinkers. Tea consumption combined with smoking or/and alcohol drinking had a greater risk than tea consumption alone, but the risk was roughly reduced from zero to Q4 (>800 ml/day). Additionally, when stratified by demographics, the protective effect of tea was especially evident in females, urban residents, normal body mass index population (18.5-23.9), farmers, office workers and those aged <60 years. CONCLUSIONS: Tea consumption protects against oral cancer in non-smokers or non-alcohol drinkers, but this effect may be obscured in smokers or alcohol drinkers. Additionally, demographics may modify the association between tea consumption and oral cancer.

Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion.

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

Development and characterization of genic-SSR markers from different Asia lotus (Nelumbo nucifera) types by RNA-seq.

Nelumbo nucifera is an important economic vegetable and traditional medicine, but available genetic resources remain limited. Next generation sequencing has proven to be a rapid and effective means of identifying genic simple sequence repeat (genic-SSR) markers. This study developed genic-SSRs for N. nucifera using Illumina sequencing technology to assess diversity across cultivated and wild lotus. A total of 105,834 uni-contigs were produced with an average read length of 722 bp. Exactly 11,178 genic-SSR loci were identified in 9523 uni-contigs. Di-nucleotide (64.5%) was the most abundant SSR, followed by tri-nucleotide (23%), tetra-nucleotide (8.9%), penta-nucleotide (2.5%), and hexa-nucleotide (1%) repeat types. The most common di- and tri-nucleotide repeat motifs were AG/CT (51%) and AAG/CTT (8%), respectively. Based on these SSRs sequences, 6568 primer pairs were designed, of which 72 primers were randomly selected for synthesis and validation, and 38 in-silico polymorphic primers were obtained using in-house perl scripts. A total of 110 primers were screened in the lotus samples and the results showed that 101 primers yielded amplification products, of which 80 were polymorphs. The number of alleles ranged from 2 to 17 and the PIC (polymorphism information content) ranged from 0.19 to 0.87 with a mean value of 0.55. An Unweighted Pair Group Method with Arithmetic Mean (UPGMA) dendrogram based on Jaccard's similarity coefficients showed that the correlation between geographical source and genotype was low. This study describes the distribution of genic-SSRs in the expressed portion of the lotus genome. These genic-SSRs have an important role to play in molecular mapping, diversity analysis, and marker-assisted selection strategies in Nelumbo.

Effects of different formulations of α-tocopherol acetate (vitamin E) on growth performance, meat quality and antioxidant capacity in broiler chickens.

The objective of this study was to investigate and compare the effects of α-tocopherol acetate (vitamin E (VE)) and microencapsulated VE (MVE) on growth performance, meat quality and antioxidant capacity in broiler chickens. A total of 360 d-old broiler chicks were procured and randomly allocated into three groups with 6 replicates. Each replicate had 20 chickens. Chickens were fed with basal diets (CON group) or experimental diets supplemented with 20 mg/kg VE (VE group) or 20 mg/kg MVE (MVE group) for 42 d. The results showed that the MVE group had higher body weight gain (BWG) than the CON and VE groups, and higher gain/feed ratio (G/F ratio) than the CON group during the period of 22-42 d. During the whole experiment, a higher increase in BWG was found in the MVE group than the CON group. Chickens fed on diets supplemented with the VE or MVE had lower abdominal fat percentage, higher pH and antioxidant enzyme activity than the CON group in the breast meat. There was an increased tendency in the hepatic glutathione peroxidase (GSH-Px) enzyme activity of the VE and MVE groups than the CON group. The hepatic mitochondrial total antioxidant capacity and GSH-Px enzyme activity in the MVE group were higher than the CON group. Hepatic 2,2-dipheny-ʟ-picrylhydrazyl scavenging activity of the MVE group was higher than the CON group. These results suggested that the dietary addition of VE or MVE could improve breast meat quality in broilers. MVE supplementation may improve growth performance, hepatic mitochondrial antioxidant capacity and free radical scavenging capacity in chickens. In addition, dietary supplementation of MVE gave better broiler growth performance than VE.

Dietary curcumin supplementation protects against heat-stress-impaired growth performance of broilers possibly through a mitochondrial pathway.

A total of 400 1-d-old Arbor Acres broiler chicks were raised at a recommended environmental temperature from d 1 to 20 (experimental day [ED] = ED1 to ED20). On ED21, the chicks were weighed and reallocated into 5 treatment groups, with 8 replicates of 10 birds each. The 5 treatment groups were as follows: the control group, in which chicks were housed at 22 ± 1°C and fed the basal diet, and the HS, HS-CUR50, HS-CUR100, and HS-CUR200 groups, in which chicks were housed at 34 ± 1°C for 8 h (0900-1700 h) and 22 ± 1°C for the rest time and fed the basal diet with 0, 50, 100, and 200 mg/kg curcumin, respectively. From ED21 to ED42, the heat treatment lasted for 20 consecutive days. The results showed that heat-stressed broilers had greater (P < 0.05) average head surface and rectal temperature on ED21 and ED42 than the non-heat-stressed broilers. Diets supplied with 50 and 100 mg/kg curcumin increased (P < 0.05) the G:F compared to the heat-stressed groups. Mitochondrial malondialdehyde levels, an index of lipid peroxidation, in the breast muscle were 15.15 and 9.09% higher (P < 0.05) in 50 and 100 mg/kg curcumin supplemented groups than that of the heat-stressed group, respectively. Curcumin supplementation (50, 100, and 200 mg/kg) increased (P < 0.05) mitochondrial glutathione content and glutathione peroxidase, glutathione S-transferase, and manganese superoxide dismutase activities compared to heat-stressed broilers. Curcumin supplementation (50, 100, and 200 mg/kg) resulted in a decrease (P < 0.05) of heat shock protein 70 mRNA levels in the breast muscle. The breast muscle mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1α and nuclear respiratory factor 1 and 2 in heat-stressed groups was increased (P < 0.05) in response to dietary 100 mg/kg curcumin treatment. Additionally, when compared to the heat-stressed group, mitochondrial transcription factor A mRNA levels were increased (P < 0.05) by 17.64% in the 200 mg/kg curcumin supplemented group. In conclusion, dietary curcumin supplementation prevented heat-stress-impaired growth performance, possibly through improving the antioxidant defense system and enhancing the mitochondrial biogenesis.

Muscle-building supplement use and increased risk of testicular germ cell cancer in men from Connecticut and Massachusetts.

BACKGROUND: No analytic epidemiological study has examined the relationship between use of muscle-building supplements (MBSs) and testicular germ cell cancer (TGCC) risk. METHODS: We conducted a population-based case-control study including 356 TGCC cases and 513 controls from Connecticut and Massachusetts. RESULTS: The odds ratio (OR) for ever use of MBSs in relation to risk of TGCC was significantly elevated (OR=1.65, 95% confidence interval (CI): 1.11-2.46). The associations were significantly stronger among early users, men with more types of MBSs used, and longer periods of use. CONCLUSIONS: MBS use is a potentially modifiable risk factor that may be associated with TGCC.

Effects of feeding fatty acid calcium and the interaction of forage quality on production performance and biochemical indexes in early lactation cow.

Multiparous early lactation Holstein cows (n = 16) were used in a randomized complete block design to determine the effects of feeding fatty acid calcium and the interaction of forage quality on production performance and biochemical indexes in early lactation cow. Treatments were as follows: (i) feeding low-quality forage without supplying fatty acid calcium (Diet A), (ii) feeding low-quality forage with supplying 400 g fatty acid calcium (Diet B), (iii) feeding high-quality forage without supplying fatty acid calcium (Diet C) and (iv) feeding high-quality forage with supplying 400 g fatty acid calcium. This experiment consisted 30 days. The milk and blood samples were collected in the last day of the trail. Intakes were recorded in the last 2 days of the trail. Supplementation of fatty acid calcium decreased significantly dry matter intake (DMI) (p < 0.01). Addition fatty acid calcium decreased milk protein percentage (p < 0.01) and milk SNF percentage (p < 0.01), but increased MUN (p < 0.05). Supplemented fatty acid decreased concentration of blood BHBA (p < 0.05), but increased TG, NEFA, glucagon, GLP-1, CCK, leptin, ApoA-IV, serotonin and MSH concentration in blood, the CCK concentration and feed intake showed a significant negative correlation (p < 0.05).

NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective, PAR-independent metabolic catastrophe and cell death induced by ß-lapachone.

Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors (e.g., FK866) target the most active pathway of NAD(+) synthesis in tumor cells, but lack tumor-selectivity for use as a single agent. Reducing NAD(+) pools by inhibiting NAMPT primed pancreatic ductal adenocarcinoma (PDA) cells for poly(ADP ribose) polymerase (PARP1)-dependent cell death induced by the targeted cancer therapeutic, ß-lapachone (ß-lap, ARQ761), independent of poly(ADP ribose) (PAR) accumulation. ß-Lap is bioactivated by NADPH:quinone oxidoreductase 1 (NQO1) in a futile redox cycle that consumes oxygen and generates high levels of reactive oxygen species (ROS) that cause extensive DNA damage and rapid PARP1-mediated NAD(+) consumption. Synergy with FK866+ß-lap was tumor-selective, only occurring in NQO1-overexpressing cancer cells, which is noted in a majority (∼85%) of PDA cases. This treatment strategy simultaneously decreases NAD(+) synthesis while increasing NAD(+) consumption, reducing required doses and treatment times for both drugs and increasing potency. These complementary mechanisms caused profound NAD(P)(+) depletion and inhibited glycolysis, driving down adenosine triphosphate levels and preventing recovery normally observed with either agent alone. Cancer cells died through an ROS-induced, µ-calpain-mediated programmed cell death process that kills independent of caspase activation and is not driven by PAR accumulation, which we call NAD(+)-Keresis. Non-overlapping specificities of FK866 for PDA tumors that rely heavily on NAMPT-catalyzed NAD(+) synthesis and ß-lap for cancer cells with elevated NQO1 levels affords high tumor-selectivity. The concept of reducing NAD(+) pools in cancer cells to sensitize them to ROS-mediated cell death by ß-lap is a novel strategy with potential application for pancreatic and other types of NQO1+ solid tumors.

Efficacy of low-level laser therapy for accelerating tooth movement during orthodontic treatment: a systematic review and meta-analysis.

This review aimed to evaluate the efficacy of low-level laser therapy (LLLT) for accelerating tooth movement during orthodontic treatment. An extensive electronic search was conducted by two reviewers. Randomized controlled trials (RCTs) and quasi-RCTs concerning the efficacy of LLLT for accelerating tooth movement during orthodontic treatment were searched in CENTRAL, Medline, PubMed, Embase, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), and Google Scholar. Six RCTs and three quasi-RCTs, involving 211 patients from six countries, were selected from 173 relevant studies. All nine articles were feasible for the systematic review and meta-analysis, five of which were assessed as moderate risk of bias, while the rest were assessed as high risk of bias. The mean difference and the 95 % confidence interval (95 % CI) of accumulative moved distance of teeth were observed among all the researches. The results showed that the LLLT could accelerate orthodontic tooth movement (OTM) in 7 days (mean difference 0.19, 95 % CI [0.02, 0.37], p = 0.03) and 2 months (mean difference 1.08, 95 % CI [0.16, 2.01], p = 0.02). Moreover, a relatively lower energy density (5 and 8 J/cm(2)) was seemingly more effective than 20 and 25 J/cm(2) and even higher ones.

Protective effect of icariin on kidney in 5/6 nephrectomized rats and its mechanism.

The aim of this study was to investigate the renal protective effect of icariin in 5/6 nephrectomized rats and the molecular mechanisms involved. Forty male Sprague-Dawley rats were randomly divided into 5 groups: sham-operated group, 5/6 nephrectomy model group, icariin groups (20 and 40 mg/kg), and benazepril group. After 12-weeks treatment, 24-h urine and serum were collected, and urine protein, serum creatinine, and blood urea nitrogen were determined. The rats were then sacrificed and fresh kidney tissues were prepared to obtain single cell suspensions. Cell cycle distribution and cell apoptosis were determined by annexin V-FITC/propidium iodide (PI) double staining using a flow cytometer. mRNA expression of Bcl-2 and Bax was examined using quantitative real-time PCR. After 12-weeks treatment, urinary protein, serum creatinine, and blood urea nitrogen in the icariin-treated group were much lower than in the untreated group compared with 5/6 nephrectomy model. Icariin reduced the percentage of S phase cells, increased the percentage of G0/M phase cells, and inhibited apoptosis in the renal cells. mRNA expression of Bcl-2 and Bax was decreased. In conclusion, icariin has a renal protective effect in 5/6 nephrectomized rats, which may be related mainly to alterations in cell cycle distribution and expression of apoptotic genes.

Efficacy of low-level laser therapy in the management of orthodontic pain: a systematic review and meta-analysis.

This review aimed to identify the efficacy of low-level laser therapy (LLLT) in the management of orthodontic pain. This systematic review and meta-analysis was carried out in accordance with Cochrane Handbook and the PRISMA statement. An extensive literature search for RCTs, quasi-RCTs, and CCTs was performed through CENTRAL, PubMed, Embase, Medline, CNKI, and CBM up to October 2011. Risk of bias assessment was performed via referring to the Cochrane tool for risk of bias assessment. Meta-analysis was implemented using Review Manager 5.1. As a result, four RCTs, two quasi-RCTs, and two CCTs were selected from 152 relevant studies, including 641 patients from six countries. The meta-analysis demonstrated that 24% risk of incidence of pain was reduced by LLLT (RR = 0.76, 95% CI range 0.63-0.92, P = 0.006). In addition, compared to the control group, LLLT brought forward "the most painful day" (MD = -0.42, 95% CI range -0.74- -0.10, P = 0.009). Furthermore, the LLLT group also implied a trend of earlier end of pain compared with the control group (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18) and the pseudo-laser group (MD = -1.04, 95% CI range -4.22-2.15, P = 0.52). However, because of the methodological shortcomings and risk of bias of included trials, LLLT was proved with limited evidence in delaying pain onset and reducing pain intensity. In the future, larger and better-designed RCTs will be required to provide clearer recommendations.

Side-by-side comparison of photodynamic therapy and pulsed-dye laser treatment of port-wine stain birthmarks.

BACKGROUND: Pulsed-dye laser (PDL)-mediated photothermolysis is the current standard treatment for port-wine stain (PWS) birthmarks. Vascular-targeted photodynamic therapy (PDT) might be an alternative for the treatment of PWS. OBJECTIVES: To compare clinical outcomes of PDT and PDL treatment of PWS. METHODS: Two adjacent flat areas of PWS lesions were selected from each of 15 patients (two male and 13 female; age 11-36 years) and randomly assigned to either single-session PDL or PDT. PDL was delivered using a 585-nm pulsed laser. PDT was carried out with a combination of haematoporphyrin monomethyl ether (HMME) and a low-power copper vapour laser (510.6 and 578.2 nm). Clinical outcomes were evaluated colorimetrically and visually during follow-up. RESULTS: A total of nine red PWS lesions and six purple PWS lesions were treated. For red PWS, colorimetric assessment showed that the blanching rates of PDL and PDT at 2 months ranged from -11% to 24% and 22% to 55%, respectively. For purple PWS, blanching rates of PDL and PDT ranged from 8% to 33% and 30% to 45%, respectively. Overall, there was a significant difference between the blanching effect of single-session PDL treatment and a single-session PDT treatment. CONCLUSIONS: This side-by-side comparison demonstrates that PDT is at least as effective as PDL and, in some cases, superior. The true value of PDT for the treatment of PWS deserves further investigation.

Impact of temperature, CO2 fixation and nitrate reduction on selenium reduction, by a paddy soil Clostridium strain.

AIMS: To elucidate the impact of CO(2) fixation, nitrate reduction and temperature on selenium reduction by a newly identified acetogenic bacterium, Clostridium sp. BXM. METHODS AND RESULTS: A series of culture experiments were designed to evaluate the impact of temperature, CO(2) fixation and nitrate reduction on the rate and extent of selenium reduction by strain BXM. The products of selenium reduction, CO(2) fixation and nitrate reduction were determined. Molecular analysis was performed to identify the functional genes involved in the selenium reduction process. CO(2) may have enhanced the activity of hydrogenase I and/or the level of cytochrome b, thus increasing selenium reduction. Nitrate may inhibit selenium reduction due to its higher reduction potential and/or by decreasing selenite/selenate reductase activity. The suitable temperature was 37 and 30 °C for selenite reduction under anaerobic and aerobic conditions, respectively. The optimum temperature was 30 °C for selenate reduction under both anaerobic and aerobic conditions. CO(2) fixation and nitrate reduction by Clostridium sp. BXM stimulated each other. CONCLUSIONS: Clostridium sp. BXM was capable of reducing up to 36-94% of 1 mmol l(-1) selenate and selenite under anaerobic or aerobic conditions over 15 days. The strain might be used for the precipitation of Se from highly selenium-contaminated water or sediments. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings contribute to the current understanding about the role that micro-organisms play in the detoxification of toxic selenium compounds in paddy soils. Micro-organisms in paddy soils can influence selenium accumulation in rice grain and hence human selenium intake.

Association of sustained cardiovascular recovery with epinephrine in the delayed lipid-based resuscitation from cardiac arrest induced by bupivacaine overdose in rats.

BACKGROUND: The role of epinephrine combined with lipid emulsion in rescuing cardiovascular collapse induced by local anaesthetic overdose remains unclear. The objective of this study was to explore the effect of epinephrine on delayed lipid-based treatment for bupivacaine-induced cardiac arrest in rats. METHODS: Thirty-two rats were subjected to bupivacaine to induce asystole. Basic life support was performed for 10 min before the rats received saline, epinephrine alone, or 20% lipid emulsion bolus with or without epinephrine pretreatment. ECG and invasive arterial pressure were monitored continuously. Arterial blood gas was analysed at 25 min; the right lungs and hearts of rats were harvested for measurement of dry-to-wet lung weight ratio and myocardial bupivacaine content, respectively. RESULTS: In the rats treated with epinephrine plus lipid emulsion, there was a marked improvement in haemodynamic parameters at 25 min compared with rats treated with lipid alone, P<0.05. The coronary perfusion pressure immediately after lipid rescue was higher in the epinephrine/lipid-treated rats when compared with rats given lipid only (70 and 24 mm Hg, respectively, P<0.05). The myocardial bupivacaine content was lower (8.34 nM g(-1)) in the epinephrine/lipid group relative to other groups (P<0.05). However, the rats treated with lipid alone which survived had higher PO(2), less severe acidosis, and better hypoxaemia relative to surviving rats given epinephrine plus lipid. CONCLUSIONS: Late intervention with epinephrine plus lipid emulsion contributed to sustained improvement in haemodynamic profile, but failed to alleviate deterioration of hypoxaemia and acidaemia in rats.

Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.

Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin neurons by activation of presynaptic adenosine A1 receptors, which may finely regulate the excitability of these neurons as well as eventually modulate the sleep-wakefulness.