[Spatial correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in a typical coal-fired pollution fluorosis area].

Objective: To investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.

[Preliminary study of the changes in blood system in pyrrolizidine alkaloid-related liver damage].

Objective: To preliminary explore the changes in blood system in pyrrolizidine alkaloids (PAs)-related liver damage. Methods: General situation, liver function, biochemical blood test, routine blood test, coagulation function markers, etc., of 77 cases with drug-induced liver damage admitted to the Zhongshan Hospital Affiliated to Fudan University from 2012 to 2019 were retrospectively analyzed. Patients' were divided into PA group, other traditional Chinese medicine group and Western medicine group according to their medication history. Simultaneously, the changes in liver function were observed in the established mice model of monocrotaline-induced liver damage. Liver tissues HE staining and blood routine indexes were observed. Results: 24 cases received PA, 24 cases received other traditional Chinese medicine, and 29 cases received western medicine. Alanine aminotransferase was lower in PA group than the other two groups (P < 0.05), and the total bilirubin and direct bilirubin were significantly lower than the other traditional Chinese medicine group (P < 0.05). The peripheral platelet count of the PA group was (84.11 ± 26.91) ×10(9)/L, which was significantly lower than the lower limit of normal, and had statistically significant difference with other traditional Chinese medicine and western medicine group (P < 0.01). Thrombocytocrit, mean platelet volume and platelet indices of PA group were statistically different from the other two groups (P < 0.05). The D-dimer level in patients with PA group was (2.62 ± 1.93) mg/L, which was higher than the upper limit of normal, and significantly higher than the D-dimer level of the other two groups of patients (P < 0.01). Meanwhile, prothrombin time was longer in PA group than that of the other two groups (P < 0.01), and platelets count were decreased significantly in the mouse model of monocrotaline-induced liver damage after alanine aminotransferase and aspartate aminotransferase elevation (P < 0.01). Conclusion: PA-related liver damage has lower peripheral platelet counts, and the peripheral platelet counts of these patients are lower than other types of drug-induced liver damage. In addition, increased D-dimer in patients with PA-related liver damage indicate a potential risk of thrombosis.

[Current status of registered drug and vaccine pediatric clinical trials in China].

Objective: To evaluate the current status of the registered pediatric drug or vaccine clinical trials in China for the purpose of providing a reference for the development of pediatric clinical trials in China. Methods: We collected the data about registered pediatric clinical trials that were conducted from September 6, 2013(Mandatory registration start date) to September 6, 2019 (Cut-off date) at Chinadrugtrials.org.cn platform. The survey items included trial name and number, drug classification, sponsor's information, current trial status, completion status, etc. The clinical trials were categorized by drug group (includes chemical medicine, traditional Chinese medicine and natural medicine, biological products) and by vaccine group. Results: During the six years 349 pediatric clinical trials were registered on the platform, including 162 pediatric drug trials and 187 vaccine trials. The numbers of chemical drugs and biological products registered in 2018 were 23 and 11, respectively, the highest in the history. The number of pediatric clinical trials of traditional Chinese medicine and natural medicine was 11 in 2014, but from 2015 to 2018 only 2 to 4 trials were registered each year. The overall completion rates of the registered drug and vaccine clinical trials were 22.8% (37/162) and 41.7%(78/187), respectively. Only 42 international multicenter pediatric clinical trial projects were registered on the platform. The numbers of drug and vaccine phase Ⅰ clinical trials were 4 and 46, respectively. Thirty-six pediatric endocrine system agent clinical trials were carried out, with the largest number of all the drug categories registered on the platform. Conclusions: In recent years the number of registered pediatric drug and vaccine clinical trials increased in China. However, the number is still very limited. It is urgent to further promote the development of pediatric clinical trials.

[Sacral neuromodulation preliminary outcomes in male patients with idiopathic dysuria].

Objective: To assess the effectiveness and safety of sacral neuromodulation (SNM) therapy for men with idiopathic dysuria. Methods: From January 2012 to December 2016, a total of 26 patients treated with SNM therapy from multi-center across the country were retrospectively studied. The age ranged from 19 to 86 years with an average age of 45.2 years. Patients suffered from one or multiple urinary symptoms such as frequency of urination, urgency, urinary retention, etc. All patients had received more than two types of conservative therapy including oral and behavioral therapy, but had poor or no improvement. The voiding diary, urgency score and the quality of life score before implantation, in stageⅠ after implantation and stage Ⅱ after permanent implantation were recorded and compared. Results: A total of 22 patients chose to receive IPG at the end of stageⅠ therapy while 4 patients refused further stage Ⅱ therapy because of dissatisfactory effect. The conversion rate of stage Ⅰ to stage Ⅱ was 84.6% (22/26). The average follow-up time was 19.2 months, ranging from 3 to 63 months. The baseline of residual urine, voiding frequency and average voiding amount and those after stage Ⅰ therapy were [5 (0, 137.5) ] ml vs [0 (0, 40) ] ml, 14.6±6.1 vs 9.1±2.8, [100 (80, 135) ] ml vs [190 (150, 210) ] ml, respectively. The differences were statistically significant(all P<0.05).However, no significant differences were found in urination volume and quality of life (QoL) before and after implantation(P>0.05). During an average follow-up time of 19.2 months after the permanent implantation, over 80% patients had an improvement of residual urine volume by more than 50% after permanent implantation while the improvement was 55.6% after stage Ⅰ therapy, suggesting that the improvement of residual urine volume might be positively correlated with the duration of regulation. No significant differences were found in other parameters between stage Ⅰ and Ⅱ therapy. No adverse events like wound infection and electrode dislocation happened during our study. Conclusions: SNM is an effective and safety procedure for male patients with idiopathic dysuria, with a relatively high transfer rate. The medium-term curative effect is stable. The duration of regulation may be positively correlated with the improvement of residual urine.

Vitamin B12 for herpetic neuralgia: A meta-analysis of randomised controlled trials.

BACKGROUND: Postherpetic neuralgia (PHN) is the most distressful complication of herpes zoster. PHN results in an impaired quality of life and higher healthcare utilization. Vitamin B12 has been proven to be effective in pain relief for various conditions. OBJECTIVE: We conducted a systematic review and a meta-analysis to evaluate the efficacy of vitamin B12 supplementation in PHN patients. METHODS: PubMed, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov registry were searched. Randomised control trials evaluating the efficacy and safety of vitamin B12 in PHN patients were selected. Eligible trials were abstracted and assessed for the risk of bias by two reviewers, and the results of pain indicators in the selected trials were analysed. RESULTS: Four trials including 383 participants were published between 2013 and 2016. Compared with the placebo group, the Vitamin B12 group exhibited a significant decrease in the Numeric Rating Scale score, with a mean difference of -4.01 (95% confidence interval = -4.70 to -3.33). Vitamin B12 administration improved the quality of life of PHN patients with moderate quality evidence and significantly decreased the number of patients using analgesics. CONCLUSION: Vitamin B12 appears to be an attractive complementary therapy for PHN patients. Further investigation is needed before conclusive recommendations can be made.

Effects of dietary vitamin C, vitamin E, and alpha-lipoic acid supplementation on the antioxidant defense system and immune-related gene expression in broilers exposed to oxidative stress by dexamethasone.

Vitamin C, vitamin E, and alpha-lipoic acid (ALA) are potent nutritional antioxidants, which are important for enhancing immunity. This study compared the effects of supplementation with vitamin C, vitamin E, or ALA on the antioxidant defense system and the expression of immune-related genes under oxidative stress induced by dexamethasone (DEX) in broilers. In total, 240 one-day-old female Recessive White Rock chickens were assigned randomly to either a basal diet (control group) or basal diet supplemented with vitamin C (200 mg/kg diet), vitamin E (100 mg/kg), or ALA (500 mg/kg) for 28 d starting from hatching. At 21 d of age, birds fed the ALA-supplemented diet had the highest plasma total antioxidant capacity (T-AOC) and superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) enzyme activities, and the lowest plasma malondialdehyde (MDA) activity, as well as the lowest mRNA gene expression levels of interferon gamma (IFN-γ) and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF). At 23 d of age, the broilers in the 3 treatment groups were injected in the thigh muscle with DEX for 3 alternating days. In addition, the control group was divided into 2 equal groups, in which one was injected with saline and the other was injected with DEX. At 28 d of age, the DEX-ALA group (P < 0.05) had the highest activity levels for T-AOC, T-SOD, and GSH-PX in the plasma and liver (P < 0.05), and the greatest reduction in the MDA level. Dietary ALA significantly decreased the mRNA expression levels of the interleukin 1 ß (IL-1ß), IL-6, IFN-γ, and LITAF genes compared with the other groups during oxidative stress by DEX. In conclusion, this study suggests that in broilers, ALA is more effective for normalizing the oxidative stress induced by DEX than vitamin C or vitamin E.

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model.

Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation. EA stimulation was applied to bilateral LI18, LI4-PC6, or ST36-GB34. The thermal pain threshold, cervicospinal ATP concentration, expression levels of purinergic P2XR and P2YR subunits mRNAs, and fractalkine, CX3CR1 and p38 MAPK proteins, were detected separately. The neck incision induced strong thermal hyperalgesia and upregulation of spinal ATP within 48 h. No significant change was found in thermal hyperalgesia after a single session of EA intervention. However, a single session of EA dramatically enhanced the neck incision-induced upregulation of ATP and upregulated the expression of P2X7R, which was reversed by two sessions of EA. Two sessions of EA at bilateral LI18 or LI4-PC6 attenuated hyperalgesia significantly, accompanied with downregulation of P2X7R/fractalkine/ CX3CR1 signaling after three sessions of EA. EA stimulation of LI18 or LI4-PC6 alleviates thermal hyperalgesia in neck-incision pain rats, which may be associated with its effects in regulating the neck incision-induced increase of ATP and P2X7R and subsequently suppressing fractalkine/CX3CR1 signaling in the cervical spinal cord.

Molecular cloning and characterization, and prokaryotic expression of the GnRH1 gene obtained from Jinghai yellow chicken.

The gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Recent studies have reported the occurrence of GnRH molecular variants in numerous species. In this study, the GnRH1 gene from Jinghai yellow chicken was cloned by reverse transcriptase-polymerase chain reaction and transformed into BL21 (DE3) competent cells. The GnRH1 gene and amino acid sequences were subjected to bioinformatic analyses. The GnRH1 gene nucleotide sequence was discovered to be 352 bp long, containing a coding, promoter, and section of the 3'-regions. The GnRH1 gene shared 93, 81, 54, 58, 61, 76, 76, 59, 76, and 66% sequence identity with Meleagris gallopavo, Columba livia, Homo sapiens, Bos taurus, swines, Capra hircus, Ovis aries, Pantholops hodgsonii, Equus caballus, and Rattus norvegicus, respectively. The GnRH1 gene showed conserved domains. The GnRH1 protein was a secreted protein comprising 92 amino acids, with a molecular weight of 10205.6 Da and a theoretical pI of 5.67. Most of the amino acid residues were observed to be hydrophilic, indicating water solubility. The predicted secondary structures of proteins included α-helices (h; 23.08%), ß-extensions (e; 10.92%), and random coils (c; 66.0%). The successful construction of prokaryotic expression vector pET32a-GnRH1 was confirmed by restriction and sequence analysis. SDS-PAGE analysis showed the successful expression of recombinant plasmid in Escherichia coli BL21 (molecular weight = 25-28 kDa). Larger quantities of protein were expressed in supernatant, indicating greater expression in soluble form. Western blot analysis confirmed the expression of the target protein.

Molecular genetic diversity and maternal origin of Chinese black-bone chicken breeds.

Chinese black-bone chickens are valued for the medicinal properties of their meat in traditional Chinese medicine. We investigated the genetic diversity and systematic evolution of Chinese black-bone chicken breeds. We sequenced the DNA of 520 bp of the mitochondrial cyt b gene of nine Chinese black-bone chicken breeds, including Silky chicken, Jinhu black-bone chicken, Jiangshan black-bone chicken, Yugan black-bone chicken, Wumeng black-bone chicken, Muchuan black-bone chicken, Xingwen black-bone chicken, Dehua black-bone chicken, and Yanjin black-bone chicken. We found 13 haplotypes. Haplotype and nucleotide diversity of the nine black-bone chicken breeds ranged from 0 to 0.78571 and 0.00081 to 0.00399, respectively. Genetic diversity was the richest in Jinhu black-bone chickens and the lowest in Yanjin black-bone chickens. Analysis of phylogenetic trees for all birds constructed based on hyplotypes indicated that the maternal origin of black-bone chickens is predominantly from three subspecies of red jungle fowl. These results provide basic data useful for protection of black-bone chickens and help determine the origin of domestic chickens.

Induction of apoptosis in human cervical carcinoma Hela cells with active components of Menispermum dauricum.

Menispermum dauricum DC possesses a wide range of pharmacological effects. In this study, the mechanism of apoptosis induced by active components of M. dauricum was investigated in the human cervical carcinoma HeLa cell line. HeLa cells were treated with different M. dauricum concentrations over different time periods. The proliferation-inhibitory rate and cytotoxic effect of HeLa cells were measured by using the methyl thiazolyl tetrazolium (MTT) assay, and the apoptotic rate was detected by flow cytometry. Expressions of caspase-9, caspase-8, caspase-3, Bcl-2, and Fas proteins, in the apoptotic pathway, and the expression of nuclear factor-kappa B (NF-κB) were detected by SP immunocytochemistry. The MTT assay showed that active components of M. dauricum could significantly inhibit the growth of HeLa cells in a dose- and time-dependent manner (P<0.01). The Sub-Gl peak was found by flow cytometry, and the maximal apoptosis rate was 24.93%. Immunocytochemistry showed that after treatment with M. dauricum, the expressions of caspase-8, caspase-9, caspase-3, Fas protein, and NF-κB all increased, and the expression of the Bcl-2 protein decreased, with significant differences relative to the control group (P<0.01). Apoptosis in HeLa cells could be induced by active components of M. dauricum through the NF-κB signal transduction pathway and the caspase pathway, which was related to the downregulation of Bcl-2 expression and the upregulation of Fas expression.

Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer.

BACKGROUND: This study was aimed to detect post-chemotherapeutic circulating tumour cells (CTCs) in stage III colon cancer patients and identify those who were at high risk of relapse. METHODS: We used human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) as the biomarkers to detect CTCs in 90 stage III colon cancer patients undergoing curative resection followed by mFOLFOX chemotherapy. RESULTS: Post-chemotherapeutic relapse occurred in 30 (33.3%) patients. By univariate analysis and multivariate proportional hazards regression analysis, perineural invasion (hazard ratio (HR): 2.752; 95% confidence interval (CI): 1.026-7.381), high post-chemotherapeutic serum CEA levels (HR: 2.895; 95% CI: 1.143-7.333) and persistent presence of post-chemotherapeutic CTCs (HR: 6.273; 95% CI: 2.442-16.117) were independent predictors of post-chemotherapeutic relapse. In addition, the persistent presence of post-chemotherapeutic CTCs strongly correlated with reduced disease-free survival and overall survival. Accuracy of detecting relapse in post-chemotherapeutic stage III colon cancer patients by analysing the persistent presence of post-chemotherapeutic CTCs was higher than that by post-chemotherapeutic CEA levels (odds ratio: 50.091 vs 5.211). CONCLUSION: The persistent presence of post-chemotherapeutic CTCs is a potential powerful surrogate marker for determining clinical outcome in stage III colon cancer patients receiving adjuvant mFOLFOX chemotherapy.

Bioactive secondary metabolites from Nigrospora sp. LLGLM003, an endophytic fungus of the medicinal plant Moringa oleifera Lam.

An endophytic fungus was isolated from the root of the medicinal plant Moringa oleifera Lam. Based on analyzing the rDNA sequence, the fungus was identified as Nigrospora sp. This is the first report of the isolation of endophytic Nigrospora from M. oleifera. By bioassay-guided fractionation, four antifungal secondary metabolites were isolated from liquid cultures of the fungus Nigrospora sp. LLGLM003, and their chemical structures were determined to be griseofulvin (1), dechlorogriseofulvin (2), 8-dihydroramulosin (3) and mellein (4) on the basis of spectroscopic analyses. Compound 2, 3 and 4 were isolated from Nigrospora sp. for the first time. In vitro antifungal assay showed that griseofulvin displayed clear inhibition of the growth of 8 plant pathogenic fungi. Dechlorogriseofulvin and mellein exhibited only weak antifungal activities, whereas 8-dihydroramulosin displayed no antifungal activities.

Remediation of TCE-contaminated groundwater using acid/BOF slag enhanced chemical oxidation.

The objective of this study was to evaluate the potential of applying acid/H(2)O(2)/basic oxygen furnace slag (BOF slag) and acid/S(2)O(8)(2-)/BOF slag systems to enhance the chemical oxidation of trichloroethylene (TCE)-contaminated groundwater. Results from the bench-scale study indicate that TCE oxidation via the Fenton-like oxidation process can be enhanced with the addition of BOF slag at low pH (pH=2-5.2) and neutral (pH=7.1) conditions. Because the BOF slag has iron abundant properties (14% of FeO and 6% of Fe(2)O(3)), it can be sustainably reused for the supplement of iron minerals during the Fenton-like or persulfate oxidation processes. Results indicate that higher TCE removal efficiency (84%) was obtained with the addition of inorganic acid for the activation of Fenton-like reaction compared with the experiments with organic acids addition (with efficiency of 10-15% lower) (BOF slag=10gL(-1); initial pH=5.2). This could be due to the fact that organic acids would compete with TCE for available oxidants. Results also indicate that the pH value had a linear correlation with the observed first-order decay constant of TCE, and thus, lower pH caused a higher TCE oxidation rate.

Neuroprotective effect of oral S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) on iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain.

AIM OF THE STUDY: S/B remedy prepared from Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd, two herbals of Xiao-Tsai-Hu-Tang or Sho-Saiko-To (TJ-9), contains active flavonoids. In this study, the protective effect of S/B remedy on iron-induced neurodegeneration was investigated in the nigrostriatal dopaminergic system of rat brain. MATERIALS AND METHODS: The antioxidative activity of S/B remedy was studied using brain homogenates incubated with ferrous citrate (iron, 1M), S/B remedy, Trolox and melatonin. Furthermore, a Parkinsonian animal model by an intranigral infusion of iron in the anesthetized rats was employed to investigate the protective effect of S/B remedy in the nigrostriatal dopaminergic system. RESULTS: Our in vitro studies showed that S/B remedy was more potent than melatonin and equal to trolox in inhibiting iron-induced lipid peroxidation of brain homogenates. Our in vivo studies found that oral administration of S/B remedy dose-dependently attenuated iron-elevated lipid peroxidation in the infused substantia nigra (SN) and iron-depleted dopamine levels in the ipsilateral striatum. Furthermore, iron-induced reductions in glutathione (GSH) content and increases in GSSG (oxidized GSH)/GSH ratio in the infused SN were inhibited in S/B remedy-treated rats. Systemic S/B remedy attenuated the iron-induced increases in heme-oxygenase-1 levels and α-synuclein aggregation in the infused SN. Moreover, S/B remedy reduced iron-induced apoptosis via attenuating mitochondrial and endoplasmic reticulum stress. In addition, S/B remedy was anti-inflammatory as indicated by the attenuation of iron-induced elevations in inducible nitric oxide synthase and cyclo-oxygenase II levels as well as glial fibrillary acidic protein (a biological marker of astrocytes) and ED-1 (a protein indicative of activated microglia) levels in the infused SN of S/B remedy-treated rats. CONCLUSIONS: These findings suggest that oral administration of S/B remedy is protective against iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain. Therefore, S/B remedy may be therapeutically useful for the treatment of CNS neurodegenerative diseases.

Adding moxifloxacin is associated with a shorter time to culture conversion in pulmonary tuberculosis.

OBJECTIVE: To investigate whether adding moxifloxacin (MXF) to the standard anti-tuberculosis regimen can shorten the time to sputum culture conversion in pulmonary tuberculosis (PTB). METHODS: Adults with culture-positive PTB were divided into two treatment groups by their choice: standard regimen alone (HERZ group) and standard regimen plus daily 400 mg MXF in the first 2 months (MXF group). Sputum samples were collected thrice weekly in the first 8 weeks. The propensity score was calculated to estimate the conditional probability of entering the MXF group. Factors influencing time to culture conversion were investigated using Cox proportional hazards regression analysis stratified by propensity score. RESULTS: Sixty-two patients were enrolled in the MXF group and 88 in the HERZ group; respectively 51 and 72 completed the study. The regimen was modified before culture conversion in respectively 6 (12%) and 12 (16%; P = 0.47) patients, due to adverse effects. The time to culture conversion was shorter in the MXF group (HR 2.1, 95%CI 1.4-3.2). The culture conversion rate after 6 weeks of treatment was respectively 82% and 61% (P = 0.011, <0.05/4, calculated using the modified Bonferroni method). CONCLUSIONS: Adding MXF to the standard anti-tuberculosis regimen in the first 2 months was associated with a shorter time to culture conversion, a higher 6-week culture conversion rate and reduced transmission of tuberculosis.

Impact of zinc supplementation on the improvement of ethanol tolerance and yield of self-flocculating yeast in continuous ethanol fermentation.

The effects of zinc supplementation were investigated in the continuous ethanol fermentation using self-flocculating yeast. Zinc sulfate was added at the concentrations of 0.01, 0.05 and 0.1 g l(-1), respectively. Reduced average floc sizes were observed in all the zinc-supplemented cultures. Both the ethanol tolerance and thermal tolerance were significantly improved by zinc supplements, which correlated well with the increased ergosterol and trehalose contents in the yeast flocs. The highest ethanol concentration by 0.05 g l(-1) zinc sulfate supplementation attained 114.5 g l(-1), in contrast to 104.1 g l(-1) in the control culture. Glycerol production was decreased by zinc supplementations, with the lowest level 3.21 g l(-1), about 58% of the control. Zinc content in yeast cells was about 1.4 microMol g(-1) dry cell weight, about sixfold higher than that of control in all the zinc-supplemented cultures, and close correlation of zinc content in yeast cells with the cell viability against ethanol and heat shock treatment was observed. These studies suggest that exogenous zinc addition led to a reprogramming of cellular metabolic network, resulting in enhanced ethanol tolerance and ethanol production.

Ginsenine, a new alkaloid from the berry of Panax ginseng C. A. Meyer.

A new indole alkaloid, ginsenine, with a seven-membered lactam unit, was isolated from the berry of Panax ginseng. Its structure was established on the basis of extensive NMR (1H- and 13C-NMR, 1H-1H COSY, DEPT, HMQC, HMBC), IR, and ESI-MS analysis.

Changes in pulmonary arteriole protein kinase calpha expression associated with supplemental L-arginine in broilers during cool temperature exposure.

The present study was conducted to examine the effect of supplemental L-arginine on pulmonary arteriole protein kinase Calpha (PKCalpha) expression in broilers exposed to cool temperature, to investigate further the molecular mechanisms of supplemental L-arginine on modulating pulmonary vascular functions in hypertensive broilers. Broilers were subjected to sub-thermoneutral (cool) temperature to induce pulmonary hypertension syndrome (PHS), and an additional 10 g/kg L-arginine was added to the basal diet to evaluate the effects of supplemental L-arginine on PHS mortality, plasma nitric oxide (NO) production and pulmonary arterioles PKCalpha expression. Supplemental L-arginine reduced PHS mortality but did not affect right/total ventricle (RV/TV) ratios in clinically healthy birds. Birds fed additional L-arginine had increased plasma NO and decreased PKCalpha protein expression in pulmonary arterioles; NO production was negatively correlated with PKCalpha expression. These results demonstrated that supplemental L-arginine diminished PKCalpha expression in birds exposed to cool temperature. It is suggested that NO-induced loss of PKCalpha expression might be partially responsible for its effects on dilating pulmonary vasculature and inhibiting pulmonary vascular remodelling in vivo.

The roles of different subtypes of opioid receptors in mediating the nucleus submedius opioid-evoked antiallodynia in a neuropathic pain model of rats.

Previous studies have indicated that thalamic nucleus submedius is involved in opioid-mediated antinociception in tail flick test and formalin test. The current study examined the effects of opioids microinjected into the thalamic nucleus submedius on the allodynia developed in neuropathic pain model rats, and determined the roles of different subtypes of opioid receptors in the thalamic nucleus submedius opioid-evoked antiallodynia. The allodynic behaviors induced by L5/L6 spinal nerve ligation were assessed by mechanical (von Frey filaments) and cold (4 degrees C plate) stimuli. Morphine (1.0, 2.5, and 5.0 microg) microinjected into the thalamic nucleus submedius contralateral to the nerve injury paw produced a dose-dependent inhibition of the mechanical and cold allodynia, and these effects were reversed by microinjection of the non-selective opioid receptor antagonist naloxone (1.0 microg) into the same site. Microinjection of endomorphin-1 (5.0 microg), a highly selective mu-opioid receptor agonist, and [D-Ala2, D-Leu5]-enkephalin (10 microg), a delta-/mu-opioid receptor agonist, also inhibited the allodynic behaviors, and these effects were blocked by selective mu-opioid receptor antagonist beta-funaltrexamine hydrochloride (3.75 microg). However, the [D-Ala2, D-Leu5]-enkephalin-evoked antiallodynic effects were not influenced by the selective delta-opioid receptor antagonist naltrindole (5.0 microg). Microinjection of the selective kappa-receptor agonist spiradoline mesylate salt (100 microg) into the thalamic nucleus submedius failed to alter the allodynia induced by spinal nerve ligation. These results suggest that the thalamic nucleus submedius is involved in opioid-evoked antiallodynia which is mediated by mu- but not delta- and kappa-opioid receptor in the neuropathic pain model rats.

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway.

Epimedium brevicornum Maxim (EbM) has been reputed to have sexual stimulation effects on males. The study is aimed to test the hypothesis that EbM extracts relaxed the corpus cavernosum (CC) smooth muscle through activation of multitargets on nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Water extract of EbM and its subfraction (EP-20) were prepared and standardized by high-performance liquid chromatography. Isolated rabbit CC strips were mounted in organ baths and isometric tension was recorded in the presence or absence of specific inhibitors related to NO/cGMP signaling such as L-N(G)-nitro-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor) or phosphodiesterase 5 (PDE 5) inhibitors. cGMP level was determined in EP-20-treated CC strips. The results showed that EP-20 enriched the content of L-arginine in the process of purification and relaxed the CC smooth muscle precontracted with phenylephrine (PE, 1 microM) in a concentration-dependent manner. Besides, EP-20 increased the amount of cGMP production in rabbit CC tissues. Coincubation with EP-20 and L-NAME or ODQ significantly decreased EP-20-induced relaxation whereas EP-20 increased sodium nitroprusside-induced relaxation in PE-precontracted CC strips. Besides, EP-20 increased the potency and the duration of the relaxation effects caused by electrical field stimulation. Finally, EP-20 could potentiate PDE 5 inhibitors in relaxation of PE-precontracted CC strips. We concluded that extract of EbM relax the CC smooth muscle through multitargets in NO/cGMP/PDE 5 pathway and might bring into perspective the treatment strategy for those patients with erectile dysfunction.