Low temperature acclimation of electroactive microorganisms may be an effective strategy to enhance the toxicity sensing performance of microbial fuel cell sensors.

Microbial fuel cell (MFC) sensing is a promising method for real-time detection of water biotoxicity, however, the low sensing sensitivity limits its application. This study adopted low temperature acclimation as a strategy to enhance the toxicity sensing performance of MFC biosensor. Two types of MFC biosensors were started up at low (10 °C) or warm (25 °C) temperature, denoted as MFC-Ls and MFC-Ws respectively, using Pb2+ as the toxic substance. MFC-Ls exhibited superior sensing sensitivities towards Pb2+ compared with MFC-Ws at both low (10 °C) and warm (25 °C) operation temperatures. For example, the inhibition rate of voltage of MFC-Ls was 22.81 % with 1 mg/L Pb2+ shock at 10 °C, while that of MFC-Ws was only 5.9 %. The morphological observation showed the anode biofilm of MFC-Ls had appropriate amount of extracellular polymer substances, thinner thickness (28.95 µm for MFC-Ls and 41.58 µm for MFC-Ws) and higher proportion of living cells (90.65 % for MFC-Ls and 86.01 % for MFC-Ws) compared to that of MFC-Ws. Microbial analysis indicated the enrichment of psychrophilic electroactive microorganisms and cold-active enzymes as well as their sensitivity to Pb2+ shock was the foundation for the effective operation and good performance of MFC-Ls biosensors. In conclusion, low temperature acclimation of electroactive microorganisms enhanced not only the sensitivity but also the temperature adaptability of MFC biosensors.

Functional investigation of a novel ANKRD11 frameshift variant identified in a Chinese family with KBG syndrome.

KBG syndrome is a rare autosomal dominant condition characterized by multisystem developmental disorder, primarily caused by loss-of-function variants in ankyrin repeat domain-containing protein 11 (ANKRD11). Approximately 80 % of ANKRD11 variants associated with KBG syndrome, are frameshift and nonsense variants. Current insight into the pathogenesis of KBG syndrome resulting from ANKRD11 truncating variants remains limited. Here, we presented two members from a non-consanguineous Chinese pedigree both exhibiting characteristics fitting the KBG syndrome-associated phenotypic spectrum. Whole-exome sequencing identified a novel heterozygous frameshift variant in ANKRD11 (NM_013275.6, c.2280_2281delGT, p.Y761Qfs*20) in the proband. Sanger sequencing confirmed that the variant was inherited from her mother and co-segregated with KBG syndrome phenotype. In vitro functional assays revealed that the frameshift variant escaped nonsense-mediated mRNA decay, and resulting in a truncated protein with significantly increased expression levels compared to full-length ANKRD11. Immunofluorescence results demonstrated that truncated protein was predominantly expressed in the nucleus of HEK293 cells, while wild-type ANKRD11 was equally distributed in both the nucleus and cytoplasm. Moreover, the truncated protein significantly reduced CDKN1A/P21-promoter luciferase activity in comparison to wild-type ANKRD11 protein, as well as a remarkably decrease in the endogenous CDKN1A/P21 mRNA level in HEK293 cells. These findings suggest a loss of transcriptional activation function and potentially a dominant-negative mechanism. Overall, our study expands the mutational spectrum of ANKRD11 gene and provides new insights into the pathogenic mechanism of KBG syndrome caused by ANKRD11 truncating variants.

Identification and functional analysis of first heterozygous frameshift mutation in the GHRH gene in a Chinese boy with isolated growth hormone deficiency.

BACKGROUND: Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR). The aim of this study was to identify the molecular etiology of a Chinese boy with IGHD. METHODS: Whole-exome sequencing, sanger sequencing and bioinformatic analysis were performed to screen for candidate mutations. The impacts of candidate mutation on gene expression, intracellular localization and protein function were further evaluated by in vitro assays. RESULTS: A novel heterozygous frameshift mutation in the GHRH gene (c.91dupC, p.R31Pfs*98) was identified in a Chinese boy clinically diagnosed as having IGHD. The mutation was absent in multiple public databases, and considered as deleterious using in silico prediction, conservative analysis and three-dimensional homology modeling. Furthermore, mRNA and protein expression levels of mutant GHRH were significantly increased than wild-type GHRH (p < 0.05). Moreover, mutant GHRH showed an aberrant accumulation within the cytoplasm, and obviously reduced ability to stimulate GH secretion and cAMP accumulation in human GHRHR-expressing pituitary GH3 cells compared to wild-type GHRH (p < 0.05). CONCLUSION: Our study discovered the first loss-of function mutation of GHRH in a Chinese boy with IGHD and provided new insights on IGHD pathogenesis caused by GHRH haploinsufficiency.

Letrozole combined with rhGH treatment increases the adult height of short pubertal boys.

OBJECTIVES: This study was performed to investigate the effectiveness of the combination of letrozole and recombinant human growth hormone (rhGH) to improve the predicted adult height (PAH) and final adult height (FAH) of Chinese short pubertal boys. METHODS: In total, 171 Chinese short pubertal boys were recruited for this study. 96 of them received letrozole (2.5 mg/d) combined with rhGH (33.3-66.6 µg/kg.d), and the others received rhGH alone. Follow-up visits were conducted at 1, 3, 6, 9, and 12 months or regularly after the first treatment. During each visit, plasma samples were collected for clinical tests and biomedical analyses, all of which were performed according to standard protocols. This study was registered at www.chictr.org.cn under ID number ChiCTR1900026142. RESULTS: After receiving treatment for at least 3 months, 68 boys (91 %) in the rhGH therapy group and 90 (94 %) in the letrozole combined with rhGH (letrozole+rhGH) therapy group achieved an increase in PAH, with the latter treatment leading to a more effective slowing of bone age (BA) advancement. Moreover, the increased PAH showed a significant positive correlation with treatment time in both groups, and letrozole+rhGH increased the PAH to a greater degree than rhGH alone (p=0.0023). And letrozole+rhGH not only slowed the increase in BA more efficiently than rhGH therapy alone (p=0.0025), but also achieved a higher FAH (p=0.0078). CONCLUSIONS: Letrozole combined with rhGH treatment is a promising therapy to increase the PAH and FAH of Chinese short pubertal boys.

Clinical Manifestations, Genetic Variants and Therapeutic Evaluation in Sporadic Chinese Patients with Idiopathic Hypogonadotropic Hypogonadism.

Purpose: Genetic factors account for a large proportion of idiopathic hypogonadotropic hypogonadism (IHH) etiologies, although not necessarily a complete genetic basis. This study aimed to characterize the clinical presentations, genetic variants, and therapeutic outcomes of patients with sporadic IHH, which may be helpful for genetic counseling and treatment decisions. Patients and Methods: Eleven Chinese patients with IHH were retrospectively analyzed. Rare genetic variants were evaluated using whole-exome sequencing and bioinformatics analysis and were further classified according to the ACMG-AMP guidelines. The therapeutic responses of patients were further evaluated. Results: Six heterozygous variants of SOX10, WDR11, PROKR2, CHD7 and FGF17 were detected in five Kallmann syndrome (KS) patients, whereas two heterozygous variants of CHD7 and PROKR2 were detected in two normosmic IHH (nIHH) patients. Among these variants, a novel likely pathogenic variant in the SOX10 (c.429-1G>C) was considered to cause the KS phenotype in patient 02, and two potential variants of uncertain significance (VUS) in CHD7 (c.3344G>A and c.7391A>G) possibly contributed to the KS phenotype in patient 05 and the nIHH phenotype in patient 07, which need to be confirmed by further evidence. Additionally, long-term testosterone or estradiol replacement treatment effectively improved the development of sexual characteristics in patients with IHH. Conclusion: Next-generation sequencing is a powerful tool for identifying the molecular etiology and early diagnosis of IHH. Efficient therapeutic outcomes strongly indicate a need for timely treatment.

Serum triglyceride glucose index is a valuable predictor for visceral obesity in patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: Since the triglyceride glucose (TyG) index can reflect insulin resistance, it has been proven to be an efficient predictor of glycolipid-metabolism-related diseases. Therefore, this study aimed to investigate the predictive value of the TyG index for visceral obesity (VO) and body fat distribution in patients with type 2 diabetes mellitus (T2DM). METHODS: Abdominal adipose tissue characteristics in patients with T2DM, including visceral adipose area (VAA), subcutaneous adipose area (SAA), VAA-to-SAA ratio (VSR), visceral adipose density (VAD), and subcutaneous adipose density (SAD), were obtained through analyses of computed tomography images at the lumbar 2/3 level. VO was diagnosed according to the VAA (> 142 cm2 for males and > 115 cm2 for females). Logistic regression was performed to identify independent factors of VO, and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance according to the area under the ROC curve (AUC). RESULTS: A total of 976 patients were included in this study. VO patients showed significantly higher TyG values than non-VO patients in males (9.74 vs. 8.88) and females (9.59 vs. 9.01). The TyG index showed significant positive correlations with VAA, SAA, and VSR and negative correlations with VAD and SAD. The TyG index was an independent factor for VO in both males (odds ratio [OR] = 2.997) and females (OR = 2.233). The TyG index ranked second to body mass index (BMI) for predicting VO in male (AUC = 0.770) and female patients (AUC = 0.720). Patients with higher BMI and TyG index values showed a significantly higher risk of VO than the other patients. TyG-BMI, the combination index of TyG and BMI, showed significantly higher predictive power than BMI for VO in male patients (AUC = 0.879 and 0.835, respectively) but showed no significance when compared with BMI in female patients (AUC = 0.865 and 0.835, respectively). CONCLUSIONS: . TyG is a comprehensive indicator of adipose volume, density, and distribution in patients with T2DM and is a valuable predictor for VO in combination with anthropometric indices, such as BMI.

Association Between the Growth Hormone/Insulin-Like Growth Factor-1 Axis and Muscle Density in Children and Adolescents of Short Stature.

Objective: To evaluate the association between the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and muscle density in children and adolescents of short stature. Methods: Participants were children and adolescents of short stature hospitalized in the Affiliated Hospital of Jining Medical University between January 2020 and June 2021. All participants had CT scan images available. We performed an analysis of the images to calculate the muscle density or skeletal muscle attenuation (SMA), skeletal muscle index (SMI), and fat mass index (FMI). Bioelectrical impedance analysis (BIA) was used to ensure that chest CT is a credible way of evaluating body composition. Results: A total of 297 subjects were included with the mean age of 10.00 ± 3.42 years, mean height standard deviation score (SDS) of -2.51 ± 0.53, and mean IGF-1 SDS of -0.60 ± 1.07. The areas of muscle and fat tissues at the fourth thoracic vertebra level in the CT images showed strong correlation with the total weights of the participants (R2  = 0.884 and 0.897, respectively). The peak of GH was negatively associated with FMI (r = - 0.323, P <.01) and IGF-1 SDS was positively associated with SMI (r = 0.303, P <.01). Both the peak GH and IGF-1 SDS were positively associated with SMA (r = 0.244, P <.01 and r = 0.165, P <.05, respectively). Multiple stepwise linear regression analysis demonstrated that the GH peak was the predictor of FMI (ß = - 0.210, P < .01), the IGF-1 SDS was the predictor of SMI (ß = 0.224, P < .01), and both the peak GH and IGF-1 SDS were predictors of SMA (ß = 0.180, P < .01 and ß = 0.222, P < .01). Conclusions: A chest CT scan is a credible method of evaluating body composition in children and adolescents of short stature. In these patients, peak GH and IGF-1 SDS are independent predictors of muscle density and the GF/IGF-1 axis may regulate body composition through complex mechanisms.

Toxicological Evaluation of Camellia euphlebia Leaves Aqueous Extract Using Acute and Subacute Toxicity Studies in Mice and Genotoxicity Studies.

Camelliaeuphlebia is a novel food source and Chinese folk medicine with multiple pharmacological properties. Our previous exploration has demonstrated the antidepressant-like activity of Camellia euphlebia leaves aqueous extract by reliable animal models of depression; however, a lack of toxicological information limits its pharmacological application. The present study aimed to evaluate the preliminary safety of C. euphlebia extract by determining acute/subacute toxicity in mice and in vivo/in vitro genotoxicity. The oral-medium lethal dose of the extract in mice was found to be higher than 5000 mg/kg body weight in the acute toxicity study. In a 14-days subacute toxicity study, C. euphlebia extract at doses of 400, 800, and 1600 mg/kg did not result in significant changes in food intake, water intake, body weight, relative organ weight, aspartate aminotransferase activity, alanine aminotransferase activity, creatinine level, and number of white blood cells and red blood cells. However, histopathology observation of organs taken from all mice showed that 1600 mg/kg extract caused slight hydropic degeneration in the cytoplasm of hepatocytes. In a 28-days subacute toxicity study, 600 mg/kg extract significantly increased the level of red blood cells but produced no negative side effects on other pathological parameters. Mice treated with the extract at doses of 200, 400, and 600 mg/kg for 28 days did not manifest any histopathological alterations of the liver, kidney, and spleen. Additionally, the extract showed no chromosomal aberrations in the in vivo micronucleus test and in vitro chromosomal aberration test. The results revealed that the extract showed no significant toxic effects and no potential genotoxicity but with the likelihood of transient erythrocytosis and slight hepatotoxicity. Further chronic toxicological evaluation involved in more physiological parameters, especially associated with liver toxicity and erythropoietin level, would be needed to determine its safety and application value.

Molecular diagnosis for growth hormone deficiency in Chinese children and adolescents and evaluation of impact of rare genetic variants on treatment efficacy of growth hormone.

BACKGROUND: Growth hormone is an effective therapy for growth hormone deficiency (GHD) but with a rather variable individual sensitivity. It is unclear whether rare genetic variants may contribute to the differential GH responsiveness. METHODS: The present study aims to investigate the molecular etiology of GHD in Chinese children and adolescents and evaluate the impact of rare variants on therapeutic efficacies of GH. RESULTS: Twenty-one rare heterozygous variant were classified as promising uncertain significance (n = 14), pathogenic (n = 5) or likely pathogenic (n = 2) for 21 of the 93 GHD patients. After GHD patients harboring these rare variants were excluded, inter-individual variability in the response to GH therapy obviously reduced and the negative correlation between initiation age of treatment and height SDS change became stronger in the group without rare variants. Among rare variants, 7 (likely) pathogenic variants (7.5%, 7/93) involved a total of 6 genes not only associated with GH secretion (PROKR2, LZTR1), but also growth plate chondrocyte signaling (ACAN, FBN1, COL9A1) or genetic syndromes (PTPN11). CONCLUSIONS: Rare genetic variants are an important factor contributing to differential GH responsiveness and genetic testing should be factored into accurate diagnosis and treatment decision making in the future. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR1900026510.

Corilagin induces apoptosis and inhibits autophagy of HL­60 cells by regulating miR­451/HMGB1 axis.

Corilagin is the primary active component of the Euphorbia phyllanthus plant and has significant anti­cancer properties. However, the biological effects and mechanisms of corilagin on acute myeloid leukemia (AML) have not been clarified. The Cell Counting Kit­8 and Carboxyfluorescein Diacetate Succinimidyl Ester assay results showed that corilagin significantly inhibited proliferation of the AML cell line HL­60 in a time­ and dose­dependent manner. Western blotting and flow cytometry analysis were performed to determine the levels of apoptosis in HL­60 cells. The protein levels of cleaved caspase­3 and Bak were upregulated, while Bcl­xl was downregulated in cells treated with corilagin. The percentage of early­ and late­stage apoptotic cells increased following corilagin treatment in a dose­dependent manner, indicating that the intrinsic mitochondrial apoptosis pathway was activated by corilagin. Simultaneously, western blotting and immunofluorescence results revealed that autophagy was suppressed; this was accompanied by a decrease in light chain 3­II (LC3­II) conversion and autophagosomes. MicroRNA (miRNA/miR) profile analysis showed that corilagin elevated the expression of the tumor suppressor miR­451, while the mRNA and protein levels of high mobility group protein B1 (HMGB1), the target of miR­451, decreased following exposure to corilagin. Knockdown of miR­451 decreased the downregulation of HMGB1 caused by corilagin, indicating negative regulation of HMGB1 by miR­451 during corilagin treatment. Furthermore, knockdown of miR­451 also attenuated corilagin­induced proliferation inhibition of HL­60 cells, implying that miR­451 was essential for the proliferation inhibitory effect of corilagin. In conclusion, these results indicated that corilagin induced apoptosis and inhibited autophagy in HL­60 cells by regulating the miR­451/HMGB1 axis, and corilagin may be a novel therapeutic drug for the treatment of AML.

A heterozygous point mutation of the ANKRD11 (c.2579C>T) in a Chinese patient with idiopathic short stature.

BACKGROUND: Pathogenic variants of ANKRD11 have been reported to cause KBG syndrome characterized by short stature, characteristic facial appearance, intellectual disability, macrodontia, and skeletal anomalies. However, the direct clinical relevance of ANKRD11 mutation with short stature is yet unknown. METHODS: Here, we report a Chinese boy with idiopathic short stature (ISS) based on clinical and genetic characteristics. Comprehensive medical evaluations were performed including metabolic studies, endocrine function tests, bone X-rays, and echocardiography. Whole-exome and Sanger sequencing was used to detect and confirm genetic mutations associated with short stature in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools and repositories of sequence variation. Twenty-four months follow-up was performed to observe the growth rate of the patient treated with recombinant human growth hormone (GH). RESULTS: One heterozygous point mutation (c.2579C>T) was confirmed in the ANKRD11 gene of the patient and inherited from his mother. This mutation site was located within the highly conservative region of ANKRD11 protein and predicted to be possibly damaging in several in silico prediction programs and repositories of sequence variation. Additionally, patient underwent GH replacement therapy for 24 months exhibited good response to the treatment. CONCLUSION: A heterozygous point mutation of AKNRD11 gene was identified in a Chinese patient with short stature phenotype. The patient was treated effectively with GH supplementation.

Correlations of Equilibrium Properties and Electronic Structure of Pure Metals.

First principles calculations were carried out to study the equilibrium properties of metals, including the electrons at bonding critical point; ebcp; cohesive energy; Ecoh; bulk modulus; B; and, atomic volume; V. 44 pure metals, including the s valence (alkali), p valence (groups III to V), and d valence (transition) metals were selected. In the present work, the electronic structure parameter ebcp has been considered to be a bridge connecting with the equilibrium properties of metals, and relationships between ebcp and equilibrium properties (V; Ecoh; and B) are established. It is easy to estimate the equilibrium properties (Ecoh; V, and B) of pure metals through proposed formulas. The relationships that were derived in the present work might provide a method to study the intrinsic mechanisms of the equilibrium properties of alloys and to develop new alloys.

Camellia euphlebia protects against corticosterone-induced apoptosis in differentiated PC12 cells by regulating the mitochondrial apoptotic pathway and PKA/CREB/BDNF signaling pathway.

Camellia euphlebia is a Chinese folk medicine, known for its multiple pharmacological properties. Our previous studies have demonstrated its antidepressant activity by several animal models of depression. The possible underlying mechanism was further explored by investigating the neuroprotective effect of Camellia euphlebia extract (CEE) on corticosterone-induced apoptosis in neuronally differentiated PC12 cells. The results of methyl-thiazolyl-tetrazolium assay, lactate dehydrogenase release assay, Hoechst 33342 staining, propidium iodide staining, AV-FITC/PI double staining and DNA fragmentation analysis consistently indicated that pretreatment of PC12 cells with CEE at 20-80 µg/mL significantly reversed 300 µmol/L corticosterone-induced apoptosis in a dose dependent manner. Furthermore, intracellular mitochondrial membrane potential, reactive oxygen species accumulation, calcium level, Bcl-2/Bax ratio, caspase activity were assessed, and the results indicated that CEE exhibited its anti-apoptotic effect through the regulation of mitochondrial apoptosis pathway. Additionally, CEE increased the cyclic adenosine monophosphate-dependent protein kinase (PKA) level, which phosphorylated cAMP response element binding protein (CREB), and finally elevated the mRNA expression of brain-derived neurotrophic factor (BDNF) gene. It is speculated that the antidepressant effect of CEE in vivo may be associated with the cytoprotection of neuron damaged by corticosterone, and the cellular mechanism involves the mitochondrial-mediated apoptosis and PKA-CREB-BDNF signaling pathway.

Effect of Different Processing Methods on Phytochemical Contents and Neuroprotective Activity of Camellia euphlebia Leaves Extract.

Camellia euphlebia is a new food source and traditional folk medicine in China. Previous studies have demonstrated the antidepressant activity of Camellia euphlebia extract by both in vivo and in vitro experiments. The effects of different pretreatments on phytochemical contents and neuroprotective activity of Camellia euphlebia extract were further investigated in order to develop an optimal processing method that makes the extraction more efficient. Six different powders of Camellia euphlebia leaves were prepared by different pretreatments. The particle size and morphology were examined by using a Malvern particle size analyzer and scanning electron microscopy, respectively. The results showed that the percentage of powder particle size within a range of 0.2∼40 µm was up to 79.18% after press-shear assisted interaction technology pretreatment by 2% addition of shellfish shell powder, and the cells were broken completely. Additionally, the contents of flavonoids, polysaccharides, polyphenols, saponins, and catechin in the extract were 11.78 ± 0.62%, 34.60 ± 3.37%, 6.15 ± 0.29%, 9.43 ± 1.19%, and 1.99 ± 0.11%, respectively, which were higher than those of the other five extracts. Moreover, the extract had the strongest neuroprotective activity by comparing the neuroprotective effect of different extracts on corticosterone-induced neurotoxicity in differentiated PC12 cells. It is concluded that press-shear assisted interaction technology with 2% addition of shellfish shell powder pretreatment, to a great extent, improved the dissolution of bioactive ingredients in Camellia euphlebia.

Orthogonal test design for optimization of the extraction of essential oil from Asarum heterotropoides var. Mandshuricum and evaluation of its antibacterial activity against periodontal pathogens.

The optimum extraction conditions of essential oil from Asarum heterotropoides var. Mandshuricum applied by an orthogonal L9(33) test were a water-to-raw material ratio of 17, a particle size of D 95 ≤ 3.8 mm and an extraction time of 2 h. In ingredient analysis, gas chromatography/mass spectrometry analysis identified the main components of essential oil as methyl eugenol (45.95%), safrole (17.48%) and 3,5-dimethoxytoluene (10.30%) orderly. In vitro, the minimum inhibitory concentration and minimum bactericidal concentration of essential oil were 0.01 and 0.02% against F. nucleatum, 0.04 and 0.08% against P. intermedia, and 0.005 and 0.005% against P. gingivalis. In vivo, administration of essential oil significantly suppressed alveolar bone resorption induced by F. nucleatum, with bone levels remaining comparable to non-infected mice. These results of antibacterial activity of essential oil in vitro and in vivo show the inhibition of periodontal pathogens and therapy of alveolar bone resorption in mice, suggesting that its essential oil could be a potential natural therapeutic agent for treatment of periodontitis in human beings.

Camellia euphlebia exerts its antidepressant-like effect via modulation of the hypothalamic-pituitary-adrenal axis and brain monoaminergic systems.

Camellia euphlebia (family, Theaceae) is a Chinese folk medicine, known for its multiple pharmacological properties. The present study aimed to provide further insights into the therapeutic basis of C. euphlebia using several animal behavioral tests and physiological indexes. Tail suspension test, forced swimming test, open-field test, chronic unpredictable mild stress (CUMS), reversal of reserpine-induced hypothermia and palpebral ptosis, and 5-hydroxytryptophane-induced head-twitch response were used to evaluate the antidepressant effect of aqueous extract of Camellia euphlebia (AEC) on mice. The possible underlying mechanism was explored by investigating the changes associated with several parameters of animal behavior, as well as the changes in monoamine neurotransmitter and stress hormone levels in these animals during the tests. Mice administered AEC at 100 and 200 mg/kg/day doses for 7 days showed significantly reduced immobility duration in forced swimming test and tail suspension test, whilst exhibiting no apparent changes in locomotor activity. Additionally, administration of AEC also effectively antagonized reserpine-induced palpebral ptosis and hypothermia and enhanced 5-hydroxytryptophane-induced head-twitch response. AEC significantly elevated the levels of serotonin, noradrenaline and dopamine in the blood and brain compared to non-treated mice. After 28 days of administration, the maximum AEC dose (100 mg/kg/day) significantly reversed CUMS-induced inhibition of weight gain and sucrose intake, while decreasing the levels of plasma adrenocorticotropic hormone and serum corticosterone. The antidepressant effect of AEC appeared to involve the alteration of hypothalamic-pituitary-adrenal axis and monoaminergic systems.

Hypolipidemic Activity of Camellia euphlebia Flower Extract in High-fat-fed Mice.

Camellia euphlebia (family, Theaceae) has been used for the prevention and treatment of cardiovascular diseases in Southern China. However, there has been no report on the hypolipidemic activity of Camellia euphlebia flower. This study evaluated the hypolipidemic activity of different preparation of Camellia euphlebia flower extracts using in vivo models. Mice intragastrically administered aqueous extract at 400 mg/kg dose or ethanol extract at 100 and 400 mg/kg doses of Camellia euphlebia flower for 28 days exhibited significant decreases in the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol, while displaying increased level of high-density lipoprotein cholesterol in the serum. The Camellia euphlebia flower extracts also improved the antioxidant ability of hyperlipidemic mice as well as protecting the animals against liver damage by lowering the level of glutamic-pyruvic transaminase activity. Furthermore, 400 mg/kg ethanol extract effectively down-regulated the mRNA levels of fatty acid synthase, 3-hydroxy-3-methylglutaryl CoA reductase and glycerol-3-phosphate acyl transferase, suggesting that Camellia euphlebia flower extract may potentially inhibit lipid accumulation in the liver by regulating the expression of fatty acid synthase, 3-hydroxy-3-methylglutaryl CoA reductase and glycerol-3-phosphate acyl transferase. These results provided support for the potential hypolipidemic activity of Camellia euphlebia flower and could partly explain the basis of using Camellia euphlebia for the treatment of hyperlipidemia.

Spectroscopic studies on the interactions between novel bisnaphthalimide derivatives and calf thymus DNA.

The types of interactions between six novel bisnaphthalimide derivatives (AITHN, BITHN, PITHN, PyITHN, DN6 and DNT6) and calf thymus DNA in a physiological buffer (Tris-HCl buffer solutions, pH=7.4) were investigated using UV-vis spectrophotometry, fluorescence spectroscopy, and a competition experiment, in order to explore the relationships between the linkers of bisnaphthalimide derivatives and their activity. The absorption spectra of the six bisnaphthalimide derivatives with DNA showed a slight red shift and hypochromic effect. DNA quenched the compounds (AITHN, PITHN, PyITHN and DN6) by a static quenching process. Using acridine orange (AO) dye as a fluorescence probe, fluorescence quenching of the emission peak was observed in the AO-DNA system with the addition of PITHN, but the maximum emission intensity was elevated for AITHN and DN6 while the other three compounds showed no obvious change. The calculated binding constants of AITHN, PITHN, PyITHN and DN6 with DNA were 2.09×105Lmol-1, 1.14×105Lmol-1, 0.95×105Lmol-1 and 2.39×105Lmol-1 respectively, and the number of binding sites were 0.618, 0.323, 0.297 and 0.769. Intercalative and electrostatic binding were the two major modes between the six bisnaphthalimide derivatives and calf thymus DNA. The strength of the intercalation was related to the type of linker. Moreover, DN6 and AITHN had the greatest intercalative ability. The electrostatic binding ability of the six compounds was independent of the type of linker present.

Evaluation of the Anxiolytic and Antidepressant Activities of the Aqueous Extract from Camellia euphlebia Merr. ex Sealy in Mice.

Camellia euphlebia Merr. ex Sealy is a traditional Chinese medicine that has been widely used for improvement of human emotions in the Guangxi Province of southern China. However, there are no studies about the anxiolytic and antidepressant activities of Camellia euphlebia. This study evaluated the anxiolytic and antidepressant activities of the aqueous extract from Camellia euphlebia (CEE) in mice. We found that administration of 400 mg/kg CEE or 20 mg/kg fluoxetine for 7 days significantly reduced the immobility time in both TST and FST. Oral administration of 100 mg/kg extract or 4 mg/kg diazepam for 7 days significantly increased the percentage of time spent and the number of entries into the open arms of the EPMT. In addition, the time spent by mice in the illuminated side of the LDBT was increased. Furthermore, pretreatment with 400 mg/kg CEE for 7 days significantly elevated the level of 5-HT and DA in the whole brain of mice. These results provide support for the potential anxiolytic and antidepressant activity of Camellia euphlebia and contribute towards validation of the traditional use of Camellia euphlebia in the treatment of emotional disorders.