Multi-element Exposure and Cognitive Function in Rural Elderly Chinese.

To investigate the relationship between selenium (Se) based multi-element combined exposure and cognitive function in rural elderly individuals, a cross-sectional study was conducted. The study involved 416 older adults aged 60 and above, residing in four different areas of Enshi county, China, with varying soil Se levels. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to measure the concentrations of Se, copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg), cadmium (Cd), arsenic (As), and lead (Pb) in whole blood. Nine standard cognitive tests were applied to assess cognitive function. Analysis of the least absolute shrinkage and selection operator regression (LASSO), covariance (ANCOVA), and generalized linear model (GLM) were utilized to investigate the relationship between element exposure and cognitive function. The results of LASSO revealed that Se, Cu, Fe, Zn, Ca, and Pb were independently identified to be associated with cognition. Both ANCOVA and GLM demonstrated that Se and Ca were correlated with cognitive function. The multi-element model showed higher composite Z scores of 0.32 (95% CI: 0.09 to 0.55) for log-transformed Se (P = 0.007), 0.75 (95% CI: 0.01 to 1.49) for log-transformed Cu (P = 0.048), and a lower score of - 0.67 (95% CI: - 1.26 to - 0.08) for log-transformed Ca (P = 0.025). Furthermore, there was evidence that Se could counteract the negative impact of Ca on cognitive function (P for interaction = 0.031). Our findings suggested that higher levels of Se and Cu were associated with better cognitive function in the elderly and Se can counteract the cognitive damage caused by Ca.

Blood Selenium and Serum Glutathione Peroxidase Levels Were Associated with Serum ß-Amyloid in Older Adults.

BACKGROUND: Studies have established the association between blood ß-amyloid (Aß) levels and Alzheimer's disease, but population-based studies concerning the association between selenium (Se) and Aß levels in blood samples are very limited. Therefore, we explored the association in an elderly population with Se status and serum Aß measures. METHODS: A cross-sectional study on 469 elderly individuals from four rural counties with diverse soil Se levels was carried out. Fasting blood Se, serum selenoprotein P (SELENOP), and glutathione peroxidase (GPX), serum Aß42, and Aß40 were measured. Quantile regression models were used to determine the associations of blood Se, serum GPX, and SELENOP with Aß levels. RESULTS: Significant negative associations were observed between blood Se and serum Aß42 and Aß40 levels at all percentiles (P < 0.05). The associations were generally stronger at higher Aß42 and Aß40 percentiles than lower Aß42 and Aß40 percentiles. Blood Se was positively associated with serum Aß42/Aß40 ratio at 25th, 50th, and 75th percentiles. Significant positive associations were observed between serum GPX and Aß42 and Aß40 levels at all percentiles (P < 0.05). The positive associations were generally stronger at higher Aß42 and Aß40 percentiles than at lower percentiles. Serum GPX was negatively associated with Aß42/Aß40 ratio at 25th, 50th, 75th, and 95th percentiles. No associations with serum SELENOP and Aß levels were observed. CONCLUSIONS: Our results suggest that higher Se levels are associated with lower serum Aß42 and Aß40 levels and with higher Aß42/Aß40 ratio, and the results are specific for different selenoproteins.

Evaluation of Gamma Amino Butyric Acid (GABA) and Glibenclamide Combination Therapy in Streptozotocin Induced Diabetes.

BACKGROUND: Type 1-diabetes (T1D) is characterized by autoimmune destruction of ß-cells and loss of endogenous insulin. A lifelong dependency on exogenous supply of insulin presents a great challenge in the pharmacotherapy of T1D that elicits a quest for alternative therapies, which can protect ß-cells and revive their insulinogenic functions. GABA (γ-aminobutyric acid) has immunoprotective and ß-cell regenerative capabilities. Co-administration of an insulin secretagogue, such as glibenclamide (Glib), along with GABA may enhance the pancreatic insulin output in T1D. OBJECTIVE: The present study evaluated the possible mechanism of GABA in the improvement of glucose tolerance and its effects in streptozotocin (STZ) induced T1D along with Glib. METHODS: Wistar rats (180-220 g) were administered a single dose of STZ (55 mg/kg, i.p.). GABA (100 mg/kg, i.p.) and Glib (5 or 10 mg/kg, i.p.) alone or in combination were administered for 28 days. Body weight (b.w.), water consumption, fasting blood glucose (FBG), oral glucose tolerance, plasma lipids, insulin, and muscle GLUT-4 (glucose transporters) protein level were assessed. RESULTS: T1D significantly decreased b.w. and increased water-intake in rats. An increase in FBG and a decrease in plasma insulin and muscle GLUT-4 indicated STZ-triggered destruction of ß-cells in diabetic rats accompanied with dyslipidemia. GABA or Glib (10 mg/kg) significantly improved b.w., plasma insulin and GLUT-4 levels, and ameliorated FBG and blood lipid profile in diabetic rats. GABA and Glib (5 mg/kg) combination therapy achieved far better control over hyperglycemia and related pathogenic conditions (b.w., water-intake, insulin, GLUT-4, lipids). The anti-diabetic effect of combination therapy was significantly more pronounced in comparison to individual drug treatments. Histopathological analysis revealed an increase in the number of functional pancreatic-islets by combination therapy. CONCLUSION: GABA revitalized ß-cells against STZ-toxicity. GABA and Glib synergistically augmented insulin secretion that can be used to manage T1D and its complications. GABA has the potential to remarkably enhance the therapeutic outcome in diabetic patients and reduce the dose of existing anti-diabetic drugs such as Glib.

Neem tree (Azadirachta indica) extract specifically suppresses the growth of tumors in H22-bearing Kunming mice.

Recently, neem tree (Azadirachta indica) extract (NTE) has been reported to have various antitumor activities against gastric, breast, prostate, and skin cancer, respectively. The current study was designed to evaluate the effect of NTE on hepatic cancer in a mouse model. The possible side effects elicited by NTE were also evaluated. The components in NTE were analyzed by liquid chromatography-mass spectrometry (LC-MS). H22 cells-bearing Kumming mice were generated by injecting H22 cells subcutaneously into the right forelimb armpit of the mice. Then the mice were treated daily for 27 days with NTE (150, 300, and 600 mg/kg body weight) by intragastric administration, using carboxymethyl cellulose (CMC, 1%) as blank control and cyclophosphamide (CTX, 20 mg/kg) as positive control. The antitumor effect of NTE was evaluated by assessment of survival rate, body weight, tumor volume and weight, tumor histology, thymus and spleen indexes, and liver histology. The tumor weight and volume in groups of NTE and CTX were significantly lower than those in the CMC group. The survival rate in the NTE group receiving the high dose (600 mg/kg) was significantly higher than that in the CTX and CMC groups. Compared with CTX, NTE was observed to have a tumor-specific cytotoxicity without impairing the normal liver tissue. Additionally, the higher indexes of thymus and spleen indicated that NTE could facilitate the growth of immune organs. The results indicate that NTE is a promising candidate for the antitumor treatment with high efficacy and safety.

[Genetic diversity analysis of Andrographis paniculata in China based on SRAP and SNP].

In order to reveal genetic diversity of domestic Andrographis paniculata and its impact on quality, genetic backgrounds of 103 samples from 7 provinces in China were analyzed using SRAP marker and SNP marker. Genetic structures of the A. paniculata populations were estimated with Powermarker V 3.25 and Mega 6.0 software, and polymorphic SNPs were identified with CodonCode Aligner software. The results showed that the genetic distances of domestic A. paniculata germplasm ranged from 0. 01 to 0.09, and no polymorphic SNPs were discovered in coding sequence fragments of ent-copalyl diphosphate synthase. A. paniculata germplasm from various regions in China had poor genetic diversity. This phenomenon was closely related to strict self-fertilization and earlier introduction from the same origin. Therefore, genetic background had little impact on variable qualities of A. paniculata in domestic market. Mutation breeding, polyploid breeding and molecular breeding were proposed as promising strategies in germplasm innovation.

[Preparation, in vitro evaluation of excipient-free dry powder inhalation of extraction of Trollius chinensis].

To prepare and evaluate dry powder inhalation (DPI) of extraction of Trollius chinensis Bunge (TCB). Orthodox design was employed to optimize the parameters of spray drying to prepare micronized TCB powder, the DPI was prepared by mixing micronized TCB powder and lactose. The results showed that the fine particle fraction (FPF) and emitted dose (ED) of micronized TCB powder was (21.07 +/- 1.74)%, (75.31 +/- 21.05)%, respectively, and for DPI was (56.4 +/- 2.2)%, (95.9 +/- 3.0)%, respectively. Therefore, the prepared DPI meeted requirements in the Chinese Pharmacopeia, indicating a good application prospect.

[Preparation and pharmacodynamic evaluation of diammonium glycyrrhizinate-loaded chitosan nanoparticles].

OBJECTIVE: To prepare the diammonium glycyrrhizinate-loaded chitosan nanoparticles (DG-CS NPs), and evaluate its pharmaceutical properties and pharmacodynamic effects on ulcerative colitis (UC). METHOD: DG-CS NPs were prepared by spray drying method and optimized by orthogonal design. The morphology, size and in vitro release of DG-CS NPs were investigated. The therapeutic effects of DG-CS NPs on UC mice induced by dextran sulfate were evaluated preliminarily through disease active index method. RESULT: The size of DG-CS NPs with loading capacity about (51.25 +/- 1.75)% was in the range of 300-600 nm. The release of DG-CS NPs was associated with environmental pH value and displayed significant therapeutic and preventive effects on UC. CONCLUSION: DG-CS NPs prepared by spray drying method showed efficacy on UC mice.

[Preparation and in vitro release of ginkgo biloba extract sustained-release tablets].

OBJECTIVE: To prepare ginkgo biloba extract (GBE) sustained-release tablets and observe its in vitro release profile. METHOD: GBE sustained-release tablets were prepared by direct compression method using sodium carboxymethylcellulose (CMC-Na) and hydroxypropyl methylcellulose HPMC) as matrix excipients. Based on the result of single-factor selecting experiment, the formulations and preparation process were optimized through orthogonal design, and release difference of tablets was evaluated with similarity factor (f2). RESULT: The ratio of HPMC and CMC-Na, the viscosity of HPMC and the different types of the diluents had pronounced effect on the release of GBE sustained release tablets, although the hardness and weight difference of tablets did not show notable influences. CONCLUSION: GBE sustained-release tablets that prepared by using the mixture of HPMC and CMC-Na display constant release profile in 12 h.

The ethanol response gene Cab45 can modulate the impairment elicited by ethanol and ultraviolet in PC12 cells.

High consumption of ethanolic beverages facilitates neurodegeneration, but the mechanism of this process still remained elusive. Suppression subtractive hybridization (SSH) is a technique for detection of rare transcripts. With SSH approach, we identified one ethanol response gene Cab45, which was down-regulated by ethanol with time-dependent manner in B104 cells. The full-length sequence of Cab45 gene was obtained by 5' -RACE (5' Rapid Amplification of cDNA Ends) for the first time in rat. Based on the sequence of deduced amino acid of rat Cab45, the alignment was conducted with its counterparts in different species and displayed a high conservation. Using different tissues in rat and cell lines, Cab45 was characterized by a ubiquitous expression and differentiation dependent down-regulation. Given that ethanol facilitates some cell differentiation, we hypothesize that Cab45 is involved in ethanol-mediated differentiation. With transient transfection, the function of Cab45 was investigated by up-regulation and down-regulation in PC12 cells. Ethanol treatment and UV exposure were conducted subsequently and cell proliferations were detected by MTT (Methyl Thiazolyl Tetrazolium) approach. It revealed that the up-regulation of Cab45 modulated the impairment elicited by ethanol and UV in transfected cells. As a member of new calcium binding protein family, the exact role of Cab45 still remains unclear.

The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells.

PURPOSE: This study aimed to evaluate the multidrug resistance (MDR) reversal activity of quercetin (Que) in combination with hyperthermia (HT) in human myelogenous leukemia cells K562/A. METHODS: The cytotoxicity of Que alone and the effect of Que and HT to doxorubicin (Dox) cytotoxicity were determined using MTT assay in K562 and K562/A cells. K562/A cells was heated with or without Que pretreatment, and the protein and mRNA levels of heat shock protein 70 (HSP70) and P-glycoprotein (P-gp) were determined by flow cytometry (FCM) and RT-PCR, respectively. Intracellular accumulation of Dox, cell cycle and apoptosis were monitored with FCM. RESULTS: Que alone inhibited cell growth in a dose-dependent manner in K562 and K562/A cells. Either Que or HT alone had a weak reversal effect on Dox resistance, however, combination HT and Que showed a much more significant reversal effect on Dox resistance (reverse fold 9.49). The elevated protein expression and mRNA level of HSP70 and P-gp in response to HT were inhibited by Que. Pretreatment with Que caused the cells to accumulate Dox 8.3-fold higher than in control cells. In addition, Que induced apoptosis and G2/M arrest in a dose-dependent manner, and the combination of Que and HT was found to have a synergistic effect on apoptosis. CONCLUSIONS: Que pretreatment could significantly enhance the MDR reversal activity of HT in resistant cell line, by sensitizing the cell to reversing MDR activity of HT.

Identification of genes induced by rapid intraoperative tissue expansion in mouse skin.

A method of rapid skin stretching, i.e. hemispherical load cycling with an inflated subcutaneous silicone balloon (Rapid Intraoperative Tissue Expansion or RITE), permits the surgeon to rapidly elongate skin and create a flap of greater length for reconstructive plastic surgery. We have previously developed an experimental mouse model to evaluate RITE, and have shown that rapid stretching prevents ischemia and significantly reduces necrosis. Although the advantages of RITE have been demonstrated both clinically and experimentally, the cellular and molecular mechanisms underlying these benefits were unknown. In the study reported here, we used differential display reverse transcription polymerase chain reaction to identify genes that are specifically induced by RITE. Among four differential gene fragments, the expression of one was confirmed by Northern blot hybridization. The cDNA fragment was extended and the resultant sequence analyzed to reveal induction of truncated long interspersed nucleotide element 1 (LINE-1 or L1). Truncated L1 elements are located inside introns of many genes and among these genes myotubularin and insulin I are known to regulate cell growth. Northern hybridization using specific cDNA probes for myotubularin and insulin I demonstrated that it also was induced by RITE. This is the first reported study to show that L1, myotubularin and insulin I are responsive to rapid hemispherical and not rapid linear stretch.