Prominent Effects of Berbamine Hydrochloride on Alzheimer's Disease Model Mice.

Very few anti-Alzheimer's disease (AD) drugs are clinically available at present due to the complex mechanism of Alzheimer's disease. For the purpose of discovering potential anti-AD drugs in bisbenzylisoquinoline alkaloids, the anti-AD function and the mechanism of the function of berbamine hydrochloride (BBMH) were studied. Three kinds of AD model mice, double transgenic APP/PS1 AD mice, Gal-Alu AD mice induced by the intraperitoneal injection of d-galactose combined with the intragastric administration of aluminum trichloride, and Alu AD-like mice induced by stereotactic brain injection of aluminum trichloride, were administered with BBMH for 40 days at a dosage of 280 mg/kg/d. The effects of BBMH on the learning and memory behavior of the AD mice were studied through the Morris water maze experiment, and the influences of BBMH on the pathological features of AD, including the deposition of Aß, the lesions of pyramidal cells (neurons), and the formation of neurofibrillary tangles, were studied by the immunohistochemical staining, hematoxylin-eosin staining, and silver staining of the brain tissues of the mice. The water maze experiment showed that BBMH could significantly improve the learning and memory abilities of three kinds of treated mice. Immunohistochemical staining showed that BBMH could significantly reduce the deposition of Aß in the brain tissues of treated mice. Hematoxylin-eosin staining showed that BBMH could significantly alleviate the lesions of pyramidal cells in the hippocampal tissue of the mice. Silver staining showed that BBMH could significantly reduce the formation of neurofibrillary tangles in the hippocampal tissue of the mice. These results indicated that BBMH has significant anti-AD effects and the potential as an anti-AD drug. Western blot analysis of the brain tissue of the mice showed that the expression level of calpain, a Ca2+-dependent proteolytic enzyme, was significantly inhibited and the expression level of SelK, a selenoprotein mainly expressed in immune cells, was significantly increased. It is speculated that the anti-AD effect of BBMH is related to the improvement of the phagocytosis of microglial cells in brain tissues and macrophages migrated into the brain as well as the regulation of calcium homeostasis and calcium-dependent proteases in the brain tissues of the mice.

Piceatannol, a Dietary Polyphenol, Alleviates Adipose Tissue Loss in Pre-Clinical Model of Cancer-Associated Cachexia via Lipolysis Inhibition.

Cancer-associated cachexia (CAC) is the nutrition-independent loss of lean muscle and adipose tissues, and results in reduced chemotherapy effectiveness and increased mortality. Preventing adipose loss is considered a key target in the early stages of cachexia. Lipolysis is considered the central driver of adipose loss in CAC. We recently found that piceatannol, but not its analogue resveratrol, exhibits an inhibitory effect on lipolysis. The objective of this study was to investigate the role of piceatannol in cancer-associated lipolysis and cachexia-induced weight loss. Cancer cell-induced lipolysis in adipocytes was stimulated using cancer-conditioned media (CCM) or co-culture with human pancreatic cancer cells and the cachexia-associated cytokines TNF-α and interleukin-6 in 3T3-L1 adipocytes. C26 colon carcinoma-bearing mice were modeled using CAC in vivo. Piceatannol reduced cancer-associated lipolysis by at least 50% in both CCM and cytokine-induced lipolysis in vitro. Further gene and protein analysis confirmed that piceatannol modulated the stability of lipolytic proteins. Moreover, piceatannol protected tumor-bearing mice against weight-loss in early stages of CAC largely through preserving adipose tissue, with no effect on survival. This study demonstrates the use of a dietary compound to preserve adipose in models of early stage CAC and provides groundwork for further investigation of piceatannol or piceatannol-rich foods as alternative medicine in the preservation of body fat mass and future CAC therapy.

Enhancement in the active site exposure in a porphyrin-based PIL/graphene composite catalyst for the highly efficient conversion of CO2.

Poly(ionic liquid)s (PILs) have gained widespread attention in recent years due to their excellent properties similar to both ionic liquids and polymers. However, their further applications are limited because abundant and flexible ions easily block nanopores in the PIL catalysts, thus blocking the active sites and ultimately leading to decreased catalytic activity. This work reports the synthesis of a PIL/graphene composite catalyst (iPOP-ZnTPy@GNFs) based on an in situ surface preparation strategy, which effectively controlled the particle size and dispersion state of ionic liquids. The iPOP-ZnTPy@GNFs exhibited a larger surface area and more exposed active sites, which intensified the catalytic activity in the CO2 cycloaddition reaction with propylene oxide with almost double the reaction rate as compared to that of iPOP-ZnTPy-2 at 100 °C and S/C = 1000. As expected, the iPOP-ZnTPy@GNF catalyst efficiently converted epoxides to cyclic carbonates at room temperature or atmospheric pressure, which can significantly reduce the process cost. In addition, iPOP-ZnTPy@GNFs exhibited excellent broad substrate scope, catalytic diversity, and remarkable reusability. The reaction mechanism of CO2 cycloaddition was studied via density functional theory calculations and was validated by experimental findings. This work provides a feasible method for improving the utilization of active sites in PILs as a highly robust catalyst for CO2 cycloaddition and can be further extended to other types of catalytic reactions in practical applications.

Integrated metabolomics and transcriptomics analysis reveals new biomarkers and mechanistic insights on atrazine exposures in MCF­7 cells.

Atrazine (ATZ) is a widely used herbicide worldwide and is a long-suspected endocrine-disrupting chemical. However, most endocrine-disrupting toxicity studies on ATZ have been based on animal models and those investigating inner mechanisms have only focused on a few genes. Therefore, the possible link between ATZ and endocrine-disrupting toxicity is still unclear. In this study, multi-omics and molecular biology techniques were used to elucidate the possible molecular mechanisms underlying the effect of ATZ exposure on MCF-7 proliferation at environmentally relevant concentrations. Our study is the first report on ATZ-induced one carbon pool by folate metabolic disorder in MCF-7 cells. A concentration of 1 µM ATZ yielded the highest cell viability and was selected for further mechanistic studies. A total of 34 significantly changed metabolites were identified based on metabolomic analysis, including vitamins, amino acids, fatty acids, and corresponding derivatives. Folate and pyridoxal have potential as biomarkers of ATZ exposure. One carbon pool by folate metabolic pathway was identified based on metabolic pathway analysis of the significantly altered pathways. Moreover, FTCD and MTHFD related to this pathway were further identified based on transcriptomic analysis and protein assays. Folate and different forms of 5,6,7,8-tetrahydrofolate, which participate in purine synthesis and associate with methyl groups (SOPC, arachidonic acid, and L-tryptophan) in one carbon pool by the folate metabolic pathway, potentially promote MCF-7 cell proliferation. These findings on the key metabolites and regulation of the related differentially expressed genes in folate metabolism will shed light on the mechanism of MCF-7 cell proliferation after ATZ exposure. Overall, this study provides new insights into the mechanistic understanding of toxicity caused by endocrine-disrupting chemicals.

Ginger and 6-gingerol prevent lipopolysaccharide-induced intestinal barrier damage and liver injury in mice.

BACKGROUND: Inflammation-related diseases present a significant public health problem. Ginger is a flavoring spice and medicinal herb with anti-inflammatory activity. This study investigated the preventive effects of ginger extract (GE) and its main bioactive component, 6-gingerol (6G), on lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and liver injury in mice. RESULTS: GE and 6G were orally administered to mice for seven consecutive days before LPS administration. After 24 h, the mice were sacrificed. GE and 6G were found to significantly reverse LPS-induced inflammation in the mouse ileum by modifying the NF-κB pathway. They also alleviated apoptosis in the ileum by downregulating Bax and cytochrome c gene expression and by inhibiting the caspase-3 pathway. Through the aforementioned mechanisms, GE and 6G restored the intestinal barrier by increasing ZO-1 and claudin-1 protein expressions. Gut-derived LPS induced inflammation and apoptosis in the liver; these effects were markedly reversed through GE and 6G treatment. 6G was the most abundant component in GE, as evidenced through liquid chromatography-mass spectrometry, and accounted for >50% of total gingerols and shogaols in GE. CONCLUSION: The current results support the use of GE and 6G as dietary supplements to protect against gut-derived endotoxemia-associated inflammatory response and disorders. © 2021 Society of Chemical Industry.

Puerarin improves hepatic glucose and lipid homeostasis in vitro and in vivo by regulating the AMPK pathway.

Obesity is an increasingly concerning global health issue, which is accompanied by disruption of glucose and lipid metabolisms. The aim of this study was to uncover the potential and molecular actions of puerarin, a phytochemical, for alleviating metabolic dysfunctions of glucose and lipid metabolisms. A rat model fed a high fat and high fructose diet and a HepG2 cell model challenged with fructose combined with free fatty acid were utilized to identify the effects of puerarin on obesity-associated insulin resistance and hepatic steatosis. The molecular mechanisms underlying puerarin treatment effects were further investigated using qRT-PCR and western blotting. Results show that puerarin significantly ameliorated features of obesity in rats, including bodyweight, hyperlipidemia, hyperglycemia, glucose/insulin intolerance, insulin resistance, hepatic steatosis, and oxidative stress, which are related to the activation of AMPK and PI3K/Akt pathways in the liver. Puerarin reduced lipid accumulation and caused a reduction of the mRNA expression of lipogenic genes such as SREBP-1c, FAS, SCD-1, and HMGCR, and an increment in the phosphorylation of AMPK and ACC in HepG2 cells. Moreover, puerarin ameliorated insulin resistance by increasing GLUT4 mRNA expression and activating the PI3K/Akt pathway. Treatment with the AMPK inhibitor compound C partially abolished the beneficial effects of puerarin on lipid accumulation and insulin resistance in HepG2 cells, which indicated that the protective effects of puerarin partially depend on the AMPK pathway. The present study indicates that puerarin shows potential as a functional food therapeutic for the treatment of obesity.

Tracking the interaction of drug molecules with individual mesoporous amorphous calcium phosphate/ATP nanocomposites - an X-ray spectromicroscopy study.

Adenosine triphosphate (ATP) biomolecules play critial roles in the biomineralization process during the formation of amorphous calcium phosphate composites (ACPC), and ACPC is an important drug carrier due to its significant advantages of biocompatibility and biodegradability. Hence, studying the behavior of ACPC nanodrug carriers is crucial to investigate the structural regulation of biomimetic minerals and calcium phosphate (CaP)-based drug delivery systems. However, it is difficult to probe these interactions using traditional characterization methods. In this paper, XANES analysis together with STXM successfully provided a method to reveal the interaction of ATP and drug molecules with individual mesoporous ACPC. We found that the adenosine and phosphate groups of ATP biomolecules coordinated with Ca2+ and played critical roles in the formation of ACPC; drug molecules with the -COOH groups were linked to Ca2+via carboxylic acid groups primarily by electrostatic interactions, and the N-containing ring structures within the drug molecules also coordinated with Ca2+.

[Methods and applications for microbiome data analysis].

Development of high-throughput sequencing stimulates a series of microbiome technologies, such as amplicon sequencing, metagenome, metatranscriptome, which have rapidly promoted microbiome research. Microbiome data analysis involves a lot of basic knowledge, software and databases, and it is difficult for peers to learn and select proper methods. This review systematically outlines the basic ideas of microbiome data analysis and the basic knowledge required to conduct analysis. In addition, it summarizes the advantages and disadvantages of commonly used software and databases used in the comparison, visualization, network, evolution, machine learning and association analysis. This review aims to provide a convenient and flexible guide for selecting analytical tools and suitable databases for mining the biological significance of microbiome data.

Water-Tolerant Lead Halide Perovskite Nanocrystals as Efficient Photocatalysts for Visible-Light-Driven CO2 Reduction in Pure Water.

Lead halide perovskite (LHP) nanocrystals have recently been actively investigated for photocatalysis, owing to their inexpensive fabrication and excellent optoelectronic properties. However, LHP nanocrystals have not been used for artificial photosynthesis in aqueous solution, owing to their high sensitivity to water. In this study, water-tolerant cobalt-doped CsPbBr3 /Cs4 PbBr6 nanocrystals have been prepared with the protection of hexafluorobutyl methacrylate. The resultant materials are employed as efficient photocatalysts for visible-light-driven CO2 reduction in pure water. The perovskite nanocrystals with 2 % cobalt doping afford an impressive overall yield of 247 µmol g-1 for photocatalytic CO2 conversion into CO and CH4 , using water as an electron source. This study represents a significant step for practical artificial photosynthesis by using LHP nanocrystals as photocatalysts in aqueous solution.

Wheat Flour, Enriched with γ-Oryzanol, Phytosterol, and Ferulic Acid, Alleviates Lipid and Glucose Metabolism in High-Fat-Fructose-Fed Rats.

(1) Background: Modern dietary patterns with a high intake of fat and fructose, as well as refined carbohydrates, closely relate to lipid/glucose metabolic disorders. The main objective of this study is to provide new thoughts in designing functional food with some lipid/glucose metabolism regulating effects for obese people. (2) Methods: The alleviating abilities of γ-oryzanol, phytosterol or ferulic acid-enriched wheat flour on lipid/glucose metabolic dysfunction were evaluated in male SD rats induced by a high-fat-fructose diet. The underlying mechanisms were clarified using western blot. (3) Results: In an in vitro cell model, γ-oryzanol, phytosterol and ferulic acid regulate lipid/glucose metabolism by increasing the phosphorylation of AMPK and Akt, and PI3K expression, as well as decreasing expressions of DGAT1 and SCD. The in vivo study shows that ferulic acid and γ-oryzanol-enriched flours are beneficial for managing body weight, improving glucose metabolism, hyperlipidemia and hepatic lipid accumulation. Phytosterol-enriched flour exerted remarkable effects in regulating hyperinsulinemia, insulin resistance and hyperuricemia. Western blot analysis of proteins from liver samples reveals that these enriched flours alleviated hepatic lipid accumulation and insulin resistance through their elevation in the phosphorylation of AMPK and Akt. (4) Conclusions: Our study indicates that these enriched flours can serve as a health-promoting functional food to regulate obesity-related lipid/glucose metabolic dysfunction in rats.

Encapsulating Perovskite Quantum Dots in Iron-Based Metal-Organic Frameworks (MOFs) for Efficient Photocatalytic CO2 Reduction.

Improving the stability of lead halide perovskite quantum dots (QDs) in a system containing water is the key for their practical application in artificial photosynthesis. Herein, we encapsulate low-cost CH3 NH3 PbI3 (MAPbI3 ) perovskite QDs in the pores of earth-abundant Fe-porphyrin based metal organic framework (MOF) PCN-221(Fex ) by a sequential deposition route, to construct a series of composite photocatalysts of MAPbI3 @PCN-221(Fex ) (x=0-1). Protected by the MOF the composite photocatalysts exhibit much improved stability in reaction systems containing water. The close contact of QDs to the Fe catalytic site in the MOF, allows the photogenerated electrons in the QDs to transfer rapidly the Fe catalytic sites to enhance the photocatalytic activity for CO2 reduction. Using water as an electron source, MAPbI3 @PCN-221(Fe0.2 ) exhibits a record-high total yield of 1559 µmol g-1 for photocatalytic CO2 reduction to CO (34 %) and CH4 (66 %), 38 times higher than that of PCN-221(Fe0.2 ) in the absence of perovskite QDs.

Engineering a CsPbBr3-based nanocomposite for efficient photocatalytic CO2 reduction: improved charge separation concomitant with increased activity sites.

Metal-halide perovskite nanocrystals have emerged as one of the promising photocatalysts in the photocatalysis field owing to their low-cost and excellent optoelectronic properties. However, this type of nanocrystals generally displays low activity in photocatalytic CO2 reduction owing to the lack of intrinsic catalytic sites and insufficient charge separation. Herein, we functionalized CsPbBr3 nanocrystals with graphitic carbon nitride, containing titanium-oxide species (TiO-CN) to develop an efficient composite catalyst system for photocatalytic CO2 reduction using water as the electron source. Compared to its congener with pristine CsPbBr3, the introduction of TiO-CN could not only increase the number of active sites, but also led to a swift interfacial charge separation between CsPbBr3 and TiO-CN due to their favorable energy-offsets and strong chemical bonding behaviors, which endowed this composite system with an obviously enhanced photocatalytic activity in the reduction of CO2 to CO with water as the sacrificial reductant. Over 3-fold and 6-fold higher activities than those of pristine CsPbBr3 nanocrystals and TiO-CN nanosheets, respectively, were observed under visible light irradiation. Our study provides an effective strategy for improving the photocatalytic activity of metal-halide perovskite nanocrystals, thus promoting their photocatalytic application in the field of artificial photosynthesis.

Stability of a type 2 diabetes rat model induced by high-fat diet feeding with low-dose streptozotocin injection.

OBJECTIVE: The present study aims at determining the stability of a popular type 2 diabetes rat model induced by a high-fat diet combined with a low-dose streptozotocin injection. METHODS: Wistar rats were fed with a high-fat diet for 8 weeks followed by a one-time injection of 25 or 35 mg/kg streptozotocin to induce type 2 diabetes. Then the diabetic rats were fed with regular diet/high-fat diet for 4 weeks. Changes in biochemical parameters were monitored during the 4 weeks. RESULTS: All the rats developed more severe dyslipidemia and hepatic dysfunction after streptozotocin injection. The features of 35 mg/kg streptozotocin rats more resembled type 1 diabetes with decreased body weight and blood insulin. Rats with 25 mg/kg streptozotocin followed by normal diet feeding showed normalized blood glucose level and pancreatic structure, indicating that normal diet might help recovery from certain symptoms of type 2 diabetes. In comparison, diabetic rats fed with high-fat diet presented decreased but relatively stable blood glucose level, and this was significantly higher than that of the control group (P<0.05). CONCLUSIONS: This model easily recovers with normal diet feeding. A high-fat diet is suggested as the background diet in future pharmacological studies using this model.

[Induction of robust senescence-associated secretory phenotype in mouse NIH-3T3 cells by mitomycin C].

Senescence-associated secretory phenotype (SASP) is often a concomitant result of cell senescence, embodied by the enhanced function of secretion. The SASP factors secreted by senescent cells include cytokines, proteases and chemokines, etc, which can exert great influence on local as well as systemic environment and participate in the process of cell senescence, immunoregulation, angiogenesis, cell proliferation and tumor invasion, etc. Relative to the abundance of SASP models in human cells, the in vitro SASP model derived from mouse cells is scarce at present. Therefore, the study aimed to establish a mouse SASP model to facilitate the research in the field. With this objective, we treated the INK4a-deficient mouse NIH-3T3 cells and the wildtype mouse embryonic fibroblasts (MEF) respectively with mitomycin C (MMC), an anticarcinoma drug which could induce DNA damage. The occurring of cell senescence was evaluated by cell morphology, ß-gal staining, integration ratio of EdU and Western blot. Quantitative RT-PCR and ELISA were used to detect the expression and secretion of SASP factors, respectively. The results showed that, 8 days after the treatment of NIH-3T3 cells with MMC (1 µg/mL) for 12 h or 24 h, the cells became enlarged and the ratios of ß-gal-positive (blue-stained) cells significantly increased, up to 77.4% and 90.4%, respectively. Meanwhile, the expression of P21 protein increased and the integration ratios of EdU significantly decreased (P < 0.01). Quantitative RT-PCR detection showed that the mRNA levels of several SASP genes, including IL-6, TNF-α, IL-1α and IL-1ß increased evidently. ELISA detection further observed an enhanced secretion of IL-6 (P < 0.01). On the contrary, although wildtype MEF could also be induced into senescence by MMC treatment for 12 h or 24 h, embodied by the enlarged cell volume, increased ratios of ß-gal-positive cells (up to 71.7% and 80.2%, respectively) and enhanced expression of P21 protein, the secretion of IL-6 displayed no significant change. Our study indicated that, although MMC could induce senescence in both mouse NIH-3T3 cells and wildtype MEF, only senescent NIH-3T3 cells displayed the canonical SASP phenomena. Current study suggested that senescent NIH-3T3 cells might be an appropriate in vitro SASP model of mouse cells.

Calcium silicate-based drug delivery systems.

INTRODUCTION: Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

Knowledge, attitudes and practices regarding human papillomavirus vaccination among young women attending a tertiary institution in Singapore.

INTRODUCTION: This study aimed to describe the knowledge, attitudes and practices of young women regarding human papillomavirus (HPV) vaccination. METHODS: We conducted a descriptive, cross-sectional, questionnaire-based study among female students at a tertiary institute in Singapore. RESULTS: A total of 255 questionnaires were completed and formed the basis of the analysis. 244 (95.7%) of the total participants were of the age group 15-22 years. 252 (98.8%) participants were unmarried and 240 (94.1%) had never had sexual intercourse. Only 25 (9.8%) women had received vaccination. Among the unvaccinated participants, 96 (41.7%) had no intention to receive HPV vaccination and 62 of them cited lack of information as a major barrier to HPV vaccination. Knowledge of cervical cancer and HPV vaccination was also assessed and graded via a point system, with a maximum score of 14. Knowledge was found to be low, with a median score of 7. There was a significant association between HPV vaccination uptake and the source from which they first heard about the vaccine (p = 0.007). Vaccinated respondents tended to first hear about it from their relatives and friends, as compared to unvaccinated respondents (60.0% vs. 27.0%). CONCLUSION: There is poor uptake of HPV vaccination amongst Singapore's susceptible youth as well as poor knowledge of cervical cancer and HPV vaccination. Public health education regarding cervical cancer and HPV vaccination is still needed and has to be targeted at not only respondents, but also their family and friends.

'Turn-on' detection of Hg2+ ion using a peroxidase-like split G-quadruplex-hemin DNAzyme.

A highly sensitive and selective Hg(2+) detection method was developed based on the Hg(2+)-mediated formation of split G-quadruplex-hemin DNAzymes. In this method, two label-free oligonucleotides are used. In the presence of Hg(2+), the two oligonucleotides hybridize to each other to form a duplex, in which T-T mismatches are stabilized by T-Hg(2+)-T base pair. As a result, the G-rich sequences of the two oligonucleotides can associate to form a split G-quadruplex, which is able to bind hemin to form the catalytically active G-quadruplex-hemin DNAzymes. This can be reflected by an absorbance increase when monitored in the H(2)O(2)-ABTS (2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid) reaction system by using UV-vis absorption spectroscopy. This 'turn-on' process allows the detection of aqueous Hg(2+) at concentrations as low as 19 nM using a simple colorimetric technique. With the development of the studies on metal-base pairs, this Hg(2+)-sensing method can be easily extended to the analysis of other metal ions.