Nifedipine or amlodipine? The choice for hypertension during pregnancy: a systematic review and meta-analysis.

BACKGROUND: There is a lack of sufficient evidence regarding efficacy and safety of amlodipine on treating hypertension during pregnancy. OBJECTIVE: To compare antihypertensive efficacy, pregnancy outcome and safety of amlodipine with nifedipine on hypertension during pregnancy. METHODS: A systematic search of PubMed, Embase, Cochrane Library, clinicaltrials.gov, Chinese National Knowledge Infrastructure, Wanfang Database and China Biology Medicine disc of randomized controlled trials (RCTs) up to April l5, 2021 was conducted on RCTs comparing amlodipine to nifedipine for the treatment of hypertension during pregnancy. Screening, data extraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a meta-analysis was conducted. RESULTS: Seventeen RCTs were included. Amlodipine was found the efficacy is slightly superior to nifedipine on treating hypertension during pregnancy (RR 1.06, 95% CI 1.01 to 1.10) with a decreased risk for maternal side effects (RR 0.42, 95% CI 0.29 to 0.61). Subgroup analysis found amlodipine can get a better control on SBP (RR - 11.68, 95% CI - 17.98 to - 5.37) and DBP (RR - 7.44, 95% CI - 13.81 to - 1.06) compared with intermediate-/long-acting nifedipine. In addition, there was no difference between amlodipine and nifedipine on pregnancy outcomes including caesarean section, premature labour, placental abruption, FGR, fetal distress, neonatal asphyxia. CONCLUSIONS: Given the results of this systematic review and meta-analysis, amlodipine can be effectively and safely used for hypertension during pregnancy.

Alisol A 24-Acetate Prevents Hepatic Steatosis and Metabolic Disorders in HepG2 Cells.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs) induced NAFLD cell model. METHODS: This study was divided into four groups including Control group, Model group (FFA group), Alisol A 24-acetate (FFA+A) group, Fenofibrate (FFA+F) group. Preventive role of Alisol A 24-acetate was evaluated using 10µM Alisol A 24-acetate plus 1 mM FFA (oleate:palmitate=2:1) incubated with HepG2 cells for 24 h, which was determined by Oil Red O Staining, Oil Red O based colorimetric assay and intracellular triglyceride (TG) content. Besides, the inflammatory cytokines tumor necrosis factor (TNF)- α, interleukin (IL)-6 levels as well as the protein and mRNA expressions that were involved in fatty acid synthesis and oxidation including Adiponectin, AMP-activated protein kinase (AMPK) α, peroxisome proliferator-activated receptor (PPAR) α, sterol regulatory element binding protein 1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1) and acyl coenzyme A oxidase 1 (ACOX1) were detected. RESULTS: Alisol A 24-acetate significantly decreased the numbers of lipid droplets, Oil Red O lipid content, and intracellular TG content. Besides, inflammatory cytokines TNF-α, IL-6 levels were markedly inhibited by Alisol A 24-acetate. Furthermore, Alisol A 24-acetate effectively increased the protein and mRNA expressions of Adiponectin, the phosphorylation of AMPKα, CPT1 and ACOX1, whereas decreased SREBP-1c, the phosphorylation of ACC and FAS at both protein and mRNA levels. However, there was no significant effect on the protein and mRNA expressions of PPARα by Alisol A 24-acetate. CONCLUSIONS: These results demonstrated that Alisol A 24-acetate effectively ameliorated hepatic steatosis likely through Adiponectin, which activated AMPKα signaling pathways via down-regulating SREBP-1c, ACC, FAS and up-regulating CPT1 and ACOX1, and inhibited inflammation. Thereby, Alisol A 24-acetate could be a promising candidate for the treatment of NAFLD.

Anti-obesity effects of artificial planting blueberry (Vaccinium ashei) anthocyanin in high-fat diet-treated mice.

This study aimed to evaluate the anti-obesity effects of artificial planting blueberry (Vaccinium ashei) anthocyanin (BA) in high-fat diet-induced obese male C57BL/6 mice. BA at doses of 50, 100, and 200 mg/kg was supplemented in the daily food of obese C57BL/6 mice during an 8-week experiment. Our findings indicate that consumption of BA at high doses reduced body weight by 19.4%, whereas both low and middle doses did not affect the body weight. Furthermore, BA supplementation at high dose could effectively decrease serum glucose, attenuate epididymal adipocytes, improve lipid profiles, and significantly down-regulate expression levels of TNFα, IL-6 PPARγ, and FAS genes. Therefour, BA might alter bodyweight by suppressing fatty acid synthesis and alleviating inflammation.

The role of cancer-associated fibroblasts in the invasion and metastasis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and has ranked the third leading cause in cancerassociated death globally. Metastasis is the leading cause of death in colorectal cancer patients. The role of tumor microenvironment (TME) in colorectal cancer metastasis has received increasing attention. As the most abundant cell type in the TME of solid tumors, cancer-associated fibroblasts (CAFs) have been demonstrated to have multiple functions in advancing tumor growth and metastasis. They can remodel the extracellular matrix (ECM) architecture, promote epithelial-mesenchymal transition (EMT), and interact with cancer cells or other stromal cells by secreting growth factors, cytokines, chemokines, and exosomes, facilitating tumor cell invasion into TME and contributing to distant metastasis. This article aims to analyze the sources and heterogeneity of CAFs in CRC, as well as their role in invasion and metastasis, in order to provide new insights into the metastasis mechanism of CRC and its clinical applications.

Fabrication and characterization of responsible approach for targeted intestinal releasing and enhancing the effectivity of kidney tea saponin upon porous starch /xanthan gum /sodium alginate-based hydrogel bead.

To enhance the intestinal targeted release of kidney tea saponins, a simple delivery system was designed through the use of porous starch (PS), sodium alginate (ALG) and xanthan gum (XG). Porous starch was prepared by hydrolysis with a combination of α-amylase and amyloglucosidase and it was characterized by scanning electron microscopy, which revealed the formation of porous structures in the starch granules. The results of one-way optimisation illustrated that this unique delivery system achieved 79.00 ± 1.22 % of the optimal encapsulation rate. The carrier structure was subjected to analysis using Fourier transform infrared spectroscopy and X-ray diffraction. The α-glucosidase inhibition assay showed better inhibition of kidney tea saponin compared to the positive control acarbose. In addition, the effectiveness of this delivery design was confirmed via an in vitro simulated digestion method. It was showed that only a 15.57 ± 1.27 % release rate of kidney tea saponin was observed in the upper gastrointestinal tract, whereas release rates of 17.51 ± 1.29 % and 41.07 ± 0.76 % were observed for xanthan gum/sodium alginate/kidney tea saponin and sodium alginate/kidney tea saponin beads, respectively. It was concluded that the utilization of PS and a xanthan gum/sodium alginate coating represents an efficacious methodology for the development of an intestinal targeted delivery system.

Label-free and turn-on aptamer strategy for cancer cells detection based on a DNA-silver nanocluster fluorescence upon recognition-induced hybridization.

We present here a label-free and turn-on aptamer strategy for cancer cell detection based on the recognition-induced conformation alteration of aptamer and hybridization-induced fluorescence enhancement effect of DNA-silver nanoclusters (DNA-Ag NCs) in proximity of guanine-rich DNA sequences. In this strategy, two tailored DNA probes were involved. One is designed as a hairpin-shaped structure consisting of a target specific aptamer sequence at the 3'-end, a guanine-rich DNA sequence, and an arm segment at the 5'-end (denote as recognition probe). The other, serving as a signal probe, contains a sequence for Ag NCs templated synthesis and a link sequence complementary to the arm segment of the recognition probe. Recognizing and binding of the aptamer to cancer cells enforces the recognition probe to undergo a conformational alteration and then initiates hybridization between the arm segment of the recognition probe and the link sequence of the signal probe. The Ag NCs are then close to the guanine-rich DNA, leading to an enhanced fluorescence readout. As proof-of-concept, the CCRF-CEM cancer cell detection were performed by using the specific aptamer, sgc8c. It was demonstrated that this strategy could specially image the CCRF-CEM cells. Determination by flow cytometry allowed for detection of as low as 150 CCRF-CEM cells in 200 µL binding buffer. The general applicability of the strategy is also achieved in the successful detection of Ramos cells. These results implied that this strategy holds considerable potential for simple, sensitive, universal, and specific cancer cell detection with no required washing and separation steps.

Highly sensitive label-free fluorescent detection of Hg2+ ions by DNA molecular machine-based Ag nanoclusters.

We present here a highly selective and sensitive label-free method to detect Hg(2+) ions in aqueous solution by using DNA molecular machine-based fluorescent Ag nanoclusters (AgNCs). This mechanism is based on the Hg(2+) ions triggering machine-like operations of DNA and the "product" of the machine being used to stabilize fluorescent AgNCs. In this method, a tailored DNA, containing a sequence for Hg(2+) ions recognition, a sequence-specific nicking site for Nb BbvC I and a sequence complementary to the DNA as a template for the synthesis of fluorescent AgNCs, was firstly designed. In the presence of Hg(2+) ions, the machine's function operations were triggered. A series of machine-like operations, including replication, scission, and displacement then occurred with the addition of polymerase/dNTPs/Nb BbvC I, which manufactured lots of "product" DNA. The "product" DNA could act as a template for the preparation of fluorescent AgNCs. Thus the fluorescence of the AgNCs could be used as a signal transduction of this DNA machine, which was related to the concentration of the Hg(2+) ions. The repeated synthesis of the "product" and its template effect for AgNCs synthesis led to signal amplification in the assay of Hg(2+) ions. A linear response to the concentration of Hg(2+) ions was observed in the range from 0.08 nM to 20 nM and a detection limit of 0.08 nM was obtained. By contrast, the operation of the machine could not be executed in an Hg(2+) ion-free system. Moreover, the detection was not only label-free but also specific for Hg(2+) ions without being affected by other metal ions.

Phytochemicals, Pharmacological Effects and Molecular Mechanisms of Mulberry.

There are numerous varieties of mulberry, and each has high medicinal value and is regarded as a promising source of traditional medicines and functional foods. Nevertheless, the nutrients and uses of mulberry differ from species (Morus alba L., Morus nigra L. and Morus rubra L.). Phenolic compounds are prominent among the biologically active ingredients in mulberry, especially flavonoids, anthocyanins and phenolic acids. Epidemiologic studies suggest that mulberry contains a rich, effective chemical composition and a wide range of biological activity, such as antioxidant, anti-inflammatory, anti-tumor and so on. However, compared with other berries, there has been a lack of systematic research on mulberry, and this hinders its further expansion as a functional fruit. The main purpose of this review is to provide the latest data regarding the effective chemical constituents and pharmacological effects of mulberry to support its further therapeutic potential and health functions.

An oral hydrogel carrier for delivering resveratrol into intestine-specific target released with high encapsulation efficiency and loading capacity based on structure-selected alginate and pectin.

Resveratrol (RES) has many beneficial effects on the human body, but it is always unstable, resulting in low oral bioavailability, especially in the gastrointestinal tract. In this study, we developed an oral intestine-specific released hydrogel carrier for targeted RES release in the intestinal tract, which was composed of alginate (ALG) with a specific ratio of α-L-guluronic (G blocks) and ß-D-mannuronic (M blocks) and low methoxyl pectin (LMP). The encapsulation efficiency and loading capacity of RES was 92.04 ± 0.32% and 6.41 ± 0.022 mg g-1 samples, respectively. Positioning release kinetics were investigated in vivo and in vitro. Also, this hydrogel carrier provides good protection for RES against the stomach. 94.71% of RES could be transported to the intestines in two hours after oral administration and released mainly in the small intestine and colon. Thus, the hydrogel carrier is conducive to RES, which is absorbed through the intestinal barrier rather than the stomach after oral administration. Moreover, the hydrogel carrier could load other health factors with expected encapsulation efficiencies, such as curcumin (93.52%), ascorbic acid (90.33%), ginsenoside Rg3 (81.54%), and EGCG (92.27%). These also implied that the hydrogel carrier holds general applicability in disease management.

Dietary intervention in depression - a review.

Depression is a mental illness that affects the normal lives of over 300 million people. Unfortunately, about 30% to 40% of patients do not adequately respond to pharmacotherapy and other therapies. This review focuses on exploring the relationship between dietary nutrition and depression, aiming to find safer and efficient ingredients to alleviate depression. Diet can affect depression in numerous ways. These pathways include the regulation of tryptophan metabolism, inflammation, hypothalamic-pituitary-adrenal (HPA) axis, microbe-gut-brain axis, brain-derived neurotrophic factor (BDNF) and epigenetics. Furthermore, probiotics, micronutrients, and other active substances exhibit significant antidepressant effects by regulating the above pathways. These provide insights for developing antidepressant foods.

Echinacoside (ECH) suppresses proliferation, migration, and invasion of human glioblastoma cells by inhibiting Skp2-triggered epithelial-mesenchymal transition (EMT).

BACKGROUND: Echinacoside (ECH) is a phenylethanoid extracted from the stems of Cistanches salsa, an herb used in Chinese medicine formulations, and is effective against glioblastoma multiforme (GBM). Epithelial-mesenchymal transition (EMT) is the cornerstone of tumorigenesis and metastasis, and increases the malignant behavior of GBM cells. The S phase kinase-related protein 2 (skp2), an oncoprotein associated with EMT, is highly expressed in GBM and significantly associated with drug resistance, tumor grade and dismal prognosis. The aim of this study was to explore the inhibitory effects of ECH against GBM development and skp2-induced EMT. METHODS: CCK-8, EdU incorporation, transwell, colony formation and sphere formation assays were used to determine the effects of ECH on GBM cell viability, proliferation, migration and invasion in vitro. The in vivo anti-glioma effects of ECH were examined using a U87 xenograft model. The expression levels of skp2 protein, EMT-associated markers (vimentin and snail) and stemness markers (Nestin and sox2) were analyzed by immunofluorescence staining and western blotting experiments. RESULTS: ECH suppressed the proliferation, invasiveness and migration of GBM cells in vitro, as well as the growth of U87 xenograft in vivo. In addition, ECH downregulated the skp2 protein, EMT-related markers (vimentin and snail) and stemness markers (sox2 and Nestin). The inhibitory effects of ECH were augmented in the skp2-knockdown GBM cells, and reversed in cells with ectopic expression of skp2. CONCLUSION: ECH inhibits glioma development by suppressing skp2-induced EMT of GBM cells.

Correction: Poly(adenine)-mediated DNA-functionalized gold nanoparticles for sensitive detection of mercury ions in aqueous media.

[This corrects the article DOI: 10.1039/C9RA03041G.].

Correction: Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway.

Correction for 'Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway' by Na Li et al., Food Funct., 2019, 10, 3430-3438, DOI.

Bifidobacterium longum subsp. longum Remodeled Roseburia and Phosphatidylserine Levels and Ameliorated Intestinal Disorders and liver Metabolic Abnormalities Induced by High-Fat Diet.

Bifidobacterium longum is considered as a potential supplement in antiobesity treatment; however, the underlying molecular mechanism has rarely been studied. To understand the contributions of B. longum subsp. longum (BL21) in the prevention of obesity, we investigated alterations in the liver metabonomic phenotype and gut microbiota by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and 16S ribosomal RNA gene sequencing in C57BL/6J male mice orally administered with BL21 for 8 weeks [high-fat diet (HFD)]. BL21 at 1 × 109 CFU·day-1 per mouse reduced the weight of mice by 16.9% relative to that of the mice fed with HFD and significantly lowered the serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. BL21 also ameliorated fat vacuolization in liver cells and epididymal fat accumulation. BL21 also lowered the Firmicutes/Bacteroidetes ratio, regulated liver remodeling in glycerophospholipids, and alleviated the levels of d-tryptophan. A positive correlation between the butyrate-producing strain Roseburia and the cell membrane component phosphatidylserine was found for the first time. Thus, BL21 can potentially prevent mice from being obese by rebalancing the gut microbiota and glycerophospholipid metabolism. BL21 can be a promising dietary supplement for weight control.

Capsanthin extract prevents obesity, reduces serum TMAO levels and modulates the gut microbiota composition in high-fat-diet induced obese C57BL/6J mice.

The present study investigated the anti-obesity effects and its mechanism of capsanthin (CAP) in high-fat diet-induced obese C57BL/6J mice. Compared with untreated mice on a high-fat diet for 12 weeks, CAP at 200 mg kg-1 reduced the body weight by 27.5%, significantly reversed glucose tolerance, effectively decreased the serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and trimethylamine N-oxide levels, markedly increased microbial diversity. Furthermore, 16S rRNA gene sequencing of the cecal microbiota suggested that CAP increased the abundance of Bacteroidetes, Bifidobacterium and Akkermansia, decreased the abundance of Ruminococcus and the ratio of Firmicutes/Bacteroidetes. Moreover, predicted functional domain analysis indicated that CAP increased the gene abundance of replication and repair, and decreased the gene abundance of membrane transports and carbohydrate metabolisms. Therefore, it seems CAP exhibit anti-obesity effect and might be used as a potential agent against obesity.

Leuconostoc pseudomesenteroides improves microbiota dysbiosis and liver metabolism imbalance and ameliorates the correlation between dihydroceramide and strains of Firmicutes and Proteobacteria in high fat diet obese mice.

Leuconostoc pseudomesenteroides is widely isolated from fermented foods; however, the underlying molecular mechanism behind its anti-obesity function has rarely been studied. This study aims to explore the role of alterations in gut microbes and liver metabolites mediated by Leuconostoc pseudomesenteroides (Tu) in obese mice for a period of 8 weeks through UPLC/Q-TOF-MS and 16S rRNA sequencing. Our results showed that Tu administration at a dosage of 1 × 109 CFU per day per mouse effectively attenuated the weight of mice, significantly reduced serum lipids, and markedly improved fecal lipid output. Tu also ameliorated the lipid profiles in the liver and epididymal fat tissues, and restored intestinal disorder caused by a high-fat diet. Moreover, glycerophospholipid metabolism in the liver was altered by increased dihydroceramide levels. Surprisingly, the correlation between dihydroceramide and strains of Firmicutes and Proteobacteria was found for the first time. Collectively, these findings highlight that Tu could be a potential dietary supplement for weight control.

Lactobacillus rhamnosus LRa05 improves lipid accumulation in mice fed with a high fat diet via regulating the intestinal microbiota, reducing glucose content and promoting liver carbohydrate metabolism.

To elucidate the anti-obesity effect of Lactobacillus rhamnosus LRa05 through the analysis of gut microbiota and liver metabolomics, we investigated changes in gut microbiota and liver metabolomic phenotypes in mice by 16S ribosomal RNA gene sequencing and ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. C57BL/6J male mice were orally administered with LRa05 for 8 weeks. Body weight, serum lipid levels, and the lipid accumulation of liver cells and epididymal fat tissues in the mice fed with a high-fat diet were inhibited after treatment with LRa05 at 1 × 109 CFU per day per mouse. LRa05 also reshaped the gut microbiota, reduced the abundance of the pro-pathogen bacterial Streptococcus, suppressed blood and liver glucose content, and promoted liver carbohydrate and energy metabolism. Moreover, Intestinimonas and palmitoyl ethanolamide exhibited a positive correlation, whereas Enterorhabdus and vitamin B2 showed a negative correlation. Therefore, LRa05 can potentially be used as an anti-obesity probiotic in further interventions.

Astragaloside IV Protects Ethanol-Induced Gastric Mucosal Injury by Preventing Mitochondrial Oxidative Stress and the Activation of Mitochondrial Pathway Apoptosis in Rats.

Alcohol consumption affects gastric mucosa by multiple and complex mechanisms depending either by direct contact of ethanol or by indirect biological damage induced by its metabolite acetaldehyde. The present study aims at further investigating the mechanism of ethanol-induced gastric mucosa injury and the protective effect of astragaloside IV (AS-IV) in an aspect of mitochondrial oxidative stress and mitochondrial pathway of apoptosis. Using an array of experimental approaches, we have shown that the development of mitochondrial oxidative stress and associated apoptosis play crucial roles in the pathogenesis of gastric injury induced by ethanol. AS-IV inhibits mitochondrial oxidative stress by scavenging accumulation of malondialdehyde and decreasing the consumption of glutathione. AS-IV also prevents ethanol-induced apoptosis by modulating the activity of caspase-3 and caspase-9, the expression of Bax/Bcl-2, and the release of cytochrome C and apoptosis inducing factor. Moreover, AS-IV reduces ethanol-mediated activation of caspase-8 and breakage of Bid. This study thus indicates that AS-IV prevented ethanol-induced gastric damage by blocking activation of mitochondrial oxidative stress and mitochondrial pathway of apoptosis induced by ethanol in the gastric mucosa.

Poly(adenine)-mediated DNA-functionalized gold nanoparticles for sensitive detection of mercury ions in aqueous media.

In this work, a facile and sensitive colorimetric sensor for Hg2+ ions based on poly (adenine)-mediated DNA-functionalized gold nanoparticles (Au NPs) is reported. One DNA sequence consisting of poly-A and T-rich DNA was designed rationally. Poly-A was used as an anchoring block to bind tightly to Au NPs, and T-rich DNA was utilized for specific recognition of Hg2+ ions. With the assistance of poly-A, T-rich DNA was easily introduced onto the surface of Au NPs and kept an upright orientation. In the presence of Hg2+ ions, T base binding with Hg2+ ions results in the formation of "T-Hg2+-T" among the Au NPs, which caused aggregation of the Au NPs and a subsequent change in the color of the solution, from wine red to grayish blue. On this occasion, the limit of detection (LOD) was 3.75 nM Hg2+ ions with a linear range from 5 nM to 200 nM, as measured by UV-Vis spectroscopy. Moreover, successful application of this method for the detection of Hg2+ ions in real samples was demonstrated.

Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway.

With aging, there is an increasing risk for women to develop perimenopause syndrome, which is harmful to women's physical and mental health. The present study investigated the health benefits of bilberry anthocyanin (BA) on aging perimenopausal Sprague-Dawley rats. Rats that entered into perimenopause through natural aging were treated for 8 weeks with BA, and received either a low dose (LD, 35 mg per kg of bodyweight), medium dose (MD, 70 mg per kg of bodyweight), or high dose (HD, 140 mg per kg of bodyweight). The experimental results suggested that all three dosages of BA, especially the high dose, significantly reduced the serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels. In addition, BA supplementation markedly reduced the serum malondialdehyde (MDA), effectively increased the activity of hepatic total superoxide dismutase (T-SOD), significantly raised the high density lipoprotein cholesterol (HDL-C), increased the number of estrogen receptors, and effectively up-regulated the expression levels of G protein-coupled receptor 30 (GPR30), protein kinase B (AKT), and extracellular regulated protein kinase 2 (ERK2). In summary, BA has a great effect on improving the serum cholesterol in natural aging perimenopausal rats via the estrogen receptor signaling pathway, and it may be used as a dietary supplement for perimenopause women to decrease the risk of cardiovascular disease.