Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability.

Astrocyte aerobic glycolysis provides vital trophic support for central nervous system neurons. However, whether and how astrocytic metabolic dysregulation contributes to neuronal dysfunction in intellectual disability (ID) remain unclear. Here, we demonstrate a causal role for an ID-associated SNX27 mutation (R198W) in cognitive deficits involving reshaping astrocytic metabolism. We generated SNX27R196W (equivalent to human R198W) knock-in mice and found that they displayed deficits in synaptic function and learning behaviors. SNX27R196W resulted in attenuated astrocytic glucose uptake via GLUT1, leading to reduced lactate production and a switch from homeostatic to reactive astrocytes. Importantly, lactate supplementation or a ketogenic diet restored neuronal oxidative phosphorylation and reversed cognitive deficits in SNX27R196W mice. In summary, we illustrate a key role for astrocytic SNX27 in maintaining glucose supply and glycolysis and reveal that altered astrocytic metabolism disrupts the astrocyte-neuron interaction, which contributes to ID. Our work also suggests a feasible strategy for treating ID by restoring astrocytic metabolic function.

[Research progress on intestinal microecology regulating mechanism and biological activities of polysaccharides].

Intestinal microecology is an important defense system in the human body. The intestinal flora is the core micro-ecosystem in the human intestine. It has a symbiotic relationship with the overall functions of the body. It has strong metabolic activity to maintain the normal functioning of the body and resist the invasion of various viral antigens in the body. Playing a protective function,the imbalanced intestinal microecology can cause various diseases. Polysaccharides can be extracted from a wide range of sources and have low toxicity and side effects. They have attracted wide attention because of their anti-tumor, anti-oxidant, anti-inflammatory and other biological activities. Studies have demonstrated that polysaccharides can regulate intestinal microecological disorders. According to the studies in recent years, this review summarizes that polysaccharides mainly modulate intestinal microecological disorders through regulating the composition of intestinal flora, improving the metabolism of the flora, and repairing the intestinal tract barrier. On the basis of these mechanisms of action, this paper elaborates the anti-tumor, immunomodulatory, and anti-inflammatory activities of polysaccharides. This paper can provide reference for the future research on the intestinal microecology-regulating mechanism and biological activities of polysaccharides.

Optimized microwave-assistant extraction combined ultrasonic pretreatment of flavonoids from Periploca forrestii Schltr. and evaluation of its anti-allergic activity.

Microwave extraction combined ultrasonic pretreatment of flavonoids from Periploca forrestii Schltr. was investigated in this study, extraction process was first performed in an ultrasonic cleaner, then treated by microwave irradiation. The optimum ultrasonic time of 25 min was selected by single-factor experiments. A response surface methodology has been used to obtain a mathematical model that describes the process and analyzes the significant parameters ethanol concentration 59.92%, liquid to raw materials ratio 21.24 mL/g, microwave radiation time 209.53 s, and microwave power 274.14 w. In these optimum conditions, the yield of flavonoids from P. forrestii (TFPF) could be up to 9.11 ± 0.08%, which was increased by 14.30 and 19.86% compared microwave extraction and ultrasonic extraction, respectively. In vitro suppress hyaluronidase experimentation showed that TFPF purified using polyamide exhibited good anti-hyaluronidase ability with IC50 value of 1.033 mg/mL, possessing certain anti-antiallergic and potential application prospect in pharmaceutical production of treating inflammation and other related fields.

[Characterization and activity effect on ADH of polysaccharides from Mori Fructus].

Mori Fructus polysaccharides (MFPs) have been used as a source of therapeutic agents. The most promising activities of these biopolymers are their immunomodulation and anti-cancer effects. It was reported that polysaccharides were a potential drug against liver injury, but the hepatoprotective effect of MFPs was ambiguous. In this study, the fractionation of crude polysaccharides on DEAE-Cellulose 52 gave four fractions (MFP-1, MFP-2, MFP-2 and MFP-4). The results showed that the contents of carbohydrates were 75.3%, 83.7%, 79.1%, 74.3%, and the molecular weight of them were 112.2, 128.8, 199.5, 181.9 kDa. Monosaccharide component analysis indicated that MFP-1 was composed of galactose, glucose, arabinose, rhamnose and mannose with the molarity rate of 26.8∶20.4∶8.74∶5∶1; MFP-2 contained arabinose, galactose, rhamnose, glucose and galacturonic acid with the molarity rate of 34.2∶38.2∶8∶17.5∶15.1; MFP-3 was composed of galacturonic acid, galactose, glucose, rhamnose and arabinose with the molarity rate of 28.3∶22.6∶20.9∶18.6∶15.1; MFP-4 contained glucose, galactose, rhamnose, galacturonic acid, arabinose and glucuronic acid with the molarity rate of 47.4∶34.9∶36.1∶33.1∶19.9∶4.1. IR analysis's results indicated that MFP-3 and MFP-4 may be polysaccharides containing ß-glycosides. The alcohol dehydrogenase (ADH) activity text showed that, all these four MFPs were found have a positive effect on the activity of ADH, with order: bifendate>MFP-3>MFP-1>MFP-2>tioprnin>MFP-4, and the MFP-3 had the highest activity and demonstrated outstanding hepatic protecting activity.

The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.

[Advance in study on hepatoprotective effects and its mechanism of polysaccharides].

Liver damage is the pathologic status in the liver system, which can lead to cirrhosis, fibrosis and cancer of the liver. So to search for effective drugs on prevention and treatment of anti-hepatic lesion have already attracted broad concern in the world. Polysaccharides widely exist in plants, microorganisms and animals, and have high efficiency but low toxicity properties. Therefore, polysaccharides had been the hotspot in the research field of liver-protecting medicines, and had undergone great progresses. In this study, the hepatoprotective effects and its mechanism of polysaccharides were summarized and reviewed, and the market prospects of development and application were prospected. The research result indicated that polysaccharides derived from plants, microorganisms, animals which had significant effects on liver protection. Results also showed that polysaccharides showed the protective effect on chemical liver injury by anti-oxidation, alleviating calcium overload, adjusting the function of mitochondria, and the protective effect on immune liver injury by regulating cytokine secretion, blocking the complement system activity, inhibiting inflammatory mediator expression, suppressing hepatocyte apoptosis. Polysaccharides had rich resource, diverse bio-effects, abundance approaches and multitarget. Therefore, there is huge potential for developing polysaccharides as novel hepatoprotective medicine candidates.

Studies on Chromatographic Fingerprint and Fingerprinting Profile-Efficacy Relationship of Saxifraga stolonifera Meerb.

This work investigated the spectrum-effect relationships between high performance liquid chromatography (HPLC) fingerprints and the anti-benign prostatic hyperplasia activities of aqueous extracts from Saxifraga stolonifera. The fingerprints of S. stolonifera from various sources were established by HPLC and evaluated by similarity analysis (SA), hierarchical clustering analysis (HCA) and principal component analysis (PCA). Nine samples were obtained from these 24 batches of different origins, according to the results of SA, HCA and the common chromatographic peaks area. A testosterone-induced mouse model of benign prostatic hyperplasia (BPH) was used to establish the anti-benign prostatic hyperplasia activities of these nine S. stolonifera samples. The model was evaluated by analyzing prostatic index (PI), serum acid phosphatase (ACP) activity, concentrations of serum dihydrotestosterone (DHT), prostatic acid phosphatase (PACP) and type II 5α-reductase (SRD5A2). The spectrum-effect relationships between HPLC fingerprints and anti-benign prostatic hyperplasia activities were investigated using Grey Correlation Analysis (GRA) and partial least squares regression (PLSR). The results showed that a close correlation existed between the fingerprints and anti-benign prostatic hyperplasia activities, and peak 14 (chlorogenic acid), peak 17 (quercetin 5-O-ß-d-glucopyranoside) and peak 18 (quercetin 3-O-ß-l-rhamno-pyranoside) in the HPLC fingerprints might be the main active components against anti-benign prostatic hyperplasia. This work provides a general model for the study of spectrum-effect relationships of S. stolonifera by combing HPLC fingerprints with a testosterone-induced mouse model of BPH, which can be employed to discover the principle components of anti-benign prostatic hyperplasia bioactivity.

Extraction, structural characterization and biological activities of polysaccharides from mulberry leaves: A review.

In recent years, plant polysaccharides have garnered attention for their impressive biological activity. Mulberry leaves have a long history of medicinal and edible use in China, polysaccharide is one of the main active components of mulberry leaves, mainly consist of xylose, arabinose, fructose, galactose, glucose and mannose, etc. The extraction methods of mulberry leaves polysaccharides (MLPs) mainly include hot water extraction, microwave-assisted extraction, ultrasonic extraction, enzyme-assisted extraction, and co-extraction. The separation and purification of MLPs involve core steps such as decolorization, protein removal, and chromatographic separation. In terms of pharmacological effects, MLPs exhibit excellent activity in reducing blood glucose, anti-oxidation, immune regulation, anti-tumor, antibacterial, anti-coagulation, and regulation of gut microbiota. Currently, there is a considerable amount of research on MLPs, however, there is a lack of systematic summarization. This review summarizes the research progress on the extraction, structural characterization, and pharmacological activities of MLPs, and points out existing shortcomings and suggests reference solutions, aiming to provide a basis for further research and development of MLPs.

Hazards of microplastics exposure to liver function in fishes: A systematic review and meta-analysis.

Microplastics (5 mm - 1 µm) have become one of the major pollutants in the environment. Numerous studies have shown that microplastics can have negative impacts on aquatic organisms, affecting their liver function levels. However, the extent of these effects and their potential toxicological mechanisms are largely unknown. In this study, a meta-analysis and systematic review were conducted to assess the effects of microplastics on fish liver function and summarize the potential toxicological mechanisms of microplastic-induced liver toxicity. The meta-analysis results indicate that compared to the control group, exposure to microplastics significantly affects fish liver indicators: aspartate aminotransferase (AST) (p < 0.001), alanine aminotransferase (ALT) (p < 0.001), alkaline phosphatase (ALP) (p < 0.001), total protein (TP) (p < 0.001), and lactate dehydrogenase (LDH) (p < 0.001), including oxidative stress indicators: superoxide dismutase (SOD) (p < 0.001), glutathione S-transferase (GST) (p < 0.001), glutathione (GSH) (p < 0.001), and malondialdehyde (MDA) (p < 0.001) in fish liver. For fish living in different environments, the potential toxicological mechanisms of microplastics exposure on fish liver may exhibit some differences. For freshwater fish, the mechanism may be that microplastics exposure causes overproduction of reactive oxygen species (ROS) in fish hepatocyte mitochondria. ROS promotes the expression of toll-like receptor 2 (TLR2) and activates downstream molecules myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) of the TLR2 signaling pathway, leading to phosphorylation of NF-κB p65. This leads to the release of inflammatory factors and oxidative stress and inflammation in fish liver. In addition, for seawater fish, the mechanism may be that microplastics exposure can cause damage or death of fish hepatocytes, leading to continuous pathological changes, inflammation, lipid and energy metabolism disorders, thereby causing significant changes in liver function indexes.

Harmful effects of microplastics on respiratory system of aquatic animals: A systematic review and meta-analysis.

The presence of microplastics in the aquatic environment has attracted widespread attention. A large number of studies have assessed the effects of microplastics on the respiratory system of aquatic animals, but the results are not directly comparable across studies due to inconsistent evaluation criteria. Therefore, we adopted an integrated research approach that can integrate and parse complex data to improve reliability, conducted a systematic review and meta-analysis of 35 published studies, and elucidated the mechanisms of microplastic damage to cells. The results showed that PE had the greatest impact on aquatic animals, and fish were the most sensitive to the effects caused by microplastics, with oxidative stress induced by exposure concentrations exceeding 1000 µg/L or exposure times exceeding 28 days, leading to depletion of antioxidant defenses, cellular damage, inflammatory responses, and behavioral abnormalities. As this review is based on existing studies, there may be limitations in terms of literature quality, data availability and timeliness. In conclusion, we suggest to combat microplastic pollution by limiting plastic use, promoting plastic substitution and recycling, and enhancing microplastic capture degradation technologies.

Circular RNA hsa_circ_0012673 Promotes Breast Cancer Progression via miR-576-3p/SOX4 Axis.

Circular RNAs (circRNAs) have been reported to exert critical roles in human cancers. In this study, we investigated the role and molecular mechanism of hsa_circ_0012673 in breast cancer. Herein, we found that the expression of hsa_circ_0012673 was upregulated in breast cancer tissues and cell lines. Knockdown of hsa_circ_0012673 using RNA interference technique suppressed the proliferation, migration, and invasion of breast cancer cells. Mechanistically, hsa_circ_0012673 sponged miR-576-3p to stabilize SRY-box transcription factor 4 (SOX4), and thereby facilitating breast cancer cell proliferation, migration and invasion. Collectively, our study identified the oncogenic properties of hsa_circ_0012673/miR-576-3p/SOX4 axis in breast cancer, providing potential and exploitable diagnostic and therapeutic molecules for breast cancer.

lncRNA ENST00000585827 Contributes to the Progression of Endometrial Carcinoma via Regulating miR-424/E2F6/E2F7 Axis.

Endometrial cancer (EC) ranks fourth among the most common gynecologic malignancies. Despite advances in medical technology, the pathogenesis is still unclear. Numerous reports have identified the involvement of lncRNA in the malignant progression of endometrial cancer. The aim of the study was to investigate the expression level of lncRNA ENST00000585827 (lncRNA E27) in endometrial cancer and the molecular mechanism that regulates the development of endometrial cancer. Combined with the results of the previous study, PCR analysis confirmed that lncRNA E27 was significantly upregulated in endometrial cancer cell lines. The results of CCK-8, wound healing assay, and transwell experiments showed that lncRNA E27 could significantly inhibit cell proliferation, migration, and invasion. Flow cytometry results confirmed that lncRNA E27 could promote apoptosis. Furthermore, based on bioinformatics predictions, dual-luciferase assay and RT-qPCR analysis confirmed that miR-424, as its downstream molecule, competitively regulates the expression of E2F6/E2F7. Rescue experiments further supported that lncRNA E27 inhibited proliferation, migration, invasion, and promoted apoptosis of endometrial cancer through miR-424/E2F6/E2F7 signaling axis. Conclusively, our findings revealed the role of lncRNA E27 in regulating the miR-424/E2F6/E2F7 signaling axis during EC progression, opening up new strategies for the treatment of endometrial cancer.

Vulgarisin-type diterpenoids from self-heal (Prunella vulgaris) and their neuroprotective effects against ischemia/reperfusion (I/R) via a mitochondria-related pathway.

Self-heal (Prunella vulgaris L.) is a perennial edible plant that is widely distributed across the world and is traditionally consumed as a food additive in soft drink beverages. In this study, to explore the functional components of P. vulgaris, an investigation of its ethanol extracts has been conducted by our group. As a result, twelve (1-12) vulgarisin-type diterpenoids with a special 5/6/4/5-fused ring skeleton, including six new ones (1-6), were obtained. Their structures including the absolute configuration were elucidated based on comprehensive spectroscopic evidence, ECD calculations, as well as single-crystal X-ray diffraction analyses. All the isolates were tested for neuroprotective effects against ischemia/reperfusion (I/R) on primary neuron cells through the oxygen and glucose deprivation and reperfusion (OGD/R) induced injury model. The results showed that all twelve vulgarisin-type diterpenoids possess promising neuroprotective activity at a concentration of 10 µM. Among them, compound 3 can significantly suppress cell apoptosis by regulating Bax/Bcl-2 protein expression and inhibiting cleaved caspase-3 and caspase-9 expression with a western blotting assay. Further research revealed that compound 3 could improve mitochondrial function by inhibiting mitochondrial cytochrome c release, reducing ROS levels, and maintaining the membrane potential. This work firstly reports vulgarisin-type diterpenoids possessing neuroprotective activity. These findings also suggest that daily consumption of P. vulgaris might prevent cerebral disorders via a mitochondria-related pathway.

Nickel nanoparticles affect the migration and invasion of HTR-8/SVneo cells by downregulating MMP2 through the PI3K/AKT pathway.

Proper migration and invasion of extravillous trophoblast cells into the endometrium in early gestation is essential for successful embryo implantation. The development of nanotechnology has led to the emergence of nickel nanoparticles (Ni NPs), for which attendant health concerns are widespread. Ni NPs are known to affect reproduction and be embryotoxic, but whether they affect the migration and invasion functions of trophoblast cells is unclear. We investigated the effects of Ni NPs on the migration and invasion of HTR-8/SVneo in extravillous trophoblast cells and explored the possible role of the PI3K/AKT/MMP2 signaling pathway in this regard. Results showed that the migration and invasion of cells was significantly inhibited by the exposure of Ni NPs. The protein and mRNA levels of PI3K/AKT/MMP2 signaling pathway were significantly reduced with the increase in Ni NPs concentration. The presence of the PI3K activator 740Y-P partially attenuated the inhibition of cell migration and invasion by Ni NPs, confirming the involvement of this pathway. Thus, Ni NPs inhibit migration and invasion of human trophoblast HTR-8/SVneo cells by downregulating the PI3K/AKT/MMP2 signaling pathway. This study is important for the development of safety evaluation criteria for Ni NPs.

Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer's brains is mediated by USP25.

Down syndrome (DS), caused by trisomy of chromosome 21, is the most significant risk factor for early-onset Alzheimer's disease (AD); however, underlying mechanisms linking DS and AD remain unclear. Here, we show that triplication of homologous chromosome 21 genes aggravates neuroinflammation in combined murine DS-AD models. Overexpression of USP25, a deubiquitinating enzyme encoded by chromosome 21, results in microglial activation and induces synaptic and cognitive deficits, whereas genetic ablation of Usp25 reduces neuroinflammation and rescues synaptic and cognitive function in 5×FAD mice. Mechanistically, USP25 deficiency attenuates microglia-mediated proinflammatory cytokine overproduction and synapse elimination. Inhibition of USP25 reestablishes homeostatic microglial signatures and restores synaptic and cognitive function in 5×FAD mice. In summary, we demonstrate an unprecedented role for trisomy 21 and pathogenic effects associated with microgliosis as a result of the increased USP25 dosage, implicating USP25 as a therapeutic target for neuroinflammation in DS and AD.

Structural characterization, modification and hepatoprotective effects of polysaccharide from Mori Fructus.

In this paper, three purified Mori Fructus (M. Fructus) polysaccharides (MFP-1, MFP-2 and MFP-3) were successfully obtained from M. Fructus. Structural modification methods, including oxidative degradated, sulfated and carboxymethylated modification, were conducted and nine MFPs derivatives were obtained. The molecular structures of MFPs were studied and the results showed that MFP-1, MFP-2 and MFP-3, mainly composed of Ara, Gal, Rha, Glc and GalA, with a molecular weight approximately of 20.93 kDa, 56.23 kDa and 118.76 kDa, respectively. FT-IR spectrum of these MFPs all revealed the characteristic polysaccharide absorption bands, while the MFPs derivatives also exhibited some differences due to the structure modification. Hepatoprotective activities tests showed that MFP derivatives could significantly improve the alcohol dehydrogenase (ADH) activity by comparing with the native MFP. And among them, the C-MFP exhibited higher protection effect than the other two modification derivatives.

Characterizations and hepatoprotective effect of polysaccharides from Mori Fructus in rats with alcoholic-induced liver injury.

Crude polysaccharides of Mori Fructus (MFPs) were found to have anti-inflammatory antioxidant, and immuno-enhancing activities. However, the structure of the polysaccharides was ambiguous and its holistic hepatic protection evaluation was defective. This study was conducted to illustrate the characterization of MFPs, and evaluate its hepatoprotective activities. The results found that MFPs contained 67.93±1.18% carbohydrates, 31.03±0.54% uronic acid, and little protein and sulfate. The average molecular weight was ranging from 112.2kDa to 181.9kDa. Monosaccharide component analysis indicated that MFPs was mainly composed of glucose, galacturonic acid, rhamnose and galactose. Both the acute and subacute alcoholic-induced liver injury animal models were adopted to evaluate the MFPs's hepatoprotective activity. After administration of MFPs, both serological indexes (aspartate aminotransferase and alanine aminotransferase) and hepatic indicators (glutathione, superoxide dismutase, glutathione peroxidase and malondialdehyde) were improved by comparing with the non-MFPs group. The hepatic histopathology results also showed a prominent lipid degeneration and microvesicular steatosis attenuation in the MFPs groups. These outstanding hepatic protecting activities of MFPs might be related to its activation of ethanol dehydrogenase, elimination of free radicals and/or inhibition of lipid peroxidation capacities. MFPs could be important active substances for preventing and remedying liver injury.

Optimization of enzyme assisted extraction of Fructus Mori polysaccharides and its activities on antioxidant and alcohol dehydrogenase.

In the present study, enzyme assisted extraction of Fructus Mori polysaccharides (FMPS) from F. mori using four kinds of enzymes and three compound enzymes were examined. Research found that glucose oxidase offered a better performance in enhancement of the extraction yields of FMPS, antioxidant and activate alcohol dehydrogenase activities. The glucose oxidase assisted extraction process was further optimized by using response surface method (RSM) to obtain maximum yield of crude FMPS. The results showed that optimized extraction conditions were ratio of enzyme amount 0.40%, enzyme treated time 38 min, treated temperature 58 °C and liquid-solid radio 11.0. Under these conditions, the mean experimental value of extraction yield (16.16 ± 0.14%) corresponded well with the predicted values and increased 160% than none enzyme treated ones. Pharmacological verification tests showed that F. mori crude polysaccharides had good antioxidant and activate alcohol dehydrogenase activities in vitro.

Adsorption of Cu(2+) and methyl orange from aqueous solutions by activated carbons of corncob-derived char wastes.

Corncob-derived char wastes (CCW) obtained from biomass conversion to syngas production through corncob steam gasification, which were often discarded, were utilized for preparation of activated carbon by calcination, and KOH and HNO3 activation treatments, on the view of environment protection and waste recycling. Their adsorption performance in the removal of heavy metal ions and dye molecules from wastewater was evaluated by using Cu(2+) and methyl orange (MO) as the model pollutant. The surface and structure characteristics of the CCW-based activated carbons (CACs) were investigated by N2 adsorption, CO2 adsorption, FT-IR, and He-TPD. The adsorption capacity varied with the activation methods of CACs and different initial solution concentrations, indicating that the adsorption behavior was influenced by not only the surface area and porosity but also the oxygen functional groups on the surface of the CACs. The equilibrium adsorption data were analyzed with the Langmuir, Freundlich, and Temkin isotherm models, and the adsorption kinetics was evaluated by the pseudo-first-order and pseudo-second-order models.

Ordered mesoporous carbon catalyst for dehydrogenation of propane to propylene.

Metal-free ordered mesoporous carbons were demonstrated to be robust catalysts for direct dehydrogenation of propane to propylene, in the absence of any auxiliary steam, exhibiting high activity and selectivity, as well as long catalytic stability, in comparison with nanostructured carbons.