Multiomics reveals the ameliorating effect and underlying mechanism of aqueous extracts of polygonatum sibiricum rhizome on obesity and liver fat accumulation in high-fat diet-fed mice.

BACKGROUND: Polygonatum sibiricum polysaccharides protect against obesity and NAFLD. However, the potential effects of PS rhizome aqueous extracts (PSRwe) on adiposity and hepatic lipid accumulation remains unexplored. PURPOSE: Elucidating the impact and underlying mechanism of PSRwe on HFD-induced obesity and liver fat depostition. STUDY DESIGN: 56 male mice, aged eight weeks, were divided into seven groups: Positive, four doses of PSRwe, Model, and Control. HFD was fed for eight weeks, followed by alternate-day gavage of orlistat and PSRwe for an additional eight-week period. Integrative analysis encompassing multiomics, physiological and histopathological, and biochemical indexes was employed. METHODS: Body weight (BW); liver, fat and Lee's indexes; TC, TG, LDL-C, HDL-C, AST, ALT, FFA, leptin, and adiponectin in the liver and blood; TNFα, IL-6, and LPS in the colon, plasma, and liver; H&E, PAS and oil red O staining on adipose and liver samples were examined. OGTT and ITT were conducted The gut microbiome, microbial metabolome, colonic and liver transcriptome, plasma and liver metabolites were investigated. RESULTS: PSRwe at the dosage of 7.5 mg/kg demonstrated significant and consistent reduction in BW and hepatic fat deposition than orlistat. PSRwe significantly decreased TC, TG, LDL-C, LEP, FFA levels in blood and liver. PSRwe significantly enhanced the relative abundance of probiotics including Akkermansia muciniphila, Bifidobacterium pseudolongum, Lactobacillus reuteri, and metabolic pathways including glycolysis and fatty acids ß-oxidation. The 70 up-regulated microbial metabolites in PSRwe-treated mice mainly involved in nucleotides and amino acids metabolism, while 40 decreased metabolites primarily associated with lipid metabolism. The up-regulated colonic differentially expressed genes (DEGs) participate in JAK-STAT/PI3K-Akt/FoxO signaling pathway, serotonergic/cholinergic/glutamatergic synapses, while the down-regulated DEGs predominantly focused on fat absorption and transport. The up-regulated liver DEGs mainly concentrated on fatty acid oxidation and metabolism. Liver metabolisms revealed 131 differential metabolites, among which carnitine and oxidized lipids significantly increased in PSRwe-treated mice. In plasma, the 58 up-regulated metabolites mainly participate in co-factors/vitamins metabolism while 154 down-regulated ones in fatty acids biosynthesis. Comprehensive multiomics association analysis revealed significant associations between gut microbiota and colonic/liver gene expression, and suggested exogenous and endogenous betaine may be active compound in alleviating HFD-induced symptoms. CONCLUSION: PSRwe effectively mitigate HFD-induced obesity and hepatic steatosis by increasing beneficial bacteria, reducing colonic fat digestion/absorption, increasing hepatic lipid metabolism, and elevating betaine levels.

The Molecular Mechanism of Potassium Absorption, Transport, and Utilization in Rice.

Potassium is essential for plant growth and development and stress adaptation. The maintenance of potassium homeostasis involves a series of potassium channels and transporters, which promote the movement of potassium ions (K+) across cell membranes and exhibit complex expression patterns and regulatory mechanisms. Rice is a major food crop in China. The low utilization rate of potassium fertilizer limits the yield and quality of rice. Elucidating the molecular mechanisms of potassium absorption, transport, and utilization is critical in improving potassium utilization efficiency in rice. Although some K+ transporter genes have been identified from rice, research on the regulatory network is still in its infancy. Therefore, this review summarizes the relevant information on K+ channels and transporters in rice, covering the absorption of K+ in the roots, transport to the shoots, the regulation pathways, the relationship between K+ and the salt tolerance of rice, and the synergistic regulation of potassium, nitrogen, and phosphorus signals. The related research on rice potassium nutrition has been comprehensively reviewed, the existing research foundation and the bottleneck problems to be solved in this field have been clarified, and the follow-up key research directions have been pointed out to provide a theoretical framework for the cultivation of potassium-efficient rice.

Gastrointestinal digestion and absorption of soybean ß-conglycinin in an early weaned piglet model: An initial step to the induction of soybean allergy.

To date, it still remains unknown how ß-conglycinin, a major soybean allergen, crosses intestinal epithelial barrier to reach immune cells. The purpose of this study was to elucidate the pathway and molecular mechanism of ß-conglycinin absorption and transport across intestinal mucosal epithelium using a ß-conglycinin allergic piglet model. Ten-day old piglets were orally sensitized with diets containing 2% and 4% ß-conglycinin. The digestion, absorption and transport of ß-conglycinin in gastrointestinal tract was investigated. The results showed that ß-conglycinin had a certain resistance to gastrointestinal digestion, and the digestion-resistant subunits and fragments were absorbed into the intestinal mucosa and then induced an anaphylaxis in early weaned piglets. The absorption occurred in the form of IgE-allergen immune complex through transcellular pathway with CD23 as the receptor. These results provided important clues for using the pathway and molecule as inhibitor target to prevent and alleviate soybean ß-conglycinin allergy in infants.

Advanced imaging techniques for tracking drug dynamics at the subcellular level.

Optical microscopes are an important imaging tool that have effectively advanced the development of modern biomedicine. In recent years, super-resolution microscopy (SRM) has become one of the most popular techniques in the life sciences, especially in the field of living cell imaging. SRM has been used to solve many problems in basic biological research and has great potential in clinical application. In particular, the use of SRM to study drug delivery and kinetics at the subcellular level enables researchers to better study drugs' mechanisms of action and to assess the efficacy of their targets in vivo. The purpose of this paper is to review the recent advances in SRM and to highlight some of its applications in assessing subcellular drug dynamics.

Efficient potassium (K) recycling and root carbon (C) metabolism improve K use efficiency in pear rootstock genotypes.

To investigate K absorption and transport mechanisms by which pear rootstock genotypes respond to low-K stress, seedlings of a potassium-efficient pear rootstock, Pyrus ussuriensis, and a potassium-sensitive rootstock, Pyrus betulifolia, were supplied with different K concentrations in solution culture. Significant differences in the absorption rate, Vmax and Km between the genotypes indicate that P. ussuriensis acclimatizes more readily to low-K stress by regulating its absorption and internal cycling. We also found that the K content in the leaves of P. betulifolia was significantly lower than that of P. ussuriensis, and the proportion of K that was returned to root from shoot, relative to K that was transported from root to shoot, was greater in P. ussuriensis, which suggests that P. ussuriensis more efficiently recycles and reuses K. When the transcriptomes of the two genotypes were compared, we found that photosynthetic genes such as CABs (Chlorophyll a/b-binding proteins), Lhcbs (Photosystem II-related proteins), and Psas (Photosystem Ⅰ associated proteins) displayed lower expression in leaves of P. betulifolia under no-K conditions, but not in P. ussuriensis. However, in the root of P. ussuriensis, carbon metabolism-related genes SS (Sucrose Synthase), HK (HexoKinase) and SDH (Sorbitol Dehydrogenase) and components of the TCA cycle (Tricarboxylic Acid cycle) were differentially expressed, indicating that changes in C metabolism may provide energy for increased K+ cycling in these plants, thereby allowing it to better adapt to the low-K environment. In addition, exogenous supply of various sugars to the roots influenced K+ influx, supporting the conclusion that sugar metabolism in roots significantly affects K+ absorption in pear.

Genetic Regulation Mechanism of Cadmium Accumulation and Its Utilization in Rice Breeding.

Cadmium (Cd) is a heavy metal whose pollution in rice fields leads to varying degrees of Cd accumulation in rice. Furthermore, the long-term consumption of Cd-contaminated rice is harmful to human health. Therefore, it is of great theoretical significance and application value to clarify the genetic regulation mechanism of Cd accumulation in rice and cultivate rice varieties with low Cd accumulation for the safe use of Cd-contaminated soils. This review summarizes the effects of Cd on rice growth, yield, and quality; the physiological and molecular mechanisms of Cd absorption in the roots, loading, and transport of Cd in the xylem, the distribution of Cd in nodes, redistribution of Cd in leaves, and accumulation of Cd in the grains; the regulation mechanism of the Cd stress response; and the breeding of rice with low Cd accumulation. Future directions on the genetic regulation of Cd in rice and application are also discussed. This review provides a theoretical basis for studies exploring the genetic regulation of Cd stress in rice. It also offers a basis for formulating effective strategies to reduce the Cd content in rice.

Physiological and Molecular Mechanisms of Plant Responses to Copper Stress.

Copper (Cu) is an essential micronutrient for humans, animals, and plants, and it participates in various morphological, physiological, and biochemical processes. Cu is a cofactor for a variety of enzymes, and it plays an important role in photosynthesis, respiration, the antioxidant system, and signal transduction. Many studies have demonstrated the adverse effects of excess Cu on crop germination, growth, photosynthesis, and antioxidant activity. This review summarizes the biological functions of Cu, the toxicity of excess Cu to plant growth and development, the roles of Cu transport proteins and chaperone proteins, and the transport process of Cu in plants, as well as the mechanisms of detoxification and tolerance of Cu in plants. Future research directions are proposed, which provide guidelines for related research.

Molecular Regulatory Networks for Improving Nitrogen Use Efficiency in Rice.

Nitrogen is an important factor limiting the growth and yield of rice. However, the excessive application of nitrogen will lead to water eutrophication and economic costs. To create rice varieties with high nitrogen use efficiency (NUE) has always been an arduous task in rice breeding. The processes for improving NUE include nitrogen uptake, nitrogen transport from root to shoot, nitrogen assimilation, and nitrogen redistribution, with each step being indispensable to the improvement of NUE. Here, we summarize the effects of absorption, transport, and metabolism of nitrate, ammonium, and amino acids on NUE, as well as the role of hormones in improving rice NUE. Our discussion provide insight for further research in the future.

Study on oil-water distribution of taxifolin and its absorption and transport mechanism in Caco-2 cell model / 中草药

Objective: To prepare the taxifolin and determine its apparent oil-water partition coefficient in different media, and to study the mechanism of absorption and transport of taxifolin in Caco-2 cell model. Methods: Taxifolin was prepared by enzymolysis. HPLC was used to determine the saturated solubility of taxifolin in 37 ℃, different pH buffer solution and water, apparent oil-water distribution coefficient of taxifolin obtained by calculation formula of oil-water distribution coefficient; CCK-8 experiment was used to investigate the safe concentration range of taxifolin in Caco-2 cells, and then the single-layer model of Caco-2 cells was used to study the mechanism of bilateral transmembrane absorption and transport. CCK-8 experiment was used to investigate the safe concentration range of taxifolin in HDMEC cells. The inflammatory model of HDMEC cells induced by lipopolysaccharide was established, and the activity of lactic dehydrogenase was detected by the intervention of floxacin. The activity of lactic dehydrogenase was detected by lactic dehydrogenase kit. Results: The lgP values of taxifolin in the following solvents were 0.29 (0.1 mol/L hydrochloric acid), 0.48 (pH 2.0), 0.46 (pH 5.8), 0.34 (pH 6.8), 0.26 (pH 7.4), and 0.38 (water), respectively; There was no significant toxic effect on Caco-2 cells in the range of 50-500 μg/mL; There was no significant difference in Papp value of bilateral transport between different concentrations of taxifolin in Caco-2 monolayer cell model, and it was less than 1 × 10-6 cm/s and ER was less than 2. There was no significant toxic effect on HDMEC cells in the range of 50-300 μg/mL; After treatment with taxifolin, compared with LPS stimulation group, the activity of LDH in each treatment group was decreased significantly (P < 0.05), and the activity of LDH was decreased significantly in the range of 50-100 μg/mL, and tended to be stable in the range of 100-250 μg/mL. Conclusion: Taxifolin is a kind of drug which is difficult to absorb in the intestine. The mechanism of transmembrane transport is passive transport. It can inhibit the inflammation of hdmec cells induced by LPS and has anti-inflammatory activity.

Advances in the Uptake and Transport Mechanisms and QTLs Mapping of Cadmium in Rice.

Cadmium (Cd), as a heavy metal, presents substantial biological toxicity and has harmful effects on human health. To lower the ingress levels of human Cd, it is necessary for Cd content in food crops to be reduced, which is of considerable significance for ensuring food safety. This review will summarize the genetic traits of Cd accumulation in rice and examine the mechanism of Cd uptake and translocation in rice. The status of genes related to Cd stress and Cd accumulation in rice in recent years will be summarized, and the genes related to Cd accumulation in rice will be classified according to their functions. In addition, an overview of quantitative trait loci (QTLs) mapping populations in rice will be introduced, aiming to provide a theoretical reference for the breeding of rice varieties with low Cd accumulation. Finally, existing problems and prospects will be put forward.

Membrane permeability evaluation method of oral drugs and their application progress in Chinese materia medica / 中草药

Chinese materia medica is mostly taken orally. The permeability of a drug’s biofilm (e.g. cell membrane) reflects its ability of absorption and transportation in the body. It is of guiding significance to evaluate the membrane permeability of the active components of Chinese materia medica by using appropriate drug permeation model, so as to clarify, the oral absorption and transport mechanism of active ingredients, pharmacodynamic substance basis and dosage form design. The evaluation method of oral drug membrane permeability, as well as the application of various methods in Chinese medicine was summarized for reference in this review.

Laboratory Microprobe X-Ray Fluorescence in Plant Science: Emerging Applications and Case Studies.

In vivo and micro chemical analytical methods have the potential to improve our understanding of plant metabolism and development. Benchtop microprobe X-ray fluorescence spectroscopy (µ-XRF) presents a huge potential for facing this challenge. Excitation beams of 30 µm and 1 mm in diameter were employed to address questions in seed technology, phytopathology, plant physiology, and bioremediation. Different elements were analyzed in several situations of agronomic interest: (i) Examples of µ-XRF yielding quantitative maps that reveal the spatial distribution of zinc in common beans (Phaseolus vulgaris) primed seeds. (ii) Chemical images daily recorded at a soybean leaf (Glycine max) infected by anthracnose showed that phosphorus, sulfur, and calcium trended to concentrate in the disease spot. (iii) In vivo measurements at the stem of P. vulgaris showed that under root exposure, manganese is absorbed and transported nearly 10-fold faster than iron. (iv) Quantitative maps showed that the lead distribution in a leaf of Eucalyptus hybrid was not homogenous, this element accumulated mainly in the leaf border and midrib, the lead hotspots reached up to 13,400 mg lead kg-1 fresh tissue weight. These case studies highlight the ability of µ-XRF in performing qualitative and quantitative elemental analysis of fresh and living plant tissues. Thus, it can probe dynamic biological phenomena non-destructively and in real time.

Development and characterization of iron-pectin beads as a novel system for iron delivery to intestinal cells.

Iron deficiency is the most common nutritional deficit worldwide. The goal of this work was to obtain iron-pectin beads by ionic gelation and evaluate their physiological behavior to support their potential application in the food industry. The beads were firstly analyzed by scanning electronic microscopy, and then physical-chemically characterized by performing swelling, thermogravimetric, porosimetry, Mössbauer spectroscopy and X-ray fluorescence analyses, as well as by determining the particle size. Then, physiological assays were carried out by exposing the beads to simulated gastric and intestinal environments, and determining the iron absorption and transepithelial transport into Caco-2/TC7 cells. Iron-pectin beads were spherical (diameter 1-2 mm), with high density (1.29 g/mL) and porosity (93.28%) at low pressure, indicating their high permeability even when exposed to low pressure. Swelling in simulated intestinal medium (pH 8) was higher than in simulated gastric medium. The source of iron [FeSO4 (control) or iron-pectin beads] did not have any significant effect on the mineral absorption. Regarding transport, the iron added to the apical pole of Caco-2/TC7 monolayers was recovered in the basal compartment, and this was proportional with the exposure time. After 4 h of incubation, the transport of iron arising from the beads was significantly higher than that of the iron from the control (FeSO4). For this reason, iron-pectin beads appear as an interesting system to overcome the low efficiency of iron transport, being a potential strategy to enrich food products with iron, without altering the sensory properties.

Congenital intestinal diarrhoeal diseases: A diagnostic and therapeutic challenge.

Congenital diarrhoeal disorders are a heterogeneous group of inherited malabsorptive or secretory diseases typically appearing in the first weeks of life, which may be triggered by the introduction of distinct nutrients. However, they may also be unrecognised for a while and triggered by exogenous factors later on. In principle, they can be clinically classified as osmotic, secretory or inflammatory diarrhoea. In recent years the disease-causing molecular defects of these congenital disorders have been identified. According to the underlying pathophysiology they can be classified into four main groups: 1) Defects of digestion, absorption and transport of nutrients or electrolytes 2) Defects of absorptive enterocyte differentiation or polarisation 3) Defects of the enteroendocrine cells 4) Defects of the immune system affecting the intestine. Here, we describe the clinical presentation of congenital intestinal diarrhoeal diseases, the diagnostic work-up and specific treatment aspects.

Dietary Lipid and Carbohydrate Interactions: Implications on Lipid and Glucose Absorption, Transport in Gilthead Sea Bream (Sparus aurata) Juveniles.

A digestibility trial was performed with gilthead sea bream juveniles (IBW = 72 g) fed four diets differing in lipid source (fish oil, FO; or a blend of vegetable oil, VO) and starch content (0 %, CH-; or 20 %, CH+) to evaluate the potential interactive effects between carbohydrates and VO on the processes involved in digestion, absorption and transport of lipids and glucose. In fish fed VO diets a decrease in lipid digestibility and in cholesterol (C), High Density Lipoprotein(HDL)-C and Low Density Lipoprotein (LDL)-C (only in CH+ group) were recorded. Contrarily, dietary starch induced postprandial hyperglycemia and time related alterations on serum triacylglycerol (TAG), phospholipid (PL) and C concentrations. Fish fed a CH+ diet presented lower serum TAG than CH- group at 6 h post-feeding, and the reverse was observed at 12 h post-feeding for TAG and PL. Lower serum C and PL at 6 h post-feeding were recorded only in VOCH+ group. No differences between groups were observed in hepatic and intestinal transcript levels of proteins involved in lipid transport and hydrolysis (FABP, DGAT, GPAT, MTP, LPL, LCAT). Lower transcript levels of proteins related to lipid transport (ApoB, ApoA1, FABP2) were observed in the intestine of fish fed the CH+ diet, but remained unchanged in the liver. Overall, transcriptional mechanisms involved in lipid transport and absorption were not linked to changes in lipid serum and digestibility. Dietary starch affected lipid absorption and transport, probably due to a delay in lipid absorption. This study suggests that a combination of dietary VO and starch may negatively affect cholesterol absorption and transport.

[Establishment of MDCK-pHaMDR cell model and standard operation procedure for assessing blood-brain barrier permeability of chemical components of traditional Chinese medicine].

To establish MDCK-pHaMDR cell model and standard operation procedure for assessing the blood-brain barrier permeability of chemical components of traditional Chinese medicine. MDCK-pHaMDR cell model was evaluated by determining the morphology features, transepithelial electrical resistance, bidirectional transport and intracellular accumulation of Rhodamine 123 and the apparent permeability of positive control drugs caffeine and atenolol. The MDCK-pHaMDR cell model had satisfactory integrity and tightness, and stable expression of P-gp. In addition, the transport results of the positive control drugs were consistent with the reported values in literature. All the parameters tested of the MDCK-pHaMDR cell model were consistent with the requirements, so the model can be used to study the blood-brain barrier permeability of chemical components of traditional Chinese medicine.

Establishment of MDCK-pHaMDR cell model and standard operation procedure for assessing blood-brain barrier permeability of chemical components of traditional Chinese medicine / 中国中药杂志

To establish MDCK-pHaMDR cell model and standard operation procedure for assessing the blood-brain barrier permeability of chemical components of traditional Chinese medicine. MDCK-pHaMDR cell model was evaluated by determining the morphology features, transepithelial electrical resistance, bidirectional transport and intracellular accumulation of Rhodamine 123 and the apparent permeability of positive control drugs caffeine and atenolol. The MDCK-pHaMDR cell model had satisfactory integrity and tightness, and stable expression of P-gp. In addition, the transport results of the positive control drugs were consistent with the reported values in literature. All the parameters tested of the MDCK-pHaMDR cell model were consistent with the requirements, so the model can be used to study the blood-brain barrier permeability of chemical components of traditional Chinese medicine.

Taurine and its effect on the protection of the central nervous system / 中华实用儿科临床杂志

Taurine is one of the extremely important amino acids in the body,and is also the most abundant free amino acids in the central nervous system(CNS).Taurine as a conditional essential amino acids exerts a wide range of physiological and pharmacological effects.Taurine,especially as a neurotransmitter in the developing CNS,can maintain the structural integrity of the membrane,regulate calcium transport and calcium homeostasis,also as nutritional factors,osmolyte,neuromodulator,neuroprotective agents,plays an important role.In this paper,physiological and biochemical properties of taurine,source and distribution in vivo,synthesis and metabolism,absorption and transport,and its protective effect on the CNS are reviewed.

Systemic oxygen delivery by peritoneal perfusion of oxygen microbubbles.

Severe hypoxemia refractory to pulmonary mechanical ventilation remains life-threatening in critically ill patients. Peritoneal ventilation has long been desired for extrapulmonary oxygenation owing to easy access of the peritoneal cavity for catheterization and the relative safety compared to an extracorporeal circuit. Unfortunately, prior attempts involving direct oxygen ventilation or aqueous perfusates of fluorocarbons or hemoglobin carriers have failed, leading many researchers to abandon the method. We attribute these prior failures to limited mass transfer of oxygen to the peritoneum and have designed an oxygen formulation that overcomes this limitation. Using phospholipid-coated oxygen microbubbles (OMBs), we demonstrate 100% survival for rats experiencing acute lung trauma to at least 2 h. In contrast, all untreated rats and rats treated with peritoneal oxygenated saline died within 30 min. For rats treated with OMBs, hemoglobin saturation and heart rate were at normal levels over the 2-h timeframe. Peritoneal oxygenation with OMBs was therefore shown to be safe and effective, and the method requires less equipment and technical expertise than initiating and maintaining an extracorporeal circuit. Further translation of peritoneal oxygenation with OMBs may provide therapy for acute respiratory distress syndrome arising from trauma, sepsis, pneumonia, aspiration, burns and other pulmonary diseases.

Auxin response factor (OsARF12), a novel regulator for phosphate homeostasis in rice (Oryza sativa).

Phosphorus (P) is crucial nutrient element for crop growth and development. However, the network pathway regulating homeostasis of phosphate (Pi) in crops has many molecular breeding unknowns. Here, we report that an auxin response factor, OsARF12, functions in Pi homeostasis. Measurement of element content, quantitative reverse transcription polymerase chain reaction analysis and acid phosphatases (APases) activity assay showed that the osarf12 mutant and osarf12/25 double mutant with P-intoxicated phenotypes had higher P concentrations, up-regulation of the Pi transporter encoding genes and increased APase activity under Pi-sufficient/-deficient (+Pi/-Pi, 0.32/0 mM NaH2 PO4) conditions. Transcript analysis revealed that Pi-responsive genes--Phosphate starvation (OsIPS)1 and OsIPS2, SYG1/Pho81/XPR1(OsSPX1), Sulfoquinovosyldiacylglycerol 2 (OsSQD2), R2R3 MYB transcription factor (OsMYB2P-1) and Transport Inhibitor Response1 (OsTIR1)--were more abundant in the osarf12 and osarf12/25 mutants under +Pi/-Pi conditions. Knockout of OsARF12 also influenced the transcript abundances of the OsPHR2 gene and its downstream components, such as OsMiR399j, OsPHO2, OsMiR827, OsSPX-MFS1 and OsSPX-MFS2. Results from -Pi/1-naphthylphthalamic acid (NPA) treatments, and auxin reporter DR5::GUS staining suggest that root system alteration and Pi-induced auxin response were at least partially controlled by OsARF12. These findings enrich our understanding of the biological functions of OsARF12, which also acts in regulating Pi homeostasis.