Effects and mechanisms of anti-diabetic dietary natural products: an updated review.

Diabetes is a global public health issue, characterized by an abnormal level of blood glucose. It can be classified into type 1, type 2, gestational, and other rare diabetes. Recent studies have reported that many dietary natural products exhibit anti-diabetic activity. In this narrative review, the effects and underlying mechanisms of dietary natural products on diabetes are summarized based on the results from epidemiological, experimental, and clinical studies. Some fruits (e.g., grape, blueberry, and cherry), vegetables (e.g., bitter melon and Lycium barbarum leaves), grains (e.g., oat, rye, and brown rice), legumes (e.g., soybean and black bean), spices (e.g., cinnamon and turmeric) and medicinal herbs (e.g., Aloe vera leaf and Nigella sativa), and vitamin C and carotenoids could play important roles in the prevention and management of diabetes. Their underlying mechanisms include exerting antioxidant, anti-inflammatory, and anti-glycation effects, inhibiting carbohydrate-hydrolyzing enzymes, enhancing insulin action, alleviating insulin resistance, modulating the gut microbiota, and so on. This review can provide people with a comprehensive knowledge of anti-diabetic dietary natural products, and support their further development into functional food to prevent and manage diabetes.

The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components.

The number of individuals experiencing mental disorders (e.g., anxiety and depression) has significantly risen in recent years. Therefore, it is essential to seek prevention and treatment strategies for mental disorders. Several gut microbiota, especially Firmicutes and Bacteroidetes, are demonstrated to affect mental health through microbiota-gut-brain axis, and the gut microbiota dysbiosis can be related to mental disorders, such as anxiety, depression, and other mental disorders. On the other hand, dietary components, including probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., dietary fiber and alpha-lactalbumin), synbiotics, postbiotics (e.g., short-chain fatty acids), dairy products, spices (e.g., Zanthoxylum bungeanum, curcumin, and capsaicin), fruits, vegetables, medicinal herbs, and so on, could exert protective effects against mental disorders by enhancing beneficial gut microbiota while suppressing harmful ones. In this paper, the mental disorder-associated gut microbiota are summarized. In addition, the protective effects of dietary components on mental health through targeting the gut microbiota are discussed. This paper can be helpful to develop some dietary natural products into pharmaceuticals and functional foods to prevent and treat mental disorders.

Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea. OBJECTIVES: This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored. METHODS: The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota. RESULTS: TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota. CONCLUSION: We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.

Metabolite Profiling and Comparative Metabolomics Analysis of Jiaozhou Chinese Cabbage (Brassica rapa L. ssp. pekinensis) Planted in Different Areas.

BACKGROUND: Chinese cabbage (Brassica rapa L. ssp. pekinensis) is one of the most popular vegetables in China because of its taste and health benefits. The area of production has obvious effects on the quality of Chinese cabbage. However, metabolite profiling and variations in different production areas are still unclear. METHODS: Here, widely targeted metabolite analyses based on the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach were performed to study the metabolite profiling of Chinese cabbage planted in the Jiaozhou and Jinan areas. RESULTS: A total of 531 metabolites were detected, of which 529 were present in the Chinese cabbage from both areas, 108 were found to be chemicals related to Chinese traditional medicine, and 79 were found to correspond to at least one disease. Chinese cabbage is rich in nutritious substances such as lipids, phenolic acids, amino acids and derivatives, nucleotides and derivatives, organic acids, flavonoids, glucosinolates, saccharides, alcohols, and vitamins. Comparative analysis showed that the metabolic profiles differed between areas, and 89 differentially altered metabolites (DAMs) were characterized. Of these, 78 DAMs showed higher levels in Jinan Chinese cabbage, whereas 11 had higher levels in Jiaozhou Chinese cabbage. Two metabolites, S-(Methyl)glutathione and nicotinic acid adenine dinucleotide, were unique in Jiaozhou Chinese cabbage. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DAMs were enriched into 23 pathways, of which tryptophan metabolism and thiamine metabolism were the significant enrichment pathways. CONCLUSIONS: This study provides new insights into the metabolite profiles and production areas affecting the metabolite variations of Chinese cabbage, which will be useful for functional Chinese cabbage cultivation.

Liangxue Tongyu Prescription Alleviates Brain Damage in Acute Intracerebral Hemorrhage Rats by Regulating Intestinal Mucosal Barrier Function.

Background: Liangxue Tongyu prescription (LTP) is a commonly used formula for acute intracerebral hemorrhage (AICH) in clinical practice that has significant ameliorative effects on neurological deficits and gastrointestinal dysfunction, yet the mechanism remains elusive. The aim of this study was to investigate the pathway by which LTP alleviates brain damage in AICH rats. Methods: The AICH rat models were established by autologous caudal arterial blood injection. The neurological function scores were evaluated before and after treatment. The water content and the volume of Evans blue staining in the brain were measured to reflect the degree of brain damage. RT-PCR was used to detect the inflammatory factors of the brain. Western blotting was used to detect the expression of the tight junction proteins zonula occludens 1 (ZO-1), occludin (OCLN), and claudin (CLDN) in the brain and colon, followed by mucin 2 (MUC2), secretory immunoglobulin A (SIgA), and G protein-coupled receptor 43 (GPR43) in the colon. Flow cytometry was used to detect the ratios of helper T cells 17 (Th17) and regulatory T cells (Treg) in peripheral blood, and the vagus nerve (VN) discharge signals were collected. Results: LTP reduced the brain damage of the AICH rats. Compared with the model group, LTP significantly improved the permeability of the colonic mucosa, promoted the secretion of MUC2, SigA, and GPR43 in the colon, and regulated the immune balance of peripheral T cells. The AICH rats had significantly faster VN discharge rates and lower amplitudes than normal rats, and these abnormalities were corrected in the LTP and probiotics groups. Conclusion: LTP can effectively reduce the degree of brain damage in AICH rats, and the mechanism may be that it can play a neuroprotective role by regulating the function of the intestinal mucosal barrier.

Preventive Effects of Different Black and Dark Teas on Obesity and Non-Alcoholic Fatty Liver Disease and Modulate Gut Microbiota in High-Fat Diet Fed Mice.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a leading public health challenge and is closely associated with metabolic syndromes, such as obesity. Intestinal microbiota dysbiosis could play a vital role in the pathogenesis and progression of NAFLD. Tea is the second most popular health drink in the world behind water, and exhibits many health-promoting effects. In this study, the protective effects of different black and dark teas on NAFLD induced by long-term high-fat diet (HFD) exposure and their regulation of gut microbiota were evaluated and explored. The results indicated that supplementation with different black and dark tea extracts could significantly suppress the energy intake, alleviate abnormal accumulation of visceral fat, and prevent obesity, hepatic abnormal lipid deposition and liver steatosis in HFD-fed mice at varying degrees. In addition, Dianhong tea and Liupao tea interventions could significantly decrease the ratio of Firmicutes to Bacteroidetes, and selenium-enriched black tea and selenium-enriched dark rea supplementation could remarkably reduce the relative abundance of Actinobacteria compared to the model group. Moreover, these teas could partly shift the relative abundances of Allobaculum, Roseburia and Dubosiella. Taken together, black teas and dark teas could prevent HFD-induced features of obesity and NAFLD, which might partly be due to the modulation of gut microbiota.

Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review.

Cancer has been a serious public health problem. Berberine is a famous natural compound from medicinal herbs and shows many bioactivities, such as antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and antimicrobial activities. In addition, berberine shows anticancer effects on a variety of cancers, such as breast, lung, gastric, liver, colorectal, ovarian, cervical, and prostate cancers. The underlying mechanisms of action include inhibiting cancer cell proliferation, suppressing metastasis, inducing apoptosis, activating autophagy, regulating gut microbiota, and improving the effects of anticancer drugs. This paper summarizes effectiveness and mechanisms of berberine on different cancers and highlights the mechanisms of action. In addition, the nanotechnologies to improve bioavailability of berberine are included. Moreover, the side effects of berberine are also discussed. This paper is helpful for the prevention and treatment of cancers using berberine.

Effects and mechanisms of resveratrol for prevention and management of cancers: An updated review.

Cancer is a severe public health problem. Resveratrol is a famous natural compound that has various bioactivities, such as antioxidant, anti-inflammatory, antidiabetic and antiaging activities. Especially, resveratrol could prevent and treat various cancers, such as oral, thyroid, breast, lung, liver, pancreatic, gastric, colorectal, bladder, prostate and ovarian cancers. The underlying mechanisms have been widely studied, such as inhibiting cell proliferation, suppressing metastasis, inducing apoptosis, stimulating autophagy, modulating immune system, attenuating inflammation, regulating gut microbiota and enhancing effects of other anticancer drugs. In this review, we summarize effects and mechanisms of resveratrol on different cancers. This paper is helpful to develop resveratrol, crude extract containing resveratrol, or foods containing resveratrol into functional food, dietary supplements or auxiliary agents for prevention and management of cancers.

Correlation between Serum Levels of Vitamin A and Vitamin D with Disease Severity in Tic Disorder Children.

Purpose: To explore and analyze the correlation between serum vitamins A and D levels and disease severity in children with tic disorder. Methods: A total of 59 children with tic disorders treated in the Linping Hospital of Traditional Chinese Medicine from April 2018 to May 2021 were selected as the observation group. 55 healthy children with matched age and sex who underwent physical examination were selected as the control group. Children in the observation group were subdivided to the mild group (n = 35) and moderate-to-severe group (n = 24) according to the Yale comprehensive tic severity scale. Afterwards, they were grouped into the temporary group (n = 25), persistent group (n = 22), and Tourette's syndrome group (n = 12) according to their clinical characteristics and course of disease. The severity and serum vitamins A and D levels were collected and compared, and then, Spearman correlation analysis was performed to analyze the correlation between the severity and serum vitamins A and D levels. Results: Compared with the control group, the serum vitamin A and D levels in the observation group were lower. Compared with the mild group, the serum vitamins A and D levels were lower in the moderate-to-severe group. Spearman correlation analysis revealed a significant negative correlation between disease severity and serum vitamins A and D levels. Regarding the serum D levels, the temporary group > the persistent group > Tourette's syndrome group. There was no significant difference in serum vitamin A levels among the three groups. Conclusion: Vitamins A and D deficiency in children is strongly associated with tic disorders, and vitamins A and D demonstrate a negative correlation with the severity of tic disorders. Vitamin D is also linked to the clinical type of tic disorder.

Mechanism of Fei-Xian Formula in the Treatment of Pulmonary Fibrosis on the Basis of Network Pharmacology Analysis Combined with Molecular Docking Validation.

OBJECTIVE: This study aimed to clarify the mechanism of Fei-Xian formula (FXF) in the treatment of pulmonary fibrosis based on network pharmacology analysis combined with molecular docking validation. METHODS: Firstly, ingredients in FXF with pharmacological activities, together with specific targets, were identified based on the BATMA-TCM and TCMSP databases. Then, targets associated with pulmonary fibrosis, which included pathogenic targets as well as those known therapeutic targets, were screened against the CTD, TTD, GeneCards, and DisGeNet databases. Later, Cytoscape was employed to construct a candidate component-target network of FXF for treating pulmonary fibrosis. In addition, for nodes within the as-constructed network, topological parameters were calculated using CytoHubba plug-in, and the degree value (twice as high as the median degree value for all the nodes) was adopted to select core components as well as core targets of FXF for treating pulmonary fibrosis, which were subsequently utilized for constructing the core network. Furthermore, molecular docking study was carried out on those core active ingredients together with the core targets using AutoDock Vina for verifying results of network pharmacology analysis. At last, OmicShare was employed for enrichment analysis of the core targets. RESULTS: Altogether 12 active ingredients along with 13 core targets were identified from our constructed core component-target network of FXF for the treatment of pulmonary fibrosis. As revealed by enrichment analysis, the 13 core targets mostly concentrated in regulating biological functions, like response to external stimulus (from oxidative stress, radiation, UV, chemical substances, and virus infection), apoptosis, cell cycle, aging, immune process, and protein metabolism. In addition, several pathways, like IL-17, AGE-RAGE, TNF, HIF-1, PI3K-AKT, NOD-like receptor, T/B cell receptor, and virus infection-related pathways, exerted vital parts in FXF in the treatment of pulmonary fibrosis. CONCLUSIONS: FXF can treat pulmonary fibrosis through a "multicomponent, multitarget, and multipathway" mean. Findings in this work lay foundation for further exploration of the FXF mechanism in the treatment of pulmonary fibrosis.

Molecular mechanisms underlying health benefits of tea compounds.

Tea is one of the three most widely consumed beverages in the world, not only because of its unique flavor but also due to its various health benefits. The bioactive components in tea, such as polyphenols, polysaccharides, polypeptides, pigments, and alkaloids, are the main contributors to its health functions. Based on epidemiological surveys, the consumption of tea and its compounds in daily life has positive effects on cardiovascular diseases, cancers, hepatopathy, obesity, and diabetes mellitus. In experimental studies, the antioxidant, anti-inflammatory, anti-cancer, anti-obesity, cardiovascular protective, liver protective, and hypoglycemic activities of tea and the related mechanisms of action have been widely investigated. The regulation of several classical signaling pathways, such as nuclear factor-κB (NF-κB), AMP activated protein kinase (AMPK), and wingless/integrated (Wnt) signaling, is involved. Clinical trials have also demonstrated the potential of tea products to be applied as dietary supplements and natural medicines. In this paper, we reviewed and discussed the recent literature on the health benefits of tea and its compounds, and specifically explored the molecular mechanisms involved.

Antioxidant Food Components for the Prevention and Treatment of Cardiovascular Diseases: Effects, Mechanisms, and Clinical Studies.

Cardiovascular diseases (CVDs) have gained increasing attention because of their high prevalence and mortality worldwide. Epidemiological studies revealed that intake of fruits, vegetables, nuts, and cereals could reduce the risk of CVDs, and their antioxidants are considered as the main contributors. Moreover, experimental studies showed that some antioxidant natural products and their bioactive compounds exerted beneficial effects on the cardiovascular system, such as polyphenols, polysaccharides, anthocyanins, epigallocatechin gallate, quercetin, rutin, and puerarin. The mechanisms of action mainly included reducing blood pressure, improving lipid profile, ameliorating oxidative stress, mitigating inflammation, and regulating gut microbiota. Furthermore, clinical trials confirmed the cardiovascular-protective effect of some antioxidant natural products, such as soursop, beetroot, garlic, almond, and green tea. In this review, we summarized the effects of some antioxidant natural products and their bioactive compounds on CVDs based on the epidemiological, experimental, and clinical studies, with special attention paid to the relevant mechanisms and clinical trials.

Effects of Different Green Tea Extracts on Chronic Alcohol Induced-Fatty Liver Disease by Ameliorating Oxidative Stress and Inflammation in Mice.

Alcoholic fatty liver disease (AFLD) is a common chronic liver disease and has become a critical global public health problem. Green tea is a popular drink worldwide and contains several bioactive compounds. Different green teas could contain diverse compounds and possess distinct bioactivities. In the present study, the effects of 10 green teas on chronic alcohol induced-fatty liver disease in mice were explored and compared. The results showed that several green teas significantly reduced triacylglycerol levels in serum and liver as well as the aminotransferase activities in mice at a dose of 200 mg/kg, suggesting that they possess hepatoprotective effects. Moreover, several green teas remarkably decreased the expression of cytochrome P450 2E1, the levels of malondialdehyde and 4-hydroxynonenoic acid, and the contents of proinflammatory cytokines, indicating that they could alleviate oxidation damage and inflammation induced by chronic alcohol exposure. In addition, Seven Star Matcha Tea and Selenium-Enriched Matcha Tea could increase glutathione level. Furthermore, the main phytochemical components in green teas were determined and quantified by high-performance liquid chromatography, and the correlation analysis showed that gallic acid, gallocatechin, catechin, chlorogenic acid, and epigallocatechin gallate might at least partially contribute to protective effects on AFLD. In conclusion, Selenium-Enriched Chaoqing Green Tea, Xihu Longjing Tea, Taiping Houkui Tea, and Selenium-Enriched Matcha Tea showed the strongest preventive effects on AFLD. This research also provides the public with new insights about the effects of different green teas on AFLD.

The second harmonic neurons in auditory midbrain of Hipposideros pratti are more tolerant to background white noise.

Although acoustic communication is inevitably influenced by noise, behaviorally relevant sounds are perceived reliably. The noise-tolerant and -invariant responses of auditory neurons are thought to be the underlying mechanism. So, it is reasonable to speculate that neurons with best frequency tuned to behaviorally relevant sounds will play important role in noise-tolerant perception. Echolocating bats live in groups and emit multiple harmonic signals and analyze the returning echoes to extract information about the target features, making them prone to deal with noise in their natural habitat. The echolocation signal of Hipposideros pratti usually contains 3-4 harmonics (H1H4), the second harmonic has the highest amplitude and is thought to play an essential role during echolocation behavior. Therefore, it is reasonable to propose that neurons tuned to the H2, named the H2 neurons, can be more noise-tolerant to background noise. Taking advantage of bat's stereotypical echolocation signal and single-cell recording, our present study showed that the minimal threshold increases (12.2 dB) of H2 neurons in the auditory midbrain were comparable to increase in bat's call intensity (14.2 dB) observed in 70 dB SPL white noise condition, indicating that the H2 neurons could work as background noise monitor. The H2 neurons had higher minimal thresholds and sharper frequency tuning, which enabled them to be more tolerant to background noise. Furthermore, the H2 neurons had consistent best amplitude spikes and sharper intensity tuning in background white noise condition than in silence. Taken together, these results suggest that the H2 neurons might account for noise-tolerant perception of behaviorally relevant sounds.

Self-Assembled Hybrid Nanocomposites for Multimodal Imaging-Guided Photothermal Therapy of Lymph Node Metastasis.

Multimodal imaging-guided therapy holds great potential for precise theranostics of cancer metastasis. However, imaging agents enabling the convergence of complementary modalities with therapeutic functions to achieve perfect theranostics have been less exploited. This study reports the construction of a multifunctional nanoagent (FIP-99mTc) that comprises Fe3O4 for magnetic resonance imaging, radioactive 99mTc for single-photon-emission computed tomography, and IR-1061 to serve for the second near-infrared fluorescence imaging, photoacoustic imaging, and photothermal therapy treatment of cancer metastasis. The nanoagent possessed superior multimodal imaging capability with high sensitivity and resolution attributing to the complement of all the imaging modalities. Moreover, the nanoagent showed ideal photothermal conversion ability to effectively kill tumor cells at low concentration and power laser irradiation. In the in vivo study, FIP-99mTc confirmed the fast accumulation and clear delineation of metastatic lymph nodes within 1 h after administration. Attributing to the efficient uptake and photothermal conversion, FIP-99mTc could raise the temperature of metastatic lymph nodes to 54 °C within 10 min laser irradiation, so as to facilitate tumor cell ablation. More importantly, FIP-99mTc not only played an active role in suppressing cancer growth in metastatic lymph nodes with high efficiency but also could effectively prevent further lung metastasis after resection of the primary tumor. This study proposes a simple but effective theranostic approach toward lymph node metastasis.

Use of Intense Pulsed Light to Mitigate Meibomian Gland Dysfunction for Dry Eye Disease.

Dry Eye Disease (DED) is a common ocular condition that needs prompt diagnosis and careful treatment interventions. If left untreated, it can lead to numerous sight-threatening complications, including ulceration of the cornea, blepharitis, alterations of the tear film, conjunctivitis, and in severe cases, may lead to scarring, thinning, and even perforation of the cornea. Intense pulsed light (IPL) is a non-laser high-intensity light source that has shown to play a valuable role in dry eye disease. Recent evidence from various research works has shown that IPL modifies the mechanism of meibomian gland dysfunction (MGD), which helps to relieve the symptoms of DED. In this review, we demonstrated the mechanism of action of IPL, including its benefits on DED. The emerging evidence shows that the role of IPL in DED is novel and therapeutic. These results direct us to conclude that IPL is a potentially beneficial tool and essential future therapy for dry eye disease. Advances in the treatment of DED will lead to a better quality of life. However, tools to recognize potentially severe side effects of DED earlier in order to treat or prevent them must be developed.

Identification of Structural Features for the Inhibition of OAT3-Mediated Uptake of Enalaprilat by Selected Drugs and Flavonoids.

Enalaprilat is the active metabolite of enalapril, a widely used antihypertension drug. The human organic anion transporter 3 (OAT3), which is highly expressed in the kidney, plays a critical role in the renal clearance of many drugs. While urinary excretion is the primary elimination route of enalaprilat, direct involvement of OAT3 has not been reported so far. In the present study, OAT3-mediated uptake of enalaprilat was first characterized, and the inhibition of OAT3 transport activity was then examined for a number of flavonoid and drug molecules with diverse structures. A varying degree of inhibition potency was demonstrated for flavonoids, with IC50 values ranging from 0.03 to 22.6 µM against OAT3 transport activity. In addition, commonly used drugs such as urate transporter 1 (URAT1) inhibitors also displayed potent inhibition on OAT3-mediated enalaprilat uptake. Pharmacophore and three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses revealed the presence of a polar center and a hydrophobic region involved in OAT3-inhibitor binding. For the polar center, hydroxyl groups present in flavonoids could act as either hydrogen bond donors or acceptors and the number and position of hydroxyl groups were critical drivers for inhibition potency, while carboxyl groups present in some drugs could form ionic bridges with OAT3. The predicted inhibition potencies by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were correlated well with experimental IC50 values. Taken together, the present study identified OAT3-mediated uptake of enalaprilat as an important mechanism for its renal clearance, which may be liable for drug-drug and herb-drug interactions. The established computational models revealed unique structural features for OAT3 inhibitors and could be used for structure-activity relationship (SAR) analysis of OAT3 inhibition. The clinical relevance of the inhibition of OAT3-mediated enalaprilat uptake warrants further investigation, particularly in populations where herbal remedies and drugs are used concomitantly.

Phosphorus supply via a fed-batch strategy improves lipid heterotrophic production of Chlorella regularis.

Intracellular phosphorus (P) accumulation can improve microalgal growth and lipid synthesis. However, large excess of P causes cell poisoning. This study utilized a P-fed-batch strategy to investigate its potential to improve the utilization of the excessive P, while avoiding toxic side effects. This strategy contributed to a more complete utilization of the intracellularly stored P, which enhanced the microalgae biomass by 10-15% by upregulating the brassinosteroid growth hormone gene at a P-fed-batch frequency of 2-8. Furthermore, the lipid content increased by 4-16% via upregulation of lipid synthesis-related genes. As a result, the P-fed-batch strategy significantly increased the lipid production by 13-19%. The content of saturated fatty acid increased by ~ 100%, implying improved combustibility and oxidative stability. This is the first study of this P-fed-batch strategy and provides a new concept for the complete utilization of excessive P.

UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3.

Ursodeoxycholic acid (UDCA) is a major effective constituent of bear bile powder, which is widely used as function food in China and is documented in the Chinese pharmacopoeia as a traditional Chinese medicine. UDCA has been developed as the only accepted therapy by the US FDA for primary biliary cholangitis. Recently, the US FDA granted accelerated approval to obeticholic acid (OCA), a semisynthetic bile acid derivative from chenodeoxycholic acid, for primary biliary cholangitis. However, some perplexing toxicities of UDCA have been reported in the clinic. The present work aimed to investigate the difference between UDCA and OCA in regard to potential metabolic activation through acyl glucuronidation and hepatic accumulation of consequent acyl glucuronides. Our results demonstrated that the metabolic fates of UDCA and OCA were similar. Both UDCA and OCA were predominantly metabolically activated by conjugation to the acyl glucuronide in human liver microsomes. UGT1A3 played a predominant role in the carboxyl glucuronidation of both UDCA and OCA, while UGT2B7 played a major role in their hydroxyl glucuronidation. Further uptake studies revealed that OATP1B1- and 1B3-transfected cells could selectively uptake UDCA acyl glucuronide, but not UDCA, OCA, and OCA acyl glucuronide. In summary, the liver disposition of OCA is different from that of UDCA due to hepatic uptake, and liver accumulation of UDCA acyl glucuronide might be related to the perplexing toxicities of UDCA.

The Neural Mechanism of Number Line Bisection: A fMRI study.

The neural networks involved in number line bisection are poorly understood. We used functional magnetic resonance imaging (fMRI) to investigate these. fMRI was analyzed from 28 healthy volunteers who performed number and physical line bisection tasks (and their respective baselines). Whole brain analyses showed that these two bisection tasks shared common neural correlates in bilateral parietal-frontal networks; furthermore, bilateral parietal-frontal areas, right cerebellum, left insula and supplementary motor area (SMA) showed higher activity when contrasting the number line with a physical line bisection task. Importantly, psychophysiological interaction (PPI) analyses further indicated that left SMA and right cerebellum were connected to parietal-frontal areas for implementing the number line bisection task. Our findings suggested that a visuospatial attention control system was recruited, and mental imagery of a number line was used to find the midpoint of a numerical interval without calculations.