Publications by authors named "Jiao Guo"

165 Publications

NLRP3 inflammasome and IL-1β pathway in type 2 diabetes and atherosclerosis: friend or foe?

Pharmacol Res 2021 Sep 15:105885. Epub 2021 Sep 15.

Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China. Electronic address:

Type 2 diabetes and atherosclerosis have gradually garnered great attention as inflammatory diseases. Previously, the fact that Interleukin-1β (IL-1β) accelerates the development of type 2 diabetes and atherosclerosis has been proved in animal experiments and clinical trials. However, the continued studies found that the effect of IL-1β on type 2 diabetes and atherosclerosis is much more complicated than the negative impact. Nucleotide-binding oligomerization domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome, whose activation and assembly significantly affect the release of IL-1β, is a crucial effector activated by a variety of metabolites. The diversity of NLRP3 activation mode is one of the fundamental reasons for the intricate effects on the progression of type 2 diabetes and atherosclerosis, providing many new insights for us to intervene in metabolic diseases. This review focuses on how NLRP3 inflammasome affects the progression of type 2 diabetes and atherosclerosis and what opportunities and challenges it can bring us.
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http://dx.doi.org/10.1016/j.phrs.2021.105885DOI Listing
September 2021

Comparative genomics provides insights into the aquatic adaptations of mammals.

Proc Natl Acad Sci U S A 2021 Sep;118(37)

BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China.

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (), vascular development (), and heat production by brown adipose tissue () had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.
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http://dx.doi.org/10.1073/pnas.2106080118DOI Listing
September 2021

Protective effect and mechanism of chitooligosaccharides on acetaminophen-induced liver injury.

Food Funct 2021 Sep 8. Epub 2021 Sep 8.

Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Currently, drug-induced liver injury caused by acetaminophen (APAP) is the second leading cause of human liver transplantation. The only clinical antidote treatment for APAP-induced liver injury is -acetyl-L-cysteine (NAC), which has many side effects. Chitooligosaccharides (COS) are processed from naturally occurring chitin through chemical desalting and deproteinization, biological enzymatic hydrolysis and other processes. In this study, we constructed and models of APAP-induced liver injury to study COS of two molecular weights (MWs), which are COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da). The results showed that COST and COSM can significantly reduce the levels of serum ALT and AST and liver MDA, TNF-α, IL-1β and IL-6, and increase the levels and activity of GSH, SOD, GSH-Px and CAT. A mechanistic study found that COST and COSM can significantly reduce the expression of liver CYP2E1, Keap1, -ASK1/ASK1, -MKK4/MKK4, -JNK/JNK, Caspase-3 and Bax and increase the expression of Nrf2, HO-1, eNOS, SOD and Bcl-XL. COST and COSM can inhibit toxic APAP metabolism, inhibit oxidative damage and the apoptosis pathway, increase activation of the liver antioxidant pathway, and ultimately ameliorate APAP-induced liver oxidative damage.
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http://dx.doi.org/10.1039/d1fo00953bDOI Listing
September 2021

Non-shivering Thermogenesis Signalling Regulation and Potential Therapeutic Applications of Brown Adipose Tissue.

Int J Biol Sci 2021 13;17(11):2853-2870. Epub 2021 Jul 13.

Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China.

In mammals, thermogenic organs exist in the body that increase heat production and enhance energy regulation. Because brown adipose tissue (BAT) consumes energy and generates heat, increasing energy expenditure via BAT might be a potential strategy for new treatments for obesity and obesity-related diseases. Thermogenic differentiation affects normal adipose tissue generation, emphasizing the critical role that common transcriptional regulation factors might play in common characteristics and sources. An understanding of thermogenic differentiation and related factors could help in developing ways to improve obesity indirectly or directly through targeting of specific signalling pathways. Many studies have shown that the active components of various natural products promote thermogenesis through various signalling pathways. This article reviews recent major advances in this field, including those the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA), cyclic guanosine monophosphate-GMP-dependent protein kinase G (cGMP-AKT), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), transforming growth factor-β/bone morphogenic protein (TGF-β/BMP), transient receptor potential (TRP), Wnt, nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κΒ), Notch and Hedgehog (Hh) signalling pathways in brown and brown-like adipose tissue. To provide effective information for future research on weight-loss nutraceuticals or drugs, this review also highlights the natural products and their active ingredients that have been reported in recent years to affect thermogenesis and thus contribute to weight loss via the above signalling pathways.
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http://dx.doi.org/10.7150/ijbs.60354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326120PMC
July 2021

Polydatin attenuates hepatic stellate cell proliferation and liver fibrosis by suppressing sphingosine kinase 1.

Biomed Pharmacother 2020 Oct 17;130:110586. Epub 2020 Aug 17.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of "Glycolipid Metabolic Diseases", Ministry of Education of China, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for the Prevention and Treatment of Metabolic Diseases, Guangzhou, 510006, China. Electronic address:

Sphingosine kinase 1 (SphK1) plays critical roles in the activation of hepatic stellate cells (HSCs) and liver fibrosis. Our previous study found that polydatin ameliorates chronic liver injury and fibrosis by inhibiting oxidative stress. However, whether polydatin exerts an anti-fibrotic effect on liver fibrosis dependent on SphK1 signaling is unknown. We aimed to investigate the role of polydatin in SphK1, which mediates HSC activation and liver fibrosis. C57BL/6 mice were induced using CCl 5 μL g i.p. twice a week for 6 weeks and treated with or without polydatin. Human immortalized HSC line (LX-2) was induced using platelet-derived growth factor-BB (PDGF-BB) or adenovirus-SphK1 and treated with polydatin. Hepatic macrophage filtration, collagen deposition, expression of α-smooth muscle, active caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were markedly increased in mice induced by CCl for 6 weeks. In contrast, polydatin attenuated collagen synthesis and hepatocyte apoptosis. Furthermore, polydatin exhibited significant anti-proliferative activity against PDGF-BB-induced activated hepatic stellate cells (HSCs). SphK1 was strongly induced in mice exposed to CCl, whereas its expression and activity were inhibited by polydatin treatment. Finally, SphK1 overexpression in LX-2 cells promoted proliferation of activated HSCs, which could not be reversed by polydatin treatment. These results demonstrate that polydatin attenuates HSC proliferation and activation through inhibition of SphK1 signaling, contributing to the suppression of liver fibrosis.
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http://dx.doi.org/10.1016/j.biopha.2020.110586DOI Listing
October 2020

Effect of different bile acids on the intestine through enterohepatic circulation based on FXR.

Gut Microbes 2021 Jan-Dec;13(1):1949095

Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, China.

Farnesoid X receptor (FXR) is a nuclear receptor for bile acids (BAs) that is widely expressed in the intestine, liver and kidney. FXR has important regulatory impacts on a wide variety of metabolic pathways (such as glucose, lipid, and sterol metabolism) and has been recognized to ameliorate obesity, liver damage, cholestasis and chronic inflammatory diseases. The types of BAs are complex and diverse. BAs link the intestine with the liver through the enterohepatic circulation. BAs derivatives have entered clinical trials for liver disease. In addition to the liver, the intestine is also targeted by BAs. This article reviews the effects of different BAs on the intestinal tract through the enterohepatic circulation from the perspective of FXR, aiming to elucidate the effects of different BAs on the intestinal tract and lay a foundation for new treatment methods.
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http://dx.doi.org/10.1080/19490976.2021.1949095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346203PMC
July 2021

FTZ attenuates liver steatosis and fibrosis in the minipigs with type 2 diabetes by regulating the AMPK signaling pathway.

Biomed Pharmacother 2021 Jun 3;138:111532. Epub 2021 Apr 3.

Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, China; Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), China; Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, China; Guangdong TCM Key Laboratory against Metabolic Diseases, China. Electronic address:

Fufang Zhenzhu Tiaozhi formula (FTZ), a preparation of Chinese herbal medicine, has various pharmacological properties, such as hypoglycemic, hypolipidemic, anticoagulant, and anti-inflammatory activities. Hepatocyte apoptosis is a marker of nonalcoholic steatohepatitis (NASH) and contributes to liver injury, fibrosis, and inflammation. Given the multiple effects of FTZ, we investigated whether FTZ can be a therapeutic agent for NASH and its mechanism. In the present study, we observed that FTZ treatment had an obviously favorable influence on hepatic steatosis and fibrosis in the histopathologic features of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) with NASH minipigs. In addition, immunohistochemical analysis showed increased expression of the fibrotic marker α-smooth muscle actin (α-SMA), and a TUNEL assay revealed increased apoptotic positive hepatic cells in the liver tissues of the model group. Furthermore, FTZ administration reduced the increased expression of α-SMA, and FTZ inhibited apoptosis by affecting Bcl-2/Bax and cleaved caspase-3 expression. Mechanistically, our data suggested that FTZ treatment attenuated hepatic steatosis and fibrosis via the adenosine monophosphate-activated protein kinase (AMPK) pathway. In vitro studies showed that FTZ also attenuated intracellular lipid accumulation in HepG2 cells exposed to palmitic acid (PA) and oleic acid (OA). FTZ upregulated the expression levels of P-AMPK and BCL-2 and downregulated BAX. The changes induced by FTZ were reversed by Compound C, an inhibitor of AMPK. In conclusion, FTZ attenuated NASH by ameliorating steatosis and hepatocyte apoptosis, which is attributable to the regulation of the AMPK pathway.
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http://dx.doi.org/10.1016/j.biopha.2021.111532DOI Listing
June 2021

Ovariectomy Impaired Hepatic Glucose and Lipid Homeostasis and Altered the Gut Microbiota in Mice With Different Diets.

Front Endocrinol (Lausanne) 2021 30;12:708838. Epub 2021 Jun 30.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong Traditional Chinese Medicine (TCM) Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou, China.

The lower incidence of metabolic diseases of women than men and the increasing morbidity of metabolic disorders of menopausal women indicated that hormones produced by ovaries may affect homeostasis of glucose and lipid metabolism, but the underlying mechanisms remain unclear. To explore the functions of ovaries on regulating glucose and lipid metabolism in females, 8 weeks old C57BL/6 mice were preformed ovariectomy and administrated with normal food diet (NFD) or high fat diet (HFD). Six weeks after ovariectomy, blood biochemical indexes were tested and the morphology and histology of livers were checked. The expression levels of genes related to glucose and lipid metabolism in liver were detected through transcriptome analysis, qPCR and western blot assays. 16S rDNA sequence was conducted to analyze the gut microbiota of mice with ovariectomy and different diets. The serum total cholesterol (TC) was significantly increased in ovariectomized (OVX) mice fed with NFD (OVXN), and serum low density lipoprotein-cholesterol (LDL-C) was significantly increased in both OVXN mice and OVX mice fed with HFD (OVXH). The excessive glycogen storage was found in livers of 37.5% mice from OVXN group, and lipid accumulation was detected in livers of the other 62.5% OVXN mice. The OVXN group was further divided into OVXN-Gly and OVXN-TG subgroups depending on histological results of the liver. Lipid drops in livers of OVXH mice were more and larger than other groups. The expression level of genes related with lipogenesis was significantly increased and the expression level of genes related with β-oxidation was significantly downregulated in the liver of OVXN mice. Ovariectomy also caused the dysbiosis of intestinal flora of OVXN and OVXH mice. These results demonstrated that hormones generated by ovaries played important roles in regulating hepatic glucose and lipid metabolism and communicating with the gut microbiota in females.
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http://dx.doi.org/10.3389/fendo.2021.708838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278766PMC
June 2021

The Efficacy and Safety of Chinese Medicine Fufang Zhenzhu Tiaozhi Capsule (FTZ) in the Treatment of Diabetic Coronary Heart Disease: Study Protocol for Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Diabetes Metab Syndr Obes 2021 14;14:2651-2659. Epub 2021 Jun 14.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, People's Republic of China.

Background: Diabetic coronary heart disease (DCHD), the main macrovascular complication of type 2 diabetes mellitus (T2DM), is greatly harmful to T2DM patients. Traditional Chinese medicine (TCM) is an alternative and effective therapy to delay the development of macrovascular diseases, but the existing evidence of its efficacy and safety is insufficient. The aim of this multicenter, randomized, double-blind, placebo-controlled trial is to evaluate the efficacy and safety of Chinese Medicine Fufang Zhenzhu Tiaozhi capsule (FTZ) in treating DCHD.

Patients And Methods: This study includes a 2-week run-in, 52-week treatment, and 52-week post-treatment follow-up. A total of 160 participants will be recruited and randomized into two groups. The treatment group will receive FTZ and basic treatment, while the control group will receive the placebo and basic treatment. The primary outcome is the combined outcome including the major adverse cardiovascular events, coronary restenosis, and unplanned revascularization. The combined secondary outcomes include all-cause mortality, acute coronary syndrome, ischemic stroke, heart failure, unplanned re-hospitalization mainly caused by acute complications of diabetes, other thromboembolic events, and TCM symptom indicators. The safety outcomes and adverse events will also be evaluated in this trial.

Discussion: This trial evaluates the clinical effectiveness and safety of FTZ in patients with DCHD. The results are important to further explore the effectiveness of the comprehensive strategy "Tiao Gan Qi Shu Hua Zhuo" (modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness) in the prevention and control of glucolipid metabolic disorders (GLMD) including DCHD and T2DM. On the other hand, this study is the first trial of FTZ to observe cardiovascular outcomes through long-term follow-up after treatment of DCHD, which is of great value.

Trial Registration: This trial was registered in the Chinese Clinical Trial Registry on April 07, 2019 (No. ChiCTR1900022345).
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http://dx.doi.org/10.2147/DMSO.S309419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214008PMC
June 2021

Mechanism through Which Retrocyclin Targets Flavivirus Multiplication.

J Virol 2021 07 12;95(15):e0056021. Epub 2021 Jul 12.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.

Currently, there are no approved drugs for the treatment of flavivirus infection. Accordingly, we tested the inhibitory effects of the novel θ-defensin retrocyclin-101 (RC-101) against flavivirus infection and investigated the mechanism underlying the potential inhibitory effects. First, RC-101 robustly inhibited both Japanese encephalitis virus (JEV) and Zika virus (ZIKV) infections. RC-101 exerted inhibitory effects on the entry and replication stages. Results also indicated that the nonstructural protein NS2B-NS3 serine protease might serve as a potential viral target. Furthermore, RC-101 inhibited protease activity at the micromolar level. We also demonstrated that with respect to the glycoprotein E protein of flavivirus, the DE loop of domain III (DIII), which is the receptor-binding domain of the E protein, might serve as another viral target of RC-101. Moreover, a JEV DE mutant exhibited resistance to RC-101, which was associated with deceased binding affinity of RC-101 to DIII. These findings provide a basis for the development of RC-101 as a potential candidate for the treatment of flavivirus infection. Retrocyclin is an artificially humanized circular θ-defensin peptide, containing 18 residues, previously reported to possess broad antimicrobial activity. In this study, we found that retrocyclin-101 inhibited flavivirus (ZIKV and JEV) infections. Retrocyclin-101 inhibited NS2B-NS3 serine protease activity, suggesting that the catalytic triad of the protease is the target. Moreover, retrocyclin-101 bound to the DE loop of the E protein of flavivirus, which prevented its entry.
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http://dx.doi.org/10.1128/JVI.00560-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274595PMC
July 2021

Role of 2‑series prostaglandins in the pathogenesis of type 2 diabetes mellitus and non‑alcoholic fatty liver disease (Review).

Int J Mol Med 2021 06 28;47(6). Epub 2021 Apr 28.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.

Nowadays, metabolic syndromes are emerging as global epidemics, whose incidence are increasing annually. However, the efficacy of therapy does not increase proportionately with the increased morbidity. Type 2 diabetes mellitus (T2DM) and non‑alcoholic fatty liver disease (NAFLD) are two common metabolic syndromes that are closely associated. The pathogenic mechanisms of T2DM and NAFLD have been studied, and it was revealed that insulin resistance, hyperglycemia, hepatic lipid accumulation and inflammation markedly contribute to the development of these two diseases. The 2‑series prostaglandins (PGs), a subgroup of eicosanoids, including PGD, PGE, PGF and PGI, are converted from arachidonic acid catalyzed by the rate‑limiting enzymes cyclooxygenases (COXs). Considering their wide distribution in almost every tissue, 2‑series PG pathways exert complex and interlinked effects in mediating pancreatic β‑cell function and proliferation, insulin sensitivity, fat accumulation and lipolysis, as well as inflammatory processes. Previous studies have revealed that metabolic disturbances, such as hyperglycemia and hyperlipidemia, can be improved by treatment with COX inhibitors. At present, an accumulating number of studies have focused on the roles of 2‑series PGs and their metabolites in the pathogenesis of metabolic syndromes, particularly T2DM and NAFLD. In the present review, the role of 2‑series PGs in the highly intertwined pathogenic mechanisms of T2DM and NAFLD was discussed, and important therapeutic strategies based on targeting 2‑series PG pathways in T2DM and NAFLD treatment were provided.
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http://dx.doi.org/10.3892/ijmm.2021.4947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083810PMC
June 2021

High dose lithium chloride causes colitis through activating F4/80 positive macrophages and inhibiting expression of Pigr and Claudin-15 in the colon of mice.

Toxicology 2021 06 24;457:152799. Epub 2021 Apr 24.

Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Disease, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China. Electronic address:

Objective: Lithium chloride (LiCl) was a mood stabilizer for bipolar affective disorders and it could activate Wnt/β-catenin signaling pathway both in vivo and in vitro. Colon is one of a very susceptible tissues to Wnt signaling pathway, and so it would be very essential to explore the toxic effect of a high dose of LiCl on colon.

Methods: C57BL/6 mice were injected intraperitoneally with 200 mg/kg LiCl one dose a day for 5 days to activate Wnt signal pathway in intestines. H&E staining was used to assess the colonic tissues of mice treated with high dose of LiCl. The expression of inflammation-associated genes and tight junction-associated genes in colons was measured using qPCR, Western blot and immunostaining methods. The gut microbiome was tested through 16S rDNA gene analysis.

Results: The differentiation of enteroendocrine cells in colon was inhibited by treatment of 200 mg/kg LiCl. The F4/80 positive macrophages in colon were activated by high dose of LiCl, and migrated from the submucosa to the lamina propria. The expression of pro-inflammatory genes TNFα and IL-1β was increased in the colon of high dose of LiCl treated mice. Clostridium_sp_k4410MGS_306 and Prevotellaceae_UCG_001 were specific and predominant for the high dose of LiCl treated mice. The expression of IgA coding genes, Pigr and Claudin-15 was significantly decreased in the colon tissues of the high dose of LiCl treated mice.

Conclusion: 200 mg/kg LiCl might cause the inflammation in colon of mice through activating F4/80 positive macrophages and inhibiting the expression of IgA coding genes in plasma cells and the expression of Pigr and Claudin-15 in colonic epithelial cells, providing evidences for the toxic effects of high dose of LiCl on colon.
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http://dx.doi.org/10.1016/j.tox.2021.152799DOI Listing
June 2021

Comparative study on the structures of intra- and extra-cellular polysaccharides from Penicillium oxalicum and their inhibitory effects on galectins.

Int J Biol Macromol 2021 Jun 15;181:793-800. Epub 2021 Apr 15.

Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China. Electronic address:

Here, we compare the content and composition of polysaccharides derived from the mycelium (40.4 kDa intracellular polysaccharide, IPS) and culture (27.2 kDa extracellular polysaccharide, EPS) of Penicillium oxalicum. Their chemical structures investigated by IR, NMR, enzymolysis and methylation analysis indicate that both IPS and EPS are galactomannans composed of α-1,2- mannopyranose (Manp) and α-1,6-Manp in a backbone ratio of ~3:1, respectively, both decorated with β-l,5-galactofuranose (Galf) side chains. A few β-l,6-Galf residues were also detected in the IPS fraction. EPS and IPS have different molecular weights (Mw) and degrees of branching. IPS obtained by alkaline extraction of P. oxalicum have been reported to be galactofuranans, a composition different from our IPS. Up to now, there have been no reports on the fine structure of EPS. Our results of galectin-mediated hemagglutination demonstrate that IPS exhibits greater inhibitory effects on five galectins compared with EPS. In addition, we find that Galf, a five-membered ring form of galactose, can also inhibit galectins. IPS may provide a new source of galectin inhibitors. These results increase our understanding of structure-activity relationships of polysaccharides as galectin inhibitors.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.042DOI Listing
June 2021

Finger Citron Extract Ameliorates Glycolipid Metabolism and Inflammation by Regulating GLP-1 Secretion via TGR5 Receptors in Obese Rats.

Evid Based Complement Alternat Med 2021 27;2021:6623379. Epub 2021 Mar 27.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, China.

Finger citron (FC) is one of many traditional Chinese herbs that have been used to treat obesity. The aim of this study was to elucidate the pharmacological effects and mechanisms of FC on obese rats. Rats were fed with a high-fat diet as a model of obesity and treated with FC at three different dosages for 6 weeks. Pathology in liver tissue was observed. Glucose levels, lipids levels, and inflammatory indicators in serum were evaluated by enzyme-linked immunosorbent assay. Furthermore, the expression of protein-coupled receptor 5 (TGR5) pathway genes in rat colon tissue was detected by reverse transcription-polymerase chain reaction analysis (RT-PCR). Our result revealed that FC alleviates obesity by reducing body weight (BW) and waist circumference, managing inflammation and improving glycolipid metabolism, liver function, and liver lipid peroxidation in vivo. In addition, the mechanism of FC on obesity is possibly the stimulation of glucagon-like peptide-1 (GLP-1) secretion by activating the TGR5 pathway in intestinal endocrine cells. Our studies highlight the obesity reduction effects of FC and one of the mechanisms may be the activation of the TGR5 pathway in intestinal endocrine cells.
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http://dx.doi.org/10.1155/2021/6623379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021467PMC
March 2021

Molecular mechanism of Fufang Zhenzhu Tiaozhi capsule in the treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease based on network pharmacology and validation in minipigs.

J Ethnopharmacol 2021 Jun 23;274:114056. Epub 2021 Mar 23.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, 510006, China. Electronic address:

Ethnopharmacological Relevance: Fufang Zhenzhu Tiaozhi formula (FTZ) of which a patented preparation of Chinese herbal medicine has been well documented with significant clinical curative effect for hyperglycemia and hyperlipidemia. Because of the complexity of the chemical constituents of Chinese herbal formulas, the holistic pharmacological mechanism of FTZ acting on type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) remains unclear.

Aim Of The Study: To investigate the pharmacological efficacy and mechanism of FTZ in the treatment of T2DM accompanied by NAFLD.

Materials And Methods: Network pharmacology and validation in minipigs were used in this study. First, potential bioactive compounds of FTZ were identified by the traditional Chinese medicine system pharmacology technology platform (TCMSP). Then, targets of compounds were gathered using DrugBank, SwissTargetPrediction and TCMSP, while targets for T2DM and NAFLD were collected from CTD (compounds-targets-diseases network) and GeneCards. Common targets were defined as direct therapeutic targets acting on T2DM with NAFLD. In addition, crucial targets were chosen by the protein-protein interaction (PPI) network and contribution to compound-therapeutic targets in T2DM with the NAFLD network. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by FTZ. Candidate patterns selected by network pharmacology were tested in the minipigs model of T2DM with NAFLD. Measurements of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and fasting blood glucose (FBG) in the blood and the expression levels of proteins, including PI3K-AKT and HIF-1α, in the livers of the minipigs were followed by the administration of FTZ.

Results: A total of 116 active compounds and 82 potential targets related to T2DM and NAFLD were found. Pathway and functional enrichment analysis showed that FTZ mainly regulates metabolism-related pathways, including PI3K-AKT, HIF-1α, TNFα and MAPK. Animal experiments showed that FTZ treatment significantly reduced the serum levels of TG, TC, LDL-C and FBG, increased serum levels of HDL-C, ameliorated systemic insulin resistance (IR), and attenuated liver damage in minipigs with T2DM and NAFLD. FTZ treatment has an obviously favorable influence on hepatic steatosis and liver lipid accumulation in the histopathologic features of HE, Oil red O staining, and electron microscopy. Mechanistically, FTZ improved liver metabolism by increasing the phosphorylation of PI3K-AKT and decreasing the expression of HIF-1α.

Conclusion: Network pharmacology was supported by experimental studies, which indicated that FTZ has demonstrated therapeutic benefits in T2DM and NAFLD by regulating the PI3K-AKT and HIF-1α signaling pathways.
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http://dx.doi.org/10.1016/j.jep.2021.114056DOI Listing
June 2021

Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats.

Evid Based Complement Alternat Med 2021 6;2021:6617586. Epub 2021 Mar 6.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, China.

The progressive increase of metabolic diseases underscores the necessity for developing effective therapies. Although we found Tian-Huang formula (THF) could alleviate metabolic disorders, the underlying mechanism remains to be fully understood. In the present study, firstly, male Sprague-Dawley rats were fed with high-fat diet plus high-fructose drink (HFF, the diet is about 60% of calories from fat and the drink is 12.5% fructose solution) for 14 weeks to induce hepatosteatosis and glucose intolerance and then treated with THF (200 mg/kg) for 4 weeks. Then, metabolomics analysis was performed with rat liver samples and following the clues illustrated by Ingenuity Pathway Analysis (IPA) with the metabolomics discoveries, RT-qPCR and Western blotting were carried out to validate the putative pathways. Our results showed that THF treatment reduced the body weight from 735.1 ± 81.29 to 616.3 ± 52.81 g and plasma triglyceride from 1.5 ± 0.42 to 0.88 ± 0.33 mmol/L; meanwhile, histological examinations of hepatic tissue and epididymis adipose tissue showed obvious alleviation. Compared with the HFF group, the fasting serum insulin and blood glucose level of the THF group were improved from 20.77 ± 6.58 to 9.65 ± 5.48 mIU/L and from 8.96 ± 0.56 to 7.66 ± 1.25 mmol/L, respectively, so did the serum aspartate aminotransferase, insulin resistance index, and oral glucose tolerance ( = 0.0019, 0.0053, and 0.0066, respectively). Furthermore, based on a list of 32 key differential endogenous metabolites, the molecular networks generated by IPA suggested that THF alleviated glucose intolerance and hepatosteatosis by activating phosphatidylinositol-3 kinase (PI3K) and low-density lipoprotein receptor (LDL-R) involved pathways. RT-qPCR and Western blotting results confirmed that THF alleviated hepatic steatosis and glucose intolerance partly through protein kinase B- (AKT-) sterol regulatory element-binding protein (SREBP) nexus. Our findings shed light on molecular mechanisms of THF on alleviating metabolic diseases and provided further evidence for developing its therapeutic potential.
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http://dx.doi.org/10.1155/2021/6617586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955866PMC
March 2021

The traditional Chinese medicine formula Fufang-Zhenzhu-Tiaozhi protects myocardia from injury in diabetic minipigs with coronary heart disease.

Biomed Pharmacother 2021 May 5;137:111343. Epub 2021 Mar 5.

Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, China; Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), China; Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory against Metabolic Diseases, China. Electronic address:

Background And Purpose: Diabetes mellitus (DM) is a major risk factor for coronary heart disease (CHD). Previous research has reported that the Fufang-Zhenzhu-Tiaozhi (FTZ) formula has obvious effects on the treatment of dyslipidemia and hyperglycemia. In the present study, we intended to establish a convenient DM-CHD model in minipigs and investigated the protective effect of FTZ against myocardial injury and its mechanism.

Methods: The DM-CHD model was established by a high-fat/high-sucrose/high-cholesterol diet (HFSCD) combined with balloon injury in the coronary artery. Subsequently, sixteen Wuzhishan minipigs were assigned to three groups: control group, model group, and FTZ group. The model group and FTZ group were given a HFSCD, while the control group was given a normal diet (ND). FTZ was given with meals in the FTZ group. During this time, biochemical parameters, such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL-C), and fasting blood glucose (FBG), were measured by using testing kits. Insulin (INS) was determined by ELISA, and the homeostasis model assessment index of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance levels. After FTZ administration, the plasma levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) were measured by using ELISA kits to evaluate myocardial injury. Coronary artery stenosis was analyzed by angiographic and HE staining. Myocardial ischemia was assayed with electrocardiogram (ECG). Moreover, cytokines, including interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), and tumor necrosis factor-alpha (TNF-α), were measured by ELISA kits to assess inflammation. The myocardial tissue was collected, and the pathological morphology was observed by transmission electron microscopy (TEM), HE staining, and Masson staining. Western blots were used to detect the expression of PI3K, AKT, p-AKT, p-NF-κB, and NF-κB.

Results: A DM-CHD model in minipigs with glucose-lipid metabolism disorder, coronary artery incrassation and myocardial damage was successfully established through balloon injury in the coronary artery combined with HFSCD. FTZ effectively inhibited coronary artery incrassation and protected the myocardium against injury in DM-CHD minipigs. FTZ decreased proinflammatory cytokine levels and upregulated the protein expression of the PI3K/Akt pathway in the myocardium.

Conclusions: A novel DM-CHD model in minipigs was successfully established through balloon injury in the coronary artery combined with HFSCD. FTZ has a protective effect against myocardial injury in DM-CHD by inhibiting inflammation and activating the PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1016/j.biopha.2021.111343DOI Listing
May 2021

RNA Interference Screening Reveals Requirement for Platelet-Derived Growth Factor Receptor Beta in Japanese Encephalitis Virus Infection.

Antimicrob Agents Chemother 2021 05 18;65(6). Epub 2021 May 18.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China

Mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide and is associated with high morbidity and mortality. To identify potential host therapeutic targets, a high-throughput receptor tyrosine kinase small interfering RNA library screening was performed with recombinant JEV particles. Platelet-derived growth factor receptor beta (PDGFRβ) was identified as a hit after two rounds of screening. Knockdown of blocked JEV infection and transcomplementation of PDGFRβ could partly restore its infectivity. The PDGFRβ inhibitor imatinib, which has been approved for the treatment of malignant metastatic cancer, protected mice against JEV-induced lethality by decreasing the viral load in the brain while abrogating the histopathological changes associated with JEV infection. These findings demonstrated that PDGFRβ is important in viral infection and provided evidence for the potential to develop imatinib as a therapeutic intervention against JEV infection.
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http://dx.doi.org/10.1128/AAC.00113-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316074PMC
May 2021

A risk score based on baseline risk factors for predicting mortality in COVID-19 patients.

Curr Med Res Opin 2021 06 10;37(6):917-927. Epub 2021 Apr 10.

Department of Orthopedics, The First People's Hospital of Jingmen affiliated to Hubei Minzu University, Jingmen, China.

Background: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources.

Methods: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses.

Results: Eight factors, namely, xygen saturation, blood rea nitrogen, espiratory rate, admission before the date the national aximum number of daily new cases was reached, ge, rocalcitonin, -reactive protein (CRP), and absolute eutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71;  < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts.

Conclusions: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.
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http://dx.doi.org/10.1080/03007995.2021.1904862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054492PMC
June 2021

Effects of N-Linked Glycan on Lassa Virus Envelope Glycoprotein Cleavage, Infectivity, and Immune Response.

Virol Sin 2021 Aug 10;36(4):774-783. Epub 2021 Mar 10.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.

Lassa virus (LASV) belongs to the Mammarenavirus genus (family Arenaviridae) and causes severe hemorrhagic fever in humans. The glycoprotein complex (GPC) contains eleven N-linked glycans that play essential roles in GPC functionalities such as cleavage, transport, receptor recognition, epitope shielding, and immune response. We used three mutagenesis strategies (asparagine to glutamine, asparagine to alanine, and serine/tyrosine to alanine mutants) to abolish individual glycan chain on GPC and found that all the three strategies led to cleavage inefficiency on the 2nd (N89), 5th (N119), or 8th (N365) glycosylation motif. To evaluate N to Q mutagenesis for further research, it was found that deletion of the 2nd (N89Q) or 8th (N365Q) glycan completely inhibited the transduction efficiency of pseudotyped particles. We further investigated the role of individual glycan on GPC-mediated immune response by DNA immunization of mice. Deletion of the individual 1st (N79Q), 3rd (N99Q), 5th (N119Q), or 6th (N167Q) glycan significantly enhanced the proportion of effector CD4 cells, whereas deletion of the 1st (N79Q), 2nd (N89Q), 3rd (N99Q), 4th (N109Q), 5th (N119Q), 6th (N167Q), or 9th (N373Q) glycan enhanced the proportion of CD8 effector T cells. Deletion of specific glycan improves the Th1-type immune response, and abolishment of glycan on GPC generally increases the antibody titer to the glycan-deficient GPC. However, the antibodies from either the mutant or WT GPC-immunized mice show little neutralization effect on wild-type LASV. The glycan residues on GPC provide an immune shield for the virus, and thus represent a target for the design and development of a vaccine.
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http://dx.doi.org/10.1007/s12250-021-00358-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945000PMC
August 2021

Cordycepin Ameliorates Nonalcoholic Steatohepatitis by Activation of the AMP-Activated Protein Kinase Signaling Pathway.

Hepatology 2021 Aug;74(2):686-703

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.

Background And Aims: Nonalcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), has become a major cause of liver transplantation and liver-associated death. NASH is the hepatic manifestation of metabolic syndrome and is characterized by hepatic steatosis, inflammation, hepatocellular injury, and different degrees of fibrosis. However, there is no US Food and Drug Administration-approved medication to treat this devastating disease. Therapeutic activators of the AMP-activated protein kinase (AMPK) have been proposed as a potential treatment for metabolic diseases such as NASH. Cordycepin, a natural product isolated from the traditional Chinese medicine Cordyceps militaris, has recently emerged as a promising drug candidate for metabolic diseases.

Approach And Results: We evaluated the effects of cordycepin on lipid storage in hepatocytes, inflammation, and fibrosis development in mice with NASH. Cordycepin attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes subjected to metabolic stress. In addition, cordycepin treatment significantly and dose-dependently decreased the elevated levels of serum aminotransferases in mice with diet-induced NASH. Furthermore, cordycepin treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration, and hepatic fibrosis in mice. In vitro and in vivo mechanistic studies revealed that a key mechanism linking the protective effects of cordycepin were AMPK phosphorylation-dependent, as indicated by the finding that treatment with the AMPK inhibitor Compound C abrogated cordycepin-induced hepatoprotection in hepatocytes and mice with NASH.

Conclusion: Cordycepin exerts significant protective effects against hepatic steatosis, inflammation, liver injury, and fibrosis in mice under metabolic stress through activation of the AMPK signaling pathway. Cordycepin might be an AMPK activator that can be used for the treatment of NASH.
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http://dx.doi.org/10.1002/hep.31749DOI Listing
August 2021

Screening of Botanical Drugs against Lassa Virus Entry.

J Virol 2021 Feb 3. Epub 2021 Feb 3.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China

Lassa virus (LASV) belongs to the Old World genus (family ). At present, there are no approved drugs or vaccines specific for LASV. In this study, high-throughput screening of a botanical drug library was performed against LASV entry using a pseudotype virus bearing the LASV envelope glycoprotein complex (GPC). Two hit compounds, bergamottin and casticin, were identified as micromolar range inhibitors of LASV entry. A mechanistic study revealed that casticin inhibited LASV entry by blocking low pH-induced membrane fusion. Analysis of adaptive mutants demonstrated that the F446L mutation, located in the transmembrane domain of GP2, conferred resistance to casticin. Furthermore, casticin antiviral activity extends to the New World (NW) pathogenic mammarenaviruses, and mutation of the conserved F446 also conferred resistance to casticin in these viruses. Unlike casticin, bergamottin showed little effect on LASV GPC-mediated membrane fusion, instead inhibiting LASV entry by blocking endocytic trafficking. Notably, both compounds showed inhibitory effects on authentic lymphocytic choriomeningitis virus. Our study shows that both casticin and bergamottin are candidates for LASV therapy and that the conserved F446 in LASV GPC is important in drug resistance in mammarenaviruses. Currently, there is no approved therapy to treat Lassa fever (LASF). Our goal was to identify potential candidate molecules for LASF therapy. Herein, we screened a botanical drug library and identified two compounds, casticin and bergamottin, that inhibited LASV entry via different mechanisms.
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http://dx.doi.org/10.1128/JVI.02429-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103687PMC
February 2021

Soil Moisture Retrieval in Farmland Areas with Sentinel Multi-Source Data Based on Regression Convolutional Neural Networks.

Sensors (Basel) 2021 Jan 28;21(3). Epub 2021 Jan 28.

College of Mechanical and Electronic Engineering, Northwest A&F University, Yangling 712100, China.

As an important component of the earth ecosystem, soil moisture monitoring is of great significance in the fields of crop growth monitoring, crop yield estimation, variable irrigation, and other related applications. In order to mitigate or eliminate the impacts of sparse vegetation covers in farmland areas, this study combines multi-source remote sensing data from Sentinel-1 radar and Sentinel-2 optical satellites to quantitatively retrieve soil moisture content. Firstly, a traditional Oh model was applied to estimate soil moisture content after removing vegetation influence by a water cloud model. Secondly, support vector regression (SVR) and generalized regression neural network (GRNN) models were used to establish the relationships between various remote sensing features and real soil moisture. Finally, a regression convolutional neural network (CNNR) model is constructed to extract deep-level features of remote sensing data to increase soil moisture retrieval accuracy. In addition, polarimetric decomposition features for real Sentinel-1 PolSAR data are also included in the construction of inversion models. Based on the established soil moisture retrieval models, this study analyzes the influence of each input feature on the inversion accuracy in detail. The experimental results show that the optimal combination of and root mean square error (RMSE) for SVR is 0.7619 and 0.0257 cm/cm, respectively. The optimal combination of and RMSE for GRNN is 0.7098 and 0.0264 cm/cm, respectively. Especially, the CNNR model with optimal feature combination can generate inversion results with the highest accuracy, whose and RMSE reach up to 0.8947 and 0.0208 cm/cm, respectively. Compared to other methods, the proposed algorithm improves the accuracy of soil moisture retrieval from synthetic aperture radar (SAR) and optical data. Furthermore, after adding polarization decomposition features, the of CNNR is raised by 0.1524 and the RMSE of CNNR decreased by 0.0019 cm/cm on average, which means that the addition of polarimetric decomposition features effectively improves the accuracy of soil moisture retrieval results.
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http://dx.doi.org/10.3390/s21030877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866275PMC
January 2021

Cigarette smoking exposure breaks the homeostasis of cholesterol and bile acid metabolism and induces gut microbiota dysbiosis in mice with different diets.

Toxicology 2021 02 10;450:152678. Epub 2021 Jan 10.

Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, 510006, PR China. Electronic address:

Exposure of humans to second-hand smoking (SHS) increases glucose and lipid metabolic disorders. The link of hepatic metabolic dysfunction to environmental cigarette smoking has been noticed, but the related mechanism is still unclear. C57BL/6 mice with normal food diet (NFD) or high fat diet (HFD) were exposed to 15 min cigarette smoking twice a day in a 0.038 m box for 4 weeks, and the concentration of nicotine in the air of the box was 21.05 mg/m during the smoke exposure. Liver tissues and serum were collected for gene expression and biochemistry test. The fecal microbiota was also checked through 16S rDNA sequences. Cigarette smoking exposure increased the accumulation of total cholesterol (TC) in liver, and the expression of cholesterol synthesis-related genes was upregulated. The expression of CYP8B1 protein was significantly down-regulated, and the ratio of cholic acid (CA) to chenodeoxycholic acid (CDCA) was significantly reduced in the liver of mice exposed to cigarette smoking especially for HFD group. Cigarette smoking exposure caused insulin resistance in the liver of mice with HFD. The composition of the gut microbiota was altered with the exposure of cigarette smoking, and the change of the distribution of primary bile acids might be one of the reasons. It was concluded that cigarette smoking would break the homeostasis of cholesterol and bile acids metabolism and changed the composition of gut microbiota. Our discoveries confirmed that smoking bans are important for the public health.
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http://dx.doi.org/10.1016/j.tox.2021.152678DOI Listing
February 2021

Advances in the preparation and assessment of the biological activities of chitosan oligosaccharides with different structural characteristics.

Food Funct 2021 Feb;12(3):926-951

Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou (510006), China.

Chitosan oligosaccharides (COSs) are widely used biopolymers that have been studied in relation to a variety of abnormal biological activities in the food and biomedical fields. Since different COS preparation technologies produce COS compounds with different structural characteristics, it has not yet been possible to determine whether one or more chito-oligomers are primarily responsible for the bioactivity of COSs. The inherent biocompatibility, mucosal adhesion and nontoxic nature of COSs are well documented, as is the fact that they are readily absorbed from the intestinal tract, but their structure-activity relationship requires further investigation. This review summarizes the methods used for COS preparation, and the research findings with regard to the antioxidant, anti-inflammatory, anti-obesity, bacteriostatic and antitumour activity of COSs with different structural characteristics. The correlation between the molecular structure and bioactivities of COSs is described, and new insights into their structure-activity relationship are provided.
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http://dx.doi.org/10.1039/d0fo02768eDOI Listing
February 2021

[Toll-like Receptor Agonists in Radiation Protection].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2020 Dec;42(6):805-809

Department of Pharmaceutica,Institute of Radiation Medicine,CAMS and PUMC,Tianjin 300192,China.

Ionizing radiation causes the massive apoptosis of human tissue cells,leading to dysfunction of the gastrointestinal tract and hematopoietic system.Thus,high-efficiency,low-toxicity radiation protection drugs are urgently needed.Toll-like receptor agonists have been developed based on the anti-apoptotic mechanism of tumor cells in recent years,which exert their radioprotective effects by activating downstream pathways,mainly nuclear factor-κB.Here we elucidate several agonists of Toll-like receptors involved in radiation protection,with an attempt to inform the research and development of new radiation protection agents.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12119DOI Listing
December 2020

EpCAM is essential for maintenance of the small intestinal epithelium architecture via regulation of the expression and localization of proteins that compose adherens junctions.

Int J Mol Med 2021 02 10;47(2):621-632. Epub 2020 Dec 10.

Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine and Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China and Institute of Chinese Medicine, Guangdong Pharmaceutical University and Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, Guangdong 510006, P.R. China.

Epithelial cell adhesion molecule (EpCAM) is highly expressed in mammalian intestines, and is essential for maintaining the homeostasis of the intestinal epithelium. EpCAM protein is localized at tight junctions and the basolateral membrane of the intestinal epithelium, where it interacts with many cell adhesion molecules. To explore the molecular functions of EpCAM in regulating adherens junctions in the intestinal epithelium, EpCAM knockout embryos and newborn pups were analyzed. Hematoxylin and eosin staining was used to assess the histology of the duodenum, jejunum, ileum and colon from wild-type and EpCAM‑/‑ mice at E18.5, P0 and P3. The expression and localization of adherens junction‑associated genes and genes that encode the proteins that participate in the assembly of adherens junctions were measured at the mRNA and protein levels using qPCR, western blot analysis and immunofluorescence staining. The results showed that although there was no significant damage to the intestines of EpCAM‑/‑ mice at E18.5 and P0, they were significantly damaged at P3 in mutant mice. The expression of adherens junction‑associated genes in EpCAM mutant mice was normal at the mRNA level from E18.5 to P3, but their protein levels were gradually reduced and mislocalized from E18.5 to P3. The expression of nectin 1, which can regulate the assembly and adhesion activity of E‑cadherin, was also gradually reduced at both the mRNA and protein levels in the intestinal epithelium of EpCAM mutant mice from E18.5 to P3. In summary, the loss of EpCAM may cause the reduction and mislocalization of proteins that compose adherens junctions partly via the downregulation of nectin 1 in the intestines.
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http://dx.doi.org/10.3892/ijmm.2020.4815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797445PMC
February 2021

Local Epidermal Endocrine Estrogen Protects Human Melanocytes against Oxidative Stress, a Novel Insight into Vitiligo Pathology.

Int J Mol Sci 2020 Dec 29;22(1). Epub 2020 Dec 29.

Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, 5450051 Osaka, Japan.

As the outermost barrier of the body, skin is a major target of oxidative stress. In the brain, estrogen has been reported synthesized locally and protects neurons from oxidative stress. Here, we explored whether estrogen is also locally synthesized in the skin to protect from oxidative stress and whether aberrant local estrogen synthesis is involved in skin disorders. Enzymes and estrogen receptor expression in skin cells were examined first by quantitative real-time PCR and Western blot analyses. Interestingly, the estrogen synthesis enzyme was mainly localized in epidermal keratinocytes and estrogen receptors were mainly expressed in melanocytes among 13 kinds of cultured human skin cells. The most abundant estrogen synthesis enzyme expressed in the epidermis was 17β-hydroxysteroid dehydrogenase 1 (HSD17β1) localized in keratinocytes, and the most dominant estrogen receptor expressed in the epidermis was G protein-coupled estrogen receptor 1 (GPER1) in melanocytes. To investigate whether keratinocyte-derived estradiol could protect melanocytes from oxidative stress, cultured human primary epidermal melanocytes (HEMn-MPs) were treated with HO in the presence or absence of 17β estradiol or co-cultured with siRNA-transfected keratinocytes. Keratinocyte-derived estradiol exhibited protective effects against HO-induced cell death. Further, reduced expression of HSD17β1 in the epidermis of skin from vitiligo patients was observed compared to the skin from healthy donors or in the normal portions of the skin in vitiligo patients. Our results suggest a possible new target for interventions that may be used in combination with current therapies for patients with vitiligo.
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http://dx.doi.org/10.3390/ijms22010269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794688PMC
December 2020

Comprehensive chemical analysis of Zhenshu Tiaozhi formula and its effect on ameliorating glucolipid metabolic disorders in diabetic rats.

Biomed Pharmacother 2021 Jan 8;133:111060. Epub 2020 Dec 8.

Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China. Electronic address:

The present study aims to reveal the compositions of Zhenshu TiaoZhi formula (FTZ) comprehensively, and investigate whether FTZ ameliorate glucolipid metabolism disorders in diabetic rats with the involvement of glucocorticoids in peripheral insulin-sensitive tissues. The fingerprint was established based on 11 batches of FTZ samples and chemical compostions of FTZ were identified by ultra performance liquid chromatography-time of flight/mass spectrometry (UPLC-TOF/MS). High-fat diet (HFD) and streptozotocin (STZ) induced diabetic rats were orally administrated with 3 and 6 g/kg body weight of FTZ for 8 weeks. Indices of glucolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI) and blood lipids were evaluated after treatment of FTZ. The levels of HPA axis hormones were examined. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to investigate the relative mRNA expressions of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and glucolipid metabolic indicators. A reference fingerprint was established and 93 compounds of FTZ were tentatively identified. In vivo, FTZ treatment exerted antidiabetic and antidyslipidemic effects while decreased the level of corticotropin releasing hormone (CRH). 11β-HSD1 mRNA showed similar trajectory in both liver, adipose and skeletal muscle tissues, which was up-regulated in diabetic group and ameliorated in FTZ groups. Furthermore, the expressions of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and adipose triglyceride lipase (ATGL) were down-regulated in liver and skeletal muscle. These results elucidated the compositions of FTZ comprehensively and indicated its effect on ameliorating glucolipid metabolism of diabetic rats involved hypothalamus-pituitary-adrenal (HPA) axis homeostasis. Down-regulating 11β-HSD1 in insulin-sensitive tissues might be a potential mechanism of FTZ in treating type 2 diabetes mellitus (T2DM).
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http://dx.doi.org/10.1016/j.biopha.2020.111060DOI Listing
January 2021
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