Publications by authors named "Guang Ji"

213 Publications

Kaempferol Alleviates Steatosis and Inflammation During Early Non-Alcoholic Steatohepatitis Associated With Liver X Receptor α-Lysophosphatidylcholine Acyltransferase 3 Signaling Pathway.

Front Pharmacol 2021 28;12:690736. Epub 2021 Jun 28.

Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Kaempferol (KP) has a variety of biological effects such as anti-inflammatory, anti-oxidant, anti-aging and cardiovascular protection. Whether KP has a therapeutic effect on non-alcoholic steatohepatitis (NASH), and the detailed mechanism is currently unclear. This study aims to explore the mechanism of KP in the treatment of NASH through and experiments. 1) experiment: In the C57BL/6 NASH mice model induced by high fat diet (HFD), KP was administered by gavage at a dose of 20 mg/kg/day. 2) experiment: Palmitic acid/Oleic acid (PA/OA, 0.375/0.75 mM) was used to intervene HepG2 and AML12 cells to establish a steatosis cell model. Three concentrations of KP, low (20 μmol/L), medium (40 μmol/L) and high (60 μmol/L) were used . The mRNA and protein expression of related molecules involved in LXRα-LPCAT3-ERS pathway were detected using RT-qPCR and Western blot. In the NASH mouse model, KP can significantly reduce the expression of LXRα, LPCAT3 and ERS-related factors PERK, eIF2α, ATF6, ATF4, XBP1, CHOP, IRE1α and GRP78. In the PA/OA-induced cell model, KP could decrease the content of triglyceride and lipid droplets, and also decrease the expression of LXR α, LPCAT3 and ERS related factors PERK, eIF2α, ATF6, ATF4, XBP1, CHOP, IRE1α and GRP78. KP may decrease the expression level of LXRα and LPCAT3, thus improve ERS and reduce hepatic steatosis and inflammation.
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http://dx.doi.org/10.3389/fphar.2021.690736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273916PMC
June 2021

The role and therapeutic implication of CPTs in fatty acid oxidation and cancers progression.

Am J Cancer Res 2021 15;11(6):2477-2494. Epub 2021 Jun 15.

Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200032, China.

Cancer cells must maintain metabolic homeostasis under a wide range of conditions and meet their own energy needs in order to survive and reproduce. In addition to glycolysis, cancer cells can also perform various metabolic strategies, such as fatty acid oxidation (FAO). It has been found that the proliferation, survival, drug resistance and metastasis of cancer cells depend on FAO. The carnitine palmitoyltransferase (CPT), including CPT1 and CPT2, located on the mitochondrial membrane, are important mediators of FAO. In recent years, many researchers have found that CPT has a close relationship with the metabolic development of tumor cells, not only provides energy for cancer cells development and metastasis by promoting FAO but also affects the occurrence and invasion through other signal pathways or cytokines or microRNA. This review summarized the role of CPTs in several kinds of tumors and the developed targeted inhibitors of CPTs, as well as the potential gene therapy and immunotherapy of CPTs, hoping to better explore the mechanism and role of CPTs in the future and providing useful ideas for clinical treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263643PMC
June 2021

Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients.

J Proteome Res 2021 May 27. Epub 2021 May 27.

Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, South Wanping Road 725, Shanghai 200032, China.

The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients. Using targeted ultraperformance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry (TQ/MS), we compared serum bile acid levels in T2DM patients with NAFL ( = 30) and age- and sex-matched T2DM patients without NAFL ( = 36) at the first time. Second, an independent cohort study of T2DM patients with NAFL ( = 17) and age- and sex-matched T2DM patients without NAFL ( = 20) was used to validate the results. The incremental benefits of serum biomarkers, clinical variables alone, or with biomarkers were then evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. The area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to evaluate the biomarker predictive abilities. The serum bile acid profiles in T2DM patients with NAFL were significantly different from T2DM patients without NAFL, as characterized by the significant elevation of LCA, TLCA, TUDCA, CDCA-24G, and TCDCA, which may be potential biomarkers for the identification of NAFL in T2DM patients. Based on the improvement in AUC, IDI, and NRI, the addition of 5 bile acids to a model with clinical variables statistically improved its predictive value. Similar results were found in the validation cohort. These results highlight that the detected biomarkers may contribute to the progression of NAFL in T2DM patients, and these biomarkers particularly in combination may help in the diagnosis of NAFL and allow earlier intervention in T2DM patients.
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http://dx.doi.org/10.1021/acs.jproteome.1c00104DOI Listing
May 2021

Salvia-Nelumbinis naturalis extract protects mice against MCD diet-induced steatohepatitis via activation of colonic FXR-FGF15 pathway.

Biomed Pharmacother 2021 Jul 14;139:111587. Epub 2021 Apr 14.

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address:

Salvia-Nelumbinis naturalis (SNN) formula is a traditional Chinese medicine prescription, and has been confirmed to be effective in treating non-alcoholic steatohepatitis (NASH), but the underlying mechanisms are still unknown. Here we showed that 4-week SNN administration alleviated methionine-choline-deficiency (MCD) diet-induced hepatic steatosis and inflammation as well as serum levels of alanine transaminase (ALT) increase in C57BL/6 mice. Fecal 16S rDNA sequencing indicated that SNN altered the structure of gut microbiota and partially reversed the gut dysbiosis. Simultaneously, we analyzed the fecal BA profile using liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS) -based metabolomics, and found that SNN modulated fecal BA profile, predominantly increased the microbiomes related BA species (e.g. nordeoxycholic acid) which in turn, activated farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway in the colon but not the ileum. The activation of intestinal FXR-FGF15 signaling was accompanied by increase of liver protein kinase B (PKB/Akt) phosphorylation, and decrease of p-65 subunit of NF-κB phosphorylation, resulting in less liver CD68 positive macrophages, and inflammatory cytokine IL-1β and TNF-α expression. Our results established the link between SNN treatment, gut microbiota, BA profile and NASH, which might shed light into the mechanisms behind the beneficial effects of SNN on NASH, thus provide evidence for the clinical application of SNN.
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http://dx.doi.org/10.1016/j.biopha.2021.111587DOI Listing
July 2021

Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation.

J Clin Invest 2021 May;131(10)

Department of Medical and Molecular Genetics.

One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell-mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non-ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I-mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient-derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.
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http://dx.doi.org/10.1172/JCI146832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121519PMC
May 2021

Progress on haptoglobin and metabolic diseases.

World J Diabetes 2021 Mar;12(3):206-214

Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Haptoglobin (Hp) is an acidic glycoprotein, existing in the serum and other body fluids of human beings and a variety of mammals. Hp is produced in the liver, white adipose tissue, and the kidney. The genetic polymorphisms and different phenotypes of Hp have different biological functions. Hp has antibacterial, antioxidant, and angiogenic effects and is associated with multiple diseases including simple obesity, vascular complications of diabetes mellitus, nonalcoholic fatty liver disease, hypertension, blood diseases, autoimmune diseases, and malignant tumors. Hp also participates in many life activities, indicating the importance of Hp in further studies. Previously, we found that the expression of serum Hp changed after treatment of simple obesity patients in clinical trials. However, the specific mechanism of Hp in patients with simple obesity is still unclear. The purpose of this article is to introduce recent research progress on Hp, emphasizing the relationship between Hp and the development of metabolic disease, which will improve the understanding of the functions of Hp underlying metabolic diseases and discuss future research directions.
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http://dx.doi.org/10.4239/wjd.v12.i3.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958475PMC
March 2021

A randomized comparison of two paclitaxel-coated balloons for the treatment of in-stent restenosis: The LONGTY ISR China randomized trial (LONGTY DCB vs. SeQuent Please DCB).

Catheter Cardiovasc Interv 2021 May 18;97 Suppl 2:988-995. Epub 2021 Mar 18.

Department of Cardiology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, Hangzhou, China.

Objectives: This study sought to compare the efficacy and clinical safety of the LONGTY drug-coated balloon (DCB) with those of SeQuent Please DCB in patients with in-stent restenosis (ISR).

Background: Although DCB technologies have evolved, little is known about the clinical efficacy of the new-generation LONGTY DCB.

Methods: This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow-up.

Results: A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow-up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority <.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow-up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups.

Conclusions: In this multicenter, head-to-head, randomized trial, the new-generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.
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http://dx.doi.org/10.1002/ccd.29589DOI Listing
May 2021

Acupuncture and Derived Therapies for Pain in Palliative Cancer Management: Systematic Review and Meta-Analysis Based on Single-Arm and Controlled Trials.

J Palliat Med 2021 Jul 10;24(7):1078-1099. Epub 2021 Mar 10.

Department of Gastrointestinal Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Acupuncture is a classical complementary therapy, but benefits in palliative cancer pain are still unclear due to lack of consistent evidence. To comprehensively evaluate the effectiveness of acupuncture and derived therapies (such as electroacupuncture, laser acupuncture, and transcutaneous electrical nerve stimulation) for analgesia in palliative cancer care based on both single-arm and controlled trials. Eight databases were searched from inception to August 31, 2020. Both single-arm trials and controlled trials were included. The primary outcome was the change in pain intensity, as evaluated by the numeric rating scale (NRS) and the visual analog scale. Adults with cancer. Forty-one controlled studies with 2685 participants and 18 single-arm studies with 1084 participants were included. For controlled trials, meta-analysis indicated that acupuncture and derived therapies in addition led to greater reductions in the NRS score than conventional analgesics alone (weighted mean difference [WMD]: 1.33 [0.85-1.82],  < 0.001). For single-arm trials, meta-analysis showed that both the immediate effect (WMD: 1.57 [1.43-1.71],  < 0.001) and long-term longitudinal effect (WMD: 1.81 [1.25-2.37],  < 0.001) of acupuncture on analgesia were positive, as evaluated by the NRS, respectively. The benefits of acupuncture and derived therapies were also seen in quality of life and the global improvement rate. LI4 (Hegu) was the most frequently used acupoint. This systematic review supported the application of acupuncture and derived therapies for managing pain during palliative cancer care from two dimensions. Further studies could explore the effect of acupuncture on other predominant symptoms in palliative cancer patients.
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http://dx.doi.org/10.1089/jpm.2020.0405DOI Listing
July 2021

Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment.

Front Pharmacol 2020 18;11:620724. Epub 2021 Jan 18.

Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. The relative abundance of 192 taxa in genus level were significantly changed in UC group, and 168 genera were significantly altered after mesalamine intervention. Meanwhile, a total of 127 metabolites were significantly changed in UC group and 129 metabolites were significantly altered after mesalamine treatment. Importantly, we observed that many candidates including 49 genera (such as and ) and 102 metatoblites (such as isoleucine, cholic acid and deoxycholic acid) were reversed by mesalamine. Spearman correlation analysis revealed that most of the candidates were significantly correlated with Mayo score of UC, and the relative abundance of specific genera were significant correlated with the perturbation of metabolites. Pathway analysis demonstrated that genera and metabolites candidates were enriched in many similar molecular pathways such as amino acid metabolism and secondary metabolites biosynthesis. Importantly, ROC curve analysis identified a gut microbiota signature composed of five genera including and [] which might be used to distinguish UC group from both NC and mesalamine group. In all, our results suggested that mesalamine might exert a beneficial role in UC by modulating gut microbiota signature with correlated metabolites in different pathways, which may provide a basis for developing novel candidate biomarkers and therapeutic targets of UC.
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http://dx.doi.org/10.3389/fphar.2020.620724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898679PMC
January 2021

Chinese medicine formulas for nonalcoholic fatty liver disease: Overview of systematic reviews.

World J Clin Cases 2021 Jan;9(1):102-117

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Background: Nonalcoholic fatty liver disease (NAFLD) affects more than one-quarter of the global population. Due to the lack of approved chemical agents, many patients seek treatment from traditional Chinese medicine (TCM) formulas. A variety of systematic reviews have been published regarding the effectiveness and safety of TCM formulas for NAFLD.

Aim: To critically appraise available systematic reviews and sort out the high-quality evidence on TCM formulas for the management of NAFLD.

Methods: Seven databases were systematically searched from their inception to 28 February 2020. The search terms included "non-alcoholic fatty liver disease," "Chinese medicines," "systematic review," and their synonyms. Systematic reviews involving TCM formulas alone or in combination with conventional medications were included. The methodological quality and risk of bias of eligible systematic reviews were evaluated by using A Measure Tool to Assess Systematic Reviews 2 (AMSTAR 2) and Risk of Bias in Systematic Review (ROBIS). The quality of outcomes was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results: Seven systematic reviews were ultimately included. All systematic reviews were conducted based on randomized controlled trials and published in the last decade. According to the AMSTAR 2 tool, one systematic review was judged as having a moderate confidence level, whereas the other studies were rated as having a low or extremely low level of confidence. The ROBIS tool showed that the included systematic reviews all had a high risk of bias due to insufficient consideration of identified concerns. According to the GRADE system, only two outcomes were determined as high quality; namely, TCM formulas with the HuoXueHuaYu principle were better than conventional medications in ultrasound improvement, and TCM formulas were superior to antioxidants in alanine aminotransferase normalization. Other outcomes were downgraded to lower levels, mainly because of heterogeneity among studies, not meeting optimal information sample size, and inclusion of excessive numbers of small sample studies. Nevertheless, the evidence quality of extracted outcomes should be further downgraded when applying to clinical practice due to indirectness.

Conclusion: The quality of available systematic reviews was not satisfactory. Researchers should avoid repeatedly conducting systematic reviews in this area and focus on designing rigorous randomized controlled trials to support TCM formula applications.
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http://dx.doi.org/10.12998/wjcc.v9.i1.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809658PMC
January 2021

A case of reversible splenial lesion syndrome secondary to Fanconi syndrome with white matter swelling as the main manifestation.

J Int Med Res 2021 Jan;49(1):300060520985713

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Reversible splenial lesion syndrome (RESLES) is a rare clinical imaging syndrome that is characterized by magnetic resonance imaging (MRI) findings of reversible abnormal signals in the splenium of the corpus callosum (SCC). There are a variety of pathogenic causes, including infection, metabolic disturbances, and antiepileptic drug use. Moreover, the disease is clinically rare and easily misdiagnosed. Here, we report a unique case of a 32-year-old man with Fanconi syndrome who had an intensified signal in the SCC and diffuse white matter swelling on MRI. We believe this to be the first adult case of RESLES as a manifestation of Fanconi syndrome, which further expands the disease spectrum leading to RESLES. The imaging features of this case included extensive lesions, symmetrical diffuse restricted signals, and reversibility. The identification of these features improves our understanding of the imaging characteristics of RESLES, thus enabling clinicians to better understand this disease, correctly establish its diagnosis, and improve its prognosis in this kind of patient.
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http://dx.doi.org/10.1177/0300060520985713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838877PMC
January 2021

CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis.

J Exp Clin Cancer Res 2020 Dec 14;39(1):283. Epub 2020 Dec 14.

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.

Background: Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.

Methods: The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.

Results: CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.

Conclusions: CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.
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http://dx.doi.org/10.1186/s13046-020-01799-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735421PMC
December 2020

Therapeutic effects of herbal formula Huangqisan on metabolic disorders via SREBF1, SCD1 and AMPK signaling pathway.

J Integr Med 2021 Mar 20;19(2):167-176. Epub 2020 Nov 20.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Objective: Metabolic syndrome is a complex medical condition that has become an alarming epidemic, but an effective therapy for this disease is still lacking. The use of the herbal formula Huangqisan (HQS) to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.; however, its therapeutic effects and underlying mechanisms remain elusive.

Methods: To investigate the beneficial effects of HQS on metabolic disorders, high-fat diet-induced obesity (DIO), leptin receptor dysfunction (db/db) and low-density lipoprotein receptor-knockout (LDLR) mice were used. Obese mice were treated with either HQS or vehicle. Blood, liver tissue, white fat tissue and brown adipose tissue were harvested at the end of the treatment. Metabolic disease-related parameters were evaluated to test effects of HQS against diabetes, obesity and hyperlipidemia. Aortic arches from LDLR mice were analyzed to investigate the effects of HQS on atherosclerosis. RNA-sequence, quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder.

Results: HQS lowered body weight, fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice (P < 0.05). HQS also blocked atherosclerotic plaque formation in LDLR mice. HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1, stearyl coenzyme A desaturase 1 and fatty acid synthase, and enhancing adenosine 5'-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments, indicating potential mechanisms for HQS's activity against diabetes.

Conclusion: HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.
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http://dx.doi.org/10.1016/j.joim.2020.11.002DOI Listing
March 2021

Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice.

Biomed Pharmacother 2020 Dec 1;132:110953. Epub 2020 Nov 1.

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address:

Berberine compounds (BC), consisting of berberine (BBR), oryzanol and vitamin B, have been used to treat diabetes and hyperlipidemia in recent years, but the potential mechanisms under the effects have not been well determined. In this study, we evaluated the effect of BC in db/db mice, and found that BC treatment reversed the increased levels of fasting glucose and hemoglobin A1c in db/db mice, which was superior to BBR treatment. Fecal 16S rRNA gene sequencing indicated that BC increased relative abundance of microbiomes Bacteroidaceae and Clostridiaceae, which may promote conversion of primary bile acid cholic acid (CA) into secondary bile acid deoxycholic acid (DCA). Gas chromatography/mass spectrometry (GC/MS)-based metabolomics revealed that BC treatment increased fecal DCA level. Since DCA processes the potential to activate bile acid receptor-takeda G protein-coupled receptor 5 (TGR5) and induce glucagon-like peptide (GLP) secretion, we detected TGR5 expression, and found that BC-treatment significantly increased the colonic TGR5 and serum GLP-1/-2 levels in db/db mice. Modulation of TGR5-GLP pathway may also affect metabolomic profiles of serum and liver, and BC treatment showed effects on restoring the altered carbohydrate, lipid, amino acid and nucleotide metabolism. Our study suggested that BC improved hyperglycemia, the effect might attribute to the increased microbiome mediated DCA production, which up-regulated colonic TGR5 expression and GLP secretion, and improved glucose, lipid and energy metabolism in db/db mice.
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http://dx.doi.org/10.1016/j.biopha.2020.110953DOI Listing
December 2020

Integrative transcriptomics and metabolomics explore the mechanism of kaempferol on improving nonalcoholic steatohepatitis.

Food Funct 2020 Nov;11(11):10058-10069

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Kaempferol has been confirmed to be effective in improving metabolic diseases such as diabetes and obesity. However, its effect and mechanism in nonalcoholic steatohepatitis (NASH) are unclear. We aim to confirm whether kaempferol could improve NASH and find the corresponding differential genes and metabolites. Transcriptomics combined with metabolomics was used to investigate the alterations in genes and metabolites expression after kaempferol treatment in mice with high-fat-diet-induced NASH. The results showed that kaempferol reduced the level of alanine transaminase (ALT), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in serum and triglyceride (TG), lipid droplets, and inflammatory cell infiltration in liver. Further, 277 differentially expressed genes (DEGs) were identified through liver transcriptomics and the five most obvious DEGs were found to be CYP2b9, Cyp4a12b, Mup17, Mup7, and Mup16, which revealed that HFD induced fatty acid degradation, ribosome, and glyoxylic acid and dicarboxylic acid metabolism. Nine serum metabolites (methylcysteine, l-tryptophan, adrenic acid, d-2-hydroxyglutaric acid, tartaric acid, p-cresol sulfate, l-alanine, l-tryosine, and glutaconic acid) and 3 liver differential metabolites (gallic acid, γ-lindenic acid, and l-phenylalanine) were also identified, while the pathways were mainly involved in phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Integrating transcriptomics and metabolomics analyses indicated that kaempferol possesses the ability to improve NASH associated with energy metabolism, lipid metabolism, oxidative stress, and inflammation-related pathways. This study provides a powerful means of multiomics data integration and reveals the potent therapy and biomarkers for kaempferol.
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http://dx.doi.org/10.1039/d0fo02123gDOI Listing
November 2020

Is vitamin D receptor a druggable target for non-alcoholic steatohepatitis?

World J Gastroenterol 2020 Oct;26(38):5812-5821

Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Nonalcoholic steatohepatitis (NASH) is a progressed stage of non-alcoholic fatty liver disease, and available therapeutic strategies for NASH are limited. Vitamin D receptor (VDR) is proposed as a druggable target for NASH due to the discovery of vitamin D deficiency in NASH patients. To date, vitamin D supplementation has not consistently conferred expected therapeutic benefits, raising the question of whether VDR can serve as a proper drug target for NASH. It is known that VDR can interact with other ligands such as bile acids in addition to vitamin D, and its expression can be induced by fatty acids, and insulin. It has also been shown that while activation of VDR in hepatic macrophages and hepatic stellate cells resulted in attenuation of hepatic inflammation and fibrosis, activation of VDR in hepatocytes could accelerate lipid accumulation. Thus, the multiplicity of VDR ligands, together with the cell type-specificity of VDR activation, must be taken into consideration in assessing the validity of VDR being a potential druggable target for NASH treatment. To this end, we have evaluated the relationship between VDR activation and various contributing factors, such as gut microbiota, bile acid, fatty acids, and insulin, in addition to vitamin D, with an expectation that a potential drug might be identified that can elicit VDR activation in a tissue- and/or cell type-specific manner and therefore achieving therapeutic benefits in NASH.
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http://dx.doi.org/10.3748/wjg.v26.i38.5812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579753PMC
October 2020

A family with riboflavin-reactive lipid deposition myopathy caused by a novel compound heterozygous mutation in the electron transfer flavoprotein dehydrogenase gene.

J Int Med Res 2020 Nov;48(11):300060520966499

Department of Neurology, The Second Hospital of Hebei Medical University, Hebei, Shijiazhuang, P. R. China.

We report a family with riboflavin-reactive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) partially caused by a novel mutation in the electron transfer flavoprotein dehydrogenase gene ). The RR-MADD family was identified by physical examination, electromyography, and muscle biopsy of the proband. Laboratory examination and electromyography suggested a muscle disease of the lipid storage myopathies. This was confirmed by a muscle biopsy that revealed lipid deposition in the muscle fibers. The proband's sister previously had a similar disease, so the family underwent genetic testing. This revealed complex heterozygous mutations c.389A > T (p. D130V) and c.1123C > A (p. P375T) in the proband and her sister, of which c.1123C > A (p. P375T) is a novel pathogenic mutation. The proband was treated with riboflavin and changes in physical symptoms and laboratory tests were evaluated before and after treatment. The discovery of a novel locus further expands the mutation spectrum and suggests that genotyping is vital for early detection of RR-MADD as it can greatly improve the prognosis.
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http://dx.doi.org/10.1177/0300060520966499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653293PMC
November 2020

Quasi-Static Two-Dimensional Infrared Spectra of the Carboxyhemoglobin Subsystem under Electric Fields: A Theoretical Study.

J Phys Chem B 2020 10 19;124(43):9570-9578. Epub 2020 Oct 19.

School of Physical Sciences, University of Science and Technology of China, Hefei 230000, China.

There is no doubt that electric fields of a specific frequency and intensity could excite certain vibrational modes of a macromolecule, which alters its mode coupling and conformation. Motivated by recent experiments and theories, we study the mode coupling between the Fe-CO mode and CO-stretch mode and vibration energy transfer among the active site and proteins in carboxyhemoglobin (HbCO) under different electric fields using the quasi-static two-dimensional infrared spectra. This study uses iron-porphyrin-imidazole-CO and two distal histidines in HbCO as the subsystem. The potential energy and dipole moment surfaces of the subsystem are calculated using an all-electron ab initio (B3LYP-D3(BJ)) method with the basis set Lanl2dz for the Fe atom and 6-31G(d,p) for C, H, O, and N atoms. Although the subsystem is reduced dimensionally, the anharmonic frequency and anharmonicity of the CO-stretch mode show excellent agreement with experimental values. We use the revealing noncovalent interaction method to confirm the hydrogen bond between the H atom of the His63 and the CO molecule. Our study confirms that the mode coupling between the Fe-CO mode and CO-stretch mode does not exist when the subsystem is free of electric field perturbation, which is coupled when the electric field is -0.5142 V/nm. In addition, with the increases of distance between the active site and the His92, there is no vibrational energy transfer between them when the electric field is 1.028 V/nm. We believe that our work could provide new ideas for increasing the dissociation efficiency of the Fe-CO bond and theoretical references for experimental research.
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http://dx.doi.org/10.1021/acs.jpcb.0c06251DOI Listing
October 2020

Encapsulation-Dependent Enhanced Emission of Near-Infrared Nanoparticles Using Three-Photon Fluorescence Imaging.

Front Bioeng Biotechnol 2020 10;8:1029. Epub 2020 Sep 10.

Department of Breast Surgery, The First Hospital, Jilin University, Changchun, China.

We discovered a unique fluorescent enhancement of dye encapsulated polymeric nanoparticles, which strongly depended on the polymeric matrix. Interestingly, the polymer nanoparticles containing a NIR emissive dye exhibited remarkable enhancement of emission encapsulated by the polymer amphiphilic polymer containing polystyrene (PS) moiety, whereas the nanoparticles showed weak fluorescence when using other polymer encapsulation. The highest fluorescent quantum yield of nanoparticles can reach 27% by using PS-PEG encapsulation, where the strong NIR fluorescence can be observed. These ultra-bright fluorescence nanoparticles also possess a strong three-photon fluorescence and show a good candidate for vascular three-photon fluorescence imaging of mouse brain and ear under 1550 nm fs laser excitation. A fine three-dimensional (3D) reconstruction with an imaging depth of 635 and 180 μm was achieved, respectively. We further demonstrate that these nanoparticles can effectively target the sentinel lymph node (SLN) of mice.
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http://dx.doi.org/10.3389/fbioe.2020.01029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511574PMC
September 2020

Effect of AAV9-hIGF-1 on inflammatory reaction in mdx mice and its mechanism.

Am J Transl Res 2020 15;12(8):4488-4497. Epub 2020 Aug 15.

Department of Neurology, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei, China.

This study aimed to the role of insulin-like growth factor 1 (IGF-1) in Duchenne muscular dystrophy (DMD), the inflammatory response and the potential mechanism of the effect hIGF1 exerted in muscle inflammation were also been explored. In this study, AAV9, a carrier of the human IGF-1 gene, was injected into mdx mice to observe the role of IGF-1 in DMD. Routine histopathological staining, immunofluorescence and western blot were used to detect the inflammatory response. In addition, we also explored the potential mechanism of the role of hIGF1 in muscle inflammation. The expression of AAV9 in myocardium and muscle tissue of AAV9-GFP group was detected by GFP method. GFP was expressed in different tissues of mdx mice, especially in anterior tibial muscle, triceps muscle and other tissues. The percentage of anterior tibial muscle inflammation area in CD68 and AAV9-hIGF-1 group was lower than that in AAV-GFP group, and the percentage of anterior tibial muscle inflammation area in AAV9-hIGF-1 group (1.78 ± 0.47%) was significantly lower than that in AAV GFP group (3.4 ± 1.22%) (P < 0.05). Western-blot showed that AAV-hIGF-1 group (0.45 + 0.07%) was lower than that of AAV-GFP group (0.76 + 0.13%), higher than the normal group (0.38 + 0.06%). The difference was statistically significant (P < 0.05). In conclusion, this study confirmed that hIGF-1 can reduce the inflammatory response and macrophage infiltration in mdx mice, and further proved that hIGF-1 can down regulate the expression of NF-κB signal pathway, which has anti-inflammatory effect.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476146PMC
August 2020

Four patients with infarction in key areas of the Papez circuit, with anterograde amnesia as the main manifestation.

J Int Med Res 2020 Jul;48(7):300060520939369

Department of MRI, Harrison International Peace Hospital, Hengshui, Hebei, China.

The Papez circuit is an important brain structure that is closely associated with learning and memory. In this report, we present four patients with anterograde amnesia as the main manifestation induced by Papez circuit infarction. In addition, we review the distribution of the responsible arteries in key and rare regions to investigate the pathogenesis of these infarctions.
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http://dx.doi.org/10.1177/0300060520939369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372620PMC
July 2020

Comprehensive analysis of 5-hydroxymethylcytosine in zw10 kinetochore protein as a promising biomarker for screening and diagnosis of early colorectal cancer.

Clin Transl Med 2020 Jul 6;10(3):e125. Epub 2020 Jul 6.

Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: As a new epigenetic biomarker, 5-hydroxymethylcytosine (5hmC) is broadly involved in various diseases including cancers. However, the function and diagnostic performance of 5hmC in colorectal cancer (CRC) remain unclear.

Results: High-throughput sequencing was used to profile 5hmC levels in adjacent normal colon, advanced adenomas, and CRC. The expression and 5hmC levels in zw10 kinetochore protein (ZW10) were significantly increased in the tissues and blood samples for patients with advanced adenoma and CRC, and were much higher in the early stages of CRC (I and II). The receiver operating characteristic analysis had potential diagnostic value for CRC. The area under the curve (AUC) of ZW10 5hmC levels in tissue samples of CRC was 0.901. In blood samples, the AUC was 0.748 for CRC. In addition, the ZW10 5hmC level had much higher diagnostic performance in early stages of CRC (AUC = 0.857) than it did in advanced stages (AUC = 0.594). Compared with FHC cell, ZW10 expression in HT29 cell was significantly increased. The ZW10 knockdown could inhibit cell proliferation and the ZW10 overexpression could promote cell proliferation in HT-29 cell. Furthermore, ZW10 knockdown inhibited AKT and mTOR phosphorylation, and ZW10 overexpression promoted AKT and mTOR phosphorylation.

Conclusions: The ZW10 5hmC level may serve as an effective epigenetic biomarker for minimally invasive screening and diagnosis of CRC, and it has higher diagnostic performance in early stages of CRC than it does in advanced stages. In addition, ZW10 could regulate CRC progression through the AKT-mTOR signaling.
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http://dx.doi.org/10.1002/ctm2.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418801PMC
July 2020

Sophoricoside is a selective LXRβ antagonist with potent therapeutic effects on hepatic steatosis of mice.

Phytother Res 2020 Dec 27;34(12):3168-3179. Epub 2020 Jun 27.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of triglycerides and associated with obesity, hyperlipidemia and insulin resistance. Currently, there is no therapy for NAFLD. Emerging evidences suggest that the inhibition of liver X receptor (LXR) activity may be a potential therapy for hepatic steatosis. Here, we identified that sophoricoside is a selective antagonist of LXRβ. Sophoricoside protected against obesity and glucose tolerance, and inhibited lipid accumulation in the liver of high-fat diet-induced obesity (DIO) mice and methionine and choline-deficient diet-induced nonalcoholic steatohepatitis mice. Furthermore, sophoricoside inhibited malondialdehyde, and increased superoxide dismutase and glutathione in the liver of the mice. In HepG2 cells, pretreatment with sophoricoside rescued GSH concentration decrease induced by H O treatment. Our data suggest that sophoricoside is a novel LXRβ selective antagonist and may improve glucose and lipid dysfunction, and attenuate lipid accumulation in the liver of DIO mice via anti-oxidant properties, which may be developed as a therapy for NAFLD.
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http://dx.doi.org/10.1002/ptr.6747DOI Listing
December 2020

Extract of Schisandra chinensis fruit protects against metabolic dysfunction in high-fat diet induced obese mice via FXR activation.

Phytother Res 2020 Nov 25;34(11):3063-3077. Epub 2020 Jun 25.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Schisandra chinensis fruit has been shown to restore carbohydrate- and lipid-metabolic disorders and has anti-hepatotoxicity and anti-hepatitis activities. However, the molecular targets mediating the pharmacological properties of S. chinensis fruit have not been clarified. Here, we assayed the effects of S. chinensis fruit ethanol extract (SCE) on farnesoid X receptor (FXR) transactivity. The pharmacological effects of SCE (1 g/100 g diet) were assessed in high-fat diet (HFD)-fed C57BL/6 mice and ob/ob mice. The FXR and Fgf15 signalling pathways were evaluated by FXR silencing, ELISA, Western blot and RT-PCR analyses. The results showed that SCE treatment increased FXR transcription activity and improved obesity, hypercholesteremia and fatty liver in HFD-fed mice, while it had limited effects on ob/ob mice. Our study suggests that SCE treatment may improve HFD-induced metabolic disorders through pharmacological activation of FXR/Fgf15 signalling, and such beneficial effects of SCE may require leptin participation.
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http://dx.doi.org/10.1002/ptr.6743DOI Listing
November 2020

Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine.

Biomed Pharmacother 2020 Jul 20;127:109976. Epub 2020 May 20.

Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address:

Background: The ling-gui-zhu-gan (LGZG) decoction is a classic formula in traditional chinese medicine (TCM) and is widely used in clinical settings. Recently, the LGZG decoction was demonstrated to have an effect in alleviating hepatic steatosis induced by a high-fat diet (HFD). However, the mechanisms underlying this therapeutic effect remain unclear. The present study was designed to evaluate the effect and explore possible mechanisms of action of the LGZG decoction in nonalcoholic fatty liver disease (NAFLD).

Methods: Liver tissue and blood samples were harvested. Liver steatosis, triglyceride (TG), liver total cholesterol (TC), liver low-density lipoprotein (LDL), serum almandine aminotransferase (ALT), aspartate aminotransferase (AST), and free fatty acid (FFA) were assayed. N6-methyladenosine (m6A) levels were estimated using an m6A RNA methylation quantification kit and immunohistochemistry. The m6A methylome was detected through methylated RNA immunoprecipitation sequencing (MeRIP-seq), followed by data analysis. The expression levels of differentially methylated genes (DMGs) were determined using real-time polymerase chain reaction and western blotting.

Results: The LGZG decoction significantly alleviated hepatic steatosis and reduced m6A levels. MeRIP-seq revealed the coding sequence (CDS) domain to be the most critical modification site for m6A methylation, and the molecular functions of DMGs predominantly included insulin-like growth factor receptor binding and fatty acid metabolism and degradation. Further, LGZG treatment could reduce the m6A methylation levels of suppressor of cytokine signaling 2 (SOCS2), along with the expression of SOCS2 at mRNA and protein levels.

Conclusions: The LGZG decoction is an effective formula for treating NAFLD, and the possible mechanisms underlying its action could be related to N6-methyladenosine modification-medicated SOCS2.
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http://dx.doi.org/10.1016/j.biopha.2020.109976DOI Listing
July 2020

Traditional Chinese medicine Lingguizhugan decoction treating non-alcoholic fatty liver disease with spleen-yang deficiency pattern: Study protocol for a multicenter randomized controlled trial.

Trials 2020 Jun 10;21(1):512. Epub 2020 Jun 10.

Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by excessive fat accumulation in the liver. One of the underlying pathophysiological mechanisms is insulin resistance (IR). Traditional Chinese medicine (TCM) has showed potential benefits in the management of NAFLD. Lingguizhugan decoction (LGZG) is a representative Chinese herbal formula; however, there is still no rigorous clinical trial supporting its application.

Methods/design: This study will be a three-arm, dose-optimization, randomized, double-blinded, placebo-controlled clinical trial. A total of 243 patients with NAFLD will be recruited and randomly assigned to the standard dose LGZG (SLGD) group, low dose LGZG (LLGD) group, or the placebo group based on a ratio of 1:1:1. The treatment period will be 12 weeks and the follow-up period will last 4 weeks. The primary outcome will be the proportions of participants with at least a 1-unit decrease of HOMA-IR from baseline to 12 weeks. Secondary outcomes will include the changes of body weight, body mass index, liver function, blood lipid metabolism, blood glucose metabolism, inflammatory responses, liver-kidney echo ratio by ultrasound, and various scales. Biological samples will also be collected for future researches on mechanism exploration.

Discussion: This study will provide initial evidence regarding the efficacy and safety of LGZG in the treatment of NAFLD with spleen-yang deficiency pattern and promote its application in community healthcare centers. In addition, potential mechanisms will be explored based on studies of oral and gut microbiota.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800014364. Registered on 1 January 2018. The final protocol version was V3.0.
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http://dx.doi.org/10.1186/s13063-020-04362-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288405PMC
June 2020

Asymmetrical ARDL correlation between fossil fuel energy, food security, and carbon emission: providing fresh information from Pakistan.

Environ Sci Pollut Res Int 2020 Sep 2;27(25):31369-31382. Epub 2020 Jun 2.

College of Economics and Management, Northeast Forestry University, Harbin, 150040, People's Republic of China.

The core objective of our study seeks to examine the asymmetrical impact of agriculture, fossil fuel consumption, and food security on carbon emission (CO) in Pakistan from 1969 to 2018. The current study applied multiple unit root tests (ADF, PP, and KPSS, Z&A) to check data stationarity and structural breaks. We used the population data as a food security proxy indicator. The outcomes disclosed that there is a long-term asymmetric relationship between the variables. The results also verified the atypical response of CO to adverse shocks in agricultural value-added. Furthermore, the results showed that population and fossil fuel consumption would further worsen environmental standards. Based on the results of the study, the government needs to take practical steps for active policy-making and assessing ecological challenges in Pakistan.
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http://dx.doi.org/10.1007/s11356-020-09346-3DOI Listing
September 2020

Metabolomic Analysis Identifies Glycometabolism Pathways as Potential Targets of Qianggan Extract in Hyperglycemia Rats.

Front Pharmacol 2020 12;11:671. Epub 2020 May 12.

Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Qianggan formula, a designed prescription according to the Traditional Chinese Medicine (TCM) theory, is widely used in treating chronic liver diseases, and indicated to prevent blood glucose increase in patients unknown mechanisms. To unravel the effects and underlying mechanisms of Qianggan formula on hyperglycemia, we administrated Qianggan extract to high fat and high sucrose (HFHS) diet rats. Results showed that four-week Qianggan extract intervention significantly decreased serum fasting blood glucose, hemoglobin A1c, and liver glycogen levels. Gas chromatography-mass spectrometry (GC-MS) approach was employed to explore metabolomic profiles in liver and fecal samples. By multivariate and univariate statistical analysis (variable importance of projection value > 1 and value < 0.05), 44 metabolites (18 in liver and 30 in feces) were identified as significantly different. Hierarchical cluster analysis revealed that most differential metabolites had opposite patterns between pair-wise groups. Qianggan extract restored the diet induced metabolite perturbations. Metabolite sets enrichment and pathway enrichment analysis revealed that the affected metabolites were mainly enriched in glycometabolism pathways such as glycolysis/gluconeogenesis, pentose phosphate pathway, fructose, and mannose metabolism. By compound-reaction-enzyme-gene network analysis, batches of genes (e.g, ) or enzymes (e.g. hexokinase and glucokinase) related to metabolites in enriched pathways were obtained. Our findings demonstrated that Qianggan extract alleviated hyperglycemia, and the effects might be partially due to the regulation of glycometabolism related pathways.
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http://dx.doi.org/10.3389/fphar.2020.00671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235344PMC
May 2020

Natural products that target macrophages in treating non-alcoholic steatohepatitis.

World J Gastroenterol 2020 May;26(18):2155-2165

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Nonalcoholic steatohepatitis (NASH) is the progressive subtype of non-alcoholic fatty liver disease and potentiates risks for both hepatic and metabolic diseases. Although the pathophysiology of NASH is not completely understood, recent studies have revealed that macrophage activation is a major contributing factor for the disease progression. Macrophages integrate the immune response and metabolic process and have become promising targets for NASH therapy. Natural products are potential candidates for NASH treatment and have multifactorial underlying mechanisms. Macrophage involvement in the development of steatosis and inflammation in NASH has been widely investigated. In this review, we assess the evidence for natural products or their active ingredients in the modulation of macrophage activation, recruitment, and polarization, as well as the metabolic status of macrophages. Our work may highlight the possible natural products that target macrophages as potential treatment options for NASH.
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http://dx.doi.org/10.3748/wjg.v26.i18.2155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235205PMC
May 2020