Publications by authors named "Shuli Man"

86 Publications

Nanoparticle conjugation of ginsenoside Rb3 inhibits myocardial fibrosis by regulating PPARα pathway.

Biomed Pharmacother 2021 May 1;139:111630. Epub 2021 May 1.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, PR China. Electronic address:

Background: Cardiac fibrosis occurs in ischemic and non-ischemic heart failure, hereditary cardiomyopathy, diabetes and aging. Energy metabolism, which serves a crucial function in the course and treatment of cardiovascular diseases, might have therapeutic benefits for myocardial fibrosis. Ginsenoside Rb3 (G-Rb3) is one of the main components of Ginseng and exhibits poor oral bioavailability but still exerts regulate energy metabolism effects in some diseases. Therefore, the study investigated the effect of chitosan (CS) @ sodium tripolyphosphate (TPP) nanoparticles conjugation with ginsenoside Rb3 (NpRb3) on myocardial fibrosis and studied its possible mechanisms. The results showed that NpRb3 directly participates in the remodeling of myocardial energy metabolism and the regulation of perixisome proliferation-activated receptor alpha (PPARα), thereby improving the degree of myocardial fibrosis. The study also verifies the protective effect of NpRb3 on energy metabolism and mitochondrial function by targeting the PPARα pathway. Therefore, the prepared nanodrug carrier may be a potential solution for the delivery of G-Rb3, which is a promising platform for oral treatment of myocardial fibrosis.
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http://dx.doi.org/10.1016/j.biopha.2021.111630DOI Listing
May 2021

Tissue distribution, metabolism and absorption of Rhizoma Paridis Saponins in the rats.

J Ethnopharmacol 2021 Jun 19;273:114038. Epub 2021 Mar 19.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin, 300072, China. Electronic address:

Ethnopharmacological Relevance: Paris polyphylla var yunnanensis as a traditional Chinese medicine has been used in the treatment of liver disease for thousands of years. Rhizoma Paridis saponins (RPS) were the main active ingredients in Paris polyphylla with an excellent antitumor effect. However, metabolic and distribution of RPS has not been known.

Aim Of The Study: The objective of this study was to research metabolic and distribution of RPS.

Materials And Methods: In this study, the separation and simultaneous determination of RPS in rat plasma and tissues were developed and validated by LC-MS/MS. The permeability and recovery of RPS were tested by Caco-2. S9 assay suggested the metabolic mode of RPS in rats.

Results: After oral administration of RPS, the metabolic compound like diosgenin was detected in different tissues although there was none in RPS. The concentration of PI, PII, PVI, PVII, PH and gracillin in the spleen was the highest among these organs. The content of diosgenin were the highest in lung and brain. Caco-2 test indicated that PI, PII, PVI and PVII were low permeability and low recovery. Efflux ratio indicated that PVI should be a potential P-gp substrate. Potential P-gp substrate may be PVI. S9 assay suggested that RPS possess slow metabolic and moderate metabolic compounds.

Conclusions: Integrated LC-MS/MS analysis of serum samples, together with Caco-2 and S9 assays provided a theoretical basis for the application of RPS in the future.
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http://dx.doi.org/10.1016/j.jep.2021.114038DOI Listing
June 2021

Potential and promising anticancer drugs from adenosine and its analogs.

Drug Discov Today 2021 Feb 25. Epub 2021 Feb 25.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address:

In recent years, many studies have shown that adenosine has efficacy for treating cancer. More importantly, some adenosine analogs have been successfully marketed to fulfill anticancer purposes. In this review, we summarize the anticancer effects of adenosine and its analogs in clinical trials and preclinical studies, with focus on their anticancer mechanisms. In addition, we link the anticancer activities of adenosine analogs with their structures through structure-activity relationship (SAR) analysis, and highlight additional promising anticancer drug candidates. We hope that this review will be of help in understanding the importance of adenosine and its analogs with anticancer activities and directing future research and development of such compounds.
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http://dx.doi.org/10.1016/j.drudis.2021.02.020DOI Listing
February 2021

Pharmacokinetics profiles of polyphyllin II and polyphyllin VII in rats by liquid chromatography with tandem mass spectrometry.

Biomed Chromatogr 2021 Feb 5:e5083. Epub 2021 Feb 5.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Polyphyllin II (PII) and polyphyllin VII (PVII) are the main active ingredients in Paris Polyphylla with an excellent antitumor effect in vitro and in vivo. In this study, a rapid and precise LC-MS/MS method was developed and validated for the separation and simultaneous determination of PII and PVII in rat plasma, tissues, feces and urine using ginsenoside Rg3 as the internal standard. Positive linearity ranged from 1 to 1,000 ng/ml in samples. At the same time, intra- and inter-day precisions were in range of 1.8-12.0%. The accuracy ranged from 95.9 to 100.8%. Mean extraction recoveries of PII and PVII ranged from 86.6 to 96.4%. The analytical method has been successfully applied to the pharmacokinetic studies of PII and PVII in rats after their i.v. administration. After entering systemic circulation, PII and PVII were rapidly distributed in organs, mainly including liver, lung and spleen. Their elimination rate was slow. All of these data provided a theoretical basis for the application of PII and PVII in the treatment of liver- and lung-related diseases.
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http://dx.doi.org/10.1002/bmc.5083DOI Listing
February 2021

Polyphenol-Rich Extract from Seeds Alleviates Hypertension-Induced Renal Damage in Rats.

J Agric Food Chem 2021 Feb 20;69(7):2138-2148. Epub 2021 Jan 20.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Laboratory of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.

seed is a valuable byproduct of the subtropical fruit litchi ( Sonn.), whose extract (LSE) has been confirmed to ameliorate dyslipidemia, hyperglycemia, and oxidative stress caused by type 2 diabetes. However, if LSE exerts an effect on anti-hypertension and hypertensive renal damage remains unknown. In this study, 13 polyphenols and one fatty acid were identified by UPLC-Q/TOF-MS. Network pharmacological analysis revealed that the therapeutic effects of LSE may be involved in multitargets and multipathways, such as the TNF signaling pathway, interleukin (IL)-6-mediated signaling pathway, NF-kappa B signaling pathway, removal of superoxide radicals, negative regulation of blood pressure, and so forth. Moreover, spontaneously hypertensive rats (SHRs) were daily gavaged with LSE (60 mg/kg) for 10 weeks. LSE remarkably reduced systolic blood pressure (SBP). The hypertension-induced renal damage was improved by suppressing inflammation and oxidative stress, which was consistent with the prediction of network pharmacology. In addition, LSE treatment remarkably increased the relative abundances of and the production of short-chain fatty acids in the intestine. Our study indicated that a byproduct of litchi, namely, litchi seed, may be effective in reducing SBP and alleviating hypertensive renal damage.
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http://dx.doi.org/10.1021/acs.jafc.0c07046DOI Listing
February 2021

Friend or foe? The roles of inulin-type fructans.

Carbohydr Polym 2021 Jan 1;252:117155. Epub 2020 Oct 1.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China. Electronic address:

Inulin-type fructans (ITFs) as functional fructans and soluble dietary fiber are a mixture of inulin, oligofructose and fructooligosaccharide with β configuration. They are modified by gut microbiota at the end of ileum, subsequently, improve digestive system, metabolic syndrome, immune system and inflammatory diseases, and prevent against infection and cancer. However, it has been reported that inadequate consumption of ITFs aggravates the development of non-alcoholic fatty liver disease, results in gastrointestinal symptoms, liver cancer and intestinal inflammation. Therefore, this review summarizes the health benefits, pharmaceutical applications and safety evaluation of ITFs, which would direct their rational applications.
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http://dx.doi.org/10.1016/j.carbpol.2020.117155DOI Listing
January 2021

Shunaoxin pills improve the antihypertensive effect of nifedipine and alleviate its renal lipotoxicity in spontaneous hypertension rats.

Environ Toxicol 2021 Mar 24;36(3):386-395. Epub 2020 Oct 24.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Shunaoxin pills (SNX) have been used to treat cerebrovascular diseases in China since 2005. Hypertension is a major risk factor for cerebrovascular disease. This study aimed to explore the synergistic antihypertensive effect of SNX and nifedipine and whether SNX could alleviate nifedipine-induced renal lipotoxicity. During administration, systolic blood pressure was measured weekly. After 5 weeks administration, we examined pathological changes of kidney, renal function, the lipid metabolism index, and adipogenesis genes expression in the kidney tissues, and explored its underlying mechanism. Finally, network pharmacology was used for supplement and verification. As a result, SNX improved the antihypertensive effect of nifedipine and apparently improved nifedipine-induced renal pathological changes, dyslipidemia and the levels of adipogenesis gene expression in kidney tissues. SNX reduced the levels of interleukin-6 and interleukin-1β in renal tissues, down-regulated the production of malondialdehyde, and increased superoxide dismutase activity and the protein expression of heme oxygenase-1 in kidney tissues. Network pharmacology also showed that SNX could improve nifedipine-induced renal lipotoxicity. The combination of SNX and nifedipine had certain benefits in the treatment of hypertension.
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http://dx.doi.org/10.1002/tox.23044DOI Listing
March 2021

Paris saponin II-induced paraptosis-associated cell death increased the sensitivity of cisplatin.

Toxicol Appl Pharmacol 2020 11 21;406:115206. Epub 2020 Aug 21.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Paris Saponin II (PSII) has been regarded as an effective and imperative component isolated from Rhizoma Paridis saponins (RPS) and exhibited strong anti-tumor effects on a variety of cancer. Our results revealed that human non-small lung cancer cell lines NCI-H460 and NCI-H520 were exposed to 1 μM of PSII, which inhibited the proliferation of lung cancer cells and activated apoptosis, autophagy and paraptosis. PSII induced paraptosis-associated cell death prior to apoptosis and autophagy. It induced paraptosis based on ER stress through activation of the JNK pathway. Meanwhile, PSII increased the cytotoxicity of cisplatin through paraptosis-associated pathway. All in all, PSII induced paraptosis based on induction of non-apoptotic cell death, which would be a possible approach to suppress the multi-drug resistant to apoptosis.
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http://dx.doi.org/10.1016/j.taap.2020.115206DOI Listing
November 2020

CRISPR-Cas13a based bacterial detection platform: Sensing pathogen Staphylococcus aureus in food samples.

Anal Chim Acta 2020 Aug 9;1127:225-233. Epub 2020 Jul 9.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China. Electronic address:

The severity of foodborne diseases caused by foods contaminated by pathogens or their toxins creates an urgent need for the development of specific and sensitive method for detection of bacteria. In this study, taking advantages of CRISPR-Cas13a system, namely, the crRNA programmability and Cas13a "collateral effect" of promiscuous RNase activity upon target RNA recognition, we developed a bacterial sensing strategy with the name of CCB-Detection (CRISPR-Cas13a based Bacterial Detection). Staphylococcus aureus (S. aureus) was chosen as a model bacteria for validating the performance of CCB-Detection. Specifically, four steps were carried out: 1) simple extraction of genome DNA; 2) specific gene amplification by PCR; 3) in vitro transcription; and 4) the "collateral effect" cleavage of reporter RNA to report the analyte signal. It was observed that CCB-Detection was capable to successfully detect the target genomic DNA (gDNA) as low as 10 aM. The limit of detection (LOD) was 1 CFU/mL with a dynamic detection range of S. aureus from 10 to 10 CFU/mL. The entire sample-to-answer time for this biosensor was less than 4 h. CCB-Detection demonstrated satisfactory selectivity for S. aureus without interference from other bacteria. Furthermore, CCB-Detection was successfully applied for sensing S. aureus in real food samples with both known and unknown amounts bacteria (spiked ones and non-spiked ones) and its performance is comparable to the conventional culture-based counting method but with short assay time and high sensitivity. With desirable reliability, sensitivity, specificity and simplicity, herein proposed CCB-Detection could be extended and generalised for other bacterial detection, and has great potential to be used in a wide range of applications such as food safety inspection, disease diagnosis, environment monitoring, etc.
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http://dx.doi.org/10.1016/j.aca.2020.06.041DOI Listing
August 2020

Integration of logic gates to CRISPR/Cas12a system for rapid and sensitive detection of pathogenic bacterial genes.

Anal Chim Acta 2020 Aug 13;1125:162-168. Epub 2020 May 13.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin Key Laboratory of Industry, Microbiology, School of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China. Electronic address:

For the first time, three 2-input elementary AND, OR, INHIBIT logic gates have been constructed by using CRISPR-Cas12a system. These logic gates utilised the intrinsic advantages of programmability, sequence specificity and high base resolution of CRISPR-Cas12a system. Among them, the AND gate owned the potentials as a built-in biosensor that responded rapidly to external pathogenic bacteria such as Staphylococcus aureus with high sensitivity and specificity. We applied the CRISPR-Cas12a based bacterial detection after a target-amplification using PCR. The total sample-to-answer time was appropriately 2.0 h, the limit of detection (LOD) was 10 CFU/mL, and the dynamic range was 10-10 CFU/mL. Also, the sequence addressability enabled this AND logic gate to accurately trace back and distinguish input genes. These above-mentioned features were highly ideal to incur a rapid response to pathogenic bacteria for decision making. Our results not only validated the possibility of using CRISPR-Cas systems for constructing bio-computing devices but also provided a prototype of biosensor for rapid and intelligent pathogenic bacteria detection.
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http://dx.doi.org/10.1016/j.aca.2020.05.017DOI Listing
August 2020

Curcumin-enhanced antitumor effects of sorafenib via regulating the metabolism and tumor microenvironment.

Food Funct 2020 Jul;11(7):6422-6432

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.

Curcumin, the main active ingredient of turmeric, is widely used as a kind of food additive and also displays a range of pharmacological activities, such as anti-inflammation, anti-tumor, liver and kidney protection, and so forth. Sorafenib was the first targeted agent against hepatocellular carcinoma (HCC), whose intolerance is related to the promotion of lipid synthesis and epithelial-to-mesenchymal transition (EMT) formation. In this study, biochemical analysis, immune cells composition, the tumor microenvironment, metabolomics, and relative metabolic enzymes and transporters were detected in H22-bearing mice treated with curcumin combined with sorafenib vs. control groups. It was found that curcumin protected against liver cancer progression through reducing the level of alpha fetoprotein in liver tissues, increasing the number of immune cells, like NK cells, inhibiting EMT via the regulation of IL-6/JAK/STAT3 and IL-1β/NF-κB pathways, suppressing anaerobic glycolysis through the inhibition of LDH and HIF-1α, and decreasing the lipid synthesis via the downregulation of FASN, and upregulated the serum HDL-C and mRNA levels of apoA1 in the sorafenib-treated mice. Furthermore, curcumin regulation of the disorder of glycolipid metabolism and EMT was also based on the PI3K/AKT pathway. A docking study was performed and proved the strong affinity between curcumin and the proteins of STAT3, FASN, and AKT. All in all, this experiment provided evidence for the addition of curcumin in the diet to enhance the antitumor efficacy of sorafenib through activating immune function, downregulating EMT, and reversing disorders of the metabolism.
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http://dx.doi.org/10.1039/c9fo01901dDOI Listing
July 2020

Antihypertensive and renal protective effect of Shunaoxin pill combined with captopril on spontaneous hypertension rats.

Biomed Pharmacother 2020 May 4;125:109977. Epub 2020 Feb 4.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China. Electronic address:

Introduction: According to previous reports, hypertension has become the most common chronic disease in the world. Captopril, an angiotensin-converting enzyme inhibitor, has been widely used for the therapy of arterial hypertension and cardiovascular diseases therapy. Besides, Shunaoxin pill (SNX) as a traditional Chinese prescription showed antihypertensive effect in our previous research.

Objective: This study means to investigate whether SNX combining with captopril could show antihypertensive and renal protective effects on spontaneous hypertension rats (SHRs).

Methods: SHRs were randomly assigned to four treatment groups, including non-treated group, captopril, SNX, and captopril + SNX-treated groups. Their body weight and systolic blood pressure (SBP) were measured weekly. Histopathological examination was analyzed through Masson staining and hematoxylin and eosin staining. Biochemical analyses, ELISA, and western blot were used to analyze their combining mechanism.

Results: In this experiment, this combinatorial therapy significantly reduced aortic wall thickness, increased the content of NO, NOS and eNOS, decreased the content of bradykinin and endothelin 1(ET-1), and regulated the levels of TG, TC and HDLC back to normal, which suggested they could induce vasodilation and lower blood pressure. Meanwhile, histological examination alleviated that captopril + SNX remarkably inhibited renal injury, including tubular disorder, inflammatory cell infiltration and fibrosis. They down-regulated the serum levels of BUN and Cr, protein expression of IL-1β, NF-κB, Bax, Cyt c, caspase 3, 8 and 9 in kidney tissues and significantly increased the levels of Bcl-2 in kidney tissues compared with monotherapy group.

Conclusion: The combinatorial treatment of SNX and captopril lowered blood pressure through adjusting NO/NOS, ET-1 and dyslipidemia profile. Furthermore, this treatment alleviated the kidney damage via reducing the release of inflammatory factors and the expression of apoptotic markers. Therefore, these results provided a rationale for future clinical use of SNX combined with captopril in antihypertensive and protecting renal functions in hypertension.
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http://dx.doi.org/10.1016/j.biopha.2020.109977DOI Listing
May 2020

Anti-cancer activity of Conyza blinii saponin against cervical carcinoma through MAPK/TGF-β/Nrf2 signaling pathways.

J Ethnopharmacol 2020 Apr 28;251:112503. Epub 2019 Dec 28.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China. Electronic address:

Ethnopharmacological Relevance: Conyza blinii H.Lév. is a type of natural plant distributed in southwest of China. Its dried overground section can be used in traditional Chinese medicine (TCM) for treating infections, inflammations and occasionally cancers. CBS (Conyza blinii saponin), mainly composed of triterpenoidal saponins of Conyza blinii H.Lév. CBS is considered as the major active fraction of this species. The current investigation have focused on the mechanisms of CBS with regard to its anti-cancer activity. Hence it is of high relevance of identifying the anti-cancer efficacy of ethnomedicine.

Aim Of The Study: To understand the anti-cancer mechanism of CBS using both in vitro and in vivo experiments.

Materials And Methods: CBS (Conyza blinii saponin) was obtained as described previously. We tested the anti-cancer activity of CBS using in vitro HeLa cell models and in vivo animal models. We adopted immunoblot, RT-PCR (reverse transcription polymerase chain reaction), luciferase reporter assay and flow cytometry to study relevant proteins, genes, pathways and cellular ROS (reactive oxygen species) responsible for anti-cancer activity of CBS. More, 24 tumour-xenografted mice were grouped randomly as 'control', 'cisplatin' (as positive control), 'low dose' and 'high dose' groups. The IL-1β, TNF-α, PGE2 and IL-2 in the blood serum and the tumour tissue of mice were measured.

Results And Conclusions: We have found that CBS is capable of inducing apoptotic cancer cell death via both caspase-dependent and -independent pathways. CBS inhibits the activation of TGF-β signaling pathway in a dose- and time-dependent manner. Phospho-ERK, phospho-JNK and phospho-p38 MAPK are significantly suppressed by CBS. Furthermore, some inflammation mediators including IL-1β, TNF-α and PGE2 from animal samples were found decreased in CBS-treated mice models. In contrast, the level of IL-2, a cytokine commonly used for treating cancers, increased reversely. Last, we have discovered that CBS is able to decrease the expression of Nrf2, inhibit the activation of ARE and increase ROS level in HeLa cells. In summary, we have confirmed that the anti-cancer activity of CBS is possibly related to its TGF-β, MAPK, Nrf2 signaling pathways as well as some cancer related inflammation mediators and cytokines.
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http://dx.doi.org/10.1016/j.jep.2019.112503DOI Listing
April 2020

Effect of brachial-ankle pulse wave velocity combined with blood pressure on cardio-cerebrovascular events.

Exp Ther Med 2019 Dec 30;18(6):4555-4566. Epub 2019 Oct 30.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P.R. China.

The aim of the present study was to evaluate the effect of brachial-ankle pulse wave velocity (baPWV) combined with blood pressure (BP) on cardio-cerebrovascular events. Participants who received health examinations during the periods 2010-2011, 2012-2013 and 2014-2015 were recruited. The participants were divided into four groups according to their BP and baPWV levels as follows: Normotension + low baPWV, normotension + high baPWV, hypertension + low baPWV, and hypertension + high baPWV. The cumulative incidence of cardio-cerebrovascular events was calculated using life-table analysis, and the associations of BP and baPWV with cardio-cerebrovascular events were analyzed using a multivariate Cox proportional hazards regression model. Receiver operating characteristic curves were used to calculate the predictive values of baPWV combined with BP, baPWV alone or BP alone for cardio-cerebrovascular events by comparing their area under the curve (AUC) using the normal approximation method. There were 20,310 participants with a mean age of 50.13±0.09 years in the present study, including 13,240 males. A total of 278 participants developed a cardio-cerebrovascular event after a mean follow-up period of 3.34±1.82 years. The cumulative incidence of cardio-cerebrovascular events in the normotension + low baPWV, normotension + high baPWV, hypertension + low baPWV and hypertension + high baPWV groups was 0.2, 0.9, 0.8 and 3.1%. Multivariate Cox proportional hazards regression analysis showed that compared with the normotension + low baPWV group, the risks of cardio-cerebrovascular events in the normotension + high baPWV, hypertension + low baPWV and hypertension + high baPWV groups were increased after adjusting for confounding factors, and their hazard ratios (95% CI) were 4.18 (2.23-7.83), 3.00 (1.39-6.47) and 9.34 (5.14-16.96), respectively. The AUC values for the predictive values of baPWV combined with BP, baPWV alone and BP alone on cardio-cerebrovascular events were calculated to be 0.744, 0.677 and 0.698, respectively. In conclusion, high baPWV accompanied by hypertension could increase the risk of cardio-cerebrovascular events. The predictive value of baPWV combined with BP on cardio-cerebrovascular events is superior compared with that of either baPWV or BP alone.
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http://dx.doi.org/10.3892/etm.2019.8149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878894PMC
December 2019

Self-assembled nano-aggregates of fluorinases demonstrate enhanced enzymatic activity, thermostability and reusability.

Biomater Sci 2020 Jan;8(2):648-656

Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology, State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin 300457, China.

Three SAP (self-assembling peptide)-tagged fluorinases (FLAs), namely, FLA-ELK16, FLA-L6KD and FLA-18A (named after the SAP used for tagging FLA) were successfully engineered. All three SAP-tagged FLAs could be highly over-expressed using engineered E. coli host cells despite being in the form of aggregates (inclusion bodies). It was noted that all three SAP-tagged FLAs exhibited enzymatic activity. It was also observed that all three SAP-tagged FLAs were capable of self-assembly to form nano-sized particles with different dimensions in aqueous solutions. Strikingly, one of the SAP-tagged FLA (FLA-L6KD) displayed improved enzyme activity, thermostability and reusability, which is potentially ideal for bio-transformation. FLA is an exotic enzyme that is capable of catalysing the formation of C-F bonds using inorganic fluorine ions as substrates. This significant feature enables it to incorporate [18F]-fluoride into different small molecules to generate radiopharmaceuticals in PET (positron emission tomography) labeling. In addition, fluorinase is greatly valuable in synthetic biology for incorporating the fluorine element into building blocks to produce non-natural organofluorines or as a biocatalyst for transforming non-native substrates. Our method would be a further step in making FLA-based biocatalysis even 'greener' by enhancing the enzymatic activity, thermostability and reusability of FLA through the introduction of nano-sized aggregates. Enzymes are such nontrivial biomaterials, which can be manifested in different scenarios. Our research expands their reach and tunes their properties by tagging SAP partners. Thus, this methodology can be put into the 'toolbox' of enzymologists, which can be further explored and generalised for others.
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http://dx.doi.org/10.1039/c9bm00402eDOI Listing
January 2020

Cardiac Glycoside Compound Isolated from Franch Displays Potent Toxicity against HeLa Cervical Carcinoma Cells through ROS-Independent Autophagy.

Chem Res Toxicol 2019 12 12;32(12):2479-2487. Epub 2019 Nov 12.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology , Tianjin University of Science & Technology , Tianjin 300457 , China.

The current study aimed to examine the anticancer activity of HTF-1, a cardiac glycoside (CG) isolated from Franch, using a cell-based model and to discover the underlying mechanisms with specific focus on autophagy. We found that HTF-1 was able to potently decrease the viability of several cancer cell lines especially for HeLa cervical carcinoma cells. It was discovered that HTF-1 dose dependently induced overproduction of ROS in HeLa cells, and the cell viability can be rescued when adding ROS scavenger -acetyl-l-cysteine (NAC). More, we found that HTF-1 induced ROS-independent autophagy in concentration- and time-dependent manners in HeLa cells. This can be collectively verified by LC3-II and p62 abundance and also eGFP-LC3 puncta assay, bafilomycin clamp experiment, and acidotropic dye fluorescent labeling experiment. Additionally, TEM examination showed more autophagic vacuoles for HTF-1-treated HeLa cells. In HeLa cells, pretreatment with wortmannin (an inhibitor of the initial stages of autophagy to block autophagosome formation, thus, it should weaken the autophagy induction effect of HTF-1) decreased the autophagic flux and partially antagonized cell death induced by HTF-1, indicating that autophagy induced by HTF-1 played a cancer-suppressing role. Furthermore, coadministration of BAF (as a distal inhibitor of autophagy) with HTF-1 demonstrated a synergistic anticancer effect against HeLa cells. We believe that our work will enrich the understanding of CGs and especially anticarcinoma activity, also, pave the way for natural-product-based anticancer drug development.
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http://dx.doi.org/10.1021/acs.chemrestox.9b00318DOI Listing
December 2019

Polyethyleneimine coated FeO magnetic nanoparticles induce autophagy, NF-κB and TGF-β signaling pathway activation in HeLa cervical carcinoma cells via reactive oxygen species generation.

Biomater Sci 2020 Jan 30;8(1):201-211. Epub 2019 Oct 30.

Key Laboratory of Industrial Fermentation Microbiology (Ministry of Education), Tianjin Key Laboratory of Industry Microbiology, School of Biotechnology, State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, Tianjin 300457, China.

FeO magnetic nanoparticles (MNPs), as one of the most intensively researched NPs, have a range of applications in cancer treatments. In current research, we have focused on the influences of MNPs on cancer cells. We chose polyethyleneimine (PEI) coated MNPs (PEI-MNPs) as a model and they are colloidally stable in biological media. It can be proved that PEI-MNPs result in autophagy induction via mTOR-Akt-p70S6 K and ATG7 signaling pathways. For the first time, we have reported that PEI-MNPs activate both NF-κB and TGF-β signaling, two key pro-inflammatory pathways, in cancer cells. More significantly, we have found that autophagy induction and NF-κB and TGF-β activation can be efficiently suppressed through the inhibition of PEI-MNP dependent reactive oxygen species (ROS) over-production. ROS are deemed as a 'double edge sword' for cancer cells, owing to the cancer-suppressing and cancer-promoting actions. Our findings would be useful for designing MNPs induced ROS anti-cancer strategies or diminishing long-term toxic effects.
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http://dx.doi.org/10.1039/c9bm01563aDOI Listing
January 2020

Diosgenyl Saponin Inducing Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptotic Pathways in Liver Cancer Cells.

J Agric Food Chem 2019 Oct 7;67(41):11428-11435. Epub 2019 Oct 7.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin 300072 , People's Republic of China.

Diosgenin and diosgenyl saponins as the major bioactive compounds isolated from dietary fenugreek seeds, yam roots, etc. possessed strong antitumor effects. To understand their detailed antitumor mechanisms, a fluorophore-appended derivative of diosgenin [Glc/CNHphth-diosgenin (GND)] was synthesized, starting from diosgenin and glucosamine hydrochloride in overall yields of 7-12% over 7-10 steps. Co-localization of GND with organelle-specific stains, transmission electron microscopy, and relative protein analyses demonstrated that GND crossed the plasma membrane through organic anion-transporting polypeptide 1B1 and distributed in the endoplasmic reticulum (ER), lysosome, and mitochondria. In this process, GND induced ER swelling, mitochondrial damage, and autophagosome and upregulating IRE-1α to induce autophagy and apoptosis. Furthermore, autophagy inhibitor chloroquine delayed the appearance of cleaved poly(ADP-ribose) polymerase and inhibited cleaved caspase 8, which indicated that GND induced autophagy to activate caspase-8-dependent apoptosis. These observations suggested that diosgenyl saponin was a potent anticancer agent that elicited ER stress and mitochondria-mediated apoptotic pathways in liver cancer.
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http://dx.doi.org/10.1021/acs.jafc.9b05131DOI Listing
October 2019

Chemotaxonomic studies of 12 Dioscorea species from China by UHPLC-QTOF-MS/MS analysis.

Phytochem Anal 2020 Mar 31;31(2):164-182. Epub 2019 Jul 31.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

Introduction: Dioscorea species, which contain abundant steroidal saponins, have been used as folk medicines or raw materials to synthesise steroid drugs.

Objective: To establish a rapid chemotaxonomic method that will comprehensively resolve confusions about genetic relationships of genus Dioscorea.

Methods: A comprehensive strategy using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) was firstly proposed to evaluate the chemotaxonomy of 12 species (27 taxa) from China by hierarchical cluster analysis (HCA) based on the variations of the identified metabolites.

Results: Twenty-eight secondary metabolites (mainly steroidal saponins) were identified. The MS fragmentation patterns of DA (a new acetylated steroidal saponin at C-7 position) were firstly reported. Moreover, eight major steroidal saponins were further quantified simultaneously by UPLC-QTOF-MS method. According to HCA results, D. bulbifera L. was distinguished with species of sect. Stenophora Uline for pennogenin-type steroidal saponins. Dioscorea zingiberensis exhibited far distance from other members of sect. Stenophora Uline for two unique saponins. Dioscorea banzhuana may be reclassified into sect. Stenophora. Dioscorea nipponica subsp. rosthornii and D. collettii var. hypoglauca might be separated from their original subspecies/varieties as new species, respectively.

Conclusion: The chemotaxonomic method was successfully applied in the study of genetic relationships of Dioscorea species. This study not only enhanced the understanding of chemical constituents, but also laid basic theoretical foundations for the rational utilisation and chemotaxonomy of genus Dioscorea.
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http://dx.doi.org/10.1002/pca.2876DOI Listing
March 2020

Preparation and Characterization of Acylcaramel.

J Agric Food Chem 2019 May 6;67(19):5614-5620. Epub 2019 May 6.

Department of Biochemistry , University of Missouri , Columbia , Missouri 65211 , United States.

Caramel is a widely used water-soluble food pigment. The acylation of caramel was conducted by aliphatic acyl chlorides with different chain lengths. Acetyl, butyryl, octyl, lauryl, palmityl, and stearyl caramels were prepared with the ratio of acyl chloride/caramel of 6. The formation of acylated caramel was confirmed by Fourier transform infrared spectra, and the acyl mass fraction in acylcaramel was determined by potentiometric titration. Thermal analysis showed that the weight loss of acylated caramel was higher than that of raw caramel. The scanning electron microscopy analysis showed that the morphology of acylated caramel was significantly different from that of raw material. The acyl mass fraction of acylated caramel increased with the increase of acyl chain lengths. Meanwhile, the lipo-hydro partition coefficient, the solubility in corn oil, and color, red, and yellow indexes increased with the increase of the mass fraction of acyl in acylcaramel. It was found that stearyl caramel has the highest lipid solubility of 5.73 mg/mL in corn oil; however, the color, red, and yellow indexes of palmityl caramel reached 25 818.60, 1.149, and 1.757, respectively. This study provides a method to improve the solubility of caramel in lipid phase and expand the application range of caramel.
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http://dx.doi.org/10.1021/acs.jafc.8b07148DOI Listing
May 2019

Protective effect of magnolol on oxaliplatin-induced intestinal injury in mice.

Phytother Res 2019 Apr 13;33(4):1161-1172. Epub 2019 Mar 13.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Oxaliplatin (OXL) is the first line treatment therapy for gastrointestinal (GI) cancers and often combines with other chemotherapy. However, few reports have studied on its GI toxicity. Magnolol (MG), one of the mainly active constituents in Magnolia, has been reported to treat digestive diseases. Therefore, the purpose of this study is to evaluate the intestinal protective effect of MG in OXL treatment group. OXL administration mice showed body weight loss, diarrhea, and intestinal damage characterized by the shortening of villi and destruction of intestinal crypts, as well as the colon length change. MG significantly reduced body weight loss, alleviated diarrhea, reversed histopathological changes, and prevented colon length reduction. Oxidative stress and inflammation were activated after OXL, and these responses were repressed by MG through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione, decreasing level of nuclear factor of kappa b and downregulating the following pro-inflammatory cytokines. Although the expression of tight junction protein occludin and numbers of proliferative crypt cells were reduced on ileum and colon after OXL, MG administration promoted these expressions. The fecal gut microbiota composition disturbed by OXL was significantly reversed by MG. Thus, MG could prevent the development and progression of mucositis induced by oxaliplatin through multipathway.
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http://dx.doi.org/10.1002/ptr.6311DOI Listing
April 2019

Discovery of Myricetin as a Potent Inhibitor of Human Flap Endonuclease 1, Which Potentially Can Be Used as Sensitizing Agent against HT-29 Human Colon Cancer Cells.

J Agric Food Chem 2019 Feb 29;67(6):1656-1665. Epub 2019 Jan 29.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology (MOE), Tianjin Key Laboratory of Industrial Microbiology, School of Biotechnology , Tianjin University of Science & Technology , Tianjin 300457 , China.

Human flap endonuclease 1 (hFEN1) is instrumental in DNA replication and repair. It is able to cleave the 5' single-stranded protrusion (also known as 5' flap) resulting from strand displacement reactions. In light of its crucial functions, hFEN1 is now deemed as a nontrivial target in the DNA damage response system for anticancer drug development. Herein, we report that myricetin and some natural flavonoids are able to inhibit hFEN1. Structure-activity relationship, inhibitory mechanisms, molecular docking, and cancer cell-based assays have been performed. Our original findings expand the activity of flavonoids and may pave the way for flavonoid-assisted targeted cancer therapy.
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http://dx.doi.org/10.1021/acs.jafc.8b05447DOI Listing
February 2019

Dioscin-6'-O-acetate inhibits lung cancer cell proliferation via inducing cell cycle arrest and caspase-dependent apoptosis.

Phytomedicine 2019 Feb 4;53:124-133. Epub 2018 Sep 4.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China; College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address:

Background: Lung cancer is the leading cause of global cancer-related mortality. Dioscin-6'-O-acetate (DA), a novel natural steroidal saponin, was firstly isolated from the rhizomes of Dioscorea althaeoides R. Knuth. Until now, there were no studies on its pharmacological activities.

Purpose: Here, we investigated the growth inhibitory effect and explored the underlying molecular mechanisms of DA against lung cancer cells.

Methods/study Designs: NSCLC H460, H1299, H520 cells and SCLC H446 cells were treated with DA. To display the cytotoxic effects and possible mechanism of DA on these cells, MTT assay, flow cytometry and western blot analysis were carried out.

Results: Our results showed that DA exerted strong anti-proliferative activity against lung cancer cells in a concentration- and time-dependent manner. Flow cytometry demonstrated DA induced the cell cycle arrest at S-phase (NCI-H460, NCI-H1299, NCI-H520) or G1-phase (NCI-H446), caused cellular apoptosis, generation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential. Western blotting analysis showed DA treatment increased the levels of caspase 3, 8, 9, Bax, p21, p53, phosphorylated JNK and p38 MAPK and markedly decreased the expression of Bcl-2, p-ERK, p-PI3K, p-AKT and NF-κB. Blockade of caspases with Z-VAD-FMK converted apoptosis-related proteins. Suppression of p53 with pifithrin-α (PFT) attenuated cell cycle-related protein. Inhibition of ROS with N-acetyl-cysteine (NAC) adjusted apoptosis-related proteins and phosphorylated MAPK and PI3K, as well as NF-κB.

Conclusion: Overall, our study indicated that DA suppressed lung cancer cells proliferation via inducing cell-cycle arrest and enhancing caspase-dependent apoptosis, at least partly, through ROS-mediated PI3K/AKT, MAPK and NF-κB signaling pathways.
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http://dx.doi.org/10.1016/j.phymed.2018.09.033DOI Listing
February 2019

The protective effects of Aquilariae Lignum Resinatum extract on 5-Fuorouracil-induced intestinal mucositis in mice.

Phytomedicine 2019 Feb 20;54:308-317. Epub 2018 Jul 20.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Background: Aquilariae Lignum Resinatum as a traditional Chinese medicine is used in prescription for treatment of gastrointestinal diseases. Phytochemical investigations show that there are many anti-ulcer and anti-inflammatory ingredients in A. agallocha methanol extract (AEE). However, scarce data is available about the constituents absorbed into the blood, activity and mechanisms of AEE on intestinal mucositis.

Hypothesis/purpose: To analyze the bioactive constituents of AEE absorbed in the blood, and further explore the potential mechanisms of the protection against chemotherapy-induced intestinal mucositis.

Methods: The serum pharmacochemistry using UHPLC-Q-TOF/MS was performed to screen the bioactive compounds of AEE absorbed in serum. The intestinal mucositis was induced by 5-Fuorouracil (5-Fu) and treated with AEE. The severity of intestinal mucositis was evaluated based on body weight, food-intake and diarrhea. Furthermore, the mechanism of AEE was investigated involved in the pathogenesis of mucositis on repairing injury of intestinal mucosa, immune functions, and inflammatory response.

Results: Altogether, 11 components were identified or tentatively characterized in dosed plasma. In pharmacodynamics study, intestinal mucositis caused by 5-Fu was effectively attenuated after AEE treatment. AEE treatment improved food-intake and injury of the intestinal mucosa, relieved body weight loss and severe diarrhea through up-regulating expression of proliferating cell nuclear antigen (PCNA) and inhibiting the levels of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in ileum segments.

Conclusions: AEE protected against 5-Fu-induced intestinal mucositis (IM) in mice through mechanisms that involved in promoting the enterocyte proliferative activity, maintaining the integrity of tight junction proteins, inhibiting oxidative stress and ameliorating the inflammatory disturbances. Accordingly, A. agallocha may be a promising therapeutic candidate used for the prevention of IM during cancer chemotherapy.
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http://dx.doi.org/10.1016/j.phymed.2018.07.006DOI Listing
February 2019

The synergistic anticancer effect of formosanin C and polyphyllin VII based on caspase-mediated cleavage of Beclin1 inhibiting autophagy and promoting apoptosis.

Cell Prolif 2019 Jan 18;52(1):e12520. Epub 2018 Oct 18.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Objectives: Drug combination has a promising and potential development prospect in the treatment of various cancers. The objective of this study is to investigate the synergistic mechanisms of polyphyllin VII (PVII) and formosanin C (FC) in lung cancer.

Materials And Methods: The combination of FC and PVII influenced on the apoptosis, autophagy, and the relative signalling pathways were analysed in lung cancer cells.

Results: The combination of FC and PVII demonstrated a concentration- dependent growth inhibition in human lung cancer cells. The combination index (CI) obtained from four lung cancer cells was smaller than 1. This synergistic antitumour effect was based on the increase of their single proapoptotic effect but inhibiting FC-induced autophagy in NCI-H460 cells. FC and PVII activated proapoptotic elements like cleaved-caspase-3, -8, and -9 to induce Beclin1 cleaved into Beclin1-C which suppressed FC-triggered autophagy and enhanced apoptosis.

Conclusions: Formosanin C and PVII showed a synergistic antitumour effect on lung cancer cells. The findings would provide the foundation for the use of combination drugs in the future.
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http://dx.doi.org/10.1111/cpr.12520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430456PMC
January 2019

A cardiac glycoside HTF-1 isolated from Helleborus thibetanus Franch displays potent in vitro anti-cancer activity via caspase-9, MAPK and PI3K-Akt-mTOR pathways.

Eur J Med Chem 2018 Oct 13;158:743-752. Epub 2018 Sep 13.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Experiments have been undertaken and for the first time, we have identified that a new cardiac glycoside (CG) isolated from Helleborus thibetanus Franch. a plant endemic to China, bears potent anti-cancer activity. We have named it as HTF-1. By using in vitro cell models, we have found that HTF-1 induces apoptosis against several types of cancer cells in a concentration- and time-dependent manner. It is able to inhibit cancer cell in proliferation, migration and invasion. HTF-1 causes S cell cycle arrest. Further-on, we have identified that HTF-1 triggers caspase-9 dependent apoptosis pathway and double strand DNA breaks (DSBs). Additionally, HTF-1 activates JNK, but suppresses ERK and PI3K-Akt-mTOR pathways. Collectively, the above-mentioned mechanisms contribute to the anti-cancer activity of HTF-1. It is rare to discover novel anti-cancer CG during the past couple of decades. We believe that our work will enrich the understanding of CGs; also, pave the way for natural product-based anti-cancer drug development.
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http://dx.doi.org/10.1016/j.ejmech.2018.09.019DOI Listing
October 2018

Combinatorial treatment of Rhizoma Paridis saponins and sorafenib overcomes the intolerance of sorafenib.

J Steroid Biochem Mol Biol 2018 10 19;183:159-166. Epub 2018 Jun 19.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China. Electronic address:

Sorafenib, as a multi-kinase inhibitor, was the first FDA-approved anti- hepatocellular carcinoma (HCC) drug. Rhizoma Paridis saponins (RPS) as natural products have shown antitumor activity through regulation of glycolytic and lipid metabolism which was regarded as the side effect limited the utility of sorafenib. In this research, we tried to use metabolomics to verify the probability of combinatorial treatment of RPS and Sorafenib. As a result, Sorafenib + RPS increased the antitumor effect of sorafenib and RPS in H22 mice. They mitigated the change of liver weight and the increasing levels of AST and ALT in serum, and AFP and MDA in liver tissues, which indicated their liver protective activity. They also up-regulated the activity of NOX and SDH, concentration of ATP, and down-regulated the mRNA and protein levels of HIF-1a and concentration of lactate, which suggested they protected against mitochondria damage and inhibited anaerobic glycolysis. Meanwhile, the combination group remarkably down-regulated the concentration of octadecanoic acid and hexadecanoic acid in serum, and tetradecanoic acid in liver tissues compared with model group (p < 0.05). Relative regulation mechanism included their decreasing mRNA levels of FASN, CPT1, GLUT1, Myc, Akt, mTOR and LDHA, and increasing the protein expression of p53 in tumor and liver tissues (p < 0.05). Furthermore, similar influence can be observed in protein levels of CPT1A, p-PI3K, p-mTOR and p53 in liver tissues and FASN in serum. All of that provided possibility to overcome the intolerance of sorafenib by drug compatibility through protection against mitochondria damage, inhibition of anaerobic glycolysis and suppression of lipid synthesis based on PI3K/Akt/mTOR pathway.
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http://dx.doi.org/10.1016/j.jsbmb.2018.06.010DOI Listing
October 2018

Modeling of the bacterial inactivation kinetics of dialdehyde cellulose in aqueous suspension.

Int J Biol Macromol 2018 Sep 29;116:920-926. Epub 2018 May 29.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology, Tianjin 300457, People's Republic of China.

The purpose of this study was to estimate the antibacterial properties of aqueous suspensions of dialdehyde microcrystalline cellulose (DAMC), and a model of the observed antibacterial kinetics was proposed and validated. The DAMC was prepared from microcrystalline cellulose by periodate oxidation. The bacterial inactivation kinetics of aqueous suspensions of DAMC was investigated by measuring the bactericidal effect after different contact times. The results indicated that with a DAMC aldehyde content of 6.34 mmol/g, the MICs for S. aureus, E. coli, B. subtilis and S. typhimurium were 15, 15, 15 and 30 mg/mL, respectively. This research thus establishes an antibacterial kinetics model of DAMC with 6.34 mmol/g of aldehyde content. At 37 °C and atmospheric pressure, the bacterial inactivation kinetic conformed to the equation: Log reduction of bacteria = - k [DAMC] t.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.05.074DOI Listing
September 2018

Curcumin enhances the anti-cancer effects of Paris Saponin II in lung cancer cells.

Cell Prolif 2018 Aug 2;51(4):e12458. Epub 2018 Apr 2.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Objectives: To investigate the synergistic mechanisms of Paris Saponin II (PSII) and Curcumin (CUR) in lung cancer.

Materials And Methods: The combination changed the cellular uptake of CUR and PSII, apoptosis, cell cycle arrest and cytokine levels were analysed on different lung cancer cells.

Results: The combination displayed a synergistic anti-cancer effect through promoting the cellular uptake of CUR on different lung cancer cells. Hoechst H33258 staining and FACS assay indicated that the combination of PSII and CUR induced cell cycle arrest and apoptosis. Western blot and cytokine antibody microarray suggested that the combination activated death receptors such as DR6, CD40/CD40L, FasL and TNF-α to induce cancer cells apoptosis, and up-regulated IGFBP-1 leading to inhibition of PI3K/Akt pathway and increase of p21 and p27, which therefore induced a G2 phase arrest in NCI-H446 cells. Meanwhile, the combination suppressed PCNA and NF-κB pathway in 4 kinds of lung cancer cells. They activated the phosphorylation of p38 and JNK, and inhibited PI3K in NCI-H460 and NCI-H446 cells, enhanced the phosphorylation of JNK in NCI-H1299 cells, and increased the phosphorylation of p38 and ERK, and suppressed PI3K in NCI-H520 cells.

Conclusions: PSII combined with CUR had a synergistic anti-cancer effect on lung cancer cells. These findings provided a rationale for using the combination of curcumin and PSII in the treatment of lung cancer in future.
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http://dx.doi.org/10.1111/cpr.12458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528905PMC
August 2018

Supplementary data for the mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl free radical.

Data Brief 2017 Dec 2;15:414-418. Epub 2017 Oct 2.

Key Laboratory of Industrial Fermentation Microbiology (Tianjin University of Science & Technology), Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, TEDA, No. 29 of 13th Street, Tianjin 300457, PR China.

The data presented in this article are related to the research article entitled "The mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl free radical" (Dai et al., 2017) [1]. This article includes the structures of three kinds of disaccharides such as maltose, fructose and cellobiose, the diagrammatic sketch of the hydrogen abstraction reaction of the disaccharides by hydroxyl radical, the structure of the transition states for pyran ring opening of moiety A and cleavage of α(1→2) glycosidic bond starting from the hydrogen abstraction of C6-H in moiety A of sucrose, the transition state structure for cleavage of α(1→2) glycosidic bond starting from the hydrogen abstraction of C1'-H in moiety B of sucrose, the transition state structure, sketch for the reaction process and relative energy change of the reaction pathway for direct cleavage of α(1→4) glycosidic bond starting from hydrogen abstraction of C6'-H of moiety B of maltose.
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http://dx.doi.org/10.1016/j.dib.2017.09.069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712059PMC
December 2017