Publications by authors named "Meimei Zhao"

20 Publications

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Malting barley carbon dots-mediated oxidative stress promotes insulin resistance in mice via NF-κB pathway and MAPK cascade.

J Nanobiotechnology 2022 Jul 16;20(1):331. Epub 2022 Jul 16.

School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China.

Background: Food-borne carbon dots (CDs) are widely generated during food processing and are inevitably ingested by humans causing toxicity. However, the toxic effects of food-borne CDs on the blood glucose metabolism are unknown.

Results: In this study, we brewed beer via a representative strategy and extracted the melting-barley CDs (MBCDs) to explore the toxic effects on blood glucose in mice. We found the accumulation of fluorescent labeled MBCDs in various organs and oral administration of MBCDs can cause visceral toxicity, manifested as liver damage. Mice were orally administered MBCDs (5 and 25 mg/kg) for 16 weeks, and increased levels of fasting blood glucose were observed in both MBCDs-treated groups. Transcriptomic analyses revealed that MBCDs activate oxidative stress, inflammatory responses, the MAPK cascade, and PI3K/Akt signaling in mice livers. Mechanistically, MBCDs exposure-induced reactive oxygen species (ROS) overproduction activates the nuclear factor-κB (NF-κB) signaling pathway and MAPK cascade, thereby promoting phosphorylated insulin receptor substrate (IRS)-1 at Ser307 and inducing insulin resistance (IR). Meanwhile, the IR promoted gluconeogenesis, which enhanced MBCDs-induced hyperglycemia of mice. Importantly, inhibition of the ROS significantly attenuated the MBCDs-induced inflammatory response and MAPK cascade, thereby alleviating IR and hyperglycemia in mice.

Conclusion: In summary, this study revealed that MBCDs promote ROS overproduction and thus induced IR, resulting in imbalance of glucose homeostasis in mice. More importantly, this study was further assessed to reveal an imperative emphasis on the reevaluation of dietary and environmental CDs exposure, and has important implications for T2DM prevention research.
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http://dx.doi.org/10.1186/s12951-022-01543-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288084PMC
July 2022

Rapid detection of the irinotecan-related UGT1A1*28 polymorphism by asymmetric PCR melting curve analysis using one fluorescent probe.

J Clin Lab Anal 2022 Jun 29:e24578. Epub 2022 Jun 29.

Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.

Background: Determination of UGT1A1 (TA) polymorphism prior to irinotecan therapy is necessary to avoid severe adverse drug effects. Thus, accurate and reliable genotyping methods for (TA) polymorphism are highly desired. Here, we present a new method for polymerase chain reaction (PCR) melting curve analysis using one fluorescent probe to discriminate the UGT1A1*1 [(TA) ] and *28 [(TA) ] genotypes.

Methods: After protocol optimization, this technique was applied for genotyping of 64 patients (including 23 with UGT1A1*1/*1, 22 with *1/*28, and 19 with *28/*28) recruited between 2016 and 2021 in China-Japan Friendship Hospital. The accuracy of the method was evaluated by comparing the results with those of direct sequencing and fragment analysis. The intra- and inter-run precision of the melting temperatures (T s) were calculated to assess the reliability, and the limit of detection was examined to assess the sensitivity.

Results: All genotypes were correctly identified with the new method, and its accuracy was higher than that of fragment analysis. The intra- and inter-run coefficients of variation for the T s were both ≤0.27%, with standard deviations ≤0.14°C. The limit of detection was 0.2 ng of input genomic DNA.

Conclusion: The developed PCR melting curve analysis using one fluorescent probe can provide accurate, reliable, rapid, simple, and low-cost detection of UGT1A1 (TA) polymorphism, and its use can be easily generalized in clinical laboratories with a fluorescent PCR platform.
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http://dx.doi.org/10.1002/jcla.24578DOI Listing
June 2022

Di-(2-ethylhexyl) phthalate increases plasma glucose and induces lipid metabolic disorders via FoxO1 in adult mice.

Sci Total Environ 2022 Jun 21;842:156815. Epub 2022 Jun 21.

School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China; State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150006, China. Electronic address:

Di-(2-ethylhexyl) phthalate (DEHP), an endocrine-disrupting chemical (EDC) commonly used as a plasticizer, is responsible for widespread environmental pollution. Epidemiological and experimental data implicate DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) in the occurrence and development of metabolic syndrome. However, the specific effects and potential mechanisms of action of DEHP on glucose and lipid metabolism in adults are currently unclear. In the current study, adult male mice were continuously exposed to DEHP (0, 5, and 25 mg/kg/day) via oral administration and changes in glucose and lipid metabolism explored. Notably, exposure to DEHP led to a significant increase in plasma glucose and hepatic lipid accumulation but had no effect on insulin secretion. Western blot and real-time quantitative PCR showed that DEHP induced insulin resistance and promoted gluconeogenesis and lipid accumulation via overexpression of forkhead box protein O1 (FoxO1), in keeping with hepatic RNA sequencing data. Variations in gut microbiota aggravated these effects while inhibition of FoxO1 reversed the adverse effects of DEHP. Our findings support a key role of FoxO1 in disorders of glucose and lipid metabolism caused by DEHP.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156815DOI Listing
June 2022

A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.

Front Oncol 2022 28;12:860701. Epub 2022 Mar 28.

Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.

Background: Because of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.

Methods: A total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.

Results: Compared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.

Conclusion: In this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.
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http://dx.doi.org/10.3389/fonc.2022.860701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995552PMC
March 2022

Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan.

Int J Hypertens 2022 19;2022:7677252. Epub 2022 Mar 19.

Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.

Background: The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor () gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 () gene polymorphism (∗3).

Methods: 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the and gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group ( = 144, SBP/DBP <140/90 mmHg) and poorly controlled group ( = 137, SBP/DBP ≥140/90 mmHg).

Results: Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of A1166C were detected in the well-controlled than the poorly controlled patients ( = 0.005 and  = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199-6.705,  = 0.018). No significant difference was observed in the allele or genotype distribution of ∗3 polymorphism between well-controlled and poorly controlled patients.

Conclusions: The current data suggested that the A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.
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http://dx.doi.org/10.1155/2022/7677252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957473PMC
March 2022

Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer.

Acta Pharm Sin B 2021 Jul 21;11(7):1853-1866. Epub 2021 Jan 21.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells. Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins. Thus, targeting myosin-actin molecular motor is considered as a promising strategy for anti-cancer. In this study, we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics pharmacologically targeting molecular motor. Here, we found J13 could directly target myosin-9 (MYH9)-actin molecular motor to promote mitochondrial fission progression, and markedly inhibited cancer cells survival, proliferation and migration. Mechanism study revealed that J13 impaired MYH9-actin interaction to inactivate molecular motor, and caused a cytoskeleton-dependent mitochondrial dynamics imbalance. Moreover, stable isotope labeling with amino acids in cell culture (SILAC) technology-coupled with pulldown analysis identified HSPA9 as a crucial adaptor protein connecting MYH9-actin molecular motor to mitochondrial fission. Taken together, we reported the first natural small-molecule directly targeting MYH9-actin molecular motor for anti-cancer translational research. Besides, our study also proved the conceptual practicability of pharmacologically disrupting mitochondrial fission/fusion dynamics in human cancer therapy.
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http://dx.doi.org/10.1016/j.apsb.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343112PMC
July 2021

Cephalotaxine Inhibits the Survival of Leukemia Cells by Activating Mitochondrial Apoptosis Pathway and Inhibiting Autophagy Flow.

Molecules 2021 May 18;26(10). Epub 2021 May 18.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

Cephalotaxine (CET) is a natural alkaloid with potent antileukemia effects. However, its underlying molecular mechanism has not been well understood. In this study, we verified that CET significantly inhibited the viability of various leukemia cells, including HL-60, NB4, Jurkat, K562, Raji and MOLT-4. RNA-sequencing and bioinformatics analysis revealed that CET causes mitochondrial function change. Mechanism research indicated that CET activated the mitochondrial apoptosis pathway by reducing the mitochondrial membrane potential, downregulating anti-apoptotic Bcl-2 protein and upregulating pro-apoptotic Bak protein. In addition, the autophagy signaling pathway was highly enriched by RNA-seq analysis. Then, we found that CET blocked the fluorescence colocation of MitoTracker Green and LysoTracker Red and upregulated the level of LC3-II and p62, which indicated that autophagy flow was impaired. Further results demonstrated that CET could impair lysosomal acidification and block autophagy flow. Finally, inhibiting autophagy flow could aggravate apoptosis of HL-60 cells induced by CET. In summary, this study demonstrated that CET exerted antileukemia effects through activation of the mitochondria-dependent pathway and by impairing autophagy flow. Our research provides new insights into the molecular mechanisms of CET in the treatment of leukemia.
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http://dx.doi.org/10.3390/molecules26102996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158396PMC
May 2021

Global identification of the cellular targets for a multi-molecule system by a photochemically-induced coupling reaction.

Chem Commun (Camb) 2021 Apr 19;57(28):3449-3452. Epub 2021 Mar 19.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Current target identification strategies mainly focus on single compounds. However, no practical experimental methodologies have been developed for multi-molecule systems. Herein, we established a cellular target identification technology for a multi-molecule system by preparing 4,4'-dihydroxybenzophenone (DHBP)-bound FeO nanoparticles (NPs) with photochemically induced crosslinking capacity. DHBP-bound NPs reacted with the chemicals from the medicinal plant extract as a multi-molecule system under ultraviolet radiation by forming carbon-carbon bonds, thus generating extract-crosslinked NPs for capturing target proteins from cell lysates. The technology, which is named the Zhao-Yao (ZY) strategy, may promote the comprehensive interpretation of the pharmacological mechanism of multi-molecule systems via the global identification of cellular targets.
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http://dx.doi.org/10.1039/d1cc00392eDOI Listing
April 2021

Characterization of selenized polysaccharides from Ribes nigrum L. and its inhibitory effects on α-amylase and α-glucosidase.

Carbohydr Polym 2021 May 3;259:117729. Epub 2021 Feb 3.

College of Art and Science, Northeast Agricultural University, Harbin, 150030, People's Republic of China. Electronic address:

The polysaccharide from Ribes nigrum L. (RCP) was modified by nitric acid-sodium selenite method. After purification by Sepharose-6B, high purity native (PRCP) and three selenized polysaccharides (PRSPs) with different selenium contents were obtained. Compared with PRCP, PRSPs possessed the lower molecular weight, better water-solubility, physical stability and rheological properties. FT-IR and NMR spectra confirmed PRSPs had the characteristic absorption peaks of polysaccharides and the glycosidic bond types were not changed after selenylation modification, whereas the selenyl groups existing in PRSPs were mainly introduced at the C-6 position of sugar residue →4)-β-d-Manp-(1→. Moreover, PRSPs displayed obviously smoother and smaller flaky structure than PRCP, and their inhibitory effects on α-amylase and α-glucosidase also were greater than PRCP. PRSPs exhibited a reversible inhibition on two enzymes in competitive manner and quenched their fluorescence through the static quenching mechanism. The polysaccharide-enzyme complex was spontaneously formed mainly driven by the hydrophobic interaction and hydrogen bonding.
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http://dx.doi.org/10.1016/j.carbpol.2021.117729DOI Listing
May 2021

Preparation, characterization, antioxidant and antiglycation activities of selenized polysaccharides from blackcurrant.

RSC Adv 2020 Sep 2;10(54):32616-32627. Epub 2020 Sep 2.

College of Art and Science, Northeast Agricultural University Harbin 150030 People's Republic of China +86 451 55190243 +86 451 55191442 +86 451 55191810.

An ultrasound-assisted enzymatic method was used to extract the polysaccharides from blackcurrant fruits (BP), and then a nitric acid-sodium selenite method was employed to prepare twelve kinds of selenized blackcurrant polysaccharides (SBPs). Among them, SBP-1, SBP-2 and SBP-3 with different selenium contents of 250 ± 11, 312 ± 15 and 643 ± 24 μg g, displayed relatively higher 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙) scavenging activities than the others. After treating with a Sepharose-6B chromatography column, the purified blackcurrant polysaccharide (PBP) and three selenized polysaccharides (PSBP-1, PSBP-2, PSBP-3) with high purity were obtained. Compared with PBP, PSBPs possessed a larger absolute value of zeta potential (ZP) and smaller particle size, indicating the positive influence of selenized modification on physical stability of polysaccharides. Ultraviolet (UV), Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra confirmed that selenium had been introduced onto the polysaccharide structure. X-ray diffraction (XRD) and I-KI reaction results indicated that selenized modification did not cause an obvious change in crystal form and branch structure of blackcurrant polysaccharides. In addition, PSBPs were superior to PBP in antioxidant and antiglycation capacities, and the bioactivities of PSBPs were significantly improved in positive correlation with selenium content. This study suggested that PSBPs may be a potential selenium source and serve as functional food and medicine.
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http://dx.doi.org/10.1039/d0ra06462aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056601PMC
September 2020

Effect and safety of acupotomy in treatment of knee osteoarthritis: a systematic review and Meta-analysis.

J Tradit Chin Med 2020 06;40(3):355-364

College of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.

Objective: To evaluate the clinical efficacy and safety of acupotomy in treatment of knee osteoarthritis (OA).

Methods: Extensive literature searches were carried out in PubMed, EMBASE, Cochrane Library (Issue 5, 2017), Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, China Science and Technology Journal Database and Wanfang Database. All databases were retrieved from their inception until May 31, 2017. Randomized controlled trials incorporating acupotomy versus intra-articular sodium hyaluronate for knee osteoarthritis were included. According to Cochrane Reviews' Handbook (5.2), two reviewers screened each article and extracted data independently and were blinded to the findings of each reviewer. Meta-analysis was performed by the Cochrane Collaboration's RevMan 5.3 software.

Results: We identified 12 studies involving 1150 patients aged between 40 and 78 years old. The pooled analysis indicated that acupotomy showed a significant improvement for short-term effect [cure rate: odds ratio (OR) = 2.04, 95% confidence interval (CI) (1.46, 2.85), P < 0.01; total effective rate: OR = 2.25, 95% CI (1.55, 3.28), P < 0.01; pain score: standard mean difference (SMD) = -1.02; 95% CI (-1.72, -0.31); P = 0.005; Western Ontario and McMaster Universities Questionnaire (WOMAC) score: SMD = -0.74; 95% CI (-1.11, -0.37); P < 0.01]; and also for long-term effect [total effective rate: OR = 2.99, 95%CI (1.88, 4.76), Z = 4.64, P < 0.01; pain score: SMD = -1.68; 95% CI (-2.14, -1.22); P < 0.001; WOMAC score: SMD = -0.91; 95% CI (-1.40, -0.41); P < 0.001]. In addition, there was no obvious difference between acupotomy group and control group in adverse events [OR = 2.13, 95%CI (0.14, 32.28), P = 0.58].

Conclusion: Acupotomy is a safe and effective treatment for KOA. However, due to the methodological deficiency of the included studies, well-designed randomized controlled trials are required to further confirm the findings.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.03.002DOI Listing
June 2020

Preparation, characteristics, and antioxidant activities of carboxymethylated polysaccharides from blackcurrant fruits.

Int J Biol Macromol 2020 Jul 9;155:1114-1122. Epub 2019 Nov 9.

College of Science, Northeast Agricultural University, Harbin 150030, People's Republic of China. Electronic address:

In the present study, the native polysaccharide (RNP) extracted from blackcurrant fruits was carboxymethylated. Physicochemical characteristics and antioxidant activities in vitro of RNP and three carboxymethylated polysaccharides (CRNPs) were determined. GC analysis proved that RNP and CRNPs were composed of the same six monosaccharides (galacturonic acid, rhamnose, arabinose, mannose, glucose and galactose), but the molar ratios of monosaccharides were different. HPLC demonstrated that the molecular weights of CRNPs were improved. The assays of the antioxidant properties indicated that CRNPs possessed stronger scavenging activities on radicals (hydroxyl and superoxide radicals) and better anti-lipid peroxidation activities, as well as better protection effects on erythrocyte hemolyses in vitro compared with RNP. The activities of CRNPs were significantly enhanced with the increase of the degree of substitution (DS). These results proved that the carboxymethylation could effectively increase the antioxidant activities of the polysaccharide.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.11.078DOI Listing
July 2020

The interaction mechanism between alkaloids and pepsin based on lum-AuNPs in the chemiluminescence analysis.

RSC Adv 2019 Aug 15;9(44):25569-25575. Epub 2019 Aug 15.

Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University Xi'an 710069 China

Herein, novel luminol functional gold nanoparticles (lum-AuNPs) were quickly prepared in an alkaline luminol solution with HAuCl, which had the unique characteristics of uniform size and excellent luminescence properties. A self-made flow injection-chemiluminescence (FI-CL) system was established to study the interaction between pepsin (Pep) and five alkaloids (anisodamine, berberine, reserpine, jatrorrhizine and matrine) using lum-AuNPs as the CL probe. Based on the abovementioned home-made CL system, the possible interaction mechanisms of Pep with five alkaloids have been comprehensively discussed by molecular docking simulation, chemical thermodynamics and kinetic studies. The results indicated that there were obvious CL enhancement and inhibition effects on the lum-AuNPs CL system for the Pep and the complex of Pep/alkaloids, respectively. The possible mechanism for the interaction of Pep-five alkaloids was mainly mediated by the hydrophobic force. The binding constant and binding site for the Pep-alkaloid interaction are consistent with the list of Ber > Res > Ani, Jat > Mat, which is relative to the potential of groups of alkaloids interacting with the active site of Pep.
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http://dx.doi.org/10.1039/c9ra02978hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070008PMC
August 2019

C1QBP Promotes Homologous Recombination by Stabilizing MRE11 and Controlling the Assembly and Activation of MRE11/RAD50/NBS1 Complex.

Mol Cell 2019 09 25;75(6):1299-1314.e6. Epub 2019 Jul 25.

Department of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address:

MRE11 nuclease forms a trimeric complex (MRN) with RAD50 and NBS1 and plays a central role in preventing genomic instability. When DNA double-strand breaks (DSBs) occur, MRN is quickly recruited to the damage site and initiates DNA end resection; accordingly, MRE11 must be tightly regulated to avoid inefficient repair or nonspecific resection. Here, we show that MRE11 and RAD50 form a complex (MRC) with C1QBP, which stabilizes MRE11/RAD50, while inhibiting MRE11 nuclease activity by preventing its binding to DNA or chromatin. Upon DNA damage, ATM phosphorylates MRE11-S676/S678 to quickly dissociate the MRC complex. Either excess or insufficient C1QBP impedes the recruitment of MRE11 to DSBs and impairs the DNA damage response. C1QBP is highly expressed in breast cancer and positively correlates with MRE11 expression, and the inhibition of C1QBP enhances tumor regression with chemotherapy. By influencing MRE11 at multiple levels, C1QBP is, thus, an important player in the DNA damage response.
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http://dx.doi.org/10.1016/j.molcel.2019.06.023DOI Listing
September 2019

Association of Depression/Anxiety Symptoms with Neck Pain: A Systematic Review and Meta-Analysis of Literature in China.

Pain Res Manag 2018 25;2018:3259431. Epub 2018 Sep 25.

College of Clinical Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Background: Due to its high morbidity and prevalence, the potential relationships of depression/anxiety symptoms in neck pain (NP) are not well demonstrated.

Objectives: This study aimed to conduct a comprehensive estimation of controlled trials of psychological problems and to test hypotheses concerning whether NP was statistically relative to anxiety/depression symptoms.

Methods: Chinese literature databases such as the China National Knowledge Infrastructure (CNKI), VIP Information (VIP), Chinese Biomedicine (CBM), and Wanfang Data (WANFANG) were scientifically searched for reports published until February 5, 2018. Controlled trials incorporating NP patients with anxiety/depression versus healthy people were contained. Two researchers screened each article and extracted data, respectively, and blinded to the findings of each other. Meta-analysis was conducted by the Cochrane Collaboration's RevMan 5.3 and Stata 14.0 (Stata Corp LP, USA) software.

Results: We identified 13 eligible studies involving 2339 patients and 3290 healthy people. Compared with healthy control participants, the findings indicated that depression/anxiety symptoms were more common or severe in NP patients (respectively, SMD = 0.89; 95% CI = (0.58, 1.20); < 0.01 and SMD = 0.92; 95% CI = (0.65, 1.20); and < 0.01), results from the pooled data demonstrated no statistical significance between depression/anxiety symptoms and gender in NP patients (resp., SMD = 0.16; 95% CI = (-0.18, 0.51); =0.35 and SMD = -0.08; 95% CI = (-0.42, 0.27); and =0.67), and the combined data of the incidence of depression or anxiety symptoms revealed significant difference between NP patients and healthy persons (resp., RR = 4.81; 95% CI = (3.30, 7.01); < 0.01 and RR = 3.29; 95% CI = (2.16, 5.00); and < 0.01). In addition, we did not find articles that met the inclusion criteria, which compared NP patients with other physical illnesses in terms of anxiety/depression symptoms.

Conclusions: This meta-analysis suggests that anxiety/depression symptoms are associated with high morbidity in NP patients. We consider these reports support the viewpoint that nonspecific mechanisms mediate mental disturbances in NP. This study may have clinical value for NP, offering an underlying target for the prevention and treatment of anxiety/depression.
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http://dx.doi.org/10.1155/2018/3259431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176305PMC
December 2018

Anticonvulsant activities of α-asaronol ((E)-3'-hydroxyasarone), an active constituent derived from α-asarone.

Pharmacol Rep 2018 Feb 31;70(1):69-74. Epub 2017 Aug 31.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, PR China. Electronic address:

Background: Epilepsy is one of chronic neurological disorders that affects 0.5-1.0% of the world's population during their lifetime. There is a still significant need to develop novel anticonvulsant drugs that possess superior efficacy, broad spectrum of activities and good safety profile.

Methods: α-Asaronol and two current antiseizure drugs (α-asarone and carbamazepine (CBZ)) were assessed by in vivo anticonvulsant screening with the three most employed standard animal seizure models, including maximal electroshock seizure (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3-mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety evaluation, acute neurotoxicity was assessed with minimal motor impairment screening determined in the rotarod test, and acute toxicity was also detected in mice.

Results: In our results, α-asaronol displayed a broad spectrum of anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in MES, PI = 8.68 in PTZ) and lower acute toxicity (LD = 2940 mg/kg) than its metabolic parent compound (α-asarone). Additionally, α-asaronol displayed a prominent anticonvulsant profile with ED values of 62.02 mg/kg in the MES and 79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED of 240 mg/kg and 115 mg/kg in the relevant test, respectively.

Conclusion: The results of the present study revealed α-asaronol can be developed as a novel molecular in the search for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity. Meanwhile, the results also suggested that α-asaronol has great potential to develop into another new aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet's syndrome.
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http://dx.doi.org/10.1016/j.pharep.2017.08.004DOI Listing
February 2018

Acetylation of 53BP1 dictates the DNA double strand break repair pathway.

Nucleic Acids Res 2018 01;46(2):689-703

Institute of Systems Biomedicine, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.

P53-binding protein 1 (53BP1) plays critical roles in DNA double strand break (DSB) repair by promoting non-homologous end joining (NHEJ), and loss of 53BP1 abolishes PARPi sensitivity in BRCA1-deficient cells by restoring homologous recombination (HR). 53BP1 is one of the proteins initially recruited to sites of DSBs via recognition of H4K20me2 through the Tudor-UDR domain and H2AK15ub through the UDR motif. Although extensive studies have been conducted, it remains unclear how the post-translational modification of 53BP1 affects DSB repair pathway choice. Here, we identified 53BP1 as an acetylated protein and determined that acetylation of 53BP1 inhibit NHEJ and promote HR by negatively regulating 53BP1 recruitment to DSBs. Mechanistically, CBP-mediated acetylation of K1626/1628 in the UDR motif disrupted the interaction between 53BP1 and nucleosomes, subsequently blocking the recruitment of 53BP1 and its downstream factors PTIP and RIF1 to DSBs. Hyperacetylation of 53BP1, similar to depletion of 53BP1, restored PARPi resistance in BRCA1-deficient cells. Interestingly, 53BP1 acetylation was tightly regulated by HDAC2 to maintain balance between the HR and NHEJ pathways. Together, our results demonstrate that the acetylation status of 53BP1 plays a key role in its recruitment to DSBs and reveal how specific 53BP1 modification modulates the choice of DNA repair pathway.
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http://dx.doi.org/10.1093/nar/gkx1208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778472PMC
January 2018

Acupotomy Therapy for Chronic Nonspecific Neck Pain: A Systematic Review and Meta-Analysis.

Evid Based Complement Alternat Med 2017 23;2017:6197308. Epub 2017 Aug 23.

Research Center for Differentiation and Development of TCM Basic Theory, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Objective: This review is to assess the efficacy and safety of acupotomy therapy in chronic nonspecific neck pain.

Methods: We searched six computerised databases. Randomized controlled trials incorporating acupotomy therapy alone or combined with other conventional treatments for chronic nonspecific neck pain were included. Two reviewers screened each literature and extracted data independently according to Cochrane Reviews' Handbook (5.1). The Cochrane Collaboration's RevMan 5.3 software was applied for meta-analysis.

Results: A total of ten trials involving 433 patients were enrolled. The pooled analysis indicated that acupotomy therapy showed a significant improving short-term and long-term effect on effective rate and cure rate. Meta-analysis demonstrated that acupotomy therapy group was superior to control group in restoring cervical lordosis and debasing VAS score. The result of continuous data did not support statistical significance of acupotomy therapy in adjusting clinical symptom score. For adverse events, acupotomy group did not reveal obvious superiority compared to control group.

Conclusions: Acupotomy therapy may be beneficial to chronic nonspecific neck pain patients. To strengthen supportive evidence, future, more rigorously designed clinical trials, adequate adverse events, and follow-up project are recommended.
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http://dx.doi.org/10.1155/2017/6197308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613650PMC
August 2017

PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair.

Cell Rep 2017 Aug;20(9):1997-2009

Institute of Systems Biomedicine, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address:

The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER) but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway. DNA-PK phosphorylates and activates PCAF upon UV damage and consequently promotes the acetylation of RPA1. Moreover, the acetylation of RPA1 is tightly regulated by HDAC6 and SIRT1. Together, our results demonstrate that the K163 acetylation of RPA1 plays a key role in the repair of UV-induced DNA damage and reveal how the specific RPA1 modification modulates the choice of distinct DNA repair pathways.
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http://dx.doi.org/10.1016/j.celrep.2017.08.015DOI Listing
August 2017

Traditional Uses, Chemical Constituents and Biological Activities of Plants from the Genus Sanguisorba L.

Am J Chin Med 2017 2;45(2):199-224. Epub 2017 Mar 2.

* Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University Xi'an 710069, P. R. China.

Plants from the genus Sanguisorba have been treated as medicinal ingredients for over 2000 years. This paper reviews advances in the botanical, phytochemical and pharmacological studies of the genus. To date, more than 120 chemical constituents have been isolated and identified from these plants, especially from S. officinalis and S. minor. Among these compounds, triterpenoids, phenols and flavonoids are the primary biologically active constituents. Triterpenoids can be used as quality control markers to determine the quality of medicinal materials and their preparations. In vivo and in vitro studies have shown that plants from the genus Sanguisorba exhibit a wide range of pharmacological properties, including hemostatic, antibacterial, antitumor, neuroprotective and hypoglycemic activities. In Chinese medical practice, many drugs (e.g., tablets and powders) that contain S. officinalis roots have been used to treat leukopenia, hemorrhaging and burns. However, there is still a multitude of Sanguisorba species that have garnered little or no attention. Indeed, there are few reports concerning the clinical use and toxic effects of these plants. Further attention should be focused on the study of these species in order to gather information on their respective toxicology data, any relevant quality-control measures, and the clinical value of the crude extracts, active compounds, and bioactive metabolites from Genus Sanguisorba.
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http://dx.doi.org/10.1142/S0192415X17500136DOI Listing
May 2017
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