Publications by authors named "Jie Shao"

265 Publications

Effect of Daily Iron Supplementation on Infantile Iron Homeostasis in Preterm Infants.

Front Pediatr 2021 28;9:687119. Epub 2021 May 28.

Department of Pediatric Health Care, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

The aim of this study was to investigate the effects of unified iron supplementation and identify the factors related to the iron homeostasis among preterm infants. A total of 250 preterm infants were divided into neonatal anemic (NA, = 154) and non-neonatal anemic group (NNA, = 96). Iron supplements at a dose of 2 mg/kg per day were given from 40 weeks' gestational age to 6 months. Iron status parameters were measured at 3 and 6 months, respectively. Prevalence of iron deficiency (ID) and iron deficiency anemia (IDA), and the correlated factors were analyzed. Growth and side-effects were monitored. There were no significant differences for the prevalence of ID or IDA between the two groups. Multivariate regression analyses showed that higher Hb at birth and early treatment of blood transfusion reduced the risk of ID/IDA at 3 months (all < 0.05); while higher level of Hb at 3 months ( = 0.004) and formula feeding reduced the occurrence of ID/IDA at 6 months ( < 0.05); males had a 3.35 times higher risk to develop ID/IDA than girls ( = 0.021). No differences in growth and side effects were found. A daily dose of 2 mg/kg iron supplement is beneficial to maintain iron homeostasis in majority preterm infants within 6 months regardless of their neonatal anemia history. Under the routine iron supplementation, Hb level at birth and at 3 months, early treatment of blood transfusion, gender and feeding patterns are the major factors affecting the prevalence of ID/IDA among preterm infants in infancy.
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http://dx.doi.org/10.3389/fped.2021.687119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192839PMC
May 2021

Caffeic Acid Phenyl Ester (CAPE) Protects against Iron-Mediated Cellular DNA Damage through Its Strong Iron-Binding Ability and High Lipophilicity.

Antioxidants (Basel) 2021 May 18;10(5). Epub 2021 May 18.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, The Chinese Academy of Sciences, Beijing 100085, China.

Caffeic acid phenethyl ester (CAPE) and its structurally-related caffeic acid (CA), ferulic acid (FA) and ethyl ferulate (EF) are constituents of honeybee propolis that have important pharmacological activities. This study found that CAPE-but not CA, FA, and EF-could effectively prevent cellular DNA damage induced by overloaded iron through decreasing the labile iron pool (LIP) levels in HeLa cells. Interestingly, CAPE was found to be more effective than CA in protecting against plasmid DNA damage induced by Fe(II)-HO or Fe(III)-citrate-ascorbate-HO via the inhibition of hydroxyl radical (•OH) production. We further provided more direct and unequivocal experimental evidences for the formation of inactive CAPE/CA-iron complexes. CAPE was found to have a stronger iron-binding ability and a much higher lipophilicity than CA. Taken together, we propose that the esterification of the carboxylic moiety with phenethyl significantly enhanced the iron-binding ability and lipophilicity of CAPE, which is also responsible for its potent protection against iron-mediated cellular DNA damage. A study on the iron coordination mechanism of such natural polyphenol antioxidants will help to design more effective antioxidants for the treatment and prevention of diseases caused by metal-induced oxidative stress, as well as help to understand the structure-activity relationships of these compounds.
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http://dx.doi.org/10.3390/antiox10050798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157578PMC
May 2021

The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets.

ASN Neuro 2021 Jan-Dec;13:17590914211018100

Department of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

Cerebrovascular diseases are pathological conditions involving impaired blood flow in the brain, primarily including ischaemic stroke, intracranial haemorrhage, and subarachnoid haemorrhage. The nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is a protein complex and a vital component of the immune system. Emerging evidence has indicated that the NLRP3 inflammasome plays an important role in cerebrovascular diseases. The function of the NLRP3 inflammasome in the pathogenesis of cerebrovascular diseases remains an interesting field of research. In this review, we first summarised the pathological mechanism of cerebrovascular diseases and the pathological mechanism of the NLRP3 inflammasome in aggravating atherosclerosis and cerebrovascular diseases. Second, we outlined signalling pathways through which the NLRP3 inflammasome participates in aggravating or mitigating cerebrovascular diseases. Reactive oxygen species (ROS)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ROS/thioredoxin-interacting protein (TXNIP) and purinergic receptor-7 (P2X7R) signalling pathways can activate the NLRP3 inflammasome; activation of the NLRP3 inflammasome can aggravate cerebrovascular diseases by mediating apoptosis and pyroptosis. Autophagy/mitochondrial autophagy, nuclear factor E2-related factor-2 (Nrf2), interferon (IFN)-β, sirtuin (SIRT), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) reportedly alleviate cerebrovascular diseases by inhibiting NLRP3 inflammasome activation. Finally, we explored specific inhibitors of the NLRP3 inflammasome based on the two-step activation of the NLRP3 inflammasome, which can be developed as new drugs to treat cerebrovascular diseases.
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http://dx.doi.org/10.1177/17590914211018100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168029PMC
May 2021

Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway.

Biosci Rep 2021 Jun;41(6)

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

Background: Triple-negative breast cancer (TNBC) is a refractory subtype of breast cancer, 25-30% of which have dysregulation in the PI3K/AKT pathway. The present study investigated the anticancer effect of erianin on TNBC cell line and its underlying mechanism.

Methods: After treatment with erianin, MTT assay was employed to determine the MDA-MB-231 and EFM-192A cell proliferation, the nucleus morphological changes were observed by DAPI staining. The cell cycle and apoptotic proportion were detected by flow cytometry. Western blot was performed to determine the cell cycle and apoptosis-related protein expression and PI3K pathways. Finally, the antiproliferative activity of erianin was further confirmed by adding or not adding PI3K agonists SC79.

Results: Erianin inhibited the proliferation of MDA-MB-231 and EFM-192A cells in a dose-dependent manner, the IC50 were 70.96 and 78.58 nM, respectively. Erianin could cause cell cycle arrest at the G2/M phase, and the expressions of p21 and p27 were up-regulated, while the expressions of CDK1 and Cyclin B1 were down-regulated. Erianin also induced apoptosis via the mitochondrial pathway, with the up-regulation of the expression of Cyto C, PARP, Bax, active form of Caspase-3, and Caspase-9. Furthermore, p-PI3K and p-Akt expression were down-regulated by erianin. After co-incubation with SC79, the cell inhibition rate of erianin was decreased, which further confirmed that the attenuated PI3K/Akt pathway was relevant to the pro-apoptotic effect of erianin.

Conclusions: Erianin can inhibit the proliferation of TNBC cells and induce cell cycle arrest and apoptosis, which may ascribe to the abolish the activation of the PI3K/Akt pathway.
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http://dx.doi.org/10.1042/BSR20210093DOI Listing
June 2021

Comparative clinical accuracy analysis of the newly developed ZZ IOL and four existing IOL formulas for post-corneal refractive surgery eyes.

BMC Ophthalmol 2021 May 25;21(1):231. Epub 2021 May 25.

Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, China.

Background: Intraocular lens (IOL) calculation using traditional formulas for post-corneal refractive surgery eyes can yield inaccurate results. This study aimed to compare the clinical accuracy of the newly developed Zhang & Zheng (ZZ) formula with previously reported IOL formulas.

Study Design: Retrospective study.

Methods: Post-corneal refractive surgery eyes were assessed for IOL power using the ZZ, Haigis-L, Shammas, Barrett True-K (no history), and ray tracing (C.S.O Sirius) IOL formulas, and their accuracy was compared. No pre-refractive surgery information was used in the calculations.

Results: This study included 38 eyes in 26 patients. ZZ IOL yielded a lower arithmetic IOL prediction error (PE) compared with ray tracing (P = 0.04), whereas the other formulas had values like that of ZZ IOL (P > 0.05). The arithmetic IOL PE for the ZZ IOL formula was not significantly different from zero (P = 0.96). ZZ IOL yielded a lower absolute IOL PE compared with Shammas (P < 0.01), Haigis-L (P = 0.02), Barrett true K (P = 0.03), and ray tracing (P < 0.01). The variance of the mean arithmetic IOL PE for ZZ IOL was significantly smaller than those of Shammas (P < 0.01), Haigis-L (P = 0.03), Barrett True K (P = 0.02), and ray tracing (P < 0.01). The percentages of eyes within ± 0.5 D of the target refraction with the ZZ IOL, Shammas, Haigis-L, Barrett True-K, and ray-tracing formulas were 86.8 %, 45.5 %, 66.7 %, 73.7 %, and 50.0 %, respectively (P < 0.05 for Shammas and ray tracing vs. ZZ IOL).

Conclusions: The ZZ IOL formula might offer superior outcomes for IOL power calculation for post-corneal refractive surgery eyes without prior refractive data.
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http://dx.doi.org/10.1186/s12886-021-01991-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146991PMC
May 2021

The cell-impermeable Ru(II) polypyridyl complex as a potent intracellular photosensitizer under visible light irradiation via ion-pairing with suitable lipophilic counter-anions.

Free Radic Biol Med 2021 May 4;171:69-79. Epub 2021 May 4.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Joint Institute for Environmental Science, Research Center for Eco-Environmental Sciences and Hong Kong Baptist University, Hong Kong, China. Electronic address:

Developing the cell-impermeable Ru(II) polypyridyl cationic complexes as effective photosensitizers (PS) which have high cellular uptake and photo-toxicity, but low dark toxicity, is quite challenging. Here we found that the highly reactive singlet oxygen (O) can be generated by the irradiation of a typical Ru(II) polypyridyl complex Ru(II)tris(tetramethylphenanthroline) ([Ru(TMP)]) under visible light irradiation by ESR with TEMPO (2,2,6,6-tetramethyl-4-piperidone-N-oxyl) as O probe. Effective cellular and nuclear delivery of cationic [Ru(TMP)] was achieved through our recently developed ion-pairing method, and 2,3,4,5-tetrachlorophenol (2,3,4,5-TeCP) was found to be the most effective among all chlorophenols tested. The accelerated cellular, especially nuclear uptake of [Ru(TMP)] results in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and DNA strand breaks, caspase 3/7 activation and cell apoptosis in HeLa cells upon light irradiation. More importantly, compared with other traditional photosensitizers, [Ru(TMP)] showed significant photo-toxicity but low dark toxicity. Similar effects were observed when 2,3,4,5-TeCP was substituted by the currently clinically used anti-inflammatory drug flufenamic acid. This represents the first report that the cell-impermeable Ru(II) polypyridyl complex ion-paired with suitable lipophilic counter-anions functions as potent intracellular photosensitizer under visible light irradiation mainly via a O-mediated mechanism. These findings should provide new perspectives for future investigations on other metal complexes with similar characteristics as promising photosensitizers for potential photodynamic therapy.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.035DOI Listing
May 2021

Effects of Infant Formula Supplemented With Prebiotics and OPO on Infancy Fecal Microbiota: A Pilot Randomized Clinical Trial.

Front Cell Infect Microbiol 2021 29;11:650407. Epub 2021 Mar 29.

Department of Child Health Care, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Several lines of evidence suggest that the intestinal microbiota plays crucial roles in infant development, and that it is highly influenced by extrinsic and intrinsic factors. Prebiotic-containing infant formula may increase gastrointestinal tolerance and improve commensal microbiota composition. However, it remains unknown whether supplementation of milk-formulas with prebiotics and 1,3-olein-2-palmitin (OPO) can achieve feeding outcomes similar to those of breastfeeding. In the present study, we investigated the effects of two kinds of infant formula with different additives on the overall diversity and composition of the fecal microbiota, to determine which was closer to breastfeeding. A total of 108 infants were enrolled, including breastfeeding (n=59) and formula feeding group (n=49). The formula feeding infants were prospectively randomly divided into a standard formula group (n=18), and a supplemented formula group(n=31). The fecal samples were collected at 4 months after intervention. Fecal microbiota analysis targeting the V4 region of the 16S rRNA gene was performed using MiSeq sequencing. The overall bacterial diversity and composition, key functional bacteria, and predictive functional profiles in the two different formula groups were compared with breastfeeding group. We found that the alpha diversity of the gut microbiota was not significantly different between the OPO and breastfeeding groups with Chaos 1 index (p=0.346). The relative abundances of and in the OPO group were more similar to those of the breastfeeding group than to those of the standard formula group. The gut microbiota metabolism function prediction analysis showed that the supplemented formula group was similar to the breastfeeding group in terms of ureolysis (p=0.297). These findings suggest that, when formula supplemented with prebiotics and OPO was given, the overall bacterial diversity and parts of the composition of the fecal microbiota would be similar to that of breastfeeding infants.
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http://dx.doi.org/10.3389/fcimb.2021.650407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039316PMC
March 2021

EEG-Based Emotion Recognition Using an Improved Weighted Horizontal Visibility Graph.

Sensors (Basel) 2021 Mar 7;21(5). Epub 2021 Mar 7.

Department of Computer Science and Media Technology, Malmö University, 20506 Malmö, Sweden.

Emotion recognition, as a challenging and active research area, has received considerable awareness in recent years. In this study, an attempt was made to extract complex network features from electroencephalogram (EEG) signals for emotion recognition. We proposed a novel method of constructing forward weighted horizontal visibility graphs (FWHVG) and backward weighted horizontal visibility graphs (BWHVG) based on angle measurement. The two types of complex networks were used to extract network features. Then, the two feature matrices were fused into a single feature matrix to classify EEG signals. The average emotion recognition accuracies based on complex network features of proposed method in the valence and arousal dimension were 97.53% and 97.75%. The proposed method achieved classification accuracies of 98.12% and 98.06% for valence and arousal when combined with time-domain features.
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http://dx.doi.org/10.3390/s21051870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962200PMC
March 2021

Can Pharmacokinetic Studies Assess the Pulmonary Fate of Dry Powder Inhaler Formulations of Fluticasone Propionate?

AAPS J 2021 03 25;23(3):48. Epub 2021 Mar 25.

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, 6550 Sanger Road, Gainesville, Florida, 32827-7445, USA.

In the context of streamlining generic approval, this study assessed whether pharmacokinetics (PK) could elucidate the pulmonary fate of orally inhaled drug products (OIDPs). Three fluticasone propionate (FP) dry powder inhaler (DPI) formulations (A-4.5, B-3.8, and C-3.7), differing only in type and composition of lactose fines, exhibited median mass aerodynamic diameter (MMAD) of 4.5 μm (A-4.5), 3.8 μm (B-3.8), and 3.7 μm (C-3.7) and varied in dissolution rates (A-4.5 slower than B-3.8 and C-3.7). In vitro total lung dose (TLD) was determined as the average dose passing through three anatomical mouth-throat (MT) models and yielded dose normalization factors (DNF) for each DPI formulation X (DNF = TLD/TLD). The DNF was 1.00 for A-4.5, 1.32 for B-3.8, and 1.21 for C-3.7. Systemic PK after inhalation of 500 μg FP was assessed in a randomized, double-blind, four-way crossover study in 24 healthy volunteers. Peak concentrations (C) of A-4.5 relative to those of B-3.8 or C-3.7 lacked bioequivalence without or with dose normalization. The area under the curve (AUC) was bio-IN-equivalent before dose normalization and bioequivalent after dose normalization. Thus, PK could detect differences in pulmonary available dose (AUC) and residence time (dose-normalized C). The differences in dose-normalized C could not be explained by differences in in vitro dissolution. This might suggest that C differences may indicate differences in regional lung deposition. Overall this study supports the use of PK studies to provide relevant information on the pulmonary performance characteristics (i.e., available dose, residence time, and regional lung deposition).
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http://dx.doi.org/10.1208/s12248-021-00569-xDOI Listing
March 2021

Structure-Activity Relationship Investigation on Reaction Mechanism between Chlorinated Quinoid Carcinogens and Clinically-Used Aldoxime Nerve-Agent Antidote under Physiological Condition.

Chem Res Toxicol 2021 Apr 3;34(4):1091-1100. Epub 2021 Mar 3.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences University of Chinese Academy of Sciences, Beijing 100085, P. R. China.

Pyridinium aldoximes are best-known therapeutic antidotes used for clinical treatment of poisonings by organophosphorus nerve-agents and pesticides. Recently, we found that pralidoxime (2-PAM, a currently clinically used nerve-agent antidote) could also detoxify tetrachloro-1,4-benzoquinone (TCBQ), which is a carcinogenic quinoid metabolite of the widely used wood preservative pentachlorophenol under normal physiological conditions, via an unusually mild and facile Beckmann fragmentation mechanism accompanied by radical homolysis. However, it is not clear whether the less-chlorinated benzoquinones (BQs, ≤ 3) act similarly; if so, what is the structure-activity relationship? In this study, we found that (1) The stability of reaction intermediates produced by different BQs and 2-PAM was dependent not only on the position but also the degree of Cl-substitution on BQs, which can be divided into TCBQ- and DCBQ (dichloro-1,4-benzoquinone)-subgroup; (2) The p value of hydroxlated quinones (BQ-OHs, the hydrolysis products of BQs), determined the stability of corresponding intermediates, that is, the decomposition rate of the intermediates depended on the acidity of BQ-OHs; (3) The p value of the corresponding BQ-OHs could also determine the reaction ratio of Beckmann fragmentation to radical homolysis in BQs/2-PAM. These new findings on the structure-activity relationship of the halogenated quinoid carcinogens detoxified by pyridinium aldoxime therapeutic agents via Beckmann fragmentation and radical homolysis reaction may have broad implications on future biomedical and environmental research.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00504DOI Listing
April 2021

Reasons of the delayed vaccination, recommendations and safety of vaccination in children with congenital heart disease in Zhejiang, China.

Hum Vaccin Immunother 2021 Jul 12;17(7):2065-2071. Epub 2021 Feb 12.

Department of Child Health Care, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

There has been a considerable controversy about vaccination practices in Children with congenital heart disease (CHD) in China. This study aims to identify the reasons for deferring vaccination among the patient population attending the Vaccination Consultation Clinic in Zhejiang Province and the safety of their vaccination. We analyzed the data of 2442 children with CHD, who visited to our clinic from January 2016 to March 2019. A questionnaire survey was conducted to investigate the reasons for their delayed vaccination. Information about the following vaccination and Adverse Events Following Immunization (AEFI) was collected. Most of the enrolled children did not receive vaccines on time before consultation. The reasons for their deferring vaccination included: 1. Providers in the community health center refused to administer vaccines (77.6%); 2. Parents' concerns about the safety of vaccines (19.0%); 3. Parents' doubts about the efficiency of vaccines after certain drug applications (3.4%). According to the evaluation reports issued by the Vaccination Consultation Clinic, 83.7% of CHD children were recommended to be vaccinated on the nationally recommended schedule, 14.4% were recommended to defer some specific vaccination, and 1.9% were recommended to defer all vaccination. Among the group who received vaccines on nationally recommended schedule, the AEFI rate was 33.5/100 000. No rare or serious rare vaccine reactions were observed. Our study provides evidence that routine vaccination is safe in the majority of this patient population.
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http://dx.doi.org/10.1080/21645515.2021.1872343DOI Listing
July 2021

Combination Therapy with iRGD-antiCD3 and PD-1 Blockade Enhances Antitumor Potency of Cord Blood-Derived T Cells.

Onco Targets Ther 2021 5;14:835-844. Epub 2021 Feb 5.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210008, People's Republic of China.

Background: T cell-redirecting bispecific antibodies (BsAbs) are emerging as a potent cancer therapy that crosslinks tumor cells and T cells by simultaneously binding to tumor-associated antigen and CD3ε. However, immune inhibitory molecules can be remarkably upregulated after BsAbs treatment, leading to a suppressive tumor microenvironment and treatment resistance. This can be partially reversed by combination with immune checkpoint inhibitors. In our previous work, we successfully constructed the recombinant protein iRGD-antiCD3 and demonstrated that it promoted antitumor efficacy of transferred T cells by promoting T cell activation and infiltration.

Methods: We detected the levels of both PD-1 and PD-L1 as resistance to iRGD-antiCD3 treatment. Using cord blood-derived T cells, we assessed the activation and effects of iRGD-antiCD3 combined with PD-1 as evidenced by activation markers, Th1/Th2-cytokines, and killing capability against tumor cells in vitro. Moreover, to better mimic the physiological characteristics of in vivo solid tumors, we generated 3D spheroids from target cell lines. Spheroids were stained with a Viability/Cytotoxicity Assay Kit and examined by confocal microscopy to study the in vitro antitumor effect of T cells co-administered with combination iRGD-antiCD3 and PD-1 blockade. The mouse peritoneal metastatic gastric tumor model was employed. The synergistic antitumor effect and safety profiles in vivo were evaluated by tumor and body weight of tumor-bearing mice.

Results: We found that expression of both PD-1 and PD-L1 were increased as resistance to iRGD-antiCD3 treatment. We found that PD-1 blockade partially restored T cell activation as evidenced by elevated activation markers, Th1-cytokines, and killing capability against tumor cells in vitro. The combination of PD-1 blockade consistently and significantly increased cord blood-derived T cell cytotoxicity against 3D tumor spheroids. In vivo, we observed synergistic antitumor activity without obvious side effects.

Conclusion: These results demonstrated that combining iRGD-antiCD3 with PD-1 blockade could further improve antitumor efficacy of T cells, and this strategy holds great potential for the treatment of solid malignancies.
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http://dx.doi.org/10.2147/OTT.S291086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873023PMC
February 2021

Clinical manifestations and polysomnography-based analysis in nine cases of probable sporadic Creutzfeldt-Jakob disease.

Neurol Sci 2021 Feb 8. Epub 2021 Feb 8.

Department of Neurology, The First Hospital of Jilin University, 1 Xinming Street, Changchun, Jilin, China.

Purpose: To summarize the clinical characteristics of patients with sporadic Creutzfeldt-Jakob disease (sCJD), analyze its sleep disorder characteristics using polysomnography (PSG), and compare sleep disturbances with those of fatal familial insomnia (FFI).

Patients And Methods: We retrospectively reviewed the sleep disturbances; cerebrospinal fluid (CSF) protein 14-3-3 (CSF-14-3-3 protein); prion protein gene, PRNP; magnetic resonance imaging; and electroencephalogram (EEG) of nine sCJD patients RESULTS: Of the nine sCJD patients, six were positive for CSF-14-3-3 protein. In the eight patients who completed diffusion-weighted imaging, seven showed cortical "ribbons sign" and two showed high signal in the basal ganglia. All nine patients had an EEG, which showed an increase in background slow waves; moreover, four showed typical periodic sharp wave complexes. The codon diversity at position 129, 219 of nine patients were MM, EE. Almost all nine patients had sleep disturbances such as insomnia, hypersomnia, and periodic limb movement disorder (PLMD). Five patients completed PSG, which demonstrated severe sleep structure disorder, prolonged total waking time, significantly reduced sleep efficiency, and absent rapid eye movement in some severe patients.

Conclusion: Sleep disturbances are common in sCJD patients, manifested as insomnia, lethargy, and PLMD. The sCJD patients often demonstrate severe sleep structure disorder through PSG, which is similar to patients with FFI.
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http://dx.doi.org/10.1007/s10072-021-05102-8DOI Listing
February 2021

Semi-mechanistic PK/PD model to assess pulmonary targeting of beclomethasone dipropionate and its active metabolite.

Eur J Pharm Sci 2021 Apr 12;159:105699. Epub 2021 Jan 12.

Department of Pharmaceutics, College of Pharmacy, University of Florida, 1225 Center Dr., Gainesville, FL 32610, USA. Electronic address:

Purpose: The objective of this study was to describe the pulmonary targeting of beclomethasone dipropionate (BDP) and its active metabolite beclomethasone 17-monopropionate (BMP) in rats using a semi-mechanistic PK/PD model.

Methods: Rat plasma and tissue concentrations of BDP and BMP, and tissue receptor occupancies of BMP after systemic and pulmonary delivery of BDP and BMP were integrated in a newly developed semi-mechanistic PK/PD model.

Results: After IV administration of BDP, 95.4% of BDP was converted to BMP, while after pulmonary delivery of BDP, 46.6% of deposited BDP was absorbed as BMP. The developed semi-mechanistic PK model described plasma and tissue concentrations of BDP and BMP as well as receptor occupancies sufficiently well. The model incorporated dissolution, metabolic activation, and drug absorption processes to describe the local fate of BDP and BMP after systemic and pulmonary delivery. Dissolution rate constants of BDP and BMP were estimated to be 0.47/h and 2.01/h, respectively, and the permeabilities in central lung were estimated to be 15.0 and 2.9 × 10 cm/s for BDP and BMP, respectively. The EC of the binding of BMP to to the receptor was estimated to be 0.0017 ng/ml. Overall, receptor occupancies in the lung were more pronounced than those in the systemic circulation after pulmonary delivery of BDP or BMP. Simulations using the developed semi-mechanistic PK/PD model demonstrated that a slow dissolution rate and low permeability can improve pulmonary targeting.

Conclusions: A semi-mechanistic model was developed to describe the fate of an inhaled glucocorticoid pro-drug and its active metabolite in lung and the systemic circulation, both after pulmonary and systemic administration , thereby facilitating the understanding of the complex interplay between drug, prodrug and pharmacodynamic properties for quantifying the degree pulmonary targeting.
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http://dx.doi.org/10.1016/j.ejps.2021.105699DOI Listing
April 2021

Gut Microbiota in Patients with Polycystic Ovary Syndrome: a Systematic Review.

Reprod Sci 2021 Jan 6. Epub 2021 Jan 6.

School of Nursing, Lanzhou University, Lanzhou, China.

Polycystic ovary Syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. Recently, the relationships between the gastrointestinal microbiome and metabolic disorders such as obesity, type 2 diabetes and PCOS have been discovered. However, the association between the gut microbiome and PCOS symptoms has not been well established. We systematically reviewed existing studies comparing gut microbial composition in PCOS and healthy volunteers to explore evidence for this association. A systematic search was carried out in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 26, 2020, for all original cross-sectional, cohort, or case-control studies comparing the fecal microbiomes of patients with PCOS with microbiomes of healthy volunteers (controls). The primary outcomes were differences in specific gut microbes between patients with PCOS and controls. The search identified 256 citations; 10 studies were included. The total population study of these articles consists of 611 participants (including PCOS group and healthy controls group). Among the included 10 studies, nine studies compared α-diversity, and six studies demonstrated that α-diversity has a significant reduction in PCOS patients. Seven of them reported that there was a significant difference of β-diversity composition between healthy controls groups and PCOS patients. The most common bacterial alterations in PCOS patients included Bacteroidaceae, Coprococcus, Bacteroides, Prevotella, Lactobacillus, Parabacteroides, Escherichia/Shigella, and Faecalibacterium prausnitzii. No consensus has emerged from existing human studies of PCOS and gut microbiome concerning which bacterial taxa are most relevant to it. In this systematic review, we identified specific bacteria associated with microbiomes of patients with PCOS vs controls. Higher level of evidence is needed to determine whether these microbes are a product or cause of PCOS.
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http://dx.doi.org/10.1007/s43032-020-00430-0DOI Listing
January 2021

The critical role of superoxide anion radicals on delaying tetrachlorohydroquinone autooxidation by penicillamine.

Free Radic Biol Med 2021 Feb 19;163:369-378. Epub 2020 Dec 19.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Joint Institute for Environmental Science, Research Center for Eco-Environmental Sciences and Hong Kong Baptist University, Beijing, Hong Kong, PR China. Electronic address:

We have recently found that penicillamine, a classic copper-chelating thiol-drug for Wilson's disease, can delay tetrachlorohydroquinone (TCHQ) autooxidation via a previously unrecognized redox-activity. However, its underlying molecular mechanism remains not fully understood. In this study, we found, interestingly and unexpectedly, that superoxide dismutase (SOD) can significantly shorten the delay of TCHQ autooxidation by penicillamine, but not by ascorbate; SOD can also markedly increase the yields of the oxidized form of penicillamine. Similar effects were observed with a recently-developed specific and sensitive superoxide anion radical (O) probe CT-02H, which was also employed to successfully measure O generated from both TCHQ and TCHQ/penicillamine systems for the first time. More importantly, addition of extra O (KO/18-crown-6) can further prolong the delaying effects by penicillamine and slow down penicillamine consumption. Taken together, an unexpected critical role of O in TCHQ/penicillamine interaction was proposed: O may regenerate penicillamine, thereby continuously reducing TCSQ to TCHQ and finally delaying TCHQ autooxidation; In contrast, if O were eliminated, which can not only markedly change the reaction equilibrium, accelerate the rate of interaction, and ultimately shorten the delay of TCHQ autooxidation by penicillamine, but can also accelerate penicillamine oxidation to form its corresponding disulfide solely via redox reaction without any minor nucleophilic reaction. These findings not only further support our previously-proposed redox mechanism for the protection against TCHQ-induced cytotoxicity by penicillamine, but also reveal a new mode of action for O in the inhibition of haloquinoids-induced toxicity by thiol antioxidants.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.014DOI Listing
February 2021

LMCD1 antisense RNA 1 (LMCD1-AS1) potentiates thyroid cancer cell growth and stemness via a positive feedback loop of LMCD1-AS1/miR-1287-5p/GLI2.

Ann Transl Med 2020 Nov;8(22):1508

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Background: LMCD1 antisense RNA 1 (LMCD1-AS1) is a certified oncogene in several tumour types. However, its role in thyroid cancer (THCA) remains unknown.

Methods: The expression level of LMCD1-AS1 in THCA cells and the normal control cell was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of LMCD1-AS1 knockdown on cell proliferation, migration and apoptosis were detected by colony formation assay, EdU assay, wound healing assay and TUNEL assay. Sphere formation assay was applied to assess sphere formation ability of THCA cells. Bioinformatics analysis and mechanism experiments, including ChIP assay, RIP assay and luciferase reporter assay were conducted to evaluate the downstream and upstream molecular mechanisms of LMCD-AS1.

Results: A marked up-regulation of LMCD1-AS1 in THCA cells relative to normal control cells was found. LMCD1-AS1 silencing suppressed proliferation and migration but induced apoptosis in THCA cells. Moreover, LMCD1-AS1 knockdown reduced the sphere formation capacity of THCA cells. The transcriptional factor GLI family zinc finger 2 (GLI2) binds to LMCD1-AS1, which contributed to LMCD1-AS1 up-regulation in THCA cells. Cytoplasmic LMCD1-AS1 sponged a shared microRNA between LMCD1-AS1 and GLI2. GLI2 was inhibited bymiR-1287-5p and disinhibited by LMCD1-AS1.

Conclusions: LMCD1-AS1exerts pro-tumorigenic function through sponging miR-1287-5p to elevate GLI2 expression in THCA development, constituting a feedback loop of LMCD1-AS1/miR-1287-5p/GLI2.
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http://dx.doi.org/10.21037/atm-20-7182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729329PMC
November 2020

MicroRNA-200c Nanoparticles Sensitized Gastric Cancer Cells to Radiotherapy by Regulating PD-L1 Expression and EMT.

Cancer Manag Res 2020 27;12:12215-12223. Epub 2020 Nov 27.

The Comprehensive Cancer Centre of Drum Tower Hospital, Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.

Introduction: Immuno-checkpoint inhibitors (ICIs) in advanced gastric cancer either as monotherapy or in combining strategies are rapidly evolving but still in early phase. Various efforts have been made to provide insights into regulating immune checkpoint molecule programmed cell death ligand-1 (PD-L1) expression to improve ICIs efficacy. The aim of this study was to investigate the effect and potential mechanism of miR-200c nanoparticles combined with radiotherapy in gastric cancer cells.

Methods: We prepared miR-200c-loaded nanoparticles (miR-200c NPs) to achieve targeted delivery of miR-200c to AGS cells. The roles of miR-200c NPs and radiotherapy in regulating the viability of AGS cells were assessed by CCK-8 toxicity test and Annexin V-FITC/PI apoptosis kit. Flow cytometry was used to analyze expression of PD-L1 and CD44 on the surface of AGS cells treated by miR-200c NPs and/or ionizing radiation. Enzyme-linked immunosorbent assay (ELISA) was used to test the level of transforming growth factor-beta 1 (TGF-β1) secreted by AGS cells. The cooperation mechanism between miR-200c NPs and radiotherapy was also explored in vitro.

Results: Compared with naked miR-200c mimics, miR-200c NPs significantly downregulated PD-L1 expression of gastric cancer cells. The combination of miR-200c NPs and radiotherapy showed significantly synergistic inhibitory effect on gastric cancer cells by inhibiting immune escape mediated by PD-L1, reversing EMT phenotype as well as abrogating cancer stem cells (CSCs)-associated properties of tumor cells.

Conclusion: MiR-200c NPs sensitized gastric cancer cells to radiotherapy by regulating PD-L1 expression and EMT.
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http://dx.doi.org/10.2147/CMAR.S279978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707438PMC
November 2020

Tetrathiafulvalene-Based Metal-Organic Framework as a High-Performance Anode for Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2020 Nov 10;12(47):52615-52623. Epub 2020 Nov 10.

College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China.

Metal-organic frameworks (MOFs) have aroused great interest as lithium-ion battery (LIB) electrode materials. In this work, we first report that a pristine three-dimensional tetrathiafulvalene derivatives (TTFs)-based zinc MOF, formulated [Zn(py-TTF-py)(BDC)]·2DMF·HO () (py-TTF-py = 2,6-bis(4'-pyridyl)tetrathiafulvalene and HBDC = terephthalic acid), can work as a high-performance electrode material for rechargeable LIBs. The TTFs-Zn-MOF electrode displayed a high discharge specific capacity of 1117.4 mA h g at a current density of 200 mA g after 150 cycles along with good reversibility. After undergoing elevated discharging/charging rates, the electrode showed superior lithium storage performance in the extreme case of 20 A g and could finally recover the capability when the current rate was back to 200 mA g. Particularly, specific capacities of 884.2, 513.8, and 327.8 mA h g were reached at high current densities of 5, 10, and 20 A g after 180, 175, and 300 cycles along with good reversibility, respectively. Such an excellent performance is first reported for the LIB anode materials. TTFs-Zn-MOF , namely, [Zn(py-TTF-py) (BDC)]·DMF·2HO (), was prepared as a contrast to explore the relationship between the structures of the electrode materials and the electrochemical properties. Based on the structural analysis of and and ex situ X-ray photoelectron spectroscopy, the TTF moiety and the twofold TTF pillar play a key role in the excellent electrochemical performance. The full cell of MOF with NMC 622 delivered the capacity of 131.9 mA h g at 100 mA g with the Coulombic efficiency of 99.45% after 70 cycles and exhibited the tolerance to high-current operation.
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http://dx.doi.org/10.1021/acsami.0c14510DOI Listing
November 2020

Signaling Mechanism of Transcriptional Bursting: A Technical Resolution-Independent Study.

Biology (Basel) 2020 Oct 19;9(10). Epub 2020 Oct 19.

School of Science, Jiangnan University, Wuxi 214122, China.

Gene transcription has been uncovered to occur in sporadic bursts. However, due to technical difficulties in differentiating individual transcription initiation events, it remains debated as to whether the burst size, frequency, or both are subject to modulation by transcriptional activators. Here, to bypass technical constraints, we addressed this issue by introducing two independent theoretical methods including analytical research based on the classic two-model and information entropy research based on the architecture of transcription apparatus. Both methods connect the signaling mechanism of transcriptional bursting to the characteristics of transcriptional uncertainty (i.e., the differences in transcriptional levels of the same genes that are equally activated). By comparing the theoretical predictions with abundant experimental data collected from published papers, the results exclusively support frequency modulation. To further validate this conclusion, we showed that the data that appeared to support size modulation essentially supported frequency modulation taking into account the existence of burst clusters. This work provides a unified scheme that reconciles the debate on burst signaling.
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http://dx.doi.org/10.3390/biology9100339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603168PMC
October 2020

First Direct and Unequivocal Electron Spin Resonance Spin-Trapping Evidence for pH-Dependent Production of Hydroxyl Radicals from Sulfate Radicals.

Environ Sci Technol 2020 11 16;54(21):14046-14056. Epub 2020 Oct 16.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. China.

Recently, the sulfate radical (SO) has been found to exhibit broad application prospects in various research fields such as chemical, biomedical, and environmental sciences. It has been suggested that SO could be transformed into a more reactive hydroxyl radical (OH); however, no direct and unequivocal experimental evidence has been reported yet. In this study, using an electron spin resonance (ESR) secondary radical spin-trapping method coupled with the classic spin-trapping agent 5,5-dimethyl-1-pyrroline -oxide (DMPO) and the typical OH-scavenging agent dimethyl sulfoxide (DMSO), we found that OH can be produced from three SO-generating systems from weakly acidic (pH = 5.5) to alkaline conditions (optimal at pH = 13.0), while SO is the predominant radical species at pH < 5.5. A comparative study with three typical OH-generating systems strongly supports the above conclusion. This is the first direct and unequivocal ESR spin-trapping evidence for OH formation from SO over a wide pH range, which is of great significance to understand and study the mechanism of many SO-related reactions and processes. This study also provides an effective and direct method for unequivocally distinguishing OH from SO.
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http://dx.doi.org/10.1021/acs.est.0c04410DOI Listing
November 2020

Long-Term Follow-up of Posterior Selective Thoracolumbar/Lumbar Fusion in Patients With Lenke 5C Adolescent Idiopathic Scoliosis: An Analysis of 10-Year Outcomes.

Global Spine J 2020 Oct 16:2192568220965566. Epub 2020 Oct 16.

12520Changhai Hospital of the Navy Medical University, Shanghai, China.

Study Design: Retrospective study.

Objective: The aim of this study was to assess long-term radiographic and clinical outcomes in Lenke 5C adolescent idiopathic scoliosis (AIS) patients after posterior selective fusion.

Methods: Lenke 5C AIS patients who underwent posterior selective thoracolumbar/lumbar (TL/L) fusion in our hospital from January 2007 to January 2010 were recruited. Radiographic parameters were measured preoperatively and at the 3-month, 1-year, 2-year, 5-year, and 10-year follow-ups. The SRS-22 (Scoliosis Research Society) questionnaire was used to assess the clinical outcomes.

Results: We included 37 patients who underwent posterior selective TL/L fusion surgery in our study, and the mean follow-up time was 11.26 ± 0.85 years. The average preoperative Cobb angles of the thoracic and TL/L curves were 24.0 ± 9.0° and 45.4 ± 6.3°, respectively, which were corrected to 12.2° and 12.4° at the 3-month follow-up postoperatively, with correction losses of 2.2° and 1.5° at the 10-year follow-up. In the sagittal plane, the degree of thoracic kyphosis (TK) gradually increased over the follow-up period. The proximal junctional angle (PJA) also gradually increased from 6.7 ± 4.6 to 13.7 ± 5.6 during the follow-up period. For the clinical outcomes, correction surgery improved the SRS-22 scores in each domain, especially in the self-image domain.

Conclusions: Posterior selective TL/L fusion can effectively correct spinal deformities, leading to stable outcomes for 10 years postoperatively. During the follow-up period, the degree of TK presented an increasing trend that remained almost constant after the 1-year follow-up. Moreover, the variation in the PJA was highly significant in the postoperative period, and it showed an increasing trend until the 2-year follow-up.
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http://dx.doi.org/10.1177/2192568220965566DOI Listing
October 2020

Pathway elucidation and engineering of plant-derived diterpenoids.

Curr Opin Biotechnol 2020 Oct 5;69:10-16. Epub 2020 Oct 5.

Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China. Electronic address:

Plant-derived diterpenoids are indispensable to plant development, stress-resistance and interaction with environmental microorganisms. Besides significant roles in plant fitness and adaption, many bioactivities beneficial to human beings are also found in diterpenoids from terrestrial plants. However, these high-value compounds are always present in limited species with low-abundance. Complicated chemosynthesis hardly meets the needs of sufficient supplies. To overcome these obstacles, it is necessary to investigate how diterpenoids are biosynthesized in planta, and followed by engineering the biosynthetic pathway to achieve high yield production. This review will summarize the recent progress of plant diterpenoid biosynthetic pathway discovery and engineering, hoping to offer an inspiration for concerned researchers.
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http://dx.doi.org/10.1016/j.copbio.2020.08.007DOI Listing
October 2020

Effects of Different Doses of Eucalyptus Oil From Labill on Respiratory Tract Immunity and Immune Function in Healthy Rats.

Front Pharmacol 2020 21;11:1287. Epub 2020 Aug 21.

School of Public Health and Interdisciplinary Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand.

Eucalyptol (1,8-cineole), the major constituent of eucalyptus oil (EO), was used in traditional medicine as a remedy for colds and bronchitis. This study aimed at clarifying the effect of eucalyptol on respiratory immune function of CD8 and CD4 cells, and alveolar macrophages (AM). Thirty male Sprague-Dawley rats were divided into experimental and control groups. The drug was given once a day for 3 weeks and the experimental group was divided according to the eucalyptol dose into: 30, 100, and 300 mg·kg groups. Flow cytometry was used to detect the phagocytic function of CD4, CD8 cells, and AM in the bronchopulmonary lavage fluid. The 30 and 100 mg·kg groups had an up-regulation effect on CD8 (p < 0.05), with no significant effect on macrophage phagocytosis. The 300 mg·kg group had an inhibitory effect on CD8 and macrophage phagocytosis (p < 0.05), with no significant difference in CD4 between groups. Further investigation was conducted to evaluate the effect of EO on immune function in rats by detecting blood T, B, and NK cells using flow cytometry, and blood IgA, IgG, IgM, and IFN-γ levels by ELISA. High dosage of eucalyptol significantly reduced the proportion of blood B and NK cells (p < 0.05). IgA was decreased in the 100 and 300 mg·kg groups (p < 0.05). There are no significant differences between the number of T cells and the IgG, IgM, and IFN-γ levels between experimental and control groups. Rational use of EO containing eucalyptol can improve the immune function of the respiratory tract and the body immunity, while high dose could have damaging effects, through modifying the phagocytic function of CD8 cells and reducing the proportion of blood B cells, NK cells, and IgA.
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http://dx.doi.org/10.3389/fphar.2020.01287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472567PMC
August 2020

A GABAergic neural circuit in the ventromedial hypothalamus mediates chronic stress-induced bone loss.

J Clin Invest 2020 12;130(12):6539-6554

Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS).

Homeostasis of bone metabolism is regulated by the central nervous system, and mood disorders such as anxiety are associated with bone metabolism abnormalities, yet our understanding of the central neural circuits regulating bone metabolism is limited. Here, we demonstrate that chronic stress in crewmembers resulted in decreased bone density and elevated anxiety in an isolated habitat mimicking a space station. We then used a mouse model to demonstrate that GABAergic neural circuitry in the ventromedial hypothalamus (VMH) mediates chronic stress-induced bone loss. We show that GABAergic inputs in the dorsomedial VMH arise from a specific group of somatostatin neurons in the posterior region of the bed nucleus of the stria terminalis, which is indispensable for stress-induced bone loss and is able to trigger bone loss in the absence of stressors. In addition, the sympathetic system and glutamatergic neurons in the nucleus tractus solitarius were employed to regulate stress-induced bone loss. Our study has therefore identified the central neural mechanism by which chronic stress-induced mood disorders, such as anxiety, influence bone metabolism.
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http://dx.doi.org/10.1172/JCI136105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685749PMC
December 2020

Contribution of iron status at birth to infant iron status at 9 months: data from a prospective maternal-infant birth cohort in China.

Eur J Clin Nutr 2021 Feb 19;75(2):364-372. Epub 2020 Aug 19.

Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA.

Background/objectives: The contribution of iron status at birth to iron status in infancy is not known. We used a physiologic framework to evaluate how iron status at birth related to iron status at 9 months, taking iron needs and sources into account.

Subjects/methods: In a longitudinal birth cohort in China, iron status measures in cord blood and venous blood in infancy (9 months) and clinical data were prospectively collected in 545 healthy term maternal-infant dyads. We used structural equation modeling (SEM) to create a 9-month iron composite and to assess direct and indirect contributions of multiple influences on 9-month iron status. Logistic regression was used to calculate odds ratios for iron deficiency (ID), iron deficiency anemia (IDA), and anemia.

Results: Approximately 15% (78/523) of infants were born with cord SF <75 µg/l, suggesting fetal-neonatal ID. At 9 months, 34.8% (186/535) and 19.6% (105/535) of infants had ID and IDA, respectively. The following factors were independently associated with poorer 9-month iron status: higher cord zinc protoporphyrin/heme (ZPP/H) (adjusted estimate -0.18, P < 0.001) and serum transferrin receptor (sTfR) (-0.11, P = 0.004), lower cord hemoglobin (Hb) (0.13, P = 0.004), lower birth weight (0.15, P < 0.001), male sex (0.10, P = 0.013), older age at testing (-0.26, P < 0.001), higher 9-month weight (-0.12, P = 0.006) and breastfeeding (0.38, P < 0.001). Breastfeeding at 9 months showed the strongest association, adjusting for all other factors. Compared to formula-fed infants, the odds of IDA were 19.1 (95% CI: 6.92, 52.49, P < 0.001) and 3.6 (95% CI: 1.04, 12.50, P = 0.043) times higher in breastfed and mixed-fed infants, respectively.

Conclusions: Indicators of iron status at birth, postnatal iron needs, and iron sources independently related to iron status at 9 months. Sex was an additional factor. Public health policies to identify and protect infants at increased risk of ID should be prioritized.
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http://dx.doi.org/10.1038/s41430-020-00705-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878278PMC
February 2021

Identification of possible reductants in the aqueous leaf extract of mangrove plant Rhizophora apiculata for the fabrication and cytotoxicity of silver nanoparticles against human osteosarcoma MG-63 cells.

Mater Sci Eng C Mater Biol Appl 2020 Nov 3;116:111252. Epub 2020 Jul 3.

Jiangsu Province Hospital of Chinese Medicine, Nanjing 210000, PR China; Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, PR China. Electronic address:

Rhizophora apiculata is a less studied tannin-rich plant of the mangrove ecosystem with potent biomedical applications. Tannins have been known to reduce silver ions into silver nanoparticles which in particular are known to possess cytotoxic effects against a variety of cancer cells. The aqueous leaf extract was prepared and quantitatively analyzed for its phytochemical content. According to the quantitative phytochemical analysis, the extract was rich in tannins and other reducing sugars. The reducing sugar-rich extract was further used for the synthesis of silver nanoparticles. Taking these facts into consideration, in this study, an eco-friendly approach was followed to biosynthesize silver nanoparticles using a tannin-rich Rhizophora apiculata aqueous leaf extract. The synthesized nanoparticles were partially characterized by our previous reports. This report further characterizes the particles by determining its average size, polydispersity index and zeta potential using dynamic light scattering. After characterization, the nanoparticles were tested for cytotoxic effects against human osteosarcoma MG-63 cells. The effects were analyzed by microscopic observation and MTT assay. The results indicate that the tannin-rich extract reduced the precursor silver nitrate into silver nanoparticles of favorable size for tumor infiltration. The nanoparticles possessed significant cytotoxic effects against MG-63 cells which could be possibly attributed to the antioxidant activity of silver nanoparticles. Further studies at the molecular level can indicate its potential in nanomedicine for the treatment of bone cancer at the clinical level.
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http://dx.doi.org/10.1016/j.msec.2020.111252DOI Listing
November 2020

High Level of IL-10 in Cerebrospinal Fluid is Specific for Diagnosis of Primary Central Nervous System Lymphoma.

Cancer Manag Res 2020 24;12:6261-6268. Epub 2020 Jul 24.

Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China.

Purpose: The pathological diagnosis of primary central nervous system lymphoma (PCNSL) by stereotactic brain biopsy and craniotomy is not often applicable due to the high cost and associated complications. In recent years, some biomarkers in cerebrospinal fluid (CSF), including interleukin 10 (IL-10), microRNAs, CXC chemokine ligand 13 (CXCL13), have been reported to be associated with PCNSL. However, this conclusion was controversial. Therefore, this study was to test whether Th17 cell-related cytokines could be used to distinguish PCNSL from other brain tumors.

Patients And Methods: Th17 cell-related cytokines in CSF were measured in 108 patients with intracranial tumors, which included 66 PCNSL patients and 42 patients with other types of brain tumors. A receiver-operating characteristic (ROC) curve was utilized to analyze the diagnostic value of the cytokines based on the area under the curve (AUC).

Results: The CSF IL-10 level and IL-10/IL-6 ratios were significantly higher in PCNSL than in the other brain tumors (58.2 pg/mL VS 1.5 pg/mL, =0.001; 24.3 VS 0.6, =0.001). When the cutoff level of IL-10 was set at 8.3 pg/mL, its sensitivity and specificity for diagnosing PCNSL were 59.0% and 98%, respectively. The CSF IL-10 levels over 5pg/mL (+LR 12.3) were of significant value for the diagnosis of PCNSL. These parameters are highly valuable in PCNSL diagnosis, but their sensitivity is less valuable. The sensitivity of IL-4 and IL-17A, the ratio of mature lymphocytes and the monocytes/macrophages ratio in CSF were relatively high. In combination, the sensitivity increased by 15% and the specificity remained above 85%. The best combination was IL-10 and IL-17A, whose sensitivity was 70% and specificity was 96%.

Conclusion: The CSF level of IL-10 is a useful diagnostic biomarker in patients with PCNSL. The CSF levels of IL-4, IL-17A, mature lymphocytes and monocytes/macrophages can be used to increase the diagnostic value of CSF IL-10 level and IL-10/IL-6 ratio.
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http://dx.doi.org/10.2147/CMAR.S255482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386815PMC
July 2020

Mechanism of synergistic DNA damage induced by caffeic acid phenethyl ester (CAPE) and Cu(II): Competitive binding between CAPE and DNA with Cu(II)/Cu(I).

Free Radic Biol Med 2020 11 2;159:107-118. Epub 2020 Aug 2.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing, 100085, PR China; Joint Institute for Environmental Science, Research Center for Eco-Environmental Sciences and Hong Kong Baptist University, Beijing, PR China. Electronic address:

Caffeic acid phenethyl ester (CAPE) is an active polyphenol of propolis from honeybee hives, and exhibits antioxidant and interesting pharmacological activities. However, in this study, we found that in the presence of Cu(II), CAPE exhibited pro-oxidative rather than antioxidant effect: synergistic DNA damage was induced by the combination of CAPE and Cu(II) together as measured by strand breakage in plasmid DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, which is dependent on the molar ratio of CAPE:Cu(II). Production of Cu(I) and HO from the redox reaction between CAPE and Cu(II), and subsequent OH formation was found to be responsible for the synergistic DNA damage. DNA sequencing investigations provided more direct evidence that CAPE/Cu(II) caused preferential cleavage at guanine, thymine and cytosine residues. Interestingly, we found there are competitive binding between CAPE and DNA with Cu(II)/Cu(I), which changed the redox activity of Cu(II)/Cu(I), via complementary applications of different analytical methods. The observed DNA damage was mainly attributed to the formation of DNA-Cu(II)/Cu(I) complexes, which is still redox active and initiated the redox reaction near the binding site between copper and DNA. Based on these data, we proposed that the synergistic DNA damage induced by CAPE/Cu(II) might be due to the competitive binding between CAPE and DNA with Cu, and site-specific production of OH near the binding site of copper with DNA. Our findings may have broad biological implications for future research on the pro-oxidative effects of phenolic compounds in the presence of transition metals.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.06.033DOI Listing
November 2020