Publications by authors named "Hong Cui"

261 Publications

Synthesis of the analogs of plocabulin and their preliminary structure-activity relationship study.

Bioorg Med Chem Lett 2021 Sep 8:128355. Epub 2021 Sep 8.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address:

Plocabulin, a marine natural polyketide isolated from the sponge Lithoplocamia lithistoides, is a novel and potent microtubule-destabilizing agent. Guided by the reported binding mode, several new analogs of plocabulin have been designed through removing the right aliphatic chain and further modifying on the carbamate group and the enamide unit. The preliminary results indicate that the right aliphatic chain in plocabulin is allowed to remove with a little loss of activity, the carbamate group plays a role in the activity, and particularly, the enamide unit has an important effect on the activity. This new finding will aid the design of novel potent tubulin-binding agents based on plocabulin.
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http://dx.doi.org/10.1016/j.bmcl.2021.128355DOI Listing
September 2021

Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile.

iScience 2021 Sep 17;24(9):102987. Epub 2021 Aug 17.

Instituto Biofisika (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain.

Broadly neutralizing antibodies (bnAbs) against HIV-1 are frequently associated with the presence of autoreactivity/polyreactivity, a property that can limit their use as therapeutic agents. The bnAb 4E10, targeting the conserved Membrane proximal external region (MPER) of HIV-1, displays almost pan-neutralizing activity across globally circulating HIV-1 strains but exhibits nonspecific off-target interactions with lipid membranes. The hydrophobic apex of the third complementarity-determining region of the heavy chain (CDRH3) loop, which is essential for viral neutralization, critically contributes to this detrimental effect. Here, we have replaced the aromatic/hydrophobic residues from the apex of the CDRH3 of 4E10 with a single aromatic molecule through chemical modification to generate a variant that preserves the neutralization potency and breadth of 4E10 but with reduced autoreactivity. Collectively, our study suggests that the localized accumulation of aromaticity by chemical modification provides a pathway to ameliorate the adverse effects triggered by the CDRH3 of anti-HIV-1 MPER bnAbs.
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http://dx.doi.org/10.1016/j.isci.2021.102987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413895PMC
September 2021

Cu-MOF/hemin: a bionic enzyme with excellent dispersity for the determination of hydrogen peroxide released from living cells.

Analyst 2021 Sep 7. Epub 2021 Sep 7.

School of Chemical Sciences, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, China.

The stability, repeatability and sensitivity of an electrochemical biosensor material are closely connected with the dispersibility of metal organic frameworks (MOFs) in aqueous media. Herein, a nanocomposite based on Cu-MOF/hemin, which is not only highly water-soluble but also simple and efficient in synthesis, was used for the construction of a non-enzymatic sensor to detect hydrogen peroxide (HO). The Cu-MOF/hemin was characterized scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS)-mapping, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and thermal gravimetric analysis (TGA), which indicate that hemin and the Cu-MOF were successfully combined. As a HO electrochemical biomimetic enzyme, the Cu-MOF/hemin exhibited excellent electrocatalytic performance, which was confirmed by the electrochemical experiments and chromogenic reactions, and the possible mechanism of the reactions has been deduced. The electrochemical sensor based on the biomimetic enzyme exhibited an extended linear detection range from 0.01-5.0 mM ( = 0.998), low detection limit of 4.14 μM, and high selectivity and stability under the optimized conditions. More importantly, the practical application ability of the sensor was verified by the test of HO in human serum samples and it could be used for the real-time detection of HO released from living cells with satisfactory results. Therefore, this novel nanocomposite has certain potential in preparing electrochemical sensing platforms for nonenzymatic biosensing and provides a new method for clinical diagnosis and real-time monitoring.
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http://dx.doi.org/10.1039/d1an01323hDOI Listing
September 2021

A GPC2 antibody-drug conjugate is efficacious against neuroblastoma and small-cell lung cancer via binding a conformational epitope.

Cell Rep Med 2021 Jul 21;2(7):100344. Epub 2021 Jul 21.

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Glypican 2 (GPC2) is a MYCN-regulated, differentially expressed cell-surface oncoprotein and target for immune-based therapies in neuroblastoma. Here, we build on GPC2's immunotherapeutic attributes by finding that it is also a highly expressed, MYCN-driven oncoprotein on small-cell lung cancers (SCLCs), with significantly enriched expression in both the SCLC and neuroblastoma stem cell compartment.By solving the crystal structure of the D3-GPC2-Fab/GPC2 complex at 3.3 Å resolution, we further illustrate that the GPC2-directed antibody-drug conjugate (ADC; D3-GPC2-PBD), that links a human GPC2 antibody (D3) to DNA-damaging pyrrolobenzodiazepine (PBD) dimers, binds a tumor-specific, conformation-dependent epitope of the core GPC2 extracellular domain. We then show that this ADC induces durable neuroblastoma and SCLC tumor regression via induction of DNA damage, apoptosis, and bystander cell killing, notably with no signs of ADC-induced toxicity. These studies provide preclinical data to support the clinical translation of ADCs targeting GPC2.
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http://dx.doi.org/10.1016/j.xcrm.2021.100344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324494PMC
July 2021

Effect of intestinal microecology on postnatal weight gain in very preterm infants in intensive care units.

Gut Pathog 2021 Aug 2;13(1):49. Epub 2021 Aug 2.

Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

Objective: To study the effect of intestinal microecology on postnatal weight gain of very preterm infants in neonatal intensive care unit (NICU).

Methods: Very preterm infants who met the inclusion criteria were enrolled. The subjects were divided into the extrauterine growth retardation (EUGR) group(defined as a body weight less than the 10th percentile of the corresponding gestational age or a weight loss between birth and a given time of  >  2SD were considered EUGR) and normal growth group, and the growth was evaluated at 2 and 4 weeks after birth. Meanwhile, the stool samples were taken to perform16S ribosomal RNA (rRNA) high -throughput 16S rRNA sequencing of the intestinal microflora was performed on stool samples.

Results: A total of 22 infants were included. There was no significant difference in the alpha diversity indexes indices between the two groups at 2 weeks or 4 weeks after birth. The beta diversity analysis showed that the two groups had similar principal components of the intestinal microflora were similar between the two groups. Linear discriminant analysis (LDA) effect size (LEfSe) showed that 2 weeks after birth, the bacteria with an absolute LDA score (log10) higher than 4 included Streptococcaceae, Streptococcus, Bacteroidetes, Bacteroidales and Stenotrophomonas in the EUGR group and Enterococcaceae and Enterococcus in the control group. At the 4th week after birth, the bacteria with an absolute LDA score (log10) higher than 3 in the EUGR group includedwere Clostriaceae, Eubacteriaceae and Eubacterium. TheBy comparing the composition of the microbial community composition comparison showed, significant differences were found in the principal components of Enterococcus and Streptococcus on the family and genus levels at 2 weeks after birth. No Bifidobacterium was found in either group at 4 weeks after birth.

Conclusion: Intestinal microecology is different between infants with EUGR and those with normal growth. The diversity and richness of the intestinal microflora in preterm infants at the NICU are significantly insufficient and change dynamically with time, and the establishment of intestinal homeostasis is obviously delayed.
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http://dx.doi.org/10.1186/s13099-021-00445-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327448PMC
August 2021

GSK-3β inhibitor TWS119 alleviates hypoxic-ischemic brain damage via a crosstalk with Wnt and Notch signaling pathways in neonatal rats.

Brain Res 2021 Oct 24;1768:147588. Epub 2021 Jul 24.

Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing 100050, China. Electronic address:

Preterm infant brain injury is a leading cause of morbidity and disability in survivors of preterm infants. Unfortunately, the effective treatment remains absent. Recent evidence suggests that GSK-3β inhibitor TWS119 has a neuroprotectiverole in adult brain injury by activation of Wnt/β-catenin signaling pathway. However, the role on neonatal brain injury is not yet explored. The study aims to evaluate the effect of TWS119 at 7 d after hypoxic-ischemic brain damage and investigate the mechanism that it regulates Wnt and Notch signaling pathways at 24 h after hypoxic-ischemic brain damage in neonatal rats. Three-day-old rats were randomly divided into 3 groups: sham group, HI group and TWS119 group. The neonatal rats were subjected to left carotid artery ligation followed by 2 h of hypoxia (8.0% O). A single dose of TWS119 (30 mg/kg) was intraperitoneally injected 20 min prior to hypoxia-ischemia (HI). At 7 d after HI, TWS119 improved the tissue structure, reduced cell apoptosis, up-regulated bcl-2 expression, up-regulated the expression of PSD-95 and Synapsin-1. At 24 h after HI, it activated Wnt/β-catenin signaling pathway by up-regulation of β-catenin protein expression and wnt3a/wnt5a/wnt7a mRNA expression. Simultaneously, it suppressed Notch signaling pathway by down-regulation of Notch1 and HES-1 proteins expression. Our study suggested that TWS119 performed a neuroprotective function at 7 d after hypoxic-ischemic brain damage via a crosstalk with Wnt/β-catenin and Notch signaling pathways at 24 h after hypoxic-ischemic brain damage in neonatal rats.
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http://dx.doi.org/10.1016/j.brainres.2021.147588DOI Listing
October 2021

Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.

J Biol Chem 2021 Aug 14;297(2):100966. Epub 2021 Jul 14.

Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Cluster of differentiation-22 (CD22) belongs to the sialic acid-binding immunoglobulin (Ig)-like lectin family of receptors that is expressed on the surface of B cells. It has been classified as an inhibitory coreceptor for the B-cell receptor because of its function in establishing a baseline level of B-cell inhibition. The restricted expression of CD22 on B cells and its inhibitory function make it an attractive target for B-cell depletion in cases of B-cell malignancies. Genetically modified T cells with chimeric antigen receptors (CARs) derived from the m971 antibody have shown promise when used as an immunotherapeutic agent against B-cell acute lymphoblastic leukemia. A key aspect of the efficacy of this CAR-T was its ability to target a membrane-proximal epitope on the CD22 extracellular domain; however, the molecular details of m971 recognition of CD22 have thus far remained elusive. Here, we report the crystal structure of the m971 fragment antigen-binding in complex with the two most membrane-proximal Ig-like domains of CD22 (CD22). The m971 epitope on CD22 resides at the most proximal Ig domain (d7) to the membrane, and the antibody paratope contains electrostatic surfaces compatible with interactions with phospholipid head groups. Together, our data identify molecular details underlying the successful transformation of an antibody epitope on CD22 into an effective CAR immunotherapeutic target.
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http://dx.doi.org/10.1016/j.jbc.2021.100966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353475PMC
August 2021

P3H4 Overexpression Serves as a Prognostic Factor in Lung Adenocarcinoma.

Comput Math Methods Med 2021 23;2021:9971353. Epub 2021 Jun 23.

Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province 266003, China.

Background: The present study is aimed at evaluating the functional and clinical values of P3H4 in lung adenocarcinoma. Moreover, we also investigated the downstream pathways that P3H4 might participate in.

Methods: The differential expression analysis was used to identify genes differentially expressed in lung adenocarcinoma tissues as compared with normal tissues. Survival analysis was used to test the association between P3H4 and survival time. Gene set enrichment analysis was conducted to explore the downstream pathways. CCK8 and transwell were employed to examine the impact of P3H4 on cell phenotypes.

Results: P3H4 was highly upregulated in LUAD tissues at both RNA and protein levels. Moreover, the LUAD patients, who had high expression of P3H4, were also observed to have shorter disease-free survival and overall survival. These results demonstrated that P3H4 could be used as a prognostic biomarker for LUAD. Moreover, we also found that it was the copy number alterations (CNAs), not DNA methylation, that regulated the RNA expression of P3H4, indicating that its upregulation might be partially resulted from the CNAs. Furthermore, functional experiments revealed that the A549 and H1299 cells with siRNA treatment (siP3H4) exhibited significantly decreased cell proliferation after 24 hours, migratory ability, and invasiveness. Functionally, the upregulated proteins in the P3H4 high expression group were mainly enriched in tumor microenvironment-related pathways such as phagosome, focal adhesion, and ECM-receptor interaction and cancer-related pathways such as bladder cancer pathway, proteoglycans in cancer, and hippo signaling pathway.

Conclusion: The present study systematically evaluated the functional and clinical values of P3H4 in LUAD, and explored the related biological pathways. P3H4 might promote LUAD progression through regulating tumor microenvironment-related pathways.
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http://dx.doi.org/10.1155/2021/9971353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249155PMC
June 2021

Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial.

Front Pharmacol 2021 9;12:635517. Epub 2021 Jun 9.

Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Early-onset neonatal sepsis (EONS), a bacterial infection that occurs within 72 h after birth, is associated with high likelihood of neonatal mortality. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has been brought back into empirical EONS treatment in recent years. In the preliminary work, we established a population pharmacokinetics (PPK) model for latamoxef in Chinese neonates. Moreover, in order to better guide clinical treatment, we conducted dose simulation and found that ascending administration frequency could improve the target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval (70% fT > MIC). Accordingly, this study is aimed to compare the 70% fT > MIC, efficacy and safety between conventional regimen and PPK model regimen for rational use of latamoxef in EONS treatment. A single-blind, multicenter randomized controlled trial (RCT) for latamoxef will be conducted in Chinese EONS patients. Neonates (≤3 days of age, expected number = 114) admitted to the hospital with the diagnosis of EONS and fulfilling inclusion and exclusion criteria will be randomized (ratio of 1:1) to either a conventional regimen (30 mg/kg q12h) or model regimen (20 mg/kg q8h) latamoxef treatment group for at least 3 days. Primary outcome measure will be 70% fT > MIC and secondary outcome indicators will be the latamoxef treatment failure, duration of antibiotic therapy, changes of white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT), blood culture results during administration and incidence of adverse event (AE)s. Assessments will be made at baseline, initial stage of latamoxef treatment (18-72 h) and before the end of latamoxef treatment. Ethical approval of our clinical trial has been granted by the ethics committee of the Beijing Children's Hospital (ID: 2020-13-1). Written informed consent will be obtained from the parents of the participants. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR 2000040064).It is hoped that our study will provide a clinical basis for the rational clinical use of latamoxef in EONS treatment.
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http://dx.doi.org/10.3389/fphar.2021.635517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220210PMC
June 2021

Which methods are the most effective in enabling novice users to participate in ontology creation? A usability study.

Database (Oxford) 2021 06;2021

Department of Biology, University of Ottawa, 30 Marie Curie Road, Ottawa, ON K1N 6N5, Canada.

Producing findable, accessible, interoperable and reusable (FAIR) data cannot be accomplished solely by data curators in all disciplines. In biology, we have shown that phenotypic data curation is not only costly, but it is burdened with inter-curator variation. We intend to propose a software platform that would enable all data producers, including authors of scientific publications, to produce ontologized data at the time of publication. Working toward this goal, we need to identify ontology construction methods that are preferred by end users. Here, we employ two usability studies to evaluate effectiveness, efficiency and user satisfaction with a set of four methods that allow an end user to add terms and their relations to an ontology. Thirty-three participants took part in a controlled experiment where they evaluated the four methods (Quick Form, Wizard, WebProtégé and Wikidata) after watching demonstration videos and completing a hands-on task. Another think-aloud study was conducted with three professional botanists. The efficiency effectiveness and user confidence in the methods are clearly revealed through statistical and content analyses of participants' comments. Quick Form, Wizard and WebProtégé offer distinct strengths that would benefit our author-driven FAIR data generation system. Features preferred by the participants will guide the design of future iterations.
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http://dx.doi.org/10.1093/database/baab035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218699PMC
June 2021

The effect of pantoprazole and somatostatin combined with thrombin in the treatment of non-esophagogastric varicosity upper gastrointestinal bleeding.

Am J Transl Res 2021 15;13(5):5484-5490. Epub 2021 May 15.

Department of Gastroenterology, The Third Hospital of Inner Mongolia Medical University (Inner Mongolia Baogang Hospital) Baotou 014010, Inner Mongolia Autonomous Region, China.

Objective: To explore the effect of pantoprazole and somatostatin combined with thrombin in the treatment of non-esophagogastric varicosity upper gastrointestinal bleeding (UGB) as well as its influence on serum hs-CRP and coagulation function.

Methods: From June 2016 to May 2018, patients with upper gastrointestinal hemorrhage due to non-esophagogastric varices in our hospital were selected as research subjects. After screening, they were randomly divided into the combined group (57 cases) and the control group (57 cases). After the two groups are treated, the therapeutic effect was observed. The two groups of patients were followed up for 6 consecutive months, and the data were statistically analyzed.

Results: It was found that there wass no significant difference between the two groups in gender, age, amount of bleeding, and etiology (P > 0.05). It was found that the immediate hemostasis rate and the hemostasis rate within 24 hours in the combined group were distinctly higher compared to the control group. The difference has statistical significance (P < 0.05). The total effective rate of the combined group was distinctly higher compared to the control group (P < 0.05). By comparing the expression levels of hs-CRP and IL-6 protein in the serum of the two groups before and after treatment, it was found that there was no significant difference in the expression levels of hs-CRP and IL-6 protein before treatment. However, after treatment, it was found that the levels of hs-CRP and IL-6 protein in the combined group were distinctly lower compared to the control group (P < 0.05). By analyzing adverse reactions, it was found that the combined group had distinctly lower adverse reactions compared to the control group (P < 0.05).

Conclusion: This work provides an experimental basis for the diagnosis and treatment of non-esophagogastric varicose UGB in the clinic.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205661PMC
May 2021

Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.

Nat Commun 2021 06 16;12(1):3661. Epub 2021 Jun 16.

Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.

SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC) values as low as 9 × 10 M are achieved as a result of up to 10,000-fold potency enhancements compared to corresponding IgGs. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and IgG-like bioavailability. The MULTi-specific, multi-Affinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity together with multi-specificity to deliver ultrapotent and broad neutralizers against SARS-CoV-2. The modularity of the platform also makes it relevant for rapid evaluation against other infectious diseases of global health importance. Neutralizing antibodies are a promising therapeutic for SARS-CoV-2.
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http://dx.doi.org/10.1038/s41467-021-23825-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209050PMC
June 2021

Delivery room resuscitation and short-term outcomes of extremely preterm and extremely low birth weight infants: a multicenter survey in North China.

Chin Med J (Engl) 2021 Jun 16;134(13):1561-1568. Epub 2021 Jun 16.

Neonatal Intensive Care Unit, Beijing United Family Hospital, Beijing 100016, China.

Background: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China.

Methods: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD.

Results: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05).

Conclusion: Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
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http://dx.doi.org/10.1097/CM9.0000000000001499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280058PMC
June 2021

Molecular mechanism for TRPC6 regulating of disturbance of calcium signals involved in podocyte injury.

Minerva Med 2021 Jun 11. Epub 2021 Jun 11.

Pediatric Department, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing, China -

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http://dx.doi.org/10.23736/S0026-4806.21.07421-8DOI Listing
June 2021

Increased proportion of Th17/Treg cells at the new diagnosed stage of chronic immune thrombocytopenia in pediatrics: the pilot study from a multi-center.

Eur J Pediatr 2021 May 27. Epub 2021 May 27.

Hematology & Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, People's Republic of China.

Chronic immune thrombocytopenia (CITP) is an autoimmune disease with many immune dysfunctions, including T helper type 17 cell (Th17)/regulatory T cells (Tregs) imbalance. Low quality of life and side effects of drugs are severe, especially in pediatrics. This study aimed to determine Th17/Treg polarization in pediatric CITP when first diagnosing ITP and evaluate its use as a predictive marker for pediatric CITP. This was a pilot study from a multi-center. Setting the effective data size to 100 patients, data entry ended in the 142nd patient who had completed a 1-year follow-up. The percentages of Treg cells and Th17 cells were quantified by flow cytometry when new diagnosed ITP patients first arrived. The association between the Th17/Treg ratio and CITP was analyzed statistically. The percentages of Treg cells and Th17 cells were lower (P = 0.0008) and higher (P = 0.0001), respectively, in the CITP-outcome group compared with the remission group. The receiver operating characteristic analysis showed that the area under the curve (AUC) of Treg and Th17 cells was 0.811 and 0.834, respectively. The ratio of Th17/Treg exhibited the largest AUC of 0.897 (cutoff value 0.076).Conclusions: Thus, the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. It is a promising predictive marker for the development of CITP to some extent.Trial registration: ChiCTR1900022419 (10 April 2019) What is Known: • The percentage of Th17 /Treg ratio of pediatric CITP is elevated. What is New: • This study shows that the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. This work may provide a new point for pediatric CITP's prediction. The imbalanced ratio of Th17/Treg was obvious when first diagnose ITP in pediatric CITP patients, rendering them as potential predictive tools for discriminating CITP to facilitate with the management of pediatric patient care. In addition, the combination of them may serve as a predictive marker in pediatric CITP.
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http://dx.doi.org/10.1007/s00431-021-04121-zDOI Listing
May 2021

Excretion from long glandular trichomes contributes to alleviation of cadmium toxicity in Nicotiana tabacum.

Environ Pollut 2021 Sep 29;285:117184. Epub 2021 Apr 29.

Key Laboratory for Cultivation of Tobacco Industry, College of Tobacco Science, Henan Agricultural University, Zhengzhou, 450002, China. Electronic address:

The B-type cyclin gene, CycB2, serves as a negative regulator of glandular trichome initiation. Through targeted knockout of NtCycB2 in Nicotiana tabacum cv. K326 using the CRISPR/Cas9 system, we created a variety, HK326, which exhibits significantly increased density and larger glandular heads of long glandular trichomes. Under Cd-stress, HK326 exhibited enhanced Cd tolerance, as demonstrated by a robust root system, strengthened cell membrane stability, and higher photosynthetic parameters. HK326 exhibited enhanced Cd-stress tolerance due to a strong excretion capacity of long glandular trichomes by forming calcium oxalate crystals. Cd mainly accumulated in tobacco shoots rather than remained in roots. Specifically, Cd levels of the HK326 shoot surface were nearly two-fold of those of K326, resulting in less Cd internally in the roots and shoots. Gene expression patterns revealed 11 Cd transporter genes that were upregulated after Cd-stress in shoots, roots, and trichomes. Among them, the NtHMA2 gene encoding heavy metal ATPases and involved in the transport of divalent heavy metal cations was expressed consistently and significantly higher in HK326 than K326, both before and after Cd-stress. NtHMA2 expression was strong in trichomes, moderate in shoots, while weak in roots. The results indicate that NtHMA2 may be involved in Cd excretion from glandular trichomes. Our findings suggest HK326 may be an appropriate candidate plant for Cd-stress tolerance.
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http://dx.doi.org/10.1016/j.envpol.2021.117184DOI Listing
September 2021

Selective Phosphoranation of Unactivated Alkynes with Phosphonium Cation To Achieve Isoquinoline Synthesis.

Org Lett 2021 May 7;23(10):4023-4028. Epub 2021 May 7.

Department of Chemistry, Capital Normal University, Beijing 100048, People's Republic of China.

We herein develop a selective phosphoranation of alkynes with phosphonium cation, which directs a concise approach to isoquinolines from unactivated alkyne and nitrile feedstocks in a single step. Mechanistic studies suggest that the annulation reaction is initiated by the unprecedented phosphoranation of alkynes, thus representing a unique reaction pattern of phosphonium salts and distinguishing it from existing protocols that largely rely on the utilization of highly functionalized imines/oximes and/or highly polarized alkynes.
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http://dx.doi.org/10.1021/acs.orglett.1c01237DOI Listing
May 2021

Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans.

Genet Med 2021 08 12;23(8):1514-1521. Epub 2021 Apr 12.

GeneDx Inc, Gaithersburg, MD, USA.

Purpose: Reports have questioned the dogma of exclusive maternal transmission of human mitochondrial DNA (mtDNA), including the recent report of an admixture of two mtDNA haplogroups in individuals from three multigeneration families. This was interpreted as being consistent with biparental transmission of mtDNA in an autosomal dominant-like mode. The authenticity and frequency of these findings are debated.

Methods: We retrospectively analyzed individuals with two mtDNA haplogroups from 2017 to 2019 and selected four families for further study.

Results: We identified this phenomenon in 104/27,388 (approximately 1/263) unrelated individuals. Further study revealed (1) a male with two mitochondrial haplogroups transmits only one haplogroup to some of his offspring, consistent with nuclear transmission; (2) the heteroplasmy level of paternally transmitted variants is highest in blood, lower in buccal, and absent in muscle or urine of the same individual, indicating it is inversely correlated with mtDNA content; and (3) paternally transmitted apparent large-scale mtDNA deletions/duplications are not associated with a disease phenotype.

Conclusion: These findings strongly suggest that the observed mitochondrial haplogroup of paternal origin resulted from coamplification of rare, concatenated nuclear mtDNA segments with genuine mtDNA during testing. Evaluation of additional specimen types can help clarify the clinical significance of the observed results.
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http://dx.doi.org/10.1038/s41436-021-01166-1DOI Listing
August 2021

Application of 2D Materials to Potassium-Ion Hybrid Capacitors.

ChemSusChem 2021 May 7;14(9):1974-1986. Epub 2021 Apr 7.

College of Medicine, Yan'an University, Yan'an, 716000, P. R. China.

Metal-ion hybrid supercapacitors (MICs) are a new type of electrochemical energy storage (EES) device, consisting of a battery-type electrode and a supercapacitor (SC)-type electrode. Exhibiting the advantages of both batteries and SCs (e. g., good energy density, excellent power density and long cycle life), these advanced energy storage devices have considerable commercial application prospects. Among MICs, potassium-ion hybrid supercapacitors (PICs) have several further advantages, including abundancy of resources, low standard electrode potential, and low cost. PICs are regarded as potential substitutes for lithium- or sodium-ion hybrid supercapacitors. However, the practical applications of PICs remain limited, owing to the imbalance of kinetics and capacity between the electrodes, the slow ion/electron diffusion rate, and the poor electrode structural stability. Recently, 2D materials with distinct structures and fascinating features have elicited widespread attention for application in PICs, thus achieving significant enhancements, ranging from charge storage capacity to reaction kinetics. This Review discusses research progress in 2D materials for PICs. Firstly, the energy storage principle and development requirements of MICs are introduced. The pivotal advantages and significant roles of 2D materials in the fabrication of PICs are then discussed in detail. Lastly, the challenges and prospects of the application of 2D materials to high-performance PICs are presented.
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http://dx.doi.org/10.1002/cssc.202100255DOI Listing
May 2021

Association between prenatal air pollution exposure and risk of hypospadias in offspring: a systematic review and meta-analysis of observational studies.

Aging (Albany NY) 2021 03 19;13(6):8865-8879. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Background: The findings of associations between prenatal air pollution exposure and hypospadias risk in offspring are inconsistent. No systematic review or meta-analysis has yet summarized the present knowledge on the aforementioned topic.

Methods: Relevant manuscripts were identified by searching PubMed and Web of Science databases through January 31, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) in meta-analyses were estimated based on a random effects model. Publication bias was evaluated by funnel plots, Begg's test, and Egger's test.

Results: The search identified 3,032 relevant studies. Sixteen studies cumulatively involving 21,701 hypospadias cases and 1,465,364 participants were included. All of these studies were classified as having a low risk of bias. We classified pollutants as nitrogen oxides, particulate matter (PM), ozone, and other exposures. The exposure window to pollutants varied from three months before conception to seven days after delivery. In the meta-analyses, only PM exposure in the first trimester was related to increased risk of hypospadias (per 10 μg/m OR = 1.34; 95% CI: 1.06-1.68).

Conclusion: We found evidence for an effect of PM exposure on hypospadias risk. Improvements in the areas of study design, exposure assessment, and specific exposure window are needed to advance this field.
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http://dx.doi.org/10.18632/aging.202698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034939PMC
March 2021

Stable oxime-crosslinked hyaluronan-based hydrogel as a biomimetic vitreous substitute.

Biomaterials 2021 04 4;271:120750. Epub 2021 Mar 4.

Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College St, Toronto, ON, M5S 3E5, Canada; Institute of Biomedical Engineering, University of Toronto, 160 College St, Toronto, ON, M5S 3E1, Canada; Institute of Medical Sciences, University of Toronto, 1 King's College Circle, ON, M5S 1A8, Canada. Electronic address:

Vitreous substitutes are clinically used to maintain retinal apposition and preserve retinal function; yet the most used substitutes are gases and oils which have disadvantages including strict face-down positioning post-surgery and the need for subsequent surgical removal, respectively. We have engineered a vitreous substitute comprised of a novel hyaluronan-oxime crosslinked hydrogel. Hyaluronan, which is naturally abundant in the vitreous of the eye, is chemically modified to crosslink with poly(ethylene glycol)-tetraoxyamine via oxime chemistry to produce a vitreous substitute that has similar physical properties to the native vitreous including refractive index, density and transparency. The oxime hydrogel is cytocompatible in vitro with photoreceptors from mouse retinal explants and biocompatible in rabbit eyes as determined by histology of the inner nuclear layer and photoreceptors in the outer nuclear layer. The ocular pressure in the rabbit eyes was consistent over 56 d, demonstrating limited to no swelling. Our vitreous substitute was stable in vivo over 28 d after which it began to degrade, with approximately 50% loss by day 56. We confirmed that the implanted hydrogel did not impact retina function using electroretinography over 90 days versus eyes injected with balanced saline solution. This new oxime hydrogel provides a significant improvement over the status quo as a vitreous substitute.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120750DOI Listing
April 2021

Clinical outcomes and survival analysis in patients with psycho-cardiological disease: a retrospective analysis of 132 cases.

J Int Med Res 2021 Mar;49(3):300060521990984

Guangdong Pharmaceutical University, Guangzhou, China.

Objectives: The deleterious effects of psychological problems on coronary heart disease (CHD) are not satisfactorily explained. We explored influential factors associated with mortality in psycho-cardiological disease in a Chinese sample.

Methods: Of 7460 cardiac patients, we selected 132 patients with CHD and mental illness. Follow-up was conducted via telephone. We analyzed clinical characteristics, clinical outcomes, and survival.

Results: The clinical detection rate of psycho-cardiological disease in the overall patient population was 1.8%. Of these, 113 patients completed follow-up; 18 died owing to cardiovascular diseases during follow-up. Kaplan-Meier analysis showed dysphagia, limb function, self-care ability, percutaneous coronary intervention, low-density lipoprotein, total cholesterol, pro-brain natriuretic peptide and high-sensitivity (hs) troponin T had significant associations with cumulative survival. Cox regression analysis showed total cholesterol (hazard ratio [HR]: 2.765, 95% confidence interval [CI]: 1.001-7.641), hs troponin T (HR: 4.668, 95% CI: 1.293-16.854), and percutaneous coronary intervention (HR: 3.619, 95% CI: 1.383-9.474) were independently associated with cumulative survival.

Conclusions: The clinical detection rate of psycho-cardiological disease was far lower than expected. Normal total cholesterol and hs troponin T were associated with reduced cardiovascular disease mortality over 2 years. Percutaneous coronary intervention is a prognostic risk factor in patients with psycho-cardiological disease.
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http://dx.doi.org/10.1177/0300060521990984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940745PMC
March 2021

S1PR2 Inhibition Attenuates Allergic Asthma Possibly by Regulating Autophagy.

Front Pharmacol 2020 10;11:598007. Epub 2021 Feb 10.

Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, China.

This study is to investigate the role of Sphingosine-1-phosphate (S1P) in the asthma progression, and the involvement of autophagy. Airway remodeling mice were subjected to the HE, PAS, and Masson staining. Protein expression levels in the tissues, samples and model cells were detected with ELISA, Western blot analysis, and immunohistochemical/immunofluorescent analysis. The S1P2 receptor antagonist JTE-013 decreased the inflammatory cell infiltration and goblet cell production in asthmatic mice tissues. The IL-1, IL-4, IL-5 and serum IgE contents were decreased in bronchoalveolar lavage fluid, while the Beclin1 expression in lung tissues was decreased. The LC3B1 to LC-3B2 conversion was decreased, with increased P62 accumulation and decreased p-P62 expression. In airway remodeling mice, JTE-013 significantly decreased collagen deposition in lung tissues and decreased smooth muscle cell smooth muscle activating protein expression. In lung tissue, the expression levels of Beclin1 were decreased, with decreased LC3B1 to LC-3B2 conversion, as well as the increased P62 accumulation and decreased p-P62 expression. However, these effects were reversed by the RAC1 inhibitor EHT 1864. Similar results were observed for the silencing of S1P2 receptor in the cells, as shown by the decreased Beclin1 expression, decreased LC3B1 to LC-3B2 conversion, increased P62 accumulation, and decreased p-P62 expression. The smooth muscle activators were significantly decreased in the JTE-013 and EHT1864 groups, and the EHT 1864 + S1P2-SiRNA expression level was increased. S1P is involved in the progression of asthma and airway remodeling, which may be related to the activation of S1PR2 receptor and inhibition of autophagy through RAC1.
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http://dx.doi.org/10.3389/fphar.2020.598007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902893PMC
February 2021

Further delineation of BCAP31-linked intellectual disability: description of 17 new families with LoF and missense variants.

Eur J Hum Genet 2021 Sep 18;29(9):1405-1417. Epub 2021 Feb 18.

Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

The BCAP31 gene, located at Xq28, encodes BAP31, which plays a role in ER-to-Golgi anterograde transport. To date, BCAP31 pathogenic variants have been reported in 12 male cases from seven families (six loss of function (LoF) and one missense). Patients had severe intellectual disability (ID), dystonia, deafness, and central hypomyelination, delineating a so-called deafness, dystonia and cerebral hypomyelination syndrome (DDCH). Female carriers are mostly asymptomatic but may present with deafness. BCAP31 is flanked by the SLC6A8 and ABCD1 genes. Contiguous deletions of BCAP31 and ABCD1 and/or SLC6A8 have been described in 12 patients. Patients with deletions including BCAP31 and SLC6A8 have the same phenotype as BCAP31 patients. Patients with deletions of BCAP31 and ABCD1 have contiguous ABCD1 and DXS1375E/BCAP31 deletion syndrome (CADDS), and demonstrate a more severe neurological phenotype with cholestatic liver disease and early death. We report 17 novel families, 14 with intragenic BCAP31 variants (LoF and missense) and three with a deletion of BCAP31 and adjacent genes (comprising two CADDS patients, one male and one symptomatic female). Our study confirms the phenotype reported in males with intragenic LoF variants and shows that males with missense variants exhibit a milder phenotype. Most patients with a LoF pathogenic BCAP31 variant have permanent or transient liver enzyme elevation. We further demonstrate that carrier females (n = 10) may have a phenotype comprising LD, ID, and/or deafness. The male with CADDS had a severe neurological phenotype, but no cholestatic liver disease, and the symptomatic female had moderate ID and cholestatic liver disease.
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http://dx.doi.org/10.1038/s41431-021-00821-0DOI Listing
September 2021

Safety, Pharmacokinetics and Pharmacodynamics of Multiple Escalating Doses of PEGylated Exenatide (PB-119) in Healthy Volunteers.

Eur J Drug Metab Pharmacokinet 2021 Mar 12;46(2):265-275. Epub 2021 Feb 12.

PegBio Co., Ltd., Su Zhou, 215000, China.

Background And Objective: At present, the deficiency of β-cell function is progressive in patients with type 2 diabetes mellitus. Exenatide cannot only control blood glucose well, but also promotes the regeneration and proliferation of islet β-cells and improves the function of β cells. However, it needs to be given twice a day, and there are many adverse reactions such as nausea. PEGylated exenatide (study code: PB-119) needs to be administered only once a week. The purpose of this experiment was to evaluate the safety, pharmacokinetics and pharmacodynamics of an escalating dose regimen of subcutaneous PEGylated exenatide injections in healthy subjects.

Methods: Twelve healthy young adult subjects in each group received once-weekly subcutaneous injections of 165 μg, 330 μg, and 660 μg PEGylated exenatide for 6 weeks. Plasma drug concentration was determined in venous blood collected across selected time points. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, and electrocardiogram. Blood glucose, insulin,  glucagon and C peptide were monitored at different time points to evaluate the pharmacodynamics of PEGylated exenatide.

Results: A total of 11, 10, and 12 subjects completed the study in 165 µg, 330 µg, and 660 µg dose groups, respectively. After 6 consecutive weeks of administration, the t in the 165 μg, 330 μg, and 660 µg dose groups was 55.67 ± 11.03 h, 56.99 ± 21.37 h, and 54.81 ± 13.87 h, respectively. The C was 4.22 ± 0.78 ng/ml, 6.03 ± 1.43 ng/ml, and 10.50 ± 3.06 ng/ml, respectively. AUCss was 708.59 ± 131.87 h•ng/ml, 1012.63 ± 240.79 h•ng/ml, and 1763.81 ± 514.50 h•ng/ml, respectively. The accumulation index was 1.15 ± 0.07, 1.17 ± 0.11, and 1.14 ± 0.07. The CLss/F was 241.25 ± 51.13 ml/h, 341.53 ± 73.62 ml/h, and 450.06 ± 313.76 ml/h, respectively. A total of 10 of 36 (27.78%) subjects in the three dose groups developed specific antibodies after consecutive subcutaneous injections of PEGylated exenatide. The C and C were higher than those of antibody-negative subjects. Furthermore, in antibody-positive subjects, CLss/F, t, AUC, accumulation index, MRT and other parameters were lower than those of antibody-negative subjects. In the 165 μg dose group, two subjects (16.67%) experienced 4 adverse events. In the 330 μg dose group, no subjects reported adverse events. In the 660 μg dose group, 8 subjects (66.67%) reported 16 adverse events, which were mostly gastrointestinal. There were no significant changes in the pharmacodynamic parameters except the glucagon level at day 36 in the 660 µg dose group, the 2h postprandial insulin and C peptide levels at day 36 and day 50 in the 165 μg dose group compared with baseline (- 1 day).

Conclusion: A once-weekly subcutaneous injection of 165 µg and 330 µg PEGylated exenatide is safe. No significant effects on blood glucose or pancreatic hormone levels were observed in the subjects within these dose groups. The pharmacokinetic parameters of PEGylated exenatide may be affected by immunogenicity.

Clinical Trials Registration: The study is registered at clinicaltrials.gov (No. NCT03062774).
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http://dx.doi.org/10.1007/s13318-020-00665-xDOI Listing
March 2021

Birthweight is an independent predictor of birth asphyxia in twins: A retrospective cross-sectional cohort study of 5337 Chinese twins.

Eur J Obstet Gynecol Reprod Biol 2021 Feb 10;257:106-113. Epub 2020 Dec 10.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Objective: Few studies are available on birth asphyxia risks in twin neonates. This retrospective multi-center cross-sectional study determined the birthweight percentiles of 5337twins and birth asphyxia incidence of the twin population.

Methods: We retrieved sociodemographic and obstetric data from the electronic records systems of participating centers. Neonate birthweight was measured within 24 h of birth. Perinatal asphyxia was diagnosed if 5-minute Apgar score was ≤5, or resuscitation was required 10 min after birth. The primary outcome was the incidence of birth asphyxia.

Results: Totally 5337 neonates were eligible. The mean neonatal birthweight was 2227.1 ± 608.99 g and the 5th, 50th, and 95th percentiles of birthweight were 970, 2400, and 3080 g, respectively. The mean Apgar score was 9.06 ± 1.73 at 1 min and 8.99 ± 1.74 at 5 min. Totally 13.5 % (705/5222) twins had asphyxia and 9.35 % and 4.16 % twins had moderate and severe asphyxia, respectively. Twins with a birthweight< 1500 g had the highest asphyxia rate (64.8 %) and twins with a birthweight between 2500 and 3000 g had the lowest asphyxia rate (3.6 %). Stepwise logistic regression analysis revealed that higher birthweight was associated with a significantly reduced risk of asphyxia [OR 0.772 (95 %CI 0.755, 0.789), P < 0.001]. The AUROC for mean twin birthweight was 0.86±0.01 (95 %CI 0.84, 0.88) using a cutoff of 1950 g, with a sensitivity of 0.84 and a specificity of 0.78.

Conclusion: Twins have lower birthweight versus singletons and a significant proportion of twins, especially twins with lower birthweight, are at risk of birth asphyxia. Birthweight is an independent predictor of asphyxia and should be further explored as a predictive marker for stratifying asphyxia risks in twin neonates.
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http://dx.doi.org/10.1016/j.ejogrb.2020.12.014DOI Listing
February 2021

[Effect of breastfeeding on the development of infection-related diseases during hospitalization in late preterm infants in 25 hospitals in Beijing, China].

Zhongguo Dang Dai Er Ke Za Zhi 2020 Dec;22(12):1245-1250

Department of Pediatrics, First Hospital of Tsinghua University, Beijing 100016, China.

Objective: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases.

Methods: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases.

Results: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, =0.033). The multivariate logistic regression analysis showed that breastfeeding was an independent protective factor against infectious diseases (=0.534, =0.004), while male sex, premature rupture of membranes, gestational diabetes mellitus, and asphyxia were risk factors for infectious diseases (=1.328, 5.386, 1.535, and 2.353 respectively, < 0.05).

Conclusions: Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735928PMC
December 2020

Antiproliferative Activity, Proapoptotic Effect, and Cell Cycle Arrest in Human Cancer Cells of Some Marine Natural Product Extract.

Oxid Med Cell Longev 2020 25;2020:7948705. Epub 2020 Nov 25.

Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt.

Bioactive constituents of numerous marine organisms have been investigated recently for their preclinical and clinical anticancer activity. Three marine organisms: black-spotted sea cucumber: (), lollyfish: (), and sea hare: (), were collected during winter 2019 from Gulf of Aqaba, Red Sea, Egypt, and macerated with ethanol into three different extracts: , , and , where each was assessed for its antiproliferative and proapoptotic properties on , , and cancer cells. dose-dependently inhibited the growth of , , and cells within IC values 16.22, 13.34, and 18.09 g/mL, respectively, while the IC values for the antiproliferative activity of were 12.48, 10.45, and 10.36 g/mL, respectively, and the IC values of were 6.51, 5.33, and 6.87 g/mL, respectively. All extracts were found to induce G/G cell cycle arrest for cells side by side with their inhibition of on all three cell lines while all extracts were also showed to induce apoptosis in cell line at pre- phase supplemented by their anticancer activity via proapoptotic protein , , and cleavage increase, and antiapoptotic protein downturn. Moreover, necrosis has been relatively noticed in cell line as an additional anticancer activity for each extract. Our data introduced three ethanolic marine extracts as natural chemotherapeutic agents to be further developed for cancer control.
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http://dx.doi.org/10.1155/2020/7948705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714591PMC
June 2021

Mitochondrial genome variant m.3250T>C as a possible risk factor for mitochondrial cardiomyopathy.

Hum Mutat 2021 Feb 1;42(2):177-188. Epub 2020 Dec 1.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

The MT-TL1 gene codes for the mitochondrial leucine transfer RNA (tRNA ) necessary for mitochondrial translation. Pathogenic variants in the MT-TL1 gene result in mitochondriopathy in humans. The m.3250T>C variant in the MT-TL1 gene has been previously associated with exercise intolerance and mitochondrial myopathy, yet disease classification for this variant has not been consistently reported. Molecular studies suggest the m.3250T>C variant does not alter tRNA structure but may have a modest impact on aminoacylation capacity. However, functional studies are limited. Our study aimed to further define the clinical presentation, inheritance pattern, and molecular pathology of the m.3250T>C variant. Families with the m.3250T>C variant were recruited from the Mitochondrial Disease Clinic at Cincinnati Children's Hospital Medical Center and GeneDx laboratory database. Affected individuals most frequently presented with cardiac findings, exercise intolerance, and muscle weakness. Hypertrophic cardiomyopathy was the most frequent cardiac finding. Many asymptomatic individuals had homoplasmic or near homoplasmic levels of the m.3250T>C variant, suggesting the penetrance is incomplete. Patient-derived fibroblasts demonstrated lowered ATP production and increased levels of reactive oxygen species. Our results demonstrate that the m.3250T>C variant exhibits incomplete penetrance and may be a possible cause of cardiomyopathy by impacting cellular respiration in mitochondria.
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http://dx.doi.org/10.1002/humu.24143DOI Listing
February 2021

Quantitative Assessment of the Pupil: An Underrecognized Yet Important Factor Related to Orbital Blowout Fracture Repair.

J Craniofac Surg 2020 Nov 25. Epub 2020 Nov 25.

Department of Ophthalmology, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.

Purpose: To investigate dynamic pupil changes after orbital blowout fracture repair. To compare postoperative changes in under photopic and mesopic pupil size and center position after orbital blowout fracture repair surgery.

Methods: The study evaluated 19 eyes. Pupils were imaged for pupil size and center position before and 3 months after orbital blowout fracture repair surgery. Pupil size changes were measured, and the correlation between preoperative and postoperative pupil centroid shift was evaluated.

Results: After repair, operative eyes exhibited a growth of 9.3% ± 8.6% in pupil size, and contralateral eyes showed a growth of 8.6% ± 8.2% (P = 0.011, P = 0.007). Similar findings were noted in mesopic conditions. Under mesopic conditions, the pupil of operative eyes in medial orbital wall fracture deviated 0.030 ± 0.019 mm towards the nasal side along the X-axis (P = 0.031). The postoperative orbital floor fracture group demonstrated statistical significance at a spatial frequency of 5 (P = 0.041).

Conclusions: Orbital blowout fracture repair surgery affects pupil size and center position.
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http://dx.doi.org/10.1097/SCS.0000000000007213DOI Listing
November 2020
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