Publications by authors named "Dandan Luo"

76 Publications

A new classification of congenital abnormalities of UPVS: sonographic appearances, screening strategy and clinical significance.

Insights Imaging 2021 Sep 6;12(1):125. Epub 2021 Sep 6.

Department of Ultrasound, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Hongli Road No. 2004, Futian, Shenzhen, 518028, Guangdong, China.

The umbilical-portal venous system (UPVS) plays an important role in embryonic development, as well as a significant blood circulation system to ensure the normal blood supply of fetal heart and brain and other vital organs. Congenital anomalies of UPVS contain many subtypes with a broad spectrum of manifestations and prognoses. Furthermore, because of fetal small lumen of UPVS, the sonographic evaluation remains difficult in utero. Appreciation of normal embryology and anatomy of UPVS is essential to an understanding of sonographic characteristics of anomalies of UPVS and fetal sequential changes. Through reviewing previous references and our experience with congenital abnormalities of UPVS, a new comprehensive classification is proposed. The new classification identifies three types of congenital abnormalities of UPVS based on morphological abnormalities and shunts. The embryology and etiology, sonographic, clinical and prognostic characteristics of each subtype of the new classification are described in detail. Knowledge of congenital abnormalities of UPVS can give sonographers a clue and aid prenatal sonographic diagnosis. The purpose of this article is to help the sonographers to understand the new classification of congenital abnormalities of UPVS, master the sonographic characteristics of each subtype and prenatal ultrasonographic screening strategy, and guide subsequent appropriate counseling and management.
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http://dx.doi.org/10.1186/s13244-021-01068-5DOI Listing
September 2021

Multivalent effects of heptamannosylated β-cyclodextrins on macrophage polarization to accelerate wound healing.

Colloids Surf B Biointerfaces 2021 Aug 26;208:112071. Epub 2021 Aug 26.

Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China; Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China. Electronic address:

Macrophages have high plasticity and heterogeneity, and can suppress or mediate inflammation, depending on their cytokine secretion and phenotype. Regulating macrophage polarization into its M2 phenotype has a remarkable effect on inflammatory inhibition, inducing the regeneration of injured tissues. Here, we synthesized two heptamannosylated β-cyclodextrin derivatives (CD-Man7 and C-CD-Man7) and demonstrated that their multivalent mannose ligands could induce M2 macrophage polarization to accelerate wound healing. Unlike hydrophilic CD-Man7, amphiphilic C-CD-Man7 can self-assemble to form nanoparticles (CD-Man-NPs) in aqueous solution. Further, in vitro results confirmed that multivalent mannose ligands of either CD-Man7 or CD-Man-NPs stimulated RAW264.7 macrophages to differentiate into the M2 phenotype, which promoted fibroblast migration via a paracrine mechanism. In vivo results confirmed that both CD-Man7 and CD-Man-NPs reduced the inflammatory response in wound tissue and accelerated wound healing. The present study demonstrates multivalent effects of CD-Man7 and CD-Man-NPs on M2 macrophage polarization, indicating the therapeutic potential of these β-cyclodextrin glycoconjugates in the treatment of inflammatory diseases and wound healing.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112071DOI Listing
August 2021

Facile synthesis of biocompatible magnetic titania nanorods for T-magnetic resonance imaging and enhanced phototherapy of cancers.

J Mater Chem B 2021 Sep 10;9(33):6623-6633. Epub 2021 Aug 10.

Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Cancer treatment has been recently energized by nanomaterials that simultaneously offer diagnostic and therapeutic effects. Among the imaging and treatment modalities in frontline research today, magnetic resonance imaging (MRI) and phototherapy have gained significant interest due to their noninvasiveness among other intriguing benefits. Herein, Fe(iii) was adsorbed on titanium dioxide to develop magnetic Fe-TiO nanocomposites (NCs) which leverage the Fe moiety in a double-edge-sword approach to: (i) achieve T-weighted MRI contrast enhancement, and (ii) improve the well-established photodynamic therapeutic efficacy of TiO nanoparticles. Interestingly, the proposed NCs exhibit classic T MRI contrast agent properties (r = 1.16 mM s) that are comparable to those of clinically available contrast agents. Moreover, the NCs induce negligible cytotoxicity in traditional methods and show remarkable support to the proliferation of intestine organoids, an advanced toxicity evaluation system based on three-dimensional organoids, which could benefit their potential safe application for in vivo cancer theranostics. Aided by the Fenton reaction contribution of the Fe component of the Fe-TiO NCs, considerable photo-killing of cancer cells is achieved upon UV irradiation at very low (2.5 mW cm) intensity in typical cancer PDT. It is therefore expected that this study will guide the engineering of other biocompatible magnetic titania-based nanosystems with multi-faceted properties for biomedical applications.
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http://dx.doi.org/10.1039/d1tb01097bDOI Listing
September 2021

Prevalence of Human Papillomavirus and Genotype Distribution in Pregnant and Non-Pregnant Women in China.

Risk Manag Healthc Policy 2021 28;14:3147-3157. Epub 2021 Jul 28.

Department of Gynecology, Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.

Purpose: The status of human papillomavirus (HPV) infection in pregnant and non-pregnant women in China remains unclear. This study aimed to compare the prevalence and genotype distributions of HPV between pregnant and non-pregnant women in China.

Patients And Methods: A case-control study was conducted of pregnant women during the second trimester and age-matched non-pregnant women attending the Fujian Maternity and Child Health Hospital between January 1, 2017 and December 31, 2018. Participants underwent cervical cytology testing and HPV genotyping. The genotyping test was able to identify 14 high-risk HPV (HR-HPV), four possible HR-HPV, and five low-risk HPV (LR-HPV) types. Further colposcopy and a cervical biopsy were performed if indicated. The primary outcomes were HPV prevalence and genotype distribution.

Results: In total, 1077 pregnant and 1077 non-pregnant women were enrolled. Compared with non-pregnant women, pregnant women had a higher prevalence of HPV (24.2% vs 14.8%), HR-HPV (20.2% vs 11.7%), and LR-HPV (8% vs 4.5%) infection. In pregnant women, the most prevalent HPV genotypes were HPV-52 (6.0%), -16 (3.5%), -58 (2.6%), -53 (2.5%), and -51 (2.5%), while in non-pregnant women the most prevalent genotypes were HPV-52 (3.6%), -81 (1.9%), -51 (1.8%), -68 (1.4%), and -16 (1.3%). In women aged ≥35 years, HR-HPV (P=0.002) and LR-HPV (P=0.001) prevalence were significantly higher in pregnant women. However, in women aged <35 years, only HR-HPV prevalence was higher in pregnant women. Pregnant and non-pregnant women with HPV-16 and HPV-58 infection had a high prevalence of high-grade squamous intra-epithelial lesions (HSIL) (HPV-16: P<0.001 and P=0.005, HPV-58: P=0.043 and P=0.005); but with other HR-HPV genotypes, only non-pregnant women had an increased HSIL prevalence.

Conclusion: In China, the HPV prevalence is higher in pregnant women than that in non-pregnant women and is also age- and genotype-dependent. HPV-infected pregnant women aged ≥35 years and those with HPV-16 should be closely monitored to enable rapid clinical intervention.
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http://dx.doi.org/10.2147/RMHP.S288838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326939PMC
July 2021

A Prenatal Ultrasound Scanning Approach: One-Touch Technique in Second and Third Trimesters.

Ultrasound Med Biol 2021 08 28;47(8):2258-2265. Epub 2021 May 28.

Department of Ultrasound, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, China. Electronic address:

This study was aimed at evaluating the performance of the innovative technique Smart Fetus (SF) developed to recognize the planes and obtain the basic biometric measurements of fetuses automatically. This prospective study included 1005 uncomplicated singleton pregnancies undergoing routine examinations. For every pregnancy, planes, including the transverse section of the thalami, transverse section of the abdomen and longitudinal section of the femur, were acquired, and standard biometric measurements, including biparietal diameter, head circumference, abdominal circumference and femur length, were obtained using SF and traditional ultrasound technique (TUT). The accuracy, reproducibility and time required for the analysis of SF were compared with those of TUT. In 998 of 1005 cases (99.30%), SF successfully acquired the sections and made all measurements. The agreement between the techniques was high for all measurements. The time to obtain sections and measure biometric parameters or solely measure biometric parameters was significantly shorter with SF than with TUT. No significant differences were found in SF repeated measurements obtained by two independent observers. The SF technique helped in the acquisition of reliable standard sections and biometric measurements and saved time. It might serve as a novel ultrasound scanning approach and improve workflow efficiency.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.04.020DOI Listing
August 2021

Effects of increasing intake of soybean oil on synthesis of testosterone in Leydig cells.

Nutr Metab (Lond) 2021 May 26;18(1):53. Epub 2021 May 26.

Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China.

Background: Soybean oil is a very common edible oil in daily life. With the changes in the dietary composition, the intake of soybean oil increased. However, the effects of dietary intake of soybean oil on testosterone production are still unclear.

Methods: In order to study the effects of increasing intake of soybean oil on the synthesis of testosterone in Leydig cells, we fed male C57BL/6 mice on the diet which added 20% soybean salad oil (SOY group). We detected the hormone levels by enzyme-linked immunosorbent assay (ELISA) kits and serum fatty acid composition by gas chromatography, and analyzed the expression of steroidogenic enzymes by Real-Time PCR or immunoblotting analysis.

Results: After the 16-week feeding period, serum linoleic acid (LA) and α-linolenic acid (ALA) significantly increased and serum palmitic acid (PA) significantly decreased in SOY group mice. Compared to the normal diet (ND group), increasing intake of soybean oil raised the luteinizing hormone (LH) levels and up-regulated luteinizing hormone/chorionic gonadotropin receptor (LHCGR), steroidogenic acute regulatory protein (StAR) and cytochrome P450 family 11 subfamily A member I (CYP11A1). Testosterone levels in SOY group were higher than that in the ND group, and significantly difference showed.

Conclusions: Increasing intake of soybean oil could raise the serum LA and ALA levels and decrease serum PA levels. This could activate the LH/LHCGR pathway and improve the function of steroid synthesis in Leydig cells, and finally lead to the elevated testosterone levels.
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http://dx.doi.org/10.1186/s12986-021-00580-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157704PMC
May 2021

Novel phage vB_CtuP_B1 for controlling Cronobacter malonaticus and Cronobacter turicensis in ready-to-eat lettuce and powered infant formula.

Food Res Int 2021 05 26;143:110255. Epub 2021 Feb 26.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China. Electronic address:

Cronobacter spp. are important foodborne pathogens that are a threat to people of all ages, but especially neonates and infants. Bacteriophages are biological agents that are potentially useful for the control of foodborne pathogens. However, there has been little research on the control of C. malonaticus and C. turicensis using bacteriophages. In the present study, a novel lytic phage vB_CtuP_B1 (hereafter referred to as B1)-which can simultaneously lyse C. malonaticus and C. turicensis- was isolated from river water in Guangzhou, China, and was used in the control of Cronobacter contaminated food. The phage has a short tail, and has been identified as a new species of Kayfunavirus based on genomic and phylogenetic analyses. One-step growth and stability assays revealed that phage B1 has a very short latent period (<5 min) and a large burst size (4006 pfu/cell), and is highly stable between 25 and 60 °C and between pH 5 and 11. Its genome encodes two lytic proteins, but does not contain any genes responsible for antibiotic resistance and virulence factors. In broth, the phage B1 completely inhibited the growth of C. malonaticus cro2475W and C. turicensis cro1541A1-1 for up to 6 h. On lettuce, phage B1 reduced the viable count of C. turicensis cro1541A1-1 to below the detection limit for bacteria on lettuce (<10 cfu/mL) after 6 h at 4 °C and 2 h at 25 °C, and also significantly reduced the viable count of C. malonaticus cro2475W at those temperatures. In powdered infant formula, the viable counts of both the phage-treated bacterial hosts were significantly reduced after 2 h of storage at 4 °C or 37 °C. Furthermore, phage B1 reduced the viable count of C. turicensis cro1541A1-1 to below the detection limit (<10 cfu/mL) from 4 h to 24 h at 37 °C. It significantly inhibited the growth of C. turicensis cro1541A1-1 than that of C. malonaticus cro2475W (P < 0.05). In conclusion, phage B1 with high stability and strong lytic ability is potentially useful for controlling C. malonaticus and C. turicensis.
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http://dx.doi.org/10.1016/j.foodres.2021.110255DOI Listing
May 2021

Characterization, antioxidant activity, and biocompatibility of selenium nanoparticle-loaded thermosensitive chitosan hydrogels.

J Biomater Sci Polym Ed 2021 Jul 6;32(10):1370-1385. Epub 2021 May 6.

Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hang zhou, China.

In this study, we recruited chitosan (CS) both for selenium nanoparticles (SeNPs) synthesis and for the development of a thermoresponsive nanocomposite hydrogel with the addition of glycerol phosphate (GP). Considering that SeNPs are toxic at high concentrations, five different ingredients of the nanocomposite hydrogel system with low concentrations of SeNPs (1.25-20 μg/mL) were prepared. The gelation conditions, structural characteristics, and mechanical properties of SeNPs-loaded thermosensitive CS/GP hydrogels were investigated. We also evaluated their antioxidizing activities and biocompatibility of the CS/GP/SeNPs hydrogels. Our study demonstrated that the incorporation of SeNPs in the hydrogel improved its mechanical properties, antioxidant activity, and degree of swelling. According to the properties of SeNPs and CS/GP thermosensitive hydrogels, the combination of these two technologies in an appropriate manner would be a promising antioxidant system for drug delivery and tissue engineering.
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http://dx.doi.org/10.1080/09205063.2021.1917813DOI Listing
July 2021

Prenatal Diagnosis of Congenital Cataract: Sonographic Features and Perinatal Outcome in 41 Cases.

Ultraschall Med 2021 Mar 16. Epub 2021 Mar 16.

Department of Ultrasound, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, China.

Purpose:  To describe the prenatal ultrasonographic characteristics and perinatal outcomes of congenital cataract.

Materials And Methods:  We analyzed congenital cataract diagnosed prenatally at four referral centers between August 2004 and February 2019. The diagnosis was confirmed by postnatal ophthalmologic evaluation of liveborn infants or autopsy for terminated cases. Maternal demographics, genetic testing results, prenatal ultrasound images, and perinatal outcomes were abstracted.

Results:  Total of 41 cases of congenital cataract diagnosed prenatally among 788 751 women undergoing anatomic survey. Based on the sonographic characteristics, 16/41 (39.0 %) had a dense echogenic structure, 15/41 (36.6 %) had a hyperechogenic spot and 10/41 (24.4 %) had the "double ring" sign. 17/41 (41.5 %) were isolated, and 24/41 (58.5 %) had associated intraocular and extraocular findings. Microphthalmia, cardiac abnormalities, and central nervous system abnormalities were the most common associated abnormalities. Regarding potential etiology, 6 cases had a known family history of congenital cataract, 4 cases had confirmed congenital rubella infection, and 2 cases had aneuploidy. 31/41 (75.6 %) elected termination and 10/41 (24.4 %) elected to continue their pregnancy. Among the 10 cases, one case died, one case was lost to follow-up, and the remaining 8 cases were referred for ophthalmologist follow-up and postnatal surgery.

Conclusion:  Once fetal cataracts are detected, a detailed fetal anatomy survey to rule out associated abnormalities and a workup to identify the potential etiology are recommended. Prenatal diagnosis of congenital cataracts provides vital information for counseling and subsequent management.
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http://dx.doi.org/10.1055/a-1320-0799DOI Listing
March 2021

Isolation and characterization of new phage vB_CtuP_A24 and application to control Cronobacter spp. in infant milk formula and lettuce.

Food Res Int 2021 03 12;141:110109. Epub 2021 Jan 12.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, Guangdong Province, China. Electronic address:

Cronobacter spp. are opportunistic pathogenic bacteria that cause severe diseases in neonates and infants. Bacteriophages are novel antibacterial agents with a potential to control this pathogen. In the current study, a novel lytic Cronobacter phage, vB_CtuP_A24, was isolated from a river in Guangzhou, China. The phage was characterized by a short, non-contractile tail and a long head and identified as a new member of the family Podoviridae. Complete genome sequence analysis of this phage indicated that its genome contained 75,106 bp of DNA, an average GC content of 44.05%, and 108 predicted open reading frames (ORFs). The annotated ORFs were associated with phage structure, packaging, host lysis, DNA manipulation, transcription, and additional functions. Genes responsible for antibiotic resistance, virulence, and toxic effects were not present. Cronobacter phage vB_CtuP_A24 is a novel lytic phage that can lyse five Cronobacter spp. It was stable over a wide range of temperatures (25-60 °C) and pH values (pH 4-11) and displayed a short latent period (approximately 10 min) and a large burst size (500 plaque-forming units (PFUs)/cell). In Luria-Bertani (LB) broth, phage A24 effectively inhibited the growth of C. dublinensis cro280B, C. sakazakii 465G, and C. malonaticus cro695W up to 9, 10, and 12 h, respectively, while in infant milk formulas, it inhibited two strains, C. sakazakii 465G and C. malonaticus cro695W, up to 24 h at 37 °C, with maximum reduction levels of approximately 5.12 ± 3.95 and 7.38 ± 3.03 log colony-forming unit (CFU)/mL, respectively. In lettuce, the reduction of all three strains was highly significant at 25 °C. However, the growth of C. dublinensis cro280B and C. sakazakii 465G were not significantly inhibited at 4 °C. In conclusion, Cronobacter spp. phage vB_CtuP_A24, which has lytic ability against five Cronobacter species, stability under different environments, and shows potential as a promising biocontrol agent against Cronobacter spp. in food production.
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http://dx.doi.org/10.1016/j.foodres.2021.110109DOI Listing
March 2021

Association of Metabolic Obesity Phenotypes and Total Testosterone in Chinese Male Population.

Diabetes Metab Syndr Obes 2021 29;14:399-408. Epub 2021 Jan 29.

Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, People's Republic of China.

Objective: Obesity and metabolic syndrome have been reported to exert an impact on the male reproductive system with decreasing levels of serum total testosterone (TT); however, the effect of different metabolic obesity phenotypes on testosterone has been poorly studied. We aimed to evaluate the association of metabolic obesity phenotypes and total testosterone levels in a Chinese male population.

Methods: We performed a retrospective study based on an epidemiological investigation, a total of 4,081 male individuals aged from 40-75 years old were recruited. The population was classified as metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO) according to normal weight (BMI<25.0) and overweight/obesity (BMI≥25.0) with or without metabolic syndrome.

Results: We collected 563 hypotestosteronemia among 4,081 male individuals. The odds ratios (ORs) (95% CIs) of hypotestosteronemia in obesity and metabolic syndrome were 3.072 (2.414-3.911) and 3.294 (2.631-4.125), respectively, after adjusting for age, luteinizing hormone, smoking status, and alcohol consumption. Compared to the MHNW group, male subjects in MHO, MUNW, and MUO groups had decreased serum TT levels. Additionally, the MUO group had a lowest concentration of serum TT and a highest proportion of hypotestosteronemia. There was no significant difference of TT levels between the MHO and MUNW groups.

Conclusion: Obesity and metabolic syndrome are independent risk factors of hypotestosteronemia in Chinese male populations. Our study also suggested that individuals with MHO, MUNW, and MUO have a higher risk of developing hypotestosteronemia.
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http://dx.doi.org/10.2147/DMSO.S293259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853434PMC
January 2021

Genetic and Epigenetic Characteristics of Autosomal Dominant Pseudohypoparathyroidism Type 1B: Case Reports and Literature Review.

Horm Metab Res 2021 Apr 29;53(4):225-235. Epub 2021 Jan 29.

Department of Endocrinology and Metabolism, Shandong University, Jinan, Shandong, China.

Autosomal dominant pseudohypoparathyroidism 1B (AD-PHP1B) is a rare endocrine and imprinted disorder. The objective of this study is to clarify the imprinted regulation of the guanine nucleotide binding-protein α-stimulating activity polypeptide 1 (GNAS) cluster in the occurrence and development of AD-PHP1B based on animal and clinical patient studies. The methylation-specific multiples ligation-dependent probe amplification (MS-MLPA) was conducted to detect the copy number variation in syntaxin-16 (STX16) gene and methylation status of the GNAS differentially methylated regions (DMRs). Long-range PCR was used to confirm deletion at STX16 gene. In the first family, DNA analysis of the proband and proband's mother revealed an isolated loss of methylation (LOM) at exon A/B and a 3.0 kb STX16 deletion. The patient's healthy grandmother had the 3.0 kb STX16 deletion but no epigenetic abnormality. The patient's healthy maternal aunt showed no genetic or epigenetic abnormality. In the second family, the analysis of long-range PCR revealed the 3.0 kb STX16 deletion for the proband but not her children. In this study, 3.0 kb STX16 deletion causes isolated LOM at exon A/B in two families, which is the most common genetic mutation of AD-PHP1B. The deletion involving NESP55 or AS or genomic rearrangements of GNAS can also result in AD-PHP1B, but it's rare. LOM at exon A/B DMR is prerequisite methylation defect of AD-PHP1B. STX16 and NESP55 directly control the imprinting at exon A/B, while AS controls the imprinting at exon A/B by regulating the transcriptional level of NESP55.
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http://dx.doi.org/10.1055/a-1341-9891DOI Listing
April 2021

Cronobacter spp. isolated from aquatic products in China: Incidence, antibiotic resistance, molecular characteristic and CRISPR diversity.

Int J Food Microbiol 2020 Dec 7;335:108857. Epub 2020 Sep 7.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong, Academy of Sciences, Guangzhou 510070, China. Electronic address:

Cronobacter species (Cronobacter spp.) are important foodborne pathogens that can infect and cause serious life-threatening diseases in infants and immunocompromised elderly. This study aimed to acquire data on Cronobacter spp. contamination of aquatic products in China from 2011 to 2016. In total, 800 aquatic products were tested, and the overall contamination rate for Cronobacter spp. was 3.9% (31/800). The average contamination level of the positive samples was 2.05 MPN/g. Four species and nine serotypes were identified among 33 isolates, of which the C. sakazakii serogroup O1 (n = 9) was the primary serotype. The majority of Cronobacter spp. strains harbored highest resistance against cephalothin (84.8%), followed by tetracycline (6.1%), trimethoprim/sulfameth-oxazole (3.0%) and chloramphenicol (3.0%). Two isolates were resistant to three antibiotics. In total, 26 sequence types and 33 CRISPR types (including 6 new STs and 26 new CTs) were identified, which indicates the extremely high diversity of Cronobacter spp. in aquatic products. Pathogenic C. sakazakii ST4, ST1, and C. malonaticus ST7 were also observed. Overall, this large-scale study revealed the relatively low prevalence and high genetic diversity of Cronobacter spp. in aquatic products in China, and the findings provide valuable information that can guide the establishment of effective measures for the control and precaution of Cronobacter spp. in aquatic products during production processes.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2020.108857DOI Listing
December 2020

Hemopexin as an Inhibitor of Hemolysis-Induced Complement Activation.

Front Immunol 2020 31;11:1684. Epub 2020 Jul 31.

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.

Hemopexin is the main plasmatic scavenger of cell-free heme, released in the context of intravascular hemolysis or major cell injury. Heme is indispensable for the oxygen transport by hemoglobin but when released outside of the erythrocytes it becomes a danger-associated molecular pattern, contributing to tissue injury. One of the mechanisms of pro-inflammatory action of heme is to activate the innate immune complement cascade. Therefore, we hypothesized that injection of hemopexin will prevent hemolysis-induced complement activation. Human plasma-derived hemopexin is compatible with the heme clearance machinery of the mice. 100 or 500 mg/kg of hemopexin was injected in C57Bl/6 mice before treatment with phenylhydrazine (inducer of erythrocytes lysis) or with PBS as a control. Blood was taken at different timepoints to determine the pharmacokinetic of injected hemopexin in presence and absence of hemolysis. Complement activation was determined in plasma, by the C3 cleavage (western blot) and in the kidneys (immunofluorescence). Kidney injury was evaluated by urea and creatinine in plasma and renal NGAL and HO-1 gene expression were measured. The pharmacokinetic properties of hemopexin (mass spectrometry) in the hemolytic mice were affected by the target-mediated drug disposition phenomenon due to the high affinity of binding of hemopexin to heme. Hemolysis induced complement overactivation and signs of mild renal dysfunction at 6 h, which were prevented by hemopexin, except for the NGAL upregulation. The heme-degrading capacity of the kidney, measured by the HO-1 expression, was not affected by the treatment. These results encourage further studies of hemopexin as a therapeutic agent in models of diseases with heme overload.
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http://dx.doi.org/10.3389/fimmu.2020.01684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412979PMC
April 2021

Gram-scale synthesis of splat-shaped Ag-TiO nanocomposites for enhanced antimicrobial properties.

Beilstein J Nanotechnol 2020 29;11:1119-1125. Epub 2020 Jul 29.

School of Material Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.

The control over contagious diseases caused by pathogenic organisms has become a serious health issue. The extensive usage of antibiotics has led to the development of multidrug-resistant bacterial strains. In this regard, metal-oxide-based antibacterial nanomaterials have received potential research interest due to the efficient prevention of microorganism growth. In this study, splat-shaped Ag-TiO nanocomposites (NCs) were synthesized on the gram scale and the enhanced antibacterial properties of TiO in the presence of silver were examined. The formation of Ag-TiO NCs was analyzed through various characterization techniques. The cell viability experimental results demonstrated that the Ag-TiO NCs have good biocompatibility. The antibacterial activity of the prepared Ag-TiO NCs was tested against the Gram-positive () and Gram-negative () bacterial strains. The Ag-TiO NCs exhibited promising and superior antibacterial properties compared to TiO nanospheres as confirmed by the bacterial growth and inhibition zone. The improvement in the antibacterial activity was attributed to the synergistic effect of the hybrid nature of TiO nanoparticles in the presence of Ag.
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http://dx.doi.org/10.3762/bjnano.11.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404300PMC
July 2020

Biosilicified oncolytic adenovirus for cancer viral gene therapy.

Biomater Sci 2020 Oct 11;8(19):5317-5328. Epub 2020 Aug 11.

School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Oncolytic adenoviruses (OAs) have shown great potential for cancer viral gene therapy in clinical studies. To date, clinical trials have shown that the curative efficacy of OAs is still limited by hepatic sequestration and preexisting neutralizing antibodies (nAbs), which decrease the accumulation of the OAs in tumors. Herein, with the biosilicification method, we encapsulated an OA encoding the anticancer gene Trail (OA-Trail) with silica, which significantly improved virus distribution and tumor inhibition. In vitro and in vivo results indicated that compared with the native OA, biosilicified OA-Trail ([email protected]) showed significantly reduced viral clearance in the liver and evaded nAb degradation, inducing an efficacious anticancer effect under the premise of biocompatibility. These achievements present an alternative strategy involving biosilicification for enhanced OA-based cancer gene therapy.
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http://dx.doi.org/10.1039/d0bm00681eDOI Listing
October 2020

Quantitative Analysis of the Proteome and the Succinylome in the Thyroid Tissue of High-Fat Diet-Induced Hypothyroxinemia in Rats.

Int J Endocrinol 2020 23;2020:3240198. Epub 2020 Jul 23.

Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, China.

Hypothyroidism is a common disease, and its molecular mechanism still needs further investigation. Lysine succinylation is found to be involved in various metabolic processes associated with hypothyroidism. We performed quantitative analysis on lysine succinylome in thyroids of rats with hypothyroxinemia, which was induced through the administration of a high-fat diet. Overall, 129 differentially expressed proteins were quantified. Downregulated proteins were enriched in the thyroid hormone synthesis and thyroid hormone signaling pathways and were mainly localized in the mitochondria. In addition, 172 lysine succinylation sites on 104 proteins were obviously changed. Decreased succinylated proteins were involved in diverse metabolic pathways and were primarily localized in mitochondria. Finally, the mitochondrial oxygen consumption rates of human normal thyroid epithelial cells were measured to further verify the role of lysine succinylation. The mitochondrial oxygen consumption rates were markedly blunted in the cells treated with palmitic acid (all < 0.05), and the changes were reversed when the cells were treated with palmitic acid and desuccinylase inhibitor together (all < 0.05). Thus, we theorize that the thyroid differentially expressed proteins and changed succinylation levels played potential roles in the mitochondria-mediated energy metabolism in the high-fat diet-induced hypothyroxinemia rat model.
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http://dx.doi.org/10.1155/2020/3240198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396117PMC
July 2020

Fetal Open and Closed Spina Bifida on a Routine Scan at 11 Weeks to 13 Weeks 6 Days.

J Ultrasound Med 2021 Feb 21;40(2):237-247. Epub 2020 Jul 21.

Department of Ultrasound and Central Laboratory, Shenzhen Maternity and Child Healthcare Hospital, First School of Clinical Medicine, Southern Medical University, Shenzhen, China.

Objectives: This study aimed to determine the sensitivity of a first-trimester routine scan in detecting spina bifida (SB) and evaluating the first-trimester intracranial signs.

Methods: This retrospective study was a review of a prospectively collected database. All cases of SB diagnosed in a tertiary center from 2008 to 2015 were identified. The ultrasound images and medical records were reviewed. All cases of SB diagnosed prenatally were confirmed at birth or autopsy.

Results: A total of 24 cases of SB were diagnosed from 53,349 pregnancy cases. Except for 10 cases with a body stalk anomaly, craniorachischisis, or iniencephaly, 7 cases with open spina bifida (OSB) and 7 cases with closed spina bifida (CSB) were analyzed. The first-trimester detection rates were 100% (7 of 7) for OSB and 28.5% (2 of 7) for CSB. Eight cases were highly suspected of SB in the first trimester because of an abnormal appearance of the posterior brain; 3 were false-positive cases. Two isolated cases of OSB had first-trimester intracranial signs. An obliterated cisterna magna (CM) showed the highest sensitivity for OSB but low specificity. Two cases of OSB had no discernible landmark of intracranial translucency and the CM, and 4 showed normal intracranial translucency with an obliterated CM. All CSB cases were coupled with a normal hind brain except for 2 cases.

Conclusions: A first-trimester routine scan has high sensitivity in screening for OSB. The CM may be the most sensitive intracranial sign.
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http://dx.doi.org/10.1002/jum.15392DOI Listing
February 2021

High fat diet impairs spermatogenesis by regulating glucose and lipid metabolism in Sertoli cells.

Life Sci 2020 Sep 29;257:118028. Epub 2020 Jun 29.

Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, China; Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China. Electronic address:

Aims: Sertoli cells (SCs) play an important role in the process of spermatogenesis. SCs provide energy for germ cells (GCs) and themselves through glycolysis and fatty acid oxidation (FAO) respectively. High fat diet (HFD) impairs spermatogenesis by damaging function of SCs, however whether HFD disrupts energy metabolism in SCs remains unclear.

Main Methods: To explore this hypothesis, we built male Wistar rat model fed on HFD and cultured rats' primary SCs with palmitic acid (PA). Rats' fertility and sperm quality were evaluated in vivo. Glycolysis, lactate production and mitochondrial respiration were assessed by using extracellular flux analyzer, and the expression of enzymes involved in glucose and FAO was analyzed by Real-Time PCR or Western Blotting.

Key Findings: The showed that the sperm concentration and pups per litter significantly decreased in rats fed on HFD compared to those rats fed on normal diet. There was an elevation of lactate levels in testicular tissue of rats fed on HFD and primary SCs exposed to PA. In vitro, PA increased glycolytic flux, and lactate production, and the levels of carnitine palmitoyltransferase I (CPT1) and long chain acyl-CoA dehydrogenase (LCAD) which were two key enzymes for fatty acid β oxidation. Further analysis showed that mitochondrial respiration was impaired by PA, followed by the decrease in ATP turnover, maximal respiration and the increase in proton leak.

Significance: Taken together, the elevated lactate level, lipid metabolism disorder and mitochondrial dysfunction caused by HFD lead to SCs dysfunction, which ultimately leads to decreased sperm quality.
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http://dx.doi.org/10.1016/j.lfs.2020.118028DOI Listing
September 2020

A novel technique to assess fetal corpus callosum by two-dimensional axial plane.

Eur Radiol 2020 Nov 16;30(11):5871-5880. Epub 2020 Jun 16.

Department of Ultrasound, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, 518028, Guangdong, China.

Objective: The definition of new normal values of the corpus callosum (CC) in axial sonographic scans and evaluation of their feasibility in diagnosing abnormal CC.

Methods: A cross-sectional study assessed CC from 20-gestational-week to full-term. CC observations across three axial planes (the largest CC length plane, trans-genu-and-splenium plane, and trans-body plane) were developed. The largest CC length, genu and splenium thickness, and body width and thickness were compared with compound scatter plots. Ultrasonographic features of normal and abnormal CC were described and the feasibility of the new approach studied. Intra-class correlation coefficient (ICC) was used for assessing the intra- and inter-observer agreements.

Results: Six hundred seventy normal and 42 abnormal fetuses from 20-gestational-week to full-term were studied. The mean normal and abnormal group maternal ages were 30.46 ± 4.36 years and 29.69 ± 4.49 years (p = 0.269). The success rate in obtaining satisfactory axial planes reached 100% but only 13.9% for sagittal plane in the normal group. The success rate of abnormal cases obtaining satisfactory axial planes was 100% and 59.5% by sagittal plane (p < 0.05). The compound scatter plots of abnormal and normal groups showed that the largest CC length and body width were significantly lower in normal fetuses, and the thickness of the genu and splenium with CC hypoplasia was significantly lower than normal fetuses. The intra- and inter-observer agreements were reproducible (all ICC > 0.850).

Conclusions: The feasibility of incorporating an evaluation of CC into routine anatomical screening was demonstrated. Additionally, a focused examination of the craniocerebral axial planes exploring CC at the time of central nervous system scanning might facilitate CC anomaly detection.

Key Points: • Three axial planes with direct CC measurements can detect CC anomalies more accurately compared with indirect CC signs. Besides, this method is simpler, more convenient, and time-saving compared with the sagittal plane. • Assessing fetal CC on the axial plane helps clinicians to diagnose fetuses with abnormal CC. • A prospective single-center study showed that our new technique provides enough diagnostic confidence.
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http://dx.doi.org/10.1007/s00330-020-06981-9DOI Listing
November 2020

Analysis of copy number variation by sequencing in fetuses with nuchal translucency thickening.

J Clin Lab Anal 2020 Aug 27;34(8):e23347. Epub 2020 Apr 27.

Prenatal Diagnosis Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China.

Objective: Copy number variation sequencing (CNV-seq) technique was used to analyze the genetic etiology of fetuses with increased nuchal translucency (NT).

Methods: A total of 139 women with gestational 11-14 weeks whose fetuses were detected with increased NT (NT ≥ 2.5 mm) in our hospital from July 2016 to December 2018 were selected. Fetal specimens were performed for karyotyping analysis and CNV sequencing.

Results: According to the nuchal translucency thickness, 2.5-3.4, 3.5-4.4, 4.5-5.4, and more than 5.5 mm, the rates of chromosomal abnormalities were 22.8% (13/57), 30.8% (12/39), 42.1% (8/19), and 62.5% (15/24), respectively. There was significant difference among the incidences of chromosomal abnormalities in four groups (χ  = 37.69, P < .01) and the incidences increased with fetal NT thickness. Among 139 cases, there were 36 cases (25.9%) with abnormal chromosome karyotypes. Meanwhile, there were 45 cases (32.3%) with abnormal CNV. In the 12 cases with abnormal CNV and normal chromosome karyotypes, there were 2 cases of pathogenic CNV, 7 cases of CNV with unknown clinical significance, and 3 cases of possibly benign CNV. There was no significant difference in CNV between pregnant women in advanced maternal age and those in normal maternal age (χ  = 1.389, P = .239). In the fetus who showed abnormalities in NT and ultrasonography (χ  = 5.13, P < .05) and the fetus aborted (χ  = 113.19, P < .05), the abnormal rate of CNV was higher with statistically significant difference.

Conclusion: CNV-seq combined karyotype analysis should be performed simultaneously in fetuses with increased NT, providing a basis for genetic counseling, which is of great significance for prenatal diagnosis.
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http://dx.doi.org/10.1002/jcla.23347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439336PMC
August 2020

Protective Effect of (L.) Lam. Fruit on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice: Role of Keap1/Nrf2 Pathway and Gut Microbiota.

Front Pharmacol 2019 3;10:1602. Epub 2020 Feb 3.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

(BG), a medicinal mangrove, and its fruit (a food material) (BGF), have traditionally been used to treat diarrhea (also known as ulcerative colitis) in folk medicine. However, the mechanism of action against colitis remains ambiguous. This study aimed to investigate the potential efficacy and mechanism of BGF on experimental colitis. Colitis was induced by oral intake of dextran sulfate sodium (DSS) and treated with aqueous extract of BGF (25, 50 and 100 mg/kg) for a week. The Disease Activity Index (DAI), colon length, and histological changes of colon were analyzed. The inflammatory and oxidative stress status was explored. The protein expression of Nrf2 and Keap1 in the colon was detected by Western blotting. The mRNA expression of Nrf2 downstream genes (, , and ) was determined by RT-PCR. Furthermore, the effect on intestinal flora was analyzed. Results indicated that BGF was rich in pinitol, and showed strong antioxidative activity . Compared with the DSS model, BGF effectively reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, and decreased the histological scores, which was superior to salicylazosulfapyridine (SASP) with smaller dosage. Moreover, BGF not only abated the levels of MDA and inflammatory mediators (TNF-α, IL-6, IL-1β, and IFN-γ), increased the level of IL-10, but also prevented the depletion of SOD and GSH. BGF upregulated the protein level of nuclear Nrf2 and mRNA levels of , , and , while significantly inhibited the protein expression of Keap1 and cytosolic Nrf2. Besides, BGF promoted the growth of probiotics (, , and ) in the gut, and inhibited the colonization of pathogenic bacteria ( and ), which contributed to the maintenance of intestinal homeostasis. BGF possessed protective effect against DSS-induced colitis. The potential mechanism of BGF may involve the amelioration of inflammatory and oxidative status, activation of Keap1/Nrf2 signaling pathway, and maintenance of micro-ecological balance of the host. This study provides experimental evidence for the traditional application of BGF in the treatment of diarrhea, and indicates that BGF may be a promising candidate against colitis.
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http://dx.doi.org/10.3389/fphar.2019.01602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008401PMC
February 2020

Prevalence, genetic analysis and CRISPR typing of Cronobacter spp. isolated from meat and meat products in China.

Int J Food Microbiol 2020 May 4;321:108549. Epub 2020 Feb 4.

Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbiology Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangzhou 510070, China. Electronic address:

Cronobacter spp. are important foodborne pathogens that infections occur in all age groups, especially cause serious life-threatening diseases in infants. This study aimed to acquire data on Cronobacter spp. contamination of meat and meat products (n = 588) in China during 2011 to 2016, and investigated the use of CRISPR typing technology as an approach for characterizing the genetics of Cronobacter spp. The overall contamination rate for Cronobacter spp. was determined to be 9.18% (54/588). Of the positive samples, 90.74% (49/54) had <10 MPN/g, with duck samples had a relatively high contamination rate (15.69%, 8/51) and highest contamination level (28.90 MPN/g). Four species and nine serotypes were identified among 69 isolates, of which C. sakazakii was the major species (n = 50) and C. sakazakii serogroup O1 and O2 (n = 17) were the primary serotypes. The majority of Cronobacter spp. strains were found to be susceptible to most antibiotics except exhibited high resistance to cephalothin (76.81%, 53/69), and total two multi-drug resistant C. sakazakii strains were isolated from duck. The genetic diversity of Cronobacter spp. was remarkably high, as evidenced by the identification of 40 sequence types (STs) and 60 CRISPR types (CTs). C. sakazakii ST64 (n = 7) was the predominant genotype and was further divided into two sub-lineages based on CRISPR diversity, showing different antibiotic resistance profile. These results demonstrate that CRISPR typing results have a good correspondence with bacterial phenotypes, and it will be a tremendously useful approach for elucidating inter-subtyping during molecular epidemiological investigations while interpreting the divergent evolution of Cronobacter. The presence of Cronobacter spp. in meat and meat product is a potential threat to human public health.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2020.108549DOI Listing
May 2020

Pharmacometric Analysis of IgPro10 in Japanese and Non-Japanese Patients With Primary Immunodeficiency.

Clin Ther 2020 01 3;42(1):196-209.e5. Epub 2020 Jan 3.

CSL Behring LLC, King of Prussia, PA, USA.

Purpose: Immunoglobulin (Ig) G replacement therapy, administered intravenously (IVIG) or subcutaneously (SCIG), is the standard treatment in patients with primary immunodeficiencies (PID). We aimed to characterize the pharmacokinetic (PK) characteristics of serum IgG following administration of IgPro10 every 3 or 4 weeks in Japanese patients with PID, and compare with PK in non-Japanese patients. A previously developed population PK (PPK) model was validated, and predicted parameters were compared with the results from the clinical study.

Methods: The previously developed PPK model, containing IgG concentration data from 5 non-Japanese studies, was supplemented with data from 3 Japanese studies of IgPro10 or IgPro20 to compare the IgG PK parameters between Japanese and non-Japanese patients. The model was externally validated by simulating IgG concentration-time profiles in Japanese patients to predict serum IgG PK characteristics and to compare them with observed Japanese PK data from Study IgPro10_3004.

Findings: The analysis included 4502 serum IgG concentration values (from 34 Japanese and 168 non-Japanese patients). PPK estimates from the current analysis demonstrated a clearance (CL) of 0.139 L/d, central volume (V2) of 4.01 L, inter-compartmental clearance (Q) of 0.30 L/d, and peripheral volume of 3.51 L. These results were consistent with those from the previously published PPK model, with similar bootstrap means and 95% CIs. Goodness-of-fit criteria indicated that the final PPK model was consistent with observed data, with no systemic bias in model prediction. Prediction-corrected visual predictive checks confirmed a good description of data on both SCIG and IVIG. PK parameters were equivalent between Japanese and non-Japanese patients. Body weight was determined to be a significant covariate on both CL and V2. Simulated and observed AUC and maximum and minimum serum IgG concentrations were similar, with 90% CIs overlapping between simulated and observed IgG concentrations in Japanese patients.

Implications: PK parameter estimates of serum IgG were similar between Japanese and non-Japanese patients with PID. The PPK model, updated with Japanese data, was consistent with the previously published PPK model and could accurately predict both individual and population serum IgG concentration-time profiles following IgPro10 IV infusions every 3 or 4 weeks. EudraCT identifier: 2016-001631-12.
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http://dx.doi.org/10.1016/j.clinthera.2019.11.013DOI Listing
January 2020

Acupuncture treatment on the motor area of the scalp for motor dysfunction in children with cerebral palsy: study protocol for a multicenter randomized controlled trial.

Trials 2020 Jan 6;21(1):29. Epub 2020 Jan 6.

Department of Rehabilitation, Children's Hospital, Fudan University, Shanghai, 201102, China.

Background: Scalp acupuncture has been widely used as treatment for motor dysfunction in children with cerebral palsy in China. Previous studies have failed to provide high-quality evidence to demonstrate the effectiveness of this treatment in children with cerebral palsy. No high-quality randomized controlled trials on scalp acupuncture have been published. The aim of this study is to evaluate the effectiveness of Jiao's scalp acupuncture when combined with routine rehabilitation treatment versus routine rehabilitation treatment alone for motor dysfunction in children with cerebral palsy.

Methods/design: This is a four-centre randomized controlled trial. One hundred cerebral palsy patients with motor dysfunction were enrolled. Patients will be allocated in a 1:1 ratio into either an acupuncture treatment group or a control group. Cerebral palsy patients in the control group will receive conventional rehabilitation treatment, whereas patients in the acupuncture group will receive a combination of scalp acupuncture and conventional rehabilitation treatment. Thirty-six treatment sessions will be performed over a 12-week period. The Gross Motor Function Measure and the Fine Motor Function Measure Scale will be assessed as the primary outcome measures. The Paediatric Evaluation of Disability Inventory and the Cerebral Palsy Quality of Life Questionnaire for Children will be selected as secondary outcome measures. All assessments will be conducted at baseline, week 4 (treatment 12), week 8 (treatment 24), week 12 (treatment 36) and week 24 (follow-up).

Discussion: This is the first trial evaluating the efficacy and safety of scalp acupuncture as a treatment for motor dysfunction in children with cerebral palsy. The results of this trial are expected to provide relevant evidence demonstrating that scalp acupuncture can be used as an effective rehabilitation treatment method for improving motor dysfunction in children with cerebral palsy.

Trial Registration: ClinicalTrials.gov, NCT03921281. Registered on 19 April 2019.
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http://dx.doi.org/10.1186/s13063-019-3986-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945653PMC
January 2020

Surfactant-Stripped Pheophytin Micelles for Multimodal Tumor Imaging and Photodynamic Therapy.

ACS Appl Bio Mater 2019 Jan 19;2(1):544-554. Epub 2018 Dec 19.

Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, United States.

Porphyrin-based nanomaterials can inherently integrate multiple contrast imaging functionalities with phototherapeutic capabilities. We dispersed pheophytin (Pheo) into Pluronic F127 and carried out low-temperature surfactant-stripping to remove the bulk surfactant. Surfactant-stripped Pheo (ss-Pheo) micelles exhibited a similar size, but higher near-infrared fluorescence, compared to two other nanomaterials also with high porphyrin density (surfactant-stripped chlorophyll micelles and porphysomes). Singlet oxygen generation, which was higher for ss-Pheo, enabled photodynamic therapy (PDT). ss-Pheo provided contrast for photoacoustic and fluorescence imaging, and following seamless labeling with Cu, was used for positron emission tomography. ss-Pheo had a long blood circulation and favorable accumulation in an orthotopic murine mammary tumor model. Trimodal tumor imaging was demonstrated, and PDT resulted in delayed tumor growth.
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http://dx.doi.org/10.1021/acsabm.8b00703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919654PMC
January 2019

Metformin Improves Fertility in Obese Males by Alleviating Oxidative Stress-Induced Blood-Testis Barrier Damage.

Oxid Med Cell Longev 2019 10;2019:9151067. Epub 2019 Sep 10.

Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China.

Background/aims: Obesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males.

Methods: An obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor B (NF-B) was assessed by immunofluorescence.

Results: High-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-B activity in Sertoli cells (SCs).

Conclusion: Metformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.
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http://dx.doi.org/10.1155/2019/9151067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754953PMC
March 2020

Association of methylenetetrahydrofolate reductase C677T polymorphism with the pre-eclampsia risk in Hakka pregnant women in Southern China.

Gynecol Endocrinol 2020 Apr 27;36(4):322-326. Epub 2019 Aug 27.

Prenatal Diagnosis Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-Sen University, Meizhou, P. R. China.

The aim of this study is to clarify the possible association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and pre-eclampsia in Hakka pregnant women in southern China. Pre-eclampsia and normal pregnant women were consecutively collected and MTHFR C677T genotypes were determined by the DNA sequencing method. One hundred and thirteen pre-eclampsia patients were CC homozygote (113 of 191, 59.2%), 68 of 191 (35.6%) were CT heterozygote, and 10 of 191 (5.2%) were TT homozygote, with the frequency of the T allele equal to 0.77. This is in comparison with the normal control group where 106 of 202 (52.5%) were CC homozygote, 83 of 202 (41.1%) were CT heterozygote, and 13 of 202 (6.4%) were TT homozygote, with the frequency of the T allele equal to 0.27. No statistically significant differences were observed in genotype or allele frequencies between the pre-eclampsia and normal control for the C677T polymorphism of MTHFR gene ( > .05). The findings of this study suggest that polymorphisms of MTHFR C677T genes were not associated with pre-eclampsia in Hakka pregnant women from southern China, but additional studies are necessary to explore the mechanisms involving it.
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http://dx.doi.org/10.1080/09513590.2019.1658188DOI Listing
April 2020

Cyclophilin D participates in the inhibitory effect of high-fat diet on the expression of steroidogenic acute regulatory protein.

J Cell Mol Med 2019 10 1;23(10):6859-6871. Epub 2019 Aug 1.

Department of Endocrinology, Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.

Objective: The high-fat diet (HFD)-induced obesity is responsible for the testosterone deficiency (TD). However, the mechanism remains unknown. Mitochondrial homeostasis is proved to be important for maintaining the function of steroidogenic acute regulatory protein (StAR), the first rate-limiting enzyme in testosterone synthesis. As the key regulator of mitochondrial membrane permeability, cyclophilin D (CypD) plays a crucial role in maintaining mitochondrial function. In this study, we sought to elucidate the role of CypD in the expression of StAR affected by HFD.

Methods: To analyse the influence of CypD on StAR in vivo and in vitro, mouse models of HFD, CypD overexpression and CypD knockout (Ppif ) as well as Leydig cells treated with palmitic acid (PA) and CypD overexpression plasmids were examined with an array of metabolic, mitochondrial function and molecular assays.

Results: Compared with the normal diet mice, consistent with reduced testosterone in testes, the expressions of StAR in both mRNA and protein levels in HFD mice were down-regulated, while expressions of CypD were up-regulated. High-fat intake impaired mitochondrial function with the decrease in StAR in Leydig cells. Overexpression of CypD inhibited StAR expressions in vivo and in vitro. Compared with C57BL/6 mice with HFD, expressions of StAR were improved in Ppif mice with HFD.

Conclusions: Mitochondrial CypD involved in the inhibitory effect of HFD on StAR expression in testes.
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http://dx.doi.org/10.1111/jcmm.14569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787510PMC
October 2019

The Protective Effect of Fruit Extract on Acetaminophen-Induced Liver Injury in Mice.

Evid Based Complement Alternat Med 2019 19;2019:6919834. Epub 2019 Jun 19.

Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Acute liver injury is a common consequence of taking overdose of acetaminophen (APAP). The aim of this study was to evaluate the antioxidant activity and hepatoprotective effect of a mangrove plant fruit extract (SAFE) on APAP-induced liver injury in mice. Mice were orally pretreated with SAFE (100, 200, and 400 mg/kg) daily for one week. The control and APAP groups were intragastrically administered with distilled water, and NAC group was treated with N-Acetyl-L-cysteine (NAC) before APAP exposure. The results manifested that SAFE significantly improved survival rates, attenuated hepatic histological damage, and decreased the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum in APAP-exposed mice. SAFE treatment also increased glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity, enhanced catalase (CAT), and total antioxidant capacity (T-AOC), as well as reducing malondialdehyde (MDA) level in liver. In addition, the formation of tumor necrosis factor-alpha (TNF-), interleukin 6 (IL-6), and elevation of myeloperoxidase (MPO) in APAP-exposed mice were inhibited after SAFE treatment. And SAFE also displayed high DPPH radical scavenging activity and reducing power . The main bioactive components of SAFE such as total phenol, flavonoid, condensed tannin, and carbohydrate were determined. The current study proved that SAFE exerted potential protective effect against APAP-induced acute liver injury, which might be associated with the antioxidant and anti-inflammatory activities of SAFE.
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http://dx.doi.org/10.1155/2019/6919834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607706PMC
June 2019
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