Publications by authors named "Lulu Huang"

129 Publications

Proteomics reveals urine apolipoprotein A-I as a potential biomarker of acute kidney injury following percutaneous coronary intervention in elderly patients.

Exp Ther Med 2021 Jul 11;22(1):745. Epub 2021 May 11.

Department of Cardiology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China.

The aim of the present study was to investigate how changes in the lipid composition are involved in early stages of acute kidney injury (AKI) following percutaneous coronary intervention (PCI-AKI) in elderly patients. A prospective nested case-control study was performed. Alterations in the urine protein accumulation were investigated in patients with and without PCI-AKI using isobaric tags for relative and absolute quantitation (iTRAQ). In addition, differentially expressed proteins (DEPs) related to lipids were confirmed using parallel reaction monitoring (PRM)-based targeted proteomics. From the cohort of elderly patients (>60 years of age), 14 (12.28%) developed AKI within 48 h after PCI. No significant differences were detected between the AKI and control (CON) groups for serum creatinine at 24 h following treatment (P=0.27). Among the DEPs that overlapped in both the AKI-24 h/AKI-Pre (AKI group at 24 h post-PCI vs. pre-PCI) and AKI-24 h/CON-24 h groups (AKI group vs. CON group at 24 h post-PCI), only apolipoprotein A-I (apoA-I) was related to lipids, which displayed a significant upregulation in expression levels. The protein expression levels of apoA-I displayed a 5.98-fold increase at 24 h after PCI from the baseline and a 2.09-fold increase compared with the control group as determined using PRM, which exhibited a similar trend to the iTRAQ results. Using protein-protein interaction analyses, apoA-I was determined to be functionally linked to the complement and coagulation cascades, the renin-angiotensin system and the hypoxia-inducible factor-1 signaling pathway. Using the pathway analysis tool from the Kyoto Encyclopedia of Genes and Genomes, several pathways were identified to be associated with apoA-I, including fat digestion and absorption, vitamin digestion and absorption, as well as the peroxisome proliferator activated receptor signaling pathway. In conclusion, apoA-I may be a promising biomarker for the early diagnosis of PCI-AKI in elderly patients. The role of apoA-I in the pathobiology of PCI-AKI requires further exploration.
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http://dx.doi.org/10.3892/etm.2021.10177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141962PMC
July 2021

Changes in anti-müllerian hormone after ultrasound guided aspiration and ethanol sclerotic therapy of ovarian cyst.

Taiwan J Obstet Gynecol 2021 May;60(3):509-512

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, No 199 Dunhua N Rd, Songshan District, Taipei, 105, Taiwan. Electronic address:

Objective: To evaluate the effect of transvaginal ultrasound-guided aspiration and ethanol sclerotherapy on anti-müllerian hormone (AMH) in patients with ovarian endometriomas.

Setting: Teaching hospital affiliated with Chang Gung University, Taipei.

Material And Methods: We retrospectively reviewed 124 patients, with ovarian endometriomas who underwent transvaginal aspiration and sclerotherapy of endometrioma(s) at a tertiary medical center, Chang Gung Memorial Hospital, Taipei, Taiwan. Preoperative evaluation included AMH, midcycle serum CA-125 level, and ultrasonography to exclude possibility of malignancies. Patients underwent ultrasonographic guided transvaginal aspiration and sclerotherapy with 95% ethanol irrigation of the cystic cavity. Patients were grouped into group 1, n = 44, retention of ethanol, and group 2, n = 80, no retention. Serum AMH level was checked at 6 months after aspiration. Those who were infertile prior to therapy were followed up for subsequent pregnancies (either by assisted reproductive technologies, or by natural conception).

Results: The mean pre-operative AMH levels for the group without retention of ethanol and with ethanol retention were 3.80 and 3.06 respectively (p > 0.05). The change in AMH at 6-month follow up for retained group patients was significantly more than for non-retained group patients, with mean decrease of 0.72 (23.6%) and 0.10 (2.7%) respectively (p < 0.05). 54.5% (retained) and 47.2% (non-retained) of patients failed to achieve pregnancy during the observation period.

Conclusions: Transvaginal aspiration of endometriomas followed by sclerotherapy with ethanol can be effective in preserving ovarian reserve, provided that no ethanol is left in situ.
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http://dx.doi.org/10.1016/j.tjog.2021.03.021DOI Listing
May 2021

Oral administration of Bacillus subtilis promotes homing of CD3 T cells and IgA-secreting cells to the respiratory tract in piglets.

Res Vet Sci 2021 May 9;136:310-317. Epub 2021 Mar 9.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China. Electronic address:

Oral probiotics are used to induce immune responses in the intestines to protect against infection. However, oral probiotics may also affect immune responses in other mucosal tissues such as in the respiratory tract. To examine this possibility, we explored the potential of immunocytes to home to the respiratory system after oral administration of Bacillus subtilis. The results showed that B. subtilis could promote intestinal development and not cause pathological changes in the respiratory tract. Following the oral administration with B. subtilis, the number of IgA-secreting cells and CD3 T cells not only significantly increased in the intestinal tracts but also in respiratory tracts (P < 0.01). Moreover, the levels of secretory IgA were significantly higher in the trachea, lungs, ileum, and jejunum after oral B. subtilis administration than in the control groups (P < 0.05). The mRNA expression of interleukin (IL)-1β, IL-5, IL-6, tumor necrosis factor-α, B cell activating factor, and IgA-inducing protein increased following B. subtilis administration (P < 0.01) in the trachea, lungs, ileum, and jejunum. These data suggest that B. subtilis administration regulates the immune response not only in the intestine but also in the respiratory tract of piglets. Our work highlights a potentially new strategy for promoting respiratory mucosal immunity and may contribute to the design of vaccines with B. subtilis as a mucosal adjuvant.
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http://dx.doi.org/10.1016/j.rvsc.2021.03.006DOI Listing
May 2021

Somatic GNAQ R183Q mutation is located within the sclera and episclera in patients with Sturge-Weber syndrome.

Br J Ophthalmol 2021 Mar 11. Epub 2021 Mar 11.

Department of Ophthalmology, Shanghai 9th People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200011, China

Aims: To determine the correspondence between GNAQ R183Q (c.548G>A) mutation in abnormal scleral tissue of patients with Sturge-Weber syndrome (SWS) secondary glaucoma and explore the role of GNAQ R183Q in glaucoma pathogenesis.

Methods: Episcleral tissues were obtained from 8 patients: SWS secondary glaucoma (n=5) and primary congenital glaucoma (PCG, n=3). Scleral tissues were obtained from 7 patients: SWS secondary glaucoma (n=2), PCG (n=1) and juvenile open-angle glaucoma (n=4). GNAQ R183Q mutation was detected in scleral tissue by droplet digital PCR. Tissue sections from SWS were examined by immunohistochemistry to determine the expression of p-ERK.

Results: The GNAQ R183Q mutation was present in 100% of the SWS abnormal sclera. Five cases were SWS patient-derived episcleral tissue, and the mutant allelic frequencies range from 6.9% to 12.5%. The other two were deep scleral tissues and the mutant frequencies were 1.5% and 5.3%. No mutations in GNAQ R183 codon were found in the sclera of PCG and juvenile open-angle glaucoma. Increased expression of p-ERK and p-JNK was detected in the endothelial cells of SWS abnormal scleral blood vessels.

Conclusions: GNAQ R183Q occurred in all abnormal scleral tissue of SWS secondary glaucoma. Increased expression of p-ERK and p-JNK in endothelial cells of blood vessels was detected in the abnormal scleral tissue. This study suggests GNAQ R183Q may regulate episcleral vessels of patients with SWS through abnormal activation of ERK and JNK, providing new genetic evidence of pathogenesis of glaucoma in SWS, and the dysplasia of scleral tissue in anterior segment may be used as an early diagnostic method or treatment targets to prevent the development and progression of glaucoma in patients with SWS.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317287DOI Listing
March 2021

Loosening Neuro-Optic Structures Dosimetric Constraints Provides High 5-Year Local Recurrence-Free Survival With Acceptable Toxicity in T4 Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy.

Front Oncol 2021 22;11:598320. Epub 2021 Feb 22.

Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Objective: Whether the original dosimetric constraints of neuro-optic structures (NOS) are appropriate for patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiotherapy (IMRT) remains controversial. The present study compared the survival rates and radiation-induced optic neuropathy (RION) occurrence between T4 NPC patients whose NOS were irradiated with a near maximum dose received by 2% of the volume (D2%) >55 Gy and ≤55 Gy. Moreover, the NOS dosimetric parameters and their correlation with RION occurrence were also evaluated.

Methods: In this retrospective study, 256 T4 NPC patients treated with IMRT between May 2009 and December 2013 were included. Patient characteristics, survival rates, dosimetric parameters, and RION incidence were compared between the D2% ≤55 Gy and D2% >55 Gy groups.

Results: The median follow-up durations were 87 and 83 months for patients in the D2% >55 Gy and D2% ≤55 Gy groups, respectively. The 5-year local recurrence-free survival rates were 92.0 and 84.0% in the D2% >55 Gy and D2% ≤55 Gy groups (P = 0.043), respectively. There was no significant difference in the 5-year overall survival (OS) between both groups (D2% >55 Gy, 81.6%; D2% ≤55 Gy, 79.4%; P = 0.586). No patients developed severe RION (Grades 3-5), and there was no significant difference (P = 0.958) in the incidence of RION between the two groups. The maximum dose of NOS significantly affected the RION incidence, with a cutoff point of 70.77 Gy.

Conclusion: Appropriately loosening NOS dosimetric constraints in order to ensure a more sufficient dose to the target volume can provide a better 5-year local recurrence-free survival and acceptable neuro-optic toxicity in T4 NPC patients undergoing IMRT.
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http://dx.doi.org/10.3389/fonc.2021.598320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937960PMC
February 2021

Mediated relationships between multiple metals exposure and fasting blood glucose by reproductive hormones in Chinese men.

Environ Pollut 2021 Jun 19;278:116791. Epub 2021 Feb 19.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China; Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, Guangxi, China. Electronic address:

Previous studies have reported metals exposure contribute to the change of fasting blood glucose (FBG) level. However, the roles of reproductive hormones in their associations have not been fully elucidated. The aim of the study is to investigate the associations of multiple serum metals with reproductive hormones, and to further explore potential roles of reproductive hormones in relationships between metals exposure and FBG level. A total of 1911 Chinese Han men were analyzed by a cross-sectional study. We measured serum levels of 22 metals by inductively coupled plasma mass spectrometer (ICP-MS). FBG, total testosterone (TT), estradiol (E2), follicle stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels were determined. Least absolute shrinkage and selection operator (LASSO) regression models were conducted to select important metals, and restricted cubic spline models were then used to estimate dose-response relationships between selected metals and reproductive hormones. We also conducted mediation analyses to evaluate whether reproductive hormones played mediating roles in the associations between metals and FBG. We found significant inverse dose-dependent trends of copper, tin and zinc with E2; zinc with SHBG; copper and nickel with TT, while significant positive dose-dependent trend of iron with E2, respectively. Moreover, approximately inverted U-shaped associations existed between lead and SHBG, iron and TT. In addition, E2, SHBG and TT were negatively associated with FBG level. In mediation analyses, the association of copper with FBG was mediated by E2 and TT, with a mediation ratio of 10.4% and 22.1%, respectively. Furthermore, E2 and SHBG mediated the relationship of zinc with FBG, with a mediation ratio of 7.8% and 14.5%, respectively. E2 mediated 11.5% of positive relationship between tin with FBG. Our study suggested that the associations of metals exposure with FBG may be mediated by reproductive hormones.
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http://dx.doi.org/10.1016/j.envpol.2021.116791DOI Listing
June 2021

Anisotropic Alginate Hydrogels Promote Axonal Growth across Chronic Spinal Cord Transections after Scar Removal.

ACS Biomater Sci Eng 2020 04 11;6(4):2274-2286. Epub 2020 Mar 11.

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, Hubei 430030, P.R. China.

We have previously reported that cell-seeded alginate hydrogels (AHs) with anisotropic capillaries can restore the continuity of the spinal cord and support axonal regeneration in a rat model of acute partial spinal cord transection. Whether similar effects can be found after transplantation into sites of complete chronic spinal cord transections without additional growth-promoting stimuli has not been investigated. We therefore implanted AHs into the cavity of a chronic thoracic transection following scar resection (SR) 4 weeks postinjury and examined electrophysiological and functional recovery as well as regeneration of descending and ascending projections within and beyond the AH scaffold up to 3 months after engraftment. Our results indicate that both electrophysiological conductivity and locomotor function are significantly improved after AH engraftment. SR transiently impairs locomotor function immediately after surgery but does not affect long-term outcomes. Histological analysis shows numerous host cells migrating into the scaffold channels and a reduction of fibroglial scaring around the lesion by AH grafts. In contrast to corticospinal axons, raphaespinal and propriospinal descending axons and ascending sensory axons regenerate throughout the scaffolds and extend into the distal host parenchyma. These results further support the pro-regenerative properties of AHs and their therapeutic potential for chronic SCI in combination with other strategies to improve functional outcomes after spinal cord injury.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01802DOI Listing
April 2020

Identification and Characterization of Cancer Cells That Initiate Metastases to the Brain and Other Organs.

Mol Cancer Res 2021 Apr 22;19(4):688-701. Epub 2020 Dec 22.

Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Specific biological properties of those circulating cancer cells that are the origin of brain metastases (BM) are not well understood. Here, single circulating breast cancer cells were fate-tracked during all steps of the brain metastatic cascade in mice after intracardial injection over weeks. A novel two-photon microscopy methodology was developed that allowed to determine the specific cellular and molecular features of breast cancer cells that homed in the brain, extravasated, and successfully established a brain macrometastasis. Those BM-initiating breast cancer cells (BMIC) were mainly originating from a slow-cycling subpopulation that included only 16% to 20% of all circulating cancer cells. BMICs showed enrichment of various markers of cellular stemness. As a proof of principle for the principal usefulness of this approach, expression profiling of BMICs versus non-BMICs was performed, which revealed upregulation of NDRG1 in the slow-cycling BMIC subpopulation in one BM model. Here, BM development was completely suppressed when NDRG1 expression was downregulated. In accordance, in primary human breast cancer, NDRG1 expression was heterogeneous, and high NDRG1 expression was associated with shorter metastasis-free survival. In conclusion, our data identify temporary slow-cycling breast cancer cells as the dominant source of brain and other metastases and demonstrates that this can lead to better understanding of BMIC-relevant pathways, including potential new approaches to prevent BM in patients. IMPLICATIONS: Cancer cells responsible for successful brain metastasis outgrowth are slow cycling and harbor stemness features. The molecular characteristics of these metastasis-initiating cells can be studied using intravital microscopy technology.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0863DOI Listing
April 2021

Sex-specific associations of plasma metals and metal mixtures with glucose metabolism: An occupational population-based study in China.

Sci Total Environ 2021 Mar 3;760:143906. Epub 2020 Dec 3.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, Guangxi, China; Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou 545006, Guangxi, China. Electronic address:

Studies with multi-pollutant approach on the relationships between multiple metals and fasting plasma glucose (FPG) are limited. Few studies are available on the potential sex-specific associations between metal exposures and glucose metabolism. We explored the associations between 22 plasma metals and FPG level among the 769 participants from the manganese-exposed workers healthy cohort in China. We applied a sparse partial least squares (sPLS) regression followed by ordinary least-squares regression to evaluate multi-pollutant association. Bayesian kernel machine regression (BKMR) model was used to deal with metal mixtures and evaluate their joint effects on FPG level. In the sPLS model, negative associations on FPG levels were observed for plasma iron (belta = -0.066), cobalt (belta = -0.075), barium (belta = -0.109), and positive associations for strontium (belta = 0.082), and selenium (belta = 0.057) in men, which overlapped with the results among the overall participants. Among women, plasma copper (belta = 0.112) and antimony (belta = 0.137) were positively associated with elevated FPG level. Plasma magnesium was negatively associated with FPG level in both sexes (belta = -0.071 in men and belta = -0.144 in women). The results of overlapped for plasma magnesium was selected as the significant contributor to decreasing FPG level in the multi-pollutant, single-metal, and multi-metal models. BKMR model showed a significantly negative over-all effect of six metal mixtures (magnesium, iron, cobalt, selenium, strontium and barium) on FPG level among the overall participants from all the metals fixed at 50th percentile. In summary, our findings underline the probable role of metals in glucose homeostasis with potential sex-dependent heterogeneities, and suggest more researches are needed to explore the sex-specific associations of metal exposures with risk of diabetes.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143906DOI Listing
March 2021

Tumor cell network integration in glioma represents a stemness feature.

Neuro Oncol 2021 05;23(5):757-769

Neurology Clinic and Neurooncology Program and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.

Background: Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes a subpopulation of glioma cells that becomes highly resistant by integration into tumor microtube (TM)-connected multicellular networks.

Methods: A novel functional approach to detect, isolate, and characterize glioma cell subpopulations with respect to in vivo network integration is established, combining a dye staining method with intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular profiling, and gene reporter studies.

Results: Glioblastoma cells that are part of the TM-connected tumor network show activated neurodevelopmental and glioma progression gene expression pathways. Importantly, many of them revealed profiles indicative of increased cellular stemness, including high expression of nestin. TM-connected glioblastoma cells also had a higher potential for reinitiation of brain tumor growth. Long-term tracking of tumor cell nestin expression in vivo revealed a stronger TM network integration and higher radioresistance of the nestin-high subpopulation. Glioblastoma cells that were both nestin-high and network-integrated were particularly able to adapt to radiotherapy with increased TM formation.

Conclusion: Multiple stem-like features are strongly enriched in a fraction of network-integrated glioma cells, explaining their particular resilience.
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http://dx.doi.org/10.1093/neuonc/noaa275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099480PMC
May 2021

Choroidal alterations of Sturge-Weber syndrome secondary glaucoma and non-glaucoma port-wine stain patients distinguished by enhanced depth imaging optical coherence tomography.

BMC Ophthalmol 2020 Dec 7;20(1):477. Epub 2020 Dec 7.

Department of Ophthalmology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Huangpu District, Shanghai, 200011, China.

Background: To evaluate the choroidal changes in Sturge-Weber syndrome (SWS) secondary glaucoma and non-glaucoma port-wine stain (PWS) patients by enhanced depth imaging optical coherence tomography (EDI-OCT).

Methods: SWS and PWS patients who were over 3 years old and treated or screened at our ophthalmology department were included in the study. Baseline demographics, EDI-OCT and fundus photography data were collected from all patients.

Results: Overall, 46 non-glaucoma PWS (NGPWS) patients and 35 SWS secondary glaucoma (SG) patients were included, with mean ages of 16.52 ± 13.63 and 13.94 ± 8.27 years, respectively (p > 0.05). Among these patients 2 exhibited bilateral PWS and unilateral glaucoma. Thus, the two eyes of each patient were divided into NGPWS and SG group, respectively. Twenty-one eyes had choroidal hemangiomas and 7 eyes had excessive thickening of the choroid without choroidal hemangiomas. Choroidal hemangiomas were only observed in ipsilateral eyes of SG patients. The choroidal thicknesses of the ipsilateral and fellow eyes of NGPWS patients were 358.10 ± 117.40 μm (45 eyes) and 288.20 ± 79.04 μm (41 eyes), respectively (p < 0.05). The choroidal thicknesses of the ipsilateral and fellow eyes of SG patients were 511.40 ± 242.10 μm (15 eyes) and 283.90 ± 92.27 μm (29 eyes), respectively (p < 0.05). Significant differences were found between the ipsilateral eyes of SWS and PWS patients (p < 0.05). Six of 13 eyes (46%) with choroidal hemangiomas exhibited post-operative posterior segment complications.

Conclusions: NGPWS and SG patients had a thicker choroid in the ipsilateral eye. The trend was even more pronounced in SG patients. Choroidal hemangiomas were only found in the ipsilateral eyes of SG. In addition, choroidal hemangioma was a risk factor for post-operative posterior segment complications in SWS patients.
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http://dx.doi.org/10.1186/s12886-020-01744-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720598PMC
December 2020

[Bacterial stress response, physiological metabolism and antimicrobial tolerance and the control strategies].

Sheng Wu Gong Cheng Xue Bao 2020 Nov;36(11):2287-2297

MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, Hubei, China.

Overuse of antibiotics in medical care and animal husbandry has led to the development of bacterial antimicrobial resistance, causing increasingly more health concern. In addition to genetic mutations and the formation of resistance, the various stresses bacteria encountered in the natural environment trigger their stress responses, which not only protect them from these stresses, but also change their tolerance to antimicrobials. The emergence of antimicrobial tolerance will inevitably affect the physiological metabolism of bacteria. However, bacteria can restore their sensitivity to drugs by regulating their own metabolism. This article reviews recent studies on the relationship between bacterial stress responses or the physiological metabolism and antimicrobial tolerance, intending to take more effective measures to control the occurrence and spread of antimicrobial resistance.
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http://dx.doi.org/10.13345/j.cjb.200144DOI Listing
November 2020

Development of Resistance in ATCC25922 under Exposure of Sub-Inhibitory Concentration of Olaquindox.

Antibiotics (Basel) 2020 Nov 10;9(11). Epub 2020 Nov 10.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

Quinoxaline1,4-di--oxides (QdNOs) are a class of important antibacterial drugs of veterinary use, of which the drug resistance mechanism has not yet been clearly explained. This study investigated the molecular mechanism of development of resistance in () under the pressure of sub-inhibitory concentration (sub-MIC) of olaquindox (OLA), a representative QdNOs drug. In vitro challenge of with 1/100× MIC to 1/2× MIC of OLA showed that the bacteria needed a longer time to develop resistance and could only achieve low to moderate levels of resistance as well as form weak biofilms. The transcriptomic and genomic profiles of the resistant induced by sub-MIC of OLA demonstrated that genes involved in tricarboxylic acid cycle, oxidation-reduction process, biofilm formation, and efflux pumps were up-regulated, while genes involved in DNA repair and outer membrane porin were down-regulated. Mutation rates were significantly increased in the sub-MIC OLA-treated bacteria and the mutated genes were mainly involved in the oxidation-reduction process, DNA repair, and replication. The SNPs were found in , , , , , and genes, which were covered in both transcriptomic and genomic profiles. This study provides new insights into the resistance mechanism of QdNOs and increases the current data pertaining to the development of bacterial resistance under the stress of antibacterials at sub-MIC concentrations.
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http://dx.doi.org/10.3390/antibiotics9110791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696260PMC
November 2020

Correction: Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22.

Cell Death Differ 2021 Jun;28(6):2025-2027

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu, 210095, China.

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http://dx.doi.org/10.1038/s41418-020-00630-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184977PMC
June 2021

Associations Between Serum Multiple Metals Exposures and Metabolic Syndrome: a Longitudinal Cohort Study.

Biol Trace Elem Res 2020 Oct 3. Epub 2020 Oct 3.

Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.

Although many studies have confirmed metabolic syndrome (MetS) is correlated with metal exposures, few studies have elucidated the associations of multiple metals with MetS risk. We aim to explore the relationship between serum 22 metals and MetS. We determined serum 22 metals using ICP-MS and used LASSO regression to select metals independently related with MetS to construct multiple-metals model. We further explored the dose-response relationship between positive metals and MetS by the restricted cubic spline regression. After screening by LASSO regression, serum 11 metals were selected to construct multiple-metals model in cross-sectional analysis, while 5 metals in longitudinal analysis. In the 11-metal model, only tin and zinc were associated with MetS in cross-sectional analysis (OR = 2.22, 95% CI:1.43, 3.45; OR = 2.17, 95% CI: 1.42, 3.32; both P < 0.05). Besides, the same results were found in the 5-metal model in longitudinal analysis (HR = 1.66, 95% CI: 0.87, 3.17; HR = 1.83, 95% CI: 1.07, 3.14; both P < 0.05). Moreover, there were positive linear relationships between serum tin and zinc concentrations and the increasing risk of MetS (both P < 0.05, P > 0.05). Furthermore, the interaction between high tin and high zinc was also associated with increasing MetS risk (P < 0.05). We found that serum tin and zinc were independently and interactively associated with MetS in the southern Chinese men. Our results suggested that high tin and zinc may be the risk factors of MetS.
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http://dx.doi.org/10.1007/s12011-020-02371-wDOI Listing
October 2020

Risk factors for abnormal postpartum glycemic states in women diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria.

J Diabetes Investig 2021 May 30;12(5):859-868. Epub 2020 Sep 30.

Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan.

Aims/introduction: To evaluate the rate of postpartum glycemic screening tests (PGST) in women with gestational diabetes mellitus (GDM), and to investigate risk factors for abnormal PGST results.

Materials And Methods: We retrospectively analyzed the obstetric data of 1,648 women with GDM who gave birth after 28 completed weeks of gestation between 1 July 2011 and 31 December 2019 at Taipei Chang Gung Memorial Hospital, Taiwan. GDM was diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria. PGST was carried out at 6-12 weeks postpartum with a 75-g, 2-h oral glucose tolerance test, and the results were classified into normal, prediabetes and diabetes mellitus. Multiple logistic regression was used to assess the associations between various risk factors and abnormal PGST results.

Results: In total, 493 (29.9%) women underwent PGST and 162 (32.9%) had abnormal results, including 135 (27.4%) with prediabetes and 27 (5.5%) with diabetes mellitus. Significant risk factors for postpartum diabetes mellitus included insulin therapy during pregnancy (adjusted odds ratio [OR] 10.79, 95% confidence interval [CI] 4.07-28.58), birthweight >4,000 g (adjusted OR 10.22, 95% CI 1.74-59.89) and preterm birth <37 weeks' gestation (adjusted OR 3.33, 95% CI 1.09-10.22); whereas prepregnancy body mass index >24.9 kg/m (adjusted OR 1.99, 95% CI 1.24-3.21) was the major risk factor for postpartum prediabetes.

Conclusions: Less than one-third of women with GDM underwent PGST, and nearly one-third of these women had abnormal results. Future efforts should focus on reducing the barriers to PGST in women with GDM.
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http://dx.doi.org/10.1111/jdi.13400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089005PMC
May 2021

Establishment of The Complete Closed Mesh Model of Rail-Surface Scratch Data for Online Repair.

Sensors (Basel) 2020 Aug 21;20(17). Epub 2020 Aug 21.

Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Rail surface scratching occurs with increasing frequency, seriously threatening the safety of vehicles and humans. Online repair of rail-surface scratches on damaged rails with scratch depths >1 mm is of increased importance, because direct rail-replacement has the disadvantages of long operation time, high manpower and high material costs. Advanced online repair of rail-surface scratch using three-dimensional (3D) metal printing technology such as laser cladding has become an increasing trend, desperately demanding a solution for the fast and precise establishment of a complete closed mesh model of rail-surface scratch data. However, there have only been limited studies on the topic so far. In this paper, the complete closed mesh model is well established based on a novel triangulation algorithm relying on the topological features of the point-cloud model (PCM) of scratch-data, which is obtained by implementing a scratch-data-computation process following a rail-geometric-feature-fused algorithm of random sample consensus (RANSAC) performed on the full rail-surface PCM constructed by 3D laser vision. The proposed method is universal for all types of normal-speed rails in China. Experimental results show that the proposed method can accurately acquire the complete closed mesh models of scratch data of one meter of 50 Kg/m-rails within 1 min.
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http://dx.doi.org/10.3390/s20174736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506854PMC
August 2020

Ultralow Thermal Conductivity and High Thermoelectric Performance of N-type BiTeSe-Based Composites Incorporated with GaAs Nanoinclusions.

ACS Appl Mater Interfaces 2020 Aug 7;12(33):37155-37163. Epub 2020 Aug 7.

Key Laboratory of Material Physics, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei 230031, China.

BiTeSe (BTS) is known to be the unique n-type commercial thermoelectric (TE) alloy used at room temperatures, but its figure of merit () is relatively low, and it is vital to improve its for its wide applications. Here, we show that incorporation of an appropriate amount of GaAs nanoparticles in BTS not only causes the large enhancement of Seebeck coefficients because of energy-dependent carrier scattering, but also gives rise to drastic reduction of lattice thermal conductivity κ. Specifically, ultralow κ ∼ 0.27W m K (at 300 K) is achieved for the composite sample incorporated with a 0.3 wt % GaAs nanophase, which is proved to originate mainly from the intensified phonon scattering by the GaAs nanoinclusions and interfaces between the GaAs and BTS matrix. As a result, a maximum = 1.19 (∼372 K) and an average = 1.01 (at = 300-550 K) are reached in the composite sample with 0.3 wt % GaAs nanoinclusions, which are respectively ∼78% and ∼82% larger than those of the BTS matrix in this study, demonstrating that incorporation of the GaAs nanophase is an effective way to improve TE performance of BTS.
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http://dx.doi.org/10.1021/acsami.0c09338DOI Listing
August 2020

Recombinant human thrombopoietin promotes platelet engraftment after umbilical cord blood transplantation.

Blood Adv 2020 08;4(16):3829-3839

Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT) accompanied by increased transplant-related complications or death. This study was designed to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) in promoting platelet engraftment after UCBT. A total of 120 patients scheduled to receive UCBT were randomly assigned to the rhTPO group (300 U/kg once daily from days 14 to 28 after UCBT, n = 60) or the control group (n = 60). The primary outcome was the 60-day cumulative incidence of platelet engraftment after single-unit cord blood transplantation. The 60-day cumulative incidence of platelet engraftment (platelet count ≥20 × 109/L) and the 120-day cumulative incidence of platelet recovery (platelet count ≥50 × 109/L) were both significantly higher in the rhTPO group than in the control group (83.1% vs 66.7%, P = .020; and 81.4% vs 65.0%, P = .032, respectively). In addition, the number of required platelet infusions was significantly lower in the rhTPO group than in the control group (6 vs 8 units, respectively; P = .026). The cumulative incidence of neutrophil engraftment and the probability of 2-year overall survival, disease-free survival, and graft-versus-host disease-free relapse-free survival did not differ between the 2 groups. Other transplant-related outcomes and complications did not differ between the 2 groups, and no severe adverse effects were observed in patients receiving rhTPO. This study demonstrated that rhTPO is well tolerated in patients and could effectively promote platelet engraftment after UCBT. This study was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) as ChiCTR-IPR-16009357.
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http://dx.doi.org/10.1182/bloodadvances.2020002257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448600PMC
August 2020

Comparison of oral and nasal immunization with inactivated porcine epidemic diarrhea virus on intestinal immunity in piglets.

Exp Ther Med 2020 Aug 3;20(2):1596-1606. Epub 2020 Jun 3.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. China.

Porcine epidemic diarrhea virus (PEDV) has proven to be a major problem for the porcine industry worldwide. Conventional injectable vaccines induce effective systemic immune responses but are less effective in preventing PEDV at mucosal invasion sites, including the nasal or oral mucosa. Additionally, antigens delivered orally are easily degraded. Nasal immunization induces intestinal mucosal immune responses, which can aid in blocking viral invasion, and requires fewer antigen inoculation doses. Therefore, nasal immunizations are considered to be a potential approach to overcome viral infections. In the present study, nasal immunization of piglets was performed using inactivated PEDV combined with as an immunopotentiator and the efficacy of nasal immunization was assessed. The results demonstrated that compared with oral immunization, piglets from the nasal immunization group exhibited higher levels of neutralizing antibodies (P<0.01) in the intestine, PEDV-specific immunoglobulin (Ig)G (P<0.01) in serum and PEDV-specific secretory IgA (SIgA) in saliva (P<0.01) and nasal secretions (P<0.01). An increased number of intestinal CD3 T cells, IgA-secreting cells and intraepithelial lymphocytes (P<0.05) were also observed. Furthermore, the protein expression levels of interleukin-6 and interferon-γ, relative to the control PEDV infection, were also significantly elevated (P<0.05). The results of the present study indicate that nasal immunization is more effective at inducing the intestinal mucosal immune response, and provide new insights into a novel vaccination strategy that may be used to decrease the incidence of PEDV infections.
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http://dx.doi.org/10.3892/etm.2020.8828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388329PMC
August 2020

Associations of prenatal exposure to multiple metals with testicular volume and anogenital distance in infant boys: A longitudinal cohort study.

Environ Int 2020 10 9;143:105900. Epub 2020 Jul 9.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, China. Electronic address:

Background: Human are widely exposed to multiple metals, some of which have suspected reproductive toxicity, but no human studies have investigated the developmental effects of prenatal metal exposure.

Objectives: We aimed to evaluate the associations between prenatal multiple metal exposure and reproductive development in boys at 2-3 years using multi-pollutant approach.

Methods: This prospective study used data of 564 mother-child pairs recruited from the Guangxi Birth Cohort Study. Twenty serum metal concentrations were measured. Least absolute shrinkage and selection operator (LASSO) penalized regression was used to identify independent associations between prenatal multiple metal exposure and testicular volume (TV), and anogenital distance (AGD). Adjusted estimates were then obtained using multiple linear regression analysis, and the regression tree method was used to explore the interactions.

Results: Boys in the highest quartile of prenatal lead exposure had a 0.064 mL (95% CI: -0.124, -0.004) smaller ln-transformed TV, 0.060 cm (95% CI: -0.110, -0.011) shorter ln-transformed anopenile distance (AGDap), and 0.115 cm (95% CI: -0.190, -0.039) shorter ln-transformed anoscrotal distance (AGDas) than boys in the lowest quartile (all Ptrend < 0.05). Chromium was inversely with ln-transformed AGDap (β = -0.078, 95% CI: -0.127, -0.030) and ln-transformed AGDas (β = -0.113, 95% CI: -0.188, -0.038), while stibium was positivity associated with ln-transformed AGDap (β = 0.091, 95% CI: 0.046, 0.136) and strontium was positivity associated with ln-transformed AGDas (β = 0.120, 95% CI: 0.051, 0.189) (all Ptrend < 0.05). And the critical window of vulnerability may be the late pregnancy (the second and third trimester). Moreover, we detected interaction effects between lead, chromium and stibium on AGDap; lead, chromium and strontium on AGDas.

Conclusions: The results suggest that prenatal exposure to lead, chromium, stibium and strontium may affect TV and/or AGD in infant boys. Potential mechanisms for the complex metal interactive effects during vulnerable periods are worthy of further investigation.
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http://dx.doi.org/10.1016/j.envint.2020.105900DOI Listing
October 2020

High manganese exposure decreased the risk of high triglycerides in workers: a cross-sectional study.

BMC Public Health 2020 Jun 5;20(1):874. Epub 2020 Jun 5.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.

Background: Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear.

Methods: This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m. Mn-TWA levels and dyslipidaemia were assessed.

Results: After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p <  0.01). The results of males and females were consistent (OR = 0.53; 95% CI: 0.34, 0.81; p <  0.01) and (OR = 0.47; 95% CI: 0.24, 0.94; p <  0.01), respectively. By performing interactions analyses of workers overall, we observed no significant interactions among confounders. Mn-TWA levels and pack-years on high TG risk (relative excess risk for the interactions (RERI = 2.29, 95% CI: - 2.07, 6.66), (RERI) = 2.98, 95% CI: - 2.30, 8.26). Similarly, smoking status, drinking status, high-fat diet frequency, and Waist-to-Hip Ratio (WHR) showed non-significant interactions with Mn-TWA levels on high TG risk.

Conclusions: This research indicates that high Mn exposure was negatively related to high TG risk in workers.
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http://dx.doi.org/10.1186/s12889-020-09011-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275562PMC
June 2020

Non-linear association of serum molybdenum and linear association of serum zinc with nonalcoholic fatty liver disease: Multiple-exposure and Mendelian randomization approach.

Sci Total Environ 2020 Jun 29;720:137655. Epub 2020 Feb 29.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address:

The homeostasis imbalance of metals is closely associated with nonalcoholic fatty liver disease (NAFLD). A total of 1594 and 566 Chinese Han men were enrolled in cross-sectional and longitudinal analyses, respectively. We measured the serum concentrations of 22 metals by ICP-MS. The traditional and the LASSO regression methods were used to construct multiple-metals models, respectively. We performed Mendelian randomization (MR) analysis to confirm the causal relationship between NAFLD and metals using three NAFLD-related SNPs as instrumental variable. After adjustment in the six-metal model, only depressed molybdenum and elevated zinc were associated with a higher NAFLD risk, in both cross-sectional and longitudinal analyses. In the twelve-metal model, similar results were still observed. Moreover, dose-response relationships were non-linear for molybdenum and positively linear for zinc with NAFLD risk. In MR analysis, no causal associations were found from NAFLD to molybdenum and zinc. Our results support that serum molybdenum levels were non-linearly associated with NAFLD risk in Chinese men, whereas serum zinc levels showed a positively linear association. Moreover, MR analysis indicated the changes in serum molybdenum and zinc levels might be not caused by NAFLD, further confirmed our findings in cross-sectional and longitudinal analyses.
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http://dx.doi.org/10.1016/j.scitotenv.2020.137655DOI Listing
June 2020

Occupational exposure to manganese and risk of creatine kinase and creatine kinase-MB elevation among ferromanganese refinery workers.

Am J Ind Med 2020 05 29;63(5):394-401. Epub 2020 Feb 29.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.

Background: Elevated exposure to manganese (Mn) could induce cardiovascular dysfunction. However, limited research is available on the effects of occupational Mn exposure on myocardial enzymes. We aimed to evaluate the relationships between Mn exposure and myocardial enzyme elevation among Mn-exposed workers.

Methods: Data were from a follow-up investigation of a Mn-exposed workers healthy cohort in 2017. A total of 744 workers were divided into low-exposure and high-exposure groups according to Mn time-weighted average (Mn-TWA) of less than or equal to 0.15 mg/m or greater than 0.15 mg/m , respectively. Serum levels of myocardial enzymes, including creatine kinase (CK) and creatine kinase-MB (CK-MB), lactic dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate transaminase, were assessed, as well as airborne Mn exposure levels.

Results: After adjustment for sex, body mass index, seniority, education, current smoking status, current drinking status, and hypertension, Mn-TWA levels were positively associated with the risk of CK elevation (odds ratio [OR] = 1.47 (95% confidence interval [CI]: 1.18-1.83) per interquartile range [IQR] increase), and risk of CK-MB elevation [OR = 1.57 (95% CI: 1.03-2.38) per IQR increase]. In a stratified analysis, Mn-TWA levels were positively correlated with CK elevation in workers of seniority greater than 19 years, male workers, current smokers, and drinkers.

Conclusion: Our results suggest that occupational exposure to Mn is associated with increased risk of CK and CK-MB elevation. The potential mechanisms of the associations between airborne exposure to Mn and increased risk of these myocardial enzyme elevations warrant further investigation.
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http://dx.doi.org/10.1002/ajim.23097DOI Listing
May 2020

Effects of Sb Deviation from Its Stoichiometric Ratio on the Micro- and Electronic Structures and Thermoelectric Properties of CuSbS.

ACS Appl Mater Interfaces 2020 Mar 10;12(12):14145-14153. Epub 2020 Mar 10.

Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei 230031, PR China.

Thermoelectric material tetrahedrite CuSbS has attracted much attention because of its intrinsic low lattice thermal conductivity, excellent electrical transport property, and environment-friendly constituents. However, its thermoelectric figure merit, , is limited because of the low Seebeck coefficient () and power factor (PF). Hence, it is indispensable to enhance its and PF to increase its . Here, we show that when Sb deviation from its stoichiometric ratio in the CuSbS band structure is modulated, it gives rise to increased density of states and enhancement of the Seebeck coefficient. Moreover, carrier concentration is tuned by changing sulfur and copper vacancies through controlling the CuSbS phase with an atomic ratio of Sb, leading to increased electrical conductivity. In addition, as large as ∼60% reduction of lattice thermal conductivity is obtained by intensified phonon scattering using an impurity phase/element and vacancy-like defects induced by different Sb contents. As a result, a high = 0.86 is achieved at 723 K for the CuSbS sample with δ = 0.2, which is ∼50% larger than that of stoichiometric CuSbS studied here, indicating that of CuSbS can be improved through simple modulation of the Sb stoichiometric ratio.
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http://dx.doi.org/10.1021/acsami.0c00094DOI Listing
March 2020

Associations between manganese exposure and multiple immunological parameters in manganese-exposed workers healthy cohort.

J Trace Elem Med Biol 2020 May 10;59:126454. Epub 2020 Jan 10.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address:

Background: Manganese (Mn) ions play a crucial role in the immune response. The immunotoxicity of Mn is rarely reported compared with the neurotoxicity of Mn.

Objectives: The purpose of this study was to investigate the associations between chronic Mn exposure and immunological parameters in occupational Mn-exposed workers.

Methods: A total of 538 workers were selected from the follow-up of manganese-exposed workers healthy cohort (MEWHC) in 2017. We divided the workers into the low-exposure group and the high-exposure group by the cutoff of the manganese-time weighted average (Mn-TWA) setting at 0.15 mg/m. We examined serum immunological parameters by the immunoturbidimetric method and leukocyte counts and ratios in blood routine. Then we used the generalized linear model analyses and spline analyses to explore the associations between external exposure of Mn and multiple immunological parameters adjusted for variables. Based on the epidemiological analyses, we used Elisa (enzyme-linked immune sorbent assay) to detect plasma complement C3 of Mn-exposed rats.

Results: In male workers, the mean value of complement C3 was 1.20 ± 0.16 g/L in the high-exposure group, which was significantly lower as compared to the low-exposure group (1.25 ± 0.18 g/L, P = 0.023). The generalize linear models' analyses showed that complement C3 value had a significantly negative association with external exposure of Mn included adjustment for variables (β = -0.04, P = 0.035). Moreover, in male rats, the high-exposure group also had a lower level of complement C3 compared with the low-exposure group (P < 0.001). None significant association was observed in immunological parameters among female workers and rats (all P > 0.05).

Conclusions: Mn exposure from inhalable dust was associated with decreased complement C3 among occupationally Mn-exposed male individuals but not in female workers, which was further confirmed by the rat model. Further research into the possible mechanism of C3 reduction is needed in the future.
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http://dx.doi.org/10.1016/j.jtemb.2020.126454DOI Listing
May 2020

New approaches to genetic therapies for cystic fibrosis.

J Cyst Fibros 2020 03 13;19 Suppl 1:S54-S59. Epub 2020 Jan 13.

Department of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London UK. Electronic address:

Gene therapy offers great promise for cystic fibrosis which has never been quite fulfilled due to the challenges of delivering sufficient amounts of the CFTR gene and expression persistence for a sufficient period of time in the lungs to have any effect. Initial trials explored both viral and non-viral vectors but failed to achieve a significant breakthrough. However, in recent years, new opportunities have emerged that exploit our increased knowledge and understanding of the biology of CF and the airway epithelium. New technologies include new viral and non-viral vector approaches to delivery, but also alternative nucleic acid technologies including oligonucleotides and siRNA approaches for gene silencing and gene splicing, described in this review, as presented at the 2019 annual European CF Society Basic Science meeting (Dubrovnik, Croatia). We also briefly discuss other emerging technologies including mRNA and CRISPR gene editing that are advancing rapidly. The future prospects for genetic therapies for CF are now diverse and more promising probably than any time since the discovery of the CF gene.
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http://dx.doi.org/10.1016/j.jcf.2019.12.012DOI Listing
March 2020

Plasma metals and serum bilirubin levels in workers from manganese-exposed workers healthy cohort (MEWHC).

Environ Pollut 2020 Mar 4;258:113683. Epub 2019 Dec 4.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China. Electronic address:

Few studies specifically address the possible associations between multiple-metal exposures and liver damage among the occupational population. This study aimed to explore the cross-sectional relationships of plasma metals with liver function parameters. For 571 on-the-spot workers in the manganese-exposed workers healthy cohort (MEWHC), we determined liver function parameters: total bilirubin (TBILI), direct bilirubin (DBILI), indirect bilirubin (IBILI), alanine transaminase (ALT) and aspartate transaminase (AST). Total concentrations of 22 plasma metals were measured by ICP-MS. The LASSO (least absolute shrinkage and selection operator) penalized regression model was applied for selecting plasma metals independently associated with liver function parameters. Multiple linear regression analyses and restricted cubic spline (RCS) were utilized for identifying the exposure-response relationship of plasma metals with liver function parameters. After adjusting for covariates and selected metals, a 1-SD increase in log-10 transformed levels of iron was associated with increases in the levels of TBILI, DBILI and IBILI by 20.3%, 12.1% and 23.7%, respectively; similar increases in molybdenum for decreases in levels of TBILI, DBILI and IBILI by 6.1%, 2.6% and 8.3%, respectively. The effect of a 1-SD increase in plasma copper corresponded decreases of 3.2%, 3.4% and 5.0% in TBILI, AST and ALT levels, respectively. The spline analyses further clarified the non-linear relationships between plasma iron and bilirubin whilst negative linear relationships for plasma molybdenum and bilirubin. Plasma iron was positively whilst plasma molybdenum was negatively associated with increased serum bilirubin levels. Further studies are needed to validate these associations and uncover the underlying mechanisms.
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http://dx.doi.org/10.1016/j.envpol.2019.113683DOI Listing
March 2020

Automated Nanoplasmonic Analysis of Spherical Nucleic Acids Clusters in Single Cells.

Anal Chem 2020 01 24;92(1):1333-1339. Epub 2019 Dec 24.

School of Chemistry and Chemical Engineering, Institute of Molecular Medicine, Renji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200240 , China.

Spherical nucleic acids (SNAs) have been extensively used in the field of biosensing, drug delivery, and theranostics. Precise engineering of SNAs and their clinical application require better understanding of their cellular internalization process. We demonstrate a colorimetry-based algorithm that can analyze the aggregation states of SNAs clusters on the basis of the changes of plasmonic colors of SNAs. The dark-field microscopy (DFM) images of cytoplasmic region of single cells are imported as raw data. All the image spots are analyzed in the interference reduction process, and the clustering states of target image spots are assigned on the basis of the distribution of coordinates of all the pixels in the CIE map. This method provides faster analysis on clustering states of extracellular and intracellular SNAs with good accuracy. Moreover, the clustering states of SNAs in 20 single cells (generally >1000) can be efficiently distinguished within 200 s. Therefore, our method provides an automatic, quantitative, objective, and repeatable way to analyze SNAs aggregations, and shows good application potential in robust and quantitative nanoplasmonic analysis in single cells.
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http://dx.doi.org/10.1021/acs.analchem.9b04500DOI Listing
January 2020

Association between long-term occupational manganese exposure and bone quality among retired workers.

Environ Sci Pollut Res Int 2020 Jan 3;27(1):482-489. Epub 2019 Dec 3.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China.

Despite well documents for manganese-induced neurological deficits, limited researches are available for effects of manganese (Mn) exposure on the bone. Here we aimed to explore the associations between long-term occupational Mn exposure and bone quality among retired workers. We conducted a cross-sectional study of 304 exposed subjects (n, male = 161 and female = 143) and 277 control retired workers (n, male = 65 and female = 212) recruited from a ferromanganese refinery. Self-reported occupation types were used as exposure classification confirmed by expert consultation. Bone quality was measured by quantitative ultrasound (QUS). In sex-stratified analyses throughout, stiffness index (SI) and T-score levels of the participants in the highest exposed group [tertile 3 of Mn cumulative exposure index (Mn-CEI)] were significantly lower as compared with the control group among female workers (SI, mean, 61.60 vs. 68.17; T-score, mean, -3.01 vs. -2.34, both P < 0.05). In addition, SI and T-score were found to be negatively associated with Mn-CEI only in the highest exposure group as compared with the female controls (both P = 0.01). However, we did not find the significant difference for SI or T-score among the male subjects in exposure models and the male controls (P > 0.05). Our results suggest that female retired workers in the highest Mn-exposed model (tertile 3 of Mn-CEI) potentially experience a higher risk of developing osteoporosis compared with the female controls. Further investigations on possible mechanisms on bone quality alteration are needed in the future.
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http://dx.doi.org/10.1007/s11356-019-06694-7DOI Listing
January 2020