Publications by authors named "Jianzhong Hu"

145 Publications

Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family.

J Ophthalmol 2020 19;2020:7054315. Epub 2020 Feb 19.

Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China.

Purpose: To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. . A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function.

Results: The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.

Conclusions: We report a novel mutation, p.C505S, and a known mutation, p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of p.C505S with iris coloboma has been demonstrated, although p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract. c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.
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http://dx.doi.org/10.1155/2020/7054315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049832PMC
February 2020

Structure and ingredient-based biomimetic scaffolds combining with autologous bone marrow-derived mesenchymal stem cell sheets for bone-tendon healing.

Biomaterials 2020 05 18;241:119837. Epub 2020 Feb 18.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, People's Republic of China; Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, People's Republic of China. Electronic address:

Tendon attaches to bone across a robust fibrocartilaginous tissue termed the bone-tendon interface (BTI), commonly injured in the field of sports medicine and orthopedics with poor prognosis. So far, there is still a lack of effective clinical interventions to achieve functional healing post BTI injury. However, tissue-engineering may be a promising treatment strategy. In this study, a gradient book-type triphasic (bone-fibrocartilage-tendon) scaffold is fabricated based on the heterogeneous structure and ingredient of BTI. After decellularization, the scaffold exhibits no residual cells, while the characteristic extracellular matrix of the original bone, fibrocartilage and tendon is well preserved. Meanwhile, the bone, fibrocartilage and tendon regions of the acellular scaffold are superior in osteogenic, chondrogenic and tenogenic inducibility, respectively. Furthermore, autologous bone marrow mesenchymal stem cell (BMSC) sheets (CS) combined with the acellular scaffolds is transplanted into the lesion site of a rabbit BTI injury model to investigate the therapeutic effects. Our results show that the CS modified scaffold not only successfully achieves triple biomimetic of BTI in structure, ingredient and cell distribution, but also effectively accelerates bone-tendon (B-T) healing. In general, this work demonstrates book-type acellular triphasic scaffold combined with autologous BMSCs sheets is a promising graft for repairing BTI injury.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119837DOI Listing
May 2020

Altered growth trajectory in children born to mothers with gestational diabetes mellitus and preeclampsia.

Arch Gynecol Obstet 2020 01 21;301(1):151-159. Epub 2020 Jan 21.

Department of Psychology, Queens College, City University of New York, 65-30 Kissena Blvd, Flushing, NY, 11367, USA.

Purpose: Gestational diabetes mellitus (GDM) and preeclampsia are leading causes of mortality and morbidity in mothers and children. High childhood body mass index (BMI) is among their myriad of negative outcomes. However, little is known about the trajectory of the child BMI exposed to GDM and co-occurring preeclampsia from early to mid-childhood. This study examined the independent and joint impact of GDM and preeclampsia on childhood BMI trajectory.

Methods: A population-based sample of 356 mothers were recruited from OB/GYN clinics in New York. Their children were then followed annually from 18 to 72 months. Maternal GDM and preeclampsia status were obtained from medical records. Child BMI was calculated based on their height and weight at annual visits.

Results: Hierarchical Linear Modeling was used to evaluate the trajectories of child BMI exposed to GDM and preeclampsia. BMI trajectory by GDM decreased (t ratio = - 2.24, [Formula: see text]0.45, 95% CI - 0.05-0.95, p = 0.07), but the trajectory by preeclampsia increased over time (t ratio = 3.153,[Formula: see text]0.65, 95% CI 0.11-1.18, p = 0.002). Moreover, there was a significant interaction between the two (t ratio = -2.24, [Formula: see text]- 1.244, 95% CI 0.15-2.33, p = 0.02), such that the BMI of children born to mothers with both GDM and preeclampsia showed consistent increases over time.

Conclusions: GDM and preeclampsia could be used as a marker for childhood obesity risk and the identification of a high-risk group, providing potential early intervention. These findings highlight the importance of managing obstetric complications, as an effective method of child obesity prevention.
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http://dx.doi.org/10.1007/s00404-020-05436-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335593PMC
January 2020

Traumatic spinal cord injury mortality from 2006 to 2016 in China.

J Spinal Cord Med 2020 Jan 16:1-6. Epub 2020 Jan 16.

National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.

To report on the national traumatic spinal cord injury (TSCI) mortality of China population, and assess sex-, age-, location-, and cause-specific mortality rates, respectively. A population-based longitudinal study based on mortality data from the Disease Surveillance Points system of China, 2006-2016. TSCI was defined according to the 10th International Classification of Disease. Negative binomial regression was used to test the significance of the change in overall and subgroup mortality rate. Age-adjusted TSCI mortality rate increased by 64% from 2006 to 2016, ranging from 0.19 to 0.34 per 100,000 population. The crude mortality was 0.31 per 100,000 population in 2016. Males and rural residents had higher TSCI mortality rates than females and urban residents. The age-adjusted TSCI mortality rate increased 53% for males, 107% for females, 75% in an urban area, and 59% in a rural area. In comparison with insignificant change in the age group of 0-44 years, TSCI mortality increased 56% and 147% in age groups of 45-64 years and 65 years. Falls accounted for 45.4% of total mortality. TSCI mortality rates were higher in males and in rural residents than in females and in urban residents during the study time period. TSCI mortality increased quickly as age increased; adults aged 65 years and older had the highest mortality rate. Falls and motor vehicle crashes were the two most common causes of TSCI mortality. More prevention efforts are needed to reduce a number of deaths from TSCI injury considering a substantial increase in TSCI mortality.
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http://dx.doi.org/10.1080/10790268.2019.1699355DOI Listing
January 2020

Author Correction: Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice.

Nat Commun 2020 Jan 6;11(1):149. Epub 2020 Jan 6.

Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-019-13970-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944687PMC
January 2020

Differential intestinal and oral microbiota features associated with gestational diabetes and maternal inflammation.

Am J Physiol Endocrinol Metab 2020 08 31;319(2):E247-E253. Epub 2019 Dec 31.

Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York.

Maternal microbiota is involved in many metabolic diseases. However, its role in the pathophysiology of gestational diabetes mellitus (GDM) remains unclear. In this case-control study, we performed a 16S rRNA sequencing-based microbial survey to compare the intestinal and oral microflora at third trimester during pregnancy between 30 GDM and 31 normal controls. Sequentially, a correlation-based network analysis was further performed to explore the interactions among microbiota, maternal and infant blood sugar, and inflammatory markers. Our results show that, compared with controls, the GDM cases showed significant differences in β-diversity and increased and in intestinal microbiota. Furthermore, the GDM cases showed lower α-diversity, increased and , and decreased and in oral microbiota. The ROC curve showed the area under the curve to be equal to 0.70 and 0.66 when using oral or gut , respectively, to predict GDM status. In addition, the components and topography of microbial cooccurrence and coexclusion network were quite distinct by GDM status. In summary, intestinal and oral microorganisms in pregnant women are closely related to the status of GDM in the third trimester of pregnancy. The changes of intestinal and oral microbial features may be noninvasive biomarkers for monitoring the health management of GDM pregnancy.
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http://dx.doi.org/10.1152/ajpendo.00266.2019DOI Listing
August 2020

Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice.

Nat Commun 2019 12 10;10(1):5643. Epub 2019 Dec 10.

Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

Spinal pain is a major clinical problem, however, its origins and underlying mechanisms remain unclear. Here we report that in mice, osteoclasts induce sensory innervation in the porous endplates which contributes to spinal hypersensitivity in mice. Sensory innervation of the porous areas of sclerotic endplates in mice was confirmed. Lumbar spine instability (LSI), or aging, induces spinal hypersensitivity in mice. In these conditions, we show that there are elevated levels of PGE2 which activate sensory nerves, leading to sodium influx through Na 1.8 channels. We show that knockout of PGE2 receptor 4 in sensory nerves significantly reduces spinal hypersensitivity. Inhibition of osteoclast formation by knockout Rankl in the osteocytes significantly inhibits LSI-induced porosity of endplates, sensory innervation, and spinal hypersensitivity. Knockout of Netrin-1 in osteoclasts abrogates sensory innervation into porous endplates and spinal hypersensitivity. These findings suggest that osteoclast-initiated porosity of endplates and sensory innervation are potential therapeutic targets for spinal pain.
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http://dx.doi.org/10.1038/s41467-019-13476-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904550PMC
December 2019

Associations of the Oral Microbiota with Obesity and Menarche in Inner City Girls.

J Child Obes 2019 13;4(1). Epub 2019 Mar 13.

Department of Environmental Medicine and Public Health, Icahn School of Medicine, Mount Sinai, 1 Gustave L. Levy Place, New York, USA.

Objective: Alterations of the oral microbiome have been associated with obesity, possibly based on inflammatory processes mediated by bacteria. Specific bacterial strains have been associated with obesity and periodontal disease. Little is known about the oral microbiome in children. Understanding the relationship between oral health and childhood growth could help identify preventable factors contributing to obesity and related conditions, including onset of menarche which is associated with obesity.

Methods: In this pilot study, we investigated the saliva microbiome among 25 girls 7-15 years old (mean 11.1) and their mothers in an inner city dental clinic in New York City. The main outcome measures were body size, presence or absence of menarche and dental practices. We examined associations of microbiome richness, diversity, and relative abundance with pubertal and demographic factors and oral health.

Results: Girls had good dental health and a typical rich oral microbiome, based on the Shannon Index of all species detected. Older girls flossed more often and younger girls had more frequent dental check-ups. Microbiome richness among girls was similar to their mothers', but diversity was greater among mothers than girls. Richness was reduced among mothers with gum bleeding, flossing and increased teeth brushing. Overweight girls had greater diversity and less richness than normal weight girls. Certain bacterial species differed in abundance with respect to whether girls had reached menarche (), overweight () and gingivitis in the girls ().

Conclusions: Differences found in specific bacteria in the oral microbiome were related to body size and menarche. With increasing interest on studying microbiome variability related to the multifactorial etiology of obesity in children, saliva is capable of providing clinically informative markers of this and related conditions.
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http://dx.doi.org/10.21767/2572-5394.100068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750217PMC
March 2019

UTX/KDM6A Deletion Promotes Recovery of Spinal Cord Injury by Epigenetically Regulating Vascular Regeneration.

Mol Ther 2019 12 22;27(12):2134-2146. Epub 2019 Aug 22.

Department of Spine Surgery, Xiangya Hospital, Central South University, 410008 Changsha, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, 410008 Changsha, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China. Electronic address:

The regeneration of the blood vessel system post spinal cord injury (SCI) is essential for the repair of neurological function. As a significant means to regulate gene expression, epigenetic regulation of angiogenesis in SCI is still largely unknown. Here, we found that Ubiquitously Transcribed tetratricopeptide repeat on chromosome X (UTX), the histone H3K27 demethylase, increased significantly in endothelial cells post SCI. Knockdown of UTX can promote the migration and tube formation of endothelial cells. The specific knockout of UTX in endothelial cells enhanced angiogenesis post SCI accompanied with improved neurological function. In addition, we found regulation of UTX expression can change the level of microRNA 24 (miR-24) in vitro. The physical binding of UTX to the promotor of miR-24 was indicated by chromatin immunoprecipitation (ChIP) assay. Meanwhile, methylation sequencing of endothelial cells demonstrated that UTX could significantly decrease the level of methylation in the miR-24 promotor. Furthermore, miR-24 significantly abolished the promoting effect of UTX deletion on angiogenesis in vitro and in vivo. Finally, we predicted the potential target mRNAs of miR-24 related to angiogenesis. We indicate that UTX deletion can epigenetically promote the vascular regeneration and functional recovery post SCI by forming a regulatory network with miR-24.
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http://dx.doi.org/10.1016/j.ymthe.2019.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904668PMC
December 2019

Effects of ultrahigh pressure and ultrasound pretreatments on properties of strawberry chips prepared by vacuum-freeze drying.

Food Chem 2020 Jan 19;303:125386. Epub 2019 Aug 19.

Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 430068, China.

The present work investigated the influences of ultrahigh pressure (UHP), ultrasound (US) and their combination (UHP-US) as pretreatments on properties of vacuum-freeze dried strawberry slices. During vacuum-freeze drying, drying duration and total energy consumption of UHP sample, US sample and UHP-US sample was decreased. After the UHP or US pretreatments, a* value (redness), antioxidative substances (total anthocyanin content, total flavonoid content, total phenolic content, diphenyl picrylhydrazyl (DPPH), hydroxyl (-OH) radical-scavenging assay), hardness and cross-section areas of matrix in the dried slices were significantly (P < 0.05) increased. Transverse relaxation times and peak area corresponding to free water in the pretreated samples were obviously decreased, indicating lower mobility in the pretreated samples. As compared with UHP or US individually, UHP in combination with US increased those parameters more pronouncedly. Therefore, UHP and US are promising techniques for the vacuum-freeze drying processing of strawberry products.
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http://dx.doi.org/10.1016/j.foodchem.2019.125386DOI Listing
January 2020

Rapid Detection of Mycoplasma-Infected Cells by an ssDNA Aptamer Probe.

ACS Sens 2019 08 12;4(8):2028-2038. Epub 2019 Aug 12.

Department of Pathology and Genomic Medicine , Houston Methodist Hospital , 6565 Fannin Street , Houston , Texas 77030 , United States.

Mycoplasmas are unique cell wall-free bacteria. Because they lack a cell wall and have resistance to β-lactam antibiotics, mycoplasma is the major pathogen that infects cultured cells in research laboratories. For rapid detection of mycoplasma-infected cells, we developed an ssDNA aptamer sequence composed of 40 nucleotides. Flow cytometry analysis showed that the synthetic aptamer probe selectively targeted mycoplasma-infected culture cells with high specificity identical to commercially available PCR-based assays. Additionally, fluorescent microscopy studies revealed that the aptamer probe rapidly stained mycoplasma-infected cells with higher sensitivity compared to Hoechst dye-mediated cellular DNA content stains. Moreover, confocal microscopy studies of trypsin-treated cells validated that the aptamer probes selectively targeted mycoplasma components on the surface of infected cells. Finally, preclinical studies of peripheral blood cells demonstrated that the aptamer probe was able to detect in vitro mycoplasma infection of primary lymphocytes. Taken together, these findings indicate that the aptamer probe will not only allow rapid detection of mycoplasma-infected culture cells for research purposes but also provide a simple method to monitor mycoplasma infection in primary cell products for clinical use.
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http://dx.doi.org/10.1021/acssensors.9b00582DOI Listing
August 2019

Epitranscriptomic RNA Methylation in Plant Development and Abiotic Stress Responses.

Front Plant Sci 2019 17;10:500. Epub 2019 Apr 17.

Department of Applied Biology, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, South Korea.

Recent advances in methylated RNA immunoprecipitation followed by sequencing and mass spectrometry have revealed widespread chemical modifications on mRNAs. Methylation of RNA bases such as -methyladenosine (mA) and 5-methylcytidine (mC) is the most prevalent mRNA modifications found in eukaryotes. In recent years, cellular factors introducing, interpreting, and deleting specific methylation marks on mRNAs, designated as "writers (methyltransferase)," "readers (RNA-binding protein)," and "erasers (demethylase)," respectively, have been identified in plants and animals. An emerging body of evidence shows that methylation on mRNAs affects diverse aspects of RNA metabolism, including stability, splicing, nucleus-to-cytoplasm export, alternative polyadenylation, and translation. Although our understanding for roles of writers, readers, and erasers in plants is far behind that for their animal counterparts, accumulating reports clearly demonstrate that these factors are essential for plant growth and abiotic stress responses. This review emphasizes the crucial roles of epitranscriptomic modifications of RNAs in new layer of gene expression regulation during the growth and response of plants to abiotic stresses.
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http://dx.doi.org/10.3389/fpls.2019.00500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499213PMC
April 2019

Synchrotron radiation micro-tomography for high-resolution neurovascular network morphology investigation.

J Synchrotron Radiat 2019 May 15;26(Pt 3):607-618. Epub 2019 Apr 15.

Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, People's Republic of China.

There has been increasing interest in using high-resolution micro-tomography to investigate the morphology of neurovascular networks in the central nervous system, which remain difficult to characterize due to their microscopic size as well as their delicate and complex 3D structure. Synchrotron radiation X-ray imaging, which has emerged as a cutting-edge imaging technology with a high spatial resolution, provides a novel platform for the non-destructive imaging of microvasculature networks at a sub-micrometre scale. When coupled with computed tomography, this technique allows the characterization of the 3D morphology of vasculature. The current review focuses on recent progress in developing synchrotron radiation methodology and its application in probing neurovascular networks, especially the pathological changes associated with vascular abnormalities in various model systems. Furthermore, this tool represents a powerful imaging modality that improves our understanding of the complex biological interactions between vascular function and neuronal activity in both physiological and pathological states.
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http://dx.doi.org/10.1107/S1600577519003060DOI Listing
May 2019

Expression of IbVPE1 from sweet potato in Arabidopsis affects leaf development, flowering time and chlorophyll catabolism.

BMC Plant Biol 2019 May 6;19(1):184. Epub 2019 May 6.

Institute of Integrative Plant Biology, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, China.

Background: Since their discovery, vacuolar processing enzymes (VPEs) have consistently been investigated as programmed cell death (PCD) initiators and participants in plant development and responses to biotic or abiotic stresses, in part due to similarities with the apoptosis regulator caspase-1. However, recent studies show additional functions of VPE in tomatoes, specifically in sucrose accumulation and fruit ripening.

Results: Herein, we evaluated the functions of VPE from sweetpotato, initially in expression pattern analyses of IbVPE1 during development and senescence. Subsequently, we identified physiological functions by overexpressing IbVPE1 in Arabidopsis thaliana, and showed reduced leaf sizes and numbers and early flowering, and elucidated the underlying molecular mechanisms.

Conclusions: The present data demonstrate functions of the VPE gene family in development and senescence and in regulation of flowering times, leaf sizes and numbers, and senescence phenotypes in Arabidopsis thaliana.
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http://dx.doi.org/10.1186/s12870-019-1789-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503384PMC
May 2019

Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice.

Gut 2020 01 29;69(1):42-51. Epub 2019 Apr 29.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.

Background And Aims: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome.

Methods: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines.

Results: Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in and depletion in . Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon.

Conclusion: Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.
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http://dx.doi.org/10.1136/gutjnl-2018-317855DOI Listing
January 2020

Microbiota of newborn meconium is associated with maternal anxiety experienced during pregnancy.

Dev Psychobiol 2019 07 25;61(5):640-649. Epub 2019 Mar 25.

Department of Psychology, Queens College, City University of New York, New York, New York.

Little is known about whether a mother's psychological state during pregnancy influences her offspring's microbiome. This study examined whether maternal anxiety, depression, and stress during pregnancy is associated with the diversity of meconium microbiome, the first internal discharge, in 75 newborns from an existing birth cohort study. The meconium microbiome was profiled using multibarcode16S rRNA sequencing at V3-V4 hypervariable region followed by taxonomic assignment to the green gene 16S references at 97% similarity and diversity analysis at the genus level. Results showed that the meconium contained diversified microbiota, and greater pregnancy-related anxiety was significantly associated with a less diverse meconium microbiota community (p = 0.001). At the specific taxa level, greater pregnancy-related anxiety was correlated with a lower level of the Enterococcaceae family (p = 2e-4, Spearman rho = -0.43). These findings support a significant role of prenatal maternal mood in the early-life bacteria colonization of their offspring.
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http://dx.doi.org/10.1002/dev.21837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588465PMC
July 2019

Unilateral Osteotomy of Lumbar Facet Joint Induces a Mouse Model of Lumbar Facet Joint Osteoarthritis.

Spine (Phila Pa 1976) 2019 Aug;44(16):E930-E938

Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Study Design: The lumbar facet joint (LFJ) osteoarthritis (OA) model that highly mimics the clinical conditions was established and evaluated.

Objective: Here, we innovatively constructed and evaluated the aberrant mechanical loading-related LFJ OA model.

Summary Of Background Data: LFJ is the only true synovial joint in a functional spinal unit in mammals. The LFJ osteoarthritis is considered to contribute 15% to 45% of low back pain. The establish of animal models highly mimicking the clinical conditions is a useful tool for the investigation of LFJ OA. However, the previously established animal models damaged the LFJ structure directly, which did not demonstrate the effect of aberrant mechanical loading on the development of LFJ osteoarthritis.

Methods: In the present study, an animal model for LFJ degeneration was established by the unilateral osteotomy of LFJ (OLFJ) in L4/5 unit to induce the spine instability. Then, the change of contralateral LFJ was evaluated by morphological and molecular biological techniques.

Results: We showed that the OLFJ induced instability accelerated the cartilage degeneration of the contralateral LFJ. Importantly, the SRμCT elucidated that the three-dimensional structure of the subchondral bone changed in contralateral LFJ, indicated as the abnormity of bone volume/total volume ratio (BV/TV), trabecular pattern factor (Tb. Pf), and the trabecular thickness (Tb. Th). Immunostaining further demonstrated the uncoupled osteoclastic bone resorption, and bone formation in the subchondral bone of contralateral LFJ, indicated as increased activity of osteoclast, osteoblast, and Type H vessels.

Conclusion: We develop a novel LFJ OA model demonstrating the effect of abnormal mechanical instability on the degeneration of LFJ. This LFJ degeneration model that highly mimics the clinical conditions is a valuable tool to investigate the LFJ osteoarthritis.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000003023DOI Listing
August 2019

Effect of Low-Intensity Pulsed Ultrasound After Autologous Adipose-Derived Stromal Cell Transplantation for Bone-Tendon Healing in a Rabbit Model.

Am J Sports Med 2019 03;47(4):942-953

Department of Sports Medicine & Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: Low-intensity pulsed ultrasound (LIPUS), as a safe biophysiotherapy, can enhance bone-tendon (B-T) healing in vivo and induce osteogenic or chondrogenic differentiation of mesenchymal stromal cells in vitro. This study aimed to determine whether LIPUS can improve the efficacy of transplanted mesenchymal stromal cells on B-T healing.

Hypothesis: LIPUS can induce lineage-specific differentiation of transplanted adipose-derived stromal cells (ASCs) at the B-T healing site, thus resulting in superior healing quality when compared with LIPUS or ASCs alone.

Study Design: Controlled laboratory study.

Methods: A total of 112 mature rabbits with partial patellectomy in the hindlimb were randomly assigned into mock sonication without ASCs (control), ultrasonication without ASCs (LIPUS), mock sonication with ASCs (ASCs), and ultrasonication with ASCs (LIPUS + ASCs). The treatment time of the mock sonication or ultrasonication was 20 minutes per day. Autologous ASCs were transplanted to the healing site by fibrin glue during the operation, and LIPUS was delivered daily starting at postoperative day 3 until euthanasia. The patella-patellar tendon junctions were postoperatively harvested at 8 and 16 weeks for radiological, histological, and mechanical evaluations. Additionally, 9 animals were used for ASC tracking with mCherry protein.

Results: Radiologically, there was more new bone formation and remodeling in the LIPUS + ASCs group as compared with the other groups. Synchrotron radiation micro-computed tomography showed that the LIPUS + ASCs group significantly increased bone volume fraction, trabecular thickness, and trabecular number at the healing site as compared with the other groups at postoperative 8 weeks ( P < .05 for all). Histologically, immunohistochemical staining confirmed that the transplanted mCherry-ASCs can differentiate into osteoblasts and fibrochondrocytic-like cells. Meanwhile, as compared with the other groups, the LIPUS + ASCs group showed more formation and maturity of the fibrocartilage layer and new bone at postoperative weeks 8 and 16 ( P < .05 for all). Biomechanically, the LIPUS + ASCs group showed significantly higher failure load and stiffness versus the other groups at postoperative weeks 8 and 16 ( P < .05 for all).

Conclusion: Autologous ASC transplantation stimulated with LIPUS can result in superior B-T healing quality when compared with LIPUS or ASCs alone.

Clinical Relevance: This study demonstrates the effectiveness of using ASC transplantation stimulated with LIPUS for B-T healing and provides a foundation for future clinical studies.
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http://dx.doi.org/10.1177/0363546518820324DOI Listing
March 2019

-Book-shaped decellularized tendon matrix scaffold combined with bone marrow mesenchymal stem cells-sheets for repair of achilles tendon defect in rabbit.

J Orthop Res 2019 04 28;37(4):887-897. Epub 2019 Mar 28.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.

Tissue-engineering approaches have great potential to improve the treatment of tendon injuries which are major musculoskeletal disorders. The purpose of this study was to assess the tissue engineering potential of a novel multilayered decellularized tendon "book" scaffold with bone marrow mesenchymal stem cells (BMSCs) sheets for repair of an Achilles tendon defect in a rabbit model. In this study, we developed a novel book-shaped decellularized scaffold derived from the extracellular matrix of tendon tissues from New Zealand white rabbits. Hematoxylin and eosin (H&E) staining, 4', 6-diamidino-2-phenylindole (DAPI) staining, DNA quantitation, and scanning electron microscopy (SEM) confirmed the efficiency of decellularization. After culturing BMSCs on decellularized scaffolds, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, SEM, quantitative real time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis demonstrated that decellularized scaffolds have the capacity to yield homogeneous distribution and alignment of BMSCs, as well as support their differentiation into tendon. Tenomodulin and Alpha-1 collagen type I are important indicators for evaluating tenogenic differentiation of BMSCs. When decellularized "book" scaffolds with BMSCs sheets were used to repair a 1 mm Achilles tendon defect, histomorphological analysis, immunohistochemical assessment, and biomechanical testing showed that the book-shaped decellularized tendon matrix scaffold and BMSCs sheets could promote the regeneration of type I collagen at the wound site during healing, and improve the mechanical properties of the repaired tendon. Therefore, the results of this study suggest that the novel decellularized "book" tendon scaffolds combined with BMSCs sheets have therapeutic effects on improving the healing quality of the Achilles tendon. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-11, 2019.
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http://dx.doi.org/10.1002/jor.24255DOI Listing
April 2019

Book-Shaped Acellular Fibrocartilage Scaffold with Cell-loading Capability and Chondrogenic Inducibility for Tissue-Engineered Fibrocartilage and Bone-Tendon Healing.

ACS Appl Mater Interfaces 2019 Jan 8;11(3):2891-2907. Epub 2019 Jan 8.

Key Laboratory of Organ Injury , Aging and Regenerative Medicine of Hunan Province , Changsha , Hunan , China , 410008.

Functional fibrocartilage regeneration is a bottleneck during bone-tendon healing, and the currently available tissue-engineering strategies for fibrocartilage regeneration are insufficient because of a lack of appropriate scaffold that can load large seeding-cells and induce chondrogenesis of stem cells. The acellular fibrocartilage scaffold (AFS) contains active growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potential scaffold for tissue-engineered fibrocartilage. A limitation to this scaffold is that its low porosity inhibits cells loading and infiltration. Here, inspired by book appearance, we sectioned native fibrocartilage tissue (NFT) into book-shape to improve cells loading and infiltration, and then decellularized with four protocols: (1) 2% SDS for 6-h, (2) 2% SDS for 24-h, (3) 4 SDS for 6-h, (4) 4% SDS for 24-h, followed by nuclease digestion. The optimal protocol was screened with respect to microstructures, DNA residence, native ingredients reservation, and chondrogenic inducibility of the AFS. In vitro studies demonstrated that this screened scaffold is noncytotoxicity and low-immunogenicity, allows adipose-derived stromal cells (ASCs) attachment and proliferation, shows superior chondrogenic inducibility, and stimulates collagen or glycosaminoglycans secretion. The underlying mechanism for this chondrogenic inducibility may be related to hedgehog pathway activating. Additionally, a novel pattern for fabricating tissue-engineered fibrocartilage was developed to enlarge seeding-cells loading, namely, cell-sheets sandwiched by book-shaped scaffold. In-vivo studies indicate that this screened scaffold alone could induce endogenous cells to satisfactorily regenerate fibrocartilage at 16-week, as characterized by fibrocartilaginous extracellular matrix (ECM) deposition and good interface integration. Interleaving this book-shaped AFS with autologous ASCs-sheets significantly enhanced its ability to regenerate fibrocartilage. Cell tracking demonstrated that fibrochondrocytes, osteoblasts, and osteocytes in the healing interface at postoperative 8-week partly originated from the sandwiched ASCs-sheets. On that basis, we propose the use of this book-shaped AFS and cell sheet technique for fabricating tissue-engineered fibrocartilage to improve bone-tendon healing.
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http://dx.doi.org/10.1021/acsami.8b20563DOI Listing
January 2019

Three-dimensional characterization of the microstructure in rabbit patella-patellar tendon interface using propagation phase-contrast synchrotron radiation microtomography.

J Synchrotron Radiat 2018 Nov 25;25(Pt 6):1833-1840. Epub 2018 Oct 25.

Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008, People's Republic of China.

Understanding the three-dimensional ultrastructure morphology of tendon-to-bone interface may allow the development of effective therapeutic interventions for enhanced interface healing. This study aims to assess the feasibility of propagation phase-contrast synchrotron radiation microtomography (PPC-SRµCT) for three-dimensional characterization of the microstructure in rabbit patella-patellar tendon interface (PPTI). Based on phase retrieval for PPC-SRµCT imaging, this technique is capable of visualizing the three-dimensional internal architecture of PPTI at a cellular high spatial resolution including bone and tendon, especially the chondrocytes lacuna at the fibrocartilage layer. The features on the PPC-SRµCT image of the PPTI are similar to those of a histological section using Safranin-O staining/fast green staining. The three-dimensional microstructure in the rabbit patella-patellar tendon interface and the spatial distributions of the chondrocytes lacuna and their quantification volumetric data are displayed. Furthermore, a color-coding map differentiating cell lacuna in terms of connecting beads is presented after the chondrocytes cell lacuna was extracted. This provides a more in-depth insight into the microstructure of the PPTI on a new scale, particularly the cell lacuna arrangement at the fibrocartilage layer. PPC-SRµCT techniques provide important complementary information to the conventional histological method for characterizing the microstructure of the PPTI, and may facilitate in investigations of the repair mechanism of the PPTI after injury and in evaluating the efficacy of a different therapy.
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http://dx.doi.org/10.1107/S160057751801353XDOI Listing
November 2018

A network-based signature to predict the survival of non-smoking lung adenocarcinoma.

Cancer Manag Res 2018 16;10:2683-2693. Epub 2018 Aug 16.

Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China,

Background: A substantial increase in the number of non-smoking lung adenocarcinoma (LAC) patients has been drawing extensive attention in the past decade. However, effective biomarkers, which could guide the precise treatment, are still limited for identifying high-risk patients. Here, we provide a network-based signature to predict the survival of non-smoking LAC.

Materials And Methods: Gene expression profiles were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. Significant gene co-expression networks and hub genes were identified by Weighted Gene Co-expression Network Analysis. Potential mechanisms and pathways of co-expression networks were analyzed by Gene Ontology. The predictive signature was constructed by penalized Cox regression analysis and tested in two independent datasets.

Results: Two distinct co-expression modules were significantly correlated with the non-smoking status across 4 Gene Expression Omnibus datasets. Gene Ontology revealed that nuclear division and cell cycle pathways were main mechanisms of the blue module and that genes in the turquoise module were involved in lymphocyte activation and cell adhesion pathways. Seventeen genes were selected from hub genes at an optimal lambda value and built the prognostic signature. The prognostic signature distinguished the survival of non-smoking LAC (training: hazard ratio [HR]=3.696, 95% CI: 2.025-6.748, <0.001; testing: HR=2.9, 95% CI: 1.322-6.789, =0.006; HR=2.78, 95% CI: 1.658-6.654, =0.022) and had moderate predictive abilities in the training and validation datasets.

Conclusion: The prognostic signature is a promising predictor of non-smoking LAC patients, which might benefit clinical practice and precision therapeutic management.
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http://dx.doi.org/10.2147/CMAR.S163918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101016PMC
August 2018

The protective effect of microRNA-21 in neurons after spinal cord injury.

Spinal Cord 2019 Feb 8;57(2):141-149. Epub 2018 Aug 8.

Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Study Design: Experimental animal study.

Objectives: To validate the anti-apoptosis effect of microRNA-21 in neurons after spinal cord injury (SCI) and explore the mechanism.

Setting: Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Methods: In situ hybridization was used to detect the expression of miR-21 in spinal cord neurons (n = 24). In a rat contusion SCI model (n = 48), we upregulated the miR-21 level around the injured area using miR-21 lentiviral vectors and evaluated the therapeutic effect with histology and behavioural scores. In neuronal cells, oxygen-glucose deprivation (OGD) was exerted to imitate SCI, and we explored the biomechanism using molecular biology and a dual-luciferase reporter assay.

Results: miR-21 was expressed in spinal cord neurons and was found to improve neuronal survival and promote functional recovery in rat SCI models. The in vitro results in PC-12 cells revealed that the augmentation of endogenous miR-21 was able to reduce neuronal cell death after OGD. In addition, overexpression of miR-21 was able to reduce cellular apoptosis via decreasing PDCD4 protein levels, and caspase-3 activity was also influenced. Transfection of miR-21 into 293T cells was able to decrease luciferase activity in a reporter assay system, including the 3' untranslated region of PDCD4.

Conclusions: miR-21 may have a protective role in neuronal apoptosis after SCI. PDCD4 may be a functional target gene involved in the miR-21-mediated anti-apoptotic effect through an miR-21/PDCD4/caspase-3 pathway.
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http://dx.doi.org/10.1038/s41393-018-0180-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358587PMC
February 2019

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging.

Bone Res 2018 18;6:21. Epub 2018 Jul 18.

1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Ross Building, Room 229, 720 Rutland Ave, Baltimore, MD USA.

Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αβ to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD.
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http://dx.doi.org/10.1038/s41413-018-0022-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050246PMC
July 2018

SR-FTIR as a tool for quantitative mapping of the content and distribution of extracellular matrix in decellularized book-shape bioscaffolds.

BMC Musculoskelet Disord 2018 Jul 18;19(1):220. Epub 2018 Jul 18.

Department of Sports Medicine, Xiangya Hospital, Central South University, 87# Xiang-ya Road, Changsha, 410008, Hunan, People's Republic of China.

Background: To evaluate synchrotron radiation-based Fourier transform infrared microspectroscopy (SR-FTIR) as a tool for quantitative mapping of the content and distribution of the extracellular matrix in decellularized fibrocartilage bioscaffolds, and to provide a new platform for quantitatively characterizing bioscaffolds for tissue engineering.

Methods: Fibrocartilage was harvested and cut into book-shape bioscaffolds (N = 54), which were then decellularized. The structures and distribution of collagen fibrous and intrinsic ultrastructure in decellularized fibrocartilage bioscaffolds were evaluated by histological staining and scanning electron microscopy (SEM), respectively. The content of collagen and proteoglycan in the cellularized or decellularized bioscaffolds were also measured by SR-FTIR and biochemical assay.

Results: Book-shape fibrocartilage decellularized bioscaffolds were successfully obtained. Histological examination revealed that the structure of extracellular matrix endured during decellularization. Histology and DNA quantification analysis confirmed substantial removal of cells during decellularization. SEM demonstrated that intrinsic ultrastructure of the fibrocartilage bioscaffold was also well preserved. SR-FTIR quantitative analysis confirmed that decellularization had a significant effect on the content and distribution of collagen and proteoglycan in fibrocartilage bioscaffolds, these results are confirmed with the biochemical assay results.

Conclusion: SR-FTIR imaging can capture the histological morphology of decellularized bioscaffolds. Moreover, it can be used for quantitative mapping of the content and distribution of collagen in the bioscaffolds.
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http://dx.doi.org/10.1186/s12891-018-2149-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052527PMC
July 2018

Anatomic reconstruction of anterior talofibular ligament with tibial tuberosity-patellar tendon autograft for chronic lateral ankle instability.

J Orthop Surg (Hong Kong) 2018 May-Aug;26(2):2309499018780874

1 Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China.

Introduction: Anatomic repair of the anterior talofibular ligament (ATFL) is challenging when the local ligamentous tissue is severely attenuated. Anatomic reconstruction of the ATFL with tibial tuberosity-patellar tendon (TT-PT) autograft is a feasible choice that can avoid the complicated tendon-bone healing and restore ankle stability.

Materials And Methods: From 2009 to 2015, 31 chronic lateral ankle instability (CLAI) patients (31 ankles), who had a serious injury on the ATFL only, were treated with anatomic reconstruction of ATFL with TT-PT. American orthopedic foot and ankle society ankle-hindfoot score (AHS), visual analog scale for pain score (VAS), Karlsson-Peterson score, Tegner activity level, and objective examination comprehending range of motion were used to evaluate the clinical outcomes before and after operation. Radiographically, talar tilt angles and anterior drawer were assessed in pre- and postoperative ankle stress views.

Results: Among the 31 ankles, 17 ankles with single-bundle ATFL and 14 ankles with double-bundle ATFL were found at operation. At a mean follow-up of 42 months (24-82 months), all patients were satisfied with the procedure. Mean AHS significantly increased from 60.5 ± 8.2 to 93.5 ± 4.8. Mean Karlsson-Peterson score significantly increased from 55.2 ± 11.0 preoperatively to 91.2 ± 6.9 at final follow-up. Average VAS significantly decreased from 5.9 ± 1.6 preoperatively to 1.4 ± 1.0 at the latest follow-up. Mean Tegner activity level was 3.7 ± 0.9 before operation, compared with 7.0 ± 0.8 after operation. On stress radiographs, mean talar tilt angle was 17.0 ± 3.4° before operation and 3.8 ± 2.1° at the latest follow-up. In addition, mean anterior tibiotalar translation was 7.5 ± 2.2 mm before operation and 1.8 ± 1.1 mm at the latest follow-up.

Conclusion: Anatomic reconstruction of the ATFL using a TT-PT autograft allows bone-bone healing in talus and tendon-tendon/periosteum healing in fibula rather than requiring tendon-bone healing, which is an alternative choice for treating CLAI caused by single ATFL insufficiency.
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http://dx.doi.org/10.1177/2309499018780874DOI Listing
September 2019

The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome.

Environ Health 2018 05 29;17(1):50. Epub 2018 May 29.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1428 Madison, New York, NY, 10029, USA.

Background: Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats.

Methods: Glyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis.

Results: Microbiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls.

Conclusions: This study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood.
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http://dx.doi.org/10.1186/s12940-018-0394-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972442PMC
May 2018

The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation.

Environ Health 2018 05 29;17(1):52. Epub 2018 May 29.

Cesare Maltoni Cancer Research Center (CMCRC), Ramazzini Institute (RI), Via Saliceto, 3, 40010 Bentivoglio, Bologna, Italy.

Background: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine.

Methods: We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA.

Results: Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA.

Conclusions: Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.
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http://dx.doi.org/10.1186/s12940-018-0393-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972408PMC
May 2018

One-stage posterior debridement and fusion combined with irrigation and drainage for the treatment of postoperative lumbar spondylodiscitis.

Acta Orthop Traumatol Turc 2018 Jul 18;52(4):277-282. Epub 2018 May 18.

Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, PR China. Electronic address:

Objective: The aim of this study was to evaluate the clinical outcomes of one-stage posterior debridement, interbody fusion, and instrumentation, combined with irrigation and drainage, for treating lumbar spondylodiscitis.

Methods: The study included 23 patients (13 male and 10 female, mean age: 45 years) who had posterior debridement, interbody fusion, and instrumentation, followed by continuous closed irrigation and drainage for lumbar postoperative spondylodiscitis. The visual analog scale, Oswestry disability index, and lumbar lordosis angle were assessed before and after surgery to evaluate the clinical outcome.

Results: The mean follow-up time was 27 (24-36) months. All patients tolerated the procedure well, and there were no instances of spondylodiscitis recurrence, though a dorsal dermal sinus developed in one patient after surgery. Infection was eliminated, as evidenced by the normalization of the erythrocyte sedimentation rates and C-reactive protein levels. The mean visual analog scale scores were significantly decreased after the operation. The mean lumbar lordosis angle before surgery was 21.61 ± 6.88° and the angle at the final follow-up was 31.61 ± 4.24°. The mean Oswestry disability index scores improved significantly both after the operation and at the follow-up visits (p < 0.05). Bone union was confirmed in all patients at a mean of 8.6 months post-operation, though this was not achieved until 2 years post-operation in one patient. All 3 patients who had neurological deficits showed great improvement at the last follow-up.

Conclusion: Surgical management using one-stage posterior debridement, interbody fusion, and instrumentation, followed by continuous closed irrigation and drainage, might be an effective treatment option for lumbar postoperative spondylodiscitis.

Level Of Evidence: Level IV, Therapeutic study.
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http://dx.doi.org/10.1016/j.aott.2018.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150443PMC
July 2018