Publications by authors named "Qianqian Pang"

42 Publications

Repetitive DNA Sequences in the Human Y Chromosome and Male Infertility.

Front Cell Dev Biol 2022 13;10:831338. Epub 2022 Jul 13.

Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, China.

The male-specific Y chromosome, which is well known for its diverse and complex repetitive sequences, has different sizes, genome structures, contents and evolutionary trajectories from other chromosomes and is of great significance for testis development and function. The large number of repetitive sequences and palindrome structure of the Y chromosome play an important role in maintaining the stability of male sex determining genes, although they can also cause non-allelic homologous recombination within the chromosome. Deletion of certain Y chromosome sequences will lead to spermatogenesis disorders and male infertility. And Y chromosome genes are also involved in the occurrence of reproductive system cancers and can increase the susceptibility of other tumors. In addition, the Y chromosome has very special value in the personal identification and parentage testing of male-related cases in forensic medicine because of its unique paternal genetic characteristics. In view of the extremely high frequency and complexity of gene rearrangements and the limitations of sequencing technology, the analysis of Y chromosome sequences and the study of Y-gene function still have many unsolved problems. This article will introduce the structure and repetitive sequence of the Y chromosome, summarize the correlation between Y chromosome various sequence deletions and male infertility for understanding the repetitive sequence of Y chromosome more systematically, in order to provide research motivation for further explore of the molecules mechanism of Y-deletion and male infertility and theoretical foundations for the transformation of basic research into applications in clinical medicine and forensic medicine.
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http://dx.doi.org/10.3389/fcell.2022.831338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326358PMC
July 2022

Bone Microarchitecture in Obese Postmenopausal Chinese Women: The Chinese Vertebral Osteoporosis Study (ChiVOS).

Front Endocrinol (Lausanne) 2022 5;13:891413. Epub 2022 Jul 5.

Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: Obesity is associated with improved bone mass and microarchitecture in Caucasian individuals, but evidence in obese Asian individuals is lacking.

Objective: To analyze the areal bone mineral density (aBMD) and bone microarchitecture in normal-weight, overweight, and obese postmenopausal Chinese women.

Methods: A total of 243 postmenopausal women from the Chinese Vertebral Osteoporosis Study (ChiVOS) were included and were divided into three groups (OB, obese group; OW, overweight group; NW, normal weight group) by BMI level. aBMD, trabecular bone score (TBS), and appendicular lean mass (ALM) were measured by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was measured by HR-pQCT at the distal radius and tibia. X-ray was performed to confirm vertebral fractures (VFs). Multiple linear regression was used to evaluate the correlations between bone parameters and ALM after adjusting for confounding variables.

Results: The prevalence of VFs and clinical fractures were similar among the groups. Participants in the OB group showed a lower level of osteocalcin with comparable levels of other bone turnover markers (BTMs). The aBMD at several skeletal sites was higher in the OB group than in the NW group after adjusting for age (<0.01 for all comparisons). At the radius, the OB group had a higher Ct.Ar, Tb.vBMD, Tb.BV/TV, Tb.N, Tb.Th, and Ct.Th than the NW group after adjusting for covariates (<0.05 for all). Differences of a similar magnitude were found at the distal tibia. There was a trend of decreasing trend in Tb.Sp, Tb.1/N/SD, and Ct.Po among groups at both sites. However, the bone microarchitecture did not differ between participants with severe obesity (BMI≥35.0kg/m) and those with 30.0≤BMI<35 kg/m. Multiple linear regression revealed that the associations between ALM and most of the bone microarchitecture parameters at both sites were much stronger than the association between body weight and bone parameters.

Conclusion: We have observed significant improvements in aBMD, bone geometry, and bone microarchitecture in obese postmenopausal Chinese women. Except for a lower level of osteocalcin in the OB group, no significant differences in BTMs were found among the groups. Compared with body weight, ALM may explain greater variance in the improvement of bone microarchitecture parameters.
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http://dx.doi.org/10.3389/fendo.2022.891413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294215PMC
July 2022

A Novel Synonymous Variant of PHEX in a Patient with X-Linked Hypophosphatemia.

Calcif Tissue Int 2022 Jul 14. Epub 2022 Jul 14.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.

X-linked dominant hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets/osteomalacia, is caused by loss-of-function phosphate-regulating endopeptidase homolog X-linked gene (PHEX) variants. However, synonymous PHEX variants are rare in XLH. We report a 7-year-old boy with hypophosphatemia, short stature, and lower limb deformity. Whole-exome sequencing, reverse transcription-polymerase chain reaction, and Sanger sequencing were performed to identify the pathogenicity of the variant. A novel synonymous PHEX variant (NM_000444.4:c.1530 C>T, p.Arg510Arg) was detected in the proband. Further analysis revealed a 58-bp deletion at the 5' site of exon 14 during splicing. This study extends the genetic spectrum of XLH and confirms the rarity and significance of synonymous PHEX variants.
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http://dx.doi.org/10.1007/s00223-022-01003-wDOI Listing
July 2022

Bone Volumetric Density, Microarchitecture, and Estimated Bone Strength in Tumor-Induced Rickets/Osteomalacia X-linked Hypophosphatemia in Chinese Adolescents.

Front Endocrinol (Lausanne) 2022 13;13:883981. Epub 2022 Jun 13.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

Tumor-induced rickets/osteomalacia (TIR/O) severely impairs bone microarchitecture and bone strength. However, no study has described the microarchitectural quality of bone in adolescent patients with TIR/O. TIR/O affects bone quality more severely than the inherited causes of hypophosphatemia, the most common form of which is X-linked hypophosphatemia (XLH). Nevertheless, differences of the microarchitectural quality of the bone between TIR/O and XLH have never been clarified. Therefore, in this study, we used high-resolution peripheral quantitative computed tomography to assess bone microarchitecture in five Chinese adolescent TIR/O patients, and these were compared with 15 age- and gender-matched XLH patients as well as 15 age- and gender-matched healthy controls. Compared with the healthy controls, the TIR/O patients presented with significantly lower volumetric bone mineral densities (vBMDs), severely affected bone microarchitecture, and profoundly weaker bone strength. The distal tibia was more severely affected than the distal radius. Compared with the XLH patients, the TIR/O patients showed deteriorated bone quality notably at the distal tibia and in the cancellous compartment, reflected by 45.9% lower trabecular vBMD ( = 0.029), 40.2% lower trabecular fraction ( = 0.020), 40.6% weaker stiffness ( = 0.058), and 42.7% weaker failure load ( = 0.039) at the distal tibia. The correlation analysis showed that a higher level of serum FGF23 and a lower level of serum phosphate were associated with a poorer bone microarchitecture and a weaker estimated bone strength in the hypophosphatemic patients of our study. In conclusion, our study demonstrated significantly lower vBMDs, severely impaired bone microarchitecture, and profoundly weaker bone strength in Chinese adolescent patients with TIR/O, notably at the distal tibia, compared with the same parameters in age- and sex-matched healthy controls and XLH patients, which was possibly caused by excessive FGF23 production and secretion, chronically severe hypophosphatemia, and weak mechanical stimulus at the lower extremities. These findings further our understanding of the impact of different kinds of hypophosphatemic rickets/osteomalacia on bone quality.
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http://dx.doi.org/10.3389/fendo.2022.883981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234144PMC
July 2022

The misdiagnose and treatment of a concealed kind of supernumerary nostril: a case report and review.

BMC Surg 2022 Jun 13;22(1):227. Epub 2022 Jun 13.

Department of Orthopedics, The First Affiliated Hospital, College of Medicine, Zhejiang University, # 79Qingchun Road, Zhejiang, 310003, Hangzhou, People's Republic of China.

Background: Supernumerary Nostril, also called triple nostrils or accessory nostril, is a rare congenital nasal malformation.

Case Presentation: We report one conceal case of supernumerary nostril in a 19-years-old men which is misdiagnosed to a simple small nasal skin pit. Ordinary surgical excision led to recurrent infection of the lesion postoperatively, and was eventually required secondary surgery and the lesion was finally confirmed by pathological biopsy as a trinasal nostrils.

Conclusions: Through this case, we stress the essential role in differential diagnosis, confirming the diagnosis and seeking for better solutions. Level of Evidence V.
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http://dx.doi.org/10.1186/s12893-022-01679-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195352PMC
June 2022

Bone microstructure evaluated by TBS and HR-pQCT in Chinese adults with X-linked hypophosphatemia.

Bone 2022 07 18;160:116423. Epub 2022 Apr 18.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Although generalized mineralization defects have been observed, elevated areal bone mineral density (aBMD) in the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) has also been found in XLH. In contrast, high-resolution peripheral quantitative computed tomography (HR-pQCT) revealed lower volumetric BMD (vBMD) and damaged bone microstructure in the peripheral bone in XLH. Trabecular bone score (TBS), which can assess the trabecular microstructure in the lumbar spine, has not been explored in XLH. This study aimed to explore TBS and its correlations with biochemical indices and HR-pQCT parameters in adult XLH patients. A total of 66 patients with XLH (26 men and 40 women) aged 29.6 ± 9.6 years and 66 age- and sex-matched healthy controls were included. Z score of lumbar spine aBMD was relatively high [2.0 (0.6, 3.7)], with normal TBS (1.475 ± 0.129) in the XLH patients. HR-pQCT revealed larger total and trabecular area in the peripheral bone in the XLH group compared with the control group. In addition, lower trabecular and cortical vBMD, lower trabecular number with greater separation, and lower bone strength at both the radius and tibia were found in the XLH group compared with the control group. Smaller cortical area, lower thickness and higher porosity in the XLH group compared with controls were only found at the radius. TBS was not associated with any biochemical indices, while better HR-pQCT parameters correlated with higher serum phosphate and lower ALP levels. TBS was positively related with aBMD but not HR-pQCT parameters. In conclusion, adult patients with XLH had high bone mass and normal TBS in the lumbar spine but compromised microarchitecture and bone strength in the peripheral bone. This finding indicated a site-specific effect of the disease on the skeleton in the XLH patients.
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http://dx.doi.org/10.1016/j.bone.2022.116423DOI Listing
July 2022

Comprehensive Analysis of Circular RNA Expression in ceRNA Networks and Identification of the Effects of hsa_circ_0006867 in Keloid Dermal Fibroblasts.

Front Mol Biosci 2022 31;9:800122. Epub 2022 Jan 31.

Department of Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Circular RNAs (circRNAs) play a crucial role in the pathogenesis of various fibrotic diseases, but the potential biological function and expression profile of circRNAs in keloids remain unknown. Herein, microarray technology was applied to detect circRNA expression in four patient-derived keloid dermal fibroblasts (KDFs) and normal dermal fibroblasts (NDFs). A total of 327 differentially expressed (DE) circRNAs (fold change > 1.5, < 0.05) were identified with 195 upregulated and 132 downregulated circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the upregulated circRNAs were mainly enriched in the cytoskeleton and tight junctions, while the downregulated circRNAs were related to morphogenesis of the epithelium and axonal guidance. To explore the function of DE circRNAs, a circRNA-miRNA-mRNA network, including five circRNAs, nine miRNAs, and 235 correlated mRNAs, was constructed using bioinformatics analyses. The expression of five DE circRNAs was validated by qRT-PCR in 18 pairs of KDFs and NDFs, and hsa_circ_0006867 showed promising regulatory function in keloids . Silencing hsa_circ_00006867 suppressed the proliferation, migration, and invasion of keloid fibroblasts. RNA-binding protein immunoprecipitation (RIP) assays indicated that hsa_circ_00006867 may serve as a platform for miRNA binding to Argonaute (AGO) 2. In addition, hsa-miR-29a-5p may be a potential target miRNA of hsa_circ_00006867. Taken together, our research provided multiple novel clues to understand the pathophysiologic mechanism of keloids and identified hsa_circ_0006867 as a biomarker of keloids.
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http://dx.doi.org/10.3389/fmolb.2022.800122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841745PMC
January 2022

Bone Geometry, Density, Microstructure, and Biomechanical Properties in the Distal Tibia in Patients With Primary Hypertrophic Osteoarthropathy Assessed by Second-Generation High-Resolution Peripheral Quantitative Computed Tomography.

J Bone Miner Res 2022 03 3;37(3):484-493. Epub 2022 Jan 3.

Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Periosteosis refers to pathological woven bone formation beneath the cortical bone of the long bones. It is an imaging hallmark of primary hypertrophic osteoarthropathy (PHO) and also considered as one of the major diagnostic criteria of PHO patients. Up to date, detailed information on bone quality changes in long bones of PHO patients is still missing. This study aimed to evaluate bone microarchitecture and bone strength in PHO patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT). The study comprised 20 male PHO patients with the average age of 27.0 years and 20 age- and sex-matched healthy controls. The areal bone mineral density (aBMD) was assessed at the lumbar spine (L -L ) and hip (total hip and femoral neck) by dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric bone mineral density (vBMD), and microstructure parameters at the distal tibia were evaluated by using HR-pQCT. Bone strength was evaluated by finite element analysis (FEA) based on HR-pQCT screening at distal tibia. Urinary prostaglandin E (PGE ), serum phosphatase (ALP), beta-C-telopeptides of type I collagen (β-CTX), soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), and neuronal calcitonin gene-related peptide (CGRP) were investigated. As compared with healthy controls, PHO patients had larger bone cross-sectional areas; lower total, trabecular, and cortical vBMD; compromised bone microstructures with more porous cortices, thinned trabeculae, reduced trabecular connectivity, and relatively more significant resorption of rod-like trabeculae at distal tibia. The apparent Young's modulus was significantly lower in PHO patients. The concentration of PGE , biomarkers of bone resorption (β-CTX and sRANKL/OPG ratio), and the neuropeptide CGRP were higher in PHO patients versus healthy controls. PGE level correlated negatively with vBMD and estimated bone strength and positively with bone geometry at distal tibia. The present HR-pQCT study is the first one illustrating the microarchitecture and bone strength features in long bones. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4488DOI Listing
March 2022

Bone Impairment in a Large Cohort of Chinese Patients With Tumor-Induced Osteomalacia Assessed by HR-pQCT and TBS.

J Bone Miner Res 2022 03 3;37(3):454-464. Epub 2022 Jan 3.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n = 113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L to L aBMD Z-score (Z ≤ -2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and β-isomerized C-terminal telopeptide of type I collagen (β-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4476DOI Listing
March 2022

Clinical, Biochemical, Radiological, Genetic and Therapeutic Analysis of Patients with COMP Gene Variants.

Calcif Tissue Int 2022 03 28;110(3):313-323. Epub 2021 Oct 28.

Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia type 1 (MED1) are two rare skeletal disorders caused by cartilage oligomeric matrix protein (COMP) variants. This study aims to analyze the genotype and phenotype of patients with COMP variants. Clinical information for 14 probands was collected; DNA was extracted from blood for COMP variant detection. Clinical manifestations and radiology scoring systems were established to evaluate the severity of each patient's condition. Serum COMP levels in PSACH patients and healthy subjects were measured. Thirty-nine patients were included, along with 12 PSACH probands and two MED1 probands. Disproportionate short stature, waddling gait, early-onset osteoarthritis and skeletal deformities were the most common features. The height Z-score of PSACH patients correlated negatively with age at evaluation (r =  - 0.603, p = 0.01) and the clinical manifestation score (r =  - 0.556, p = 0.039). Over 50% of the PSACH patients were overweight/obese. The median serum COMP level in PSACH patients was 16.75 ng/ml, which was significantly lower than that in healthy controls (98.53 ng/ml; p < 0.001). The condition of MED1 patients was better than that of PSACH patients. Four novel variants of COMP were detected: c.874T>C, c.1123_1134del, c.1531G>A, and c.1576G>T. Height Z-scores and serum COMP levels were significantly lower in patients carrying mutations located in calmodulin-like domains 6, 7, and 8. As the two phenotypes overlap to different degrees, PSACH and MED1 are suggested to combine to produce "spondyloepiphyseal dysplasia, COMP type". Clinical manifestations and radiology scoring systems, serum COMP levels and genotype are important for evaluating patient condition severity.
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http://dx.doi.org/10.1007/s00223-021-00920-6DOI Listing
March 2022

Alteration of Bone Density, Microarchitecture, and Strength in Patients with Camurati-Engelmann Disease: Assessed by HR-pQCT.

J Bone Miner Res 2022 01 28;37(1):78-86. Epub 2021 Sep 28.

Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Camurati-Engelmann disease (CED) is a rare autosomal-dominant skeletal dysplasia caused by mutations in the transforming growth factor-β1 (TGFB1) gene. In this study, a retrospective review of patients with CED evaluated at Peking Union Medical College Hospital in Beijing, China, between November 30, 2000 and November 30, 2020 was conducted. Data including demographic data, manifestations, and examination results were characterized. Furthermore, bone geometry, density, and microarchitecture were assessed and bone strength was estimated by HR-pQCT. Results showed the median age at onset was 2.5 years. Common manifestations included pain in the lower limbs (94%, 17/18), abnormal gait (89%, 16/18), genu valgum (89%, 16/18), reduced subcutaneous fat (78%, 14/18), delayed puberty (73%, 8/11), muscle weakness (67%, 12/18), hearing loss (39%, 7/18), hepatosplenomegaly (39%, 7/18), exophthalmos or impaired vision or visual field defect (33%, 6/18), and anemia (33%, 7/18). Twenty-five percent (4/16) of patients had short stature. Serum level of alkaline phosphatase was elevated in 41% (7/17) of patients whereas beta-C-terminal telopeptide was elevated in 91% of patients (10/11). Among 12 patients, the Z-scores of two patients were greater than 2.5 at the femur neck and the Z-scores of five patients were lower than -2.5 at the femur neck and/or lumbar spine. HR-pQCT results showed lower volumetric BMD (vBMD), altered bone microstructure and lower estimated bone strength at the distal radius and tibia in patients with CED compared with controls. In addition, total volume bone mineral density and cortical volumetric bone mineral density at the radius were negatively correlated with age in patients with CED, but positively correlated with age in controls. In conclusion, the largest case series of CED with characterized clinical features in a Chinese population was reported here. In addition, HR-pQCT was used to investigate bone microstructure at the distal radius and tibia in nine patients with CED, and the alteration of bone density, microstructure, and strength was shown for the first time. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4436DOI Listing
January 2022

Low Levels of Serum Sclerostin in Adult Patients With Tumor-Induced Osteomalacia Compared With X-linked Hypophosphatemia.

J Clin Endocrinol Metab 2022 01;107(1):e361-e371

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

Context: Sclerostin inhibits Wnt-β-catenin signaling, regulating bone formation. Circulating sclerostin was reported to be elevated in X-linked hypophosphatemia (XLH) patients, and sclerostin antibody (Scl-Ab) increased bone mass and normalized circulating phosphate in Hyp mice. However, circulating sclerostin levels in patients with acquired hypophosphatemia due to tumor-induced osteomalacia (TIO) are rarely reported.

Objective: This study was designed to evaluate serum sclerostin levels in TIO patients compared with age- and sex-matched healthy controls and XLH patients to analyze correlations with bone mineral density (BMD) and laboratory parameters.

Methods: This cross-sectional study determined serum sclerostin levels in 190 individuals, comprising 83 adult TIO patients, 83 adult healthy controls and 24 adult XLH patients.

Results: TIO patients (43 male, 40 female) aged 44.3 ± 8.7 (mean ± SD) years had lower levels of circulating sclerostin than controls (94.2 ± 45.8 vs 108.4 ± 42.3 pg/mL, P = 0.01), adjusted for age, gender, BMI, and diabetes rate. Sclerostin levels were positively associated with age (r = 0.238, P = 0.030). Male patients had higher sclerostin than female patients (104.7 ± 47.3 vs 83.0 ± 41.8 pg/mL, P = 0.014). Sclerostin levels were positively associated with L1-4 BMD (r = 0.255, P = 0.028), femoral neck BMD (r = 0.242, P = 0.039), and serum calcium (r = 0.231, P = 0.043). Comparison of sclerostin levels in TIO patients (n = 24, age 35.9 ± 7.3 years) vs XLH patients vs healthy controls revealed significant differences (respectively, 68.4 ± 31.3, 132.0 ± 68.8, and 98.6 ± 41.1 pg/mL, P < 0.001).

Conclusion: Circulating sclerostin was decreased in TIO patients but increased in XLH patients, possibly due to histological abnormality and bone mass.
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http://dx.doi.org/10.1210/clinem/dgab579DOI Listing
January 2022

Biodegradable magnesium combined with distraction osteogenesis synergistically stimulates bone tissue regeneration via CGRP-FAK-VEGF signaling axis.

Biomaterials 2021 08 23;275:120984. Epub 2021 Jun 23.

Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong SAR, China; CHUK Hong Kong - Shenzhen Innovation and Technology Institute (Futian), China. Electronic address:

Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union. Here, we demonstrated that magnesium (Mg) nail implantation into the marrow cavity degraded gradually accompanied with about 4-fold increase of new bone formation and over 5-fold of new vessel formation as compared with DO alone group in the 5 mm femoral segmental defect rat model at 2 weeks after distraction. Mg nail upregulated the expression of calcitonin gene-related peptide (CGRP) in the new bone as compared with the DO alone group. We further revealed that blockade of the sensory nerve by overdose capsaicin blunted Mg nail enhanced critical size bone defect repair during the DO process. CGRP concentration-dependently promoted endothelial cell migration and tube formation. Meanwhile, CGRP promoted the phosphorylation of focal adhesion kinase (FAK) at Y397 site and elevated the expression of vascular endothelial growth factor A (VEGFA). Moreover, inhibitor/antagonist of CGRP receptor, FAK, and VEGF receptor blocked the Mg nail stimulated vessel and bone formation. We revealed, for the first time, a CGRP-FAK-VEGF signaling axis linking sensory nerve and endothelial cells, which may be the main mechanism underlying Mg-enhanced critical size bone defect repair when combined with DO, suggesting a great potential of Mg implants in reducing DO treatment time for clinical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120984DOI Listing
August 2021

Early Discrimination Between Tumor-Induced Rickets/Osteomalacia and X-Linked Hypophosphatemia in Chinese Children and Adolescents: A Retrospective Case-Control Study.

J Bone Miner Res 2021 09 19;36(9):1739-1748. Epub 2021 May 19.

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

In children and adolescents, distinguishing tumor-induced rickets/osteomalacia (TIR/O) from hereditary hypophosphatemic rickets/osteomalacia (HR/O) is a medical challenge. We retrospectively studied 10 Chinese children and adolescents with TIR/O who underwent surgery at a mean age of 17.4 ± 2.1 years and compared their characteristics to 24 age- and sex-matched patients with X-linked hypophosphatemia (XLH). Positive family history of HR/O and dental problems, such as enamel hypoplasia and dental abscess, were reported in 8 (33.3%) and 5 (20.8%) patients with XLX, respectively, but not in patients with TIR/O. In addition, in comparison with XLH patients, TIR/O patients had an older disease onset age (150 versus 24 months, p < 0.001), a higher height standard deviation score (SDS; -1.2 ± 1.8 versus -4.0 ± 1.4, p < 0.001), a lower Z-score of bone mineral density (BMD) at lumbar spine (LS) (-3.9 [6.0] versus +1.8 [7.0], p < 0.001), and a higher serum intact fibroblast growth factor 23 (FGF23) level (500.27 ± 87.20 versus 121.71 ± 70.94 pg/mL, p < 0.001), corresponding to a lower serum phosphate level (0.52 ± 0.07 versus 0.64 ± 0.11 mmol/L, p = 0.005) and a higher serum alkaline phosphatase (ALP) level (557 [631] versus 305 [249] U/L, p = 0.005). We generated receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). The AUCs of onset age, FGF23, and LS Z-score were equal to 1, suggesting that these are excellent indices for the differential diagnosis between TIR/O and XLH. In summary, our study furthers our understanding of the spectrum of clinical, biochemical, and pathologic findings associated with TIR/O. For children and adolescent patients with HR/O, a comprehensive and careful clinical and laboratory evaluation is of great importance, and we recommend enquiry of the family history, onset age, and dental problems, as well as measurement of serum FGF23 and BMD. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4331DOI Listing
September 2021

Molecular characterization of the Yp11.2 region deletion in the Chinese Han population.

Int J Legal Med 2021 Jul 26;135(4):1351-1358. Epub 2021 Apr 26.

Jining Medical University, Jining, 272067, China.

The Y chromosome is male-specific and is important for spermatogenesis and male fertility. However, the Y chromosome is poorly characterized due to massive palindromes and inverted repeats, which increase the likelihood of genomic rearrangements, resulting in short tandem repeats on the Y chromosome or long fragment deletions. The present study reports a large-scale (2.573~2.648 Mb) deletion in the Yp11.2 region in a Chinese population based on the analysis of 34 selected Y-specific sequence-tagged sites and subsequent sequencing of the breakpoint junctions on the Y chromosome from 5,068,482-5,142,391 bp to 7,715,462-7,716,695 bp. The results of sequence analysis indicated that the deleted region included part or all of the following five genes: PCDH11Y, TSPY, AMELY, TBL1Y, and RKY. These genes are associated with spermatogenesis or amelogenesis and various other processes; however, specific physiological functions and molecular mechanisms of these genes remain unclear. Notably, individuals with this deletion pattern did not have an obvious pathological phenotype but manifested some degree of amelogenesis imperfecta.
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http://dx.doi.org/10.1007/s00414-021-02596-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205872PMC
July 2021

GM130 regulates pulmonary surfactant protein secretion in alveolar type II cells.

Sci China Life Sci 2022 01 16;65(1):193-205. Epub 2021 Mar 16.

Department of Health Sciences, Institute of Physical Science and Information Technology, Anhui University, Hefei, 230601, China.

Pulmonary surfactant is a lipid-protein complex secreted by alveolar type II epithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier. The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking. However, the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear. In the present study, deletion of GM130, which encodes for a matrix protein of the cis-Golgi cisternae, was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids. Specifically, the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum, Sftpb and Sftpc accumulation in the Golgi apparatus, and an increase in the compensatory secretion of Sftpd. Moreover, global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy; however, surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice. Therefore, our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.
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http://dx.doi.org/10.1007/s11427-020-1875-xDOI Listing
January 2022

Proliferation of MDA-MB-231 can be suppressed by dimeric-epigallocatechin gallate through competitive inhibition of amphiregulin-epidermal growth factor receptor signaling.

Anticancer Drugs 2021 06;32(6):647-656

Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University.

Triple-negative breast cancer (TNBC) is highly aggressive, with high rates of early relapse and very poor overall prognosis. Amphiregulin (AREG) is the most abundant epidermal growth factor receptor (EGFR) agonist in MDA-MB-231 TNBC cells, whose proliferation can be inhibited by (-)-epigallocatechin gallate (EGCG), a constituent of green tea that is prone to oxidative polymerization. The effect of dimeric-EGCG, a dimer of oxidized and polymerized EGCG, on MDA-MB-231 cell the proliferation warrants further exploration. In the present study, MTT, flow cytometry, migration scratch, transwell, western blotting, and surface plasmon resonance assays were used to evaluate the effect of dimeric-EGCG on MDA-MB-231 cells and explore the underlying mechanism. MDA-MB-231 cell proliferation and migration were significantly inhibited by dimeric-EGCG at concentrations as low as 10 μM. Levels of EGFR and p44/42 MAPK phosphorylation in MDA-MB-231 cells were significantly reduced by treatment with 10 μM dimeric-EGCG (P < 0.01). In addition, the levels of phosphorylation induced by exogenous AREG were also inhibited by dimeric-EGCG (P < 0.01); however, no significant effects of dimeric-EGCG were observed on epidermal growth factor or transforming growth factor-alpha signaling. Surface plasmon resonance analysis demonstrated that 10 μM dimeric-EGCG bound directly to the extracellular domain of EGFR, competitively inhibiting the binding of AREG to EGFR. These results suggest a novel mechanism underlying the inhibitory effect of dimeric-EGCG on MDA-MB-231 cells, with potential application in the development of drugs for the treatment of TNBC.
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http://dx.doi.org/10.1097/CAD.0000000000001038DOI Listing
June 2021

Demethylation alters transcriptome profiling of buds and leaves in 'Kyoho' grape.

BMC Plant Biol 2020 Dec 4;20(1):544. Epub 2020 Dec 4.

Key Laboratory of Genetics and Fruit Development, College of Horticultural, Nanjing Agricultural University, Nanjing, China.

Background: Grape buds and leaves are directly associated with the physiology and metabolic activities of the plant, which is monitored by epigenetic modifications induced by environment and endogenous factors. Methylation is one of the epigenetic regulators that could be involved in DNA levels and affect gene expression in response to stimuli. Therefore, changes of gene expression profile in leaves and bud through inhibitors of DNA methylation provide a deep understanding of epigenetic effects in regulatory networks.

Results: In this study, we carried out a transcriptome analysis of 'Kyoho' buds and leaves under 5-azacytidine (5-azaC) exposure and screened a large number of differentially expressed genes (DEGs). GO and KEGG annotations showed that they are mainly involved in photosynthesis, flavonoid synthesis, glutathione metabolism, and other metabolic processes. Functional enrichment analysis also provided a holistic perspective on the transcriptome profile when 5-azaC bound to methyltransferase and induced demethylation. Enrichment analysis of transcription factors (TFs) also showed that the MYB, C2H2, and bHLH families are involved in the regulation of responsive genes under epigenetic changes. Furthermore, hormone-related genes have also undergone significant changes, especially gibberellin (GA) and abscisic acid (ABA)-related genes that responded to bud germination. We also used protein-protein interaction network to determine hub proteins in response to demethylation.

Conclusions: These findings provide new insights into the establishment of molecular regulatory networks according to how methylation as an epigenetic modification alters transcriptome patterns in bud and leaves of grape.
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http://dx.doi.org/10.1186/s12870-020-02754-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716455PMC
December 2020

Transcriptome analysis of strawberry fruit in response to exogenous arginine.

Planta 2020 Oct 10;252(5):82. Epub 2020 Oct 10.

Key Laboratory of Genetics and Fruit Development, Horticultural College, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.

Main Conclusion: Transcriptome and physiological analysis showed that exogenous arginine can delay the ripening process of postharvest strawberry fruit. Arginine (Arg) plays an important role in the growth and development of plants, but its growth and development regulatory mechanisms in strawberry fruit are unknown. In this study, we found that the content of Arg decreased after the onset of fruit coloration and exogenous Arg inhibited fruit coloration. We comprehensively analyzed the transcriptome of 'Sweet Charlie' strawberry fruit with or without Arg treatment and identified a large number of differential genes and metabolites. Based on the transcriptome data, we also found that Arg inhibited ripening, which coincided with changes in several physiological parameters and their corresponding gene transcripts, including firmness, anthocyanin content, sugar content, Arg content, indole-acetic acid (IAA) content, abscisic acid (ABA) content, and ethylene emissions. We also found that Arg induced the expression of heat-shock proteins (HSPs) and antioxidant enzyme genes, which improved strawberry stress resistance. This study elucidated the molecular mechanism by which exogenous Arg delays strawberry fruit ripening, providing some genetic information to help guide the future improvement and cultivation of strawberry.
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http://dx.doi.org/10.1007/s00425-020-03489-wDOI Listing
October 2020

Antidementia effects, metabolic profiles and pharmacokinetics of GJ-4, a crocin-rich botanical candidate from .

Food Funct 2020 Oct;11(10):8825-8836

Institute of TCM & Natural Products, College of Pharmacy, Jinan University, Guangzhou 510623, People's Republic of China.

Crocins, a series of hydrophilic carotenoids that are either mono- or di-glycosyl polyene esters of crocetin extracted from dried saffron stigma or fruits of gardenia, are attracting much attention due to their wide range of pharmacological effects. In our previous study, GJ-4, a mixture of crocin analogues, was obtained and derived from gardenia fruits. Mainly 18 crocin analogues were identified from GJ-4 and found to exhibit neuroprotective effects in in vitro and in vivo models. In this present study, we continue to investigate the therapeutic effects of GJ-4 on learning and memory impairments in a 2VO-induced VaD model, and the potential mechanism. In addition, the metabolic profiles and pharmacokinetic properties of GJ-4 were determined using liquid chromatography-electrospray ionization-mass spectrometry after single and multiple oral doses. All these findings presented here will serve as a solid basis to develop GJ-4 as a new therapeutic agent for dementia.
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http://dx.doi.org/10.1039/d0fo01678kDOI Listing
October 2020

Chitosan induces jasmonic acid production leading to resistance of ripened fruit against Botrytis cinerea infection.

Food Chem 2021 Feb 4;337:127772. Epub 2020 Aug 4.

Key Laboratory of Genetics and Fruit Development, Horticultural College, Nanjing Agricultural University, Nanjing, China. Electronic address:

Chitosan can function a key role in plant resistant against Botrytis cinerea infection, while its mechanism is unclear in ripened fruits. In this study, we investigated the chitosan effect on two type of ripened fruits including strawberry and grapes (Kyoho and Shine-Muscat) when were infected with B. cinerea. Results showed that chitosan inhibited B. cinerea growth, increased phenolic compounds and cell wall composition, modulated oxidative stress and induced jasmonic acid (JA) production in ripened fruits. Data-independent acquisition (DIA) showed that 224 and 171 proteins were upregulated 1.5-fold by chitosan in Kyoho and Shine-Muscat grape, respectively. Topless-related protein 3 (TPR3) were identified and interacted with histone deacetylase 19 (HDAC19) and negatively regulated by JA and chitosan. Meanwhile, overexpression of VvTPR3 and VvHDAC19 reduced the stability of cell wall against B. cinerea in strawberry. Taken together, chitosan induces defense related genes and protect the fruit quality against Botrytis infection through JA signaling.
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http://dx.doi.org/10.1016/j.foodchem.2020.127772DOI Listing
February 2021

Sumoylation enhances the activity of the TGF-β/SMAD and HIF-1 signaling pathways in keloids.

Life Sci 2020 Aug 29;255:117859. Epub 2020 May 29.

Department of Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. Electronic address:

Excessive fibrosis and extracellular matrix deposition resulting from upregulation of target genes expression mediated by transforming growth factor-beta (TGF-β)/SMAD and hypoxia inducible factor-1 (HIF-1) signaling pathways are the main mechanisms that drive keloid formation. Sumoylation is a protein posttranslational modification that regulates the function of proteins in many biological processes. In the present study, we aimed to investigate the mechanism underlying the effects of sumoylation on the TGF-β/SMAD and HIF-1 signaling pathways in keloids. We used 2-D08 to block sumoylation and silenced the expression of sentrin sumo-specific protease 1 (SENP1) to enhance sumoylation in human foreskin fibroblasts (HFFs) and human keloid fibroblasts (HKFs). We also reduced and increased intracellular SUMO1 levels by silencing SUMO1 and transfecting cells with a SUMO1 overexpression lentivirus, respectively. Sumoylation has the ability to amplify TGF-β/SMAD and HIF-1 signals in keloids, while SUMO1, especially the SUMO1-RanGAP1 complex, is the key molecule affecting the TGF-β/SMAD and HIF-1 signaling pathways. In addition, we also found that hypoxia promotes sumoylation in keloids and that HIF-1α is covalently modified by SUMO1 at Lys 391 and Lys 477 in HKFs. In summary, we elucidated the role and molecular mechanism of sumoylation in the formation of keloids, providing a new perspective for a potential therapeutic target of keloids.
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http://dx.doi.org/10.1016/j.lfs.2020.117859DOI Listing
August 2020

TM4SF1 involves in miR-1-3p/miR-214-5p-mediated inhibition of the migration and proliferation in keloid by regulating AKT/ERK signaling.

Life Sci 2020 Aug 3;254:117746. Epub 2020 May 3.

Department of Plastic Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Aims: Transmembrane 4 L six family member 1 (TM4SF1) is a small plasma membrane glycoprotein that is highly expressed in cancers. However, the role of TM4SF1 that plays in keloids remains unknown. We investigated the expression, function and the microRNA (miRNA) regulatory network of TM4SF1 in keloids.

Main Methods: Small interfering RNAs and lentivirus were used to alter the expression of TM4SF1 in fibroblasts. Dual-luciferase reporter assays were applied to determine the miRNA targets. Immunohistochemistry, western blotting, qRT-PCR, wound healing assays, Transwell assays, cell count kit-8 assays and flow cytometry were also employed in this study.

Key Findings: TM4SF1 was frequently upregulated in human keloid fibroblasts (HKFs) compared with human normal skin fibroblasts (HSFs). The downregulation of TM4SF1 significantly inhibited proliferation and migration, and induced apoptosis in HKFs. Furthermore, si-TM4SF1 inhibited the AKT/ERK signaling. Meanwhile, the upregulation of TM4SF1 promoted proliferation, migration and the activation of AKT/ERK signaling in human foreskin fibroblasts (HFF-1). Moreover, TM4SF1 can be regulated by miRNAs, which have been validated to play important roles in keloids by posttranscriptional regulation of gene expression. After screening, we found miR-1-3p and miR-214-5p targeted TM4SF1, inhibited TM4SF1 expression, cell proliferation, migration, and induced apoptosis in HKFs. And the level of miR-1-3p and miR-214-5p were found lower in HKFs than in HSFs.

Significance: Our study demonstrates a novel regulatory mechanism by which miR-1-3p, miR-214-5p, and TM4SF1 are involved in proliferation, cell motility, and apoptosis, suggesting that they may be potential targets in therapies for keloids.
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http://dx.doi.org/10.1016/j.lfs.2020.117746DOI Listing
August 2020

Defective O-glycosylation of novel FGF23 mutations in a Chinese family with hyperphosphatemic familial tumoral calcinosis.

Bone 2020 08 1;137:115401. Epub 2020 May 1.

Department of Endocrinology, NHC Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address:

Objectives: Hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome (HFTC/HHS) is a rare disorder caused by deficiency or resistance of fibroblast growth factor 23 (FGF23). Here we reported a Chinese family with HFTC/HHS, aiming at clarifying the clinical features, bone microarchitectures and molecular mechanisms of the disease.

Methods: Clinical manifestations, laboratory examinations and genetic analyses were collected from two HFTC patients. Bone microarchitectures were detected by HR-pQCT. In vitro expression and glycosylation of mutant and wild-type FGF23 proteins were analyzed by western blotting and wheat germ agglutinin affinity chromatography. Subcellular localizations of FGF23 proteins were detected by immunocytochemistry.

Results: The two brothers carried previously unreported c.413T > G, p.Leu138Arg and c.491T > A, p.Ile164Asn compound heterozygous variants in the FGF23 gene, which was "likely pathogenic" according to American College of Medical Genetics (ACMG) Standards and Guidelines. Both patients had severe hyperphosphatemia and significantly elevated C-terminal FGF23. With HHS, patient 1 presented with lower extremity pain and widespread cardiovascular calcification. HR-pQCT of his distal radius and tibia revealed decreased volume BMD and cortical thickness, which were inconsistent with hyperostosis manifestations in X-ray. He received etidronate treatment, which improved his BMD and the ectopic calcification. His brother exhibited less bone involvement but had experienced recurrent painful calcified mass from a young age and undergone several resections. In vitro experiments showed that the mutant FGF23 proteins had defective O-glycosylation and impaired secretion. However, no difference in subcellular localization was found between the wild-type and mutant FGF23 proteins.

Conclusion: We have presented a Chinese HFTC/HHS family with novel FGF23 c.413T > G, p.Leu138Arg and c.491T > A, p.Ile164Asn variants. We clarified the bone microarchitectures of HFTC/HHS patients by HR-pQCT, and expanded the genotype-phenotype spectrum of the disease. In vivo studies suggested that O-glycosylation of FGF23 plays an important role in the pathogenesis of HFTC/HHS, providing further understanding of the disease mechanism.
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http://dx.doi.org/10.1016/j.bone.2020.115401DOI Listing
August 2020

Triacontanol Promotes the Fruit Development and Retards Fruit Senescence in Strawberry: A Transcriptome Analysis.

Plants (Basel) 2020 Apr 10;9(4). Epub 2020 Apr 10.

Key Laboratory of Genetics and Fruit Development, Horticultural College, Nanjing Agricultural University, Nanjing 210095, China.

Triacontanol (TA) is a non-toxic, pollution-free, low-cost, high-efficiency, broad-spectrum plant growth regulator that plays an important role in plant growth and development, but its regulation mechanism of strawberry (Sweet charlie, × Duch.) fruit development is still unclear. In this study, we showed that TA treatment (50 μM) could promote fruit development by up-regulating factors related to fruit ripening-related growth and development. TA increased fruit sugar content and anthocyanin accumulation, and many stress-related enzyme activities. In the meantime, Illumina RNA-Seq technology was used to evaluate the effect of TA treatment on strawberry fruit senescence. The results showed that 9338 differentially expressed genes (DEGs) were obtained, including 4520 up-regulated DEGs and 4818 down-regulated DEGs. We performed gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these DEGs. The results showed that TA treatment caused changes in transcript levels related to cellular processes, hormones and secondary metabolism, such as DNA metabolic processes, flavonoid synthesis, and plant hormone signal transduction. Bioinformatics analysis showed that many transcription factors were related to fruit maturity. Taken together, this study will provide new insights into the mechanism of strawberry development and postharvest response to TA treatment.
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http://dx.doi.org/10.3390/plants9040488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238246PMC
April 2020

Population genetic data from 23 autosomal STR loci of Huaxia Platinum system in the Jining Han population.

Mol Genet Genomic Med 2020 04 29;8(4):e1142. Epub 2020 Jan 29.

Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong, PR China.

Background: Genetic polymorphisms at 23 short tandem repeat (STR) loci were investigated in 1,215 Jining Han individuals from Jining city, Shandong province, eastern China.

Methods: We used population genetic data of 23 autosomal STR loci included in the Huaxia Platinum system to evaluate 1,215 unrelated Chinese Han individuals in the Jining Han population. Allele frequencies and forensic parameters of the STR loci were determined and genetic relationships among the Jining Han and other Chinese populations were evaluated.

Results: In total, we observed 321 alleles, with frequencies ranging from 0.00041 to 0.52222. The combined discrimination power and probability of excluding paternity were 0.99999999999999999999999999919 and 0.99999999962, respectively. No deviations from HWE were observed at any loci. Population comparisons showed that the Xinjiang groups (Uyghur and Kazakh) and the Mongolian and Tibetan groups were isolated, while the Jining Han population clustered together with other populations, except the Guizhou Han population.

Conclusion: This study demonstrated that 23 autosomal STR loci included in the Huaxia Platinum system are highly polymorphic and suitable for personal forensic identification and paternity testing in this population.
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http://dx.doi.org/10.1002/mgg3.1142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196486PMC
April 2020

Monoterpene glycosides with anti-inflammatory activity from Paeoniae Radix.

Fitoterapia 2019 Oct 6;138:104290. Epub 2019 Aug 6.

Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drug Research, Jinan University, Guangzhou 510632, China. Electronic address:

Six new monoterpene glycosides, named 6'-O-nicotinoylalbiflorin (1), 4'-O-vanillylalbiflorin (2), paeonidanin L (3), paeoniflorigenin-1-O-β-d-xyloside (4), 6'-(2-hydroxypropanoyl)-paeoniflorin (5), oxylactiflorin (6), together with 16known ones (7-22) were isolated from the 70% ethanol extract of Paeoniae Radix. Their structures were elucidated based on spectroscopic analysis (1D and 2D NMR, HRESIMS, IR and UV), chemical evidences and comparison with literatures. The inhibitory effects of all the isolates were evaluated against lipopolysaccharide (LPS) stimulated PGE production in RAW 264.7 macrophages.
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http://dx.doi.org/10.1016/j.fitote.2019.104290DOI Listing
October 2019

The first case of primary hypertrophic osteoarthropathy with soft tissue giant tumors caused by HPGD loss-of-function mutation.

Endocr Connect 2019 Jun;8(6):736-744

Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Background: Primary hypertrophic osteoarthropathy (PHO) is a rare genetic multi-organic disease characterized by digital clubbing, periostosis and pachydermia. Two genes, HPGD and SLCO2A1, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and prostaglandin transporter (PGT), respectively, have been reported to be related to PHO. Deficiency of aforementioned two genes leads to failure of prostaglandin E2 (PGE2) degradation and thereby elevated levels of PGE2. PGE2 plays an important role in tumorigenesis. Studies revealed a tumor suppressor activity of 15-PGDH in tumors, such as lung, bladder and breast cancers. However, to date, no HPGD-mutated PHO patients presenting concomitant tumor has been documented. In the present study, we reported the first case of HPGD-mutated PHO patient with soft tissue giant tumors at lower legs and evaluated the efficacy of selective COX-2 inhibitor (etoricoxib) treatment in the patient.

Methods: In this study, we summarized the clinical data, collected the serum and urine samples for biochemical test and analyzed the HPGD gene in our patient.

Results: A common HPGD mutation c.310_311delCT was identified in the patient. In addition to typical clinical features (digital clubbing, periostosis and pachydermia), the patient demonstrated a new clinical manifestation, a giant soft tissue tumor on the left lower leg which has not been reported in HPGD-mutated PHO patient before. After 6-month treatment with etoricoxib, the patient showed decreased PGE2 levels and improved PHO-related symptoms. Though the soft tissue tumor persisted, it seemed to be controlled under the etoricoxib treatment.

Conclusion: This finding expanded the clinical spectrum of PHO and provided unique insights into the HPGD-mutated PHO.
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http://dx.doi.org/10.1530/EC-19-0149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547301PMC
June 2019

Clinical and genetic analysis in a large Chinese cohort of patients with X-linked hypophosphatemia.

Bone 2019 04 23;121:212-220. Epub 2019 Jan 23.

Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Shuaifuyuan No. 1, Wangfujing, Dongcheng District, Beijing 100730, China. Electronic address:

X-linked Hypophosphatemia (XLH) is caused by loss of function mutations in the PHEX gene. Given the recent availability of a new therapy for XLH, a retrospective analysis of the most recent 261 Chinese patients with XLH evaluated at Peking Union Medical College Hospital was conducted. Clinical, biochemical, radiographic studies, as well as genetic analyses, including Sanger sequencing for point mutations and Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large deletions/duplications were employed. Based on the structure of Neprilysin (NEP), a member of M13 family that includes PHEX, a three-dimensional (3D) model of PHEX was constructed, missense and nonsense mutations were positioned on the predicted structure to visualize relative positions of these two types of variants. Sex differences and genotype-phenotype correlations were also undertaken. Genetic analyses identified 166 PHEX mutations in 261 XLH patients. One hundred and eleven of the 166 mutations were unreported. Four mutational 'hot-spots' were identified in this cohort (P534L, G579R, R747X, c.1645+1 G>A). Missense mutations, but not nonsense mutations, clustered in the two putative lobes of the PHEX protein, suggesting these are functionally important regions of the molecule. Circulating levels of intact FGF23 were significantly elevated (median level 101.9 pg/mL; reference range 16.1-42.2 pg/mL). No significant sex differences, as well as no phenotypic differences were identified between patients with putative truncating and non-truncating PHEX mutations. However, patients with N-terminal PHEX mutations had an earlier age of onset of disease (P = 0.015) and higher iFGF23 levels (P = 0.045) as compared to those with C-terminal mutations. These data provide a comprehensive characterization of the largest cohort of patients with XLH reported to date from China, which will help in evaluating the applicability of emerging therapies for this disease in this ethnic group.
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http://dx.doi.org/10.1016/j.bone.2019.01.021DOI Listing
April 2019

MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts.

BMB Rep 2019 Mar;52(3):202-207

Department of Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Keloids are the most common pathological form of trauma healing, with features that seriously affect appearance and body function, are difficult to treat and have a high recurrence rate. Emerging evidence suggests that miRNAs are involved in a variety of pathological processes and play an important role in the process of fibrosis. In this study, we investigated the function and regulatory network of miR-152-5p in keloids. The miRNA miR-152-5p is frequently downregulated in keloid tissue and primary cells compared to normal skin tissue and fibroblasts. In addition, the downregulation of miR-152-5p is significantly associated with the proliferation, migration and apoptosis of keloid cells. Overexpression of miR-152-5p significantly inhibits the progression of fibrosis in keloids. Smad3 is a direct target of miR-152-5p, and knockdown of Smad3 also inhibits fibrosis progression, consistent with the overexpression of miR-152-5p. The interaction between miR-152-5p and Smad3 occurs through the Erk1/2 and Akt pathways and regulates collagen3 production. In summary, our study demonstrates that miR-152-5p/Smad3 regulatory pathways involved in fibrotic progression may be a potential therapeutic target of keloids. [BMB Reports 2019; 52(3): 202-207].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476487PMC
March 2019
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