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1.
Acta Biomater ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34852300

RESUMO

Ligament injuries are common in sports and other rigorous activities. It is a great challenge to achieve ligament regeneration after an injury due the avascular structure and low self-renewal capability. Herein, we developed vascular endothelial growth factor (VEGF)-binding aligned electrospun poly(caprolactone)/gelatin (PCL/Gel) scaffolds by incorporating prominin-1-binding peptide (BP) sequence and exploited them for patellar ligament regeneration. The adsorption of BP onto scaffolds was discerned by various techniques, such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscope. The accumulation of VEGF onto scaffolds correlated with the concentration of the peptide in vitro. BP-anchored PCL/Gel scaffolds (BP@PCL/Gel) promoted the tubular formation of human umbilical vein endothelial cells (HUVECs) and wound healing in vitro. Besides, BP containing scaffolds exhibited higher content of CD31+ cells than that of the control scaffolds at 1 week after implantation in vivo. Moreover, BP containing scaffolds improved biomechanical properties and facilitated the regeneration of matured collagen in patellar ligament 4 weeks after implantation in mice. Overall, this strategy of peptide-mediated orchestration of VEGF provides an enticing platform for the ligament regeneration, which may also have broad implications for tissue repair applications. STATEMENT OF SIGNIFICANCE: Ligament injuries are central to sports and other rigorous activities. Given to the avascular nature and poor self-healing capability of injured ligament tissues, it is a burgeoning challenge to fabricate tissue-engineered scaffolds for ligament reconstruction. Vascular endothelial growth factor (VEGF) is pivotal to the neo-vessel formation. However, the high molecular weight of VEGF as well as its short half-life in vitro and in vivo limits its therapeutic potential. To circumvent these limitations, herein, we functionalized aligned electrospun polycaprolactone/gelatin (PCL/Gel)-based scaffolds with VEGF-binding peptide (BP) and assessed their biocompatibility and performance in vitro and in vivo. BP-modified scaffolds accumulated VEGF, improved tube formation of HUVECs, and induced wound healing in vitro, which may have broad implications for regenerative medicine and tissue engineering.

2.
Food Chem ; 376: 131868, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34968904

RESUMO

In this work, we design a sensitive and quantitative on-site detecting solution for Aflatoxin B1 (AFB1), Ochratoxin A (OTA) and Zearalenone (ZEN) as often found in moldy grains and harmful to human health. Using quantum dot microsphere-based immunochromatography test strip, the proposed method can sensitively detect AFB1, OTA and ZEN in low detection limits of 0.01 ng/mL, 0.2 ng/mL and 0.032 ng/mL, and quantitatively measure their concentrations from 0.01 ng/mL to 1 ng/mL, from 0.2 ng/mL to 200 ng/mL and from 0.032 ng/mL to 32 ng/mL in high accuracy and good selectivity. More importantly, these multiple mycotoxin detections only relying on simple manual operations and portable handheld test strip reader can be finished on site within 45 min. Therefore, the proposed method is a promising solution supporting sensitive and quantitative on-site detections for multiple mycotoxins.

3.
Oxid Med Cell Longev ; 2021: 6715758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777691

RESUMO

Age-associated decline in retina function is largely responsible for the irreversible vision deterioration in the elderly population. It is also an important risk factor for the development of degenerative and angiogenic diseases. However, the molecular mechanisms involved in the process of aging in the retina remain largely elusive. This study investigated the role of mTORC1 signaling in aging of the retina. We showed that mTORC1 was activated in old-aged retina, particularly in the ganglion cells. The role of mTORC1 activation was further investigated in Chx10-Cre;Tsc1fx/fx mouse (Tsc1-cKO). Activation of mTORC1 was found in bipolar and some of the ganglion and amacrine cells in the adult Tsc1-cKO retina. Bipolar cell hypertrophy and Müller gliosis were observed in Tsc1-cKO since 6 weeks of age. The abnormal endings of bipolar cell dendritic tips at the outer nuclear layer resembled that of the old-aged mice. Microglial cell activation became evident in 6-week-old Tsc1-cKO. At 5 months, the Tsc1-cKO mice exhibited advanced features of old-aged retina, including the expression of p16Ink4a and p21, expression of SA-ß-gal in ganglion cells, decreased photoreceptor cell numbers, decreased electroretinogram responses, increased oxidative stress, microglial cell activation, and increased expression of immune and inflammatory genes. Inhibition of microglial cells by minocycline partially prevented photoreceptor cell loss and restored the electroretinogram responses. Collectively, our study showed that the activation of mTORC1 signaling accelerated aging of the retina by both cell autonomous and nonautonomous mechanisms. Our study also highlighted the role of microglia cells in driving the decline in retina function.

4.
Macromol Biosci ; : e2100342, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706143

RESUMO

Recently, various tissue engineering based strategies have been pursued for the regeneration of tracheal tissues. However, previously developed tracheal scaffolds do not accurately mimic the microstructure and mechanical behavior of the native trachea, which restrict their clinical translation. Here, tracheal scaffolds are fabricated by using 3D printing and short nanofibers (SF) dispersion of poly(l-lactide)/gelatin (0.5-1.5 wt%) to afford tracheal constructs. The results display that the scaffolds containing 1.0 wt % of SF exhibit low density, good water absorption capacity, reasonable degradation rate, and stable mechanical properties, which were comparable to the native trachea. Moreover, the designed scaffolds possess good biocompatibility and promote the growth and infiltration of chondrocytes in vitro. The biocompatibility of tracheal scaffolds is further assessed after subcutaneous implantation in mice for up to 4 and 8 weeks. Histological assessment of tracheal constructs explanted at week 4 shows that scaffolds can maintain their structural integrity and support the formation of neo-vessels. Furthermore, cell-scaffold constructs gradually form cartilage-like tissues, which mature with time. Collectively, these engineered tracheal scaffolds not only possess appropriate mechanical properties to afford a stabilized structure but also a biomimetic extracellular matrix-like structure to accomplish tissue regeneration, which may have broad implications for tracheal regeneration.

5.
STAR Protoc ; 2(4): 100814, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34585155

RESUMO

N-Methyl-N-nitrosourea, an N-nitroso compound converted from dietary nitrite by Helicobacter pylori, causes somatic mutations in epithelial cells and induces gastric premalignancy. Here, we describe a detailed protocol for induction of gastric tumor and analysis of tumor phenotypes in mice. This model can be widely used for studying the initiation and growth of gastric cancer. For complete details on the use and execution of this protocol, please refer to Li et al. (2021).

6.
Sci Total Environ ; 789: 148003, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34323836

RESUMO

Following implementation of the most stringent clean air policy in China, the emissions of NOx, SO2, and fine particles have greatly reduced since 2013. However, the emissions of polycyclic aromatic hydrocarbons (PAHs), which are highly toxic pollutants, and their spatiotemporal changes remain unclear. In this study, a 0.05° × 0.05° gridded PAH emission inventory was developed for mainland China during 2013-2017. The results show that the total PAH emissions have decreased from 112.92 Gg in 2013 to 100.09 Gg in 2017, with the fastest declines in the industrial (17.32%) and residential/commercial (10.58%) sectors. However, the decline in the PAH emissions is smaller than that of the NOX and SO2 emissions. The average emission density of PAHs in mainland China in 2017 was 10.43 kg/km2. North and East China have the largest PAH emissions. The residential/commercial, industrial, and transportation sectors are the major emission sources, accounting for 48.59%, 29.26%, and 17.21%, respectively. Carcinogenic PAH emissions accounted for 7.49% in mainland China, higher than those of developed countries (5.73%) and the global average (6.19%). Differences in the energy structures lead to significant differences in the spatial distribution of PAH emissions in various sectors. From 2013 to 2017, the emissions declined in most Chinese regions. The emission density in East China decreased the most, reaching 3.39 kg/km2, followed by North China (2.91 kg/km2). The magnitude of the decline in the PAH emissions and reasons for the decline significantly differ in different regions. Particular attention must be paid to the limited decline (5.22%) in Northwest China over the study period. Although China's emission density has been declining, it is still significantly higher than the global average. Therefore, China must further reduce the PAH emissions through technological innovation and reductions of energy consumption and, thus, reduce the regional lung cancer risk.

7.
Sci Transl Med ; 13(603)2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290057

RESUMO

Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Here, we report the discovery of an intrinsic counter regulatory mechanism in colitis pathogenesis that may be targeted for IBD treatment. In response to microbial invasion, resident Vimentin+ stromal cells, connective tissue cells genetically marked by Twist2, are activated during the propagation phase of the disease, but not during initiation and resolution phases, and become a primary source of prostaglandin E2 (PGE2). PGE2 induction requires a nuclear factor κB-independent, TLR4-p38MAPK-Cox2 pathway activation. Ablation of each of the pathway genes, but not Rela or Tgfb1, in Twist2 cells enhanced M1 macrophage polarization and granulocyte/T helper 1 (TH1)/TH17 infiltration and aggravated colitis development. PGE2 administration ameliorated colitis in mouse models with defective PGE2 production but not in animals with normal PGE2 induction. Analysis of clinical samples and public domain data revealed increased expression of Cox2, the rate-limiting enzyme of PGE2 biosynthesis, in inflamed tissues, and especially in colon Vimentin+Twist2+ stromal cells, in about 60% of patients with active Crohn's disease or ulcerative colitis. Moreover, Cox2 protein expression was negatively correlated with disease severity, suggesting an involvement of stromal cells in IBD pathogenesis. Thus, the study uncovers an active immune pathway in colitic inflammation that may be targeted to treat patients with IBD with defects in PGE2 production.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Colo , Humanos , Imunidade Inata , Camundongos , Células Estromais
8.
Nat Commun ; 12(1): 4441, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290255

RESUMO

BRD4, a Bromodomain and Extraterminal (BET) protein family member, is a promising anti-cancer drug target. However, resistance to BET inhibitors targeting BRD4 is common in solid tumors. Here, we show that cancer-associated fibroblast (CAF)-activated stromal signaling, interleukin-6/8-JAK2, induces BRD4 phosphorylation at tyrosine 97/98 in colorectal cancer, resulting in BRD4 stabilization due to interaction with the deubiquitinase UCHL3. BRD4 phosphorylation at tyrosine 97/98 also displays increased binding to chromatin but reduced binding to BET inhibitors, resulting in resistance to BET inhibitors. We further show that BRD4 phosphorylation promotes interaction with STAT3 to induce chromatin remodeling through concurrent binding to enhancers and super-enhancers, supporting a tumor-promoting transcriptional program. Inhibition of IL6/IL8-JAK2 signaling abolishes BRD4 phosphorylation and sensitizes BET inhibitors in vitro and in vivo. Our study reveals a stromal mechanism for BRD4 activation and BET inhibitor resistance, which provides a rationale for developing strategies to treat CRC more effectively.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Montagem e Desmontagem da Cromatina , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fatores de Transcrição/metabolismo , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Fibroblastos Associados a Câncer/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Cromatina/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Janus Quinase 2/metabolismo , Fosforilação , Domínios Proteicos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fatores de Transcrição/antagonistas & inibidores , Microambiente Tumoral , Ubiquitina Tiolesterase/metabolismo
9.
Elife ; 102021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34085926

RESUMO

Disorders of the transparent cornea affect millions of people worldwide. However, how to maintain and/or regenerate this organ remains unclear. Here, we show that Rela (encoding a canonical NF-κB subunit) ablation in K14+ corneal epithelial stem cells not only disrupts corneal regeneration but also results in age-dependent epithelial deterioration, which triggers aberrant wound-healing processes including stromal remodeling, neovascularization, epithelial metaplasia, and plaque formation at the central cornea. These anomalies are largely recapitulated in normal mice that age naturally. Mechanistically, Rela deletion suppresses expression of Aldh1a1, an enzyme required for retinoic acid synthesis from vitamin A. Retinoic acid administration blocks development of ocular anomalies in Krt14-Cre; Relaf/f mice and naturally aged mice. Moreover, epithelial metaplasia and plaque formation are preventable by inhibition of angiogenesis. This study thus uncovers the major mechanisms governing corneal maintenance, regeneration, and aging and identifies the NF-κB-retinoic acid pathway as a therapeutic target for corneal disorders.


Assuntos
Queimaduras Químicas/tratamento farmacológico , Senescência Celular/efeitos dos fármacos , Neovascularização da Córnea/prevenção & controle , Epitélio Corneano/efeitos dos fármacos , Queimaduras Oculares/tratamento farmacológico , Regeneração/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Tretinoína/farmacologia , Fatores Etários , Família Aldeído Desidrogenase 1/genética , Família Aldeído Desidrogenase 1/metabolismo , Animais , Queimaduras Químicas/etiologia , Queimaduras Químicas/metabolismo , Queimaduras Químicas/patologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/patologia , Substância Própria/efeitos dos fármacos , Substância Própria/metabolismo , Substância Própria/patologia , Modelos Animais de Doenças , Epitélio Corneano/metabolismo , Epitélio Corneano/patologia , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/metabolismo , Queimaduras Oculares/patologia , Camundongos Knockout , Retinal Desidrogenase/genética , Retinal Desidrogenase/metabolismo , Transdução de Sinais , Células-Tronco/metabolismo , Células-Tronco/patologia , Fator de Transcrição RelA/genética
10.
Environ Sci Pollut Res Int ; 28(43): 60753-60764, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34165741

RESUMO

Microplastic pollution is ubiquitous in the marine environment and the consumption of shellfish containing microplastics may pose a risk to human health. This study investigated the occurrence and characteristics of microplastics in three commonly consumed shellfish in the coastal region of Jiangsu Province, China. The average abundance of microplastics in shellfish varied from 0.33 to 9.33 items/individual (0.06-0.92 items/g, wet weight of soft tissue). Microplastic abundance in Jiangsu was relatively low compared to studies from other regions of China and worldwide. Synthetic fibers (66.20%) were predominant and included rayon (34.84%) and polyester (23.23%), indicating that the majority of particles originated from the discharge of clothing fibers in domestic sewage. Transparent (66.20 %) particles were the most common, particle size was generally less than 500 µm (62.30%), and abundance decreased as the particle size increased. The average annual intake of microplastics by Jiangsu coastal residents via the consumption of common bivalves was estimated to be 1088.64 items/person/year. This study provides data to support ecological and health risk assessments for microplastics in the Jiangsu coastal region.


Assuntos
Microplásticos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Humanos , Plásticos , Frutos do Mar/análise , Poluentes Químicos da Água/análise
11.
Cell Rep ; 35(5): 109069, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33951440

RESUMO

mTOR, the sensor of nutrients and growth factors, has important roles in tissue homeostasis and tumorigenesis. However, how mTOR controls gastric epithelial cell turnover and gastric cancer development, a leading malignancy, remains poorly understood. Here, we provide genetic evidence that mTOR activation promotes proliferation and inhibits differentiation of Lgr5+ gastric epithelial progenitors (GEPs) in gastric homeostasis and tumorigenesis. mTOR signaling increases MEK1 and Smad1 expression and enhances activation of MEK1-ERKs and BMP-Smad1 pathways, respectively, in GEPs and gastric tumors. Mek1 deletion or inhibition rescues hyperproliferation, whereas Bmpr1a ablation or inhibition rescues differentiation defects of Tsc1-/- GEPs. Tsc1 deficiency in Lgr5+ GEPs accelerates gastric tumor initiation and development, which require MEK1-ERKs for hyperplasia and BMP-Smad1 for differentiation suppression. These findings reveal how mTOR signaling controls Lgr5+ GEP homeostasis and cancerization and suggest that ERKs and Smad1 signaling can be safely targeted to substitute mTOR inhibitors in gastric cancer therapy.

12.
Anal Chim Acta ; 1164: 338524, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992218

RESUMO

Avian influenza virus (AIV) is a serious zoonotic disease causing severe damages to both poultry industry and human health. To rapidly detect AIV on-site with high sensitivity and accuracy, we design sensitive antibody fluorescence immunosorbent assay (SAFIA) on AIV H9N2 antibody. In SAFIA, hemagglutinin (HA1) protein coated sample chamber specifically binds targets but remarkably reduces non-specific absorption; Protein L coated polystyrene microsphere captures target through secondary antibody to significantly amplify the fluorescence signal; and a portable fluorescence counter automatically measures the fluorescence spot density for AIV H9N2 antibody detection. Proved by practical applications, SAFIA could probe AIV H9N2 antibody in high sensitivity and selectivity, and distinguish positive and negative serum samples in high accuracy. Additionally, SAFIA can rapidly detect AIV H9N2 antibody at room temperature only requiring simple operations as well as cost-effective and compact devices. Therefore, SAFIA is a potential new-generation tool in rapid on-site testing for agricultures.


Assuntos
Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Animais , Galinhas , Fluorescência , Humanos , Imunoadsorventes , Influenza Aviária/diagnóstico
13.
Cancer Res ; 81(12): 3174-3186, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33863779

RESUMO

Renal cell carcinoma (RCC) mainly originates from renal proximal tubules. Intriguingly, disruption of genes frequently mutated in human RCC samples thus far has only generated RCC originated from other renal tubule parts in mouse models. This hampers our understanding of the pathogenesis of RCC. Here we show that mTOR signaling, often activated in RCC samples, initiates RCC development from renal proximal tubules. Ablation of Tsc1, encoding an mTOR suppressor, in proximal tubule cells led to multiple precancerous renal cysts. mTOR activation increased MEK1 expression and ERK activation, and Mek1 ablation or inhibition diminished cyst formation in Tsc1-deficient mice. mTOR activation also increased MKK6 expression and p38MAPK activation, and ablation of the p38α-encoding gene further enhanced cyst formation and led to RCC with clear cell RCC features. Mechanistically, Tsc1 deletion induced p53 and p16 expression in a p38MAPK-dependent manner, and deleting Tsc1 and Trp53 or Cdkn2a (encoding p16) enhanced renal cell carcinogenesis. Thus, mTOR activation in combination with inactivation of the p38MAPK-p53/p16 pathway drives RCC development from renal proximal tubules. Moreover, this study uncovers previously unidentified mechanisms by which mTOR controls cell proliferation and suggests the MEK-ERK axis to be a potential target for treatment of RCC. SIGNIFICANCE: Mouse modeling studies show that mTOR activation in combination with inactivation of the p38MAPK-p53/p16 axis initiates renal cell carcinoma that mimics human disease, identifying potential therapeutic targets for RCC treatment.

14.
FASEB J ; 35(4): e21345, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33715219

RESUMO

Obesity is common in the middle aged population and it increases the risks of diabetes, cardiovascular diseases, certain cancers, and dementia. Yet, its etiology remains incompletely understood. Here, we show that ectopic expression of HB-EGF, an important regulator of neurogenesis, in Nestin+ neuroepithelial progenitors with the Cre-LoxP system leads to development of spontaneous middle age obesity in male mice accompanied by hyperglycemia and insulin resistance. The Nestin-HB-EGF mice show decreases in food uptake, energy expenditure, and physical activity, suggesting that reduced energy expenditure underlies the pathogenesis of this obesity model. However, HB-EGF expression in appetite-controlling POMC or AgRP neurons or adipocytes fails to induce obesity. Mechanistically, HB-EGF suppresses expression of Hypocretin/Orexin, an orexigenic neuropeptide hormone, in the hypothalamus of middle aged Nestin-HB-EGF mice. Hypothalamus Orexin administration alleviates the obese and hyperglycemic phenotypes in Nestin-HB-EGF mice. This study uncovers an important role for HB-EGF in regulating Orexin expression and energy expenditure and establishes a midlife obesity model whose pathogenesis involves age-dependent changes in hypothalamus neurons.


Assuntos
Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Nestina/metabolismo , Células-Tronco Neurais/metabolismo , Obesidade/metabolismo , Orexinas/metabolismo , Adiponectina/sangue , Envelhecimento , Animais , Composição Corporal , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Humanos , Insulina/sangue , Leptina/sangue , Camundongos , Nestina/genética , Orexinas/genética
15.
Mar Pollut Bull ; 166: 112237, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33711604

RESUMO

We investigated the pollution characteristics, the spatial distributions of microplastics, and the source compositions in the Jiangsu Coastal Area, China. The average abundance of microplastics in the surface water and sediment were 0.0998 ± 0.0720 items/m3 (using a trawl with 333-µm mesh)and 0.1858 ± 0.0927items/g, respectively. The concentration of microplastics showed a distribution trend of high near shore and low far shore in the east-west direction, and were the highest in the southernmost part. According to microplastics found in the surface water, the results of a quantitative source apportionment indicate that the most common source in the northernmost and southernmost regions were clothing fibers, accounting for 38.40% and 40.44% of the total source, respectively. While the major source type in the middle region was the decomposition of hard, large plastic waste. Finally, we suggested some control measures for the main types of microplastics observed in the different regions.


Assuntos
Microplásticos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Plásticos , Poluentes Químicos da Água/análise
16.
J Bone Miner Res ; 36(6): 1088-1103, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33599011

RESUMO

Paget's disease of bone (PDB) is a late-onset chronic progressive bone disease characterized by abnormal activation of osteoclasts that results in bone pain, deformities, and fractures. PDB is very rare in Asia. A subset of PDB patients have early onset and can develop malignant giant cell tumors (GCTs) of the bone (PDB/GCTs), which arise within Paget bone lesions; the result is a significantly higher mortality rate. SQSTM1, TNFRSF11A, OPG, VCP, and HNRNPA2B1 have been identified as pathogenic genes of PDB, and ZNF687 is the only confirmed gene to date known to cause PDB/GCT. However, the molecular mechanism underlying PDB/GCT has not been fully elucidated. Here, we investigate an extended Chinese pedigree with eight individuals affected by early-onset and polyostotic PDB, two of whom developed GCTs. We identified a heterozygous 4-bp deletion in the Profilin 1 (PFN1) gene (c.318_321delTGAC) by genetic linkage analysis and exome sequencing for the family. Sanger sequencing revealed another heterozygous 1-bp deletion in PFN1 (c.324_324delG) in a sporadic early-onset PDB/GCT patient, further proving its causative role. Interestingly, a heterozygous missense mutation of PFN1 (c.335 T > C) was identified in another PDB/GCT family, revealing that not only deletion but also missense mutations in PFN1 can cause PDB/GCT. Furthermore, we established a Pfn1-mutated mouse model (C57BL/6J mice) and successfully obtained Pagetic phenotypes in heterozygous mice, verifying loss of function of PFN1 as the cause of PDB/GCT development. In conclusion, our findings reveal mutations in PFN1 as the pathological mechanism in PDB/GCT, and we successfully established Pfn1-mutated mice as a suitable animal model for studying PDB-associated pathological mechanisms. The identification of PFN1 mutations has great diagnostic value for identifying PDB individuals predisposed toward developing GCTs. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Assuntos
Tumores de Células Gigantes , Osteíte Deformante , Animais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Osteíte Deformante/genética , Profilinas/genética , Proteína Sequestossoma-1/genética
17.
Sci Total Environ ; 765: 144263, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33385811

RESUMO

The lack of long-term observations and satellite retrievals of health-damaging fine particulate matter in China has demanded the estimates of historical PM2.5 (particulate matter less than 2.5 µm in diameter) concentrations. This study constructs a gridded near-surface PM2.5 concentration dataset across China covering 1980-2019 using the space-time random forest model with atmospheric visibility observations and other auxiliary data. The modeled daily PM2.5 concentrations are in excellent agreement with ground measurements, with a coefficient of determination of 0.95 and mean relative error of 12%. Besides the atmospheric visibility which explains 30% of total importance of variables in the model, emissions and meteorological conditions are also key factors affecting PM2.5 predictions. From 1980 to 2014, the model-predicted PM2.5 concentrations increased constantly with the maximum growth rate of 5-10 µg/m3/decade over eastern China. Due to the clean air actions, PM2.5 concentrations have decreased effectively at a rate over 50 µg/m3/decade in the North China Plain and 20-50 µg/m3/decade over many regions of China during 2014-2019. The newly generated dataset of 1-degree gridded PM2.5 concentrations for the past 40 years across China provides a useful means for investigating interannual and decadal environmental and climate impacts related to aerosols.

18.
Stem Cell Res Ther ; 12(1): 25, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413643

RESUMO

Umbilical cord mesenchymal stem cells (UC-MSCs) have certain advantages over other MSCs and about 300 clinical trials have been registered using UC-MSCs to treat diseases such as osteoarthritis, autoimmune diseases, and degenerative disorders, yet, only limited success has been achieved. One reason is that in vitro expanded UC-MSCs show tremendous heterogeneity and their relationship to in vivo UC-MSCs remains unknown. Here, we investigated freshly isolated, uncultured UC-MSCs by single-cell RNA sequencing (scRNA-seq) and found two populations of UC-MSCs. Although UC-MSCs share many expressed genes and may have the same origin, they can be clearly separated based on differentially expressed genes including CD73 and other markers. Moreover, group 1 MSCs are enriched in expression of genes in immune response/regulatory activities, muscle cell proliferation and differentiation, stemness, and oxidative stress while group 2 MSCs are enriched with gene expression in extracellular matrix production, osteoblast and chondrocytes differentiation, and bone and cartilage growth. These findings suggest that UC-MSCs should be separated right after isolation and individually expanded in vitro to treat different diseases.


Assuntos
Células-Tronco Mesenquimais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Perfilação da Expressão Gênica , Humanos , Análise de Célula Única , Cordão Umbilical
19.
Medicine (Baltimore) ; 99(50): e23515, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327295

RESUMO

BACKGROUND: Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, intravenous (IV) versus oral acetaminophen (APAP) treatment is still a controversial subject in TKA. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of IV versus oral APAP on pain and recovery after TKA. METHODS: Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials, cohort studies were included in our meta-analysis. Five studies that compared IV APAP groups with oral APAP groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines to ensure the reliability and verity of results. RESULTS: Pooled results indicated that no significant difference between the IV APAP groups and oral APAP groups in term of VAS score at 24 hours (P = .67), 48 hours (P = 0.08), and total morphine consumption at 24 hours (P = .07), but there was a significant difference in terms of length of hospital stay (LOS) (P = .0004). CONCLUSION: IV APAP was not found to be superior to oral APAP in patients undergoing TKA in terms of VAS scores at 24 hours, 48 hours, and total morphine consumption at 24 hours. However, it can significantly reduce the LOS. We still need a large of high-quality research to verify the relationship between the oral and the IV APAP to give the conclusion.


Assuntos
Acetaminofen/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Artroplastia do Joelho , Dor Pós-Operatória/tratamento farmacológico , Administração Oral , Humanos , Infusões Intravenosas , Recuperação de Função Fisiológica
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