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1.
BMC Genomics ; 22(Suppl 3): 405, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34082708

RESUMO

BACKGROUND: Transposable elements (TE) account for more than 50% of human genome. It has been reported that some types of TEs are dynamically regulated in the reprogramming of human cell lines. However, it is largely unknown whether some TEs in Macaca mulatta are also regulated during the reprogramming of cell lines of monkey. RESULTS: Here, we systematically examined the transcriptional activities of TEs during the conversion of Macaca mulatta fibroblast cells to neuroepithelial stem cells (NESCs). Hundreds of TEs were dynamically regulated during the reprogramming of Macaca mulatta fibroblast cells. Furthermore, 48 Long Terminal Repeats (LTRs), as well as some integrase elements, of Macaca endogenous retrovirus 3 (MacERV3) were transiently activated during the early stages of the conversion process, some of which were further confirmed with PCR experiments. These LTRs were potentially bound by critical transcription factors for reprogramming, such as KLF4 and ETV5. CONCLUSION: These results suggest that the transcription of TEs are delicately regulated during the reprogramming of Macaca mulatta fibroblast cells. Although the family of ERVs activated during the reprogramming of fibroblast cells in Macaca mulatta is different from those in the reprogramming of human fibroblast cells, our results suggest that the activation of some ERVs is a conserved mechanism in primates for converting fibroblast cells to stem cells.


Assuntos
Elementos de DNA Transponíveis , Sequências Repetidas Terminais , Animais , Elementos de DNA Transponíveis/genética , Fibroblastos , Humanos , Macaca mulatta , Células-Tronco
2.
Biomed Eng Online ; 20(1): 52, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074299

RESUMO

BACKGROUND: Establishing a high-accuracy and non-invasive method is essential for evaluating cardiovascular disease. Skin cholesterol is a novel marker for assessing the risk of atherosclerosis and can be used as an independent risk factor of early assessment of atherosclerotic risk. METHODS: We propose a non-invasive skin cholesterol detection method based on absorption spectroscopy. Detection reagents specifically bind to skin cholesterol and react with indicator to produce colored products, the skin cholesterol content can be obtained through absorption spectrum information on colored products detected by non-invasive technology. Gas chromatography is used to measure cholesterol extracted from the skin to verify the accuracy and reliability of the non-invasive test method. A total of 342 subjects were divided into normal group (n = 115), disease group (n = 110) and risk group (n = 117). All subjects underwent non-invasive skin cholesterol test. The diagnostic accuracy of the measured value was analyzed by receiver-operating characteristic (ROC) curve. RESULTS: The proposed method is able to identify porcine skin containing gradient concentration of cholesterol. The values measured by non-invasive detection method were significantly correlated with gas chromatography measured results (r = 0.9074, n = 73, p < 0.001). Bland-Altman bias was - 72.78 ± 20.03 with 95% limits of agreement - 112.05 to - 33.51, falling within the prespecified clinically non-significant range. We further evaluated the method of patients with atherosclerosis and risk population as well as normal group, patients and risk atherosclerosis group exhibited higher skin cholesterol content than normal group (all P < 0.001). The area under the ROC curve for distinguishing Normal/Disease group was 0.8642 (95% confidence interval, 0.8138 to 0.9146), meanwhile, the area under the ROC curve for distinguishing Normal/Risk group was 0.8534 (95% confidence interval, 0.8034 to 0.9034). CONCLUSIONS: The method demonstrated its capability of detecting different concentration of skin cholesterol. This non-invasive skin cholesterol detection system may potentially be used as a risk assessment tool for atherosclerosis screening, especially for a large population.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33961190

RESUMO

In-situ catalytic pyrolysis has simple process configuration and low cost. Ex-situ catalytic pyrolysis can optimize the pyrolysis capacity and upgrade catalysis, and the catalytic can be reused. But there have been few studies researched on compare in-situ and ex-situ catalytic pyrolysis of the OS performed in similar reactor with two kinds of catalytic. This paper study the pyrolysis of oily sludge (OS) uses CaO and oily pyrolysis char as catalytic at 700 °C. Through analysis the pyrolysis oil (PO), pyrolysis solid (PS) and pyrolysis gas (PG) during pyrolysis procedure to research the difference between in-situ and ex-situ catalytic pyrolysis. The gas chromatography-mass spectrometry (GC-MS) results show that CaO was conducive to the synthesis of aromatics, which content more than aliphatics and heterocyclics in CaO-i (i: in-situ) and CaO-e (e: ex-situ) groups. However, char greatly inhibits the production of aromatic compounds and promotes the production of aliphatic compounds. Gas chromatography (GC) results present that the char and CaO can greatly increase the content of combustible gas and the content reach to 85.85%, the pyrolysis gas (PG) keep at the highest combustion performance in char-CaO-i group. Meanwhile, compared with uncatalyzed groups, the content of CH4 and CO increased about 2.05% and 3.93%, respectively. Fourier transform infrared spectroscopy (FT-IR) show that char and CaO reduce the function groups number of pyrolysis solid (PS), and it shows that the pyrolysis reaction is more complete. This research is expecting to provide theory support for catalytic pyrolysis of OS.

4.
Clin Lab ; 67(5)2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33978388

RESUMO

BACKGROUND: Suppurative arthritis induced by Scedosporium apiospermum (S. apiospermum) or Mycobacterium fortuitum (MF) was rare, and even more so when caused by a mixed infection of the two. In this paper, we report the rare case of suppurative arthritis induced by S. apiospermum and MF. METHODS: A 46-year-old patient whose left knee was accidentally injured by a rotary tiller. His left knee joint was clearly swollen although debridement and suturing had been performed twice at a local hospital. Bacterial culture result was MF and S. apiospermum after admission. Definitive therapy (debridement combined with treatment using three antibiotics) was initiated. RESULTS: Although the fungus reappeared when he tried to discontinue the drug, after the third debridement combined with treatment using three antibiotics for 8 months, the infection was controlled and did not recur. CONCLUSIONS: This demonstrates that early bacteriological examination is essential. Treatment of fungus generally requires a long course. However, course of medication should be related to the patient's specific conditions and the implementation of the operation.

5.
Microbiome ; 9(1): 119, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020714

RESUMO

BACKGROUND: In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions. RESULTS: In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn ) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (n = 11,647) and cultured 24 "most-wanted" and "medium priority" taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially "dark taxa" that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the "most wanted" functionally unknown proteins in the FUnkFams database. CONCLUSIONS: A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. Video abstract.

6.
Stem Cell Res Ther ; 12(1): 313, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051854

RESUMO

BACKGROUND: Mesenchymal stem cells including adipose-derived stem cells (ASCs) have a considerable potential in the field of translational medicine. Unfortunately, multiple factors (e.g., older age, co-existing diabetes, and obesity) may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs-including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)-have been shown to play important roles in stem cell biology. However, the overall diabetes-related and aging-related expression patterns and interactions of these RNAs in ASCs remain unknown. METHOD: The phenotypes and functions of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donors were evaluated by in vitro assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to identify the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses were performed to investigate mRNAs with significant differences among groups. The lncRNA- or circRNA-associated competing endogenous RNA (ceRNA) networks were constructed based on bioinformatics analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into O-ASCs and verified by PCR. RESULTS: ASCs from diabetic and old donors showed inferior migration ability and increased cellular senescence. Furthermore, O-ASCs have decreased capacities for promoting endothelial cell angiogenesis and fibroblast migration, compared with Y-ASCs. The DE miRNAs, mRNAs, lncRNAs, and circRNAs were successfully identified by RNA-seq in O-ASCs vs. Y-ASCs and D-ASCs vs. O-ASCs. GO and KEGG analyses demonstrated that DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks revealed critical DE mRNAs in the above groups. RNAs with high fold changes and low p values were validated by PCR. ceRNA networks were constructed based on bioinformatics analyses and validated RNAs. Additionally, the lncRNA RAET1E-AS1-miR-145-5p-WNT11/BMPER axis was validated by PCR and correlation analyses. Finally, the overexpression of miR-145-5p was found to rejuvenate O-ASCs phenotype and augment the functionality of these cells. CONCLUSION: Our research may provide insights regarding the underlying mechanisms of ASC dysfunction; it may also offer novel targets for restoring therapeutic properties in ASCs.

7.
World Neurosurg ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940255

RESUMO

OBJECTIVE: To compare the clinical and radiologic outcomes of patients with different 3-dimensional (3D) hemivertebra morphologies undergoing posterior-only hemivertebra resection and fusion. METHODS: The files of patients with congenital scoliosis (CS) due to single hemivertebra undergoing posterior-only hemivertebra resection and fusion from January 2010 to January 2018 were reviewed. After evaluating the 3D computed tomography images, CS patients were divided into a unison hemivertebra group and a discordant hemivertebra group. Clinical outcomes, radiologic outcomes, and incidence of complications were compared. RESULTS: A total of 42 consecutive patients with CS patients due to a single hemivertebra undergoing posterior-only hemivertebra resection and fusion were included in this study. The Cobb angle of the segmental curve was significantly improved postoperatively and at the last follow-up in both groups (all P < 0.05). At both postoperation and the last follow-up, no significant differences were found in the incidence of complications, Cobb angle of the segmental curve, correction rate of the segmental curve, or other radiologic outcomes between the unison hemivertebra group and discordant hemivertebra group (all P > 0.05). Compared with the unison hemivertebra group, increased operation time (P = 0.006) and intraoperative blood loss (P = 0.037) were found in the discordant hemivertebra group. CONCLUSIONS: For CS patients with unison hemivertebra or discordant hemivertebra, satisfactory radiologic results were obtained by posterior-only hemivertebra resection and fusion. In terms of surgery, the radiologic outcomes of discordant hemivertebra patients were similar to those of unison hemivertebra patients, but discordant hemivertebrae could easily result in longer operation time and more intraoperative blood loss.

8.
Mikrochim Acta ; 188(6): 211, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34050442

RESUMO

A porous nanostructured covalent-organic framework (COF) has been prepared via condensation polymerization between the two building blocks of melem and hexaketocyclohexane octahydrate (represented as M-HO-COF). Basic characterizations revealed that the M-HO-COF network was composed of C=N and highly conjugated aromatic moieties, along with a high surface area, large pore size, remarkable electrochemical activity, and strong bioaffinity toward aptamer strands. Given that the vascular endothelial growth factor 165 (VEGF165)-targeted aptamer was stably anchored over M-HO-COF via weak intermolecular forces, the prepared M-HO-COF network exhibited great potential as a sensitive and selective platform for the impedimetric VEGF165 aptasensor. Consequently, the M-HO-COF-based aptasensor displayed an ultralow limit of detection of 0.18 fg mL-1 within a wide range of VEGF165 concentrations from 1 fg mL-1 to 10 ng mL-1. Considering its strong fluorescence performance, excellent biocompatibility, and small nanosheet-like structure, the obtained COF-based aptasensor showed a superior sensing performance and regeneration capability after 7 regeneration cycles for the detection of osteosarcoma cells (K7M2 cells), which overexpressed with VEGF165, with a low limit of detection of 49 cells mL-1. For real f human serum samples, the obtained COF-based aptasensor exhibits acceptable mean apparent recoveries of 97.41% with a relative standard deviation of 4.60%. Furthermore, the proposed bifunctional aptasensor for the detection VEGF165 and K7M2 cells exhibited good stability, appropriate selectivity toward other biomarkers or normal cells, acceptable reproducibility, and applicability. A bifunctional sensing system was constructed for detecting osteosarcoma cells (K7M2 cells) and VEGF165 based on the a porous nanostructured covalent-organic framework (M-HO-COF) via condensation polymerization between melem and hexaketocyclohexane octahydrate. The M-HO-COF-based aptasensor displayed ultralow detection limit of 0.18 fg mL-1 toward VEGF165 and 49 cell mL-1 for K7M2 cells with high selectivity, acceptable reproducibility, and good stability.

9.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(3): 328-335, 2021 Jun 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34041883

RESUMO

OBJECTIVES: The effect of isoprenylcysteine carboxymethyltransferase (ICMT) silencing on the migration and invasion of tongue squamous cell carcinoma was investigated by constructing the small interfering RNA (siRNA) of ICMT. METHODS: Through liposomal transfection, siRNA was transfected into human tongue squamous cell carcinoma CAL-27 and SCC-4 cells (ICMT-siRNA group) with a negative control group (transfected with NC-siRNA) and a blank control group (transfected with a transfection reagent but not with siRNA). Quantitative real-time polymerase chain reaction was performed to analyze the mRNA expression of ICMT and RhoA in each group of cells after transfection and to measure the silencing efficiency. Western blot was applied to examine the expression levels of ICMT, total RhoA, membrane RhoA, ROCK1, matrix metalloproteinase (MMP)-2, and MMP-9 proteins in each group. The migration and invasion abilities were evaluated via wound healing and Transwell motility assays. RESULTS: After CAL-27 and SCC-4 cells were transfected with ICMT-siRNA, the expression levels of ICMT genes and proteins decreased significantly in the experimental group compared with those in the negative and blank control groups (P<0.05). The mRNA and total protein expression levels of RhoA in the two groups were not significantly different (P>0.05). The expression levels of RhoA membrane protein, ROCK1, MMP-2, and MMP-9 decreased (P<0.05). The migration and invasion abilities were inhibited (P<0.05). CONCLUSIONS: The migration and invasion abilities of CAL-27 and SCC-4 cells were reduced significantly after the transfection of ICMT-siRNA, and the involved mechanism might be related to the RhoA-ROCK signaling pathway.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Invasividade Neoplásica , Proteínas Metiltransferases , RNA Interferente Pequeno , Língua , Transfecção , Quinases Associadas a rho
11.
Nat Commun ; 12(1): 2537, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953170

RESUMO

Metastasis accounts for 90% of cancer-related deaths and, currently, there are no effective clinical therapies to block the metastatic cascade. A need to develop novel therapies specifically targeting fundamental metastasis processes remains urgent. Here, we demonstrate that Salmonella YB1, an engineered oxygen-sensitive strain, potently inhibits metastasis of a broad range of cancers. This process requires both IFN-γ and NK cells, as the absence of IFN-γ greatly reduces, whilst depletion of NK cells in vivo completely abolishes, the anti-metastatic ability of Salmonella. Mechanistically, we find that IFN-γ is mainly produced by NK cells during early Salmonella infection, and in turn, IFN-γ promotes the accumulation, activation, and cytotoxicity of NK cells, which kill the metastatic cancer cells thus achieving an anti-metastatic effect. Our findings highlight the significance of a self-regulatory feedback loop of NK cells in inhibiting metastasis, pointing a possible approach to develop anti-metastatic therapies by harnessing the power of NK cells.


Assuntos
Interferon gama/metabolismo , Interferon gama/farmacologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/efeitos dos fármacos , Metástase Neoplásica/imunologia , Infecções por Salmonella/metabolismo , Salmonella/genética , Animais , Citocinas/metabolismo , Feminino , Imunidade Inata , Imunoterapia/métodos , Interferon gama/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Infecções por Salmonella/tratamento farmacológico
12.
Environ Sci Technol ; 55(11): 7225-7236, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33971713

RESUMO

Making a cost-effective governance of greenhouse gas (GHG) emissions and air pollution is of great importance for megacities to pursue a sustainable future. To achieve this, the present study advocates megacities to implement a two-tier synergic governance system consisting of both synergic governance between GHG and air pollutant emission reductions and between megacities and their surrounding regions. Based on the LEAP model and WRF-SMOKE-CMAQ simulation platform, this study found that climate governance of China's megacity, Shenzhen, could synergistically contribute to decreasing urban annual PM2.5 concentration by 5.6% in 2030. Using synergic governance with surrounding regions could further help cap and then quickly decrease the megacity's GHG emissions and lower its PM2.5 concentrations by an additional 11.8%. The results demonstrated the substantial effects of transdepartment and transregional synergic governance on Shenzhen's GHG emission reduction and air quality improvement. Furthermore, this study suggested road transportation and power generation and supply as the two priority fields for wide-ranging megacities to promote two-tier synergic governance, highlighting an integration of improved urban electrification with high-efficiency electricity use and a renewable-based power supply.

13.
Vaccines (Basel) ; 9(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799516

RESUMO

The mRNA-based vaccine approach is a promising alternative to traditional vaccines due to its ability for prompt development, high potency, and potential for secure administration and low-cost production. Nonetheless, the application has still been limited by the instability as well as the ineffective delivery of mRNA in vivo. Current technological improvements have now mostly overcome these concerns, and manifold mRNA vaccine plans against various forms of malignancies and infectious ailments have reported inspiring outcomes in both humans and animal models. This article summarizes recent mRNA-based vaccine developments, advances of in vivo mRNA deliveries, reflects challenges and safety concerns, and future perspectives, in developing the mRNA vaccine platform for extensive therapeutic use.

14.
J Hazard Mater ; 416: 125813, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33862486

RESUMO

The arsenic long-term leaching behavior of the cemented paste backfill obtained from the construction and demolition waste (CPB-CDW) is captured, which can be utilized in the potential engineering application. Laboratory studies were conducted on samples obtained from a mining site and the test results were imported into a numerical simulation model. It was found that the Elovich equation can describe well the As leaching behavior. Initially, the As concentrations decreased in the roadway in the mine and then increased along the roadway and attained a maximum concentration (8.149 × 10-3 mg/L) at the lower segment. When the groundwater was in the static mode, the As concentration increased dramatically followed by a gradual increase. Eventually, the concentration decreased gradually. For the dynamic condition, the As tended to move in a cluster form and the associated leaching and mass transfer process of As in the CPB-CDW were similar to those observed when the groundwater was in a static condition. However, the difference in the distribution of the amount of As in the leachate fluctuated continuously and the overall trend was to approach a steady state. As such, the time frame of such a mass transfer in the mobilized water is reduced significantly.

15.
Nature ; 592(7856): 789-793, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33854235

RESUMO

D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer1, but the mechanisms that regulate their turnover are still being debated2,3. Here, by combining biochemical and genetics studies in somatic cells, we identify CRL4AMBRA1 (also known as CRL4DCAF3) as the ubiquitin ligase that targets all three D-type cyclins for degradation. During development, loss of Ambra1 induces the accumulation of D-type cyclins and retinoblastoma (RB) hyperphosphorylation and hyperproliferation, and results in defects of the nervous system that are reduced by treating pregnant mice with the FDA-approved CDK4 and CDK6 (CDK4/6) inhibitor abemaciclib. Moreover, AMBRA1 acts as a tumour suppressor in mouse models and low AMBRA1 mRNA levels are predictive of poor survival in cancer patients. Cancer hotspot mutations in D-type cyclins abrogate their binding to AMBRA1 and induce their stabilization. Finally, a whole-genome, CRISPR-Cas9 screen identified AMBRA1 as a regulator of the response to CDK4/6 inhibition. Loss of AMBRA1 reduces sensitivity to CDK4/6 inhibitors by promoting the formation of complexes of D-type cyclins with CDK2. Collectively, our results reveal the molecular mechanism that controls the stability of D-type cyclins during cell-cycle progression, in development and in human cancer, and implicate AMBRA1 as a critical regulator of the RB pathway.

16.
Bioresour Technol ; 330: 124947, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33735728

RESUMO

Aging is inevitable when biochar uses for remediate Cadmium (Cd) pollution, but the variation of adsorption mechanism remains unclear. This study uses ramie residue to prepare fresh biochar, and adopt it with acidification and oxidation to simulate the aging process. The difference of physicochemical properties between fresh and aged biochar are studied through microstructure. Then, two kinds of biochar are making adsorption experiments in Cd solution for analyzing their adsorption mechanism. The results show that, both chemisorption and physisorption are exist, chemisorption and physisorption is the predominant way of fresh biochar and aged biochar respectively. Cation exchange is important but weaker in aged biochar than fresh biochar. Carboxyl plays a leading role in complexation of fresh biochar and hydroxy in aged biochar. Coprecipitation and cation-π mechanism impair apparently in aged biochar. This study indicates that aging change ramie biochar's main adsorption mechanism and the primary chemisorption way.


Assuntos
Boehmeria , Cádmio , Adsorção , Carvão Vegetal
17.
Am J Physiol Renal Physiol ; 320(5): F838-F858, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645317

RESUMO

Alteration of bladder morphology and function was the most important consequence of bladder outlet obstruction (BOO). Using a rat model of partial BOO (pBOO), we found that rats treated with metformin showed lower baseline pressures with a reduced inflammatory reaction in the early phase (2 wk) after pBOO. The NLR family pyrin domain containing 3 inflammasome pathway was inhibited in pBOO rat bladders with treatment of metformin in the early phase. Metformin reduced the activity of NLR family pyrin domain containing 3 in primary urothelial cells. In the chronic phase (9 wk after pBOO), metformin treatment ameliorated bladder fibrosis and improved the reduced compliance. Treatment with metformin suppressed the activation of Smad3 and compensated the diminished autophagy in 9-wk pBOO rat bladders. Autophagy was inhibited with upregulation of profibrotic proteins in primary fibroblasts from chronic pBOO bladders, which could be restored by administration of metformin. The antifibrotic effects of metformin on fibroblasts were diminished after silencing of AMP-activated protein kinase or light chain 3B. In summary, this study elucidates that oral administration of metformin relieves inflammation in the bladder during the early phase of pBOO. Long-term oral administration of metformin can prevent functional and histological changes in the pBOO rat bladder. The current study suggests that metformin might be used to prevent the development of bladder dysfunction secondary to BOO.NEW & NOTEWORTHY The present study in a rat model showed that oral administration of metformin alleviated inflammation following partial bladder outlet obstruction in the early phase and ameliorated bladder fibrosis as well as bladder dysfunction by long-term treatment. Our study indicated that metformin is a potential drug to inhibit bladder remodeling and alleviate bladder dysfunction. Clinical trials are needed to validate the effect of metformin on the bladder dysfunction and bladder fibrosis in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Metformina/farmacologia , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Humanos , Mediadores da Inflamação/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Fatores de Tempo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/metabolismo , Obstrução do Colo da Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Urodinâmica/efeitos dos fármacos , Urotélio/efeitos dos fármacos , Urotélio/metabolismo , Urotélio/patologia
18.
J Cell Mol Med ; 25(9): 4195-4203, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33745198

RESUMO

To determine whether the deletion of p16 can correct tooth and mandible growth retardation caused by Bmi1 deficiency, we compared the tooth and mandible phenotypes of homozygous p16-deficient (p16-/- ) mice, homozygous Bmi1-deficient (Bmi1-/- ) mice, double homozygous Bmi1 and p16-deficient (Bmi1-/- p16-/- ) mice to those of their wild-type littermates at 4 weeks of age by radiograph, histochemistry and immunohistochemistry. Results showed that compared to Bmi1-/- mice, the dental mineral density, dental volume and dentin sialoprotein immunopositive areas were increased, whereas the ratio of the predentin area to total dentin area and that of biglycan immunopositive area to dentin area were decreased in Bmi1-/- p16-/- mice. These results indicate that the deletion of p16 can improve tooth development in Bmi1 knockout mice. Compared to Bmi1-/- mice, the mandible mineral density, cortical thickness, alveolar bone volume, osteoblast number and activity, alkaline phosphatase positive area were all increased significantly in Bmi1-/- p16-/- mice. These results indicate that the deletion of p16 can improve mandible growth in Bmi1 knockout mice. Furthermore, the protein expression levels of cyclin D, CDK4 and p53 were increased significantly in p16-/- mice compared with those from wild-type mice; the protein expression levels of cyclin D and CDK4 were decreased significantly, whereas those of p27 and p53 were increased significantly in Bmi1-/- mice; these parameters were partly rescued in Bmi1-/- p16-/- mice compared with those from Bmi1-/- mice. Therefore, our results indicate that Bmi1 plays roles in regulating tooth and mandible development by inhibiting p16 signal pathway which initiated entry into cell cycle.

19.
J Behav Addict ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33704083

RESUMO

Background and aims: Deficits in cognitive control represent a core feature of addiction. Internet Gaming Disorder (IGD) offers an ideal model to study the mechanisms underlying cognitive control deficits in addiction, eliminating the confounding effects of substance use. Studies have reported behavioral and neural deficits in reactive control in IGD, but it remains unclear whether individuals with IGD are compromised in proactive control or behavioral adjustment by learning from the changing contexts. Methods: Here, fMRI data of 21 male young adults with IGD and 21 matched healthy controls (HC) were collected during a stop-signal task. We employed group independent component analysis to investigate group differences in temporally coherent, large-scale functional network activities during post-error slowing, the typical type of behavioral adjustments. We also employed a Bayesian belief model to quantify the trial-by-trial learning of the likelihood of stop signal - P(Stop) - a broader process underlying behavioral adjustment, and identified the alterations in functional network responses to P(Stop). Results: The results showed diminished engagement of the fronto-parietal network during post-error slowing, and weaker activity in the ventral attention and anterior default mode network in response to P(Stop) in IGD relative to HC. Discussion and conclusions: These results add to the literatures by suggesting deficits in updating and anticipating conflicts as well as in behavioral adjustment according to contextual information in individuals with IGD.

20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(1): 64-73, 2021 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33723939

RESUMO

OBJECTIVES: This study aimed to explore the effects of silencing isoprenylcysteine carboxyl methyltransfe-rase (Icmt) through small interfering RNA (siRNA) interference on the proliferation and apoptosis of tongue squamous cell carcinoma (TSCC). METHODS: Three siRNA were designed and constructed for the Icmt gene sequence and were then transfected into TSCC cells CAL-27 and SCC-4 to silence Icmt expression. The tested cells were divided as follows: RNA interference groups Icmt-siRNA-1, Icmt-siRNA-2, and Icmt-siRNA-3, negative control group, and blank control group. The transfection efficiency of siRNA was detected by the fluorescent group Cy3-labeled siRNA, and the expression of Icmt mRNA was screened by quantitive real-time polymerase chain reaction (qRT-PCR) selected the experimental group for subsequent experiments. The expression of Icmt, RhoA, Cyclin D1, p21, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) were analyzed by Western blot. The proliferation abilities of TSCC cells were determined by cell counting kit-8 assay. The change in apoptosis was detected by AnnexinV-APC/propidium staining (PI) assay. Cell-cycle analysis was conducted by flow cytometry. RESULTS: The expression of Icmt mRNA and protein in TSCC cells significantly decreased after Icmt-siRNA transfection (P<0.05). No significant difference in RhoA mRNA and protein expression was detected (P>0.05), but the expression of RhoA membrane protein decreased compared with the negative control group and blank control groups (P<0.05). Cyclin D1 expression decreased, whereas p21 expression significantly increased and the relative expression of ERK protein in the experimental group did not significantly different that in the control group (P>0.05). However, the phosphorylation level of ERK was significantly reduced (P<0.05). The cell cycles of TSCC CAL-27 and SCC-4 were altered in G1/S, cell proliferation activity was inhibited, and apoptosis was induced (P<0.05). CONCLUSIONS: Silencing Icmt can effectively downregulate its expression in TSCC cells, reduce the RhoA membrane targeting localization and cell proliferation, and induce apoptosis. Thus, Icmt may be a potential gene therapy target for TSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteínas Metiltransferases , RNA Interferente Pequeno , Língua
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