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1.
Biology (Basel) ; 10(2)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546519

RESUMO

Metabolic disorders of the circulatory system of animals (e.g., hyperglycemia and hyperlipidemia) can significantly affect immune function; however, since there is currently no reliable animal model for hyperproteinemia, its effects on immunity remain unclear. In this study, we established an animal model for hyperproteinemia in an invertebrate silkworm model, with a controllable plasma protein concentration (PPC) and no primary disease effects. We evaluated the influence of hyperproteinemia on innate immunity. The results showed that high PPC enhanced hemolymph phagocytosis via inducing a rapid increase in granulocytes. Moreover, while oenocytoids increased, the plasmacytes quickly dwindled. High PPC inhibited hemolymph melanization due to decreased phenoloxidase (PO) activity in the hemolymph via inhibiting the expression of the prophenoloxidase-encoding genes, PPO1 and PPO2. High PPC upregulated the gene expression of antimicrobial peptides via differential activation of the Toll and Imd signaling pathways associated with NF-κB signaling, followed by an induction of inconsistent antibacterial activity towards Gram-positive and Gram-negative bacteria in an animal model of high PPC. Therefore, high PPC has multiple significant effects on the innate immune function of the silkworm circulatory system.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33538056

RESUMO

Near-infrared (NIR) organic solid-state lasers play an essential role in applications ranging from laser communication to infrared night vision, but progress in this area is restricted by the lack of effective excited-state gain processes. Herein, we originally proposed and demonstrated the cascaded occurrence of excited-state intramolecular proton transfer for constructing the completely new energy systems. Cascading by the first ultrafast proton transfer of <430 fs and the subsequent irreversible second proton transfer of ~1.6 ps, the stepwise proton transfer process favors the true six-level photophysical cycle, which supports efficient population inversion and thus NIR single-mode lasing at 854 nm. This work realizes longest wavelength beyond 850 nm of organic single-crystal lasing to date and originally exploits the cascaded excited-state molecular proton transfer energy level systems for organic solid-state lasers.

3.
Insect Sci ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475237

RESUMO

Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), transmits the causal pathogen of huanglongbing and is a global pest of citrus. D. citri populations exhibit resistance to multiple insecticide modes of action in areas where these chemicals have been overused. We performed genome-wide transcriptional analysis for two field populations of D. citri (Wauchula and Lake Alfred, Florida, USA) that exhibit 1300-fold resistance to the neonicotinoid insecticide, thiamethoxam, and compared it to that of susceptible psyllids collected from the same area and without imposed selection. The Lake Alfred population responded to insecticide resistance by up-regulation of 240 genes and down-regulation of 148 others. The Wauchula population exhibited similar patterns to the Lake Alfred population with up-regulation of 253 genes and down-regulation of 115 others. Gene Ontology annotation associated with cellular processes, cell, and catalytic activity were assigned to differentially expressed genes (DEGs). The DEGs from Lake Alfred and Wauchula populations were mapped to Kyoto Encyclopedia of Gene and Genomes pathways and implicated enrichment of metabolic pathways, oxidative phosphorylation, extracellular matrix-receptor interaction, terpenoid backbone biosynthesis, and insect hormone biosynthesis in the resistant populations. Up-regulation of 60s ribosomal proteins, UDP-gluscoyltransferases, cytochrome c oxidases, and CYP and ABC transporters among thiamethoxam-resistant D. citri implicates a broad array of novel and conventionally understood resistance mechanisms.

4.
BMC Cancer ; 21(1): 59, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33435902

RESUMO

BACKGROUND: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. METHODS: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. RESULTS: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129). CONCLUSIONS: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 70-75, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33474892

RESUMO

Personnel training is the core and cornerstone of stomatology education. This paper introduces the background and connotation of "New Medicine Department", and discusses the influence of new medicine on the development of stomatology from the aspects of precision medicine, transformation medicine and intelligent medicine, the new requirements of stomatology education in the new medical department construction under the health China strategy were analyzed, this paper puts forward some thoughts on how to promote the development of stomatology education in new medical disciplines from aspects of promoting the cross-integration of disciplines, consolidating the basis of talents training, promoting the training mode of general education, integrating moral education into the whole teaching process, promoting the coordination of Medical Education and education in all aspects, cultivating different types of stomatology talents, and building up a contingent of teachers in all dimensions, in order to provide reference for the reform and development of stomatology education in China.


Assuntos
Medicina Bucal , China
6.
Pest Manag Sci ; 77(1): 464-473, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32770656

RESUMO

BACKGROUND: We investigated rotation using insecticides with multiple modes of action as a resistance management strategy for Asian citrus psyllid, Diaphorina citri, Kuwayama (Hemiptera: Liviidae), in Florida. The stability of thiamethoxam resistance was investigated in the laboratory by establishing populations of field-collected, resistant D. citri and rearing them under no insecticide exposure. Furthermore, recovery of susceptibility was investigated in the field by initiating rotation to insecticides in plots that previously were treated with consecutive thiamethoxam applications. RESULTS: The resistance ratio (RR) for thiamethoxam reached between 1266.29- and 1395.00-fold after three and four consecutive applications of thiamethoxam, respectively. However, the RR for thiamethoxam remained low (1.71-5.28-fold) under both rotations at both Lake Alfred and Wauchula. Thiamethoxam was cross-resistant with imidacloprid (RR site 1 = 1059.65-fold, RR site 2 = 1595.43-fold) and clothianidin (RR site 1 = 1798.78-fold, RR site 2 = 1270.57-fold) in the nonrotated treatment at both sites. There was very low cross-resistance to other insecticides with different modes of action. Both laboratory and field investigations indicated that susceptibility to thiamethoxam fully recovered after five D. citri generations. Expression of CYP4C67 was significantly increased in resistant populations. CONCLUSION: Our results revealed that D. citri populations develop a high level of resistance following only three or four consecutive neonicotinoid sprays; this was associated with subsequent product failure. Our data suggest that metabolic detoxification by cytochrome P450s contributes to thiamethoxam resistance in D. citri. Overall, the investigation demonstrated that resistance to thiamethoxam can be managed readily in populations of D. citri by rotating modes of action.


Assuntos
Citrus , Hemípteros , Inseticidas , Animais , Florida , Inseticidas/farmacologia , Tiametoxam
7.
Int Immunol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258927

RESUMO

BACKGROUND: We previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC antigen (DST-antibodies). METHODS: We examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model. We also examined an anti-donor class II MHC (MHCII) antibody that recognizes donor DCs more selectively. RESULTS: Preoperative transfer of DST-antibodies and DST pretreatments eliminated all passenger leukocytes, including both DC subsets and depleted the sessile DCs in the graft to ~20% of control. The CD172a +CD11b/c + immunogenic subset was almost abolished. The intrahost direct or semi-direct allorecognition pathway was successfully blocked, leading to a significant suppression of the CD8 + T-cell response in the recipient lymphoid organs and the graft with delayed graft rejection. Anti-donor MHCII antibody had similar effects without temporary graft damage. Although DST pretreatment had a priming effect on the recipient Treg proliferative response, DST-primed sera and the anti-donor MHCII antibody did not. CONCLUSION: DST-antibodies and anti-donor MHCII antibodies could suppress the CD8 + T-cell-mediated liver transplant rejection by depleting donor immunogenic DCs, blocking the direct or semi-direct pathway of allorecognition. Donor MHCII-specific antibodies may be applicable as a selective suppressant of anti-donor immunity for clinical liver transplantation without the cellular damage of donor MHCII - graft cells and recipient cells.

8.
Gland Surg ; 9(5): 1551-1563, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224831

RESUMO

The purpose of this study was to systematically evaluate guidelines for surgery in patients with severe pancreatitis and to identify gaps limiting evidence-based medicine practice. A systematic search of databases and related websites was conducted to identify surgical guidelines for patients with severe pancreatitis. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. The similarities among key recommendations were compared, and the evidence supporting them was extracted and analysed. Seven surgical guidelines for patients with severe pancreatitis were included. Only two guidelines, those of the World Society of Emergency Surgery (WSES) and the European Society of Gastrointestinal Endoscopy (ESGE), scored more than 60% for overall quality and were worthy of clinical recommendation. We found that the quality of the severe acute pancreatitis surgical guidelines have much room for improvement, especially in the field of application, the participation of stakeholders and editorial independence. The heterogeneity and causes of surgical recommendations were further analysed, and the latest evidence was retrieved. It was found that the surgical guidelines for severe pancreatitis lacked high-quality evidence, some of the recommendations were controversial, and evidence citation was unreasonable. The quality of surgical guidelines for patients with severe pancreatitis varies widely. In the past 5 years, the key recommendations of the surgical guidelines for severe pancreatitis have been somewhat consistent and controversial, and improvement in these existing problems and controversies will be an effective way for developers to upgrade the surgical guidelines for severe pancreatitis.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33184920

RESUMO

A photochemical C-N coupling of aryl halides with nitroarenes is demonstrated for the first time. Catalyzed by a Ni(II) complex in the absence of any external photosensitizer, readily available nitroarenes undergo coupling with a variety of aryl halides, providing a step-economic extension to the widely used Buchwald-Hartwig C-N coupling reaction. The method tolerates coupling partners with steric-congestion and functional groups sensitive to bases and nucleophiles. Mechanistic studies suggest that the reaction proceeds via the addition of an aryl radical, generated from a Ni (I)/Ni (III) cycle, to a nitrosoarene intermediate.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33172374

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the fourth most prevalent cancer in the world. However, the molecular mechanism underlying CRC is largely unknown. OBJECTIVE: To explore the pathogenic mechanism of CRC and to facilitate better diagnosis and treatment of this disease. METHODS: Differentially expressed miRNAs (DEMs) and genes (DEGs) in CRC vs. Control samples from the miRNA expression data in GSE115513 and the miRNA and mRNA expression data in TCGA-COAD dataset were screened, followed by the construction of miRNA-mRNA regulatory network. Functional and pathway enrichment analysis, protein-protein interaction (PPI) analysis, and survival analysis were then performed for these DEGs and DEMs. RESULTS: We identified 64 DEMs from GSE115513 dataset and 265 DEMs and 2218 DEGs from TCGA-COAD dataset. miR-27a-3p was a hub DEM with the highest degree in miRNA-mRNA network, while GRIN2B and PCDH10 were hub DEGs targeted by multiple miRNAs, including miR-27a-3p. SNAP25 and GRIN2B were also hub DEGs with the highest degree of interactions in PPI network. These DEMs and DEGs were significantly enriched in multiple KEGG pathways, including proteoglycans expression and cAMP signaling pathway in cancer. Finally, seven DEGs, including FJX1 Dsc2, and hsa-miR-375, were revealed to be correlated with CRC prognosis. CONCLUSIONS: Aberrant expression of genes and miRNAs were involved in the pathogenesis of CRC probably by regulating proteoglycans expression and cAMP signaling. miR-27a-3p, PCDH10, GRIN2B, FJX1, Dsc2, and hsa-miR-375 were identified as potential targets for understanding the pathogenic mechanism of CRC. In addition, FJX1, Dsc2 and hsa-miR-375 were identified as potential predictive markers for CRC prognosis.

13.
Onco Targets Ther ; 13: 11595-11606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33209036

RESUMO

Objective: The microRNA expression profile of plasma exosomes in prostate cancer (PCa) is of critical importance in the disease exploration. This study aimed to explore the clinical application of exosomal miRNAs as biomarkers for PCa. Methods: Exosome-like vesicles of PCa patients and healthy controls were purified by differential centrifugation. The purified vesicles within the ranges of 50 and 100 nm were classified as exosomes according to the results of transmission electron microscopy and Western blot. Both, in vitro and in vivo, validations were performed by small RNA sequencing, CCK8, RT-qPCR, flow cytometry, Western blot, transwell and immunofluorescent staining assays. Results: High-throughput sequencing identified that 94 miRNAs were differentially expressed in PCa patients in comparison with healthy controls (P<0.01; fold change ≥2). Among them, 64 miRNAs were upregulated, and 30 miRNAs were downregulated. In comparison to the healthy controls, the expression levels of miR-217 were significantly upregulated, while miR-23b-3p were significantly downregulated in the exosomes and serum collected from PCa patients. Both, in vitro and in vivo, studies revealed that exosomes secreted by PCa cells with up-regulated miR-217 levels promoted cell proliferation and invasion; meanwhile, the exosomes with up-regulated miR-23b-3p levels inhibited cell proliferation and invasion. The epithelial-mesenchymal transition process may have been involved in the above-mentioned regulation. Conclusion: This study identified the dysregulated expression of exosomal miRNAs in PCa patients, including miR-217 and miR-23b-3p, by validating their function on proliferation and invasion in PCa cells. This regulation may have been affected by the epithelial-mesenchymal transition process, suggesting that they can be used as potential targets in the diagnosis and treatment of PCa.

14.
Respir Res ; 21(1): 287, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129326

RESUMO

BACKGROUND: Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in more than 20 human malignancies, among which lung cancer is the leading cause of cancer-associated deaths worldwide. Thus, the mechanism of CXCR7 in the progression of lung cancer is urgently needed. METHODS: First, we explored CXCR4 and CXCR7 expression in human lung cancer specimens and cell lines by immunohistochemistry, western blot and flow cytometry. Then, we chose the human lung adenocarcinoma cell line A549 that stably overexpressed CXCR7 through the way of lentivirus-mediated transduction. Next, "wound healing" assay and transwell assay were applied to compare the cell migration and invasion ability, and stripe assay was used to evaluate the cell polarization. Last, our team established a mouse xenograft model of human lung cancer and monitored tumor proliferation and metastasis by firefly luciferase bioluminescence imaging in SCID/Beige mice. RESULTS: In clinical lung cancer samples, CXCR7 expression was almost not detected in normal tissue but upregulated in lung tumor tissue, whereas, CXCR4 was highly expressed in both normal and tumor tissues. Furthermore, overexpression of CXCR7 enhanced A549 cell migration and polarization in vitro. Besides, mouse xenograft model of human lung cancer showed that CXCR7 promoted primary lung tumor's growth and metastasis to the second organ, such as liver or bone marrow in SCID/Beige mice in vivo. CONCLUSIONS: This study describes the multiple functions of CXCR7 in lung cancer. Thus, these results suggest that CXCR7 may be a malignancy marker and may provide a novel target for anticancer therapy.

15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(6): 742-748, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33236594

RESUMO

Objective: To investigate the effect of Candida albicans ( C. albicans) on proliferation and virulence of Streptococcus mutans ( S. mutans), and to verify the role of the ergosterol pathway in it. Methods: After single- and co-cultivation of C. albicans wild-type 5314 and S. mutansUA159, the absorbance value of OD 600and colony-forming units (CFU) were detected to reflect the influence of C. albicans on the growth of S. mutans. To reflect the influence of C. albicanson the virulence of S. mutans, the production of extracellular polysaccharides was detected by anthrone-vitriol method, and the acid production capacity was detected by a pH meter. After single- and co-cultivation of C. albicans mutant strains and S. mutans, the growth of S. mutans was evaluated by CFU. After inhibiting the ergosterol pathway by 0 mg/L, 0.012 5 mg/L, and 0.025 mg/L fluconazole for 24 h, the CFU of single- and co-cultivated C. albicans wild-type and S. mutans were detected. Results: The OD 600absorbance value and CFU in theco-cultivation of C. albicans wild-type and S. mutans was higher than that in the single culture ( P<0.05), and the production of extracellular polysaccharides in S. mutans was increased when S. mutans was co-cultured with C. albicans ( P<0.05), accompanied with a more obvious decrease of pH ( P<0.05). Fourteen strains in whole 42 C. albicans mutant strains lost the growth-promoting effect on S. mutans, including 6 ergosterol synthesis-related mutant strains. After co-cultivation of the 6 ergosterol synthesis-related mutant strains and S. mutans, the CFU of S. mutans remained unchanged or decreased. After inhibiting the ergosterol pathway by 0.012 5 mg/L and 0.025 mg/L fluconazole, the CFU of S. mutans in the co-cultivation of C. albicans wild-type and S. mutans was lower than that without fluconazole treatment ( P<0.05), while the CFU of C. albicans and S. mutans single-cultivations did not change significantly ( P>0.05) and the CFU of C. albicans in the co-cultivation of C. albicans wild-type and S. mutans did not change significantly ( P>0.05). Conclusion: C.albicans can enhance the growth ability and virulence of S. mutans through the ergosterol-related pathway. This process can be inhibited by fluconazole, which is expected to become a novel strategy to prevent and treat dental caries.

16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(6): 749-754, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33236595

RESUMO

Objective: To study the antibacterial effect of berberine combined with amylmetacresol on Enterococcus faecalis. Methods: Both dilution method and live bacteria CFU were used to determine the minimum inhibitory concentration (MIC) of berberine and amylmetacresol on E. faecalis. The killing effect of berberine and amylmetacresol on planktonic E. faecalis was detected by suspension quantitative germicidal test and live/dead bacteria staining. The effects of berberine and amylmetacresol on the structure of mature biofilm of E. faecalis was observed by scanning electron microscopy (SEM). The toxicity of berberine and amylmetacresol on human oral keratinocytes (HOK) was determined by CCK-8 cell proliferation and cytotoxicity assay and cytotoxicity LDH assay. Results: The MIC of berberine was 512 µg/mL, and the MIC of amylmetacresol was 0.023 3%. 512 µg/mL berberine and 0.002 33% amylmetacresol had a weak killing effect on planktonic E. faecalis alone, while they showed a synergistic antibacterial effect in combination. Cell survival in the biofilm was only slightly changed by berberine and amylmetacresol. The structure of biofilm was obviously changed by berberine and amylmetacresol. 512 µg/mL berberine and 0.002 33% amylmetacresol alone or in combination showed the survival rate was much higher than the injury rate, suggesting berberine and amylmetacresol had a low cytotoxicity. Conclusion: Berberine and amylmetacresol had synergism against E. faecalis, and the biological safety of the combination use was better.

17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(6): 760-766, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33236597

RESUMO

The oral environment provides suitable conditions for the colonization of various microorganisms. However, the oral microbials could be the initial factors of some kinds of oral infectious diseases, therefore the treatment against oral microbial pathogens has become an effective strategy. Artemisinin, a kind of sesquiterpene lactone extracted from Traditional Chinese Medicine Artemisia annua L., is the first-line therapy to treat tertian malaria, subtertian malaria and anti-chloroquine malaria for its high efficiency and low toxicity. In recent years, artemisinin and its derivatives have also been proven to be effective against bacteria, fungi, viruses, parasites, and tumors, some of which are closely related to oral diseases. In this review, we summarize the potential effects of artemisinin and its derivatives on oral microorganism by analyzing previous research and latest progress to provide the evidence for further improvement, and look forward to the new research directions. Further studies are needed to improve existing technologies and standards to clarify the effects of artemisinin and its derivatives on microorganisms with controversial effects, to expand the detection of microorganisms associated with oral infectious diseases, and to clarify the interaction with existing antifungal agents in the field of antifungal diseases. In addition, in the study of anti-oral infectious diseases, artemisinin and its derivatives' administration scheme, potential drug interactions, toxic and side effects and other aspects are necessary conditions for further research, which is also a new direction of research. With the maturity of the production process, the improvement of relevant research and the potential demand for the treatment of oral infectious diseases, artemisinin and its derivatives have a broad prospect in the field of oral microorganisms, and provide a new opportunity for the research and development of oral drugs.

18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(6): 771-776, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33236599

RESUMO

Connexins and Pannexins play important roles in osteocytes and osteoblasts differentiation, intracellular signal transduction, maintenance of bone balance, and bone regeneration. This article reviews the progress and limitations of Connexins-mediated gap junctions and Pannexins mediated hemichannel in bone. Current research has shown that these molecules, in the form of gap junctions or separate hemichannels, deliver external stimuli to the skeletal system. However, little is known about the role of other cell types in bone development and homeostasis, such as pre-osteoblasts and bone marrow mesenchymal stem cells, in maintaining normality. In addition, at present, the most well-studied member of the Connexins family is Connexin43 (Cx43), while the roles and mechanisms of other members in bone development are still behind the veil. Gene-edited animal models provide basic information on the role of Connexins and Pannexins in the skeletal system, but the similarities and differences between Connexins and Pannexins remain to be discovered. Targeting a specific function of Connexins or Pannexins for bone stimulation and bone disease remains a challenge, with pharmacological selective overlap between channels, compensation of other subtypes, differences in methods for assessing channel function, and genetic changes associated with transgenic mouse models. Therefore, better tools and research pathways are needed to understand the role of these pathways in bone and cartilage. An essential task for future research will be to identify specific compounds that regulate Connexins or Pannexins subtypes to enable them to be used as pharmaceutical agents in the treatment of bone diseases, providing the possibility to develop new therapeutic strategies for improving bone health and treating diseases of the skeletal system.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1757-1761, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067986

RESUMO

OBJECTIVE: To explore the clinical significance of G6PD gene mutation detection in female heterozygote with G6PD deficiency. METHODS: G6PD activity and fourteen common G6PD gene mutations in female blood samples were detected by biochemical phenotype detection and PCR-reverse dot blotting, respectively. Unidentified genotype of G6PD positive samples was further ascertained by direct DNA sequencing. The results from two methods were compared and analyzed. RESULTS: A total of 493 unrelated females were enrolled, and the G6PD activity and G6PD mutations was detected. Among them, 473 females were found to be normal in G6PD activity and 20 females with G6PD deficiency, and the detection rate by G6PD activity method was 4.06%. In all enrolled females, G6PD gene mutations, including the mutation of c.1311 C>T, were identified in 130 females, and the detection rate was 26.3%. Detection rate of the mutations that can lead to G6PD deficiency was 8.11%. The detection rates between the two methods were significantly different (P<0.01). The misdiagnosis rate of the G6PD activity detection reached 49. 94% for the female heterozygotes. Eight G6PD mutations and 13 mutation patterns were identified in the research, and most of mutation patterns were single nucleotide missense mutation. In addition to c.1311C>T mutation, the most common mutations were c.1376G>T, c.1388G>A and c.95 A>G. G6PD mutations were identified in 19 of 20 females with G6PD deficiency, and were also detected in 21 of 473 females with normal G6PD activity, of which the rate of heterozygous mutation was 90.88%. CONCLUSION: The phenotype detection based on G6PD enzyme activity alone is not sufficient for the diagnosis of female heterozygotes. The detection of G6PD mutations that covers the common mutations in specified region can effectively identify the female heterozygotes with normal G6PD activity.


Assuntos
Deficiência de Glucosefosfato Desidrogenase , Feminino , Genótipo , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Heterozigoto , Humanos , Mutação
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