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1.
BMC Musculoskelet Disord ; 24(1): 756, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37749526

RESUMO

BACKGROUND: Both closed platform and open platform robotic-assisted total hip arthroplasty (THA) have recently been recommended as a viable treatment option for achieving accurate positioning of components. Yet, limited studies paid attention to the differences between the closed platform robotic system and the open platform robotic system. Hence, this study aimed to investigate clinical outcomes, radiographic outcomes, complication rates and learning curve of two systems. MATERIALS AND METHODS: We retrospectively included 62 patients (31 closed robotic system and 31 open robotic system) who underwent THA between February 2021 and January 2023. The demographics, operating time, cup positioning, complications and hip Harris score were evaluated. Learning curves of operation time was conducted using cumulative sum (CUSUM) analysis. RESULTS: There were no differences in surgical time (76.7 ± 12.1 min vs. 72.3 ± 14.8 min), estimated blood loss (223.2 ± 13.2 ml vs. 216.9 ± 17 ml) and Harris Hip score (HHS) between closed platform robotic system and the open platform robotic system. The closed robotic system and the open robotic system were associated with a learning curve of 9 cases and 7 cases for surgical time respectively, based on the satisfying rate of Lewinnek's safe zone outliers (1/31, 96.8%) and no occurrence of complication. Both robotic systems had significant reduction in overall surgical time, the duration of acetabulum registration, and estimated blood loss between learning phase and proficiency phase. CONCLUSION: The authors suggest that the surgical outcomes and safe zone outlier rate of the open robotic-assisted THA were similar to those of the closed robotic-assisted THA. These two robotic-assisted are associated with comparable learning curves and both have the precise positioning of acetabular component. From learning phase to proficiency phase, the rate of positions within the safe zone differed only marginally (88.9-100% vs. 85.7-100%) based on a rather low number of patients. This is not a statistically significant difference. Therefore, we suggest that THA undergoing with the robotic-assisted system is the relatively useful way to achieve planned acetabular cup position so far.


Assuntos
Artroplastia de Quadril , Procedimentos Cirúrgicos Robóticos , Humanos , Curva de Aprendizado , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Acetábulo
2.
Int J Mol Sci ; 24(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37047484

RESUMO

Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein-protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein-protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.


Assuntos
COVID-19 , Cardiomiopatias , MicroRNAs , Isquemia Miocárdica , Humanos , Biologia de Sistemas , Simulação de Acoplamento Molecular , Vindesina , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/genética , SARS-CoV-2 , Biologia Computacional , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/genética , Comorbidade , MicroRNAs/genética , Biomarcadores , Fatores de Transcrição , Perfilação da Expressão Gênica
3.
Int Orthop ; 46(3): 489-496, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34580745

RESUMO

BACKGROUND: Patients with poliomyelitis underwent total hip arthroplasty (THA) are known to be at higher risk of dislocation on account of muscular atrophy. This study aimed to investigate clinical outcomes, radiographic outcomes, complication rates, and survivorship of dual mobility THA in displaced femoral neck fractures of elderly with poliomyelitis. MATERIALS AND METHODS: We retrospectively included 17 patients (17 hips) with residual poliomyelitis who underwent THA with dual mobility articulation. Clinical outcomes were assessed with the visual analog scale (VAS) pain score, Oxford hip score, and University of California Los Angeles activity (UCLA) score. Radiographic outcomes were examined by radiographs. Complications and re-operations following THA were recorded. RESULTS: The mean follow-up period was 77.05 months. The mean VAS, Oxford hip score, and UCLA score were improved significantly. In all but one patient, no complications were occurred. Re-operation was carried out in one patient due to posterior dislocation. The Kaplan-Meier survivorship with an end point of re-operation for any reason was 94.1%. CONCLUSIONS: THA with dual mobility system is proved to be effective in strengthening stability and reducing the risk of dislocation, which is suitable for patients with neuromuscular disease. Hence, in elderly with residual poliomyelitis, dual mobility THA is a valid choice as a treatment for displaced femoral neck fractures.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Luxação do Quadril , Prótese de Quadril , Poliomielite , Idoso , Fraturas do Colo Femoral/cirurgia , Luxação do Quadril/cirurgia , Humanos , Poliomielite/complicações , Desenho de Prótese , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
4.
Biotechnol Lett ; 43(4): 791-802, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33404903

RESUMO

Osteoarthritis (OA) is a chronic joint disease, which occurs in the elderly. The regulatory mechanisms of circRNAs were involved in the occurrence and development of various diseases. However, the potential regulatory network of circRNA in OA remains further research and clarification. The expression of circ_0114876 was increased in OA tissues and inhibition of circ_0114876 could induce cell viability and suppress inflammation as well as inhibit cell apoptosis in IL-1ß induced CHON-001 cells. Circ_0114876 regulated TRAF2 expression via sponging miR-671 in CHON-001 cells. Down-regulated miR-671 expression could reverse the effects of low circ_0114876 expression on cell progression and inflammation in IL-1ß induced CHON-001 cells. Overexpression of TRAF2 could weaken the promotion effects of high miR-671 expression on cell progression and inflammation in IL-1ß induced CHON-001 cells. Circ_0114876 targeted miR-671 to regulate cell progression and inflammation via modulating TRAF2 expression in IL-1ß induced CHON-001 cells, and played an important regulatory mechanism in IL-1ß-induced chondrocyte injury, providing a novel diagnostics and therapeutics in OA.


Assuntos
Condrócitos/citologia , Interleucina-1beta/metabolismo , MicroRNAs/genética , Osteoartrite/genética , RNA Circular/genética , Fator 2 Associado a Receptor de TNF/genética , Regiões 3' não Traduzidas , Linhagem Celular , Sobrevivência Celular , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Progressão da Doença , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/farmacologia , Modelos Biológicos , Regulação para Cima
5.
BMC Musculoskelet Disord ; 22(1): 806, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34537036

RESUMO

BACKGROUND: Performing postoperative laboratory tests following joint arthroplasty is a regular practice. However, the role of routine postoperative laboratory tests in primary hip arthroplasty is currently in doubt. This study aimed to assess the role of routine postoperative laboratory tests for femoral neck fractures in elderly patients who underwent hip hemiarthroplasty and to evaluate the risk factors for postoperative laboratory testing abnormalities and related interventions. METHODS: This retrospective study reviewed 735 consecutive patients with femoral neck fractures (FNFs) who underwent hip hemiarthroplasty at a single tertiary academic organization. Patient characteristic features and laboratory testing values were recorded. Logistic regression models were calculated to identify risk factors. RESULTS: A total of 321 elderly patients (> 75 years of age) were ultimately enrolled for analysis. Abnormal postoperative laboratory tests were found in 265 patients (82.6%). Only a minority of the included patients (7.5%) needed medical intervention to treat postoperative laboratory testing abnormalities. Multivariate logistic regression analysis reported that a higher Charlson comorbidity index (CCI) (P = 0.03), abnormal preoperative haemoglobin level (P < 0.01), higher intraoperative blood loss (P < 0.01) and less frequent tranexamic acid use (P = 0.05) were risk factors for abnormal postoperative laboratory tests. Furthermore, a higher CCI has been identified as a risk factor for patients needing clinical interventions related to laboratory abnormalities. CONCLUSIONS: Because 92.5% of laboratory tests did not influence postoperative management, the authors suggest that routine laboratory tests after hip hemiarthroplasty for FNFs are less instructive for the majority of elderly patients. Nevertheless, for patients with identified risk factors, postoperative laboratory tests are still required to identify the abnormalities that need to be managed.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Hemiartroplastia , Idoso , Artroplastia de Quadril/efeitos adversos , Fraturas do Colo Femoral/diagnóstico , Fraturas do Colo Femoral/epidemiologia , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Humanos , Período Pós-Operatório , Estudos Retrospectivos
6.
Cancer Cell Int ; 20: 366, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774160

RESUMO

BACKGROUND: Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that transgelin was up-regulated in node-positive colorectal cancer (CRC) versus node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms through which transgelin participates in the metastasis of colon cancer cells. METHODS: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with transgelin. The 256 downstream transcripts regulated by transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with transgelin. The interaction between transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence. RESULTS: Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven key genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1, which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with transgelin. The interaction between PARP1 and transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays. CONCLUSIONS: Our results suggest that transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.

7.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2694-2701, 2020 Jun.
Artigo em Zh | MEDLINE | ID: mdl-32627505

RESUMO

Coicis Semen is widely used as a raw material which can be used as both medicine and food among people. According to the ancient monographs on materia medica and relevant documents on the processing specifications in various provinces and cities, herba logical study on the historical evolution of the processing methods of Coicis Semen was conducted in this paper from the aspects of collecting and processing methods of Coicis Semen, the processing methods in the past dynasties and the nature, flavour and efficacy of Coicis Semen. The results showed that the processing methods of Coicis Semen recorded in monographs on materia medica mainly included stir-frying, glutinous rice stir-frying, salt processing(including salt cooking and salt stir-frying), stir-frying with the earth scraped from the wall facing east, and ginger juice stir-frying, etc. Among them, stir-frying, and stir-frying with the earth scraped from the wall facing east are still used nowadays. The bran stir-frying is the improved version of glutinous rice stir-frying in order to be adaptive to the modern-day situation and the needs of the present. In addition, the ancient shell removal and kernel keeping method are also included in the processing procedures in modern local processing specifications, which are combined with frying to form a new method named "Fazhi" processing( "Fazhi" means a processing method of multiple procedures). The 2015 edition of Chinese Pharmacopoeia records that Coicis Semen is helpful to clear dampness and promote diuresis, strengthen the spleen and prevent diarrhea, eliminate impediment, discharge pus, resolve toxin and a mass, etc., which are consistent with those contained in ancient monographs on materia medica. After the "Fazhi" processing, the cold nature of Coicis Semen has been removed and its nature,flavour and meridian tropism have been changed, so its application scopes expanded. The results of this study clearly traced the history of the collecting and proces-sing of Coicis Semen, summarized the nature, flavour and efficacy of Coicis Semen contained in both ancient and modern literature, and provided a historical basis for the standardization of the subsequent processing technology of Coicis Semen, the clinical application of various processed products, and the further development and utilization of medicinal materials.


Assuntos
Coix , Medicamentos de Ervas Chinesas , Materia Medica , Oryza , Zingiber officinale , Culinária , Medicina Tradicional Chinesa
8.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3997-4003, 2020 Aug.
Artigo em Zh | MEDLINE | ID: mdl-32893600

RESUMO

Citri Sarcodactylis Fructus is a both medicinal and edible species specified by the China Ministry of Health, with a long history in China. According to the ancient monographs about materia medica, it was found that the records of the Citri Sarcodactylis Fructus on the original plants were confused. This paper reviewed the ancient monographs about materia medica, and made a summarization and textual research on the name, origin, habitat, processing methods, medicinal properties and clinicacy efficacy of Citri Sarcodactylis Fructus based the comprehensive analysis on modern literatures and authoritative books of Chinese herbal medicine. The results indicated that there were many bynames of Citri Sarcodactylis Fructus. Before the Yuan Dynasty, there was a mixed use of Citri Sarcodactylis Fructus and Citri Fructus, which were not distinguished from each other in terms of nature and taste until the Yuan dynasty. Citri Sarcodactylis Fructus was a varietas of Citri Fructus. The main shape of the original plant of Citri Sarcodactylis Fructus is "like a human hand with fingers" as recorded in ancient monographs about materia medica. The main places of origin of Citri Sarcodactylis Fructus were Guangdong, Zhejiang, Fujian, Sichuan, which were relatively stable. There were fewer records about medicinal proces-sing methods of Citri Sarcodactylis Fructus. Only steaming and baking methods were found in ancient monographs about materia medica, and the steaming method could reduce the irritability of Citri Sarcodactylis Fructus. The processing of therapeutic dietary of Citri Sarcodactylis Fructus was widely used in folk, which was represented by Chaozhou Laoxianghuang, a traditional succade made of Citri Sarcodactylis Fructus. According to the 2015 edition of Chinese Pharmacopoeia, Citri Sarcodactylis Fructus had effects in soothing liver and regulating gas, relieving pain in the stomach, eliminating dampness and resolving phlegm, which was basically consistent with the descriptions in ancient monographs about materia medica. This paper defined the original plant of Citri Sarcodactylis Fructus, and sorted out and summarized the processing methods, nature and taste of Citri Sarcodactylis Fructus, so as to provide data support for the standardization of the processing technology and the development and utilization of Citri Sarcodactylis Fructus.


Assuntos
Medicamentos de Ervas Chinesas , Materia Medica , China , Frutas , Humanos , Medicina Tradicional Chinesa
9.
Front Public Health ; 12: 1280163, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435294

RESUMO

Background: The relationships between heavy metals and fatty liver, especially the threshold values, have not been fully elucidated. The objective of this research was to further investigate the correlation between blood heavy metal exposures and the risk of Metabolic dysfunction Associated Fatty Liver Disease (MAFLD) in adults. Methods: Laboratory data on blood metal exposure levels were obtained from National Health and Nutrition Examination Survey (NHANES) data for the period 2015 to 2020 for a cross-sectional study in adults. Associations between blood levels of common heavy metals and the risk of MAFLD in adults were analyzed using multifactorial logistic regression and ranked for heavy metal importance using a random forest model. Finally, thresholds for important heavy metals were calculated using piecewise linear regression model. Results: In a multifactorial logistic regression model, we found that elevated levels of selenium (Se) and manganese (Mn) blood exposure were strongly associated with the risk of MAFLD in adults. The random forest model importance ranking also found that Se and Mn blood exposure levels were in the top two positions of importance for the risk of disease in adults. The restricted cubic spline suggested a non-linear relationship between Se and Mn blood exposure and adult risk of disease. The OR (95% CI) for MAFLD prevalence was 3.936 (2.631-5.887) for every 1 unit increase in Log Mn until serum Mn levels rose to the turning point (Log Mn = 1.10, Mn = 12.61 µg/L). This correlation was not significant (p > 0.05) after serum Mn levels rose to the turning point. A similar phenomenon was observed for serum Se levels, with a turning point of (Log Se = 2.30, Se = 199.55 µg/L). Conclusion: Blood heavy metals, especially Se and Mn, are significantly associated with MAFLD in adults. They have a non-linear relationship with a clear threshold.


Assuntos
Metais Pesados , Hepatopatia Gordurosa não Alcoólica , Selênio , Adulto , Humanos , Estudos Transversais , Inquéritos Nutricionais , Metais Pesados/efeitos adversos
10.
Biomed Pharmacother ; 170: 116039, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38157643

RESUMO

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.


Assuntos
Produtos Biológicos , Medicamentos de Ervas Chinesas , Nefropatias , Humanos , Medicina Tradicional Chinesa , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Nefropatias/tratamento farmacológico , Fibrose , Sistemas de Liberação de Medicamentos
11.
Nat Cell Biol ; 26(2): 294-304, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38263276

RESUMO

Base editors (BEs) introduce base substitutions without double-strand DNA cleavage. Besides precise substitutions, BEs generate low-frequency 'stochastic' byproducts through unclear mechanisms. Here, we performed in-depth outcome profiling and genetic dissection, revealing that C-to-G BEs (CGBEs) generate substantial amounts of intermediate double-strand breaks (DSBs), which are at the centre of several byproducts. Imperfect DSB end-joining leads to small deletions via end-resection, templated insertions or aberrant transversions during end fill-in. Chromosomal translocations were detected between the editing target and off-targets of Cas9/deaminase origin. Genetic screenings of DNA repair factors disclosed a central role of abasic site processing in DSB formation. Shielding of abasic sites by the suicide enzyme HMCES reduced CGBE-initiated DSBs, providing an effective way to minimize DSB-triggered events without affecting substitutions. This work demonstrates that CGBEs can initiate deleterious intermediate DSBs and therefore require careful consideration for therapeutic applications, and that HMCES-aided CGBEs hold promise as safer tools.


Assuntos
Ácidos Alcanossulfônicos , Quebras de DNA de Cadeia Dupla , Translocação Genética , Humanos , Reparo do DNA por Junção de Extremidades , Reparo do DNA/genética , Sistemas CRISPR-Cas
12.
J Cell Biochem ; 114(10): 2221-30, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23553680

RESUMO

Transplantation of functional insulin-producing cells (IPCs) provides a novel mode for insulin replacement, but is often accompanied by many undesirable side effects. Our previous studies suggested that IPCs could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. To obtain a better method through which to acquire more similar IPCs, we compared the difference between IPCs of the GLP-1 group and IPCs of the non-GLP-1 group in the morphological features in cellular level and physiological function. The levels of insulin secretion were measured by ELISA. The insulin and glucagon-like peptide-1 (GLP-1) mRNA gene expression was determined by real-time quantitative PCR. The morphological features were detected by atomic force microscopy (AFM) and laser confocal scanning microscopy (LCSM). Intracellular Ca(2+) levels and Glucagon-like peptide-1 receptor (GLP-1R) levels were determined by flow cytometer (FCM). We found that IPCs of the GLP-1 group had bigger membrane particle size and average roughness (Ra ) than IPCs of the non-GLP-1 group but still smaller than normal human pancreatic beta cells. The physiology function of IPCs of the GLP-1 group were much closer to normal human pancreatic beta cells than IPCs of the non-GLP-1 group. GLP-1 could improve the similarity of IPCs from human adipose tissue-derived mesenchymal stem cells and pancreatic beta cells in cellular ultrastructure and function.


Assuntos
Células Secretoras de Insulina/metabolismo , Receptores de Glucagon/metabolismo , Cálcio/metabolismo , Células Cultivadas , Citometria de Fluxo , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Microscopia de Força Atômica , Receptores de Glucagon/genética
13.
Diabetes Metab Syndr Obes ; 16: 1297-1321, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37179788

RESUMO

Animal models play a crucial role in studying the pathogenesis of diseases, developing new drugs, identifying disease risk markers, and improving means of prevention and treatment. However, modeling diabetic kidney disease (DKD) has posed a challenge for scientists. Although numerous models have been successfully developed, none of them can encompass all the key characteristics of human DKD. It is essential to choose the appropriate model according to the research needs, as different models develop different phenotypes and have their limitations. This paper provides a comprehensive overview of biochemical and histological phenotypes, modeling mechanisms, advantages and limitations of DKD animal models, in order to update relevant model information and provide insights and references for generating or selecting the appropriate animal models to fit different experimental needs.

14.
Front Oncol ; 13: 1276976, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869095

RESUMO

Aim: The aim of this study was to identify potential safety concerns associated with Sacituzumab Govitecan (SG), an antibody-drug conjugate targeting trophoblastic cell-surface antigen-2, by analyzing real-world safety data from the largest publicly available worldwide pharmacovigilance database. Methods: All data obtained from the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2020 to the fourth quarter of 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the adverse event signals of SG, considering statistical significance when the lower limit of the 95% CI >1, based on at least 3 reports. Results: Total of 1072 cases were included. The main safety signals were blood and lymphatic system disorders [ROR(95CI)=7.23 (6.43-8.14)], gastrointestinal disorders [ROR(95CI)=2.01 (1.81-2.22)], and relative infection adverse events, such as neutropenic sepsis [ROR(95CI)=46.02 (27.15-77.99)] and neutropenic colitis [ROR(95CI)=188.02 (120.09-294.37)]. We also noted unexpected serious safety signals, including large intestine perforation [ROR(95CI)=10.77 (3.47-33.45)] and hepatic failure [ROR(95CI)=3.87 (1.45-10.31)], as well as a high signal for pneumonitis [ROR(95CI)=9.93 (5.75-17.12)]. Additionally, age sub-group analysis revealed that geriatric patients (>65 years old) were at an increased risk of neutropenic colitis [ROR(95CI)=282.05 (116.36-683.66)], neutropenic sepsis [ROR(95CI)=101.11 (41.83-244.43)], acute kidney injury [ROR(95CI)=3.29 (1.36-7.94)], and atrial fibrillation [ROR(95CI)=6.91 (2.86-16.69)]. Conclusion: This study provides crucial real-world safety data on SG, complementing existing clinical trial information. Practitioners should identify contributing factors, employ monitoring and intervention strategies, and focus on adverse events like neutropenic sepsis, large intestine perforation, and hepatic failure. Further prospective studies are needed to address these safety concerns for a comprehensive understanding and effective management of associated risks.

15.
Sci Immunol ; 8(81): eade1167, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-36961908

RESUMO

Insertions and deletions (indels) are low-frequency deleterious genomic DNA alterations. Despite their rarity, indels are common, and insertions leading to long complementarity-determining region 3 (CDR3) are vital for antigen-binding functions in broadly neutralizing and polyreactive antibodies targeting viruses. Because of challenges in detecting indels, the mechanism that generates indels during immunoglobulin diversification processes remains poorly understood. We carried out ultra-deep profiling of indels and systematically dissected the underlying mechanisms using passenger-immunoglobulin mouse models. We found that activation-induced cytidine deaminase-dependent ±1-base pair (bp) indels are the most prevalent indel events, biasing deleterious outcomes, whereas longer in-frame indels, especially insertions that can extend the CDR3 length, are rare outcomes. The ±1-bp indels are channeled by base excision repair, but longer indels require additional DNA-processing factors. Ectopic expression of a DNA exonuclease or perturbation of the balance of DNA polymerases can increase the frequency of longer indels, thus paving the way for models that can generate antibodies with long CDR3. Our study reveals the mechanisms that generate beneficial and deleterious indels during the process of antibody somatic hypermutation and has implications in understanding the detrimental genomic alterations in various conditions, including tumorigenesis.


Assuntos
Genes de Imunoglobulinas , Mutação INDEL , Animais , Camundongos , Mutação , Reparo do DNA/genética , DNA/genética
16.
Mol Cell Biochem ; 365(1-2): 223-31, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22403013

RESUMO

Chondroid cell from human adipose-derived stem cells (ADSCs) has emerged as an alternative treatment option for articular cartilage defects. Herein, we successfully compared ADSCs, normal chondrocytes, and chondroid cells. The comparative study of ADSCs and chondroid cells revealed type II collagen (COL II) and glycosaminoglycans expression of chondroid cells were similar to those in normal chondrocytes, and much higher than ADSCs. Using atomic force microscope (AFM) and laser confocal scanning microscopy (LCSM), we compared the differences in morphology, mechanical properties, and F-actin distribution between chondroid cells and normal chondrocytes. Our results showed no differences observed between these two types of cells regarding morphology, stiffness, and F-actin distribution. However, found that the adhesion force in chondroid cells was lower than that in normal chondrocytes. Taken together, our AFM and LCSM analyses suggest that the lower adhesion force in chondroid cells may contribute to the dedifferentiation of ADSC-derived chondroid cells. Future examination of surface adhesion force-related protein expression will likely provide new insight into the molecular mechanisms underlying the dedifferentiation of ADSC-derived chondroid cells.


Assuntos
Tecido Adiposo/citologia , Células-Tronco Adultas/fisiologia , Condrócitos/fisiologia , Microscopia de Força Atômica , Adolescente , Adulto , Células-Tronco Adultas/metabolismo , Antígenos CD/metabolismo , Fenômenos Biomecânicos , Adesão Celular , Desdiferenciação Celular , Diferenciação Celular , Forma Celular , Condrócitos/metabolismo , Perfilação da Expressão Gênica , Humanos , Fenótipo , Resistência ao Cisalhamento , Análise de Célula Única , Adulto Jovem
17.
Appl Microbiol Biotechnol ; 94(2): 479-86, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22395905

RESUMO

We successfully differentiated human adipose tissue-derived mesenchymal stem cells (haMSCs) into insulin-producing cells (IPCs) in vitro and did not use any insulin which might be absorbed by cells during in vitro culture. Expression of insulin gene was massively increased by 28,000-fold at day 12 compared with haMSCs (P < 0.05). IPCs could secrete insulin after glucose was stimulated. The higher the concentration of glucose, the more production of insulin was noted. We reported AFM images of IPCs for the first time. AFM images showed that the sizes of cells were similar to each other, and all IPC surface had a porous structure in the cytoplasm area. In sugar-free group, the size of holes was similar (diameter, 1,086.98 ± 156.70 nm; depth, 185.22 ± 52.14 nm). In higher sugar-stimulated group, there were more holes with bigger diameter and smaller depth. (diameter, 3,183.65 ± 2,229.18 nm; depth 109.42 ± 56.26 nm, P < 0.05). We found that the hole diameter and depth could change with the concentration of glucose in media. Concurrently, laser scanning confocal microscopy images indicated that cortical actin network beneath plasma membrane in IPCs was dense and continuous. After glucose stimulation, we found the actin web depolymerized and became discontinuous in IPCs. We speculated that diameter augmentation of holes located in the cytoplasm area in IPCs was one manifestation of excytosis increase.


Assuntos
Tecido Adiposo/citologia , Insulina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Microscopia de Força Atômica/métodos , Actinas/análise , Diferenciação Celular , Meios de Cultura/química , Citoplasma/química , Perfilação da Expressão Gênica , Glucose/metabolismo , Humanos , Secreção de Insulina , Microscopia Confocal
18.
Water Sci Technol ; 65(12): 2200-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22643416

RESUMO

Owing to high levels of residual antibiotics, antibiotic manufacturing waste is hazardous to the environment. As a result, such wastes are usually treated by expensive incineration. The high organic content of antibiotic manufacturing biowaste suggests its feasibility for anaerobic treatment, but the presence of ammonia and antibiotics in the waste may be inhibitory factors. After evaluating the peak concentrations of volatile fatty acids (VFAs), ammonia and lincomycin in 10 d bio-liquefaction, different methods for the removal of ammonia from hydrolysate and removal of lincomycin from biowaste were employed to relieve ammonia and lincomycin inhibition respectively. Prior to ammonia elimination on the tenth day, 38.0% of the organic carbon was degraded into hydrolysate. Water replacement, struvite precipitation and nitrogen stripping removed 100, 76 and 30% of the ammonia, respectively. The hydrolysate obtained from the water replacement could be immediately utilized for liquefaction. Lincomycin elution through butanol and water prior to liquefaction removed a large amount of carbohydrate and protein, resulting in poor liquefaction efficiency. The residual lincomycin in the bio-liquefaction process could be co-treated with lincomycin manufacturing wastewater, which made it suitable for the treatment of lincomycin manufacturing biowaste.


Assuntos
Antibacterianos/síntese química , Indústria Farmacêutica , Resíduos Industriais , Lincomicina/síntese química , Amônia/isolamento & purificação , Anaerobiose , Hidrólise
19.
Cell Biochem Biophys ; 80(2): 443-455, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35257277

RESUMO

Adipose-derived stem cells are one of the potential sources of cells for the treatment of cartilage defects. This study aimed to investigate the molecular mechanisms that account for the chondrogenic differentiation of human adipose-derived stem cells (hADSCs). We employed integrin ß1 (ITGB1) overexpression to induce chondrogenic differentiation of hADSCs. Next-generation sequencing was used to determine the mRNAs and circular RNAs (circRNAs) expression profiles in ITGB1-overexpresing and negative control cells. The potential functions of differentially expressed mRNAs were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Moreover, differentially expressed circRNAs with the greatest fold change were validated by polymerase chain reaction (PCR), Sanger sequencing, and quantitative real-time PCR (qRT-PCR). These three circRNAs and their downstream microRNAs and mRNAs were used to construct a circRNA-microRNA-mRNA interaction network. The results showed that we identified 713 differentially expressed circRNAs (150 upregulated and 563 downregulated in ITGB1-overexpressing hADSCs versus negative control cells, respectively). Meanwhile, 2383 mRNAs were differentially expressed between two groups (1672 upregulated and 711 downregulated in ITGB1-overexpressing cells compared with the negative control cells). The GO and KEGG analysis results showed that the differentially expressed mRNAs were enriched in biological processes, cellular components, and molecular functions, especially in the phosphatidylinositol 3-kinase (PI3K)-AKT and mitogen-activated protein kinase signaling pathways. Three differentially expressed circRNAs, including hsa_circ_0071127, hsa_circ_0008637, and hsa_circ_0020028, were validated by qRT-PCR. Moreover, the circRNA-microRNA-mRNA network predicted that fibroblast growth factor 2 (FGF2) was a common node regulated by these three circRNAs through several microRNAs, including miR-195-3p, miR-205-3p, and miR-152-3p. We further found that the knockdown of hsa_circ_0020028, but not the two other circRNAs, significantly reduced FGF2 mRNA expression in hADSCs. Furthermore, the knockdown of hsa_circ_0020028 significantly inhibited the protein expression of FGF2, chondrogenic differentiation markers (COL II, aggrecan, and SOX9), and PI3K/AKT signaling in ITGB1-overexpressing hADSCs. This study uncovered the differentially expressed mRNA and circRNA profiles in the chondrogenic differentiation of hADSCs induced by ITGB1 overexpression. Our findings demonstrate that hsa_circ_0020028 regulates the ITGB1 overexpression-mediated chondrogenic differentiation of hADSCs through regulation of FGF2-related signaling pathways.


Assuntos
MicroRNAs , RNA Circular , Fator 2 de Crescimento de Fibroblastos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/genética , RNA Circular/genética , RNA Mensageiro/genética , Células-Tronco/metabolismo
20.
Water Res ; 220: 118592, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35613481

RESUMO

Samples from fifty-five surface water resources and twenty-five drinking water treatment plants in Europe, Africa, Asia, and USA were used to analyse the fluorescence composition of global surface waters and predict aromaticity and treatability from fluorescence excitation emission matrices. Nine underlying fluorescence components were identified in the dataset using parallel factor analysis (PARAFAC) and differences in aromaticity and treatability could be predicted from ratios between components Hii (λex/λem= 395/521), Hiii (λex/λem= 330/404), Pi, (λex/λem=290/365) and Pii (λex/λem= 275/302). Component Hii tracked humic acids of primarily plant origin, Hiii tracked weathered/oxidised humics and the "building block" fraction measured by LC-OCD, while Pi and Pii tracked amino acids in the "low molecular weight neutrals" LC-OCD fraction. Ratios between PARAFAC components predicted DOC removal at lab scale for French rivers in standardized tests involving coagulation, powdered activated carbon (PAC), chlorination, ion exchange (IEX), and ozonation, alone and in combination. The ratio Hii/Hiii, for convenience named "PARIX" standing for "PARAFAC index", predicted SUVA according to a simple relationship: SUVA = 4.0 x PARIX (RMSEp=0.55) Lmg-1m-1. These results expand the utility of fluorescence spectroscopy in water treatment applications, by demonstrating the existence of previously unknown relationships between fluorescence composition, aromaticity and treatability that appear to hold across diverse surface waters at various stages of drinking water treatment.


Assuntos
Água Potável , Purificação da Água , Matéria Orgânica Dissolvida , Água Potável/análise , Análise Fatorial , Substâncias Húmicas/análise , Rios , Espectrometria de Fluorescência/métodos , Purificação da Água/métodos
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