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1.
Cell Mol Life Sci ; 81(1): 69, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294557

RESUMO

Fibrosis is a typical aging-related pathological process involving almost all organs, including the heart, kidney, liver, lung, and skin. Fibrogenesis is a highly orchestrated process defined by sequences of cellular response and molecular signals mechanisms underlying the disease. In pathophysiologic conditions associated with organ fibrosis, a variety of injurious stimuli such as metabolic disorders, epigenetic changes, and aging may induce the progression of fibrosis. Sirtuins protein is a kind of deacetylase which can regulate cell metabolism and participate in a variety of cell physiological functions. In this review, we outline our current understanding of common principles of fibrogenic mechanisms and the functional role of SIRT3/6 in aging-related fibrosis. In addition, sequences of novel protective strategies have been identified directly or indirectly according to these mechanisms. Here, we highlight the role and biological function of SIRT3/6 focus on aging fibrosis, as well as their inhibitors and activators as novel preventative or therapeutic interventions for aging-related tissue fibrosis.


Assuntos
Sirtuína 3 , Sirtuínas , Humanos , Fígado , Fibrose
2.
Nucleic Acids Res ; 51(20): e105, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37843111

RESUMO

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells. We then perform deaminase engineering for two deaminases lamprey LjCDA1 and human APOBEC3A, and generate divergent CBE variants with eliminated DSB-associated DNA damage risks, in addition to minimized DNA/RNA off-target edits. Furthermore, the editing scopes and sequence preferences of APOBEC3A-derived CBEs could be further diversified by internal fusion strategy. Taken together, this study provides updated evaluation platform for DSB-associated DNA damage risks of CBEs and further generates a series of safer toolkits with diversified editing signatures to expand their applications.


Assuntos
Citosina , Edição de Genes , Humanos , RNA/genética , Dano ao DNA , DNA/genética , Sistemas CRISPR-Cas
3.
EMBO J ; 39(8): e102961, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32090361

RESUMO

Both metabolic switch from oxidative phosphorylation to glycolysis (OGS) and epithelial-mesenchymal transition (EMT) promote cellular reprogramming at early stages. However, their connections have not been elucidated. Here, when a chemically defined medium was used to induce early EMT during mouse reprogramming, a facilitated OGS was also observed at the same time. Additional investigations suggested that the two events formed a positive feedback loop via transcriptional activation, cooperated to upregulate epigenetic factors such as Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5, and accelerated pluripotency induction at the early stage. However, at late stages, by over-inducing glycolysis and preventing the necessary mesenchymal-epithelial transition, the two events trapped the cells at a new pluripotency state between naïve and primed states and inhibited further reprogramming toward the naïve state. In addition, the pluripotent stem cells at the new state have high similarity to epiblasts from E4.5 and E5.5 embryos, and have distinct characteristics from the previously reported epiblast-like or formative states. Therefore, the time-dependent cooperation between OGS and EMT in regulating pluripotency should extend our understanding of related fields.


Assuntos
Reprogramação Celular , Transição Epitelial-Mesenquimal/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Glicólise , Fosforilação Oxidativa , Células-Tronco Pluripotentes/metabolismo , Animais , Blastocisto , Feminino , Humanos , Camundongos , Camundongos Endogâmicos ICR , Regulação para Cima
4.
Arch Virol ; 169(5): 96, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619633

RESUMO

In recent years, the pig industry in Xinjiang, China, has been severely impacted by outbreaks of porcine epidemic diarrhea (PED), despite vaccination efforts. In this study, we investigated the genetic characteristics of currently prevalent porcine epidemic diarrhea virus (PEDV) strains in the region. We collected 548 samples from animals with suspected PED on large-scale pig farms in Xinjiang. Of these, 258 tested positive for PEDV by RT-PCR, yielding an overall positivity rate of 47.08%. S1 gene sequencing and phylogenetic analysis were conducted on 23 randomly selected RT-PCR-positive samples. Three endemic strains of PEDV (PEDV/CH/XU/2020, PEDV/CH/XK/2020, and PEDV/CH/XA/2020) were isolated, and their complete genome sequences were analyzed for evidence of genetic recombination. Sequence comparison of the S gene indicated significant variations in the S1 gene of the Xinjiang strains compared to the vaccine strains CV777, AJ1102, and LWL, with 90.2%-98.5% nucleotide sequence identity. Notably, both the N-terminal and C-terminal domains of the S protein showed significant variation. Genetic evolutionary analysis identified the GIIa subtype as the dominant genotype among the epidemic strains in Xinjiang. Recombination analysis revealed inter-subtype recombination events in the PEDV/CH/XK/2020 and XJ1904-34 strains. These findings highlight the extensive genetic variation in the predominant GIIa genotype of PEDV in Xinjiang, which does not match the genotype of the currently used vaccine strains. These data may guide further efforts toward the development of effective vaccines for the control of PED.


Assuntos
Disenteria , Vírus da Diarreia Epidêmica Suína , Vacinas , Animais , Suínos , Filogenia , Vírus da Diarreia Epidêmica Suína/genética , Evolução Biológica , China/epidemiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38940779

RESUMO

Objective: To investigate the effect of icariin (ICA) on cognitive function and NO/cGMP/PKGI signaling pathway in mice with Alzheimer's disease (AD). Methods: Wild-type C57BL/6 mice were used as the Control group, and APP/PS1 double transgenic mice were used to establish the AD model. The mice were randomly divided into AD group, AD+L-icariin group (10 mg/kg), and AD+H-icariin group (40 mg/kg), with 10 mice in each group. Water maze and Y-maze tests were used to evaluate the learning and memory abilities of mice. ELISA was used to measure the levels of serum Aß and cGMP. Tunel staining was used to determine the apoptosis of neurons in the hippocampus. Immunohistochemistry was used to measure the expression of Brdu, Dcx, and NeuN in the hippocampus. The protein expressions of iNOS, sGC, PKGI, Caspase3, Bax, and Bcl-2 in brain tissue were determined by Western blot. Results: Compared with the control group, the learning and memory ability of the AD group was significantly decreased, the serum levels of Aß and cGMP were increased, the neuronal apoptosis was increased, the contents of Brdu, Dcx and NeuN were decreased, the expression of iNOS, sGC, PKGI, Caspase-3 and Bax proteins was increased, and the expression of Bcl-2 protein was decreased (P < .05). Compared with the AD group, the AD mice treated with icariin (40mg/kg) showed improved learning and memory abilities, decreased serum Aß and cGMP contents, decreased neuronal apoptosis, increased Brdu, Dcx, and NeuN contents, and decreased iNOS, sGC, PKGI, Caspase-3, and Bax protein expressions. The expression of Bcl-2 protein was increased (P < .05). Conclusion: Icariin improves AD in mice by activating the NO/cGMP/PKGI signaling pathway.

6.
J Minim Access Surg ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38214313

RESUMO

ABSTRACT: Post-operative bile leakage (POBL) is a serious complication following hepatobiliary surgery, with potentially life-threatening consequences if left untreated. This article presents a successful case of POBL management without surgical intervention. A 31-year-old male, diagnosed with bile leakage before hospitalisation, underwent percutaneous biliary drainage (PTBD) to address bilomas. Follow-up after 3 months indicated biloma atrophy and POBL healing but revealed bile duct stenosis. The patient received a larger biliary drainage tube, and after 1 month, the biloma and tube were removed. A 1-year follow-up confirmed the patient's excellent health. This case underscores the safety and efficacy of PTBD for managing POBL, offering a non-invasive alternative for patients with this complication. PTBD presents a viable treatment option for POBL cases, minimising the need for surgical interventions and their associated risks.

7.
J Med Virol ; 95(2): e28562, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36755354

RESUMO

People's lifestyles have changed dramatically during the coronavirus disease 2019 (COVID-19) pandemic, yet data on physical examinations in the Chinese population before and during the pandemic are rarely reported. The study was based on the data from the physical examination center of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. We collected the data of physical examinations information between January 2017 and March 2022. The data of participants before December 31, 2019 were classified as "before COVID-19 pandemic group," while data after December 31, 2019 were classified as "during COVID-19 pandemic group." We used t-test and χ2  test to compare the differences before and during COVID-19 pandemic. A total of 72 257 individuals participated in the physical examinations, and finally retained 65 629 individuals for analysis. During the COVID-19 pandemic, body mass index (BMI), high-density lipoprotein, total cholesterol levels, as well as pulmonary nodule and thyroid nodule proportion of participants were higher than those before the pandemic, and the levels of systolic blood pressure and diastolic blood pressure of participants were lower than those before the pandemic. Ongoing assessment and surveillance are necessary to assess whether lifestyle changes caused by the COVID-19 pandemic are likely to increase chronic disease risk in the future.


Assuntos
COVID-19 , Humanos , Pandemias , Estudos Transversais , SARS-CoV-2 , Estilo de Vida
8.
Rapid Commun Mass Spectrom ; 37(8): e9481, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36721310

RESUMO

RATIONALE: The chemical constituents of Chinese patent medicine are usually different from those of crude medicine because of specific preparation processes. Chimonanthus nitens Oliv. leaf granule is widely used for prevention against COVID-19 in China. However, no research has been reported on the chemical constituents of the granule and their variation during the preparation process. METHODS: Fragmentation patterns of reference compounds were investigated using electrospray ionization mass spectrometry, and the new gas-phase reaction was demonstrated by electronic and steric effects and calculated chemistry. Then, a strategy based on new fragmentation patterns was used to profile aromatic constituents. In addition, based on untargeted metabolomics analytical workflow, a comparison was made on the chemical constituents of the leaf and granule. RESULTS: New fragmentation patterns related to two competing reactions, ring-opening and ring-closing reactions for coumarin, have been proposed and investigated in depth. The newly established diagnostic ion at m/z 81.0331 worked strongly in the assignment of OH-7 and substituent at C-8 of coumarin. McLafferty rearrangement occurring in coumarin glycoside while sugar group locating at C-4 was first observed, and new diagnostic ions at m/z 147.0440, 119.0488, and 91.0543 were constructed. CONCLUSIONS: Aromatic constituents of the granule were first profiled. A total of 114 aromatic compounds were identified; of these 85 compounds were identified first. Kaempferol-7-O-neohesperidoside and its homologues were mostly enriched in the granule. Considering their reported bioactivities, these analogues possibly contribute greatly to clinical efficacy. Our results provided a new fragmentation theory for coumarins and a new material basis for the quality control of the granule.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Espectrometria de Massas por Ionização por Electrospray/métodos , Medicamentos de Ervas Chinesas/química , Íons/química , Folhas de Planta/química , Cromatografia Líquida de Alta Pressão/métodos
9.
Exp Cell Res ; 421(1): 113360, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36122769

RESUMO

Cervical cancer is a major gynecological tumor worldwide. Unfortunately, the molecular mechanisms involved in cervical cancer tumorigenesis still requires more clarification. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), an enzyme involved in phosphatidylcholine metabolism, has been reported to regulate the proliferation, epithelial-mesenchymal transition (EMT) and recurrence of malignancies. Here in our study, we found that LPAT1 was over-expressed in clinical cervical cancer tissues, and its high expression was closely correlated with poor outcomes of patients. We further showed that LPCAT1 knockdown remarkably restrained the proliferation, migration and invasion of cervical cancer cells, while it significantly induced apoptosis. RNA-seq and bioinformatics assays initially showed that interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) pathway was a key mechanism for LPCAT1 to regulate cervical cancer progression. LPCAT1 silence strongly decreased IL-6, p-Janus kinase 2 (JAK2) and p-STAT3 expression levels in cervical cancer cells. Similarly, the expression levels of IL-6/STAT3 target genes were also highly down-regulated in cervical cancer cells with LPCAT1 deletion. Importantly, we found that human recombinant IL-6 addition considerably abolished the function of LPCAT1-knockdown to suppress the proliferation and EMT process in cervical cancer cells, accompanied with mitigated apoptotic cell death. Furthermore, our animal experiment results validated that stable LPCAT1 deletion efficiently reduced the tumor growth rates of xenograft mouse models and lung metastasis in vivo. Collectively, all our findings revealed that LPCAT1 may be a promising alternative prognostic biomarker and therapeutic target for cervical cancer through regulating JAK2/STAT3 signaling pathway.


Assuntos
Janus Quinase 2 , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , 1-Acilglicerofosfocolina O-Aciltransferase/genética , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Oncogenes , Fosfatidilcolinas , Transdução de Sinais/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias do Colo do Útero/patologia , Proteínas Oncogênicas
10.
Plant Dis ; 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36916847

RESUMO

Red clover (Trifolium pratense) is becoming increasingly important in grassland systems (sheep and beef) due to its high productivity, protein content and nitrogen-fixing ability which allows lower N fertilizer use (Murray et al. 2007). In June 2021, an unidentified foliar disease occurred seriously in experimental fields of red clover (25.61°N, 102.48°E) in Kunming city, Yunnan Province, China. Disease incidence was approximately 55% with an average disease severity of 41.1% in the fields (about 1.5 ha). Initially, the symptoms consisted of cicular to oval leaf spots with dark brown edges. In severely diseased plots, the diseased spots continued to expand and fuse along the leaf veins, forming long and narrow leaf spots, and the middle of the leaves were decayed and hollow. To isolate the pathogen, small pieces (3×3 mm) from the margin of infected lesions were surface-sterilized in 75% ethanol solution for 30 s, 1% NaClO solution for 90 s, rinsed three times with sterilized distilled water, air dried, and plated onto potato dextrose agar (PDA). The same fungus was isolated in 90% of the samples and purified by transferring the hyphal tip from the edge of colonies to fresh PDA plates. The colonies produced relatively dense light-grayish aerial mycelium in the early stage, which turned grayish upon mature, and then dark brown on the back of the colonies with dense small black patches. Conidiophores were unbranched, straight or flexuous, accompanied by slight or obvious swelling of its apical cells. Conidia were olive brown, irregularly round, 1 to 3 transverse septa, 0 to 2 longitudinal or oblique septa, and measured 16.0 - (24.8)- 30.1 × 13.9 - (21.4) - 28.6 µm (n = 50). Morphological characteristics were consistent with those described for Stemphylium vesicarium (Simmons, 1967). For molecular identification, total genomic DNA was isolated from mycelia collected from 6 day-old colonies of three representative isolates LZQF-1-LZQF-3 using the Omega D3195 fungal genomic DNA extraction kit. Fragments of three genes, including those encoding the ITS region of rDNA, calmodulin gene (cmdA), and glyceraldehyde-3-phosphate dehydrogenase (gpd) regions of isolates LZQF-1-LZQF-3 were amplified by the primers described previously (Woudenberg et al. 2017) and sequenced. Resulting sequences of representative strain LZQF-1 were deposited in GenBank with accession numbers of OL615093 (ITS), OL624541 (cmdA) and OL624538 (gpd), respectively. A nucleotide BLAST search revealed ITS, cmdA and gpd sequences to be 100%, 100% and 99.0% similar to the corresponding sequences (accessions numbers KU850563.1, KU850853.1 and KU850710.1) of ex-type strain CBS 370.51 of S. vesicarium. The three locus datasets were combined by SequenceMatrix 1.8 (Vaidya et al. 2011), and the strain LZQF-1-LZQF-3 and S. vesicarium (CBS 192.86, CBS 370.51 and CBS 205.82) formed a subclade with 99% bootstrap support. Pathogenicity tests were performed on LZQF-1 in a greenhouse at 18 °C-26 °C with 75% relative humidity. Three pots each containing three 50-day-old red clover were sprayed with the conidial suspension (3 × 105 conidia/ml) while another three pots were sprayed with sterile water as a control. Two weeks later, the inoculated leaves showed oval leaf spots with dark brown edges, distinctive symptoms of S. vesicarium infection. S. vesicarium was reisolated and confirmed by morphological and molecular features. There were no symptoms on the control leaves. S. vesicarium as a pathogen causing leaf spot disease has been reported on red clover in Canada (Jasalavich et al. 1995) and in Russia (Babuschkina et al. 1995). To our knowledge, this is the first report of leaf spot of red clover caused by S. vesicarium in China. The identification of Stemphylium leaf spot lays the groundwork for future investigations into epidemiology and management of S. vesicarium on red clover.

11.
Int J Mol Sci ; 24(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38139310

RESUMO

The present challenge in dental pulp tissue engineering scaffold materials lies in the development of tissue-specific scaffolds that are conducive to an optimal regenerative microenvironment and capable of accommodating intricate root canal systems. This study utilized porcine dental pulp to derive the decellularized extracellular matrix (dECM) via appropriate decellularization protocols. The resultant dECM was dissolved in an acid pepsin solution to form dECM hydrogels. The analysis encompassed evaluating the microstructure and rheological properties of dECM hydrogels and evaluated their biological properties, including in vitro cell viability, proliferation, migration, tube formation, odontogenic, and neurogenic differentiation. Gelatin methacrylate (GelMA) hydrogel served as the control. Subsequently, hydrogels were injected into treated dentin matrix tubes and transplanted subcutaneously into nude mice to regenerate dental pulp tissue in vivo. The results showed that dECM hydrogels exhibited exceptional injectability and responsiveness to physiological temperature. It supported the survival, odontogenic, and neurogenic differentiation of dental pulp stem cells in a 3D culture setting. Moreover, it exhibited a superior ability to promote cell migration and angiogenesis compared to GelMA hydrogel in vitro. Additionally, the dECM hydrogel demonstrated the capability to regenerate pulp-like tissue with abundant blood vessels and a fully formed odontoblast-like cell layer in vivo. These findings highlight the potential of porcine dental pulp dECM hydrogel as a specialized scaffold material for dental pulp regeneration.


Assuntos
Matriz Extracelular Descelularizada , Hidrogéis , Camundongos , Animais , Suínos , Hidrogéis/farmacologia , Hidrogéis/química , Polpa Dentária , Camundongos Nus , Regeneração , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Matriz Extracelular
12.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677669

RESUMO

Scavenger receptor class B type 1 (SR-B1), a multiligand membrane receptor, is expressed in a gradient along the gastrocolic axis. SR-B1 deficiency enhances lymphocyte proliferation and elevates inflammatory cytokine production in macrophages. However, whether SR-B1 affects intestinal metabolites is unclear. In this study, we detected metabolite changes in the intestinal tissue of SR-B1-/- mice, including amino acids and neurotransmitters, by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and HPLC. We found that SR-B1-/- mice exhibited changes in intestinal lipid metabolites and metabolic pathways, including the glycerophospholipid, sphingolipid, linoleic acid, taurine, and hypotaurine metabolic pathways. SR-B1 deficiency influenced the contents of amino acids and neurotransmitters in all parts of the intestine; the contents of leucine (LEU), phenylalanine (PHE), tryptophan (TRP), and tyrosine (TYR) were affected in all parts of the intestine; and the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were significantly decreased in both the colon and rectum. In summary, SR-B1 deficiency regulated intestinal lipids, amino acids, and neurotransmitter metabolism in mice.


Assuntos
Aminoácidos , Intestinos , Camundongos , Animais , Camundongos Knockout , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão
13.
Rapid Commun Mass Spectrom ; 36(9): e9269, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35156244

RESUMO

RATIONALE: Norpimarane diterpenes possess plentiful bioactivities and are widely distributed in herbs, such as Flickingeria fimbriata. Rapid characterization of these natural products in complicated plant extracts is of great importance, and electrospray ionization tandem mass spectrometry is a powerful tool for chemical constituent profiling. However, limited researches on their fragmentation mechanisms seriously hinder identification via mass spectrometry. METHODS: Three norpimarane diterpenes isolated from F. fimbriata via multiple types of column chromatography served as reference compounds, and collision-induced dissociation experiments were performed on them with a series of variable collision energies. Plausible fragmentation pathways were proposed based on product ions. To further validate the fragmentation mechanisms, the proton affinity and product ion energy were simulated by density functional theory at the B3LYP/6-31+G(d, p) level. RESULTS: Three main cleavage reactions induced skeleton breakage and resulted in characteristic ions, methyl (CH3 -20) migration, hydrogen arrangement and Retro-Diels-Alder reaction, among which methyl migration was firstly proposed for pimarane diterpenes. A series of common diagnostic ions were identified, such as m/z 133.1012, 121.1012, 119.0805 and 107.0855. Additionally, the constructed fragmentation mechanisms were successfully applied for fragment ion rationalization of previously reported isopimarane diterpenes. CONCLUSIONS: Fragmentation mechanisms of norpimarane diterpenes have been uncovered. Carbocation located at the C ring tends to result in methyl (CH3 -20) migration which has been rarely reported before. This characteristic dissociation reaction allows multiple diagnostic ions to be rationalized and aids in rationalizing fragmentation patterns of other diterpenes. The uncovered mechanisms also shed light on rapid identification of norpimarane diterpenes.


Assuntos
Diterpenos , Espectrometria de Massas em Tandem , Química Computacional , Íons/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
14.
Future Oncol ; 18(26): 2919-2931, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35893704

RESUMO

Aim: The study aimed to clarify the diagnostic value of exosomal miRNAs in epithelial ovarian cancer (EOC). Methods: Plasma exosomes were isolated from peripheral blood of EOC patients and healthy donors by ultracentrifugation and verified by transmission electron microscopy, qNano and western blot. The expression of exosomal miRNAs was detected by quantitative PCR, and the diagnostic efficiency of exosomal miRNAs was evaluated by receiver operating characteristic analysis. Results: Exosomal miR-1260a, miR-7977 and miR-192-5p were significantly decreased in EOC as compared with healthy controls. The area under the curve of the combination of three exosomal miRNAs was 0.8337. Moreover, the level of exosomal miR-7977 was related to the neutrophil-lymphocyte ratio, which decreased in EOC patients with a high neutrophil-lymphocyte ratio. Conclusion: Exosomal miR-1260a, miR-7977 and miR-192-5p act as potentially EOC diagnostic and prognostic biomarkers.


This study aimed to identify some miRNAs that can act as predictive and diagnostic markers of ovarian cancer (OC). To do this, miRNAs were isolated from blood samples of OC patients and healthy donors. The level of miRNAs was tested, and the diagnostic value was analyzed using software. Three miRNAs were identified that could be predictive of OC and OC outcome.


Assuntos
Exossomos , MicroRNAs , Neoplasias Ovarianas , Feminino , Humanos , Biomarcadores Tumorais , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Exossomos/genética , Exossomos/metabolismo , MicroRNAs/metabolismo , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética
15.
Clin Lab ; 68(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377989

RESUMO

BACKGROUND: Metastatic or recurrent endometrial cancers with low survival rate had no standard or limited therapy choice. The aim of our study was to determine the efficiency and safety of tislelizumab combined with carboplatin-paclitaxel as a front-line therapy for patients with metastatic or recurrent endometrial cancer. METHODS: This clinical retrospective cohort study examined 24 Chinese patients with metastasis or recurrence but had not yet received treatment. The therapeutic regimen consisted of 6 cycles of intravenous paclitaxel (175 mg/m2) and carboplatin (target AUC: 5 mg/mL/min) with tislelizumab (200 mg) once every 3 weeks, and then intravenous tislelizumab (200 mg) once every 3 weeks until disease progression or unacceptable toxicity. RESULTS: At the 18-month follow-up, 8 patients were still receiving treatment, 13 were dead, and 3 withdrew. The objective response rate (ORR) was 62.5%, the disease control rate was 75.00%. The ORR was 77.78% for patients positive for PD-L1 and 69.23% for patients positive for MSI-H. The median overall survival time was 11.50 months, and the median progression-free survival time was 6.00 months. Half of the patients experienced 3 - 4 grade adverse events. There were no allergic reactions or treatment-related deaths. CONCLUSIONS: Tislelizumab combined with carboplatin-paclitaxel was used as a front-line therapy, had a beneficial effect and was safe for patients with metastatic or recurrent endometrial cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Feminino , Humanos , Carboplatina/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/induzido quimicamente , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Neoplasias do Endométrio/tratamento farmacológico
16.
J Craniofac Surg ; 33(7): 2118-2121, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35275862

RESUMO

ABSTRACT: Posttraumatic chronic maxillary sinusitis deleteriously affects the life quality of patients with recurrent episodes and related discomfort. However, few studies have been performed to investigate the prevalence of chronic maxillary sinusitis after surgery of mid-facial fracture and related risk factors. The early prevention and cure of posttraumatic chronic maxillary sinusitis have received little attention. This study aimed to investigate the prevalence of chronic maxillary sinusitis after surgery for mid-facial fracture and to identify related risk factors. The authors retrospectively collected the medical history, radiographic examination, and clinical examination of patients with mid-facial fracture (experimental group) and patients with mandibular cyst (control group) in our department between January 2015 and December 2020. A total of 298 patients (416 maxillary sinuses) in the experimental group and 172 patients (344 maxillary sinuses) in the control group were included for analyses. The prevalence of chronic maxillary sinusitis in the experimental group and control group were, respectively, 9.14% and 2.04% ( P < 0.05). History of sinusitis/rhinitis (odds ratio = 63.70, P = 0.000) was an independent risk factor for posttraumatic chronic maxillary sinusitis. In conclusion, these findings showed that the prevalence of chronic maxillary sinusitis after surgery for midfacial fracture was significantly higher than that in the control group and long-term follow-up may be beneficial for these patients. Moreover, patients with a history of sinusitis/rhinitis should be informed of the increased risk.


Assuntos
Sinusite Maxilar , Rinite , Sinusite , Fraturas Cranianas , Doença Crônica , Estudos Transversais , Humanos , Sinusite Maxilar/epidemiologia , Sinusite Maxilar/etiologia , Sinusite Maxilar/cirurgia , Prevalência , Estudos Retrospectivos , Rinite/complicações , Fatores de Risco , Sinusite/complicações , Fraturas Cranianas/complicações
17.
Sensors (Basel) ; 22(12)2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35746409

RESUMO

As the existing processing algorithms for LiDAR echo decomposition are time-consuming, this paper proposes an FPGA-based improved Gaussian full-waveform decomposition method. The proposed FPGA architecture consists of three modules: (i) a pre-processing module, which is used to pipeline data reading and Gaussian filtering, (ii) the inflection point coordinate solution module, applied to the second-order differential operation and to calculate inflection point coordinates, and (iii) the Gaussian component parameter solution and echo component positioning module, which is utilized to calculate the Gaussian component and echo time parameters. Finally, two LiDAR datasets, covering the Congo and Antarctic regions, are used to verify the accuracy and speed of the proposed method. The experimental results show that (i) the accuracy of the FPGA-based processing is equivalent to that of PC-based processing, and (ii) the processing speed of the FPGA-based processing is 292 times faster than that of PC-based processing.

18.
Molecules ; 27(10)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35630667

RESUMO

Polysaccharides are abundant in natural resources and perform numerous physiological functions. Polysaccharide structures often lack chromophore groups; thus, current analytical methods cannot distinguish polysaccharide metabolites in the body or polysaccharide prototypes in biological samples. Thus, the measurement of polysaccharides in blood, bodily fluid, and cell-culture medium is difficult. Our early-stage research resulted in the isolation of two homogeneous polysaccharides from Pseudostellaria heterophylla, PHP0.5MSC-F and PHPH-1-2, which have anti-hyperglycemia and insulin resistance improvement effects for type 2 diabetes. In this study, the reducing terminal sugars of PHP0.5MSC-F and PHPH-1-2 were labeled with 2-aminobenzamide (2-AB) to prepare novel fluorescent probes for HPLC-coupled fluorescence detection (HPLC-FLD). Quantitative analysis was performed in reference to T40, and the detection limit for PHP0.5MSC-F was found to be 8.84 µg/mL with a linear range of 29.45-683.28 µg/mL. In reference to T70, the detection limit for PHPH-1-2 was found to be 13.89 µg/mL with a linear range of 46.29-462.76 µg/mL. This method was used to measure the bidirectional transport of polysaccharides across caco-2 cells from apical to basolateral (AP→BL) or from basolateral to apical (BL→AP) directions and to evaluate the polysaccharide bioavailability. The drug absorption capacity was determined based on the apparent permeability coefficient (Papp), and the Papp values for the two polysaccharides were found to be greater than 1 × 10-6 cm/s, which suggests easy absorption. Regarding bidirectional transport, the AP→BL Papp values were greater than the BL→AP values; thus, PHP0.5MSC-F and PHPH-1-2 mainly underwent passive transference. The two membrane permeable polysaccharides were not P-gp efflux transporter substrates. The absorption mechanism of PHP0.5MSC-F complies with passive diffusion under a concentration gradient, whereas PHPH-1-2 mainly utilizes a clathrin-mediated endocytic pathway to enter caco-2 cells. This innovative HPLC-FLD method can help to track polysaccharide internalization in vitro and in vivo to facilitate cellular uptake and biodistribution exploration.


Assuntos
Diabetes Mellitus Tipo 2 , Transporte Biológico , Células CACO-2 , Humanos , Polissacarídeos , Distribuição Tecidual
19.
Entropy (Basel) ; 24(2)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35205552

RESUMO

Studying heart rate dynamics would help understand the effects caused by a hyperkinetic heart in patients with hyperthyroidism. By using a multiscale entropy (MSE) analysis of heart rate dynamics derived from one-channel electrocardiogram recording, we aimed to compare the system complexity of heart rate dynamics between hyperthyroid patients and control subjects. A decreased MSE complexity index (CI) computed from MSE analysis reflects reduced system complexity. Compared with the control subjects (n = 37), the hyperthyroid patients (n = 37) revealed a significant decrease (p < 0.001) in MSE CI (hyperthyroid patients 10.21 ± 0.37 versus control subjects 14.08 ± 0.21), sample entropy for each scale factor (from 1 to 9), and high frequency power (HF) as well as a significant increase (p < 0.001) in low frequency power (LF) in normalized units (LF%) and ratio of LF to HF (LF/HF). In conclusion, besides cardiac autonomic dysfunction, the system complexity of heart rate dynamics is reduced in hyperthyroidism. This finding implies that the adaptability of the heart rate regulating system is impaired in hyperthyroid patients. Additionally, it might explain the exercise intolerance experienced by hyperthyroid patients. In addition, hyperthyroid patients and control subjects could be distinguished by the MSE CI computed from MSE analysis of heart rate dynamics.

20.
J Gene Med ; 23(1): e3282, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33047422

RESUMO

BACKGROUND: The source and availability of cells for tissue engineering in large scale research or clinical trials requires special attention. We propose the idea of applying rabbit umbilical cord mesenchymal stem cells for this purpose. METHODS: Here, the structure of the rabbit umbilical cord was analyzed and compared to that of human umbilical cord, both macroscopically and histologically. Next, we isolated, cultured and identified the proliferative activity and immunological characteristics of rabbit umbilical cord mesenchymal stem cells in vitro using mixed lymphocyte reaction, flow cytometry and an enzyme-linked immunosorbent assay. Furthermore, we evaluated the effects of biphasic calcium phosphate ceramic scaffolds seeded with rabbit umbilical cord mesenchymal stem cells in rat cranial defect models using multiple techniques, including radiological, histological and immunohistochemistry. RESULTS: In vitro studies demonstated a high level of proliferation and multi-lineage differentiation potential in rabbit umbilical cord mesenchymal stem cells. Rabbit umbilical cord mesenchymal stem cells exibited low immunogenicity properties and immune suppression capability with respect to both the allogeneic and xenogeneic immune response. The results of the in vivo study showed that rabbit umbilical cord mesenchymal stem cells could promote osteogenesis in heterogeneous hosts. CONCLUSIONS: The rabbit umbilical cord mesenchymal stem cells may be a new source for tissue engineering.


Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual , Cordão Umbilical/citologia , Animais , Biomarcadores , Linhagem da Célula/genética , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Humanos , Imunomodulação , Imunofenotipagem , Transplante de Células-Tronco Mesenquimais , Osteogênese/genética , Coelhos , Engenharia Tecidual/métodos
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