Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 141
Filtrar
1.
Neurochem Res ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782837

RESUMO

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.

2.
J Med Chem ; 67(8): 6624-6637, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38588467

RESUMO

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ-02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide-protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ-02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ-02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis.


Assuntos
Desenho de Fármacos , Elastina , Fibrose Pulmonar , Receptores de Superfície Celular , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Animais , Camundongos , Elastina/química , Elastina/metabolismo , Humanos , Metaloproteinase 12 da Matriz/metabolismo , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/síntese química , Camundongos Endogâmicos C57BL , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino
3.
J Food Sci ; 89(5): 2814-2826, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38551189

RESUMO

Conventional methods for inhibiting browning in wine are not suitable for cili (Roxburgh rose) wine, which is naturally rich in ascorbic acid and subject to restrictions on SO2 addition. In this study, the capacity of various additives to suppress the browning of cili wine caused by ascorbic acid degradation was investigated. SO2, pure reduced glutathione (GSH), regular inactive dry yeast (IDY), and IDY with various levels of glutathione enrichment (g-IDY) were separately introduced into cili wine following the completion of alcoholic fermentation. Over a period of 12 months, the color parameters, levels of ascorbic acid, phenolic compounds, antioxidant activity, and GSH content of the aged cili wine were analyzed. Among the investigated additives, g-IDY exhibited the strongest inhibitory effect on browning. Moreover, adding 800 mg L-1 g-IDY increased the total reducing power and residual GSH content by factors of 1.52 and 2.44, respectively, with respect to those of the SO2-treated cili wine, thus enhancing its antioxidant capacity. Using ultra-performance liquid chromatography-tandem mass spectrometry analysis, a total of 22 monomeric phenolic compounds were identified. After g-IDY treatment, the contents of 15 easily oxidizable o-diphenols decreased, preventing the depletion of ascorbic acid as an antioxidant. As a result, the levels of ascorbic acid and total phenolics were 1.5-fold and 1.17-fold higher than those in the SO2-treated wine, respectively. This study demonstrates that g-IDY provides a new approach to preventing the browning of wine caused by ascorbic acid degradation. PRACTICAL APPLICATION: Cili wine, characterized by its high ascorbic acid content, can decelerate cellular senescence and bolster immune function, which has contributed to its popularity. Ascorbic acid, a potent antioxidant, can be spiked into white wines to significantly enhance their antioxidative properties. Nevertheless, the high ascorbic acid content in cili wine renders it susceptible to oxidation under both aerobic and anaerobic conditions, which alters the wine's hue from golden to dark brown, thus diminishing its commercial value. Overcoming this browning associated with ascorbic acid degradation is therefore of considerable importance and could facilitate the advancement of the cili industry.


Assuntos
Antioxidantes , Ácido Ascórbico , Cor , Fermentação , Glutationa , Fenóis , Dióxido de Enxofre , Vinho , Vinho/análise , Ácido Ascórbico/análise , Ácido Ascórbico/farmacologia , Antioxidantes/análise , Antioxidantes/farmacologia , Fenóis/análise , Glutationa/metabolismo , Dióxido de Enxofre/análise , Saccharomyces cerevisiae
4.
BMC Med Imaging ; 24(1): 69, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515047

RESUMO

BACKGROUND: MRI has been widely used to predict the preoperative proliferative potential of pituitary adenoma (PA). However, the relationship between the cyst/tumor volume ratio (C/T ratio) and the proliferative potential of PA has not been reported. Herein, we determined the predictive value of the C/T ratio of PA for tumor cell proliferation. METHODS: The clinical data of 72 patients with PA and cystic change on MRI were retrospectively analyzed. PA volume, cyst volume, and C/T ratio were calculated. The corresponding intraoperative specimens were collected. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the Ki67 index and nuclear atypia. Patients were categorized according to the Ki67 index (< 3% and ≥ 3%) and nuclear atypia (absence and presence). Univariate and multivariate analyses were used to identify the significant predictors of the Ki67 index and nuclear atypia. The receiver operating characteristic curve assessed the prediction ability of the significant predictors. RESULTS: Larger tumor volumes, smaller cyst volumes, and lower C/T ratios were found in patients with higher Ki67 indexes and those with nuclear atypia (P < 0.05). C/T ratio was an independent predictor of the Ki67 index (odds ratio = 0.010, 95% confidence interval = 0.000-0.462) and nuclear atypia (odds ratio = 0.010, 95% confidence interval = 0.000-0.250). The predictive value of the C/T ratio did not differ significantly from that of tumor volume (P > 0.05) but was better than that of cyst volume (P < 0.05). The area under the curve of the C/T ratio for predicting the Ki67 index and nuclear atypia was larger than that for predicting cyst volume and tumor volume. CONCLUSIONS: C/T ratios can be used to predict PA tumor proliferation preoperatively. Our findings may facilitate the selection of surgery timing and the efficacy evaluation of surgery.


Assuntos
Adenoma , Cistos , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Antígeno Ki-67/análise , Estudos Retrospectivos , Carga Tumoral , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Proliferação de Células
5.
Clin Lab ; 70(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345966

RESUMO

BACKGROUND: Based on research, c.609G>A (p.W203X) is a universal mutation site for MMACHC in methylmalonic acidemia (MMA) combined with homocystinuria, cblC type (cblC disease), and c.467G>A (p.G156D) mutation in families with such disease have not yet been reported. To conduct clinical and molecular genetic analysis of a family with cblC disease. METHODS: This work followed the Declaration of Helsinki. All testing methods were performed under the informed consent of our children patients' parents. A second-generation cblC family with 5 members, was selected as the research subject, including sick siblings and parents and an older sister with normal phenotype, given newborn screening for acylcarnitine spectrum via liquid chromatography tandem mass spectrometry (LC-MS/MS), and diagnosed through combining urine organic acid with homocysteine detection via gas chromatography-mass spectrometry (GC-MS) with second-generation gene sequencing technology. The peripheral blood of five family members was collected for genomic DNA extraction, and the changes were screened in disease-related MMACHC sequence via PCR and direct DNA sequencing. RESULTS: The family conformed to the autosomal recessive inheritance, the proband and younger sister were cblC patients, diagnosed in February and at 22d given relevant treatment. The proband died, whereas the younger sister received follow-up treatment. Their parents and sister had normal phenotype. In 2 cases, there was compound heterozygous mutation in MMACHC called c.609G>A (p.W203X) nonsense mutation and c.467G>A (p.G156D) missense mutation in exon 4, while the father with normal phenotype had heterozygous mutation c.609G>A in exon 4 coding area. In its protein, the 203rd amino acid changed from tryptophan to a stop codon (p.W203 x). The normal mother and sister had a heterozygous mutation c.467G>A in exon 4 coding area. In its protein, the 156th amino acid changed from glycine to aspartic acid (p.G156D). CONCLUSIONS: The cblC family results from c.609G>A (p.W203X) and c.467G>A (p.G156D) compound heterozygous mutations in MMACHC, which has a pathogenic impact.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Homocistinúria , Recém-Nascido , Criança , Humanos , Homocistinúria/complicações , Homocistinúria/diagnóstico , Homocistinúria/genética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , Mutação , Aminoácidos , Biologia Molecular , Vitamina B 12 , Ácido Metilmalônico , Oxirredutases
8.
J Clin Ultrasound ; 51(6): 1078-1086, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37235536

RESUMO

OBJECTIVE: We aim to study the MRI features of pituitary adenoma (PA) apoplexy and their relationship with hypoxia, proliferation, and pathology. METHODS: Sixty-seven patients with MRI signs of PA apoplexy were selected. According to the MRI signs, they were divided into the parenchymal group and the cystic group. The parenchymal group had a low signal area on T2WI without cyst >2 mm and this area was not significantly enhanced on the corresponding TW1 enhancement. The cystic group had a cyst >2 mm on T2WI, and the cyst showed liquid stratification on T2WI or high signal on T1WI. The relative T1WI (rT1WI) enhancement value and relative T2WI (rT2WI) value of non-apoplexy areas were measured. Protein levels of hypoxia-inducible factor-1 (HIF-1α), pyruvate dehydrogenase kinase 1 (PDK1), and Ki67 were detected with immunohistochemistry and Western blot. Nuclear morphology was observed with HE staining. RESULTS: The rT1WI enhancement average value, rT2WI average value, Ki67 protein expression level, and the number of abnormal nuclear morphology of non-apoplexy lesions in the parenchymal group were significantly lower than those in the cystic group. The protein expression levels of HIF-1α and PDK1 in the parenchymal group were significantly higher than those in the cystic group. HIF-1α protein was positively correlated with PDK1 but negatively correlated with Ki67. CONCLUSION: When there is PA apoplexy, the ischemia and hypoxia of the cystic group are lesser than those of the parenchymal group, but the proliferation is stronger.


Assuntos
Cistos , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Antígeno Ki-67 , Imageamento por Ressonância Magnética , Hipóxia , Proliferação de Células
9.
ACS Omega ; 8(12): 11138-11150, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37008152

RESUMO

The Simiao pill (SMP) is a classic prescription that has shown anti-inflammatory, analgesic, and immunomodulatory effects and is clinically used to treat inflammatory diseases, such as rheumatoid arthritis (RA) and gouty arthritis, for which the effects and mechanism of action remain largely unknown. In this study, serum samples from RA rats were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry based metabolomics technology and liquid chromatography with tandem mass spectrometry proteomics technology together with network pharmacology to explore the pharmacodynamic substances of SMP. To further verify the above results, we constructed a fibroblast-like synoviocyte (FLS) cell model and administered phellodendrine for the test. All these clues suggested that SMP can significantly reduce the level of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in complete Freund's adjuvant rat serum and improve the degree of foot swelling; combined with metabolomics, proteomics, and network pharmacological technology, it is determined that SMP plays a therapeutic role through the inflammatory pathway, and phellodendrine is found to be one of the pharmacodynamic substances. By constructing an FLS model, it is further determined that phellodendrine could effectively inhibit the activity of synovial cells and reduce the expression level of inflammatory factors by downregulating the expression level of related proteins in the TLR4-MyD88-IRAK4-MAPK signal pathway to alleviate joint inflammation and cartilage injury. Overall, these findings suggested that phellodendrine is an effective component of SMP in the treatment of RA.

10.
Reprod Biomed Online ; 46(6): 1005-1016, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37085428

RESUMO

RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women? DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated. RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25). CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.


Assuntos
Microbiota , Síndrome do Ovário Policístico , Feminino , Humanos , Estudos Transversais , RNA Ribossômico 16S/genética , Hormônio Antimülleriano
11.
Ann Med ; 55(1): 388-400, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36629738

RESUMO

BACKGROUND: Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated. OBJECTIVE: To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML. STUDY DESIGN: From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed. RESULTS: At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52-632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2-36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9-26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5-81.4%) and 3.2% (95%CI, 0.4-22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5-93.6%) and 81.3% (95%CI, 64.2-93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8-26.3%) and 11.7% (95%CI, 3.9-35.0%). CONCLUSION: Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Infecções por Vírus Epstein-Barr/complicações , Viremia/complicações , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Herpesvirus Humano 4 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas Cromossômicas não Histona , Proteínas Oncogênicas
12.
Plant Cell ; 35(1): 390-408, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36321994

RESUMO

Germinated plants grow in darkness until they emerge above the soil. To help the seedling penetrate the soil, most dicot seedlings develop an etiolated apical structure consisting of an apical hook and folded, unexpanded cotyledons atop a rapidly elongating hypocotyl. Brassinosteroids (BRs) are necessary for etiolated apical development, but their precise role and mechanisms remain unclear. Arabidopsis thaliana SMALL AUXIN UP RNA17 (SAUR17) is an apical-organ-specific regulator that promotes production of an apical hook and closed cotyledons. In darkness, ethylene and BRs stimulate SAUR17 expression by transcription factor complexes containing PHYTOCHROME-INTERACTING FACTORs (PIFs), ETHYLENE INSENSITIVE 3 (EIN3), and its homolog EIN3-LIKE 1 (EIL1), and BRASSINAZOLE RESISTANT1 (BZR1). BZR1 requires EIN3 and PIFs for enhanced DNA-binding and transcriptional activation of the SAUR17 promoter; while EIN3, PIF3, and PIF4 stability depends on BR signaling. BZR1 transcriptionally downregulates EIN3-BINDING F-BOX 1 and 2 (EBF1 and EBF2), which encode ubiquitin ligases mediating EIN3 and PIF3 protein degradation. By modulating the EBF-EIN3/PIF protein-stability circuit, BRs induce EIN3 and PIF3 accumulation, which underlies BR-responsive expression of SAUR17 and HOOKLESS1 and ultimately apical hook development. We suggest that in the etiolated development of apical structures, BRs primarily modulate plant sensitivity to darkness and ethylene.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Escuridão , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Etilenos/metabolismo , Plântula/genética , Plântula/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
13.
Int Wound J ; 20(3): 699-705, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35922093

RESUMO

To evaluate the efficacy and safety of wet dressing combined with chitosan wound dressing for deep II degree burn wounds, and provide the basis for clinical application. From October 2019 to October 2021, 80 patients with second-degree deep burn treated in the Department of burn and plastic surgery of our hospital were selected as the research objects. Patients were randomly divided into two groups. The control group (40n) was treated with wet compress, and the study group (40n) was treated with wet compress combined with chitosan wound dressing. The wound healing time, wound healing percentage and pain score were used as the effectiveness indexes, and the incidence of adverse events and serious adverse events and the detection rate of bacterial culture of wound exudates were used as the safety indexes. The efficacy and safety of the two groups were compared. The wound healing time of the study group (19.53 ± 2.74 days) was shorter than that of the control group (24.78 ± 4.86 days), the difference was significant (t = 3.571, P = 0.015). The percentage of wound healing at the 14th after treatment in the study group was higher than that in the control group (65.00% versus 37.50%) (X2  = 6.054, P = 0.014). There was no significant difference in pain scores between the two groups at each time point. The scar growth was observed 3 months after wound healing. The scar score of the study group (6.00 ± 0.98) was lower than that of the control group (8.77 ± 1.19) (t = 2.571, P = 0.031). The positive rate of wound secretion culture on the 7th and 14th day was statistically significant (X2  = 4.528, P = 0.033; X2  = 6.646, P = 0.010), and the study group was lower than the control group (29.03% versus 81.82%; 8.11% versus 42.86%). There was no significant difference in treatment cost between the study group and the control group (1258.7 ± 223.6 versus 1248.9 ± 182.3) (t = 1.571, P = 0.071). No adverse events or serious adverse events occurred in both groups. Chitosan wound dressing can significantly shorten the time of wound healing and reduce wound pain and wound infection in patients with deep second-degree burns. And it can effectively improve the situation of scar hyperplasia, which is worthy of clinical application.


Assuntos
Queimaduras , Quitosana , Humanos , Cicatriz , Quitosana/uso terapêutico , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Bandagens , Queimaduras/tratamento farmacológico , Dor
14.
Exp Cell Res ; 421(1): 113385, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228736

RESUMO

Circulating tumor cells (CTCs) play a vital role in the metastasis and recurrence of breast cancer. CTCs are highly heterogeneous at the stage of Epithelial-to-Mesenchymal Transition (EMT), but the phenotypic and biological characteristics in different EMT stages remain poorly defined. We conducted an orthotopic mouse (4T1) model of breast cancer to isolate CTCs and identified two phenotypes of CTCs: intermediate E/M and mesenchymal CTCs. MTT, Colony formation, Transwell migration and invasion assays were utilized to examined cell proliferation, colony forming, migration and invasion ability. Both the intermediate E/M and mesenchymal CTCs exhibited lower rates of proliferation, colony formation and invasion, as compared to primary tumor cells. The mesenchymal CTCs had a higher rate of invasion but lower rates of proliferation and colony formation than the intermediate E/M CTCs. They also exhibited lower rates of growth and metastasis than the primary tumor cells in vivo, but the mesenchymal CTCs had a higher rate of metastasis than the intermediate E/M CTCs. Fluid shear stress induced the EMT transition of CTCs. The comprehensive analysis of CTCs proteomics discovered proteins that differentially expressed in the two types of CTCs and their primary tumor cells.


Assuntos
Células Neoplásicas Circulantes , Camundongos , Animais , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética , Contagem de Células , Metástase Neoplásica
15.
Int Immunopharmacol ; 112: 109237, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36152535

RESUMO

Fibroblast activation protein (FAPα) is a tumor stromal antigen expressed by cancer-associated fibroblasts (CAFs) in more than 90 % of malignant epithelial carcinomas. FAPα-based immunotherapy has been reported and showed that FAPα-specific immune response can remold immune microenvironment and contribute to tumor regression. Many FAPα-based vaccines have been investigated in preclinical trials, which can elicit strong and durable cytolytic T lymphocytes (CTL) with good safety. However, epitope-based FAPα vaccines are rarely reported. To break tolerance against self-antigens, analogue epitopes with modified peptides at the anchor residues are typically used to improve epitope immunogenicity. To investigate the feasibility of a FAPα epitope-based vaccine for cancer immunotherapy in vivo, we conducted a preclinical study to identify a homologous CTL epitope of human and mouse FAPα and obtained its analogue epitope in BALB/c mice, and explored the anti-tumor activity of their minigene vaccines in 4 T1 tumor-bearing mice. By using in silico epitope prediction tools and immunogenicity assays, immunodominant epitope FAP.291 (YYFSWLTWV) and its analogue epitope FAP.291I9 (YYFSWLTWI) were identified. The FAP.291-based epitope minigene vaccine successfully stimulated CTLs targeting CAFs and exhibited anti-tumor activity in a 4 T1 murine breast cancer model. Furthermore, although the analogue epitope FAP.291I9 enhanced FAP.291-specific immune responses, improvement of anti-tumor immunity effects was not observed. Check of immunosuppressive factors revealed that the high levels of IL-10, IL-13, myeloid-derived suppressor cells and iNOS induced by FAP.291I9 increased, which considered the main cause of the failure of the analogue epitope-based vaccine. Thus, we demonstrated for the first time that the FAP.291 minigene vaccine could induce mouse CTLs and also function as a tumor regression antigen, providing the basis for future studies of FAPα epitope-based vaccines. This study may also be valuable for further improvement of the immunogenicity of analogue epitope vaccines.


Assuntos
Neoplasias da Mama , Vacinas Anticâncer , Camundongos , Humanos , Animais , Feminino , Gelatinases/metabolismo , Interleucina-10 , Serina Endopeptidases/metabolismo , Interleucina-13 , Epitopos , Epitopos Imunodominantes , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Antígenos de Neoplasias , Imunidade , Autoantígenos , Microambiente Tumoral
16.
Front Neurol ; 13: 945640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928122

RESUMO

Purpose: We aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery (TSS) in patients with a non-functional pituitary adenoma (NFPA). Methods: We retrospectively collected the clinical data of patients who underwent TSS for NFPA between January 2016 and January 2021. The pituitary region was preoperatively scanned with 3.0 T magnetic resonance imaging. The risk factors for delayed postoperative hyponatremia for NFPA were identified by univariate and multivariable logistic regression analysis. Results: We selected 166 patients with NFPA who fulfilled the inclusion criteria. Delayed postoperative hyponatremia occurred in 28 patients and did not in 138. Multivariable logistic regression analyses demonstrated that higher odds of developing delayed postoperative hyponatremia were independently associated with larger craniocaudal dimension (OR = 1.128, P = 0.034), as well as preoperative hyperprolactinemia (OR = 2.618, P = 0.045) and larger preoperative pituitary stalk deviation angle (OR = 3.033, P = 0.022). Conclusion: We identified the independent risk factors for delayed hyponatremia after TSS for NFPA; these included preoperative hyperprolactinemia, craniocaudal diameter, and preoperative pituitary stalk deviation angle.

17.
Orthop Surg ; 14(8): 1759-1767, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35818320

RESUMO

OBJECTIVE: To investigate associations between femoral head necrosis (FHN) and injury to the retinaculum of Weitbrecht in patients with femoral neck fractures who had undergone initial trials of either closed reduction or direct open reduction. METHODS: This prospective observational study included 110 patients with displaced femoral neck fractures admitted to the Sixth People's Hospital Affiliated to Shanghai Jiaotong University and Shanghai Tongji Hospital between January 2008 and May 2017. Among these, 25 patients underwent initial closed reductions, and 85 patients underwent an open reduction directly. Watson-Jones anterolateral approach was used during the surgery for injury to the retinaculum of Weitbrecht, and FHN was assessed as a surgical outcome. The severity of injury to the retinaculum of Weitbrecht was evaluated using a scoring system developed by our surgical team. Follow-up was at least 24 months. RESULTS: The initial closed reduction treatment group had significantly higher total scores of injury to the retinaculum of Weitbrecht (6.24 ± 2.20 vs 4.62 ± 2.12, p = 0.009) compared to the open reduction group. High total scores were significantly associated with initial trials of closed reduction treatment, especially for the broken and released injury to the superior and anterior retinacula (both p = 0.01). Twenty-six patients experienced FHN postoperatively, with mean onset time of 19.42 ± 3.87 months. FHN was significantly associated with the severity of injury to the retinaculum of Weitbrecht (p < 0.001) at the superior, anterior, and inferior retinacula. FHN was significantly associated with injury to the retinaculum of Weitbrecht in females. CONCLUSIONS: Femoral neck displacement in patients treated initially with closed reduction is associated with subsequent injury to the retinaculum of Weibrecht, which may lead to FHN. Severity of injury to the retinaculum of Weibrecht may be used as a biomarker to evaluate bone necrosis in patients with femoral neck fractures.


Assuntos
Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , China , Feminino , Fraturas do Colo Femoral/cirurgia , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/etiologia , Colo do Fêmur , Fixação Interna de Fraturas , Humanos
18.
Front Cell Infect Microbiol ; 12: 830684, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663463

RESUMO

Background: There is no information on the commonality and specificity of oral and fecal microbiota in patients with gastric cancer (GC) and colorectal cancer (CRC). Methods: The high-throughput 16S rRNA gene V4 region sequencing was used to perform bioinformatics analysis of oral, fecal, and tissue microbiota in GC (76 subjects), CRC (53), and healthy controls (HC, 70). Furthermore, we determined the microbial characteristics of each part, constructed and verified three classifiers for GC and CRC, and evaluated curves of receiver operating characteristic and precision-recall with probability of disease. Results: Compared to HC, the microbial richness and diversity of GC and CRC decreased in oral cavity and increased in stool; additionally, these indexes in GC tissue were higher than those in CRC tissue. In GC and CRC patients, Haemophilus, Neisseria, Faecalibacterium, and Romboutsia were significantly reduced compared to the relative abundance value of oral or fecal bacterial genera in the HC group, while the Streptococcus, Gemella, Escherichia-Shigella, and Fusobacterium were significantly increased. The oral and tissue microbiota have similar and abundant shared bacterial networks. The single and combined microbial detection have good AUC values based on POD indices for predicting GC, CRC, and gastrointestinal (GI) cancers (GC and CRC). Conclusion: This study is the first to examine the characteristics of oral, fecal, and tumor microbiota in GC and CRC patients, and the similarities and differences in their microbial changes are reported. These oral or fecal bacteria (Haemophilus, Neisseria, Faecalibacterium, Romboutsia, Streptococcus, Gemella, Escherichia-Shigella, and Fusobacterium) may be involved in tumor evolution as potentially characteristic genera. In addition, both oral and fecal microbial detection may provide a solid theoretical foundation for the non-invasive prediction of these cancers.


Assuntos
Neoplasias Colorretais , Microbiota , Neoplasias Gástricas , Bactérias/genética , Biomarcadores , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/microbiologia , Fezes/microbiologia , Fusobacterium/genética , Humanos , Microbiota/genética , RNA Ribossômico 16S/genética , Neoplasias Gástricas/diagnóstico
19.
Inflamm Res ; 71(7-8): 847-858, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35438360

RESUMO

OBJECTIVES: We identified functional genes and studied the underlying molecular mechanisms of diabetic cardiomyopathy (DCM) using bioinformatics tools. METHODS: Original gene expression profiles were obtained from the GSE21610 and GSE112556 data sets. We used GEO2R to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on DEGs. Protein-protein interaction (PPI) networks of DEGs were constructed using STRING and hub genes of signaling pathways were identified using Cytoscape. Aberrant hub gene expression was verified using The Cancer Genome Atlas data set. RESULTS: The DEGs in DCM were mainly enriched in the nuclei and cytoplasm and involved in DCM and chemokine-related signaling pathways. In the PPI network, 32 nodes were chosen as hub nodes and an RNA interaction network was constructed with 517 interactions. The expression of key genes (JPIK3R1, CCR9, XIST, WDFY3.AS2, hsa-miR-144-5p, and hsa-miR-146b-5p) was significantly different between DCM and normal tissues. CONCLUSIONS: The identified hub genes could be associated with DCM pathogenesis and could be used for treating DCM.


Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Biologia Computacional , Cardiomiopatias Diabéticas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição/metabolismo
20.
World J Clin Cases ; 10(6): 1922-1928, 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35317138

RESUMO

BACKGROUND: Proliferative myositis is a rare benign tumor that is typically self-limiting and does not become malignant. It can be cured by simple resection without reported recurrence. Due to its rapid growth, hard structure and ill-defined borders, it can however be mistaken for malignant tumors such as sarcomas. CASE SUMMARY: We investigate the case of a 64-year-old male with proliferative myositis of the abdominal wall, who was preoperatively administered a needle aspiration biopsy and given a simple excision and patch repair. We then compared it with other similar cases to determine the effectiveness of this treatment method. CONCLUSION: Resection with follow-up observation has shown to be an effective treatment method for proliferative myositis. To avoid unnecessarily extended or destructive resection, a thorough and conclusive diagnosis is crucial, which requires adequate imaging and pathological knowledge.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA