Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 183
Filtrar
1.
Clin Neurol Neurosurg ; 240: 108273, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38608351

RESUMO

BACKGROUND: The effectiveness of cervical perivascular sympathectomy (CPVS) in enhancing upper limb motor function in children with cerebral palsy is unclear, and the factors that influence the effectiveness of the surgery have not been documented. OBJECTIVE: To investigate the effectiveness of CPVS in enhancing upper limb motor function in children with cerebral palsy and develop a predictive chart for potential associated adverse outcomes METHODS: The study included 187 children with cerebral palsy who underwent CPVS at the Cerebral Palsy Center, Second Affiliated Hospital of Xinjiang Medical University, between January 2018 and January 2022. Patients were categorized into two groups based on prognostic outcomes: those with adverse and favorable prognoses. Demographic and laboratory data were collected and analyzed from both groups. To identify independent predictors of poor post-CPVS upper limb motor function outcomes, statistical techniques, including univariate analysis and binary logistic regression, were applied. Subsequently, these predictors were integrated to formulate a comprehensive predictive model. RESULTS: In this cohort of 187 children with cerebral palsy undergoing CPVS, 68 (36.36%) exhibited a favorable prognosis for upper limb motor function and 119 (63.64%) demonstrated an adverse prognosis. Age, motor function, and serum albumin levels were identified as significant prognostic factors via logistic regression analysis. To develop the model, we divided the sample into a training set (70%, n = 131) and a validation set (30%, n = 56). Employing motor function, serum albumin levels, and age as variables, we crafted a predictive model. The model's performance, reflected by the area under the curve was 0.813 (0.732, 0.894) in the training set and 0.770 (0.647, 0.892) in the validation set, demonstrating its robust predictive capability for post-CPVS adverse outcomes. Furthermore, the consistency curve and Hosmer-Lemeshow test (χ2 = 8.808, p = 0.359) illustrated a strong concordance between the model's predictions of poor prognosis and the actual incidence rate. CONCLUSION: CPVS has been shown to be effective in improving upper limb motor function in patients with cerebral palsy. Independent prognostic factors identified encompass motor function, age, and serum albumin levels. The composite predictive model shows potential for clinical applications.

2.
Neurosurg Rev ; 47(1): 142, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587684

RESUMO

Cervical perivascular sympathectomy (CPVS) can improve communication disorders in children with cerebral palsy (CP); however, there are no research reports on the factors affecting surgical efficacy. This study aimed to establish a nomogram for poor prognosis after CPVS. We collected data from 313 CP patients who underwent CPVS at the Neurosurgery Cerebral Palsy Center of the Second Affiliated Hospital of Xinjiang Medical University from January 2019 to January 2023. Among them, 70% (n = 216) formed the training cohort and 30% (n = 97) the validation cohort. The general data and laboratory examination data of both groups were analyzed. In training cohort, 82 (37.96%) showed improved postoperative communication function. Logistic analysis identified motor function, serum alkaline phosphatase, serum albumin, and prothrombin activity as the prognostic factors. Using these four factors, a prediction model was constructed with an area under the curve (AUC) of 0.807 (95% confidence interval [CI], 0.743-0.870), indicating its ability to predict adverse outcomes after CPVS. The validation cohort results showed an AUC of 0.76 (95% CI, 0.650-0.869). The consistency curve and Hosmer-Lemeshow test (χ2 = 10.988 and p = 0.202, respectively) demonstrated good consistency between the model-predicted incidence and the actual incidence of poor prognosis. Motor function, serum alkaline phosphatase, serum albumin, and prothrombin activity are independent risk factors associated with the prognosis of communication disorders after CPVS. The combined prediction model has a good clinical prediction effect and has promising potential to be used for early prediction of prognosis of CPVS.


Assuntos
Paralisia Cerebral , Transtornos da Comunicação , Criança , Humanos , Fosfatase Alcalina , Paralisia Cerebral/complicações , Paralisia Cerebral/cirurgia , Protrombina , Simpatectomia , Albumina Sérica
3.
ACS Appl Mater Interfaces ; 16(15): 19519-19528, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38580622

RESUMO

The inherent flammability of most polymeric materials poses a significant fire hazard, leading to substantial property damage and loss of life. A universal flame-retardant protective coating is considered as a promising strategy to mitigate such risks; however, simultaneously achieving high transparency of the coatings remains a great challenge. Here, inspired by the moth eye effect, we designed a nanoporous structure into a protective coating that leverages a hydrophilic-hydrophobic interactive assembly facilitated by phosphoric acid protonated amino siloxane. The coating demonstrates robust adhesion to a diverse range of substrates, including but not limited to fabrics, foams, paper, and wood. As expected, its moth-eye-inspired nanoporous structure conferred a high visible light transparency of >97% and water vapor transmittance of 96%. The synergistic effect among phosphorus (P), nitrogen (N), and silicon (Si) largely enhanced the char-forming ability and restricted the decomposition of the coated substrates, which successfully endowed the coating with high fire-fighting performance. More importantly, for both flexible and rigid substrates, the coated samples all possessed great mechanical properties. This work provides a new insight for the design of protective coatings, particularly focusing on achieving high transparency.

4.
Chemosphere ; 357: 141808, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548086

RESUMO

Owing to the huge amounts and perishable character of vegetable wastes, composting is one of the best options for recycling vegetable wastes post-harvest. The initial moisture content (MC) is critical for optimizing composting process, but the effect of high MC in undehydrated vegetable wastes on composting was rarely reported. For this, the plant-scale windrows were prepared by mixing cauliflower waste and maize straw at different ratios to control initial MC of 70 % (T1-70) and 80 % (T2-80), respectively, and composted in winter. As composting progressed, substantial organic matter degradation, progressive humification, decreases in electrical conductivity and increases of pH and germination index (GI) were observed in both treatments. Nonetheless, T1-70 accelerated heating rate early during composting, prolonged high temperature period (>50 °C) by 30 d, thus increased the harmless level of composting, and significantly improved the humification of end-products compared to T2-80. Results also revealed that T1-70 activated more indigenous microbes and enhanced microbial interactions early during composting, with the fungi enriched in T1-70 playing an important role in accelerating the composting process. Remarkably, the difference in composting temperatures, humification degree, and microbial communities between the two treatments was most significant during the maturation phase. In this phase, MWH_CFBk5, Planktosalinus, Pseudopedobacter, and Luteimonas enriched in T1-70 were positively correlated with humification indices. It is suggested that the effect of initial MC, resulting from different ratios of vegetable waste to maize straw, on their composting was mediated by the composting temperature and microbial communities at low temperatures.

5.
Eur J Med Chem ; 269: 116309, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38471357

RESUMO

The colchicine binding site on tubulin has been widely acknowledged as an attractive target for anticancer drug exploitation. Here, we reported the structural optimization of the lead compound 4, which was proved in our previous work as a colchicine binding site inhibitor (CBSI). Based on docking researches for the active binding conformation of compound 4, a series of novel 6-aryl-1-(3,4,5-trimethoxyphenyl)-1H-benzo[d][1,2,3]triazole derivatives (9a-9x) were developed by replacing a CH group in the 1H-benzo[d]imidazole skeleton of compound 4 with a nitrogen atom as a hydrogen bond acceptor. Among them, compound 9a showed the strongest antiproliferative activity with IC50 values ranging from 14 to 45 nM against three human cancer cell lines (MCF-7, SGC-7901 and A549), lower than that of compound 4. Mechanistic studies indicated that compound 9a could inhibit tubulin polymerization, destroy the microtubule skeleton, block the cell cycle in G2/M phase, induce cancer cell apoptosis, prevent cancer cell migration and colony formation. Moreover, compound 9a significantly inhibited tumor growth in vivo without observable toxicity in the mice 4T1 xenograft tumor model. In conclusion, this report shows a successful case of the structure-based design approach of a potent tubulin polymerization inhibitor for cancer treatment.


Assuntos
Antineoplásicos , Moduladores de Tubulina , Animais , Humanos , Camundongos , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Colchicina/farmacologia , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Polimerização , Relação Estrutura-Atividade , Triazóis/farmacologia , Triazóis/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química
6.
Biodegradation ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530488

RESUMO

Triadimefon, a type of triazole systemic fungicide, has been extensively used to control various fungal diseases. However, triadimefon could lead to severe environmental pollution, and even threatens human health. To eliminate triadimefon residues, a triadimefon-degrading bacterial strain TY18 was isolated from a long-term polluted site and was identified as Enterobacter hormaechei. Strain TY18 could grow well in a carbon salt medium with triadimefon as the sole nitrogen source, and could efficiently degrade triadimefon. Under triadimefon stress, a total of 430 differentially expressed genes (DEGs), including 197 up-regulated and 233 down-regulated DEGs, were identified in strain TY18 using transcriptome sequencing (RNA-Seq). Functional classification and enrichment analysis revealed that these DEGs were mainly related to amino acid transport and metabolism, carbohydrate transport and metabolism, small molecule and pyrimidine metabolism. Interestingly, the DEGs encoding monooxygenase and hydrolase activity acting on carbon-nitrogen were highly up-regulated, might be mainly responsible for the metabolism in triadimefon. Our findings in this work suggest that strain E. hormaechei TY18 could efficiently degrade triadimefon for the first time. They provide a great potential to manage triadimefon biodegradation in the environment successfully.

7.
Cancer Lett ; 586: 216695, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325769

RESUMO

Given the limitations of the response rate and efficacy of immune checkpoint inhibitors (ICIs) in clinical applications, exploring new therapeutic strategies for cancer immunotherapy is necessary. We found that 5-(3,4,5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl)imidazole (BZML), a microtubule-targeting agent, exhibited potent anticancer activity by inducing mitotic catastrophe in A549/Taxol and L929 cells. Nuclear membrane disruption and nuclease reduction provided favorable conditions for cGAS-STING pathway activation in cells with mitotic catastrophe. Similar results were obtained in paclitaxel-, docetaxel- and doxorubicin-induced mitotic catastrophe in various cancer cells. Notably, the surface localization of CALR and MHC-I and the release of HMGB1 were also significantly increased in cells with mitotic catastrophe, but not in apoptotic cells, suggesting that mitotic catastrophe is an immunogenic cell death. Furthermore, activated CD8+T cells enhanced the anticancer effects originating from mitotic catastrophe induced by BZML. Inhibiting the cGAS-STING pathway failed to affect BZML-induced mitotic catastrophe but could inhibit mitotic catastrophe-mediated anticancer immune effects. Interestingly, the expression of p-TBK1 first increased and then declined; however, autophagy inhibition reversed the decrease in p-TBK1 expression and enhanced mitotic catastrophe-mediated anticancer immune effects. Collectively, the inhibition of autophagy can potentiate mitotic catastrophe-mediated anticancer immune effects by regulating the cGAS-STING pathway, which explains why the anticancer immune effects induced by chemotherapeutics have not fully exerted their therapeutic efficacy in some patients and opens a new area of research in cancer immunotherapy.


Assuntos
Nucleotidiltransferases , Paclitaxel , Humanos , Paclitaxel/farmacologia , Nucleotidiltransferases/metabolismo , Morte Celular , Imunidade , Autofagia
8.
J Exp Clin Cancer Res ; 43(1): 62, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38419081

RESUMO

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.


Assuntos
Diterpenos do Tipo Caurano , Hipertermia Induzida , MicroRNAs , Neoplasias Nasofaríngeas , Animais , Humanos , Neoplasias Nasofaríngeas/patologia , Sincalida/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 311: 123995, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38341934

RESUMO

In this study, a simple, rapid and sensitive method combining surface-enhanced Raman spectroscopy and Schiff base reaction was developed for the detection of tryptophan. This method does not require product separation to obtain a significant Raman signal of the derivatized product, and the derivatization reaction can be controlled by experimental parameters such as reaction temperature, time, concentration of derivatization reagent and concentration of sodium nitrite. The characteristic peak of the derivative of tryptophan (1620 cm-1) was selected for quantitative analysis, and the intensity of the characteristic Raman spectrum peak showed a linear relationship with the concentration of tryptophan (10-8-10-4 mol/L) in the range of with a correlation coefficient R2 of 0.9922. This assay combines surface-enhanced Raman spectroscopy and Schiff base reaction, which is characterized by high sensitivity and easy operation, and has good application prospects in the detection of tryptophan in food.


Assuntos
Nanopartículas Metálicas , Triptofano , Triptofano/química , Prata/química , Análise Espectral Raman/métodos , Bases de Schiff , Nanopartículas Metálicas/química
10.
Nat Commun ; 14(1): 8082, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057310

RESUMO

The pathogenesis of thyroid dysgenesis (TD) is not well understood. Here, using a combination of single-cell RNA and spatial transcriptome sequencing, we identify a subgroup of NF-κB-activated thyrocytes located at the center of thyroid tissues in postnatal mice, which maintained a partially mesenchymal phenotype. These cells actively protruded out of the thyroid primordium and generated new follicles in zebrafish embryos through continuous tracing. Suppressing NF-κB signaling affected thyrocyte migration and follicle formation, leading to a TD-like phenotype in both mice and zebrafish. Interestingly, during thyroid folliculogenesis, myeloid cells played a crucial role in promoting thyrocyte migration by maintaining close contact and secreting TNF-α. We found that cebpa mutant zebrafish, in which all myeloid cells were depleted, exhibited thyrocyte migration defects. Taken together, our results suggest that myeloid-derived TNF-α-induced NF-κB activation plays a critical role in promoting the migration of vertebrate thyrocytes for follicle generation.


Assuntos
NF-kappa B , Células Epiteliais da Tireoide , Animais , Camundongos , Células Mieloides , Fator de Necrose Tumoral alfa , Peixe-Zebra
11.
Mikrochim Acta ; 191(1): 28, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093122

RESUMO

The aim of this study is to develop a simple but rapid method for the determination of foodborne pathogens in complex matrices (beverages) by surface enhanced Raman spectroscopy (SERS) combined with Au nanostar solid-phase substrates. The star-shaped singlet Au nanostructure was formed on the surface of a stainless steel sheet by chemical replacement reaction. Rhodamine 6G verified the sensitivity and reproducibility of this substrate, and the relative standard deviations of the SERS intensity at 1312 cm-1, 1364 cm-1, and 1510 cm-1 displacements were 3.40%, 5.64%, and 3.48%, respectively. By detecting four pathogens in beverage samples on Au nanostar substrates, the utility of the SERS assay was demonstrated, while the combination of principal component analysis (PCA) and hierarchical cluster analysis (HCA) further enabled the isolation and identification of pathogens. The results of spiked beverages were validated in conventional culture identification and Vitek 2 Compact biochemical identification system experiments. Thus, this research demonstrated that Au nanostar substrates can be effectively utilized for the recognition of pathogenic bacteria and have immense promise to advance the progress of quick detection of foodborne pathogens and food safety.


Assuntos
Nanopartículas Metálicas , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Ouro/química , Análise Espectral Raman/métodos , Bebidas
12.
Anal Methods ; 15(44): 6088-6096, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37933465

RESUMO

The design and preparation of various effective three-dimensional (3D) silver nanostructures is a frontier area of research in the field of surface-enhanced Raman scattering (SERS). This paper demonstrates a simple and novel method for the preparation of a substrate, whose surface was covered by a 3D interconnected network of Ag nanostructures, and the resulting network structure surface is free of organic contaminants. The EDS measurements confirm the metallic nature of the formed 3D Ag nanonetwork substrate. Additionally, the influence of experimental parameters on the morphology of the 3D Ag nanonetwork was also investigated, such as reaction time, hydrofluoric acid concentration, silver nitrate concentration and sodium citrate concentration. The 3D Ag nanonetwork has good uniformity. Importantly, the 3D Ag nanonetwork substrate was used to accurately and reliably detect amaranth (AR) and sunset yellow (SY) in beverages, with the lowest detection limit of 3 and 0.1 µg L-1, respectively. Therefore, this substrate is expected to be a promising candidate for SERS detection and offers attractive potential for a wider range of applications.

13.
Childs Nerv Syst ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37870563

RESUMO

BACKGROUND: There is a lack of research to determine the efficacy of cervical perivascular sympathectomy (CPVS) in children with cerebral palsy (CP). OBJECTIVE: This study aimed to evaluate the efficacy of CPVS in children with CP and analyze the associated influential factors. METHODS: Using the method of retrospective cohort studies, children who underwent CPVS were included in the CPVS group, whereas those who underwent selective posterior rhizotomy (SPR) were included in the SPR group. The Communication Function Classification System (CFCS) and Teacher Drooling Scale (TDS) were used to evaluate the communication function and salivation in the two groups before and 12 months after surgery and compare the surgical efficiency between the two groups, and the factors affecting the efficacy were screened by binary logistic regression. RESULTS: The study included 406 patients, 202 in the CPVS group and 204 in the SPR group. No significant differences were observed in the baseline characteristics (p > 0.05). The surgical efficacy of the CPVS group (47.01%) was significantly higher than that in the SPR group (9.81%) (χ2 = 71.08, p < 0.001). Binary logic regression analysis showed that preterm birth and Gross Motor Function Classification System (GMFCS) grade were influencing factors of surgical efficacy. Eighteen patients developed postoperative complications. CONCLUSION: CPVS is a safe and effective surgery for cerebral palsy. Preterm birth and GMFCS grade are independent factors affecting the efficacy of surgery.

14.
J Asian Nat Prod Res ; 25(11): 1076-1084, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37724355

RESUMO

The investigation of chemical constituents from the rhizomes of Ruscus aculeatus resulted in the isolation of two new biphenyl derivatives, aculebiphenyls A and B (1-2), together with two known analogs (3-4). Their chemical structures were elucidated based on extensive spectroscopic interpretation and HR-ESI-MS analysis. Compounds 3-4 were isolated from the Ruscus genus for the first time. The isolated compounds were tested for anti-inflammatory activities and antibacterial activities. Compound 1 exhibited significant inhibitory effects on LPS-induced NO production and COX-2 with IC50 values of 10.8 µM and 0.4 µM. Compound 1 also significantly down-regulated the levels of inflammatory cytokines IL-1ß, IL-6, and TNF-α. Compound 1 showed moderate antibacterial activities.


Assuntos
Ruscus , Ruscus/química , Rizoma , Antibacterianos/farmacologia
15.
Gastroenterology ; 165(6): 1430-1442.e14, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37625498

RESUMO

BACKGROUND & AIMS: The benefit of radiotherapy for rectal cancer is based largely on a balance between a decrease in local recurrence and an increase in bowel dysfunction. Predicting postoperative disability is helpful for recovery plans and early intervention. We aimed to develop and validate a risk model to improve the prediction of major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy using perioperative features. METHODS: Eligible patients more than 1 year after restorative resection following radiotherapy were invited to complete the low anterior resection syndrome (LARS) score at 3 national hospitals in China. Clinical characteristics and imaging parameters were assessed with machine learning algorithms. The post-radiotherapy LARS prediction model (PORTLARS) was constructed by means of logistic regression on the basis of key factors with proportional weighs. The accuracy of the model for major LARS prediction was internally and externally validated. RESULTS: A total of 868 patients reported a mean LARS score of 28.4 after an average time of 4.7 years since surgery. Key predictors for major LARS included the length of distal rectum, anastomotic leakage, proximal colon of neorectum, and pathologic nodal stage. PORTLARS had a favorable area under the curve for predicting major LARS in the internal dataset (0.835; 95% CI, 0.800-0.870, n = 521) and external dataset (0.884; 95% CI, 0.848-0.921, n = 347). The model achieved both sensitivity and specificity >0.83 in the external validation. In addition, PORTLARS outperformed the preoperative LARS score for prediction of major events. CONCLUSIONS: PORTLARS could predict major bowel dysfunction after rectal cancer resection following radiotherapy with high accuracy and robustness. It may serve as a useful tool to identify patients who need additional support for long-term dysfunction in the early stage. CLINICALTRIALS: gov, number NCT05129215.


Assuntos
Gastroenteropatias , Enteropatias , Neoplasias Retais , Humanos , Reto/diagnóstico por imagem , Reto/cirurgia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Síndrome de Ressecção Anterior Baixa
16.
IEEE/ACM Trans Comput Biol Bioinform ; 20(6): 3499-3510, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37527304

RESUMO

Due to the complexity of cancer pathogenesis at different omics levels, it is necessary to find a comprehensive method to accurately distinguish and find cancer subtypes for cancer treatment. In this paper, we proposed a new cancer multi-omics subtype identification method, which is based on variational autoencoder measured by Wasserstein distance and graph autoencoder (WVGMO). This method depends on two foremost models. The first model is a variational autoencoder measured by Wasserstein distance (WVAE), which is used to extract potential spatial information of each omic data type. The second model is the graph autoencoder (GAE) with the second-order proximity. It has the capability to retain the topological structure information and feature information of the multi-omics data. And then, the identification of cancer subtypes via k-means clustering. Extensive experiments were conducted on seven different cancers based on four omics data from TCGA. The results show that WVGMO provides equivalent or even better results than the most of advanced synthesis methods.


Assuntos
Neoplasias , Humanos , Análise por Conglomerados , Neoplasias/genética
17.
Genes Dis ; 10(3): 771-785, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37396555

RESUMO

Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis.

18.
J Agric Food Chem ; 71(23): 9135-9147, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37265398

RESUMO

Flavonoids have always been considered as the chemical basis for the hypoglycemic effect of mulberry leaves. In the course of our search for hypoglycemic effect agents from natural sources, a systematic study was launched to explore prenylated flavonoids from mulberry leaves. Herein, chemical investigation led to the isolation of 10 characteristic prenylated flavonoids, including two new compounds (1 and 3). Their structures were elucidated based on spectroscopic data. All compounds exhibited good α-glucosidase inhibitory activity in vitro, among which compound 2 had the best activity (IC50 = 2.6 µM), better than acarbose (IC50 = 19.6 µM). Additional in vivo tests have further demonstrated compound that compound 2 has a good ability to reduce postprandial blood glucose. Then, multi-spectroscopic methods and molecular simulation studies were used to study the inhibition mechanism. The results showed that compound 2 was a mixed inhibition of α-glucosidase and the binding process was spontaneous, with van der Waals forces as the main driving force, followed by hydrogen bonding and electrostatic forces. The above studies enriched the chemical basis of mulberry leaves, and the application of computational chemistry also provided a reference for future research on such structures.


Assuntos
Flavonoides , Morus , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Morus/química , alfa-Glucosidases/metabolismo , Simulação de Dinâmica Molecular , Hipoglicemiantes/química , Análise Espectral , Folhas de Planta/química , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Simulação de Acoplamento Molecular
19.
Artigo em Inglês | MEDLINE | ID: mdl-37170873

RESUMO

A taxonomic study was carried out on strain yzlin-01T, isolated from Dongshan Island seawater. The bacterium was Gram-stain-negative, catalase-positive, oxidase-negative, rod-shaped, and motile by polar flagella. Growth was observed at temperatures of 10-40 °C, at salinities of 0.5-18 %, and at pH of 6-10. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain yzlin-01T belonged to the genus Halomonas, with the highest sequence similarity to Halomonas malpeensis YU-PRIM-29T (96.7 %), followed by Halomonas johnsoniae T68687T (96.4 %) and Halomonas gomseomensis M12T (96.4 %), and other species of the genus Halomonas (93.4-96.3 %). The ANI and digital DNA-DNA hybridization estimate values between strain yzlin-01T and the closest type strain Halomonas malpeensis YU-PRIM-29T were 77.44 and 21.6 %, respectively. The principal fatty acids were summed feature 8 (consisting of C18 : 1 ω7c and/or C18 : 1 ω6c; 55.7 %), C16 : 0 (20.6 %), C12 : 0 3-OH (6.8 %), summed feature 3 (consisting of C16 : 1 ω7c and/or C16 : 1 ω6c; 5.1 %). The G+C content of the chromosomal DNA was 60.0 mol %. The respiratory quinone was identified as Q-9 (100 %). Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminophospholipid, and three unidentified phospholipids were present. Combined genotypic and phenotypic data suggest that strain yzlin-01T represents a novel species within the genus Halomonas, for which the name Halomonas dongshanensis sp. nov. is proposed, with the type strain yzlin-01T (=GDMCC 1.3202T=KCTC 92467T).


Assuntos
Ácidos Graxos , Halomonas , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Água do Mar/microbiologia
20.
Eur J Med Chem ; 256: 115402, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37182330

RESUMO

Tubulin/colchicine-binding site inhibitors (CBSIs) co-crystal structures play an important role in the exploration of novel small molecules for oncotherapy. Based on the analysis of the binding models of tubulin and reported CBSIs, a series of 6-aryl-2-(3,4,5-trimethoxyphenyl)thiazole[3,2-b][1,2,4]triazoles were designed as potential tubulin polymerization inhibitors by binding to distinct colchicine domain of tubulin. Among the compounds synthesized, 7w not only shown noteworthy potency against SGC-7901 cancer cell line (IC50 = 0.21 µM) but also exhibited lower cytotoxicity than colchicine in normal cell line (HUVEC). The mechanism studies elucidated that 7w could cause the apoptosis of cancer cells by inhibiting tubulin polymerization to trigger G2/M arrest. In 4T1-xenograft mice model, 7w significantly inhibited tumor growth without losing weight, demonstrating a promising potential for further development with a unique binding mode at the colchicine-binding site.


Assuntos
Antineoplásicos , Moduladores de Tubulina , Humanos , Animais , Camundongos , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/química , Estrutura Molecular , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Tiazóis/farmacologia , Linhagem Celular Tumoral , Triazóis/farmacologia , Triazóis/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células , Colchicina/metabolismo , Polimerização , Ensaios de Seleção de Medicamentos Antitumorais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...