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1.
Anal Chim Acta ; 1307: 342619, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719412

RESUMO

BACKGROUND: The micro gas chromatography column (µGCC) is one of the key components of the miniaturized gas chromatography system. However, light alkanes are difficult to be separated by a micro gas chromatography column, especially for methane and ethane, because the length of µGCC is limited by the area of a silicon substrate. More importantly, the heterogeneous microchannel surface formed by silicon glass bonding causes uneven stationary phase coating and the forces between the untreated microchannel surfaces and the stationary phase materials are weak, which will prevent the improvement of separation performance. RESULTS: In this paper, a micro gas chromatography column (µGCC) with uniform HKUST-1 stationary phase is reported. Significantly, an alumina film prepared by the atomic layer deposition (ALD) technique is used to homogenize the heterogeneous microchannels. The alumina is a hydrophilic material and the alumina made by the ALD technique is uniform. The forces between hydrophilic alumina film and HKUST-1 are strong, which can greatly improve the coating uniformity of the hydrophilic stationary phase HKUST-1. The test results show that the µGCC could baseline separate the light alkane mixtures (CH4, C2H6, C3H8, and C4H10) at the high testing temperature of 120 °C. The maximum resolution of the difficult-separated methane and ethane reached 19.2, which is 108 % higher than the µGCC using the same stationary phase without homogenizing the microchannel inner surface. SIGNIFICANCE: The µGCC uses ALD alumina film to homogenize the microchannel inner surface; meanwhile, hydrophilic ALD alumina has a strong electrostatic attraction with the hydrophilic stationary phase HKUST-1. Homogeneous microchannel surface and strong electrostatic attraction are favorable to obtain uniform stationary phase which greatly improves the separation performance, resulting in a large resolution for methane and ethane. The µGCC has broad application prospects in light alkane separation.

2.
Med Princ Pract ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772352

RESUMO

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer globally, poses a substantial health burden. HCC development is influenced by multiple risk factors including hepatitis B and C infections, excessive alcohol consumption, nonalcoholic steatohepatitis (NASH), and demographic variables like gender, race, and age. Although the exact etiology of HCC is not fully understood, HCC formation is a multi-step process that is contributed by the interplays of viral infection, hepatocyte oncogenic mutations, and chronic liver diseases such as alcoholic cirrhosis and NASH. Disease stage significantly impacts HCC prognosis, with 5-year survival rates ranging from 36% in early-stage cases to 13% in late-stage metastatic cases. Therefore, there is significant potential for life-saving and socioeconomic benefits through the implementation of surveillance programs and the introduction of low-cost screening measures for high-risk groups, such as ultrasound imaging and blood tests. Treatment options for HCC encompass surgery, liver transplantation, radiation therapy, chemotherapy, targeted therapy, and immunotherapy. Despite therapeutic advances, the treatment of advanced HCC remains a challenge. The prognosis of advanced HCC could be greatly improved with continued efforts in prevention, early detection, and treatment development. These efforts will ultimately lead to improved patient outcomes and increased chances of long-term survival.

3.
Discov Oncol ; 15(1): 135, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679635

RESUMO

Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/ß-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.

4.
Hortic Res ; 11(1): uhad258, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38298899

RESUMO

Scutellaria baicalensis Georgi, also known as huang-qin in traditional Chinese medicine, is a widely used herbal remedy due to its anticancer, antivirus, and hepatoprotective properties. The S. baicalensis genome was sequenced many years ago; by contrast, the proteome as the executer of most biological processes of S. baicalensis in the aerial parts, as well as the secondary structure of the roots (xylem, phloem, and periderm), is far less comprehensively characterized. Here we attempt to depict the molecular landscape of the non-model plant S. baicalensis through a multi-omics approach, with the goal of constructing a highly informative and valuable reference dataset. Furthermore, we provide an in-depth characterization dissection to explain the two distinct flavonoid biosynthesis pathways that exist in the aerial parts and root, at the protein and phosphorylated protein levels. Our study provides detailed spatial proteomic and phosphoproteomic information in the context of secondary structures, with implications for the molecular profiling of secondary metabolite biosynthesis in non-model medicinal plants.

5.
Analyst ; 149(5): 1579-1585, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38288594

RESUMO

A semi-packed gas chromatographic column has the advantages of high specific surface area and low column pressure. We report that the stagnation regions formed in the adjacent posts along the channel of the semi-packed columns can decrease the area and height of chromatographic peaks, which makes it difficult to detect low-concentration mixed gases. A semi-packed column with staggered elliptic cylindrical post arrays (SC-S) made using a micro-electro-mechanical system technique is presented, and the separation performance of SC-S is compared with that of a semi-packed column with aligned elliptic cylindrical post arrays (SC-A). The simulation results show that the width of stagnation regions in SC-S is 86.89% smaller than that in SC-A. The experimental results indicate that the area and height of chromatographic peaks increased as stagnation regions reduced. In the separation of the alkane mixture from C8 through C10 with 10 ppm concentration, the chromatographic peak of decane was hardly identified in SC-A while the chromatographic peak in SC-S was still clearly visible. The chromatographic peak heights of octane and nonane were increased by 65.06% and 130.00%, respectively, in SC-S. The peak areas of octane and nonane were increased by 120.45% and 168.18%, respectively.

6.
EJNMMI Phys ; 11(1): 4, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38177565

RESUMO

PURPOSE: To investigate the optimal threshold for measuring thyroid volume in patients with Grave's hyperthyroidism (GH) by SPECT/CT. MATERIALS AND METHODS: A 53 mL butterfly-shaped hollow container made of two 45-degree transparent elbows was put into a NEMA IEC phantom tank. The butterfly-shaped container and the tank were then filled with Na99mTcO4 of different radioactive concentrations, respectively, which could simulate thyroid gland with GH by different target-to-background ratios (T/B) (200:1, 600:1, 1000:1). The different T/B of planar imaging and SPECT/CT were acquired by a Discovery NM/CT 670 Pro SPECT/CT. With Thyroid software (Version 4.0) of GE-Xeleris workstation, the region of the thyroid gland in planar imaging was delineated. The thyroid area and average long diameter of both lobes were substituted into the Allen formula to calculate the thyroid volume. The calculation error was compared with the actual volume. Q-Metrix software was used to perform CT-based attenuation correction, scatter correction, resolution recovery. Ordered-subsets expectation maximization was used to reconstruct SPECT data. 20%, 25%, 30%, 40%, 50%, 60% thresholds were selected to automatically delineate the volume of interest and compared with the real volume, which determinated the optimal threshold. We measured the thyroid volume of 40 GH patients using the threshold and compared the volumes obtained by planar imaging and ultrasound three-dimensional. The differences of the volumes with different T/B and thresholds were compared by the ANOVA and least significant difference t test. The volumes delineated by SPECT/CT were evaluated using ANOVA, least significant difference t test, correlation analysis and, linear regression and Bland-Altman concordance test plot. The differences and consistency of thyroid volume were compared among the above three methods. RESULTS: There was no significant difference in the results between different T/B models (P > 0.05). The thyroid volume calculated by the planar imaging formula method was higher than the real volume, with an average overestimation of 22.81%. The volumes delineated by SPECT/CT threshold automatically decreased while the threshold increased. There were significant differences between groups with different thresholds (P < 0.001). With an average error of 3.73%, the thyroid volume analyzed by the threshold of 25% was close to the results of ultrasound measurement (P > 0.05). Thyroid volume measured by planar imaging method was significantly higher than ultrasound and SPECT/CT threshold automatic delineation method (P < 0.05). The agreement between the SPECT/CT 25% threshold and ultrasound (r = 0.956, b = 0.961) was better than that between the planar imaging and ultrasound (r = 0.590, b = 0.574). The Bland-Altman plot also showed that the thyroid volume measured by the 25% threshold automatic delineation method was in good agreement with the ultrasound measurement. CONCLUSIONS: The T/B has no effect on the measurement of thyroid volume in GH patients; planar imaging method can significantly overestimate thyroid volume in GH patients, and 25% threshold automatic delineation method can obtain more accurate thyroid volume in GH patients.

7.
Anal Chim Acta ; 1287: 342057, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38182335

RESUMO

BACKGROUND: The gas chromatography column is one of the key components of the gas chromatograph and typically be miniaturized using micro-electro-mechanical system (MEMS) technology. Due to the limited area of the Si wafer, the column length of micro gas chromatographic column (µGCC) is usually much smaller than that of commercial chromatographic columns. Therefore, it is always difficult to use µGCCs to separate small molecule gas components such as light hydrocarbons. More importantly, the heterogeneous microchannel surface formed by silicon glass bonding causes uneven stationary phase coating, further preventing the improvement of separation performance. RESULTS: In this paper, a novel all-glass based µGCC with 2 m length for the separation of light hydrocarbons is proposed. The microchannels of the µGCC were directly prepared in the glass substrate by ultrafast laser assisted chemical etching (ULAE). The all-glass microchannels make the coating of the hydrophilic metal-organic frameworks (MOFs) stationary phase continuously because of the homogeneous material composition. Therefore, a widely used copper based hydrophilic MOFs HKUST-1 was used as stationary phase for coating and testing. The test results show that the µGCC which is an open tubular column can realize the baseline separation of light hydrocarbons at 100 °C. And the resolution of difficult separated compounds, methane and ethane, can reach 12.98, which is 201.86 % higher than the silica-based monolithic capillary column in the relevant research. The resolution of ethane and ethylene reaches 6.81 at 120 °C. SIGNIFICANCE: The µGCC fabricated by ULAE method is composed of all-glass and has the uniform stationary phase coating because of the homogeneous microchannel surface which greatly improve the separation performance, resulting in a large resolution for methane and ethane. The all-glass µGCC has broad application prospects in light hydrocarbon separation.

8.
Analyst ; 149(4): 1074-1080, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-37955046

RESUMO

Breath analysis may provide a convenient and non-invasive method for clinical monitoring of chronic kidney disease (CKD) progression. However, few breath volatile organic compounds (VOCs) indicating progression of CKD have been reported. In this study, we used gas chromatography-mass spectrometry (GC-MS) for untargeted detection of breath VOCs in stage 1, 3, and 5 CKD patients. The results showed that, the levels of breath 4-heptanone, n-octane, and n-dodecane gradually increased from CKD stage 1 to stage 5, and their increasing rates from CKD stage 3 to stage 5 were higher than those from CKD stage 1 to stage 3. Gender, smoking habits, age, and body mass index (BMI) had insignificant impact on the levels of the three breath VOCs. The accuracies of the polynomial support vector machine (SVM) and K-nearest neighbour (KNN) models based on 4-heptanone + n-octane + n-dodecane combination in distinguishing CKD stages 1, 3, and 5 were 76.3% and 72.8%, respectively. The combination of 4-heptanone + n-octane + n-dodecane was superior to any single component for monitoring CKD progression. These discoveries have valuable implications for long-term clinical monitoring of CKD and improving our understanding of CKD.


Assuntos
Alcanos , Cetonas , Octanos , Insuficiência Renal Crônica , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Insuficiência Renal Crônica/diagnóstico , Testes Respiratórios/métodos
9.
Artigo em Inglês | MEDLINE | ID: mdl-37979084

RESUMO

Polyferric sulfate (PFS), an economical coagulant widely used for removing heavy metal contaminants from water, is susceptible to reduction and transformation by iron-reducing bacteria prevalent in sediments. However, the effect of heavy metal ions adsorbed in PFS flocs on this biological process remains unclear. According to our results, compared with other heavy metal cations (e.g., Cu2+, Cd2+, Zn2+, Ni2+, Pb2+, and Co2+), Cu2+ had a stronger inhibitory effect on PFS floc reduction by Shewanella putrefaciens CN32, a typical dissimilatory iron-reducing bacterium. The presence of Cu2+ remarkably influenced the global transcription of CN32, resulting in 782 upregulated genes and 713 downregulated genes that are mainly annotated in energy production, amino acid metabolism, protein biosynthesis, and oxidation‒reduction processes. The anaerobic TCA cycle for energy (electron) production was significantly activated in the presence of Cu2+, while the transcription of many genes related to the extracellular electron transfer pathway was downregulated, which is responsible for the decreased Fe3+ reduction. Moreover, the pathways of assimilatory sulfate reduction and subsequent cysteine biosynthesis were significantly enriched, which is hypothesized to result in the consumption of abundant energy produced from the enhanced anaerobic TCA cycle, revealing a strategy to address the oxidative stress caused by Cu2+. This work elucidates the unusual suppressive effects of Cu2+ on the microbial reduction of PFS flocs, which reveals the high resistance of PFS flocs to microbial destruction when used to treat Cu2+ pollution in water, thus demonstrating their tremendous practical prospects.

10.
Shanghai Kou Qiang Yi Xue ; 32(3): 225-229, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37803973

RESUMO

PURPOSE: To evaluate the shaping ability and microcrack formation of ProTaper Next (PTN) and XP-endo Shaper (XPS) systems in the mesial curved root canals of mandibular molars by using micro-CT scans. METHODS: Sixteen mandibular molars with two independent mesial root canals and curvature ranging from 25° to 35° were randomly divided into two groups. The preparation time was recorded. Pre-and-postoperative images were scanned by micro-CT. The following parameters were evaluated: canal transportation, centering ratio, changes in canal volume, canal/root width ratio and microcrack formation. SPSS 22.0 software package was used to analyze the data. RESULTS: Significant difference (P<0.05) was found for canal transportation at the section of 1, 3, 5, 7 mm from the apical foramen and centering ratio at the section of 1, 3, 7 mm from the apical foramen, where XPS files were superior. There was no significant difference for centering ratio at the section of 5 mm from the apical foramen(P>0.05). XPS groups significantly consumed less time during the preparation(P<0.05). There was no significant difference between the two groups for the increase amount of volume, and canal/root width ratio(P>0.05). Both instruments did not induce new microcrack after preparation. CONCLUSIONS: PTN and XPS can both shape curved canals effectively and safely. XPS showed better centering ability and reduced preparation time during preparation.


Assuntos
Níquel , Preparo de Canal Radicular , Cavidade Pulpar/diagnóstico por imagem , Desenho de Equipamento , Preparo de Canal Radicular/métodos , Titânio , Microtomografia por Raio-X/métodos
11.
J Chromatogr A ; 1710: 464418, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37797421

RESUMO

A composite material was synthesized at room temperature by performing modification of the copper benzene-1,3,5-tricarboxylate (HKUST-1) metal-organic framework material by multilayer fluorinated graphene (FG). The FG-HKUST-1 composite was used as a stationary phase for a micro gas chromatography column (µGCC) fabricated using micro-electro-mechanical system (MEMS) technology. The separation results showed that the µGCC with the FG-HKUST-1 composite stationary phase achieved a baseline separation of C1-C4 in 8 min. The retention factors for C2-C4 were 2.13, 7.14, and 12.04, respectively. The maximum relative standard deviation (RSD) of the retention times was 0.14 %. The difference in the retention time between methane and ethane was 1.11 min, with a resolution of 9.2 for methane and ethane. The retention factor of ethane and the resolution of methane and ethane were increased by 166 % and 114 %. Therefore, this µGCC is promising for separating light hydrocarbons with widely differing concentrations.


Assuntos
Benzeno , Grafite , Grafite/química , Cobre , Cromatografia Gasosa/métodos , Gases , Etano , Metano
12.
Front Pharmacol ; 14: 1202676, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37637421

RESUMO

Pulmonary hypertension (PH) is a pathophysiological condition of increased pulmonary circulation vascular resistance due to various reasons, which mainly leads to right heart dysfunction and even death, especially in critically ill patients. Although drug interventions have shown some efficacy in improving the hemodynamics of PH patients, the mortality rate remains high. Hence, the identification of new targets and treatment strategies for PH is imperative. Heparanase (HPA) is an enzyme that specifically cleaves the heparan sulfate (HS) side chains in the extracellular matrix, playing critical roles in inflammation and tumorigenesis. Recent studies have indicated a close association between HPA and PH, suggesting HPA as a potential therapeutic target. This review examines the involvement of HPA in PH pathogenesis, including its effects on endothelial cells, inflammation, and coagulation. Furthermore, HPA may serve as a biomarker for diagnosing PH, and the development of HPA inhibitors holds promise as a targeted therapy for PH treatment.

13.
Exp Ther Med ; 26(2): 379, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37456170

RESUMO

Sepsis-related acute kidney injury (S-AKI) is a common and significant complication of sepsis in critically ill patients, which can often only be treated with antibiotics and medications that reduce S-AKI symptoms. The precise mechanism underlying the onset of S-AKI is still unclear, thus hindering the development of new strategies for its treatment. Therefore, it is necessary to explore the pathogenesis of S-AKI to identify biomarkers and therapeutic targets for its early diagnosis and treatment. Heparanase (HPA), the only known enzyme that cleaves the side chain of heparan sulfate, has been widely studied in relation to tumor metabolism, procoagulant activity, angiogenesis, inflammation and sepsis. It has been reported that HPA plays an important role in the progression of S-AKI. The aim of the present review was to provide an overview of the function of HPA in S-AKI and to summarize its underlying molecular mechanisms, including mediating inflammatory response, immune response, autophagy and exosome biogenesis. It is anticipated that emerging discoveries about HPA in S-AKI will support HPA as a potential biomarker and therapeutic target to combat S-AKI.

14.
Braz J Med Biol Res ; 56: e12370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37042867

RESUMO

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.


Assuntos
Mastócitos , Neoplasias da Glândula Tireoide , Humanos , Mastócitos/patologia , Linfócitos T CD8-Positivos , Fator de Células-Tronco , Galectinas , Microambiente Tumoral
15.
Mol Genet Genomics ; 298(3): 767-776, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37029297

RESUMO

Microscopic polyangiitis (MPA) is an autoimmune disease, characterized by ANCA in blood and necrotizing inflammation of small and medium-sized vessels, one of the three clinical phenotypes of ANCA-associated vasculitis (AAV). Autophagy has been confirmed to be involved in the pathogenesis of AAV. AKT1 is one of the autophagy-regulated proteins. Its single nucleotide polymorphisms (SNPs) are associated with multiple immune-related diseases, but there are rarely studies in AAV. The incidence rate of AAV has a notable geographic difference, and MPA is predominant in China. The aim of this study was to investigate the association between AKT1 SNP and MPA risk. Genotypes of 8 loci in AKT1 were evaluated by multiplex polymerase chain reaction (PCR) and high-throughput sequencing in 416 people, including 208 MPA patients and 208 healthy volunteers from Guangxi in China. Additionally, data of 387 healthy volunteers from China were obtained from the 1000Genomes Project on public database. Differences were observed between the loci (rs2498786, rs2494752, and rs5811155) genotypes in AKT1 and MPA risk (P = 7.0 × 10-4, P = 3.0 × 10-4, and P = 5.9 × 10-5, respectively). A negative association was detected in the Dominant model (P = 1.2 × 10-3, P = 2.0 × 10-4 and P = 3.6 × 10-5, respectively). A haplotype (G-G-T) was associated with MPA risk negatively (P = 7.0 × 10-4). This study suggests that alleles (rs2498786 G, rs2494752 G and rs5811155 insT) are protective factors for MPA and alleles (rs2494752 G and rs5811155 insT) for MPO-ANCA in patients with MPA. There is a haplotype (G-G-T), which is a protective factor for MPA. It suggests that the role of AKT1 in MPA/AAV needs further study to provide more intervention targets for MPA/AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Poliangiite Microscópica , Humanos , Poliangiite Microscópica/genética , Polimorfismo de Nucleotídeo Único/genética , Anticorpos Anticitoplasma de Neutrófilos/genética , População do Leste Asiático , China/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Proteínas Proto-Oncogênicas c-akt/genética
16.
Geriatr Orthop Surg Rehabil ; 14: 21514593231158277, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36798633

RESUMO

Introduction: This article introduced the management of a case with severe left lower extremity pain and forced hip flexion after posterior lumbar interbody fusion and a final diagnosis of left psoas hematoma. Materials and methods: Here we reported a case of a 65-year-old female received posterior lumbar interbody fusion (PLIF) for L4-L5 spondylolisthesis and L4 instability. On the postoperative day one, the hemoglobin level decreased from 108 g/L to 78 g/L. Meanwhile, the patient presented low back pain and inner thigh radiating pain (VAS pain scale = 8). The pain was so severe that it could be barely relieved by keeping left hip in flexion position. On the postoperative day 6, the pain was still severe even after taking mecobalamin, ankylosaurus, dehydrant agents and central pain relievers(VAS pain scale = 9). Computed Tomography indicated a left intramuscular hematoma image extending down to the left iliac fossa. Active hemorrhage of lumbar segmental arterial was detected by B-ultrasound. The patient then received vascular embolization under angiography on the postoperative day 7. Results: The pain in the low back and inner thigh were significantly relieved after the procedure (VAS3-4). On the postoperative day nineteen, the left hip can be fully extended, but the patient was still not able to stand on left leg without a walking stick. On the postoperative day 27, she was able to walk independently. Discussion: The main reason for the complication was the second conical dilation channel slipped and entered the lateral side of the vertebral body along the transverse process. After timely embolization, pain was significantly relieved and muscle strength was improved. Conclusions: Angiographic embolization is an effective treatment for psoas hematoma after posterior lumbar interbody fusion.

17.
Acta Pharmacol Sin ; 44(7): 1429-1441, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36697978

RESUMO

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (KD = 4.198 µmol/L) and inhibitory activity (IC50 = 2.87 µmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect.


Assuntos
Ácidos Aristolóquicos , Camundongos , Humanos , Animais , Ácidos Aristolóquicos/toxicidade , NAD(P)H Desidrogenase (Quinona)/metabolismo , Rim/patologia , Fígado/metabolismo
18.
J Mech Behav Biomed Mater ; 137: 105544, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332398

RESUMO

The uterine suspensory tissue (UST) complex includes the cardinal (CL) and uterosacral "ligaments" (USL), which are mesentery-like structures that play a role in resisting pelvic organ prolapse (POP). Since there is no information on the time-dependent material properties of the whole structure in situ and in vivo, we developed and tested an intraoperative technique to quantify in vivo whether there is a significant difference in visco-hyperelastic behavior of the CL and USL between women with and without POP. Thirteen women with POP (cases) and four controls scheduled for surgery were selected from an ongoing POP study. Immediately prior to surgery, a computer-controlled linear servo-actuator with a series force transducer applied a continuous, caudally directed traction force while simultaneously recording the resulting cervical displacement in the same direction. After applying an initial 1.1 N preload, a ramp rate of 4 mm/s was used to apply a maximum force of 17.8 N in three "ramp-and-hold" test trials. A simplified bilateral four-cable biomechanical model was used to identify the material behavior of each ligament. For this, the initial cross-section areas of the CL and USL were measured on 3-T magnetic resonance image-based 3D models from each subject. The time-dependent strain energy function of CL/USL was defined with a three-parameter hyperelastic Mooney-Rivlin material model and a two-term Prony series in relaxation form. When cases were compared with controls, the estimated time-dependent material constants of CL and USL did not differ significantly. These are the first measurements that compare the in vivo and in situ visco-hyperelastic response of the tissues comprising the CL and USL to loading in women with and without prolapse. Larger sample sizes would help improve the precision of intergroup differences.


Assuntos
Prolapso de Órgão Pélvico , Feminino , Humanos , Útero/fisiologia , Ligamentos/fisiologia , Imageamento por Ressonância Magnética
19.
Braz. j. med. biol. res ; 56: e12370, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1430026

RESUMO

As an important component of solid tumors, mast cells show specific phenotypes in various tumor microenvironments. However, the precise mechanism of mast cell accumulation and the phenotypic features of thyroid cancer (TC) remain largely unknown. Here, we found that mast cells were obviously recruited to tumor tissue by TC-derived stem cell factor (SCF). With tumor progression, mast cell levels increased gradually. In addition, intratumoral mast cells expressed higher levels of the immunosuppressive molecule galectin-9, which effectively suppresses CD8+ T-cell antitumor immunity in vitro. Blocking galectin-9 on tumor-infiltrating mast cells reversed the immunosuppression of CD8+ T cells. In conclusion, our data elucidated novel protumorigenic and immunosuppressive roles of mast cells in TC. In addition, our results indicated that blocking mast cells may impede tumor progression and ameliorate the prognosis of TC patients.

20.
J Obstet Gynaecol ; 42(8): 3429-3434, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36373471

RESUMO

The difficulty in maintaining the balance between oxides and antioxidants causes a phenomenon named oxidative stress. Oxidative stress often leads to tissue damage and participates in the pathogenesis of a series of diseases. Decidua provides the 'soil' for embryo implantation, and the normal decidualization shows the characteristics of strong antioxidation. Once the mechanism of antioxidant stress goes awry, it will lead to a series of pregnancy-related diseases. In recent years, more and more studies have shown that oxidative stress is involved in pregnancy-related diseases caused by abnormal decidualization of the endometrium. In order to have a more comprehensive understanding of the role of oxidative stress in decidual defect diseases, this paper reviews the common decidual defect diseases in conjunction with relevant regulatory molecules, in order to arouse thinking about the importance of oxidative stress, and to provide more theoretical basis for the aetiology of decidual defects.


Assuntos
Decídua , Complicações na Gravidez , Gravidez , Feminino , Humanos , Endométrio/patologia , Implantação do Embrião , Complicações na Gravidez/patologia , Estresse Oxidativo , Células Estromais
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