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1.
Front Cardiovasc Med ; 11: 1388313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957328

RESUMO

Background: Hypertension is the most significant global risk factor for mortality and morbidity, making standardized blood pressure measurement crucial. Objectives: To investigate whether the location of blood pressure monitors and the positioning of cuffs yield differing results in blood pressure measurements. Methods: Patients admitted to the Affiliated Hospital of Jiujiang College between 1 January 2022 and 30 June 2023 were enrolled in this study and randomly allocated into four groups. These groups were defined based on the positioning of monitoring equipment as follows: varied placements of cuffs on automatic blood pressure monitors, different heights for mercury column blood pressure monitors, varied heights for automatic blood pressure monitors, and different orientations for the cuff airbag tubes on electrocardiogram monitors. Blood pressure was measured and recorded for each group, followed by an analysis of the variations in readings across the different setups. Results: In the first cohort of 763 individuals, mean systolic blood pressure measured at the standard upper arm site was 128.8 ± 10.5 mmHg, compared to 125.3 ± 10.4 mmHg at the elbow fossa. The corresponding diastolic pressures were 79.2 ± 10.7 and 75.0 ± 10.6 mmHg, respectively. The difference in systolic pressure between these positions was significant at 3.48 ± 3.22 mmHg (t1 = 29.91, p1 < 0.001) and for diastolic pressure at 4.23 ± 1.31 mmHg (t2 = 88.98, p2 < 0.001). For the subsequent groups, involving 253, 312, and 225 individuals, respectively, blood pressure measurements were analyzed and compared across different methods within each group. All p-values exceeded 0.05, indicating no statistically significant differences. Conclusions: Blood pressure values measured at the elbow fossa position using an upper arm-type automatic sphygmomanometer were found to be lower than those measured at the upper arm position, with a difference of 3.48 mmHg for systolic and 4.23 mmHg for diastolic pressures. It is therefore essential to position the cuff correctly, specifically 2-3 cm above the elbow fossa, when utilizing an upper arm-type automatic sphygmomanometer for blood pressure monitoring. Conversely, the placement of the mercury column sphygmomanometer and the automated sphygmomanometer at varying heights had no significant effect on blood pressure readings. Similarly, the orientation of the electrocardiogram's cuffed balloon tube, whether facing upward or downward, did not influence blood pressure measurement outcomes.

2.
Am J Epidemiol ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965764

RESUMO

Environmental exposures such as cadmium might be contributing to the increasing incidence of pancreatic cancer. Few prospective studies have examined the association between trace elements and pancreatic ductal adenocarcinoma (PDAC). We conducted a nested case-control study in participants aged 55-74 years at baseline from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort to examine the association between 12 trace elements measured in predignostic whole blood and PDAC. From May 1998 through December 2014, 318 incident PDAC cases were identified during follow-up to 16.7 years. Two controls (n = 636) alive when each case was diagnosed were selected and matched by age (+ 5 years), sex, calendar date of blood draw (2-month blocks), and race and ethnic group. We used multivariable adjusted conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Cadmium and molybdenum were associated with PDAC [highest compared to lowest quintile: cadmium OR=1.81; 95% CI: 01.12, 2.95; P-trend = 0.03; molybdenum OR=0.50; 95% CI: 0.32, 0.80; P-trend = 0.02]. The inverse molybdenum association was only observed among ever smokers (OR=0.31, 95% CI: 0.17, 0.58, P-trend= 0.003, P-interaction=0.03) with no association in never smokers. Lead, arsenic, and other trace elements were not associated with PDAC. Our results support that increasing prediagnostic whole blood cadmium increases while molybdenum reduces PDAC risk.

4.
Neurospine ; 21(2): 665-675, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38955536

RESUMO

OBJECTIVE: This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans. METHODS: Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net's segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness. RESULTS: The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements. CONCLUSION: Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.

5.
Nat Commun ; 15(1): 5587, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961076

RESUMO

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.


Assuntos
Alelos , Metilação de DNA , Animais , Suínos/genética , Feminino , Cromatina/genética , Cromatina/metabolismo , Especificidade de Órgãos/genética , Fígado/metabolismo , Placenta/metabolismo , Masculino , Encéfalo/metabolismo , Sus scrofa/genética , Sequenciamento Completo do Genoma , Gravidez , Multiômica
7.
Sci Rep ; 14(1): 15389, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965256

RESUMO

The objective was to explore the efficacy of single-port laparoscopic percutaneous extraperitoneal closure using double-modified hernia needles with hydrodissection (SLPEC group) and two-port laparoscopic percutaneous extraperitoneal closure (TLPEC group) for the treatment of giant indirect inguinal hernias in children. We performed a retrospective review of all children with giant indirect inguinal hernias (inner ring orifice diameter ≥ 1.5 cm) who underwent laparoscopic high ligation of the hernia sac at FuJian Children's Hospital from January 2019 to December 2021. We collected data from the medical records of all the children and analysed their clinical characteristics and operation-related and follow-up information. Overall, this study included a cohort of 219 patients with isolated giant inguinal hernias who had complete clinical data and who had undergone laparoscopic high ligation of the hernia sac at our centre. All procedures were successfully performed for the 106 patients who underwent SLPEC and for the 113 patients who underwent TLPEC at our centre. There were no statistically significant differences in patient age, sex, body weight, follow-up time or the side of inguinal hernia between the SLPEC group and the TLPEC group (P = 0.123, 0.613, 0.121, 0.076 and 0.081, respectively). However, there were significant differences in the bleeding volume, visual analogue scale (VAS) score, and postoperative activity time between the two groups (P ≤ 0.001). The operation times in the TLPEC group were significantly longer than those in the SLPEC group (P = 0.048), but there were no significant differences in hospital length of stay or hospitalization costs between the two groups (P = 0.244 and 0.073, respectively). Incision scars were found in 2 patients in the SLPEC group and 9 patients in the TLPEC group, and there was a significant difference between the two groups (P = 0.04). However, the incidence of ipsilateral hernia recurrence, surgical site infection, suture-knot reactions and chronic inguinodynia did not significantly differ between the two groups (P = 0.332, 0.301, 0.332 and 0.599, respectively). Postoperative hydrocele occurred in only 1 male child in the SLPEC group and in no male children in the TLPEC group, and there was no difference between the two groups (P = 0.310). In this study, there were no cases of testicular atrophy or iatrogenic ascent of the testis. Compared with the TLPEC group, the SLPEC group had the advantages of a concealed incision, light scarring, minimal invasiveness, a reduced operation time, minimal bleeding, mild pain and rapid recovery. In conclusion, SLPEC using double-modified hernia needles with hydrodissection and high ligation of the hernia sac is a safe, effective and minimally invasive surgery. The cosmetic results are impressive, and the follow-up results are promising.


Assuntos
Hérnia Inguinal , Herniorrafia , Laparoscopia , Humanos , Hérnia Inguinal/cirurgia , Masculino , Laparoscopia/métodos , Feminino , Estudos Retrospectivos , Pré-Escolar , Criança , Herniorrafia/métodos , Herniorrafia/instrumentação , Agulhas , Lactente , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
8.
BMC Med ; 22(1): 282, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38972973

RESUMO

BACKGROUND: The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. METHODS: We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. RESULTS: The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. CONCLUSIONS: We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Aprendizado Profundo , Humanos , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Processamento de Imagem Assistida por Computador/métodos , Idoso
9.
HGG Adv ; 5(3): 100315, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845201

RESUMO

Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association study (GWAS) summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p < 0.05/12,192 = 4.10 × 10-6) associations in whole blood and 39 statistically significant (p < 0.05/13,844 = 3.61 × 10-6) associations in prostate tissue, with 18 genes associated in both tissues. Cross-tissue analyses identified 155 statistically significantly (p < 0.05/22,249 = 2.25 × 10-6) genes. Out of 173 unique PSA-associated genes across analyses, we replicated 151 (87.3%) in a TWAS of 209,318 PCa-free individuals from the Million Veteran Program. Based on conditional analyses, we found 20 genes (11 single tissue, nine cross-tissue) that were associated with PSA levels in the discovery TWAS that were not attributable to a lead variant from a GWAS. Ten of these 20 genes replicated, and two of the replicated genes had colocalization probability of >0.5: CCNA2 and HIST1H2BN. Six of the 20 identified genes are not known to impact PCa risk. Fine-mapping based on whole blood and prostate tissue revealed five protein-coding genes with evidence of causal relationships with PSA levels. Of these five genes, four exhibited evidence of colocalization and one was conditionally independent of previous GWAS findings. These results yield hypotheses that should be further explored to improve understanding of genetic factors underlying PSA levels.

10.
Adv Respir Med ; 92(3): 230-240, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38921062

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD), characterized by high-energy metabolism, often leads to malnutrition and is linked to exacerbations. This study investigates the association of malnutrition-related body composition and handgrip strength changes with exacerbation frequencies in COPD patients. METHODS: We analyzed 77 acute exacerbation COPD (AECOPD) patients and 82 stable COPD patients, categorized as frequent and infrequent exacerbators. Assessments included body composition, handgrip strength, nutritional risk, dyspnea scale, and COPD assessment. RESULTS: Among AECOPD patients, there were 22 infrequent and 55 frequent exacerbators. Infrequent exacerbators showed better muscle parameters, extracellular water ratio, phase angle, and handgrip strength. Significant differences in intracellular water, total cellular water, protein, and body cell mass were observed between groups. Logistic regression indicated that extracellular water ratio (OR = 1.086) and phase angle (OR = 0.396) were independently associated with exacerbation risk. Thresholds for exacerbation risk were identified as 0.393 for extracellular water ratio and 4.85° for phase angle. In stable COPD, 13 frequent and 69 infrequent exacerbators were compared, showing no significant differences in weight, muscle, and adipose parameters, but significant differences in extracellular water ratio, phase angle, and handgrip strength. CONCLUSIONS: These findings suggest that increased exacerbations in COPD patients correlate with higher extracellular water ratios and lower phase angles.


Assuntos
Composição Corporal , Força da Mão , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Força da Mão/fisiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Progressão da Doença
11.
Int J Biol Macromol ; 272(Pt 1): 132799, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38830496

RESUMO

Peritrophic membrane (PM) is a pellicle structure present in the midgut of some invertebrates, such as insects and crustaceans. It could isolate harmful components and pathogens in food from intestinal epithelial cells; and it also plays a role in improving digestion and absorption efficiency. So PM is important for survival of its owner. In current study, 44 PM proteins were identified in Litopenaeus vannamei by PM proteome analysis. Among these PM proteins, the Peritrophin-44 homologous protein (LvPT44) was further studied. Chitin-binding assay indicated that LvPT44 could bind to colloidal chitin, and immunoeletron microscopy analysis shown that it was located to PM of L. vannamei. Furthermore, LvPT44 promoter was found to be activated by L. vannamei STAT and c-Jun. Besides, LvPT44 was induced by ER-stress as well as white spot syndrome virus infection. Knocked-down expression of LvPT44 by RNA inference increased the cumulative mortality of shrimp that caused by ER-stress or white spot syndrome virus. These results suggested that LvPT44 has an important role in disease resistance.


Assuntos
Resistência à Doença , Penaeidae , Vírus da Síndrome da Mancha Branca 1 , Animais , Penaeidae/genética , Penaeidae/virologia , Penaeidae/metabolismo , Resistência à Doença/genética , Vírus da Síndrome da Mancha Branca 1/genética , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Quitina/metabolismo , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica
13.
Hepatobiliary Surg Nutr ; 13(3): 393-411, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38911213

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death. Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis, metastasis, and prognosis. Choline is an essential nutrient related to prolonged survival and reduced risk of HCC. However, it remains unclear whether this phenomenon is mediated by autophagy. Methods: Two HCC cell lines (HUH-7 and Hep3B) were used in the present study. Cell growth was evaluated by cell counting kit 8 (CCK-8), colony formation, and in vivo mouse xenografts assays. Cell motility was calculated by wound healing and transwell assays. Autophagosomes were measured by transmission electron microscope (TEM), and autophagy flux was detected by mRFP-GFP-labeled LC3 protein. The mRNA level of genes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were detected by Western blotting (WB). Results: We found that choline inhibited the proliferation, migration, and invasion of HCC cells by downregulating autophagy in vitro and in vivo. Upregulated expression of the solute carrier family 5 member 7 (SLC5A7), a specific choline transporter, correlated with better HCC prognosis. We further discovered that choline could promote SLC5A7 expression, upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway, and attenuate autophagy. Finally, we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo. Conclusions: Our findings provide novel insights into choline-mediated autophagy in HCC, providing the foothold for its future application in HCC treatment.

14.
Cell Mol Life Sci ; 81(1): 270, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886218

RESUMO

Early trophoblast differentiation is crucial for embryo implantation, placentation and fetal development. Dynamic changes in DNA methylation occur during preimplantation development and are critical for cell fate determination. However, the underlying regulatory mechanism remains unclear. Recently, we derived morula-like expanded potential stem cells from human preimplantation embryos (hEPSC-em), providing a valuable tool for studying early trophoblast differentiation. Data analysis on published datasets showed differential expressions of DNA methylation enzymes during early trophoblast differentiation in human embryos and hEPSC-em derived trophoblastic spheroids. We demonstrated downregulation of DNA methyltransferase 3 members (DNMT3s) and upregulation of ten-eleven translocation methylcytosine dioxygenases (TETs) during trophoblast differentiation. While DNMT inhibitor promoted trophoblast differentiation, TET inhibitor hindered the process and reduced implantation potential of trophoblastic spheroids. Further integrative analysis identified that glutamyl aminopeptidase (ENPEP), a trophectoderm progenitor marker, was hypomethylated and highly expressed in trophoblast lineages. Concordantly, progressive loss of DNA methylation in ENPEP promoter and increased ENPEP expression were detected in trophoblast differentiation. Knockout of ENPEP in hEPSC-em compromised trophoblast differentiation potency, reduced adhesion and invasion of trophoblastic spheroids, and impeded trophoblastic stem cell (TSC) derivation. Importantly, TET2 was involved in the loss of DNA methylation and activation of ENPEP expression during trophoblast differentiation. TET2-null hEPSC-em failed to produce TSC properly. Collectively, our results illustrated the crucial roles of ENPEP and TET2 in trophoblast fate commitments and the unprecedented TET2-mediated loss of DNA methylation in ENPEP promoter.


Assuntos
Diferenciação Celular , Metilação de DNA , Proteínas de Ligação a DNA , Dioxigenases , Proteínas Proto-Oncogênicas , Trofoblastos , Feminino , Humanos , Gravidez , Blastocisto/metabolismo , Blastocisto/citologia , Linhagem da Célula/genética , Dioxigenases/metabolismo , Dioxigenases/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Trofoblastos/metabolismo , Trofoblastos/citologia
15.
Nature ; 631(8019): 134-141, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38867047

RESUMO

Mosaic loss of the X chromosome (mLOX) is the most common clonal somatic alteration in leukocytes of female individuals1,2, but little is known about its genetic determinants or phenotypic consequences. Here, to address this, we used data from 883,574 female participants across 8 biobanks; 12% of participants exhibited detectable mLOX in approximately 2% of leukocytes. Female participants with mLOX had an increased risk of myeloid and lymphoid leukaemias. Genetic analyses identified 56 common variants associated with mLOX, implicating genes with roles in chromosomal missegregation, cancer predisposition and autoimmune diseases. Exome-sequence analyses identified rare missense variants in FBXO10 that confer a twofold increased risk of mLOX. Only a small fraction of associations was shared with mosaic Y chromosome loss, suggesting that distinct biological processes drive formation and clonal expansion of sex chromosome missegregation. Allelic shift analyses identified X chromosome alleles that are preferentially retained in mLOX, demonstrating variation at many loci under cellular selection. A polygenic score including 44 allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile. Our results support a model in which germline variants predispose female individuals to acquiring mLOX, with the allelic content of the X chromosome possibly shaping the magnitude of clonal expansion.


Assuntos
Aneuploidia , Cromossomos Humanos X , Células Clonais , Leucócitos , Mosaicismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Doenças Autoimunes/genética , Bancos de Espécimes Biológicos , Segregação de Cromossomos/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Células Clonais/metabolismo , Células Clonais/patologia , Exoma/genética , Proteínas F-Box/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa , Leucemia/genética , Leucócitos/metabolismo , Modelos Genéticos , Herança Multifatorial/genética , Mutação de Sentido Incorreto/genética
16.
Nat Commun ; 15(1): 5193, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890366

RESUMO

Multichannel meta-imaging, inspired by the parallel-processing capability of neuromorphic computing, offers considerable advancements in resolution enhancement and edge discrimination in imaging systems, extending even into the mid- to far-infrared spectrum. Currently typical multichannel infrared imaging systems consist of separating optical gratings or merging multi-cameras, which require complex circuit design and heavy power consumption, hindering the implementation of advanced human-eye-like imagers. Here, we present printable graphene plasmonic photodetector arrays driven by a ferroelectric superdomain for multichannel meta-infrared imaging with enhanced edge discrimination. The fabricated photodetectors exhibited multiple spectral responses with zero-bias operation by directly rescaling the ferroelectric superdomain instead of reconstructing the separated gratings. We also demonstrated enhanced and faster shape classification (98.1%) and edge detection (98.2%) using our multichannel infrared images compared with single-channel detectors. Our proof-of-concept photodetector arrays simplify multichannel infrared imaging systems and offer potential solutions in efficient edge detection in human-brain-type machine vision.

17.
Cancer Res ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861363

RESUMO

Colorectal cancer (CRC) is the second most common malignant tumor world-wide. Analysis of the changes that occur during CRC progression could provide insights into the molecular mechanisms driving CRC development and identify improved treatment strategies. Here, we performed an integrated multi-omics analysis of 435 trace-tumor-samples from 148 colorectal cancer (CRC) patients, covering non-tumor (NT), intraepithelial neoplasia (IEN), infiltration (IFT), and advanced-stage CRC (A-CRC) phases. Proteogenomics analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidation phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, occurred predominantly in the IEN and IFT phases, respectively, and impacted the cell cycle. Mutation of TP53 was frequent in the A-CRC phase and associated with tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of CRC based on CMS and CRIS classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of CRC based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided CRC. The AOM/DSS-induced CRC carcinogenesis mouse model in mice indicated that DDX5 deletion due to chr17q loss promoted CRC development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of CRC and identifying the potential therapeutic targets.

18.
Metab Brain Dis ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848024

RESUMO

The nature of brain redox metabolism in health, aging, and disease remains to be fully established. Reversible oxidations, to disulfide bonds, of closely spaced (vicinal) protein thiols underlie the catalytic maintenance of redox homeostasis by redoxin enzymes, including thioredoxin peroxidases (peroxiredoxins), and have been implicated in redox buffering and regulation. We propose that non-peroxidase proteins containing vicinal thiols that are responsive to physiological redox perturbations may serve as intrinsic probes of brain redox metabolism. Using redox phenylarsine oxide (PAO)-affinity chromatography, we report that PAO-binding vicinal thiols on creatine kinase B and alpha-enolase from healthy rat brains were preferentially oxidized compared to other selected proteins, including neuron-specific (gamma) enolase, under conditions designed to trap in vivo protein thiol redox states. Moreover, measures of the extents of oxidations of vicinal thiols on total protein, and on creatine kinase B and alpha-enolase, showed that vicinal thiol-linked redox states were stable over the lifespan of rats and revealed a transient reductive shift in these redox couples following decapitation-induced global ischemia. Finally, formation of disulfide-linked complexes between peroxiredoxin-2 and brain proteins was demonstrated on redox blots, supporting a link between protein vicinal thiol redox states and the peroxidase activities of peroxiredoxins. The implications of these findings with respect to underappreciated aspects of brain redox metabolism in health, aging, and ischemia are discussed.

19.
Sci Rep ; 14(1): 13950, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886395

RESUMO

Tumor-to-normal ratio (T/N) measurement of 18F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (- 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on 18F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on 18F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor , Compostos de Boro , Fenilalanina/análogos & derivados
20.
World J Clin Cases ; 12(16): 2713-2721, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38899303

RESUMO

BACKGROUND: Photoaging, a result of chronic sun exposure, leads to skin damage and pigmentation changes. Traditional treatments may have limitations in high-altitude areas like Yunnan Province. Intradermal Col Ι injections stimulate collagen production, potentially improving skin quality. This study aims to assess the efficacy and safety of this treatment for photoaging. AIM: To evaluate the efficacy and safety of intradermal type Ι collagen (Col Ι) injection for treating photoaging. METHODS: This prospective, self-controlled study investigated the impact of intradermal injections of Col Ι on skin photodamage in 20 patients from the Yunnan Province. Total six treatment sessions were conducted every 4 wk ± 3 d. Before and after each treatment, facial skin characteristics were quantified using a VISIA skin detector. Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector. The Face-Q scale was used for subjective evaluation of the treatment effect by the patients. RESULTS: The skin thickness of the right cheek consistently increased after each treatment session compared with baseline. The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline. The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions, whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions. The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline (P < 0.05). These findings were also supported by skin ultrasound images. The feature count for the red areas and wrinkle feature count decreased following the treatment (P < 0.05). VISIA assessments also revealed a decrease in the red areas after treatment. The Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session. The overall appearance of the patients improved after treatment. CONCLUSION: Intradermal Col Ι injection improves photoaging, with higher patient satisfaction and fewer adverse reactions, and could be an effective treatment method for populations residing in high-altitude areas.

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