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1.
Curr Microbiol ; 81(6): 160, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695903

RESUMEN

Salt stress can adversely affect plant seed germination, growth and development, and eventually lead to slow growth and even death of plants. The purpose of this study was to investigate the effects of different concentrations of NaCl and Na2SO4 stress on the physicochemical properties, enzyme activities, rhizosphere microbial community and seven active components (L-phenylalanine, Protocatechuic acid, Eleutheroside B, Chlorogenic acid, Caffeic acid, Eleutheroside E, Isofraxidin) of Acanthopanax senticosus rhizosphere soil. Statistical analysis was used to explore the correlation between the rhizosphere ecological factors of Acanthopanax senticosus and its active components. Compared with Acanthopanax senticosus under NaCl stress, Na2SO4 generally had a greater effect on Acanthopanax senticosus, which reduced the richness of fungi in rhizosphere soil and adversely affected the content of multiple active components. Pearson analysis showed that pH, organic matter, ammonium nitrogen, available phosphorus, available potassium, catalase and urease were significantly correlated with active components such as Caffeic acid and Isofraxidin. There were 11 known bacterial genera, 12 unknown bacterial genera, 9 known fungal genera and 1 unknown fungal genus significantly associated with the active ingredient. Salt stress had great changes in the physicochemical properties, enzyme activities and microorganisms of the rhizosphere soil of Acanthopanax senticosus. In conclusion, different types and concentrations of salts had different effects on Acanthopanax senticosus, and the active components of Acanthopanax senticosus were regulated by rhizosphere soil ecological factors.


Asunto(s)
Bacterias , Eleutherococcus , Hongos , Rizosfera , Estrés Salino , Microbiología del Suelo , Bacterias/clasificación , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Hongos/clasificación , Hongos/efectos de los fármacos , Hongos/genética , Hongos/aislamiento & purificación , Eleutherococcus/metabolismo , Microbiota/efectos de los fármacos , Suelo/química , Cloruro de Sodio/metabolismo , Raíces de Plantas/microbiología
2.
PLoS One ; 19(5): e0304403, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38809931

RESUMEN

BACKGROUND: In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the question of whether a causal relationship exists between gut microbiota and specific types of brain tumors, such as gliomas, remains unresolved. To address this gap, we employed publicly available Genome-Wide Association Study (GWAS) and MIOBEN databases, conducting an in-depth analysis using Two-Sample Mendelian Randomization (MR). METHOD: We carried out two sets of MR analyses. The preliminary analysis included fewer instrumental variables due to a high genome-wide statistical significance threshold (5×10-8). To enable a more comprehensive and detailed analysis, we adjusted the significance threshold to 1×10-5. We performed linkage disequilibrium analysis (R2 <0.001, clumping distance = 10,000kb) and detailed screening of palindromic SNPs, followed by MR analysis and validation through sensitivity analysis. RESULTS: Our findings reveal a causal relationship between gut microbiota and gliomas. Further confirmation via Inverse Variance Weighting (IVW) identified eight specific microbial communities related to gliomas. Notably, the Peptostreptococcaceae and Olsenella communities appear to have a protective effect, reducing glioma risk. CONCLUSION: This study not only confirms the causal link between gut microbiota and gliomas but also suggests a new avenue for future glioma treatment.


Asunto(s)
Neoplasias Encefálicas , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Glioma , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Glioma/genética , Glioma/microbiología , Microbioma Gastrointestinal/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/microbiología , Eje Cerebro-Intestino , Desequilibrio de Ligamiento
3.
PLoS One ; 19(4): e0300835, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38652719

RESUMEN

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Infecciones por Helicobacter , Helicobacter pylori , Análisis de la Aleatorización Mendeliana , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/genética , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Anticuerpos Antibacterianos/sangre , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/complicaciones , Obesidad/complicaciones , Obesidad/microbiología , Estudio de Asociación del Genoma Completo , Úlcera Péptica/microbiología , Úlcera Péptica/epidemiología , Gastritis/microbiología , Gastritis/complicaciones , Chaperonina 60/genética , Factores de Riesgo
4.
Adv Sci (Weinh) ; : e2309298, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639382

RESUMEN

M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by ß-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of ß-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

5.
Cell Res ; 34(5): 370-385, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38575718

RESUMEN

CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing.


Asunto(s)
Sistemas CRISPR-Cas , Humanos , Sistemas CRISPR-Cas/genética , ARN Guía de Sistemas CRISPR-Cas/metabolismo , ADN/metabolismo , Edición Génica , Endonucleasas/metabolismo , Células HEK293 , División del ADN
6.
Phys Chem Chem Phys ; 26(18): 13915-13922, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38666431

RESUMEN

We design a multifunctional THz polarization modulation meta-mirror integrated with polarization conversion and dichroism functions switched by temperature and voltage. The meta-mirror is composed of two-layered graphene metasurfaces and a layer of vanadium dioxide (VO2) on a gold film substrate. Linear-to-linear polarization conversion and linear dichroism (LD) can be switched by temperature control in the VO2 film and Fermi level adjustments in the graphene metasurfaces, where the polarization conversion ratio (PCR) is higher than 0.9 in the range of 2.89 THz to 4.02 THz, LD value reached a maximum of 0.6 at 3.84 THz, and linear-to-circular polarization conversion and circular dichroism (CD) can also be tuned with ellipticity higher than 0.9 in the range of 2.32 THz to 2.69 THz and CD value as high as 0.71 at 2.45 THz. The proposed meta-mirror is the first THz metamaterial device integrating four switchable functions, including linear-to-linear polarization conversion, linear-to-circular polarization conversion, linear dichroism and circular dichroism. The meta-mirror is a promising design for compact system integration in THz imaging, sensing and biological detection applications.

7.
Front Endocrinol (Lausanne) ; 15: 1345605, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38435749

RESUMEN

Background: Previous observational studies have demonstrated a correlation between metabolic syndrome related diseases and an elevated susceptibility to ulcers of lower limb. It has been suggested that this causal relationship may be influenced by the presence of peripheral artery disease (PAD). Nevertheless, the precise contribution of these factors as determinants of ulcers of lower limb remains largely unexplored. Method: This research incorporated information on hypertension, BMI, hyperuricemia, type 2 diabetes, PAD, and ulcers of lower limb sourced from the GWAS database. Univariate Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) methods were employed to assess the association between metabolic syndrome related diseases, including hypertension, obesity, hyperuricemia, and type 2 diabetes, as well as to investigate whether this association was influenced by PAD. Results: Univariate Mendelian randomization analysis showed that genetically predicted hypertension, BMI, and type 2 diabetes were associated with an increased risk of PAD and ulcers of lower limb, and PAD was associated with an increased risk of ulcers of lower limb, but there is no causal relationship between hyperuricemia and ulcers of lower limb. The results of multivariate Mendelian randomization showed that PAD mediated the causal relationship between hypertension, obesity and ulcers of lower limb, but the relationship between type 2 diabetes and ulcers of lower limb was not mediated by PAD. Conclusion: Hypertension, BMI and type 2 diabetes can increase the risk of ulcers of lower limb, and PAD can be used as a mediator of hypertension and obesity leading to ulcers of lower limb, These findings may inform prevention and intervention strategies directed toward metabolic syndrome and ulcers of lower limb.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipertensión , Hiperuricemia , Enfermedades Metabólicas , Síndrome Metabólico , Enfermedad Arterial Periférica , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Análisis de la Aleatorización Mendeliana , Úlcera , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Hiperuricemia/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/genética , Extremidad Inferior , Obesidad
8.
Int J Oncol ; 64(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38488025

RESUMEN

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 1D on p. 1134, the data panels showing the results for the 'Control' and '1 µmol/l GW9662' experiments (on the left hand side of the figure) were overlapping, such that these data had been derived from the same original source where they were intended to show the results from differently performed experiments. The authors were able to re­examine their original data, and realize that the data for the '1 µmol/l GW9662' panel had been selected incorrectly. The corrected version of Fig. 1, now featuring the correct data for the '1 µmol/l GW9662' experiment in Fig. 1D, is shown on the next page, The authors confirm their error did not grossly affect either the results of the conclusions reported in the paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum. They also apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 1131-1140, 2015; DOI: 10.3892/ijo.2015.2829].

9.
Inorg Chem ; 63(10): 4747-4757, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38412230

RESUMEN

Low dimensional organic inorganic metal halide materials have shown broadband emission and large Stokes shift, making them widely used in various fields and a promising candidate material. Here, the zero-dimensional lead-free bromide single crystals (C6H14N)3Bi2Br9·H2O (1) and (C6H14N)3Sb3Br12 (2) were synthesized. They crystallized in the monoclinic crystal system with the space group of P21 and P21/n, respectively. Through ultraviolet-visible-near-infrared (UV-vis-NIR) absorption analysis, the band gaps of (C6H14N)3Bi2Br9·H2O and (C6H14N)3Sb3Br12 are found to be 2.75 and 2.83 eV, respectively. Upon photoexcitation, (C6H14N)3Bi2Br9·H2O exhibit broad-band red emission peaking at 640 nm with a large Stokes shift of 180 nm and a lifetime of 2.94 ns, and the emission spectrum of (C6H14N)3Sb3Br12 are similar to those of (C6H14N)3Bi2Br9·H2O. This exclusive red emission is ascribed to the self-trapping exciton transition caused by lattice distortion, which is confirmed through both experiments and first-principles calculations. In addition, due to the polar space group structure and the large spin-orbit coupling (SOC) associated with the heavy elements of Bi and Br of crystal 1, an obvious Rashba effect was observed. The discovery of organic inorganic metal bromide material provides a critical foundation for uncovering the connection between 0D metal halide materials' structures and properties.

10.
Medicine (Baltimore) ; 103(7): e36679, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363903

RESUMEN

Studies have indicated that Vascular mimicry (VM) could contribute to the unfavorable prognosis of skin cutaneous melanoma (SKCM). Thus, the objective of this study was to identify therapeutic targets associated with VM in SKCM and develop a novel prognostic model. Gene expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were utilized to identify differentially expressed genes (DEGs). By intersecting these DEGs with VM genes, we acquired VM-related DEGs specific to SKCM, and then identified prognostic-related VM genes. A VM risk score system was established based on these prognosis-associated VM genes, and patients were then categorized into high- and low-score groups using the median score. Subsequently, differences in clinical characteristics, gene set enrichment analysis (GSEA), and other analyses were further presented between the 2 groups of patients. Finally, a novel prognostic model for SKCM was established using the VM score and clinical characteristics. 26 VM-related DEGs were identified in SKCM, among the identified DEGs associated with VM in SKCM, 5 genes were found to be prognostic-related. The VM risk score system, comprised of these genes, is an independent prognostic risk factor. There were significant differences between the 2 patient groups in terms of age, pathological stage, and T stage. VM risk scores are associated with epithelial biological processes, angiogenesis, regulation of the SKCM immune microenvironment, and sensitivity to targeted drugs. The novel prognostic model demonstrates excellent predictive ability. Our study identified VM-related prognostic markers and therapeutic targets for SKCM, providing novel insights for clinical diagnosis and treatment.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Neoplasias Cutáneas/genética , Pronóstico , Sistemas de Liberación de Medicamentos , Factores de Riesgo , Microambiente Tumoral
12.
Nurs Open ; 11(1): e2060, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38268266

RESUMEN

AIM: To understand and report on the perceptions and experiences of registered nurses in the aged care sector. DESIGN: An exploratory qualitative study. METHODS: Semi-structured telephone interviews were utilised as the primary data collection method. Fifteen registered nurses were interviewed. All interviews were recorded, transcribed verbatim and analysed using conventional content analysis. Participants were quoted verbatim to ensure authenticity. RESULTS: The results indicated a demand for increased administrative and staffing support in the aged care workplace. Poor morale and unethical practices contributed to negative perceptions and attitudes among nurses towards aged care. Managing and communicating with older people was reported as challenging, which impacts nursing staff recruitment and retention. Future work is needed to ensure that outstanding clinical role models and leadership support nursing staff recruitment and retention. Incorporating aged care content into the nursing curriculum and providing professional development opportunities to aged care professionals would be the foundation towards solutions, as the study primarily explored nurses' perspectives.


Asunto(s)
Enfermeras y Enfermeros , Personal de Enfermería , Humanos , Anciano , Curriculum , Liderazgo , Moral
13.
Forensic Sci Int Genet ; 69: 102979, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38043150

RESUMEN

Biological traces discovered at crime scenes hold significant significance in forensic investigations. In cases involving mixed body fluid stains, the evidentiary value of DNA profiles depends on the type of body fluid from which the DNA was obtained. Recently, coding region polymorphism analysis has proved to be a promising method for directly linking specific body fluids to their respective DNA contributors in mixtures, which may help to avoid "association fallacy" between separate DNA and RNA evidence. In this study, we present an update on previously reported coding region Single Nucleotide Polymorphisms (cSNPs) by exploring the potential application of coding region Insertion/Deletion polymorphisms (cInDels). Nine promising cInDels, selected from 70 mRNA markers based on stringent screening criteria, were integrated into an existing mRNA profiling assay. Subsequently, the body fluid specificity of our cInDel assay and the genotyping consistency between complementary DNA (cDNA) and genomic DNA (gDNA) were examined. Our study demonstrates that cInDels can function as important multifunctional genetic markers, as they provide not only the ability to confirm the presence of forensically relevant body fluids, but also the ability to associate/dissociate specific body fluids with particular donors.


Asunto(s)
Líquidos Corporales , Humanos , ARN Mensajero/genética , ARN , Marcadores Genéticos , ADN/genética , Genética Forense/métodos , Semen , Saliva
14.
Int J Palliat Nurs ; 29(12): 588-596, 2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38085613

RESUMEN

BACKGROUND: Decisions about end-of-life care often raise clinical and ethical challenges, especially when the person's capacity to contribute in the decision making at the end of life is limited. AIM: This study aimed to explore Taiwanese adults' preferences associated with communication, healthcare planning, life-sustaining treatments and palliative care and experiences of end-of-life care. METHODS: Semi-structured interviews were conducted with 16 adults aged 20 years and above. The sampling approach was a convenience strategy in a community centre located in a metropolitan area in the Southern region of Taiwan. A qualitative content analysis approach was used to elicit key themes from the data. RESULTS: Significant findings related to the two main themes of adults' experiences, including the observed distress of those who were dying and the distress experienced by the family. Other key findings pertain to personal preferences for end-of-life care, such as preferred end-of-life communication, preparing for the end-of-life and maintenance of quality of life. CONCLUSIONS: This exploratory study offers insight into 16 Taiwanese community-dwelling adults' views of preferences regarding end-of-life communication, preparation for the end of life and maintenance of quality of life, as well as their experiences of end-of-life care. A further exploration is suggested to elicit how personal end-of-life experiences shape individuals' health practices in advance care planning for end-of-life care.


Asunto(s)
Planificación Anticipada de Atención , Cuidados Paliativos al Final de la Vida , Cuidado Terminal , Adulto , Humanos , Calidad de Vida , Toma de Decisiones , Muerte , Investigación Cualitativa
15.
Heliyon ; 9(12): e23003, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38076120

RESUMEN

Background: Diabetic foot ulcers (DFUs) are among the most prevalent and dangerous complications of diabetes. Angiogenesis is pivotal for wound healing; however, its role in the chronic wound healing process in DFU requires further investigation. We aimed to investigate the pathogenic processes of angiogenesis in DFU from a molecular biology standpoint and to offer insightful information about DFU prevention and therapy. Methods: Differential gene and weighted gene co-expression network analyses (WGCNA) were employed to screen for genes related to DFU using the downloaded and collated GSES147890 datasets. With the goal of identifying hub genes, an interaction among proteins (PPI) network was constructed, and enrichment analysis was carried out. Utilizing a variety of machine learning techniques, including Boruta, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), we were able to determine which hub genes most strongly correspond to DFU. This allowed us to create an ideally suited DFU forecasting model that was validated via an external dataset. Finally, by merging 36 angiogenesis-related genes (ARGs) and machine learning models, we identified the genes involved in DFU-related angiogenesis. Results: By merging 260 genes located in the green module and 59 differentially expressed genes (DEGs), 35 candidate genes highly associated with DFU were found for more investigation. 35 candidate genes were enriched in epidermal growth factor receptor binding, nuclear division regulation, fluid shear stress, atherosclerosis, and negative regulation of chromosomal structure for the enrichment study. Fifteen hub genes were found with the aid of the CytoHubba plug. The LASSO method scored better in terms of prediction performance (GSE134341) (LASSO:0.89, SVM:0.65, Boruta:0.66) based on the validation of the external datasets. We identified thrombomodulin (THBD) as a key target gene that potentially regulates angiogenesis during DFU development. Based on the external validation dataset (GSE80178 and GSE29221), receiver operating characteristic (ROC) curves with higher efficiency were generated to confirm the potential of THBD as a biomarker of angiogenesis in DFU. Furthermore supporting this finding were the results of Western blot and real-time quantitative polymerase chain reaction (RT-qPCR), which showed decreased THBD expression in human umbilical vein endothelial cells (HUVECs) cultivated under high glucose. Conclusions: The findings implicate that THBD may influence DFU progression as a potential target for regulating angiogenesis, providing a valuable direction for future studies.

16.
Clin Transl Med ; 13(12): e1516, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38148640

RESUMEN

BACKGROUND: Cancer-associated fibroblasts (CAFs), integral to the tumour microenvironment, are pivotal in cancer progression, exhibiting either pro-tumourigenic or anti-tumourigenic functions. Their inherent phenotypic and functional diversity allows for the subdivision of CAFs into various subpopulations. While several classification systems have been suggested for different cancer types, a unified molecular classification of CAFs on a single-cell pan-cancer scale has yet to be established. METHODS: We employed a comprehensive single-cell transcriptomic atlas encompassing 12 solid tumour types. Our objective was to establish a novel molecular classification and to elucidate the evolutionary trajectories of CAFs. We investigated the functional profiles of each CAF subtype using Single-Cell Regulatory Network Inference and Clustering and single-cell gene set enrichment analysis. The clinical relevance of these subtypes was assessed through survival curve analysis. Concurrently, we employed multiplex immunofluorescence staining on tumour tissues to determine the dynamic changes of CAF subtypes across different tumour stages. Additionally, we identified the small molecule procyanidin C1 (PCC1) as a target for matrix-producing CAF (matCAF) using molecular docking techniques and further validated these findings through in vitro and in vivo experiments. RESULTS: In our investigation of solid tumours, we identified four molecular clusters of CAFs: progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF) and matCAF, each characterised by distinct molecular traits. This classification was consistently applicable across all nine studied solid tumour types. These CAF subtypes displayed unique evolutionary pathways, functional roles and clinical relevance in various solid tumours. Notably, the matCAF subtype was associated with poorer prognoses in several cancer types. The targeting of matCAF using the identified small molecule, PCC1, demonstrated promising antitumour activity. CONCLUSIONS: Collectively, the various subtypes of CAFs, particularly matCAF, are crucial in the initiation and progression of cancer. Focusing therapeutic strategies on targeting matCAF in solid tumours holds significant potential for cancer treatment.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Simulación del Acoplamiento Molecular , Neoplasias/patología , Perfilación de la Expresión Génica , Transcriptoma/genética , Microambiente Tumoral/genética
17.
Fa Yi Xue Za Zhi ; 39(5): 465-470, 2023 Oct 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38006266

RESUMEN

OBJECTIVES: To explore the feasibility of genetic marker detection of semen-specific coding region single nucleotide polymorphism (cSNP) based on SNaPshot technology in semen stains and mixed body fluid identification. METHODS: Genomic DNA (gDNA) and total RNA were extracted from 16 semen stains and 11 mixtures composed of semen and venous blood, and the total RNA was reverse transcribed into complementary DNA (cDNA). The cSNP genetic markers were screened on the validated semen-specific mRNA coding genes. The cSNP multiplex detection system based on SNaPshot technology was established, and samples were genotyped by capillary electrophoresis (CE). RESULTS: A multiplex detection system containing 5 semen-specific cSNPs was successfully established. In 16 semen samples, except the cSNP located in the TGM4 gene showed allele loss in cDNA detection results, the gDNA and cDNA typing results of other cSNPs were highly consistent. When detecting semen-venous blood mixtures, the results of cSNP typing detected were consistent with the genotype of semen donor and were not interfered by the genotype of venous blood donor. CONCLUSIONS: The method of semen-specific cSNPs detection by SNaPshot technology method can be applied to the genotyping of semen (stains) and provide information for determining the origin of semen in mixed body fluids (stains).


Asunto(s)
Líquidos Corporales , Semen , Marcadores Genéticos , Polimorfismo de Nucleótido Simple , ADN Complementario/genética , ARN Mensajero/genética , ADN , Saliva , Genética Forense/métodos
18.
Clin Transl Med ; 13(11): e1481, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37983931

RESUMEN

BACKGROUND: Gastric cancer (GC) is one of the most common tumours in East Asia countries and is associated with Helicobacter pylori infection. H. pylori utilizes virulence factors, CagA and VacA, to up-regulate pro-inflammatory cytokines and activate NF-κB signaling. Meanwhile, the PIEZO1 upregulation and cancer-associated fibroblast (CAF) enrichment were found in GC progression. However, the mechanisms of PIEZO1 upregulation and its involvement in GC progression have not been fully elucidated. METHODS: The CAF enrichment and clinical significance were investigated in animal models and primary samples. The expression of NF-κB and PIEZO1 in GC was confirmed by immunohistochemistry staining, and expression correlation was analysed in multiple GC datasets. GSEA and Western blot analysis revealed the YAP1-CTGF axis regulation by PIEZO1. The stimulatory effects of CTGF on CAFs were validated by the co-culture system and animal studies. Patient-derived organoid and peritoneal dissemination models were employed to confirm the role of the PIEZO1-YAP1-CTGF cascade in GC. RESULTS: Both CAF signature and PIEZO1 were positively correlated with H. pylori infection. PIEZO1, a mechanosensor, was confirmed as a direct downstream of NF-κB to promote the transformation from intestinal metaplasia to GC. Mechanistic studies revealed that PIEZO1 transduced the oncogenic signal from NF-κB into YAP1 signaling, a well-documented oncogenic pathway in GC progression. PIEZO1 expression was positively correlated with the YAP1 signature (CTGF, CYR61, and c-Myc, etc.) in primary samples. The secreted CTGF by cancer cells stimulated the CAF infiltration to form a stiffened collagen-enrichment microenvironment, thus activating PIEZO1 to form a positive feedback loop. Both PIEZO1 depletion by shRNA and CTGF inhibition by Procyanidin C1 enhanced the efficacy of 5-FU in suppressing the GC cell peritoneal metastasis. CONCLUSION: This study elucidates a novel driving PIEZO1-YAP1-CTGF force, which opens a novel therapeutic avenue to block the transformation from precancerous lesions to GC. H. pylori-NF-κB activates the PIEZO1-YAP1-CTGF axis to remodel the GC microenvironment by promoting CAF infiltration. Targeting PIEZO1-YAP1-CTGF plus chemotherapy might serve as a potential therapeutic option to block GC progression and peritoneal metastasis.


Asunto(s)
Fibroblastos Asociados al Cáncer , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Peritoneales , Neoplasias Gástricas , Animales , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Neoplasias Gástricas/patología , Helicobacter pylori/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/metabolismo , Microambiente Tumoral/genética , Canales Iónicos
19.
Prev Med Rep ; 36: 102433, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37781107

RESUMEN

The prevention of diabetic foot ulcers (DFU) precedes treatment, in that early prevention significantly reduces the incidence of foot ulcers. The main objectives of this study were to examine the current prevalence of proactive foot ulcer examinations among diabetic patients and analyze influencing factors, in order to provide a scientific reference for the prevention of DFU in diabetic patients. The National Health and Nutrition Examination Survey (NHANES) 2011-2018 (n = 1278) data were utilized in this cross-sectional study. The dependent variable was whether patients underwent self-initiated foot ulcer inspections; risk factors that may lead to foot ulcers were included as independent variables. To explore the connection between the patient's subjective motivation to inspect foot ulcers and risk variables, the weighted logistic regression model was further carried out. Among all risk factors, race, body mass index (BMI) and hypertension were statistically significant between whether patients were examined for foot ulcers or not. In the fully adjusted logistic regression model, only hypertension was positively correlated with diabetic patient-initiated examination for foot ulcers. This study suggests that there is still room for improvement in the knowledge and behavior of diabetic patients to be proactive in preventing DFU. Health care and community workers should conduct targeted training on diabetic foot prevention to reduce and prevent DFU by reinforcing knowledge to build positive attitudes and drive preventive behavior change.

20.
Biomed Opt Express ; 14(10): 5199-5207, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37854577

RESUMEN

In this work, we design multi-parameter phase imaging flow cytometry based on dual-view transport of intensity (MPFC), which integrates phase imaging and microfluidics to a microscope, to obtain single-shot quantitative phase imaging on cells flowing in the microfluidic channel. The MPFC system has been proven with simple configuration, accurate phase retrieval, high imaging contrast, and real-time imaging and has been successfully employed not only in imaging, recognizing, and analyzing the flowing cells even with high-flowing velocities but also in tracking cell motilities, including rotation and binary rotation. Current results suggest that our proposed MPFC provides an effective tool for imaging and analyzing cells in microfluidics and can be potentially used in both fundamental and clinical studies.

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