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1.
Urolithiasis ; 52(1): 126, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39237840

RESUMEN

Kidney Stone Disease (KSD) constitutes a multifaceted disorder, emerging from a confluence of environmental and genetic determinants, and is characterized by a high frequency of occurrence and recurrence. Our objective is to elucidate potential causative proteins and identify prospective pharmacological targets within the context of KSD. This investigation harnessed the unparalleled breadth of plasma protein and KSD pooled genome-wide association study (GWAS) data, sourced from the United Kingdom Biobank Pharma Proteomics Project (UKBPPP) and the FinnGen database version R10. Through Mendelian randomization analysis, proteins exhibiting a causal influence on KSD were pinpointed. Subsequent co-localization analyses affirmed the stability of these findings, while enrichment analyses evaluated their potential for pharmacological intervention. Culminating the study, a phenome-wide association study (PheWAS) was executed, encompassing all phenotypes (2408 phenotypes) catalogued in the FinnGen database version R10. Our MR analysis identified a significant association between elevated plasma levels of proteins FKBPL, ITIH3, and SERPINC1 and increased risk of KSD based on genetic predictors. Conversely, proteins CACYBP, DAG1, ITIH1, and SEMA6C showed a protective effect against KSD, documented with statistical significance (PFDR<0.05). Co-localization analysis confirmed these seven proteins share genetic variants with KSD, signaling a shared genetic basis (PPH3 + PPH4 > 0.8). Enrichment analysis revealed key pathways including hyaluronan metabolism, collagen-rich extracellular matrix, and serine-type endopeptidase inhibition. Additionally, our PheWAS connected the associated proteins with 356 distinct diseases (PFDR<0.05), highlighting intricate disease interrelations. In conclusion, our research elucidated a causal nexus between seven plasma proteins and KSD, enriching our grasp of prospective therapeutic targets.


Asunto(s)
Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Proteoma , Humanos , Nefrolitiasis/genética , Nefrolitiasis/sangre , Nefrolitiasis/metabolismo , Fenotipo , Proteómica
2.
Appl Environ Microbiol ; : e0228723, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235242

RESUMEN

The composition and stability of the microbial community structure of roots and root zone soils play a key role in the healthy growth of plants. We examined the distribution characteristics of phenolic acids and saponins, as well as microbial communities in the root space (root endosphere, rhizoplane soil, rhizosphere soil, and bulk soil) of healthy and root rot disease-affected Panax notoginseng. The results showed that after infection with root rot, the rhizoplane soil exhibited significant decreases in organic matter and hydrolyzable nitrogen and significant increases in available phosphorus, available potassium, and total nitrogen. The contents of phenolic acids (except benzoic acid) and ginsenoside Rg2 in the root endosphere significantly increased. Ferulic acid and p-hydroxybenzoic acid in the rhizoplane soil significantly increased. Rhodococcus increased significantly in the root endosphere, rhizoplane, and rhizosphere soil; Nitrospira decreased significantly in the rhizoplane, rhizosphere, and bulk soil; and Plectosphaerella decreased significantly in the root endosphere and rhizoplane soil. Moreover, the accumulation of most autotoxins can promote the growth of pathogens. In summary, the spatial autotoxic substances and microbial community differences in P. notoginseng roots jointly induce the occurrence of root rot.IMPORTANCEPanax notoginseng is highly susceptible to soil-borne diseases induced during planting, and root rot, which usually occurs in the root and stem parts of the plant, is the most severe. We divided the root environment of P. notoginseng into four parts (root endosphere, rhizoplane soil, rhizosphere soil, and bulk soil) and studied it with unplanted soil as the control. In this study, we examined the changes in the content of autotoxic substances in the root space of P. notoginseng, along with the interplay between these substances and microorganisms. This study revealed the mechanism underlying root rot and provided a theoretical basis for alleviating continuous cropping obstacles in P. notoginseng.

3.
Cell Biosci ; 14(1): 118, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267141

RESUMEN

BACKGROUND: The cell development atlas of transition stage from late Carnegie to fetal development (7-9 weeks) remain unclear. It can be seen that the early period of human embryos (7-9 weeks) is a critical research gap. Therefore, we employed single­cell RNA sequencing to identify cell types and elucidate differentiation relationships. RESULTS: The single­cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7-9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. CONCLUSIONS: We provide the cell development atlas for human embryos (7-9 weeks). Two distinct cell development and differentiation pathways are revealed.

4.
J Robot Surg ; 18(1): 316, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120845

RESUMEN

Robotic pyelolithotomy continues to gain attention as an alternative to percutaneous nephrolithotomy (PCNL) for managing complex renal stones. We performed a single-arm meta-analysis and systematically searched the English-language literature published in PubMed, Web of Science, Scopus, and Google Scholar databases up to June 2024. The risk of non-randomized bias was assessed using ROBINS-I, and the quality of the literature was assessed using MINORS (Methodological Index for Non-Randomized Studies). Merger parameters were calculated using Stata16/SE under a random-effects model. Five non-comparative single-arm studies were included in the meta-analysis. Results showed that the operative time for robotic pyelolithotomy was 168.10 min (95% CI 133.63, 202.56). The hospital stay was 2.63 days (95% CI 0.96, 4.29), and blood loss was 44.13 ml (95% CI 19.76, 68.51). The stone clearance rate was 87% (95% CI 79-93%). The incidence of minor postoperative complications (Clavien grade I-II) was 23.7% (95% CI 13.4-35.8%), and the incidence of major complications (Clavien grade ≥ III) was 7% (95% CI 0.3-20.7%).The safety and efficacy of robotic pyelolithotomy in treating complex renal stones are acceptable, but future large prospective cohort studies are needed to validate the treatment.


Asunto(s)
Cálculos Renales , Tempo Operativo , Procedimientos Quirúrgicos Robotizados , Humanos , Cálculos Renales/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Nefrolitotomía Percutánea/métodos , Nefrolitotomía Percutánea/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Pelvis Renal/cirugía , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Femenino , Masculino
5.
J Cancer ; 15(15): 4902-4921, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39132155

RESUMEN

Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. Lb. plantarum AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that Lb. plantarum AY01 can block cell proliferation in the S phase. In addition, Lb. plantarum AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, Lb. plantarum AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC.

6.
Diabetes Metab Syndr Obes ; 17: 3079-3085, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184552

RESUMEN

Background: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China. Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression. Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345-1.957) and 1.990 (95%CI: 1.709-2.316) in women with NAFLD, compared with the subjects without NAFLD. Conclusions: NAFLD is independently associated with increased risk of CVD development.

7.
RSC Adv ; 14(36): 26239-26245, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39211530

RESUMEN

In this work, the excited state intramolecular double proton transfer (ESIDPT) mechanism of 2,2'-(benzo[1,2-d:4,5-d']bis(thiazole)-2,6-diyl)diphenol (BTAP) is proposed using density functional theory (DFT) and time-dependent DFT (TDDFT). The changes in bond lengths, bond angles and IR vibrational spectra associated with two intramolecular hydrogen bonds of BTAP upon photoexcitation indicate that the hydrogen bonds are strengthened in the excited state, facilitating the ESIDPT process. Investigation of the constructed S1-state potential energy surface proposes that BTAP prefers a stepwise ESIDPT mechanism. Electronic spectra and frontier molecular orbitals (FMOs) are also presented to illustrate the luminescent properties of BTAP.

8.
Behav Sci (Basel) ; 14(8)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39199050

RESUMEN

Based on the chain-mediating role of mindfulness and sense of control, this study examines the mediating role of mindfulness and sense of control on employees' mental health. A total of 720 questionnaires were collected from employees of select enterprises and institutions in China; 53 invalid questionnaires were excluded, with a response rate of 93%, leaving 667 employees as the study sample (average age = 38 years, 71.8% female). The study findings show that: (1) Work-family conflict had a significant positive correlation with mental health problems and a significant negative correlation with mindfulness and sense of control. (2) The influence on the mental health state was due to the mediating effect of mindfulness, sense of control, and the chain-mediating effect of mindfulness and sense of control. The study adopted self-report scales for measuring mindfulness and a sense of control; therefore, further experimental methods must be included in the future to explore these results. This study shows that mindfulness and sense of control can reduce the impact of work-family conflict on mental health problems. Additionally, the chain-mediating effect of mindfulness and sense of control plays an important role in mental health problems.

9.
Front Endocrinol (Lausanne) ; 15: 1386021, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39140031

RESUMEN

Background: The correlation between oxidative stress and female infertility pathogenesis was established, and the oxidative balance score (OBS) can serve as a measure of overall oxidative stress burden within an individual. Prior reports have not addressed the relationship between OBS and female infertility. This study endeavors to investigate the association between infertility risk in female and OBS. Methods: The analysis focused on data from the National Health and Nutrition Examination Survey 2013-2018. OBS was determined from 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and female infertility. Further stratified analysis was conducted to examine the associations across various subgroups. To elucidate the dose-response relationship between infertility risk in female and OBS, a restricted cubic spline function was employed. Results: The study included a total of 1410 participants. Through weighted multivariable logistic regression analysis, we observed a consistent inverse correlation between OBS and the risk of female infertility [OR (95% CI) = 0.97 (0.95, 0.99), p = 0.047]. When participants were segregated into quartiles based on OBS, those in the highest quartile had a 61% [OR (95% CI) = 0.39 (0.2, 0.79), p = 0.01] reduced risk of infertility compared to those in the lowest quartile of OBS. A trend test assessing OBS by quartile also revealed the relationship between OBS and female infertility. This correlation remained constant across both dietary and lifestyle OBS. Additionally, lifestyle OBS and female infertility exhibited a nonlinear association. A sensitivity analysis verified the consistency of our findings. Conclusion: The study found that a higher OBS is associated with a lower prevalence of female infertility. These results emphasized the potential role of oxidative homeostasis in the pathogenesis of infertility and highlighted the importance of follow-up studies and prevention strategies.


Asunto(s)
Infertilidad Femenina , Encuestas Nutricionales , Estrés Oxidativo , Humanos , Femenino , Adulto , Infertilidad Femenina/epidemiología , Infertilidad Femenina/metabolismo , Estilo de Vida , Adulto Joven , Estudios Transversales , Estados Unidos/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Dieta
10.
J Med Microbiol ; 73(8)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39150452

RESUMEN

Introduction. Klebsiella spp. are important bacteria that colonize the human intestine, especially in preterm infants; they can induce local and systemic disease under specific circumstances, including inflammatory bowel disease, necrotizing enterocolitis and colorectal cancer.Hypothesis. Klebsiella spp. colonized in the intestine of the neonates in the neonatal intensive care unit (NICU) may be associated with disease and antibiotic resistance, which will be hazardous to the children.Aim. Our aim was to know about the prevalence, antimicrobial resistance and genome characteristics of Klebsiella spp. in neonate carriers.Methodology. Genome sequencing and analysis, and antimicrobial susceptibility testing were mainly performed in this study.Results. The isolation rates of Klebsiella spp. strains were 3.7% (16/436) in 2014 and 4.3% (18/420) in 2021. Cases with intestinal-colonized Klebsiella spp. were mainly infants with low birth weights or those with pneumonia or hyperbilirubinemia. According to the core-pan genomic analysis, 34 stains showed gene polymorphism and a sequence type (ST) of an emerging high-risk clone (ST11). Eight strains (23.5%) were found to be resistant to 2 or more antibiotics, and 46 genes/gene families along with nine plasmids were identified that conferred resistance to antibiotics. In particular, the two strains were multidrug-resistant. Strain A1256 that is related to Klebsiella quasipneumoniae subsp. similipneumoniae was uncommon, carrying two plasmids similar to IncFII and IncX3 that included five antibiotic resistance genes.Conclusion. The prevention and control of neonatal Klebsiella spp. colonization in the NICU should be strengthened by paying increased attention to preventing antimicrobial resistance in neonates.


Asunto(s)
Antibacterianos , Heces , Genoma Bacteriano , Unidades de Cuidado Intensivo Neonatal , Infecciones por Klebsiella , Klebsiella , Pruebas de Sensibilidad Microbiana , Humanos , Recién Nacido , Klebsiella/genética , Klebsiella/efectos de los fármacos , Klebsiella/aislamiento & purificación , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/epidemiología , Heces/microbiología , Antibacterianos/farmacología , Femenino , Masculino , Farmacorresistencia Bacteriana/genética , Secuenciación Completa del Genoma , Farmacorresistencia Bacteriana Múltiple/genética
11.
BMC Pulm Med ; 24(1): 378, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090583

RESUMEN

BACKGROUND: Plague is an acute infectious disease caused by the Yersinia pestis. Historically, it has been a major pandemic with high mortality rates, known as the "Black Death" in the 14th century, which resulted in millions of deaths in Europe. With increasing economic prosperity, more and more people are traveling to Xizang. However, this trend also hides significant safety hazards. Currently, there are few recent reports on plague, especially those with imaging manifestations available. In this study, we report the detailed clinical and radiological data of the patient with pneumonic plague in Xizang, China, in 2023. CASE PRESENTATION: We report a case of pneumonic plague in Xizang, which occurred in a herdsman living in an area where dead marmots were found. The patient presented with symptoms such as fever, hemoptysis, dyspnea and coma. Chest computed tomography (CT) scans showed multiple nodules distributed in the central regions of lung lobes, consolidation distributed in secondary pulmonary lobules, and had a gravity-dependent distribution pattern. These imaging findings were consistent with pulmonary hemorrhage and diffuse alveolar damage. Despite emergency treatment, the patient died within 48 h of admission. Through retrospective medical history investigation, laboratory examination and autopsy, the final diagnosis was confirmed as pneumonic plague. CONCLUSION: Pneumonic plague is the most deadly infectious disease, and its pathological features mainly include damage to the alveoli, pulmonary hemorrhage, and pulmonary edema. Corresponding to CT, it manifests as acute and rapidly progressing pneumonia, alveolar damage, and pulmonary hemorrhage. The value of this article lies in the completeness and typicality of the imaging data, vivid hand-drawn illustrations of transmission pathways, and comprehensive literature review, all of which serve to enhance public understanding of plague and play an important warning role.


Asunto(s)
Peste , Tomografía Computarizada por Rayos X , Humanos , Peste/diagnóstico , China , Masculino , Resultado Fatal , Pulmón/diagnóstico por imagen , Pulmón/patología , Yersinia pestis/aislamiento & purificación , Animales , Marmota
12.
Crit Rev Anal Chem ; : 1-20, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978228

RESUMEN

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

13.
J Robot Surg ; 18(1): 301, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078530

RESUMEN

This investigation sought to conduct a comprehensive meta-analysis to assess the comparative effectiveness and safety of percutaneous ablation (PCA) versus robotic-assisted partial nephrectomy (RAPN) among individuals diagnosed with cT1 renal tumors. This study rigorously followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. A systematic search was carried out in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English through February 2024. We focused on evaluating primary outcomes, specifically perioperative outcomes, functional outcomes, and oncological outcomes. In this analysis, data from 1534 patients across 13 studies were evaluated. PCA was found to have advantageous outcomes in comparison to RAPN regarding hospital stay durations, with a Weighted Mean Difference (WMD) of - 2.03 days (95% Confidence Interval [CI]: -3.78 to - 0.27; p = 0.02), operative times (WMD: -106.75 min; 95% CI: - 170.78 to - 42.72; p = 0.001), and overall complication rates (Odds Ratio [OR]: 0.61; 95% CI: 0.42 to 0.89; p = 0.01). Conversely, PCA showed a higher incidence of local recurrence compared to RAPN, with an OR of 3.20 (95% CI: 1.91 to 5.35; p < 0.00001). Moreover, there were no statistically significant differences between the two treatments in terms of major complications, declines in estimated glomerular filtration rates (eGFR), variations in creatinine levels, overall survival rates, and recurrence-free survival. While PCA exhibits higher local recurrence rates than RAPN, it also presents significant advantages, such as shorter hospital stays, decreased operative durations, and lower complication rates. This juxtaposition underscores the urgent need for further, more rigorous research to substantiate these findings.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Nefrectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Nefrectomía/métodos , Neoplasias Renales/cirugía , Carcinoma de Células Renales/cirugía , Resultado del Tratamiento , Tempo Operativo , Tiempo de Internación/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
14.
Sci Rep ; 14(1): 16942, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043787

RESUMEN

Quantum computing, with its superior computational capabilities compared to classical approaches, holds the potential to revolutionize numerous scientific domains, including pharmaceuticals. However, the application of quantum computing for drug discovery has primarily been limited to proof-of-concept studies, which often fail to capture the intricacies of real-world drug development challenges. In this study, we diverge from conventional investigations by developing a hybrid quantum computing pipeline tailored to address genuine drug design problems. Our approach underscores the application of quantum computation in drug discovery and propels it towards more scalable system. We specifically construct our versatile quantum computing pipeline to address two critical tasks in drug discovery: the precise determination of Gibbs free energy profiles for prodrug activation involving covalent bond cleavage, and the accurate simulation of covalent bond interactions. This work serves as a pioneering effort in benchmarking quantum computing against veritable scenarios encountered in drug design, especially the covalent bonding issue present in both of the case studies, thereby transitioning from theoretical models to tangible applications. Our results demonstrate the potential of a quantum computing pipeline for integration into real world drug design workflows.


Asunto(s)
Descubrimiento de Drogas , Teoría Cuántica , Descubrimiento de Drogas/métodos , Diseño de Fármacos/métodos , Profármacos/química , Termodinámica
15.
Clin Case Rep ; 12(6): e9024, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38883220

RESUMEN

Key Clinical Message: Good's syndrome (GS) presents with thymoma, hypogammaglobulinemia, and recurrent infection. The manifestations of patients diagnosed with GS and Cytomegalovirus (CMV) gastroenteritis are rare and non-specific. Early diagnosis and treatment can improve the prognosis of the rare disease. Abstract: Good's syndrome (GS), a rare acquired immunodeficiency condition, is characterized by thymoma, hypogammaglobulinemia, and low peripheral B-lymphocyte count. GS tends to occur in individuals aged 40-60 years, resulting in increased risk of recurrent infections with various conditional pathogenic bacteria, viruses, and fungi. Cytomegalovirus (CMV) can cause pneumonia, retinitis, encephalitis, and enteritis in GS patient, but CMV infection in the alimentary tract is usually underestimated, delayed diagnosed and misdiagnosed. In this study, we reported a female patient with GS and chronic diarrhea due to CMV infection and reviewed the literature to conclude the characteristics of this rare condition to improve the clinical diagnosis and prognosis of CMV gastroenteritis in patients with GS.

16.
Talanta ; 277: 126395, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38865958

RESUMEN

In this study, an original molecularly imprinted electrochemical sensor (MIECS) is prepared using layer-by-layer modification of sensitization nanomaterials (CuCo2O4/BPC-E) coupled with molecularly imprinted polymers (MIPs) for the ultrasensitive and rapid determination of dimetridazole (DMZ) contaminants. The biomass waste of eggshell (ES) powders subtly introduced in situ in the carbonization process of psyllium husk (PSH) substantially promotes the physicochemical properties of the resulting biomass-derived porous carbon (BPC-E). The large specific surface area and abundant pores provide a favourable surface for loading mesoporous CuCo2O4 with a spinel structure. The assembly of CuCo2O4/BPC-E on the gold electrode (GE) surface enhances the electrochemical sensing signal. The MIPs constructed using DMZ and o-phenylenediamine (oPD) as templates and functional monomers boost the targeted recognition performance of the analyte. The combined DMZ targets then undergo an electrochemical reduction reaction in situ with the transfer of four electrons and four protons. Under optimum conditions, the current response of differential pulse voltammetry (DPV) exhibits two linear ranges for DMZ detection, 0.01-10 µM and 10-200 µM. The limit of detection (LOD) is 1.8 nM (S/N = 3) with a sensitivity of 5.724 µA µM-1 cm-2. The obtained MIECS exhibits excellent selectivity, reproducibility, repeatability and stability. This electrochemical sensing system is applied to the detection of real samples (tap water, coarse fodder and swine urine), yielding satisfactory recoveries (90.6%-98.1 %), which are consistent with those obtained via HPLC. This finding verifies that the utility of MIECS for monitoring pharmaceutical and environmental contaminants and ensuring food safety.


Asunto(s)
Carbono , Técnicas Electroquímicas , Polímeros Impresos Molecularmente , Nanocompuestos , Nanocompuestos/química , Porosidad , Carbono/química , Polímeros Impresos Molecularmente/química , Técnicas Electroquímicas/métodos , Biomasa , Límite de Detección , Animales , Cobre/química , Electrodos , Contaminantes Químicos del Agua/análisis
17.
Expert Opin Ther Pat ; 34(8): 701-721, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38884569

RESUMEN

INTRODUCTION: KRAS is a critical oncogenic protein intricately involved in tumor progression, and the difficulty in targeting KRAS has led it to be classified as an 'undruggable target.' Among the various KRAS mutations, KRASG12D is highly prevalent and represents a promising therapeutic target, yet there are currently no approved inhibitors for it. AREA COVERED: This review summarizes numerous patents and literature featuring inhibitors or degraders of KRASG12D through searching relevant information in PubMed, SciFinder and Web of Science databases from 2021 to February 2024, providing an overview of the research progress on inhibiting KRASG12D in terms of design strategies, chemical structures, biological activities, and clinical advancements. EXPERT OPINION: Since the approval of AMG510 (Sotorasib), there has been an increasing focus on the inhibition of KRASG12D, leading to numerous reports of related inhibitors and degraders. Among them, MRTX1133, as the first KRASG12D inhibitor to enter clinical trials, has demonstrated excellent tumor suppression in various KRASG12D-bearing human tumor xenograft models. It is important to note, however, that understanding the mechanisms of acquired resistance caused by KRAS inhibition and developing additional combination therapies is crucial. Moreover, seeking covalent inhibition of KRASG12D also holds significant potential.


Asunto(s)
Antineoplásicos , Neoplasias , Patentes como Asunto , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Animales , Antineoplásicos/farmacología , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Mutación , Diseño de Fármacos , Desarrollo de Medicamentos , Resistencia a Antineoplásicos , Terapia Molecular Dirigida , Piperazinas , Piridinas , Pirimidinas
18.
Oncol Lett ; 28(2): 339, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38855503

RESUMEN

3,3'-Diindolylmethane (DIM) is a natural phytochemical derived from cruciferous plants that has inhibitory effects on a wide range of tumor cells; however, its relevant effects on esophageal cancer cells have been poorly studied. Therefore, in the present study, a pharmacology network approach was used to predict the possible core targets of DIM acting on esophageal cancer. Subsequently, using in vitro experiments, TE-1 human esophageal cancer cells were treated with different concentrations of DIM (0, 40, 60 and 80 µM) for 24 h. Changes in cell activity were detected by Cell Counting Kit-8 assay, and changes in the expression levels of stromal interaction molecule 1 (STIM1) and apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2) and Bax, were assessed by western blotting, followed by the upregulation of STIM1 by thapsigargin (Tg). Network pharmacology analysis showed that there were 39 potential core targets of DIM in esophageal cancer. The results of the in vitro experiments showed that DIM could inhibit the viability of esophageal cancer cells, downregulate the expression of STIM1 and Bcl-2 proteins and upregulate the expression of Bax protein, all in a concentration-dependent manner. The results also demonstrated that toxic carotenoids were agonist against STIM1 protein and upregulated STIM1 and Bax protein expression. After agonizing STIM1 protein expression using Tg, DIM was able to counteract the expression trend of STIM1, Bcl-2 and Bax protein in TE-1 cells. In summary, DIM induced apoptosis and inhibited the viability of esophageal cancer cells by downregulating the expression of STIM1 protein; therefore, the natural phytochemical, DIM, may be a potential substance for the early prevention and treatment of esophageal cancer cells.

19.
Diagnostics (Basel) ; 14(10)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38786304

RESUMEN

BACKGROUND: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. METHODS: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. RESULTS: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1-90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. CONCLUSIONS: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

20.
ACS Nano ; 18(19): 12341-12354, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38695772

RESUMEN

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.


Asunto(s)
Nanofibras , Animales , Ratas , Nanofibras/química , Cicatrización de Heridas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/patología , Adherencias Tisulares/prevención & control , Ratas Sprague-Dawley , Adhesión Celular/efectos de los fármacos , Cerio/química , Cerio/farmacología , Propiedades de Superficie , Ratones , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología
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