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1.
PeerJ ; 12: e18023, 2024.
Article in English | MEDLINE | ID: mdl-39224828

ABSTRACT

Background: Hemorrhoids are common conditions at or around the anus, to which numerous people suffer worldwide. Previous research has suggested that microbes may play a role in the development of hemorrhoids, and the origins of these microbes have been preliminarily investigated. However, no detailed research on the microbes related to hemorrhoid patients has been conducted. This work aims to provide an initial investigation into the microbes related to hemorrhoid patients with high quality whole genome sequencing. Methods: Forty-nine bacterial strains were isolated from seven hemorrhoid patients. Third-generation nanopore sequencing was performed to obtain high quality whole genome sequences. The presence of plasmids, particularly new plasmids, along with antibiotic resistance genes, was investigated for these strains. Phylogenetic analysis and genome comparisons were performed. Results: Out of the 31 plasmids found in the strains, 15 new plasmids that have not been observed previously were discovered. Further structural analysis revealed new multidrug-resistant conjugative plasmids, virulent plasmids, and small, high-copy mobile plasmids that may play significant functional roles. These plasmids were found to harbor numerous integrases, transposases, and recombinases, suggesting their ability to quickly obtain genes to change functions. Analysis of antibiotic resistance genes revealed the presence of antibiotic resistant-integrons. Together with the surprising number of new plasmids identified, as well as the finding of transmission and modification events for plasmids in this work, we came to the suggestion that plasmids play a major role in genetic plasticity. Conclusion: This study reveals that the diversity of plasmids in human-associated microbes has been underestimated. With the decreasing cost of whole-genome sequencing, monitoring plasmids deserves increased attention in future surveillance efforts.


Subject(s)
Bacteria , Hemorrhoids , Phylogeny , Plasmids , Humans , Plasmids/genetics , Hemorrhoids/microbiology , Hemorrhoids/genetics , Bacteria/genetics , Bacteria/isolation & purification , Whole Genome Sequencing , Male , Drug Resistance, Multiple, Bacterial/genetics , Female , Adult
2.
Zookeys ; 1210: 197-206, 2024.
Article in English | MEDLINE | ID: mdl-39220724

ABSTRACT

A new species Serangiumxinpingensis Huang & Wang, sp. nov. is described from Yunnan Province, China, as a newly discovered predator on Bemisiatabaci Gennadius (Hemiptera, Sternorrhyncha, Aleyrodidae). The new species is a valuable addition to the 14 species of this genus in China known before. A diagnosis, detailed description, including the structure of its immature stages, illustrations, and the distribution of the new species are provided.

3.
Ther Clin Risk Manag ; 20: 543-556, 2024.
Article in English | MEDLINE | ID: mdl-39220772

ABSTRACT

Background and Aim: The Global Leadership Initiative on Malnutrition (GLIM) has proposed criteria for the diagnosis of malnutrition. No studies validated the GLIM criteria in acute pancreatitis (AP). The present study aimed to validate the predictive capacity of GLIM criteria for adverse outcomes in AP patients. Patients and Methods: Clinical data of 269 patients with AP were analyzed retrospectively. The Nutritional Risk Screening 2002 (NRS2002) was chosen as the screening tool. Multivariate logistic regression analyses evaluated the adverse clinical outcomes in malnourished patients. Results: Overall, 160 patients (59.5%) were at nutritional risk and 38 (14.1%) were malnourished. Reduced muscle mass/ low body mass index + inflammation combinations contributed most to malnutrition overall and in each subgroup. The malnourished group had lower hemoglobin, neutrophils, albumin, total cholesterol, and triglycerides than the well-nourished group. The malnourished group had higher hospitalization costs (CNY, 11319.34 vs 9258.22, p <0.001) and more local complications (34.2% vs 14.7%, p =0.009) than the well-nourished group. There was an interaction between malnutrition and overweight/obesity on local complications (p for interaction = 0.023). Multivariate logistic regression showed malnutrition was significantly associated with local complications (OR 12.2, 95% CI: 2.51-59.37), infectious complications (OR 9.95, 95% CI: 1.25-79.44) and composite adverse outcome (OR 4.78, 95% CI: 1.05-21.73) in the overweight/obesity subgroup. There was no association between malnutrition and the rate of various adverse outcomes in the non-overweight/obesity subgroup. Additionally, we observed an association between malnutrition and composite adverse outcome (OR 6.75, 95% CI: 1.49-30.68) in patients <70 years only in females. Conclusion: Malnourished AP patients were more likely to have adverse outcomes than well-nourished patients. Malnutrition was associated with various adverse outcomes only in the overweight/obesity subgroups.

4.
Acta Biomater ; 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39222705

ABSTRACT

Islet transplantation has been developed as an effective cell therapy strategy to treat the progressive life-threatening disease Type 1 diabetes (T1DM). To mimic the natural islets and achieve immune isolation, hydrogel encapsulation of multiple islet cell types is the current endeavor. Here, we present a microfiber loading with pancreatic α and ß cells by microfluidic spinning for diabetes treatment. Benefiting from microfluidic technology, the cells could be controllably and continuously loaded in the alginate and methacrylated hyaluronic acid (Alg-HAMA) microfiber and maintained their high bioactivity. The resultant microfiber could then hold the capacity of dual-mode glucose responsiveness attributed to the glucagon and insulin secreted by the encapsulated pancreatic α and ß cells. After transplantation into the brown adipose tissue (BAT), these cell-laden microfibers showed successful blood glucose control in rodents and avoided the occurrence of hypoglycemia. These results conceived that the multicellular microfibers are expected to provide new insight into artificial islet preparation, diabetes treatment, and regenerative medicine as well as tissue engineering. STATEMENT OF SIGNIFICANCE: The microfibers were generated with a double network of alginate and methacrylated hyaluronic acid. The microfibers could simultaneously encapsulate pancreatic α and ß cells and showed dual-mode glucose responsiveness. The cell-laden microfibers maintained a long-term hormone-releasing function in vivo. Cell-laden microfibers transplanted into diabetic mice could achieve glycemic control for 6 weeks.

5.
Adv Healthc Mater ; : e2402292, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240055

ABSTRACT

Perianal fistulas represent a common, aggressive, and disabling complication of Crohn's disease (CD). Despite recent drug developments, novel surgical interventions as well as multidisciplinary treatment approaches, the outcome is dismal, with >50% therapy failure rates. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) offer potential therapeutic benefits for treating fistulizing CD, due to the pro-regenerative paracrine signals. However, a significant obstacle to clinical translation of EV-based therapy is the rapid clearance and short half-life of EVs in vivo. Here, an injectable, biodegradable nanofiber-hydrogel composite (NHC) microgel matrix that serves as a carrier to deliver MSC-derived EVs to a rat model of CD perianal fistula (PAF) is reported. It is found that EV-loaded NHC (EV-NHC) yields the best fistula healing when compared to other treatment arms. The MRI assessment reveals that the EV-NHC reduces inflammation at the fistula site and promotes tissue healing. The enhanced therapeutic outcomes are contributed by extended local retention and sustained release of EVs by NHC. In addition, the EV-NHC effectively reduces inflammation at the fistula site and promotes tissue healing and regeneration via macrophage polarization and neo-vascularization. This EV-NHC platform provides an off-the-shelf solution that facilitates its clinical translation.

6.
Diabetes Care ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235839

ABSTRACT

OBJECTIVE: We explored the potential value of continuous glucose monitoring (CGM) in early pregnancy in predicting gestational diabetes mellitus (GDM) and pregnancy outcomes. RESEARCH DESIGN AND METHODS: The study recruited 103 multiethnic Asian pregnant women with overweight/obesity from a hospital-based, prospective cohort. All of them had worn blinded CGM devices in early pregnancy and underwent the universal GDM screening at 24-28 gestation weeks. Models were selected based on early pregnancy risk factors and CGM-derived parameters to compare their respective predictive values for GDM and pregnancy outcomes. RESULTS: Eighteen GDM cases were ascertained. CGM-derived novel parameters demonstrated greater performance (e.g., area under the curve: 0.953 vs. 0.722) for predicting incident GDM compared with the model using traditional risks. Such novel CGM-derived parameters significantly differentiated primary cesarean and large-for-gestational age babies. CONCLUSIONS: Our data suggest CGM's potential clinical utility in the first trimester for predicting GDM and adverse pregnancy outcomes, particularly in overweight or obese individuals.

7.
Digit Health ; 10: 20552076241277021, 2024.
Article in English | MEDLINE | ID: mdl-39229462

ABSTRACT

Introduction: ChatGPT can serve as an adjunct informational tool for ophthalmologists and their patients. However, the reliability and readability of its responses to myopia-related queries in the Chinese language remain underexplored. Purpose: This study aimed to evaluate the ability of ChatGPT to address frequently asked questions (FAQs) about myopia by parents and caregivers. Method: Myopia-related FAQs were input three times into fresh ChatGPT sessions, and the responses were evaluated by 10 ophthalmologists using a Likert scale for appropriateness, usability, and clarity. The Chinese Readability Index Explorer (CRIE) was used to evaluate the readability of each response. Inter-rater reliability among the reviewers was examined using Cohen's kappa coefficient, and Spearman's rank correlation analysis and one-way analysis of variance were used to investigate the relationship between CRIE scores and each criterion. Results: Forty-five percent of the responses of ChatGPT in Chinese language were appropriate and usable and only 35% met all the set criteria. The CRIE scores for 20 ChatGPT responses ranged from 7.29 to 12.09, indicating that the readability level was equivalent to a middle-to-high school level. Responses about the treatment efficacy and side effects were deficient for all three criteria. Conclusions: The performance of ChatGPT in addressing pediatric myopia-related questions is currently suboptimal. As parents increasingly utilize digital resources to obtain health information, it has become crucial for eye care professionals to familiarize themselves with artificial intelligence-driven information on pediatric myopia.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125070, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39232313

ABSTRACT

Four rhodamine 6G-PAH probes with pyrene (R6G-Pyr), anthracene (R6G-Ant), acenaphthene (R6G-Acp) or phenanthrene (R6G-PA) as fluorophore were designed and synthesized for Hg(II) detection. Probe R6G-PA, which had the lowest detection limit of 0.84 nmol/L, displayed the best fluorescence performance as compared to the other three probes. This type of probe had good anti-interference properties against most common metal ions except Cu(II). Metal Cu(II) had a certain quenching effect on the fluorescence generated by Hg(II), with a minimum detection limit of 0.31 nmol/L (for R6G-Acp), indicating its potential practicability for Cu(II) detection. The structure-fluorescence relationship was discussed based on density functional theory (DFT) calculations, and R6G-PA + Hg(II), which had the minimum dihedral angle between polycyclic aromatic rings and rhodamine spiro ring, produced the strongest π-π accumulation and provided the brightest fluorescence. Probe R6G-PA was successfully employed for fluorescence detection of Hg(II) in biological samples. Its solid-phase sensor PS@R6G-PA was developed by immobilizing R6G-PA on PS microspheres for the determination of Hg(II) in water and food samples, with excellent reproducibility and fluorescence "on/off" response. The relative error of the spiked recovery rate was less than 10 %.

9.
Eur J Med Chem ; 278: 116821, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39232359

ABSTRACT

Currently, as the largest family of E3 ubiquitin ligases, Skp1-Cullin 1-F-box (SCF) E3 ligase complexes have attracted extensive attention. Among SCF complexes, Skp2, ß-TrCP, and FBXW7 have undergone extensive research on their structures and functions. Previous studies suggest Skp2, ß-TrCP, and FBXW7 are overexpressed in numerous cancers. Thus, the SCF E3 ligase complex has become a significant target for the development of anti-cancer drugs. Over the past few decades, a variety of anti-tumor inhibitors targeting the SCF E3 ligase complex have been attempted. However, since almost none of the SCF E3 ligase inhibitors passed clinical trials, the design and synthesis of the new inhibitors are needed. Here, we will introduce the structure and function of Skp2, ß-TrCP, and FBXW7, their connections with cancer development, the relevant in vitro and in vivo activities, selectivity, structure-activity relationships, and the therapeutic or preventive application of small molecule inhibitors targeting these three F-box proteins reported in the patent (2010-present). This information will help develop drugs targeting the SCF E3 ubiquitin ligase, providing new strategies for future cancer treatments.

10.
Nurs Open ; 11(9): e2223, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39219148

ABSTRACT

AIMS: To understand the perceptions and experiences of family caregivers of adult patients with dysphagia. BACKGROUND: Dysphagia is a common symptom and burdens caregivers greatly. There is a growing body of studies concentrating on caregivers and caregiving experiences. However, no qualitative meta-synthesis has been conducted to explore the perceptions and experiences of family caregivers. DESIGN: A qualitative meta-ethnography. METHODS: A search was conducted for relevant articles in six electronic databases (PubMed, Web of Science, CINAHL, Ovid, Cochrane Library, ProQuest) and two Chinese databases (CNKI, Wanfang Data) from inception to February 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to evaluate study quality. The meta-ethnographic method was used to synthesize data from qualitative studies. The study was reported according to EQUATOR guidelines. RESULTS: Eleven studies were included and three themes emerged: (1) emotion and perception, (2) change and challenge (3) adaption and coping. CONCLUSION: This review highlighted the challenges and positive coping experienced by caregivers. Findings directly inform the development and implementation of supportive interventions to reduce caregivers' stress and promote adaptive coping. RELEVANCE TO CLINICAL PRACTICE: Pay attention to the needs of family caregivers of dysphagia. Family caregivers' perceived severity of dysphagia requires assessment. Caregivers need knowledge, support, and guidance to reduce their burden and fulfill their role.


Subject(s)
Caregivers , Deglutition Disorders , Perception , Qualitative Research , Humans , Caregivers/psychology , Deglutition Disorders/psychology , Deglutition Disorders/nursing , Adaptation, Psychological
11.
J Am Chem Soc ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39226482

ABSTRACT

The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level of commonly used lysosome-targeting receptors (LTRs) varies in different cell lines, thus limiting the broad applications of LYTACs. To overcome this difficulty, we herein report the development of integrin α3ß1 (ITGA3B1)-facilitated bispecific aptamer chimeras (ITGBACs) as a platform for the degradation of membrane proteins. ITGBACs consist of two aptamers, one targeting ITGA3B1 and another binding to the membrane-associated protein of interest (POI), effectively transporting the POI into lysosomes for degradation. Our findings demonstrate that ITGBACs effectively eliminate pathological membrane proteins, such as CD71 and PTK7, inducing significant cell-cycle arrest and apoptosis and markedly inhibiting tumor growth in tumor-bearing mice models. Therefore, this work provides a novel and versatile membrane protein degradation platform, offering a promising targeted therapy based on tumor-specific LTRs.

12.
Front Immunol ; 15: 1429523, 2024.
Article in English | MEDLINE | ID: mdl-39100675

ABSTRACT

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.


Subject(s)
Macrophages , Monocytes , Venous Thrombosis , Humans , Monocytes/immunology , Monocytes/metabolism , Macrophages/immunology , Macrophages/metabolism , Animals , Venous Thrombosis/immunology , Venous Thrombosis/metabolism , Venous Thromboembolism/immunology , Venous Thromboembolism/pathology , Venous Thromboembolism/drug therapy
13.
Environ Sci Technol ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39115222

ABSTRACT

Ammonia-oxidizing archaea (AOA) are widely distributed in marine and terrestrial habitats, contributing significantly to global nitrogen and carbon cycles. However, their genomic diversity, ecological niches, and metabolic potentials in the anoxic intertidal aquifers remain poorly understood. Here, we discovered and named a novel AOA genus, Candidatus Nitrosomaritimum, from the intertidal aquifers of Yancheng Wetland, showing close metagenomic abundance to the previously acknowledged dominant Nitrosopumilus AOA. Further construction of ammonia monooxygenase-based phylogeny demonstrated the widespread distribution of Nitrosomaritimum AOA in global estuarine-coastal niches and marine sediment. Niche differentiation among sublineages of this new genus in anoxic intertidal aquifers is driven by salinity and dissolved oxygen gradients. Comparative genomics revealed that Candidatus Nitrosomaritimum has the genetic capacity to utilize urea and possesses high-affinity phosphate transporter systems (phnCDE) for surviving phosphorus-limited conditions. Additionally, it contains putative nosZ genes encoding nitrous-oxide (N2O) reductase for reducing N2O to nitrogen gas. Furthermore, we gained first genomic insights into the archaeal phylum Hydrothermarchaeota populations residing in intertidal aquifers and revealed their potential hydroxylamine-detoxification mutualism with AOA through utilizing the AOA-released extracellular hydroxylamine using hydroxylamine oxidoreductase. Together, this study unravels the overlooked role of priorly unknown but abundant AOA lineages of the newly discovered genus Candidatus Nitrosomaritimum in biological nitrogen transformation and their potential for nitrogen pollution mitigation in coastal environments.

14.
Cogn Neurodyn ; 18(4): 1671-1687, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39104678

ABSTRACT

Major depressive disorder (MDD) is a prevalent psychiatric disorder globally. There are many assays for MDD, but rapid and reliable detection remains a pressing challenge. In this study, we present a fusion feature called P-MSWC, as a novel marker to construct brain functional connectivity matrices and utilize the convolutional neural network (CNN) to identify MDD based on electroencephalogram (EEG) signal. Firstly, we combine synchrosqueezed wavelet transform and coherence theory to get synchrosqueezed wavelet coherence. Then, we obtain the fusion feature by incorporating synchrosqueezed wavelet coherence value and phase-locking value, which outperforms conventional functional connectivity markers by comprehensively capturing the original EEG signal's information and demonstrating notable noise-resistance capabilities. Finally, we propose a lightweight CNN model that effectively utilizes the high-dimensional connectivity matrix of the brain, constructed using our novel marker, to enable more accurate and efficient detection of MDD. The proposed method achieves 99.92% accuracy on a single dataset and 97.86% accuracy on a combined dataset. Moreover, comparison experiments have shown that the performance of the proposed method is superior to traditional machine learning methods. Furthermore, visualization experiments reveal differences in the distribution of brain connectivity between MDD patients and healthy subjects, including decreased connectivity in the T7, O1, F8, and C3 channels of the gamma band. The results of the experiments indicate that the fusion feature can be utilized as a new marker for constructing functional brain connectivity, and the combination of deep learning and functional connectivity matrices can provide more help for the detection of MDD.

15.
BMC Infect Dis ; 24(1): 806, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123120

ABSTRACT

BACKGROUND: Mean perfusion pressure (MPP) has recently emerged as a potential biomarker for personalized management of tissue perfusion in critically ill patients. However, its association with the occurrence of acute kidney injury (AKI) in septic patients and the optimal MPP range remain uncertain. Therefore, this study aims to investigate the relationship between MPP and AKI in critically ill patients with sepsis. METHODS: We identified 5867 patients with sepsis from the MIMIC-IV database who met the inclusion and exclusion criteria. The exposure variable was the first set of MPP measured within 24 h after ICU admission with invasive hemodynamic monitoring. The primary outcome was the incidence of AKI at 7 days following ICU admission according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes included in-hospital mortality, lengths of ICU, and hospital stay. Optimal cut-off point for MPP were determined using the Youden index, and multivariable logistic regression was employed to examine the association between MPP and AKI. Subgroup analyses were conducted to enhance result robustness. Kaplan-Meier survival analysis was utilized to evaluate in-hospital mortality rates categorized by MPP. RESULTS: A total of 5,867 patients with sepsis were included in this study, and the overall incidence of AKI was 82.3%(4828/5867). Patients were categorized into low MPP (< 63 mmHg) and high MPP (≥ 63 mmHg) groups using the optimal ROC curve-derived cut-off point. The incidence of AKI in the low MPP group was higher than that in the high MPP group (87.6% vs. 78.3%, P < 0.001). Multivariable logistic regression analysis adjusted for confounding factors revealed that each 1 mmHg increase in MPP as a continuous variable was associated with a 2% decrease in AKI incidence within 7 days of ICU admission (OR:0.98, 95%CI:0.97-0.99, P < 0.001). When MPP was used as a categorical variable, patients in the high MPP group had a lower risk of AKI than those in the low MPP group (OR:0.71, 95%CI:0.61-0.83, P = 0.001). Subgroup analyses demonstrated a consistent association between MPP and AKI risk across all variables assessed (P for interaction all > 0.05). Kaplan-Meier curve analysis demonstrated a higher survival rate during hospitalization in the high MPP group compared to the low MPP group (Log-rank test, P < 0.0001). CONCLUSIONS: Lower levels of MPP are associated with an increased incidence of AKI at 7 days in critically ill patients with sepsis.


Subject(s)
Acute Kidney Injury , Critical Illness , Hospital Mortality , Intensive Care Units , Sepsis , Humans , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Male , Female , Middle Aged , Sepsis/complications , Retrospective Studies , Aged , Incidence , Risk Factors , Length of Stay/statistics & numerical data
16.
Article in English | MEDLINE | ID: mdl-39127084

ABSTRACT

PURPOSE: radiotherapy stands as an important complementary treatment for head and neck squamous cell carcinoma (HNSCC), yet it does not invariably result in complete tumor regression. The infiltration of immunosuppressive macrophages is believed to mediate the radiotherapy resistance, which mechanism remains largely unexplored. This study aimed to elucidate the role of immunosuppressive macrophages during radiotherapy and the associated underlying mechanisms. MATERIALS AND METHODS: Male C3H mice bearing syngeneic SCC-VII tumor were received irradiation (2 × 8Gy). The impact of irradiation on tumor-infiltrating macrophages were assessed. Bone marrow derived macrophages were evaluated in differentiation, proliferation, migration, and inflammatory cytokines after treatment of irradiated tumor culture medium (irCM) and irradiated tumor derived extracellular vesicles (irTEVs). A comprehensive metabolomics profiling of the irTEVs was conducted using liquid chromatography-mass spectrometry, while key metabolites were investigated the mechanism in macrophage in vitro and in vivo. RESULTS: Radiotherapy on SCC-VII syngeneic graft tumors increased polarization of both M1 and M2 macrophages in tumor microenvironment and drove infiltrated macrophages towards an immunosuppressive phenotype. Irradiation-induced polarization and immunosuppression of macrophages were dependent on irTEVs which delivered an increased amount of nicotinamide (NAM) to macrophages. NAM directly bound to the NF-κB transcriptional activity regulator USP7, through which NAM reduced translocation of NF-κB into the nucleus, thereby decreasing the release of cytokines IL6 and IL8. Increased enzyme activity of nicotinamide phosphoribosyl transferase (NAMPT) which is the rate-limiting enzyme of NAD+ metabolism, contributed to the irradiation-induced accumulation levels of NAM in irradiated HNSCC and irTEVs. Inhibition of NAMPT decreased NAM levels in irTEVs and increased radiotherapy sensitivity through alleviating immunosuppressive function of macrophages. CONCLUSIONS: Radiotherapy could induce NAD+ metabolic reprogramming of HNSCC cells, which regulate macrophage towards an immunosuppressive phenotype. Pharmacological targeting NAD+ metabolism might be a promising strategy for radiotherapy sensitization of HNSCC.

17.
Cells ; 13(15)2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39120321

ABSTRACT

BACKGROUND: Obesity, a major component of cardiometabolic syndrome, contributes to the imbalance between pro- and anti-atherosclerotic factors via dysregulation of adipocytokine secretion. Among these adipocytokines, the C1q/TNF-related proteins (CTRPs) play a role in the modulation of atherosclerosis development and progression. Here, we investigated the vascular effects of CTRP13. RESULTS: CTRP13 is not only expressed in adipose tissue but also in vessels/endothelial cells (ECs) of mice, rats, and humans. Obese individuals (mice, rats, and humans) showed higher vascular CTRP13 expression. Human Umbilical Vein Endothelial Cells (HUVECs), cultured in the presence of serum from obese mice, mimicked this obesity-associated effect on CTRP13 protein expression. Similarly, high glucose conditions and TNF-alpha, but not insulin, resulted in a strong increase in CTRP13 in these cells. Recombinant CTRP13 induced a reduction in EC proliferation via AMPK. In addition, CTRP13 reduced cell cycle progression and increased p53 phosphorylation and p21 protein expression, but reduced Rb phosphorylation, with the effects largely depending on alpha-2 AMPK as suggested by adenoviral overexpression of dominant-negative (DN) or wild-type (WT) alpha 1/alpha 2 AMPK. CONCLUSION: The present study demonstrates that CTRP13 expression is induced in ECs under diabetic conditions and that CTRP13 possesses significant vaso-modulatory properties which may have an impact on vascular disease progression in patients.


Subject(s)
Cell Proliferation , Human Umbilical Vein Endothelial Cells , Obesity , Humans , Animals , Obesity/metabolism , Obesity/pathology , Human Umbilical Vein Endothelial Cells/metabolism , Mice , Male , Rats , Adipokines/metabolism , Mice, Inbred C57BL , Endothelial Cells/metabolism , AMP-Activated Protein Kinases/metabolism , Cell Cycle , Phosphorylation
18.
J Clin Anesth ; 98: 111564, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39089119

ABSTRACT

STUDY OBJECTIVE: This study aims to evaluate the impact of Supreme™ laryngeal masks versus endotracheal tubes on atelectasis during general anesthesia using lung ultrasound (LUS), and provide evidence for respiratory management. DESIGN: A single-center, double-blind, randomized controlled trial was conducted. SETTING: The study was conducted in both the operating room and the post-anesthesia care unit, with follow-up assessments performed in the ward. PATIENTS: Enrollment included 180 cases undergoing non-laparoscopic surgeries in gynecology, urology, and orthopedic limb surgeries. INTERVENTIONS: Patients were randomly assigned 1:1 to the endotracheal intubation or laryngeal mask group. MEASUREMENTS: LUS scores were recorded across 12 lung regions at baseline, 15 min after airway establishment, at the end of surgery, and 30 min following airway removal. Outcome measures encompassed the oxygenation index, dynamic lung compliance, incidence of postoperative pulmonary complications, throat pain, and other postoperative complications assessed at 24 and 48 h postoperatively. The primary outcome focused on the LUS score in all 12 lung regions at 15 min after airway establishment. MAIN RESULTS: Intention-to-treat analysis of 177 subjects revealed endotracheal intubation led to significantly higher LUS scores at 15 min {P < 0.001, mean difference 4.15 ± 0.60, 95% CI [2.97, 5.33]}, end of surgery (P < 0.001, mean difference 3.37 ± 0.68, 95% CI [2.02, 4.72]), and 30 min post-removal (P < 0.001, mean difference 2.63 ± 0.48, 95% CI [1.68, 3.58]). No major complications occurred in the two groups. CONCLUSIONS: Compared to endotracheal intubation, laryngeal masks effectively reduce atelectasis formation and progression in gynecological, urological non-laparoscopic, and orthopedic limb surgeries. However, caution is warranted when generalizing these findings to surgeries with a higher risk of laryngeal mask leakage or obese patients. Additionally, the efficacy of laryngeal masks in reducing postoperative atelectasis remains uncertain when comprehensive monitoring of muscle relaxation and reversal therapy is employed.

19.
Arthritis Rheumatol ; 2024 08 20.
Article in English | MEDLINE | ID: mdl-39165013

ABSTRACT

OBJECTIVES: i) To explore the agreement between the OMERACT ultrasound lesions of enthesitis and physical examination in assessing enthesitis in spondyloarthritis (SpA) patients; ii) To investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centres participated in this cross-sectional study. SpA patients, including axial SpA (axSpA) and psoriatic arthritis (PsA) patients, underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for 'active enthesitis' by our group. Subclinical enthesitis was defined as the presence of 'active enthesitis' in ≥1 enthesis in SpA patients without clinical enthesitis (i.e., number of positive entheses on physical examination and Leeds Enthesitis Index score =0). RESULTS: 4130 entheses in 413 SpA patients (224 axSpA/189 PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (i.e., enthesophytes) to almost perfect (i.e., power Doppler and 'active enthesitis'). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158/413 (38.3%) SpA patients with clinical enthesitis, 108 (68.4%) exhibited no 'active enthesitis' on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of SpA patients with and without subclinical enthesitis. CONCLUSIONS: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in SpA patients.

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