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1.
Cancer Med ; 13(9): e7235, 2024 May.
Article in English | MEDLINE | ID: mdl-38716626

ABSTRACT

BACKGROUND: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS: A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Ipilimumab , Nivolumab , Humans , Ipilimumab/administration & dosage , Ipilimumab/therapeutic use , Ipilimumab/adverse effects , Nivolumab/administration & dosage , Nivolumab/therapeutic use , Male , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Middle Aged , Aged , Follow-Up Studies , Adult , Progression-Free Survival , B7-H1 Antigen/metabolism , Aged, 80 and over
2.
Front Nutr ; 11: 1351797, 2024.
Article in English | MEDLINE | ID: mdl-38751736

ABSTRACT

Background: AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR. Methods: This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively. Results: Compared with group A, patients in group B had higher midterm mortality (p < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029-1.584; p = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426-8.553; p = 0.006) was an independent risk factor. Kaplan-Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p < 0.001). Conclusion: Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR.

3.
Brain ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739753

ABSTRACT

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

4.
Gene ; 921: 148499, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38718970

ABSTRACT

Cell wall invertase (CIN) is a vital member of plant invertase (INV) and plays a key role in the breakdown of sucrose. This enzyme facilitates the hydrolysis of sucrose into glucose and fructose, which is crucial for various aspects of plant growth and development. However, the function of CIN genes in foxtail millet (Setaria italica) is less studied. In this research, we used the blast-p of NCBI and TBtools for bidirectional comparison, and a total of 13 CIN genes (named SiCINs) were identified from foxtail millet by using Arabidopsis and rice CIN sequences as reference sequences. The phylogenetic tree analysis revealed that the CIN genes can be categorized into three subfamilies: group 1, group 2, and group 3. Furthermore, upon conducting chromosomal localization analysis, it was observed that the 13 SiCINs were distributed unevenly across five chromosomes. Cis-acting elements of SiCIN genes can be classified into three categories: plant growth and development, stress response, and hormone response. The largest number of cis-acting elements were those related to light response (G-box) and the cis-acting elements related to seed-specific regulation (RY-element). qRT-PCR analysis further confirmed that the expression of SiCIN7 and SiCIN8 in the grain was higher than that in any other tissues. The overexpression of SiCIN7 in Arabidopsis improved the grain size and thousand-grain weight, suggesting that SiCIN7 could positively regulate grain development. Our findings will help to further understand the grain-filling mechanism of SiCIN and elucidate the biological mechanism underlying the grain development of SiCIN.

5.
J Med Chem ; 67(10): 7836-7858, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38695063

ABSTRACT

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment.


Subject(s)
Antineoplastic Agents , Mutation , Proto-Oncogene Proteins c-bcl-2 , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Humans , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Mice , Cell Line, Tumor , Sulfonamides/pharmacology , Sulfonamides/chemistry , Rats , Drug Discovery
6.
Mol Biol Rep ; 51(1): 607, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704801

ABSTRACT

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.


Subject(s)
Endoplasmic Reticulum Stress , Neurons , Neuroprotective Agents , Oxidative Stress , Peroxiredoxins , Pyroptosis , Reactive Oxygen Species , Pyroptosis/drug effects , Endoplasmic Reticulum Stress/drug effects , Animals , Oxidative Stress/drug effects , Neurons/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Mice , Reactive Oxygen Species/metabolism , Peroxiredoxins/metabolism , Signal Transduction/drug effects , Cell Line , Mitochondria/metabolism , Mitochondria/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Cerebral Hemorrhage/metabolism , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/complications
7.
BMJ Neurol Open ; 6(1): e000651, 2024.
Article in English | MEDLINE | ID: mdl-38770161

ABSTRACT

Objective: We aim to describe the long-term outcome of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) after immune treatment in a Chinese cohort. Methods: Between March 2015 and March 2023, 89 patients fulfilling the criteria for CIDP were followed up for a median of 22 months after treatment. Nine had positive antibodies against nodal-paranodal cell-adhesion molecules. Patients were treated according to clinical requirements with prednisone, intravenous immunoglobulin (IVIg) and/or immunosuppressant. Results: A total of 78/89 patients had decreased inflammatory neuropathy cause and treatment (INCAT) scores at the last follow-up. For CIDP patients treated with steroids, 35 were stable without relapse after cessation or with a small maintenance dose; 2 relapsed at a high dose (20 mg/day); 15 relapsed at a low dosage (<20 mg/day) and 11 did not respond. The INCAT before treatment was significantly lower in those without relapse (median INCAT 2 vs 3, p=0.030). IVIg was effective in 37/52 CIDP patients. 28 CIDP patients and 4 autoimmune nodopathy patients were treated with immunosuppressants. The average INCAT was 3.3±1.9 before and 1.9±1.3 after immunosuppressant treatment (p=0.001) in CIDP. Conclusion: The long-term prognosis of CIDP patients was generally favourable. Nearly half of our patients treated with steroid were stable without relapse after cessation or with a small maintenance dose. The risk of relapse was higher in those with high INCAT. We recommend slowly tapering prednisone based on clinical judgement.

8.
Clin Transl Oncol ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38769216

ABSTRACT

PURPOSE: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. METHODS: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), ß-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. RESULTS: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing. CONCLUSION: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

9.
Risk Manag Healthc Policy ; 17: 1015-1025, 2024.
Article in English | MEDLINE | ID: mdl-38680475

ABSTRACT

Objective: To explore the prognostic outcomes associated with different types of septic cardiomyopathy and analyze the factors that exert an influence on these outcomes. Methods: The data collected within 24 hours of ICU admission included cardiac troponin I (cTnI), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP); SOFA (sequential organ failure assessment) scores, and the proportion of vasopressor use. Based on echocardiographic outcomes, septic cardiomyopathy was categorized into left ventricular (LV) systolic dysfunction, LV diastolic dysfunction, and right ventricular (RV) systolic dysfunction. Differences between the mortality and survival groups, as well as between each cardiomyopathy subgroup and the non-cardiomyopathy group were compared, to explore the influencing factors of cardiomyopathy. Results: A cohort of 184 patients were included in this study, with LV diastolic dysfunction having the highest incidence rate (43.5%). The mortality group had significantly higher SOFA scores, vasopressor use, and cTnI levels compared to the survival group; the survival group had better LV diastolic function than the mortality group (p < 0.05 for all). In contrast to the non-cardiomyopathy group, each subgroup within the cardiomyopathy category exhibited elevated levels of cTnI. The subgroup with left ventricular diastolic dysfunction demonstrated a higher prevalence of advanced age, hypertension, diabetes mellitus, coronary artery disease, and an increased mortality rate; the RV systolic dysfunction subgroup had higher SOFA scores and NT-proBNP levels, and a higher mortality rate (P < 0.05 for all); the LV systolic dysfunction subgroup had a similar mortality rate (P > 0.05). Conclusion: Patients with advanced age, hypertension, diabetes mellitus, or coronary artery disease are more prone to develop LV diastolic dysfunction type of cardiomyopathy; cardiomyopathy subgroups had higher levels of cTnI. The RV systolic dysfunction cardiomyopathy subgroup had higher SOFA scores and NT-proBNP levels. The occurrence of RV systolic dysfunction in patients with sepsis significantly increased the mortality rate.

10.
Nat Commun ; 15(1): 3400, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649374

ABSTRACT

Marine organisms are simultaneously exposed to anthropogenic stressors associated with ocean acidification and ocean warming, with expected interactive effects. Species from different trophic levels with dissimilar characteristics and evolutionary histories are likely to respond differently. Here, we perform a meta-analysis of controlled experiments including both ocean acidification and ocean warming factors to investigate single and interactive effects of these stressors on marine species. Contrary to expectations, we find that synergistic interactions are less common (16%) than additive (40%) and antagonistic (44%) interactions overall and their proportion decreases with increasing trophic level. Predators are the most tolerant trophic level to both individual and combined effects. For interactive effects, calcifying and non-calcifying species show similar patterns. We also identify climate region-specific patterns, with interactive effects ranging from synergistic in temperate regions to compensatory in subtropical regions, to positive in tropical regions. Our findings improve understanding of how ocean warming, and acidification affect marine trophic levels and highlight the need for deeper consideration of multiple stressors in conservation efforts.


Subject(s)
Aquatic Organisms , Global Warming , Oceans and Seas , Seawater , Seawater/chemistry , Animals , Hydrogen-Ion Concentration , Food Chain , Climate Change , Carbon Dioxide , Ocean Acidification
11.
Anal Methods ; 16(19): 3067-3073, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38683672

ABSTRACT

Cortisol is a vital glucocorticoid hormone reflecting stress levels and related disease processes. In this study, we report an aptamer-functionalized plasmonic nano-urchin (α-FeOOH@Au-aptamer)-aided cortisol-capturing and surface-enhanced Raman spectroscopy (SERS) analysis approach. The designed α-FeOOH@Au-aptamer exhibits a well-patterned plasma structure, which combines the good SERS enhancement ability of reduced nanogaps between the Au plasma and the hot spot-favored structure of anisotropic tips from α-FeOOH urchins, with the high affinity of the aptamer towards cortisol molecules. The α-FeOOH@Au-aptamer achieved reporter-free SERS quantification for cortisol with good sensitivity (limit of detection <0.28 µmol L-1), robust salt (1.0 mol per L NaCl) and protein (5.0 mg per mL bovine serum protein) tolerance, favorable reproducibility, as well as good reusability. We further demonstrated the good cortisol-capturing ability and SERS efficacy of the α-FeOOH@Au-aptamer profiling in the serum and urine samples. Our approach provides an alternative tool for cortisol analysis and a reference strategy for report-free SERS detection of small molecules.


Subject(s)
Aptamers, Nucleotide , Gold , Hydrocortisone , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Hydrocortisone/blood , Hydrocortisone/analysis , Hydrocortisone/urine , Hydrocortisone/chemistry , Aptamers, Nucleotide/chemistry , Gold/chemistry , Humans , Metal Nanoparticles/chemistry , Limit of Detection , Animals , Reproducibility of Results , Biosensing Techniques/methods
12.
Nat Med ; 30(4): 990-1000, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38605166

ABSTRACT

Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsed or refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in real time to the FPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsed or refractory solid and hematological cancers were enrolled; 21 patients underwent DST and 20 also completed genomic profiling. Median turnaround times for DST and genomics were within 10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienced a greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPM to positively impact clinical care for pediatric and adolescent patients with relapsed or refractory cancers and warrant further validation in large prospective studies. ClinicalTrials.gov registration: NCT03860376 .


Subject(s)
Hematologic Neoplasms , Neoplasms , Adolescent , Child , Humans , Precision Medicine , Prospective Studies , Feasibility Studies , Neoplasms/genetics , Neoplasms/therapy
13.
Ann Transplant ; 29: e943282, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38685698

ABSTRACT

BACKGROUND This study aimed to investigate the incidence of post-transplant diabetes mellitus (PTDM) in renal transplant (RT) patients at our center and to explore new risk factors for PTDM. MATERIAL AND METHODS This retrospective study included RT patients from 2010 to 2022. Clinic data on RT patients were obtained from hospital electronic medical records. CYP3A5*3, POR*28, ABCB1 (3435 C>T), and ABCB1 (1236 C>T) were genotyped in RT patients. The associations between age, BMI, concentration of tacrolimus (TAC), polymorphism of genes, antibiotics (eg, penicillins, cephalosporins, oxazolidinones, quinolones), numbers and days of antibiotic use, and PTDM were analyzed. RESULTS In this study, 409 patients with RT were included. The cumulative incidence of PTDM in the first year after RT was 9.05%. The numbers and days of antibiotic use in PTDM patients were significantly higher than those in non-PTDM patients. Multivariate logistic regression analysis identified age (OR=1.047, P=0.014), body mass index (BMI) (OR=1.178, P=0.007), dose-adjusted trough concentration of TAC (TAC C0/D) at 7 days after RT (OR=1.159, P=0.042), trough concentration of TAC (TAC C0) at 28 days after RT (OR=1.094, P=0.042), and levofloxacin (OR=5.975, P=0.003) as independent risk factors for PTDM. CONCLUSIONS In addition to age, BMI, and TAC concentration after RT, antibiotic use may be a novel factor affecting PTDM. The use of antibiotics may influence the development of PTDM.


Subject(s)
Anti-Bacterial Agents , Diabetes Mellitus , Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Male , Female , Middle Aged , Diabetes Mellitus/epidemiology , Diabetes Mellitus/etiology , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Adult , Risk Factors , Incidence , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Tacrolimus/adverse effects , Tacrolimus/therapeutic use
14.
Cell Commun Signal ; 22(1): 231, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637880

ABSTRACT

BACKGROUND: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. METHODS: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs. RESULTS: Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca2+ homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases. CONCLUSIONS: This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions.


Subject(s)
MicroRNAs , Mitochondrial Diseases , Neurodegenerative Diseases , Humans , Peroxiredoxins/genetics , Reactive Oxygen Species/metabolism , Oxidative Stress , Apoptosis , Endoplasmic Reticulum Stress , MicroRNAs/metabolism
15.
Article in English | MEDLINE | ID: mdl-38648145

ABSTRACT

Soft robotic glove controlled by a brain-computer interface (BCI) have demonstrated effectiveness in hand rehabilitation for stroke patients. Current systems mostly rely on static visual representations for patients to perform motor imagination (MI) tasks, resulting in lower BCI performance. Therefore, this study innovatively used MI and high-frequency steady-state visual evoked potential (SSVEP) to construct a friendly and natural hybrid BCI paradigm. Specifically, the stimulation interface sequentially presented decomposed action pictures of the left and right hands gripping a ball, with the pictures flashing at specific stimulation frequencies (left: 34 Hz, right: 35 Hz). Integrating soft robotic glove as feedback, we established a comprehensive "peripheral - central - peripheral" hand rehabilitation system to facilitate the hand rehabilitation of patients. Filter bank common spatial pattern (FBCSP) and filter bank canonical correlation analysis (FBCCA) algorithms were used to identify MI and SSVEP signals, respectively. Additionally, to fuse the features of these two signals, we proposed a novel fusion algorithm for improving the recognition accuracy of the system. The feasibility of the proposed system was validated through online experiments involving 12 healthy subjects and 9 stroke patients, achieving accuracy rates of 95.83 ± 6.83% and 63.33 ± 10.38%, respectively. The accuracy of MI and SSVEP in 12 healthy subjects reached 81.67 ± 15.63% and 95.14 ± 7.47%, both lower than the accuracy after fusion, these results confirmed the effectiveness of the proposed algorithm. The accuracy rate was more than 50% in both healthy subjects and patients, confirming the effectiveness of the proposed system.

16.
Mater Horiz ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629134

ABSTRACT

High-performance elastomers are essential in daily life and various industrial sectors such as personal protection, soft electronics, and vibration control. Nevertheless, despite massive efforts, concurrently achieving ultrahigh flexibility and remarkable impact resistance continues to be elusive. Herein, we report an innovative modular construction strategy that employs a topology-tailoring polymer network consisting of stereoscopic (epoxy-oligosiloxane nanoclusters) and linear (amino-terminated polyurea) building blocks as independent modules to develop intelligent anti-impact elastomers via an epoxy-amine mechanism. By precisely tailoring the topology of building blocks, the elastomers demonstrate high flexibility and toughness, remarkable impact responsiveness and ultrahigh energy dissipation. Their anti-impact ability surpasses those of most common soft and rigid materials such as steel, plastic, rubber, foam, or even polyborosiloxane. Moreover, the elastomers are well-qualified for use in flexible display technologies, owing to their high transparency (>92% transmittance), exceptional fold-resistance (no creasing after 10 000 bends), and good thermal stability (no discoloration at 100 °C). Furthermore, the elastomers exhibit excellent versatility, enabling them to be combined with either soft or rigid materials to generate composites with ultrahigh puncture and ballistic resistance. This study offers a promising framework for the design and fabrication of intelligent anti-impact elastomers and provides valuable insights into the development of next-generation protective materials.

17.
Foods ; 13(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38611335

ABSTRACT

The glutinous rice starch (GRS) regeneration process could lead to decreased product quality and shorter shelf life. The purpose of this study was to analyze the effect of an ethanol extract of tea (EET) on the regeneration properties of GRS. The microstructure of starch was determined via scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy was used to determine the microstructure of starch-polyphenol molecular groups, an X-ray diffraction (XRD) instrument was used to determine the starch crystal structure, a differential scanning calorimeter (DSC) was used to determine the thermodynamic properties of starch, and the inhibitory effect of EET on GRS regeneration was comprehensively evaluated. The effect of EET on the in vitro digestion properties of GRS was also determined. The results showed that the addition of EET in GRS resulted in an increase in solubility and swelling power and a decrease in crystallinity and ΔHr. Compared to the control group, when retrograded for 10 days, the ΔHr of GRS with 1%, 2.5%, 5%, and 10% addition of EET decreased by 34.61%, 44.53%, 52.93%, and 66.79%, respectively. Furthermore, the addition of EET resulted in a decrease in the content of RDS and an increase in the content of SDS and RS in GRS. It was shown that the addition of EET could significantly inhibit the retrogradation of GRS, improve the processability, and prolong the shelf life of GRS products.

18.
Sci Rep ; 14(1): 8506, 2024 04 12.
Article in English | MEDLINE | ID: mdl-38605164

ABSTRACT

Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value < 0.05) in subgroup analysis. The calculation of E-value revealed robustness of unmeasured confounding. The combination of liver surgical resection with RT is safe and effective towards patients with centrally located HCC, which would notably enhance the prognosis and decrease the early relapse of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/radiotherapy , Liver Neoplasms/surgery , Radiotherapy, Adjuvant , Retrospective Studies , Prognosis , Hepatectomy , Propensity Score , Recurrence , Treatment Outcome
19.
J Health Care Poor Underserved ; 35(1): 186-208, 2024.
Article in English | MEDLINE | ID: mdl-38661866

ABSTRACT

OBJECTIVES: This study evaluated how high versus low-intensity community wellness coaching and health behaviors were associated with changes in depression screen results over one year. METHODS: This was an analysis of secondary data collected in a 12-month obesity-related community health worker (CHW) program for 485 Utah women of color. Depression screen (Patient Health Questionnaire-2 score ³3) and self-reported fruit/vegetable consumption and physical activity (FV/PA) were recorded quarterly. Associations between FV/PA and changes in depression screen over time were evaluated in multivariable models. RESULTS: Positive depression screen prevalence declined over 12 months (21.7% to 9.5%) with no difference between study arms. Overall, FV ³5 times/day (AOR=1.5; 95% CI 1.0-2.2), any PA (AOR=3.1; 95% CI 1.5-6.4), and muscle strengthening activities (AOR=1.13; 95% CI 1.01-1.26) were associated with improved depression screen results over time. CONCLUSION: These results indicate value in addressing and evaluating depression in obesity-related interventions in underserved communities.


Subject(s)
Community Health Workers , Depression , Exercise , Health Behavior , Obesity , Humans , Female , Utah/epidemiology , Obesity/prevention & control , Obesity/epidemiology , Adult , Depression/epidemiology , Depression/prevention & control , Middle Aged , Mentoring , Young Adult , Health Promotion/methods , Health Promotion/organization & administration
20.
Article in English | MEDLINE | ID: mdl-38561514

ABSTRACT

AIM/INTRODUCTION: The National Nuclear Medicine Quality Control Center of China conducted the first official survey to investigate the nationwide situation of nuclear medicine in 2020. The survey aimed to unveil the current nuclear medicine situation and its quality control in China. MATERIALS AND METHODS: The web-based survey was conducted and the data was collected via the National Clinical Improvement System (NCIS) of China from 1st April to 31st May 2021. RESULTS: A total of 808 institutes across 30 provinces responded to the national survey. For human resources, there are 4460 physicians, 3077 technologists, 339 physicists, and 309 radiochemists. There are 887 single-photon imaging instruments, including 823 SPECT or SPECT/CT, and 365 PET instruments including 314 PET/CT. Six hundred twenty-four institutes perform SPECT examinations and 319 institutes perform PET examinations. 60% of SPECT scans are bone scintigraphy. A total of 97% of PET scans use an [18F]F-FDG tracer. Furthermore, 587 institutes provide radionuclide therapy services but only 280 institutes have admission rooms. The top three radionuclide therapies are [131I] therapy of hyperthyroidism with 546 institutes, [89Sr] therapy of bone metastasis with 400 institutes, and [131I] therapy of differentiated thyroid cancer with 286 institutes. Finally, for the frequency of equipment quality control per year, there are about 67 times self-test within the department for SPECT instruments and 111 times for PET instruments on average in each province. There are about three failures of SPECT and five failures of PET on average per year in each province. There are 408 institutes (of 624 SPECT institutes) performing quality control of SPECT radiopharmaceuticals, 216 (of 319) for PET radiopharmaceuticals, and 373 (of 587) for radionuclide therapy. CONCLUSION: These results of the first official survey towards current status of nuclear medicine in China are the foundation for the establishment of the quality control management system.

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