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1.
World J Gastrointest Surg ; 16(6): 1749-1755, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983316

ABSTRACT

BACKGROUND: Intestinal colic is a common complication in patients who have undergone radical surgery for colorectal cancer. Traditional Chinese medicine has advantages, including safety and stability, for the treatment of intestinal colic. Lamp irradiation for abdominal ironing has been applied in the treatment of many gastrointestinal diseases. Purple gromwell oil has the effects of clearing heat, cooling blood, reducing swelling, and relieving pain. AIM: To investigate the impact of lamp irradiation combined with purple gromwell oil gauze on ameliorating intestinal colic in patients after radical surgery for colorectal cancer. METHODS: A total of 120 patients who experienced postoperative intestinal colic complications after radical surgery for colorectal cancer and who were admitted to Foshan Traditional Chinese Medicine Hospital between June 2019 and March 2023 were enrolled as study subjects. The patients were divided into a control group (60 patients) and an observation group (60 patients) based on treatment method. The control group was treated with lamp irradiation, while the observation group was treated with lamp irradiation and external application of purple gromwell oil gauze. The clinical efficacy, Numeric Rating Scale (NRS) score, duration of symptoms, and rate of adverse reaction occurrence were further compared between the two groups. RESULTS: The general effective rate in the observation group was 95.00%, which was significantly higher than that in the control group (86.67%, P < 0.05). Before treatment, there was no significant difference in the duration of symptoms between the groups (P > 0.05). After 1, 2, 3, and 4 d of treatment, the duration of symptoms in both groups were decreased, and the duration in the observation group was significantly lower than that in the control group (96.54 ± 9.57 vs 110.45 ± 11.23, 87.26 ± 12.07 vs 104.44 ± 11.68, 80.45 ± 16.21 vs 99.44 ± 14.95, 73.18 ± 15.58 vs 92.17 ± 14.20; P < 0.05). After 1, 3, 5, and 7 d of treatment, the NRS scores in both groups were decreased, and the NRS scores in the observation group were significantly lower than those in the control group (3.56 ± 0.41 vs 4.04 ± 0.58, 3.07 ± 0.67 vs 3.74 ± 1.02, 2.52 ± 0.76 vs 3.43 ± 0.85, 2.03 ± 0.58 vs 3.03 ± 0.82; P < 0.05). There was no significant difference in the rate of adverse reaction occurrence between the groups (P > 0.05). CONCLUSION: The use of lamp irradiation combined with purple gromwell oil gauze in patients with intestinal colic after radical surgery for colorectal cancer can reduce symptom duration, alleviate intestinal colic, and improve treatment efficacy, and this approach is safe. It is worth promoting the use of this treatment in clinical practice.

2.
BMC Public Health ; 24(1): 1616, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886693

ABSTRACT

BACKGROUND: This study aimed to explore the association of female reproductive factors (age at first birth (AFB), age at last birth (ALB), number of pregnancies, and live births) with history of cardiovascular disease (CVD). METHODS: A total of 15,715 women aged 20 years or over from the National Health and Nutrition Examination Surveys from 1999 to 2018 were included in our analysis. Weighted multivariable logistic regression analysis and restricted cubic spline (RCS) model were used to evaluate the association of AFB and ALB with history of CVD in women. Additionally, the relationship between the number of pregnancies, and live births and history of CVD was also explored. RESULTS: After adjusting for potential confounding factors, the RCS plot showed a U-curve relationship between AFB, ALB and history of CVD. Among them, AFB was associated with congestive heart failure (CHF), heart attack, and stroke in a U-shaped curve. Additionally, this U-shaped correlation also exists between ALB and CHF and stroke. However, the number of pregnancies and live births was liner positive associated with history of CVD, including coronary heart disease, CHF, angina pectoris, heart attack, and stroke. CONCLUSIONS: Women with younger or later AFB and ALB have higher odds of CVD in later life. Further study is warranted to verify the underlying mechanisms of this association.


Subject(s)
Cardiovascular Diseases , Nutrition Surveys , Humans , Female , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Adult , Middle Aged , Pregnancy , Reproductive History , Young Adult , Risk Factors , Maternal Age , Aged , United States/epidemiology
3.
New Phytol ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853449

ABSTRACT

Modern cultivated rice (Oryza sativa) typically experiences limited growth benefits from arbuscular mycorrhizal (AM) symbiosis. This could be due to the long-term domestication of rice under favorable phosphorus conditions. However, there is limited understanding of whether and how the rice domestication has modified AM properties. This study compared AM properties between a collection of wild (Oryza rufipogon) and domesticated rice genotypes and investigated the mechanisms underlying their differences by analyzing physiological, genomic, transcriptomic, and metabolomic traits critical for AM symbiosis. The results revealed significantly lower mycorrhizal growth responses and colonization intensity in domesticated rice compared to wild rice, and this change of AM properties may be associated with the domestication modifications of plant phosphorus utilization efficiency at physiological and genomic levels. Domestication also resulted in a decrease in the activity of the mycorrhizal phosphorus acquisition pathway, which may be attributed to reduced mycorrhizal compatibility of rice roots by enhancing defense responses like root lignification and reducing carbon supply to AM fungi. In conclusion, rice domestication may have changed its AM properties by modifying P nutrition-related traits and reducing symbiotic compatibility. This study offers new insights for improving AM properties in future rice breeding programs to enhance sustainable agricultural production.

4.
ACS Appl Bio Mater ; 7(6): 3556-3567, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38777621

ABSTRACT

Skin tissue engineering (STE) is widely regarded as an effective approach for skin regeneration. Several synthetic biomaterials utilized for STE have demonstrated favorable fibrillar characteristics, facilitating the regeneration of skin tissue at the site of injury, yet they have exhibited a lack of in situ degradation. Various types of skin regenerative materials, such as hydrogels, nanofiber scaffolds, and 3D-printing composite scaffolds, have recently emerged for use in STE. Electrospun nanofiber scaffolds possess distinct advantages, such as their wide availability, similarity to natural structures, and notable tissue regenerative capabilities, which have garnered the attention of researchers. Hence, electrospun nanofiber scaffolds may serve as innovative biological materials possessing the necessary characteristics and potential for use in tissue engineering. Recent research has demonstrated the potential of electrospun nanofiber scaffolds to facilitate regeneration of skin tissues. Nevertheless, there is a need to enhance the rapid degradation and limited mechanical properties of electrospun nanofiber scaffolds in order to strengthen their effectiveness in soft tissue engineering applications in clinical settings. This Review centers on advanced research into electrospun nanofiber scaffolds, encompassing preparation methods, materials, fundamental research, and preclinical applications in the field of science, technology, and engineering. The existing challenges and prospects of electrospun nanofiber scaffolds in STE are also addressed.


Subject(s)
Biocompatible Materials , Nanofibers , Skin , Tissue Engineering , Tissue Scaffolds , Nanofibers/chemistry , Tissue Scaffolds/chemistry , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Materials Testing , Animals , Particle Size
5.
J Biomech ; 169: 112156, 2024 May.
Article in English | MEDLINE | ID: mdl-38761747

ABSTRACT

Disturbed fluid flow is well understood to have significant ramifications on endothelial function, but the impact disturbed flow has on endothelial biomechanics is not well understood. In this study, we measured tractions, intercellular stresses, and cell velocity of endothelial cells exposed to disturbed flow using a custom-fabricated flow chamber. Our flow chamber exposed cells to disturbed fluid flow within the following spatial zones: zone 1 (inlet; length 0.676-2.027 cm): 0.0037 ± 0.0001 Pa; zone 2 (middle; length 2.027-3.716 cm): 0.0059 ± 0.0005 Pa; and zone 3 (outlet; length 3.716-5.405 cm): 0.0051 ± 0.0025 Pa. Tractions and intercellular stresses were observed to be highest in the middle of the chamber (zone 2) and lowest at the chamber outlet (zone 3), while cell velocity was highest near the chamber inlet (zone 1), and lowest near the middle of the chamber (zone 2). Our findings suggest endothelial biomechanical response to disturbed fluid flow to be dependent on not only shear stress magnitude, but the spatial shear stress gradient as well. We believe our results will be useful to a host of fields including endothelial cell biology, the cardiovascular field, and cellular biomechanics in general.


Subject(s)
Stress, Mechanical , Humans , Endothelial Cells/physiology , Biomechanical Phenomena , Human Umbilical Vein Endothelial Cells/physiology
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(5): 601-605, 2024 May 10.
Article in Chinese | MEDLINE | ID: mdl-38684309

ABSTRACT

OBJECTIVE: To explore the genetic etiology of a fetus with short limbs identified by prenatal ultrasonography. METHODS: A fetus detected with short limb malformations at Shengjing Hospital Affiliated to China Medical University on October 25, 2021 was selected as the study subject. Prenatal ultrasound and post-abortion imaging were carried out to determine the phenotypic characteristics of the fetus. Amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected. Following extraction of genomic DNA, whole-exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. Online software was used to predict the structural changes of the mutant proteins. RESULTS: Prenatal ultrasound showed that the fetus had a small bell-shaped thorax, markedly shortened limbs, flat midface, a small nose with anteriorly tilted nostrils, and a small mandible. Post-abortion CT showed typical short and wide fetal ribs, cupped metaphyses at both ends, short long bones with wide metaphyses, resulting in a dumbbell-shaped appearance and curved thoracic vertebrae. Whole-exome sequencing revealed that the fetus had harbored compound heterozygous variants of the COL11A1 gene, namely c.2251G>T and c.3790G>T, both of which were predicted to alter the important Gly-X-Y structure of collagen protein. Sanger sequencing confirmed that the variants were respectively inherited from its parents. CONCLUSION: A rare fetus with Fibrochondrogenesis type 1 due to compound heterozygous variants of the COL11A1 gene has been diagnosed. Above finding has enabled genetic counseling and reproductive guidance for this family.


Subject(s)
Collagen Type XI , Fetus , Heterozygote , Phenotype , Ultrasonography, Prenatal , Humans , Female , Pregnancy , Collagen Type XI/genetics , Fetus/abnormalities , Exome Sequencing , Adult , Mutation , Prenatal Diagnosis , Genetic Testing
7.
PLoS One ; 19(4): e0301476, 2024.
Article in English | MEDLINE | ID: mdl-38687815

ABSTRACT

Graph neural networks (GNNs), with their ability to incorporate node features into graph learning, have achieved impressive performance in many graph analysis tasks. However, current GNNs including the popular graph convolutional network (GCN) cannot obtain competitive results on the graphs without node features. In this work, we first introduce path-driven neighborhoods, and then define an extensional adjacency matrix as a convolutional operator. Second, we propose an approach named exopGCN which integrates the simple and effective convolutional operator into GCN to classify the nodes in the graphs without features. Experiments on six real-world graphs without node features indicate that exopGCN achieves better performance than other GNNs on node classification. Furthermore, by adding the simple convolutional operator into 13 GNNs, the accuracy of these methods are improved remarkably, which means that our research can offer a general skill to improve accuracy of GNNs. More importantly, we study the relationship between node classification by GCN without node features and community detection. Extensive experiments including six real-world graphs and nine synthetic graphs demonstrate that the positive relationship between them can provide a new direction on exploring the theories of GCNs.


Subject(s)
Neural Networks, Computer , Algorithms , Humans
8.
J Biotechnol ; 391: 1-10, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38636846

ABSTRACT

The methylotrophic yeast, Pichia pastoris (P. pastoris; syn. Komagataella spp.), known for its ability to grow to high cell densities, its strong and tightly regulated promoters, and mammalian liked secretion pathway, has been widely used as a robust system to secrete heterologous proteins. The α-mating factor (MF) secretion signal leader from Saccharomyces cerevisiae (S. cerevisiae) is currently the most successfully used secretion signal sequence in the P. pastoris system. In this study, the secretion efficiency mediated by the α-MF secretion signal leaders from Komagataella pastoris (K. pastoris) and Komagataella phaffii (K. phaffii) was assessed using Enhanced Green Fluorescent Protein (EGFP) as a reporter. The results indicated that the secretion efficiency associated with the α-MF secretion signal leaders from K. pastoris and K. phaffii was notably lower in comparison to the α-MF secretion signal leader from S. cerevisiae. Further research indicated that N-linked glycosylation of the α-MF secretion signal leader enhanced the secretion of EGFP. Disruption of calnexin impaired the secretion of EGFP mediated by the N-linked glycosylated α-MF secretion signal leader, without affecting EGFP secretion mediated by the non-N-linked glycosylation α-MF secretion signal leader. The N-linked glycosylated of the α-MF secretion signal leader reduced the unfolded protein response (UPR) in the endoplasmic reticulum (ER). The enhancement of EGFP secretion by the N-linked glycosylated α-MF secretion signal leader might be achieved through the acceleration of proper folding of glycoproteins by the molecular chaperone calnexin. This study enhances the understanding of protein secretion in P. pastoris, specifically highlighting the influence of N-linked glycosylation on secretion efficiency, and could have implications for the production of recombinant proteins in bioengineering and biotechnological applications in P. pastoris.


Subject(s)
Green Fluorescent Proteins , Mating Factor , Protein Sorting Signals , Saccharomycetales , Glycosylation , Saccharomycetales/metabolism , Saccharomycetales/genetics , Green Fluorescent Proteins/metabolism , Green Fluorescent Proteins/genetics , Protein Sorting Signals/genetics , Mating Factor/metabolism , Mating Factor/genetics , Recombinant Proteins/metabolism , Recombinant Proteins/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Fungal Proteins/metabolism , Fungal Proteins/genetics , Calnexin/metabolism , Calnexin/genetics , Pichia/metabolism , Pichia/genetics , Endoplasmic Reticulum/metabolism
10.
Environ Pollut ; 352: 124035, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38670424

ABSTRACT

The exact mechanisms underlying the initiation and exacerbation of Parkinson's disease (PD) by paraquat remain unclear. We have revealed that exosomes mediate neurotoxicity induced by low dose paraquat exposure by transmitting intercellular signaling. Exposure to 40 µM paraquat promoted exosome release from mouse microglia cells (BV2) in vitro. Paraquat exposure at 100 µM caused degeneration of mouse dopaminergic MN9D cells and inhibited microglia exosome uptake by fluorescently labeling exosomes. We established an incubation model for exosomes and dopaminergic neuron cells under PQ treatment. The results indicated that microglial exosomes alleviated degeneration, increasing proliferation and PD-related protein expression of dopaminergic neurons; however, paraquat reversed this effect. Then, through exosome high-throughput sequencing and qRT-PCR experiments, miR-92a-3p and miR-24-3p were observed to transfer from exosomes to dopaminergic neurons, inhibited by paraquat. The specificity of miR-92a-3p and miR-24-3p was verified in PD patients exosomes, indicating the potential diagnostic value of the exosomal miRNAs in paraquat-induced PD. These results suggest glia-neuron communication in paraquat-induced neurodegeneration and may identify stable paraquat-mediated PD biomarkers, offering clues for early recognition and prevention of pesticide-induced degenerative diseases.


Subject(s)
Biomarkers , Dopaminergic Neurons , Exosomes , MicroRNAs , Microglia , Paraquat , Parkinson Disease , Paraquat/toxicity , Exosomes/metabolism , Animals , Microglia/drug effects , Microglia/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Dopaminergic Neurons/drug effects , Biomarkers/metabolism , Neuroprotection/drug effects , Humans , Cell Line
11.
J Ethnopharmacol ; 329: 118118, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38614261

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical efficacy of the Yiqi Kaimi prescription has been confirmed in slow transit constipation. However, the effects and biological mechanism of Yiqi Kaimi prescription are still unclear. AIMS OF THE STUDY: To identify the effects of Yiqi Kaimi prescription on intestinal motility; To reveal the potential key targets and pathways of Yiqi Kaimi prescription for the treatment of slow transit constipation. MATERIALS AND METHODS: The effects of Yiqi Kaimi prescription on slow transit constipation were investigated in a mouse model. The terminal ink propulsion experiment and fecal indocyanine green imaging was used to measure the intestinal transit time. Protein phosphorylation changes in colon tissues treated with Yiqi Kaimi prescription were detected using a Phospho Explorer antibody microarray. Bioinformatic analyses were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID) and the Search Tool for the Retrieval of Interacting Genes (STRING). Western blot analysis and immunohistochemistry confirmed the observed changes in phosphorylation. RESULT: s: Yiqi Kaimi prescription significantly increased the intestinal transit rate (P < 0.05 vs. model) and reduced the time to first discharge of feces containing fecal indocyanine green imaging in mice (P < 0.05 vs. model). The administration of Yiqi Kaimi prescription induced phosphorylation changes in 41 proteins, with 9 upregulated proteins and 32 downregulated proteins. Functional classification of the phosphorylated proteins with DAVID revealed that the critical biological processes included tyrosine protein kinases, positive regulation of calcium-mediated signaling and response to muscle stretch. The phosphorylation of the spleen tyrosine kinase (SYK) at Tyr348 increased 2.19-fold, which was the most significant change. The phosphorylation level of the transcription factor p65 (RELA) at Thr505 was decreased 0.57-fold. SYK was a hub protein in the protein-protein interaction network and SYK and RELA formed the core of the secondary subnetwork. The key protein phosphorylation after treatment with Yiqi Kaimi prescription were verified by Western blot analysis and immunohistochemistry. CONCLUSION: Yiqi Kaimi prescription significantly enhanced intestinal motility. This effect was attributed to alterations in the phosphorylation levels of various target proteins. The observed changes in protein phosphorylation, including SYK and RELA, may serve as crucial factors in the treatment of slow transit constipation.


Subject(s)
Constipation , Drugs, Chinese Herbal , Gastrointestinal Motility , Phosphorylation , Phosphorylation/drug effects , Proteins/metabolism , Gastrointestinal Motility/drug effects , Constipation/drug therapy , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Disease Models, Animal , Mice, Inbred C57BL , Feces/chemistry , Computational Biology , Animals , Mice
12.
Sci Total Environ ; 925: 171492, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38458465

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are hydrocarbons characterized by the presence of multiple benzene rings. They are ubiquitously found in the natural environment, especially in environmental pollutants, including atmospheric particulate matter, cigarette smoke, barbecue smoke, among others. PAHs can influence human health through several mechanisms, including the aryl hydrocarbon receptor (AhR) pathway, oxidative stress pathway, and epigenetic pathway. In recent years, the impact of PAHs on inflammatory skin diseases has garnered significant attention, yet many of their underlying mechanisms remain poorly understood. We conducted a comprehensive review of articles focusing on the link between PAHs and several inflammatory skin diseases, including psoriasis, atopic dermatitis, lupus erythematosus, and acne. This review summarizes the effects and mechanisms of PAHs in these diseases and discusses the prospects and potential therapeutic implications of PAHs for inflammatory skin diseases.


Subject(s)
Air Pollutants , Environmental Pollutants , Polycyclic Aromatic Hydrocarbons , Skin Diseases , Humans , Polycyclic Aromatic Hydrocarbons/toxicity , Polycyclic Aromatic Hydrocarbons/analysis , Particulate Matter , Receptors, Aryl Hydrocarbon/metabolism , Air Pollutants/toxicity , Air Pollutants/analysis
13.
Front Public Health ; 12: 1249971, 2024.
Article in English | MEDLINE | ID: mdl-38532970

ABSTRACT

Background: China is among the 10 high-burden tuberculosis (TB) countries in the world; thus, investigation and management of household contacts is an essential part of TB prevention strategy. Objective: To explore the knowledge, attitude, and practice (KAP) toward TB prevention and management among household contacts of TB patients. Methods: This cross-sectional study enrolled household contacts in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine between September 2022 and January 2023; KAP and demographic characteristics were assessed with the self-designed questionnaire and analyzed by multivariate logistic regression. Results: A total of 503 participants were included; of them, 280 (55.78%) were female, and 303, (60.36%) aged ≥45 years. The KAP scores were 6.24 ± 2.20 (possible range: 0-12), 18.69 ± 2.80 (possible range: 0-36), and 20.37 ± 5.15 (possible range: 0-36), respectively. Suburban (OR = 0.18, 95% CI: 0.04-0.79, p = 0.023) and rural (OR = 0.12, 95% CI: 0.03-0.57, p = 0.008) were independently associated with knowledge. Positive attitude (OR = 7.03, 95% CI: 2.92-16.96, p < 0.001), education (high school or technical secondary school, OR = 4.91, 95% CI: 1.63-14.73, p = 0.005; college and above, OR = 14.94, 95% CI: 3.51-63.58, p < 0.001), and shorter disease duration (3-6 months, OR = 0.40, 95% CI: 0.18-0.90, p = 0.026) were independently associated with better practice scores. Conclusion: Household contacts of TB patients demonstrated insufficient knowledge, unfavorable attitude, and suboptimal practice toward TB prevention and management. Tailored interventions are needed to ensure information accessibility, especially for individuals living in suburban and rural areas.


Subject(s)
Tuberculosis , Humans , Female , Male , Tuberculosis/prevention & control , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Hospitals , China
14.
Molecules ; 29(6)2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38542973

ABSTRACT

The meta-diamide (m-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m-diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, 1H NMR, 13C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds A-D exhibited 100% lethality against Plutella xylostella (P. xylostella) and Aphis craccivora Koch (A. craccivora) at 500 mg·L-1. Notably, for P. xylostella, compounds C-2, C-3, C-4 and D-2 demonstrated 60.00-100.00% insecticidal activity even at a concentration as low as 0.625 mg·L-1. As determined by structure-activity relationship (SAR) analysis, compounds with R1 = CH3 and R2 = Br (B-1, C-2 and D-2) and sulfoxide compound C-3 contained 100.00% lethality against A. craccivora at 500 mg·L-1, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound (C-3) requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing m-diamide compounds.


Subject(s)
Benzamides , Fluorocarbons , Insecticides , Moths , Pesticides , Animals , Molecular Structure , Diamide/chemistry , Structure-Activity Relationship , Insecticides/pharmacology , Insecticides/chemistry , Sulfoxides
15.
Adv Sci (Weinh) ; 11(16): e2305715, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38417117

ABSTRACT

Drug-induced liver injury (DILI) is a significant global health issue that poses high mortality and morbidity risks. One commonly observed cause of DILI is acetaminophen (APAP) overdose. GSDME is an effector protein that induces non-canonical pyroptosis. In this study, the activation of GSDME, but not GSDMD, in the liver tissue of mice and patients with APAP-DILI is reported. Knockout of GSDME, rather than GSDMD, in mice protected them from APAP-DILI. Mice with hepatocyte-specific rescue of GSDME reproduced APAP-induced liver injury. Furthermore, alterations in the immune cell pools observed in APAP-induced DILI, such as the replacement of TIM4+ resident Kupffer cells (KCs) by monocyte-derived KCs, Ly6C+ monocyte infiltration, MerTk+ macrophages depletion, and neutrophil increase, reappeared in mice with hepatocyte-specific rescue of GSDME. Mechanistically, APAP exposure led to a substantial loss of interferon-stimulated gene 15 (ISG15), resulting in deISGylation of carbamoyl phosphate synthetase-1 (CPS1), promoted its degradation via K48-linked ubiquitination, causing ammonia clearance dysfunction. GSDME deletion prevented these effects. Delayed administration of dimethyl-fumarate inhibited GSDME cleavage and alleviated ammonia accumulation, mitigating liver injury. This findings demonstrated a previously uncharacterized role of GSDME in APAP-DILI by promoting pyroptosis and CPS1 deISGylation, suggesting that inhibiting GSDME can be a promising therapeutic option for APAP-DILI.


Subject(s)
Acetaminophen , Chemical and Drug Induced Liver Injury , Gasdermins , Pyroptosis , Animals , Humans , Male , Mice , Acetaminophen/adverse effects , Chemical and Drug Induced Liver Injury/metabolism , Disease Models, Animal , Liver Failure/metabolism , Liver Failure/chemically induced , Mice, Inbred C57BL , Mice, Knockout , Pyroptosis/drug effects
16.
Nat Commun ; 15(1): 1835, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38418488

ABSTRACT

B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.


Subject(s)
Acute-On-Chronic Liver Failure , Hepatitis B, Chronic , Animals , Humans , Mice , Acute-On-Chronic Liver Failure/complications , CD4-Positive T-Lymphocytes , Cytokines/metabolism , Hepatitis B, Chronic/complications , Phosphatidylinositol 3-Kinases , Receptors, Immunologic/metabolism , T-Cell Exhaustion
17.
ACS Appl Mater Interfaces ; 16(9): 11194-11205, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38391151

ABSTRACT

Osteomyelitis is primarily caused by bacterial infections, and treatment requires precise sequential therapy, including antibacterial therapy in the early stages and bone defect reconstruction in later stages. We aimed to synthesize core-shell-structured zinc oxide/silver sulfide heterogeneous nanoparticles (ZnO/Ag2S NPs) using wet chemical methods. Using density functional theory and ultraviolet photoelectron spectroscopy, we showed that the optimized band structure endowed ZnO/Ag2S NPs with photodynamic properties under near-infrared (NIR) irradiation. Moreover, ZnO/Ag2S NPs exhibited a distinguished and stable photothermal performance within the same wavelength range. With single-wavelength irradiation, ZnO/Ag2S NPs achieved a bifunctional antibacterial effect during the acute stage of osteomyelitis. Antibacterial action was confirmed through colony-forming unit (CFU) counting assays, scanning electronic microscopy (SEM) observations, live-dead staining, growth curves, and quantitative real-time polymerase chain reaction (qPCR) assays. The Ag2S coating on the NPs realized the sustained release of zinc ions, thereby controlling the zinc ion concentration. Alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, and qPCR assays confirmed that the ZnO/Ag2S NPs exhibited good osteogenic effects in vitro. These effects were verified in an in vivo mouse femur model during chronic stages using micro-computed tomography (micro-CT) and histological analysis. This study provides a novel biocompatible core-shell nanomaterial for the two-phase treatment of osteomyelitis, contributing to versatile nanotherapies for infections and inflammation.


Subject(s)
Metal Nanoparticles , Nanoparticles , Osteomyelitis , Silver Compounds , Zinc Oxide , Animals , Mice , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , X-Ray Microtomography , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Zinc , Osteomyelitis/diagnostic imaging , Osteomyelitis/drug therapy
18.
Article in English | MEDLINE | ID: mdl-38295722

ABSTRACT

A facial and rapid method for glycoproteins enrichment by capillary electrophoresis was developed. The 3-aminophenylboronic acid-functionalized poly(glycidyl methacrylate) microparticles (PGMA@APBA) were attached to the capillary inlet (length of ∼1.5 cm) by electrostatic self-assemble action to prepare a partially coated capillary column. The process is simple and reversible, allowing for easy renewal of the PGMA@APBA coating when its enrichment efficiency decreases. By utilizing the coated column, glycoproteins can be enriched within 2 min. The column exhibits a specific enrichment for glycoproteins and can be consecutively used for approximately 60 runs. The relative standard deviations (RSDs) of peak area of run-to-run (n = 5) and batch-to-batch (n = 3) were 1.5 % and 1.0%, respectively. The method was successfully applied to enrich glycoproteins from 1 × 1012-fold diluted real egg white sample, indicating its practical applicability.


Subject(s)
Electrophoresis, Capillary , Epoxy Compounds , Methacrylates , Polymethacrylic Acids , Glycoproteins
19.
Int Urol Nephrol ; 56(6): 2085-2092, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38289547

ABSTRACT

OBJECTIVE: To investigate the correlation among sleep disorders, physical frailty, and depression in elderly patients with chronic kidney disease (CKD), and to explore the mediating role of depression. METHODS: This was a cross-sectional study, simple sampling was used to investigate the elderly CKD patients from one tertiary hospital in Shanghai. Those CKD patients who were diagnosed as CKD1-5 phase and were admitted to the Renal Medicine Ward from January to June 2022 and provided formal consent were considered for inclusion in our study. They were investigated with frailty phenotype (FP), Pittsburgh sleep quality index (PSQI), Center for Epidemiological Studies Depression Scale (CES-D), and self-made general information questionnaire. Linear regression was used to assess the associations between the variables, before this, PROCESS v4.1 was used to transform PSQI, CES-D and FP score to improve its normality, and conduct intermediary analysis. A difference of p < 0.05 was statistically significant. RESULTS: A total of 504 elderly patients with CKD completed the questionnaire survey, aged 60-91. The incidence of sleep disorders among elderly patients with CKD was 60%, and the incidence of physical frailty was 18%. The depression was positively correlated with physical frailty (r = 0.418, p < 0.01) and sleep disorders (r = 0.541, p < 0.01). Physical frailty was positively correlated with sleep disorders (r = 0.320, p < 0.01). The depression plays a significant mediating role in the model, and the effect ratio of depression is 52%. CONCLUSION: Depression is a mediating variable between sleep disorders and frailty. Improving depression in elderly patients with CKD accompanied by sleep disorders can help delay the occurrence of frailty.


Subject(s)
Depression , Frailty , Renal Insufficiency, Chronic , Sleep Wake Disorders , Humans , Cross-Sectional Studies , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/psychology , Sleep Wake Disorders/epidemiology , Aged , Male , Female , Depression/epidemiology , China/epidemiology , Aged, 80 and over , Frailty/epidemiology , Frailty/complications , Middle Aged , Frail Elderly
20.
Psychol Health Med ; 29(1): 1-14, 2024.
Article in English | MEDLINE | ID: mdl-37676014

ABSTRACT

Informal caregivers play an increasingly important role in the provision of care services, especially for the ageing population. At present, the evidence on the resilience of the Internet to family caregivers is still limited. The purpose of this study was to evaluate the factors related to the resilience of the Internet to family caregivers. We searched retrieved randomized controlled trials (rct) of the effects of Internet interventions on resilience in informal caregivers from the beginning of the database to 1 November 2022. A preliminary search identified 3348 studies, 5 of which met the inclusion criteria. The studies involved 482 participants from four countries. Our results show that compared to the control group, internet intervention can effectively improve the resilience level of caregivers [SMD = 0.65, 95%CI(0.04,1.26), P ≤ 0.05]. In our study, Web-based interventions can significantly improve the adaptability of informal caregivers. In addition, our research also pointed out many resources that can be used, such as online learning, online answers and online psychological counseling provided for caregivers through the Internet, which can effectively reduce their burden of care and thus improve their resilience. In the future, these findings can be used to develop projects to improve the resilience of caregivers through personalized Internet intervention, so as to meet the care needs of patients.


Subject(s)
Internet-Based Intervention , Resilience, Psychological , Humans , Caregivers/psychology , Psychotherapy , Quality of Life
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