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1.
Aging Clin Exp Res ; 36(1): 182, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235675

ABSTRACT

BACKGROUND: Existing research indicates that the Mediterranean diet has a positive impact on preventing and treating hypertension. However, its specific effect on hypertension among elderly Chinese individuals is unclear. AIMS: The objective of this research was to explore the association between the Chinese version of the Mediterranean-DASH Intervention for Neurodegenerative Delay (cMIND) diet and hypertension among elderly Chinese individuals, aiming to offer novel strategies for alleviating the burden of hypertension in this demographic. METHODS: In this study, we used cross-sectional data published in 2018 by the China Longitudinal Health and Longevity Survey (CLHLS) to develop a binary logistic regression model to investigate the correlation between cMIND diet and hypertension in a Chinese elderly population. Restricted cubic spline was used to test for linear associations, and further subgroup analyses were performed to test for interactions. RESULTS: In total, 7,103 older adults were included in the study, with a prevalence of hypertension of 39.0%. When the cMIND diet score was used as a continuous variable, a significant protective effect against hypertension was present (OR = 0.955, 95% CI:0.923-0.988, p = 0.008); when used as a categorical variable, this protective effect was still present at higher levels (compared to lower levels) of the cMIND diet (OR = 0.869, 95% CI: 0.760-0.995, p = 0.042). DISCUSSION: Although the Mediterranean diet has great potential to reduce the chance of hypertension, it should also consider the effect on the Chinese population. The results of this study provide new ways to reduce the disease burden of hypertension in Chinese older adults and improve quality of life in later life. CONCLUSION: The cMIND diet can considerably reduce the risk of hypertension among older adults in China.


Subject(s)
Diet, Mediterranean , Hypertension , Humans , Hypertension/epidemiology , Hypertension/prevention & control , Aged , Male , China/epidemiology , Female , Cross-Sectional Studies , Dietary Approaches To Stop Hypertension , Aged, 80 and over , Middle Aged , Prevalence
2.
CNS Neurosci Ther ; 30(9): e70037, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39268632

ABSTRACT

Vestibular compensation is the natural process of recovery that occurs with acute peripheral vestibular lesion. Here, we summarize the current understanding of the mechanisms underlying vestibular compensation, focusing on the role of the medial vestibular nucleus (MVN), the central hub of the vestibular system, and its associated neural networks. The disruption of neural activity balance between the bilateral MVNs underlies the vestibular symptoms after unilateral vestibular damage, and this balance disruption can be partially reversed by the mutual inhibitory projections between the bilateral MVNs, and their top-down regulation by other brain regions via different neurotransmitters. However, the detailed mechanism of how MVN is involved in vestibular compensation and regulated remains largely unknown. A deeper understanding of the vestibular neural network and the neurotransmitter systems involved in vestibular compensation holds promise for improving treatment outcomes and developing more effective interventions for vestibular disorders.


Subject(s)
Nerve Net , Vestibular Diseases , Vestibular Nuclei , Humans , Animals , Vestibular Nuclei/physiology , Nerve Net/physiology , Nerve Net/physiopathology , Vestibular Diseases/physiopathology , Vestibular Diseases/therapy , Vestibule, Labyrinth/physiology , Vestibular System/physiology
3.
J Infect ; 89(5): 106273, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39278277

ABSTRACT

OBJECTIVE: To explore the risk factors for pulmonary bacterial infection (PBI) after lung transplantation (LTX) and to evaluate the impact of PBI on short-term postoperative mortality. METHODS: We retrospectively analyzed data on 549 recipients who underwent LTX at the Affiliated Wuxi People's Hospital of Nanjing Medical University, China, between January 2018 and December 2021. The risk factors for PBI after LTX were explored by univariate analysis and multivariate logistic regression. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of one-, two-, and three-year mortality. Subgroup analysis was performed by the time of postoperative PBI (≤7 days or 8-30 day after surgery). RESULTS: The incidence of postoperative PBI in 549 recipients was 82.70% (454/549). Preoperative history of infections with multidrug-resistant bacteria (OR 12.34, 95% CI 1.69-1572.39), Acinetobacter baumannii infection in donor (OR 3.08, 95% CI 1.26-9.66), and longer cold ischemia time (OR 1.16, 95% CI 1.03-1.32) were risk factors for postoperative PBI. Postoperative PBI was associated with one-year (HR 1.80, 95% CI 1.09-2.96), two-year (HR 1.91, 95% CI 1.20-3.04), and three-year mortality (HR 2.03, 95% CI 1.29-3.19). Subgroup analysis showed that PBI within 7 days after surgery was associated with one-year (HR 1.86, 95% CI 1.12-3.08), two-year (HR 1.99, 95% CI 1.25-3.17), and three-year mortality (HR 2.13, 95% CI 1.35-3.36), while PBI at 8-30 days after surgery was not associated with short-term mortality (one-year: HR 1.36, 95% CI 0.69-2.69; two-year: HR 1.48, 95% CI 0.80-2.76; three-year: HR 1.51, 95% CI 0.82-2.77). CONCLUSIONS: Donor-recipient and surgical factors are risk factors for PBI after LTX. Active prevention and treatment of PBI within the first 7 days after surgery may improve short-term survival.

4.
Chem Sci ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39328194

ABSTRACT

Chiral hydrazone photoswitch features are its high thermal stability and negative photochromy, making it desirable in the fabrication of thermally stable optical device. However, chiral hydrazones capable of reversibly inversing chirality is scarcely reported. Herein, a series of new chiral hydrazone switches, HI-1, HI-2 and HI-3, were designed and synthesized. Due to the photoinduced configuration changes, the newly synthesized hydrazone photoswitch presents a surprising chirality inversion upon light stimulation. Photoisomerization of light-driven hydrazone switch molecules was investigated by nuclear magnetic resonance (NMR) spectra and Raman spectroscopy. The effect of the intramolecular hydrogen bond on photoresponsiveness was analyzed. By incorporating the photoswitch into a liquid crystal (LC) host, light-driven cholesteric liquid crystals (CLCs) with handedness invertibility, a feasible photonic bandgap tunability, and superior thermal stability were achieved. In addition, according to the optical-driven thermal stability of the hydrazone switches, the fine regulation of light-driven CLC materials with multistage photo stationary states was realized, and the application of CLC materials in erasable and rewritable display panels was also demonstrated.

5.
J Neurosci ; 44(37)2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39134421

ABSTRACT

Although the locus ceruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (LC-NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential and single-unit activity in multiple cortical regions associated with auditory-motor processing, including the auditory cortex, posterior parietal cortex, secondary motor cortex, anterior cingulate cortex, prefrontal cortex, and orbitofrontal cortex (OFC), in response to optogenetic activation (40 Hz and 0.5 s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillation (50-80 Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in norepinephrine levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a go/no-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing.


Subject(s)
Auditory Perception , Discrimination, Psychological , Locus Coeruleus , Optogenetics , Animals , Locus Coeruleus/physiology , Mice , Male , Auditory Perception/physiology , Discrimination, Psychological/physiology , Mice, Inbred C57BL , Norepinephrine/metabolism , Acoustic Stimulation/methods , Gamma Rhythm/physiology , Neurons/physiology , Cerebral Cortex/physiology
6.
Respir Res ; 25(1): 326, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39210401

ABSTRACT

OBJECTIVES: In this study, we investigated whether neural precursor cell-expressed developmentally down-regulated gene 4-like (NEDD4L) is the E3 enzyme of angiotensin-converting enzyme 2 (ACE2) and whether NEDD4L degrades ACE2 via ubiquitination, leading to the progression of pulmonary arterial hypertension (PAH). METHODS: Bioinformatic analyses were used to explore the E3 ligase that ubiquitinates ACE2. Cultured pulmonary arterial smooth muscle cells (PASMCs) and specimens from patients with PAH were used to investigate the crosstalk between NEDD4L and ACE2 and its ubiquitination in the context of PAH. RESULTS: The inhibition of ubiquitination attenuated hypoxia-induced proliferation of PASMCs. The levels of NEDD4L were increased, and those of ACE2 were decreased in lung tissues from patients with PAH and in PASMCs. NEDD4L, the E3 ligase of ACE2, inhibited the expression of ACE2 in PASMCs, possibly through ubiquitination-mediated degradation. PAH was associated with upregulation of NEDD4L expression and downregulation of ACE2 expression. CONCLUSIONS: NEDD4L, the E3 ubiquitination enzyme of ACE2, promotes the proliferation of PASMCs, ultimately leading to PAH.


Subject(s)
Angiotensin-Converting Enzyme 2 , Nedd4 Ubiquitin Protein Ligases , Pulmonary Arterial Hypertension , Ubiquitination , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/biosynthesis , Nedd4 Ubiquitin Protein Ligases/metabolism , Nedd4 Ubiquitin Protein Ligases/genetics , Humans , Cells, Cultured , Male , Pulmonary Arterial Hypertension/metabolism , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/pathology , Pulmonary Arterial Hypertension/enzymology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/enzymology , Myocytes, Smooth Muscle/pathology , Animals , Cell Proliferation/physiology , Peptidyl-Dipeptidase A/metabolism , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/biosynthesis , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Pulmonary Artery/enzymology , Female , Rats , Rats, Sprague-Dawley
7.
BMC Pulm Med ; 24(1): 410, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39187801

ABSTRACT

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension with a low incidence. Despite pulmonary endarterectomy(PEA) being the preferred treatment for CTEPH, for patients who failed medical therapy and who are not suitable candidates for PEA, lung transplantation (LT) is still the only effective treatment for end-stage CTEPH; however, there are currently very few reports on the efficacy of LT for CTEPH. METHODS: We retrospectively analyzed the clinical data of seven patients diagnosed with CTEPH between July 2019 and July 2021. The follow-up deadline was March, 2022. RESULTS: The mean age at admission was 54 ± 12 years. The average value of mean pulmonary artery pressure (mPAP) was 40 ± 5 mmHg. The mean preoperative oxygenation index(PaO2/FiO2) was 203 ± 56 mm Hg. After evaluation, one patient underwent left LT and the rest underwent bilateral LT. Three patients received intraoperative veno-venous extracorporeal membrane oxygenation (ECMO) support, and four patients received intraoperative veno-arterial ECMO support. The average postoperative mPAP was 19 ± 4 mmHg. The mean postoperative oxygenation index(PaO2/FiO2) was 388 ± 83 mmHg. There was a significant difference between the preoperative and postoperative mPAP and oxygenation index(PaO2/FiO2). All patients recovered well and were discharged 37 ± 19 days postoperatively. The mean follow-up duration was 19 ± 8 months. There was no recurrence of CTEPH. CONCLUSIONS: LT is an effective treatment for end-stage CTEPH, which can improve cardiopulmonary function and quality of life and prolong survival. Patients who are unable to tolerate PEA should be considered for LT as early as possible when internal medicine failed.


Subject(s)
Hypertension, Pulmonary , Lung Transplantation , Pulmonary Embolism , Humans , Middle Aged , Female , Male , Retrospective Studies , Hypertension, Pulmonary/surgery , Pulmonary Embolism/surgery , Pulmonary Embolism/complications , Adult , Chronic Disease , Treatment Outcome , Extracorporeal Membrane Oxygenation/methods , Aged , Endarterectomy/methods
8.
BMC Med Inform Decis Mak ; 24(1): 229, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160522

ABSTRACT

BACKGROUND: Patients with airway stenosis (AS) are associated with considerable morbidity and mortality after lung transplantation (LTx). This study aims to develop and validate machine learning (ML) models to predict AS requiring clinical intervention in patients after LTx. METHODS: Patients who underwent LTx between January 2017 and December 2019 were reviewed. The conventional logistic regression (LR) model was fitted by the independent risk factors which were determined by multivariate LR. The optimal ML model was determined based on 7 feature selection methods and 8 ML algorithms. Model performance was assessed by the area under the curve (AUC) and brier score, which were internally validated by the bootstrap method. RESULTS: A total of 381 LTx patients were included, and 40 (10.5%) patients developed AS. Multivariate analysis indicated that male, pulmonary arterial hypertension, and postoperative 6-min walking test were significantly associated with AS (all P < 0.001). The conventional LR model showed performance with an AUC of 0.689 and brier score of 0.091. In total, 56 ML models were developed and the optimal ML model was the model fitted using a random forest algorithm with a determination coefficient feature selection method. The optimal model exhibited the highest AUC and brier score values of 0.760 (95% confidence interval [CI], 0.666-0.864) and 0.085 (95% CI, 0.058-0.117) among all ML models, which was superior to the conventional LR model. CONCLUSIONS: The optimal ML model, which was developed by clinical characteristics, allows for the satisfactory prediction of AS in patients after LTx.


Subject(s)
Lung Transplantation , Machine Learning , Humans , Male , Retrospective Studies , Middle Aged , Female , Adult , Case-Control Studies , Constriction, Pathologic , Postoperative Complications , Risk Factors
9.
Environ Res ; 261: 119692, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39068968

ABSTRACT

BACKGROUND: Dyslipidemia is increasingly recognized as an essential risk factor for cardiovascular diseases. However, few studies illustrated the effects of ambient temperature exposure (TE) on lipid levels in children. The study aimed to examine the association between ambient TE and lipid levels in children. METHODS: Based on a prospective cohort, a total of 2423 children (with 4466 lipids measure person-time) were collected from 2014 to 2019. The meteorological observation data and adjusted variables were collected. Mixed-effect models and generalized additive mixed model (GAMM) were applied to investigate the association between ambient TE and lipid levels. RESULTS: A significant negative association was observed between TE and low-density lipoprotein cholesterol (LDL-C) or total cholesterol (TC) levels both in all children [LDL-C, ß(95%CI) = -0.350(-0.434,-0.265), P < 0.001; TC, ß(95%CI) = -0.274(-0.389,-0.160), P < 0.001] and by different sex group. However, no significant association was found in low-density lipoprotein cholesterol (HDL-C) or triglycerides (TG) levels. The estimated optimal ambient TEs for LDL-C were 18.273 °C and 18.024 °C for girls and boys, respectively. For TC, the optimal ambient TEs were 17.949 °C and 18.024 °C, respectively. With ambient TE decreased, the risk of dyslipidemia increased for both boys [OR = 0.032(0.006,0.179), P < 0.001] and girls [OR = 0.582(0.576,0.587), P < 0.001]. CONCLUSION: This study provided a comprehensive illustration about the associations between ambient TE and lipid levels in different sex and ages from a prospective cohort study. The findings will provide evidence for the government to prevent dyslipidemia in vulnerable children through regulating TE.


Subject(s)
Lipid Metabolism , Temperature , Humans , Child , Female , Male , Prospective Studies , Child, Preschool , Dyslipidemias/epidemiology , Adolescent , Triglycerides/blood , Cholesterol/blood , Cholesterol, LDL/blood , Lipids/blood , China
10.
J Cell Mol Med ; 28(14): e18532, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39039705

ABSTRACT

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the central nervous system, yet their role in vestibular compensation remains elusive. To address this knowledge gap, we employed unilateral labyrinthectomy (UL) in rats to establish animal models of peripheral vestibular dysfunction. Utilizing ribonucleic acid sequencing (RNA-seq), we comprehensively analysed the expression profiles of genes dysregulated in the medial vestibular nucleus (MVN) of these rats at distinct time points: 4 h, 4 days, and 14 days post-UL. Through trans-target prediction analysis integrating differentially co-expressed messenger RNAs (mRNAs) and lncRNAs, we constructed lncRNA-mRNA regulatory networks. Validation of selected mRNAs and lncRNAs was performed using RT-qPCR. Our RNA-seq analysis revealed significant aberrant expression of 3054 lncRNAs and 1135 mRNAs compared to control samples. By applying weighted gene co-expression network analysis (WGCNA), we identified 11 co-expressed modules encompassing all genes. Notably, within the MEmagenta module, we observed an initial upregulation of differentially expressed genes (DEGs) at 4 h, followed by downregulation at 4- and 14-days post-UL. Our findings indicated that 3068 lncRNAs positively regulated 1259 DEGs, while 1482 lncRNAs negatively regulated 433 DEGs in the MVN. The RT-qPCR results corroborated the RNA-seq data, validating our findings. This study offers novel insights into the lncRNA-mRNA expression landscape during vestibular compensation, paving the way for further exploration of lncRNA functions in this context.


Subject(s)
Gene Expression Profiling , Gene Regulatory Networks , RNA, Long Noncoding , RNA, Messenger , Vestibular Nuclei , Vestibule, Labyrinth , Animals , Vestibular Nuclei/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Male , Vestibule, Labyrinth/surgery , Vestibule, Labyrinth/metabolism , Gene Expression Regulation , Rats, Sprague-Dawley , Transcriptome/genetics
11.
Mol Cancer ; 23(1): 148, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39048965

ABSTRACT

Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin-proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.


Subject(s)
Deubiquitinating Enzymes , Neoplasms , Proteasome Endopeptidase Complex , Ubiquitination , Humans , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Animals , Proteasome Endopeptidase Complex/metabolism , Deubiquitinating Enzymes/metabolism , Proteolysis , Ubiquitin/metabolism , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Protein Processing, Post-Translational , Molecular Targeted Therapy , Ubiquitin-Protein Ligases/metabolism
12.
Sensors (Basel) ; 24(14)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39066074

ABSTRACT

Edge servers frequently manage their own offline digital twin (DT) services, in addition to caching online digital twin services. However, current research often overlooks the impact of offline caching services on memory and computation resources, which can hinder the efficiency of online service task processing on edge servers. In this study, we concentrated on service caching and task offloading within a collaborative edge computing system by emphasizing the integrated quality of service (QoS) for both online and offline edge services. We considered the resource usage of both online and offline services, along with incoming online requests. To maximize the overall QoS utility, we established an optimization objective that rewards the throughput of online services while penalizing offline services that miss their soft deadlines. We formulated this as a utility maximization problem, which was proven to be NP-hard. To tackle this complexity, we reframed the optimization problem as a Markov decision process (MDP) and introduced a joint optimization algorithm for service caching and task offloading by leveraging the deep Q-network (DQN). Comprehensive experiments revealed that our algorithm enhanced the utility by at least 14.01% compared with the baseline algorithms.

13.
World J Clin Oncol ; 15(7): 867-894, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39071464

ABSTRACT

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) has been identified as a possible biomarker for breast cancer (BC) and may play a role in the development and advancement of triple-negative BC (TNBC). AIM: To explore the PGK1 and BC research status and PGK1 expression and mechanism differences among TNBC, non-TNBC, and normal breast tissue. METHODS: PGK1 and BC related literature was downloaded from Web of Science Core Collection Core Collection. Publication counts, key-word frequency, cooperation networks, and theme trends were analyzed. Normal breast, TNBC, and non-TNBC mRNA data were gathered, and differentially expressed genes obtained. Area under the summary receiver operating characteristic curves, sensitivity and specificity of PGK1 expression were determined. Kaplan Meier revealed PGK1's prognostic implication. PGK1 co-expressed genes were explored, and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Disease Ontology applied. Protein-protein interaction networks were constructed. Hub genes identified. RESULTS: PGK1 and BC related publications have surged since 2020, with China leading the way. The most frequent keyword was "Expression". Collaborative networks were found among co-citations, countries, institutions, and authors. PGK1 expression and BC progression were research hotspots, and PGK1 expression and BC survival were research frontiers. In 16 TNBC vs non-cancerous breast and 15 TNBC vs non-TNBC datasets, PGK1 mRNA levels were higher in 1159 TNBC than 1205 non-cancerous breast cases [standardized mean differences (SMD): 0.85, 95% confidence interval (95%CI): 0.54-1.16, I² = 86%, P < 0.001]. PGK1 expression was higher in 1520 TNBC than 7072 non-TNBC cases (SMD: 0.25, 95%CI: 0.03-0.47, I² = 91%, P = 0.02). Recurrence free survival was lower in PGK1-high-expression than PGK1-low-expression group (hazard ratio: 1.282, P = 0.023). PGK1 co-expressed genes were concentrated in ATP metabolic process, HIF-1 signaling, and glycolysis/gluconeogenesis pathways. CONCLUSION: PGK1 expression is a research hotspot and frontier direction in the BC field. PGK1 may play a strong role in promoting cancer in TNBC by mediating metabolism and HIF-1 signaling pathways.

14.
Exp Ther Med ; 28(3): 352, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39071899

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer. Although it has a high mortality rate, there is currently no effective treatment for HCC. Lenvatinib has traditionally been used as the first-line treatment for advanced HCC (aHCC); however, resistance to this therapy is common. It can be difficult to select effective second-line drugs to overcome lenvatinib resistance when treating aHCC. For patients with aHCC, poor treatment efficacy can result in patients missing the optimal treatment window and can lead to an irreversible situation. Lenalidomide has begun to be used to treat HCC; however, to the best of our knowledge, its efficacy in patients with lenvatinib-resistant HCC remains to be reported on in the literature. The present case report, to the best of our knowledge, describes the first case in the literature of a patient with lenvatinib-resistant aHCC who achieved a partial response after the treatment regimen was switched to lenalidomide. The present case report provides a promising novel route for the treatment of lenvatinib-resistant HCC.

15.
Biomed Pharmacother ; 178: 117132, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39047418

ABSTRACT

Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500 µM, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5 % ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5 % ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.


Subject(s)
Aminolevulinic Acid , Diabetes Mellitus, Experimental , Methicillin-Resistant Staphylococcus aureus , Photochemotherapy , Rats, Sprague-Dawley , Wound Healing , Wound Infection , Animals , Aminolevulinic Acid/pharmacology , Photochemotherapy/methods , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/pathology , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/complications , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Wound Healing/drug effects , Rats , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Chronic Disease , Staphylococcal Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests , Reactive Oxygen Species/metabolism
16.
Hypertension ; 81(8): 1785-1798, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38832511

ABSTRACT

BACKGROUND: The N6-methyladenosine (m6A) modification of RNA and its regulators have important roles in the pathogenesis of pulmonary hypertension (PH). Ythdf2 (YTH N6-methyladenosine RNA binding protein 2) is best known for its role in degrading m6A-modified mRNAs such as Hmox1 mRNA, which leads to alternative activation of macrophages in PH. Recent studies have also linked Ythdf2 to the proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its specific roles in PASMCs and downstream targets during the development of PH remain unclear. METHODS: The expression and biological function of Ythdf2 in PASMCs were investigated in human and experimental models of PH. Smooth muscle cell-specific Ythdf2-deficient mice were used to assess the roles of Ythdf2 in PASMCs in vivo. Proteomic analysis, m6A sequencing, and RNA immunoprecipitation analysis were used to screen for potential downstream targets. RESULTS: Ythdf2 was significantly upregulated in human and rodent PH-PASMCs, and smooth muscle cell-specific Ythdf2 deficiency ameliorated PASMC proliferation, right ventricular hypertrophy, pulmonary vascular remodeling, and PH development. Higher expression of Ythdf2 promoted PASMC proliferation and PH by paradoxically stabilizing Myadm mRNA in an m6A-dependent manner. Loss of Ythdf2 decreased the expression of Myadm in PASMCs and pulmonary arteries, both in vitro and in vivo. Additionally, silencing Myadm inhibited the Ythdf2-dependent hyperproliferation of PASMCs by upregulating the cell cycle kinase inhibitor p21. CONCLUSIONS: We have identified a novel mechanism where the increased expression of Ythdf2 stimulates PH-PASMC proliferation through an m6A/Myadm/p21 pathway. Strategies targeting Ythdf2 in PASMCs might be useful additions to the therapeutic approach to PH.


Subject(s)
Cell Proliferation , Hypertension, Pulmonary , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Pulmonary Artery , RNA-Binding Proteins , Vascular Remodeling , Animals , Humans , Male , Mice , Cells, Cultured , Disease Models, Animal , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/genetics , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Pulmonary Artery/metabolism , RNA Stability , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Vascular Remodeling/physiology , Vascular Remodeling/genetics
17.
BMC Med ; 22(1): 226, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840198

ABSTRACT

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.


Subject(s)
Autistic Disorder , Brain , Cognition , Problem Behavior , Humans , Female , Male , Child , Brain/growth & development , Adolescent , Cognition/physiology , Family Conflict , Mothers , Adult , Pregnancy , Young Adult , Pregnancy in Adolescence , Sex Factors
18.
J Int Med Res ; 52(6): 3000605241259442, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38867540

ABSTRACT

OBJECTIVE: To investigate the association between driving pressure (ΔP) and 90-day mortality in patients following lung transplantation (LTx) in patients who developed primary graft dysfunction (PGD). METHODS: This prospective, observational study involved consecutive patients who, following LTx, were admitted to our intensive care unit (ICU) from January 2022 to January 2023. Patients were separated into two groups according to ΔP at time of admission (i.e., low, ≤15 cmH2O or high, >15 cmH2O). Postoperative outcomes were compared between groups. RESULTS: In total, 104 patients were involved in the study, and of these, 69 were included in the low ΔP group and 35 in the high ΔP group. Kaplan-Meier analysis of 90-day mortality showed a statistically significant difference between groups with survival better in the low ΔP group compared with the high ΔP group. According to Cox proportional regression model, the variables independently associated with 90-day mortality were ΔP and pneumonia. Significantly more patients in the high ΔP group than the low ΔP group had PGD grade 3 (PGD3), pneumonia, required tracheostomy, and had prolonged postoperative extracorporeal membrane oxygenation (ECMO) time, postoperative ventilator time, and ICU stay. CONCLUSIONS: Driving pressure appears to have the ability to predict PGD3 and 90-day mortality of patients following LTx. Further studies are required to confirm our results.


Subject(s)
Lung Transplantation , Humans , Lung Transplantation/mortality , Lung Transplantation/adverse effects , Male , Female , Prospective Studies , Middle Aged , Adult , Primary Graft Dysfunction/mortality , Primary Graft Dysfunction/etiology , Intensive Care Units , Kaplan-Meier Estimate , Postoperative Complications/mortality , Pressure , Extracorporeal Membrane Oxygenation/mortality , Risk Factors
19.
Transpl Immunol ; 85: 102056, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38797337

ABSTRACT

The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a fundamental role in surfactant homeostasis. Most children with ABCA3 gene mutations develop pulmonary interstitial fibrosis leading to the development of interstitial lung disease. Since traditional medicine does not offer effective therapy, the best option is lung transplantations, especially bilateral lung transplantations. We are reporting the case of a successful bilateral lung transplantation in a five-year-old child with pulmonary interstitial fibrosis caused by ABCA3 gene mutations. This successful transplantation enabled the patient to get rid of chronic cough and tachypnea.


Subject(s)
ATP-Binding Cassette Transporters , Lung Transplantation , Mutation , Humans , ATP-Binding Cassette Transporters/genetics , Child, Preschool , Male , Lung Diseases, Interstitial/genetics , Lung Diseases, Interstitial/surgery , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/surgery , Treatment Outcome
20.
Chem Phys Lipids ; 262: 105405, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38795837

ABSTRACT

At present, consumers increasingly favored the natural food preservatives with fewer side-effects on health. The green tea catechins and black tea theaflavins attracted considerable interest, and their antibacterial effects were extensively reported in the literature. Epicatechin (EC), a green tea catechin without a gallate moiety, showed no bactericidal activity, whereas the theaflavin (TF), also lacking a gallate moiety, exhibited potent bactericidal activity, and the antibacterial effects of green tea catechins and black tea theaflavins were closely correlated with their abilities to disrupt the bacterial cell membrane. In our present study, the mechanisms of membrane interaction modes and behaviors of TF and EC were explored by molecular dynamics simulations. It was demonstrated that TF exhibited markedly stronger affinity for the POPG bilayer compared to EC. Additionally, the hydrophobic interactions of tropolone/catechol rings with the acyl chain part could significantly contribute to the penetration of TF into the POPG bilayer. It was also found that the resorcinol/pyran rings were the key functional groups in TF for forming hydrogen bonds with the POPG bilayer. We believed that the findings from our current study could offer useful insights to better understand the stronger antibacterial effects of TF compared to EC.


Subject(s)
Biflavonoids , Catechin , Lipid Bilayers , Molecular Dynamics Simulation , Catechin/chemistry , Catechin/metabolism , Catechin/analogs & derivatives , Catechin/pharmacology , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Biflavonoids/chemistry , Biflavonoids/metabolism , Biflavonoids/pharmacology , Hydrogen Bonding
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