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1.
J Biol Chem ; : 107516, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960036

ABSTRACT

Focal segmental glomerulosclerosis (FSGS), a common cause of primary glomerulonephritis, has a poor prognosis and is pathologically featured by tubulointerstitial injury. Thrombospondin-1 (TSP-1) is an extracellular matrix protein that acts in combination with different receptors in the kidney. Here, we analyzed the tubular expression of TSP-1 and its receptor integrin ß3 (ITGB3) in FSGS. Previously the renal interstitial chip analysis of FSGS patients with tubular interstitial injury showed that the expressions of TSP-1 and ITGB3 were up-regulated. We found that the level of TSP-1 and ITGB3 increased in the tubular cells of FSGS patients. The serum level of TSP-1 increased and was correlated to the degree of tubulointerstitial lesions in FSGS patients. THBS1/ITGB3 signaling induced renal tubular injury in HK-2 cells exposure to BSA and the ADR-induced nephropathy model. THBS1 knockout ameliorated tubular injury and renal fibrosis in ADR-treated mice. THBS1 knockdown decreased the expression of KIM-1 and caspase 3 in the HK-2 cells treated with BSA, while THBS1 overexpression could induce tubular injury. In vivo, we identified cyclo-RGDfK as an agent to block the binding of TSP-1 to ITGB3. Cyclo-RGDfK treatment could alleviate ADR-induced renal tubular injury and interstitial fibrosis in mice. Moreover, TSP-1 and ITGB3 were colocalized in tubular cells of FSGS patients and ADR-treated mice. Taken together, our data showed that TSP-1/ITGB3 signaling contributed to the development of renal tubulointerstitial injury in FSGS, potentially identifying a new therapeutic target for FSGS.

2.
Front Neurol ; 15: 1396673, 2024.
Article in English | MEDLINE | ID: mdl-38952466

ABSTRACT

Introduction: The online study investigated the sleep, psychological conditions, and risk factors during the wave of transmission of COVID-19 since December 7, 2022. Methods: We distributed questionnaires through networking mediums to residents to gather information about COVID-19 infection, sleep, and mental status. Results: During the extraordinary period in China, 91.9% of 1094 participants claimed to be infected with COVID-19, 36.8% reported poor sleep quality, 75.9% reported anxiety, and 65.5% reported depression. In retrospect, people have experienced lower sleep quality, longer sleep latency, enhanced rising time, and decreased sleep efficiency after the infection wave. After adjusting confounding factors, the elderly, women, urban residents, people with comorbidity, anxiety, depression, stress state, and COVID-19 infection have high risks for sleep disorders during the period. Discussion: The survey indicates that sleep disturbance caused by COVID-19 involves multiple dimensions, such as physiology, psychology, and society. The COVID-19 infection-related sleep problem should be taken seriously. Apart from conventional treatment, psychological issues of insomnia can not be ignored.

3.
J Cell Mol Med ; 28(13): e18508, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38953556

ABSTRACT

Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.


Subject(s)
Antioxidants , Osteoporosis , Oxidative Stress , Reactive Oxygen Species , Tendinopathy , Humans , Osteoporosis/metabolism , Osteoporosis/therapy , Osteoporosis/drug therapy , Antioxidants/therapeutic use , Tendinopathy/metabolism , Tendinopathy/therapy , Tendinopathy/pathology , Reactive Oxygen Species/metabolism , Animals
4.
Aging (Albany NY) ; 162024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950328

ABSTRACT

The current study aims to develop a new technique for the precise identification of Escherichia coli strains, utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with a long short-term memory (LSTM) neural network. A total of 48 Escherichia coli strains were isolated and cultured on tryptic soy agar medium for 24 hours for the generation of MALDI-TOF MS spectra. Eight hundred MALDI-TOF MS spectra were obtained per strain, resulting in a database of 38,400 spectra. Fifty percent of the data was utilized for LSTM neural network training, with fine-tuned parameters for strain-level identification. The other half served as the test set to assess model performance. Traditional PCA dimension reduction of MALDI-TOF MS spectra indicated 47 out of 48 strains to be unclassifiable. In contrast, the LSTM neural network demonstrated remarkable efficacy. After 20 training epochs, the model achieved a loss value of 0.0524, an accuracy of 0.999, a precision of 0.985, and a recall of 0.982. When tested on the unseen data, the model attained an overall accuracy of 92.24%. The integration of MALDI-TOF MS and LSTM neural network markedly enhances the identification of Escherichia coli strains. This innovative approach offers an effective and accurate tool for MALDI-TOF MS-based strain-level identification, thus expanding the analytical capabilities of microbial diagnostics.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 646-651, 2024 Jun 15.
Article in Chinese | MEDLINE | ID: mdl-38926383

ABSTRACT

Neonatal necrotizing enterocolitis (NEC) is the most common inflammatory intestinal disease in preterm infants, with a high incidence and mortality rate. The etiology and mechanisms of NEC are not yet fully understood, and multiple factors contribute to its occurrence and development. Recent studies have found that anemia is a risk factor for NEC in neonates, but the specific pathogenic mechanism remains unclear. This article reviews recent research on the relationship between anemia and NEC, providing a reference for further understanding the impact of anemia on intestinal injury and its association with NEC.


Subject(s)
Anemia , Enterocolitis, Necrotizing , Enterocolitis, Necrotizing/etiology , Humans , Infant, Newborn , Anemia/etiology
6.
Polymers (Basel) ; 16(12)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38931991

ABSTRACT

Different chemical treatment methods were employed to modify the surface of cotton stalk fibers, which were then utilized as fillers in composite materials. These treated fibers were incorporated into polylactic acid/polypropylene melt blends using the melt blending technique. Results indicated that increasing the surface roughness of cotton stalk fibers could enhance the overall mechanical properties of the composite materials, albeit potentially leading to poor fiber-matrix compatibility. Conversely, a smooth fiber surface was found to improve compatibility with polylactic acid, while Si-O-C silane coating increased fiber regularity and interfacial interaction with the matrix, thereby enhancing heat resistance. The mechanical properties and thermal stability of the composite materials made from alkali/silane-treated fibers exhibited the most significant improvement. Furthermore, better dispersion of fibers in the matrix and more regular fiber orientation were conducive to increasing the overall crystallinity of the composite materials. However, such fiber distribution was not favorable for enhancing impact resistance, although this drawback could be mitigated by increasing the surface roughness of the reinforcing fibers.

7.
Immun Inflamm Dis ; 12(6): e1327, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923408

ABSTRACT

BACKGROUND: Systemic immune-inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle-aged and elderly males. MATERIALS AND METHODS: Analysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests. RESULTS: Among 3359 participants, those with elevated SII displayed higher total prostate-specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (ß: 0.22, 95% confidence intervals [CI] 0.05-0.38), a 2.22% decline in f/t PSA ratio (ß: -2.22, 95% CI -3.20 to -1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13-2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (ß: 0.55, 95% CI 0.19-0.90), 4.39% reduced f/t PSA ratio (ß: -4.39, 95% CI -6.50 to -2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32-5.46) compared to those in the bottom quartile. CONCLUSION: Systemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle-aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.


Subject(s)
Inflammation , Nutrition Surveys , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/immunology , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Middle Aged , Aged , Inflammation/blood , Inflammation/immunology , Inflammation/epidemiology , United States/epidemiology , Prostate-Specific Antigen/blood , Risk Factors
8.
Cancer Med ; 13(11): e7383, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38864483

ABSTRACT

OBJECTIVE: The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC. METHODS: Thirty-five patients with ground-glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA-Seq were subsequently analyzed. RESULTS: The findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co-mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD. CONCLUSIONS: Our findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.


Subject(s)
Adenocarcinoma of Lung , Exome Sequencing , Lung Neoplasms , Mutation , Neoplasm Invasiveness , Humans , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Female , Middle Aged , Aged , Disease Progression , Gene Expression Regulation, Neoplastic , Transcriptome , Gene Expression Profiling , Adenocarcinoma in Situ/genetics , Adenocarcinoma in Situ/pathology , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Biomarkers, Tumor/genetics
9.
Anesth Analg ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38870069

ABSTRACT

BACKGROUND: Increasing the temperature of intrathecal local anesthetics has been shown to increase the speed of onset and block height of spinal anesthesia. However, how this influences dose requirement has not been fully quantified. The aim of this study was to determine and compare the effective dose for anesthesia for cesarean delivery in 50% of patients (ED50) of intrathecal bupivacaine given at temperatures of 37 °C (body temperature) or 24 °C (room temperature). METHODS: Eighty healthy parturients having elective cesarean delivery under combined spinal-epidural anesthesia were randomly assigned to receive intrathecal hyperbaric bupivacaine stored at 37 °C (body temperature group) or 24 °C (room temperature group). The first subject in each group received a bupivacaine dose of 10 mg. The dose for each subsequent subject in each group was varied with an increment or decrement of 1 mg based on the response (effective or noneffective) of the previous subject. Patients for whom the dose was noneffective received epidural supplementation after data collection with lidocaine 2% as required until anesthesia was sufficient for surgery. Values for ED50 were calculated using modified up-down sequential analysis with probit analysis applied as a backup sensitivity analysis. These values were compared and the relative mean potency was calculated. RESULTS: The ED50 (mean [95% confidence interval, CI]) of intrathecal hyperbaric bupivacaine was lower in the body temperature group (6.7 [5.7-7.6] mg) compared with the room temperature group (8.1 [7.7-8.6] mg) (P < .05). The relative potency ratio for intrathecal bupivacaine for the room temperature group versus the body temperature group was 0.84 (95% CI, 0.77-0.93). CONCLUSIONS: Warming hyperbaric bupivacaine to body temperature reduced the dose requirement for spinal anesthesia for cesarean delivery by approximately 16% (95% CI, 7%-23%).

10.
Neuroscience ; 551: 237-245, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838979

ABSTRACT

The ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC) have been found to play important roles in negative emotion processing. However, the specific time window of their involvement remains unknown. This study addressed this issue in three experiments using single-pulse transcranial magnetic stimulation (TMS). We found that TMS applied over the VLPFC at 400 ms after negative emotional exposure significantly enhanced negative feelings compared to the vertex condition. Furthermore, TMS applied over the DLPFC at both 0 ms and 600 ms after negative emotional exposure also resulted in deteriorated negative feelings. These findings provide potential evidence for the VLPFC-dependent semantic processing (∼400 ms) and the DLPFC-dependent attentional and cognitive control (∼0/600 ms) in negative emotion processing. The asynchronous involvement of these frontal cortices not only deepens our understanding of the neural mechanisms underlying negative emotion processing but also provides valuable temporal parameters for neurostimulation therapy targeting patients with mood disorders.

11.
World J Emerg Med ; 15(3): 181-189, 2024.
Article in English | MEDLINE | ID: mdl-38855366

ABSTRACT

BACKGROUND: This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium (GIK) therapy on clinical outcomes in acute coronary syndrome (ACS) patients receiving reperfusion therapy. METHODS: We searched the PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library databases from inception to April 26, 2022, for randomized controlled trials (RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy. The primary endpoint was major adverse cardiovascular events (MACEs). RESULTS: Eleven RCTs with 884 patients were ultimately included. Compared with placebos, high-dose GIK markedly reduced MACEs (risk ratio [RR] 0.57, 95% confidence interval [95% CI]: 0.35 to 0.94, P=0.03) and the risk of heart failure (RR 0.48, 95% CI: 0.25 to 0.95, P=0.04) and improved the left ventricular ejection fraction (LVEF) (mean difference [MD] 2.12, 95% CI: 0.40 to 3.92, P=0.02) at 6 months. However, no difference was observed in all-cause mortality at 30 d or 1 year. Additionally, high-dose GIK was significantly associated with increased incidences of phlebitis (RR 4.78, 95% CI: 1.36 to 16.76, P=0.01), hyperglycemia (RR 9.06, 95% CI: 1.74 to 47.29, P=0.009) and hypoglycemia (RR 6.50, 95% CI: 1.28 to 33.01, P=0.02) but not reinfarction, hyperkalemia or secondary reperfusion. In terms of oxidative stress-lowering function, high-dose GIK markedly reduced superoxide dismutase (SOD) activity but not glutathione peroxidase (GSH-Px) or catalase (CAT) activity. CONCLUSION: Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK. Moreover, with a higher incidence of complications such as phlebitis, hyperglycemia, and hypoglycemia. Furthermore, there were no observed survival benefits associated with high-dose GIK. More trials with long-term follow-up are still needed.

12.
Front Pharmacol ; 15: 1409506, 2024.
Article in English | MEDLINE | ID: mdl-38855749

ABSTRACT

Introduction: Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms. Methods: We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity. Results: Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models. Conclusion: Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.

13.
Carbohydr Polym ; 340: 122301, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38858023

ABSTRACT

Chemical modification is a reliable and efficient strategy for designing cellulose-based functional materials. Herein, porous quaternized cellulose beads (QCBs) as cationic superabsorbent were fabricated by homogeneous in-situ chemical grafting cellulose molecular chains with glycidyl trimethylammonium chloride (GTAC) in tetraethylammonium hydroxide (TEAOH)/urea aqueous solution followed by acetic acid induced regeneration. The influence of GTAC dosage on the physicochemical-structural properties of cationic QCBs was deeply investigated. Results revealed that cotton liner could well-dissolved in TEAOH/urea aqueous solution, leading to a homogeneous and efficient quaternization medium for cellulose, thereby giving the high DS and positive charge density for quaternized cellulose. NMR results demonstrated the main substitution of GTAC groups at 2-OH and 6-OH positions of the cellulose chains during quaternization reaction. With increasing GTAC dosage, the network skeleton of QCBs gradually transformed from thick fibrils to thin aggregates, as well as enhanced pore volumes and hydrophilicity. Accordingly, QCBs-1.5 with high pore volume (99.70 cm3/g) exhibited excellent absorption capacity and efficiency, absorbing 122.32 g of water and 0.45 g of moisture per gram of the beads in 20 min. This work not only offers a simple strategy for the homogeneous quaternization modification of cellulose, but also provides a porous cellulose-based cationic superabsorbent material.

14.
Talanta ; 277: 126421, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38876032

ABSTRACT

A sensitive and robust multiclass analytical method was established to simultaneously determine 55 antibiotics in aquatic products through liquid chromatography-tandem mass spectrometry. A simple one-step purification process was successfully developed, which combined post-acidic acetonitrile extraction directly by an enhanced matrix removal cartridge. This approach eliminated the need for solvent transition. The established method for 55 antibiotics achieved an excellent linear relationship with R2 values ≥ 0.9921 in the range of 0.05-200 µg/L. The quantitation limits ranged within 0.04-5.0 µg/kg. Satisfactory recoveries (76.2%-99.7 %) were achieved with the relative standard deviations below 13.9 %. Furthermore, the antibiotic residues in aquatic products were analyzed, and the health and antibiotic resistance risk assessments were conducted. Although the health risks of target antibiotics were acceptable, a resistance risk was observed. Therefore, monitoring antibiotic residue levels in aquatic products requires considerable attention and further research to ensure the quality of marine products and consumer safety.

15.
Adv Mater ; : e2313059, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871341

ABSTRACT

Artificial moiré superlattices created by stacking 2D crystals have emerged as a powerful platform with unprecedented material-engineering capabilities. While moiré superlattices are reported to host a number of novel quantum states, their potential for spintronic applications remains largely unexplored. Here, the effective manipulation of spin-orbit torque (SOT) is demonstrated using moiré superlattices in ferromagnetic devices comprised of twisted WS2/WS2 homobilayer (t-WS2) and CoFe/Pt thin films by altering twisting angle (θ) and gate voltage. Notably, a substantial enhancement of up to 44.5% is observed in SOT conductivity at θ ≈ 8.3°. Furthermore, compared to the WS2 monolayer and untwisted WS2/WS2 bilayers, the moiré superlattices in t-WS2 enable a greater gate-voltage tunability of SOT conductivity. These results are related to the generation of the interfacial moiré magnetic field by the real-space Berry phase in moiré superlattices, which modulates the absorption of the spin-Hall current arising from Pt through the magnetic proximity effect. This study highlights the moiré physics as a new building block for designing enhanced spintronic devices.

16.
Pestic Biochem Physiol ; 202: 105932, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38879298

ABSTRACT

The marine antifungal peptide epinecidin-1 (EPI) have been shown to inhibit Botrytis cinerea growth, while the molecular mechanism have not been explored based on omics technology. This study aimed to investigate the molecular mechanism of EPI against B. cinerea by transcriptome technology. Our findings indicated that a total of 1671 differentially expressed genes (DEGs) were detected in the mycelium of B. cinerea treated with 12.5 µmol/L EPI for 3 h, including 773 up-regulated genes and 898 down-regulated genes. Cluster analysis showed that DEGs (including steroid biosynthesis, (unsaturated) fatty acid biosynthesis) related to cell membrane metabolism were significantly down-regulated, and almost all DEGs involved in DNA replication were significantly inhibited. In addition, it also induced the activation of stress-related pathways, such as the antioxidant system, ATP-binding cassette transporter (ABC) and MAPK signaling pathways, and interfered with the tricarboxylic acid (TCA) cycle and oxidative phosphorylation pathways related to mitochondrial function. The decrease of mitochondrial related enzyme activities (succinate dehydrogenase, malate dehydrogenase and adenosine triphosphatase), the decrease of mitochondrial membrane potential and the increase content of hydrogen peroxide further confirmed that EPI treatment may lead to mitochondrial dysfunction and oxidative stress. Based on this, we speculated that EPI may impede the growth of B. cinerea through its influence on gene expression, and may lead to mitochondrial dysfunction and oxidative stress.


Subject(s)
Antifungal Agents , Antimicrobial Cationic Peptides , Botrytis , Transcriptome , Transcriptome/physiology , Antifungal Agents/metabolism , Antimicrobial Cationic Peptides/toxicity , Botrytis/drug effects , Botrytis/physiology , Real-Time Polymerase Chain Reaction , Hydrogen Peroxide , Gene Expression , ATP-Binding Cassette Transporters/metabolism , Mitogen-Activated Protein Kinase Kinases , Mitochondria , Oxidative Stress
17.
Cell Death Discov ; 10(1): 289, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879653

ABSTRACT

Peroxisomal L-bifunctional enzyme (EHHADH) plays a role in the classic peroxisomal fatty acid ß-oxidation pathway; however, the relationship between EHHADH expression and diabetic kidney disease has not been well understood. Here, we found that endogenous EHHADH levels were strongly correlated with the progression and severity of diabetic nephropathy in T2D patients. EHHADH knockout mice exhibited worsened renal tubular injury in diabetic mice. Furthermore, EHHADH is a modulator of pexophagy. In renal tubular epithelial cells (RTECs) in vitro, the knockdown of EHHADH induced a dramatic loss of peroxisomes. The loss of peroxisomes in EHHADH-deficient RTECs was restored by either an autophagic inhibitor 3-methyladenine or bafilomycin A1 both in vitro and in vivo. NBR1 was required for pexophagy in EHHADH-knockdown cells, where the level of reactive oxygen species (ROS) was increased, while inhibition of ROS blocked pexophagy. In summary, our findings revealed EHHADH deficiency accelerated renal injury in DKD as a modulator of pexophagy.

18.
Int J Hyperthermia ; 41(1): 2365388, 2024.
Article in English | MEDLINE | ID: mdl-38880505

ABSTRACT

OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.


Subject(s)
High-Intensity Focused Ultrasound Ablation , Leiomyoma , Humans , Female , Leiomyoma/therapy , Leiomyoma/diagnostic imaging , Adult , Risk Factors , High-Intensity Focused Ultrasound Ablation/methods , Middle Aged , Retrospective Studies , Uterine Neoplasms/therapy , Uterine Neoplasms/diagnostic imaging , Treatment Outcome
19.
Biomed Pharmacother ; 177: 116976, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38906022

ABSTRACT

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

20.
BMC Urol ; 24(1): 131, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909202

ABSTRACT

OBJECTIVE: The incidence of recurrent hernia after radical resection of prostate cancer is high, so this article discusses the incidence and risk factors of inguinal hernia after radical resection of prostate cancer. METHODS: This case control study was conducted in The First People's Hospital of Huzhou clinical data of 251 cases underwent radical resection of prostate cancer in this hospital from March 2019 to May 2021 were retrospectively analyzed. According to the occurrence of inguinal hernia, the subjects were divided into study group and control group, and the clinical data of each group were statistically analyzed, Multivariate Logistic analysis was performed to find independent influencing factors for predicting the occurrence of inguinal hernia. The Kaplan-Meier survival curve was drawn according to the occurrence and time of inguinal hernia. RESULTS: The overall incidence of inguinal hernia after prostate cancer surgery was 14.7% (37/251), and the mean time was 8.58 ± 4.12 months. The average time of inguinal hernia in patients who received lymph node dissection was 7.61 ± 4.05 (month), and that in patients who did not receive lymph node dissection was 9.16 ± 4.15 (month), and there was no significant difference between them (P > 0.05). There were no statistically significant differences in the incidence of inguinal hernia with age, BMI, hypertension, diabetes, PSA, previous abdominal operations and operative approach (P > 0.05), but there were statistically significant differences with surgical method and pelvic lymph node dissection (P < 0.05). The incidence of pelvic lymph node dissection in the inguinal hernia group was 24.3% (14/57), which was significantly higher than that in the control group 11.8% (23/194). Logistic regression analysis showed that pelvic lymph node dissection was a risk factor for inguinal hernia after prostate cancer surgery (OR = 0.413, 95%Cl: 0.196-0.869, P = 0.02). Kaplan-Meier survival curve showed that the rate of inguinal hernia in the group receiving pelvic lymph node dissection was significantly higher than that in the control group (P < 0.05). CONCLUSION: Pelvic lymph node dissection is a risk factor for inguinal hernia after radical resection of prostate cancer.


Subject(s)
Hernia, Inguinal , Postoperative Complications , Prostatectomy , Prostatic Neoplasms , Humans , Male , Hernia, Inguinal/epidemiology , Hernia, Inguinal/surgery , Prostatic Neoplasms/surgery , Risk Factors , Incidence , Case-Control Studies , Aged , Middle Aged , Prostatectomy/adverse effects , Prostatectomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Lymph Node Excision , Correlation of Data
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