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1.
Article in English | MEDLINE | ID: mdl-39352683

ABSTRACT

The disruption of lipid droplet function is associated with the pathogenesis of various diseases. Clarifying the response behavior of lipid droplets to the microenvironment at the cellular level is of great significance. Plant lipids not only exist in phospholipids in cell membranes, but also in aromatic essential oils. Monitoring the level of lipid droplets in plant cells using fluorescent probes provides a simple method for screening lipid-rich varieties. We synthesized a polarity-viscosity responsive coumarin fluorescent probe, Cou-CN, which achieved sensitive detection of polarity and viscosity in dilute solution environments by constructing this simple probe with ICT and TICT properties and verifying it using Gaussian computational simulation. Cou-CN exhibited good lipid droplet illumination effects in HepG2 cells with a correlation coefficient of 0.92 compared to the commercial lipid droplet dye BODIPY. Additionally, co-staining the probe with the lipophilic commercial dye Nile Red in tobacco root stem seedling cells resulted in a high correlation coefficient of 0.9.

2.
Sci Adv ; 10(40): eado5560, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39365865

ABSTRACT

A broad spectrum of electromagnetic waves has been explored for wireless neuromodulation. Transcranial magnetic stimulation, with long wavelengths, cannot provide submillimeter spatial resolution. Visible light, with its short wavelengths, suffers from strong scattering in the deep tissue. Microwaves have centimeter-scale penetration depth and have been shown to reversibly inhibit neuronal activity. Yet, microwaves alone do not provide sufficient spatial precision to modulate target neurons without affecting surrounding tissues. Here, we report a split-ring resonator (SRR) that generates an enhanced microwave field at its gap with submillimeter spatial precision. With the SRR, microwaves at dosages below the safe exposure limit are shown to inhibit the firing of neurons within 1 mm of the SRR gap site. The microwave SRR reduced seizure activity at a low dose in both in vitro and in vivo models of epilepsy. This microwave dosage is confirmed to be biosafe via histological and biochemical assessment of brain tissue.


Subject(s)
Microwaves , Wireless Technology , Wireless Technology/instrumentation , Animals , Neurons/physiology , Epilepsy/therapy , Rats , Mice , Brain/physiology , Humans
3.
World J Gastrointest Oncol ; 16(9): 3932-3954, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39350988

ABSTRACT

BACKGROUND: Cancer is one of the most serious threats to human health worldwide. Conventional treatments such as surgery and chemotherapy are associated with some drawbacks. In recent years, traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians, and has become an indispensable part of the comprehensive treatment for gastric cancer. AIM: To investigate the mechanism of Xiaojianzhong decoction (XJZ) in the treatment of gastric cancer (GC) by utilizing network pharmacology and experimental validation, so as to provide a theoretical basis for later experimental research. METHODS: We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics. Subsequently, we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8, apoptosis, cell cycle, and clone formation assays. Additionally, we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins. RESULTS: XJZ mainly regulates IL6, PTGS2, CCL2, MMP9, MMP2, HMOX1, and other target genes and pathways in cancer to treat GC. The inhibition of cell viability, the increase of apoptosis, the blockage of the cell cycle at the G0/G1 phase, and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment. In addition, XJZ induced a decrease in the mRNA expression of IL6, PTGS2, MMP9, MMP2, and CCL2, and an increase in the mRNA expression of HOMX1. XJZ significantly inhibited the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein. CONCLUSION: XJZ exerts therapeutic effects against GC through multiple components, multiple targets, and multiple pathways. Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

4.
Oncol Lett ; 28(6): 557, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39355785

ABSTRACT

The present study describes the case of a 71-year-old male patient that presented with generalized lymphadenopathy and a pelvic mass, but no signs of bone and visceral metastasis. Their total prostate-specific antigen level was >100 ng/ml. A biopsy of the pelvic mass, situated near the left iliac vessels, confirmed the existence of an adenocarcinoma originating from the prostate and a subsequent prostate biopsy indicated a Gleason score of 4+5. Endocrine treatment with bicalutamide and goserelin (androgen deprivation therapy) resulted in only a partial response of the left iliac metastatic lesions to the treatment. The subsequent treatment plan of androgen deprivation therapy and abiraterone plus docetaxel did not change the progression of the disease. The patient finally developed inferior vena cava syndrome. Subsequently, the patient declined both a re-biopsy of the prostate and enlarged cervical lymph nodes, and interventions by a vascular surgeon. To the best of our knowledge, the present study is the first documented case of a natural progression of metastatic prostate cancer with inferior vena cava syndrome.

5.
Int J Public Health ; 69: 1607640, 2024.
Article in English | MEDLINE | ID: mdl-39386997

ABSTRACT

Objectives: We aim to investigate the associations between lifestyle, ambient air pollution with crucial outcomes in the progression of adult asthma, including asthma new-onset and asthma hospitalisation. Methods: 176,800 participants were included to assess the prospective association between baseline risk exposures and the subsequent asthma onset, 17,387 participants were used to evaluate asthma hospitalisation. Cox regression models were employed to examine the associations. Results: In terms of lifestyle factors, the HRs (95% CIs) of the least healthy lifestyle categories for asthma incidence and hospitalization were 1.099 (1.017-1.187) and 1.064 (1.008-1.123), respectively. For pollutants, PM2.5, especially the traffic-related PM2.5 component, was consistently recognized as a significant risk factor for asthma onset (HR = 1.064, 95% CI: 1.034-1.094) and hospitalisation (HR = 1.031, 95% CI: 1.010-1.052) under various model adjustments. Low socioeconomic status also played a major role in the progression of adult asthma. Conclusion: Our study provides crucial insights into factors influencing the progression of adult asthma. Monitoring and reducing exposure to air pollution, particularly PM2.5, promoting healthier lifestyle, and addressing socioeconomic inequity are important in preventing and managing asthma.


Subject(s)
Air Pollution , Asthma , Disease Progression , Hospitalization , Life Style , Particulate Matter , Humans , Asthma/epidemiology , Asthma/etiology , Male , Female , Air Pollution/adverse effects , Middle Aged , United Kingdom/epidemiology , Adult , Particulate Matter/adverse effects , Particulate Matter/analysis , Hospitalization/statistics & numerical data , Prospective Studies , Risk Factors , Air Pollutants/adverse effects , Air Pollutants/analysis , Environmental Exposure/adverse effects , Aged , Biological Specimen Banks , Incidence , UK Biobank
6.
Redox Biol ; 77: 103373, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39357422

ABSTRACT

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

8.
Anal Methods ; 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39365151

ABSTRACT

Correction for 'Selective fluorescence detection of acetylsalicylic acid, succinic acid and ascorbic acid based on a responsive lanthanide metal fluorescent coordination polymer' by Guo-Ying Chen et al., Anal. Methods, 2024, 16, 4981-4994, https://doi.org/10.1039/d4ay00696h.

9.
Int J Gen Med ; 17: 4465-4474, 2024.
Article in English | MEDLINE | ID: mdl-39372134

ABSTRACT

Purpose: Worldwide, chronic hepatitis B virus (CHB) infection is a public health concern, ultimately leading to liver cirrhosis and hepatocellular carcinoma. Currently, patients with CHB can be treated using polyethylene glycol (PEG)ylated interferon (PEG-IFN) antiviral therapy, which has both immune modulatory and antiviral properties. This study aimed to reveal the mechanism underlying the effect of PEG-IFN therapy, to rationally optimize this therapeutic option. Patients and Methods: Ten patients with CHB who were positive for the hepatitis B virus e antigen (HBeAg) and were receiving PEG-IFN treatment were enrolled. Clinical and virological parameters were monitored during 48 weeks of treatment. In addition, peripheral blood mononuclear cells (PBMCs) were collected from the 10 patients at 0, 24, and 36 weeks. RNA sequencing technology was used to analyze the RNA expression profile in the PBMC samples. Results: Following PEG-IFN treatment, we identified 217 differentially expressed genes (DEGs), most of which were upregulated. Gene ontology enrichment analysis of the DEGs revealed that they were enriched in 29 clusters, mainly associated with "antiviral defense", "innate immunity", "immunity", "defense response to virus", "response to virus", "type I interferon signaling pathway", "negative regulation of viral genome replication", "innate immune response", and "RNA-binding". Conclusion: After PEG-IFN treatment, a certain mRNA expression profile was observed in patients with CHB, providing further mechanistic insights into the antiviral effect of this therapy.

10.
Int Immunopharmacol ; 143(Pt 1): 113193, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39368132

ABSTRACT

BACKGROUND: The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown. PURPOSE: This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms. METHODS: A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/ß-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC. RESULTS: CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/ß-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/ß-catenin pathway. CONCLUSIONS: This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG.

11.
Int J Biol Macromol ; 280(Pt 4): 135811, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39322145

ABSTRACT

Owing to the rapid advancement of in vitro synthetic biology, functional carriers capable of covalently binding target proteins from crude lysates under mild conditions have garnered escalating attention. Herein, a magnetic nanoparticle with affinity/covalent bifunction (MNP@Affi-Cova) was developed for the direct covalent immobilization of the recombinant enzyme of His-tagged birA (r-birA) from crude cell lysates in a single step. This innovative approach is attributed to the presence of chelated Ni2+ ions and epoxy groups on the surface of the beads. The fabricated magnetic nanoparticles were characterized by SEM, FT-IR spectrum, and zeta potential. The application conditions and stability of the MNP@Affi-Cova beads were systematically evaluated. Notably, the MNP@Affi-Cova beads exhibited a covalent capture efficiency of 91.25 µg r-birA/mg beads from a cell lysate supernatant containing 2.62 mg/mL crude protein. The immobilized r-birA exhibited significantly enhanced pH and thermal stability compared to the free counterpart. Additionally, the reusability of the immobilized r-birA on MNP@Affi-Cova demonstrated the retention of 76.1 % of its initial activity over ten cycles. These results suggest that the MNP@Affi-Cova presents considerable potential as a support for the covalent immobilization of recombinant His-tagged enzymes directly from crude lysates, thereby circumventing the labor-intensive purification process typically required before enzyme immobilization.

12.
Trends Biotechnol ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39237385

ABSTRACT

The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration.

13.
Front Psychiatry ; 15: 1440641, 2024.
Article in English | MEDLINE | ID: mdl-39290302

ABSTRACT

Background: Mental health challenges are encountered by frail older adults as the population ages. The extant literature is scant regarding the correlation between depressive symptoms and social participation among frail older adults. Methods: This study is based on an analysis of data from China Health and Retirement Longitudinal Study (CHARLS) participants aged 60 and older who are frail. A frailty index (FI) was developed for the purpose of assessing the frailty level of the participants. Additionally, latent class analysis (LCA) was employed to classify the participants' social engagement patterns in 2015 and 2018. The study used ordered logistic regression to examine the relationship between social participation type and depressive symptoms. We also used Latent Transition Analysis (LTA) methods to explore the impact of changes in social activity types on depressive symptoms after three years of follow-up in 2018. In addition, the response surface analysis (RSM) investigation explored the relationship among FI, depression, and social participation. Results: A total of 4,384 participants completed the baseline survey; three years later, 3,483 were included in the follow-up cohort. The baseline survey indicates that female older adults in rural areas who are single, have lower incomes, shorter sleep durations, and lighter weights exhibited more severe depressive symptoms. Social participation patterns were categorized into five subgroups by LCA. The findings indicate that individuals classified as "board game enthusiasts" (OR, 0.62; 95% CI, 0.47-0.82) and those as "extensive social interaction" (OR,0.67; 95% CI, 0.49-0.90) have a significantly lower likelihood of developing depressive symptoms compared to the "socially isolated" group. We also discovered that "socially isolated" baseline participants who transitioned to the "helpful individual" group after three years had significantly greater depressed symptoms (OR, 1.56; 95% CI, 1.00-2.44). More social activity types and less FI are linked to lower depression in our study. Conclusion: The results of the study emphasize the importance of social participation patterns and the number of social participation types in relation to the severity of depression among frail older adults individuals. This study's findings may provide important insights for addressing depressive symptoms in frail older adults person.

14.
Bioact Mater ; 42: 85-111, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39280582

ABSTRACT

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

15.
bioRxiv ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39282448

ABSTRACT

Retinal degenerative diseases of photoreceptors are a leading cause of blindness with no effective treatment. Retinal prostheses seek to restore sight by stimulating remaining retinal cells. We here present a photoacoustic retinal stimulation technology. We designed a polydimethylsiloxane and carbon-based flexible film that converts near-infrared laser pulses into a localized acoustic field, aiming at high-precision acoustic activation of mechanosensitive retinal cells. This photoacoustic stimulation of wild-type and degenerated ex vivo retinae resulted in robust and localized retinal ganglion cell activation with sub-100-µm resolution in both wild-type and degenerated ex vivo retinae. Our millimeter-size photoacoustic film generated neural activation in vivo along the visual pathway to the superior colliculus, as measured by functional ultrasound imaging when the film was implanted in the rat subretinal space and stimulated by pulsed laser. Biosafety of the film was indicated by absence of short-term adverse effect under optical coherence tomography retinal imaging, while local thermal increase was measured below 1 °C. These findings demonstrate the potential of our photoacoustic stimulation for visual restoration in blind patients with a high spatial precision and a large field of view.

16.
Bioresour Technol ; : 131448, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39244106

ABSTRACT

Gamma-Aminobutyric acid (GABA) is a derivative of L-glutamate, also a precursor for the synthesis of 2-pyrrolidone, which is a monomer of nylon-4. This study achieved a one-step biosynthesis of GABA and 2-pyrrolidone by Halomonas bluephagenesis overexpressing key genes involved in GABA and 2-pyrrolidone synthesis and deleting GABA degradation genes combined with reducing the degradation of 2-pyrrolidone precursor. The resulting H. bluephagenesis strain WLp07 was employed in whole-cell catalysis, producing 357 g/L of GABA and 72 wt% of PHA. Furthermore, a self-flocculating H. bluephagenesis allowed rapid, convenient recycling of the cells, achieving 880 g/L of GABA over three cycles. Shake flask studies showed that engineered H. bluephagenesis harboring ß-alanine CoA transferase was able to synthesized 2-pyrrolidone from GABA. H. bluephagenesis as a chassis of next generation industrial biotechnology (NGIB), demonstrated its diverse ability to produce GABA and 2-pyrrolidone in addition to intracellular PHA.

17.
World J Otorhinolaryngol Head Neck Surg ; 10(3): 165-172, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39233853

ABSTRACT

Objective: The objective of this study was to explore the clinical characteristics and management of sudden hearing loss (HL) during pregnancy, thus better guiding the clinical practice. Methods: The clinical and follow-up data of 17 patients (17 ears) with sudden HL during pregnancy were analyzed retrospectively (the observe group). Twelve nonpregnant female patients (12 ears) with sudden HL of similar clinical characteristics were selected as the control group. The prognosis of the two groups was compared. All the patients were followed up after delivery, and two of them were readmitted to the hospital 1-2 months after delivery. Results: The observe group had better improvement in hearing and a higher response rate compared to the control group. The pure tone hearing and speech recognition rate of patients could still be improved after the readmitted treatment, and the hearing could partially recover spontaneously during follow-up. The laboratory indicators that affect the inflammatory response and coagulation pathway were significantly different between the two groups. Conclusions: The hearing condition of sudden HL during pregnancy is severe, and the prognosis of these patients is better than nonpregnant patients of similar clinical characteristics. Postpartum treatment is still effective, and some patients showed self-healing with time during follow-up. The inflammatory response and coagulation function may affect the hearing of patients through a metabolic pathway.

18.
Front Biosci (Landmark Ed) ; 29(9): 336, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39344310

ABSTRACT

BACKGROUND: Partial bladder outlet obstruction (pBOO) causes deposition of extracellular matrix (ECM), promotes bladder fibrosis, and decreases bladder compliance. METHODS: To investigate the effect of ß-adrenoceptor (ADRB) on the ECM deposition of pBOO rat model and explore its underlying mechanism, human bladder smooth muscle cells (hBSMCs) were exposed to the pathological hydrostatic pressure (100 cm H2O) for 6 h, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were employed. Then the rats of sham operation and pBOO model were treated with vehicle or ADRB agonists for 3 weeks, and the alterations of the bladder were observed via Masson staining and immunohistochemical analysis. RESULTS: 100 cm H2O hydrostatic pressure significantly upregulated the expression of collagen I (COL1), collagen III (COL3) and fibronectin (FN), and downregulated the expression of ADRB2 and ADRB3 of hBSMCs at 6 h. The agonists of ADRB2 and ADRB3, Formoterol and BRL 37344, decreased COL1 and FN expression of hBSMCs under 100 cm H2O for 6 h compared with the cells exposed to hydrostatic pressure only. As the classic downstream pathways of ADRB, the EPAC pathway inhibited COL1 and FN expression of hBSMCs via regulating SMAD3 and SMAD2 activities, respectively. In pBOO rats, Procaterol (ADRB2 agonist), and Mirabegron (ADRB3 agonist) inhibited the formation of collagen and decreased the expression of FN and COL1 in the bladders of pBOO rats. CONCLUSIONS: The bladder fibrosis of pBOO and deposition of hBSMCs ECM under hydrostatic pressure were regulated by ADRB2, and ADRB3 via EPAC/SMAD2/FN and EPAC/SMAD3/COL1 pathways, these findings pave an avenue for effective treatment of pBOO.


Subject(s)
Extracellular Matrix , Fibrosis , Signal Transduction , Urinary Bladder Neck Obstruction , Urinary Bladder , Urinary Bladder Neck Obstruction/metabolism , Urinary Bladder Neck Obstruction/pathology , Animals , Extracellular Matrix/metabolism , Urinary Bladder/metabolism , Urinary Bladder/pathology , Urinary Bladder/drug effects , Rats , Humans , Rats, Sprague-Dawley , Receptors, Adrenergic, beta/metabolism , Myocytes, Smooth Muscle/metabolism , Thiazoles/pharmacology , Formoterol Fumarate/pharmacology , Acetanilides/pharmacology , Ethanolamines/pharmacology , Ethanolamines/metabolism , Fibronectins/metabolism , Fibronectins/genetics , Female , Adrenergic beta-Agonists/pharmacology
19.
Anal Methods ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39344492

ABSTRACT

Lipid droplets (LDs) and lysosomes were dynamic organelles present in most eukaryotic cells that were interconnected and worked closely together to ensure the smooth physiological activities of organisms. The interaction between lipid droplets and lysosomes was thought to play a role in the development of certain diseases. In this paper we designed and synthesised a lipid droplet lysosomal probe. The Nap-Lyso-Ph-OH probe was constructed according to the ICT mechanism and exhibited sensitivity to both polarity and viscosity. The probe exhibited low cytotoxicity, a large Stokes shift, excellent selectivity and photostability. The probe was successfully used for labelling and imaging of lipid droplets and lysosomes in cells and zebrafish. Interestingly, we used tobacco seedling cells to explore the ability of Nap-Lyso-Ph-OH for imaging lipid droplet labelling in plant cells.

20.
Medicina (Kaunas) ; 60(9)2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39336451

ABSTRACT

Background and Objectives: Microvascular invasion (MVI) significantly impacts recurrence and survival rates after liver resection in hepatocellular carcinoma (HCC). Pre-operative prediction of MVI is crucial in determining the treatment strategy. This study aims to develop a nomogram model to predict the probability of MVI based on clinical features in HCC patients. Materials and Methods: A total of 489 patients with a pathological diagnosis of HCC were enrolled from our hospital. Those registered from 2012-2015 formed the derivation cohort, and those from 2016-2019 formed the validation cohort for pre-operative prediction of MVI. A nomogram model for prediction was created using a regression model, with risk factors derived from clinical and tumor-related features before surgery. Results: Using the nomogram model to predict the odds ratio of MVI before hepatectomy, the AFP, platelet count, GOT/GPT ratio, albumin-alkaline phosphatase ratio, ALBI score, and GNRI were identified as significant variables for predicting MVI. The Youden index scores for each risk variable were 0.287, 0.276, 0.196, 0.185, 0.115, and 0.112, respectively, for the AFP, platelet count, GOT/GPT ratio, AAR, ALBI, and GNRI. The maximum value of the total nomogram scores was 220. An increase in the number of nomogram points indicated a higher probability of MVI occurrence. The accuracy rates ranged from 55.9% to 64.4%, and precision rates ranged from 54.3% to 68.2%. Overall survival rates were 97.6%, 83.4%, and 73.9% for MVI(-) and 80.0%, 71.8%, and 41.2% for MVI(+) (p < 0.001). The prognostic effects of MVI(+) on tumor-free survival and overall survival were poor in both the derivation and validation cohorts. Conclusions: Our nomogram model, which integrates clinical factors, showed reliable calibration for predicting MVI and provides a useful tool enabling surgeons to estimate the probability of MVI before resection. Consequently, surgical strategies and post-operative care programs can be adapted to improve the prognosis of HCC patients where possible.


Subject(s)
Carcinoma, Hepatocellular , Hepatectomy , Liver Neoplasms , Nomograms , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Female , Hepatectomy/methods , Middle Aged , Aged , Neoplasm Invasiveness , Microvessels/pathology , Adult , Retrospective Studies , Risk Factors
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