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1.
Mol Med ; 30(1): 163, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39333897

ABSTRACT

BACKGROUND: Fibrosis cataract occurs in patients receiving cataract extraction. Still, no medication that can cure the disease exists in clinical. This study aims to investigate the effects and mechanisms of Entrectinib on fibrotic cataract in vitro and in vivo. METHODS: The human lens cells line SRA 01/04 and C57BL/6J mice were applied in the study. Entrectinib was used in animals and cells. Cataract severity was assessed by slit lamp and Hematoxylin and Eosin staining. Expression of alpha-smooth muscle actin, fibronectin, and collagen I were examined by real-time quantitative PCR, western blotting, and immunofluorescence. Cell proliferation was evaluated by Cell Counting Kit-8. Cell migration was measured by wound healing and transwell assays. Molecular docking, Drug Affinity Responsive Target Stability, and Cellular Thermal Shift Assay were applied to seek and certify the target of Entrectinib treating fibrosis cataract. RESULTS: Entrectinib can ameliorate fibrotic cataract in vitro and in vivo. At the RNA and the protein levels, the expression of alpha-smooth muscle actin, collagen I, and fibronectin can be downgraded by Entrectinib, while E-cadherin can be upregulated. The migration and proliferation of cells were inhibited by Entrectinib. Mechanistically, Entrectinib obstructs TGFß2/Smad and TGFß2/non-Smad signaling pathways to hinder the fibrosis cataract by targeting PYK2 protein. CONCLUSIONS: Targeting with PYK2, Entrectinib can block TGF-ß2/Smad and TGF-ß2/non-Smad signaling pathways, lessen the activation of EMT, and alleviate fibrosis cataract. Entrectinib may be a potential treatment for fibrosis cataract in clinic.


Subject(s)
Cataract , Focal Adhesion Kinase 2 , Signal Transduction , Transforming Growth Factor beta2 , Animals , Mice , Signal Transduction/drug effects , Cataract/etiology , Cataract/drug therapy , Cataract/metabolism , Cataract/pathology , Humans , Transforming Growth Factor beta2/metabolism , Focal Adhesion Kinase 2/metabolism , Cell Proliferation/drug effects , Disease Models, Animal , Cell Movement/drug effects , Cell Line , Mice, Inbred C57BL , Molecular Docking Simulation , Indazoles/pharmacology , Indazoles/therapeutic use , Male , Focal Adhesion Kinase 1
2.
Cell Prolif ; : e13723, 2024 Sep 08.
Article in English | MEDLINE | ID: mdl-39245637

ABSTRACT

The vocal fold is an architecturally complex organ comprising a heterogeneous mixture of various layers of individual epithelial and mesenchymal cell lineages. Here we performed single-cell RNA sequencing profiling of 5836 cells from the vocal folds of adult Sprague-Dawley rats. Combined with immunostaining, we generated a spatial and transcriptional map of the vocal fold cells and characterized the subpopulations of epithelial cells, mesenchymal cells, endothelial cells, and immune cells. We also identified a novel epithelial-to-mesenchymal transition-associated epithelial cell subset that was mainly found in the basal epithelial layers. We further confirmed that this subset acts as intermediate cells with similar genetic features to epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma. Finally, we present the complex intracellular communication network involved homeostasis using CellChat analysis. These studies define the cellular and molecular framework of the biology and pathology of the VF mucosa and reveal the functional importance of developmental pathways in pathological states in cancer.

3.
Parasitol Res ; 123(8): 289, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39096422

ABSTRACT

Chicken coccidiosis causes retarded growth and low production performance in poultry, resulting in huge economic losses to the poultry industry. In order to prevent and control chicken coccidiosis, great efforts have been made to develop new drugs and vaccines, which require pure isolates of Eimeria spp. In this study, we obtained the Eimeira tenella Xiantao isolate by single oocyst isolation technology and compared its genome with the reference genome GCF_000499545.2_ETH001 of the Houghton strain. The results of the comparative genomic analysis indicated that the genome of this isolate contained 46,888 single nucleotide polymorphisms (SNPs). There were 15,107 small insertion and deletion variations (indels), 1693 structural variations (SV), and 3578 copy number variations (CNV). In addition, 64 broilers were used to determine the resistance profile of Xiantao strain. Drug susceptibility testing revealed that this isolate was completely resistant to monensin, diclazuril, halofuginone, sulfachlorpyrazine sodium, and toltrazuril, but sensitive to decoquinate. These data improve our understanding of drug resistance in avian coccidia.


Subject(s)
Chickens , Coccidiosis , Drug Resistance , Eimeria tenella , Poultry Diseases , Eimeria tenella/genetics , Eimeria tenella/drug effects , Eimeria tenella/isolation & purification , Animals , China , Chickens/parasitology , Poultry Diseases/parasitology , Coccidiosis/veterinary , Coccidiosis/parasitology , Drug Resistance/genetics , Coccidiostats/pharmacology , Polymorphism, Single Nucleotide , Genome, Protozoan
4.
Int J Biol Macromol ; 279(Pt 1): 135097, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39197604

ABSTRACT

Hemoadhican (HD) is an exopolysaccharide with a branched structure that has been reported for its high hemostatic ability. In this study, a HD-based hemostatic sponge was prepared through ultrasonic dissolution and freeze-drying without using any cross-linking agent. The sponge could spontaneously cross-link using hydrogen bonds to form adhesive mud within 3 s upon contact with blood. This sponge-mud mixture adhered tightly to the wound tissue, forming a pressure-resistant physical barrier that captures and locks in blood cells and platelets. Simultaneously, the hydrophobic methyl groups of HD sponges repel blood inwardly, effectively sealing the wound. The brush-like structure of HD molecules was suspected to penetrate wet tissues through topological entanglement, thereby enhancing wet adhesion. Compared with gauze and gelatin sponges, HD sponges achieved more effective hemostasis in animal models using rat and rabbit femoral arteries. In particular, HD sponges showed excellent hemostasis in heparin-induced hemorrhage models in mice and pigs. The in vivo experiment demonstrated the excellent biosafety of the HD sponge. Conclusively, the HD sponge is a safe and efficient rapid hemostatic material that is expected to become an alternative material for clinical hemostatic procedures.


Subject(s)
Hemorrhage , Heparin , Animals , Hemorrhage/drug therapy , Rabbits , Heparin/chemistry , Heparin/pharmacology , Rats , Mice , Swine , Hemostatics/pharmacology , Hemostatics/chemistry , Hemostasis/drug effects , Disease Models, Animal , Polysaccharides/chemistry , Polysaccharides/pharmacology , Male
5.
Int J Surg ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39196877

ABSTRACT

INTRODUCTION: Evidence on the association between early-life malnutrition exposure at different developmental stages and the subsequent risk of osteoporosis and fractures in adulthood remains sparse and equivocal. This study sought to elucidate the relationship between malnutrition exposure in early life and the occurrence of osteoporosis and fractures later in life. METHODS: This research is a cross-sectional analysis carried out within the framework of the China Community-based Cohort of Osteoporosis (CCCO), an ongoing community-based cohort study. Participants were stratified by birthdate into several categories: non-exposed, fetal, early childhood, mid-childhood, late childhood, and adolescence exposure groups. The non-exposure and adolescence exposure groups were consolidated into an "age-matched group" to provide a robust comparative framework for analyzing the probability of developing osteoporosis (defined as a T-score ≤ -2.5 in bone mineral density) and the frequency of self-reported fracture. Multiple logistic regression models were utilized to investigate the association between early-life malnutrition exposure and the risks of osteoporosis and fracture. Additionally, we validated our findings using the China Northwest Cohort (CNC). RESULTS: A total of 12,789 participants were included into the final analysis. After adjusting for various covariates, individuals exposed to malnutrition during their fetal and childhood stages (early, middle, and late) increased the likelihood of developing osteoporosis in adulthood, compared to their age-matched counterparts. In these four groups, the ORs (95% CI) for osteoporosis risk were 1.223 (1.035 to 1.445), 1.208 (1.052 to 1.386), 1.249 (1.097 to 1.421), and 1.101 (1.001 to 1.210), respectively (all P values < 0.05). Specifically, the late childhood exposure group showed a heightened risk of fracture, with an OR (95% CI) of 1.155 (1.033 to 1.291) and a P-value of 0.01127. Stratified analyses further found a significant correlation between early-life exposure to malnutrition and an elevated risk of osteoporosis in participants with lower educational attainment, overweight or obese participants. Additionally, corroborating evidence from the CNC confirmed the influence of malnutrition exposure on osteoporosis risk. CONCLUSIONS: Early-life exposure to malnutrition had a detrimental impact on bone health. Individuals who had experienced malnutrition during fetal and childhood stages (early, middle, and late) exhibited a high susceptibility to osteoporosis in adulthood, compared to age-matched cohorts. This susceptibility was particularly pronounced in women, and individuals who were overweight or obese, or had lower levels of education.

6.
RSC Adv ; 14(35): 25678-25684, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39148762

ABSTRACT

In conventional metasurface structural colour design, simulations combined with human intuition are used for design and optimization, making it challenging to find the best solution. Here we introduce an innovative AI-assisted design process that bypasses the need for complex simulations, enabling swift and precise mapping between metasurface parameters and colour coordinates. Instead of assigning one colour to one geometry, we demonstrate that multiple colours can be generated from a single geometry under varying levels of strain. This can be achieved through a single model, facilitating the development of active metasurfaces using AI. This finding enables designers to create active metasurfaces that account for both geometric properties and dynamic responses in a unified model which could accelerate the development of active metamaterials closer to practical applications in the real world.

7.
bioRxiv ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39211171

ABSTRACT

Eukaryotic cells direct toxic misfolded proteins to various protein quality control pathways based on their chemical features and aggregation status. Aggregated proteins are targeted to selective autophagy or specifically sequestered into the "aggresome," a perinuclear inclusion at the microtubule-organizing center (MTOC). However, the mechanism for selectively sequestering protein aggregates into the aggresome remains unclear. To investigate aggresome formation, we reconstituted MTOC-directed aggregate transport in Xenopus laevis egg extract using AgDD, a chemically inducible aggregation system. High-resolution single-particle tracking revealed that dynein-mediated transport of aggregates was highly episodic, with average velocity positively correlated with aggregate size. Our mechanistic model suggests that the recurrent formation of the dynein transport complex biases larger aggregates towards the active transport state, compensating for the slowdown due to viscosity. Both episodic transport and positive size selectivity are specifically associated with aggresome-dynein adaptors. Coupling conventional dynein-activating adaptors to the aggregates perturbs aggresome formation and reverses size selectivity.

8.
Parasit Vectors ; 17(1): 327, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095927

ABSTRACT

BACKGROUND: Chicken coccidiosis is an intracellular parasitic disease that presents major challenges to the development of the commercial poultry industry. Perennial drug selective pressure has led to the multi-drug resistance of chicken coccidia, which makes the prevention and control of chicken coccidiosis extremely difficult. In recent years, natural plant products have attracted the attention of researchers due to their inherent advantages, such as the absence of veterinary drug residues. The development of these natural products provides a new direction for the prevention and treatment of chicken coccidiosis. METHODS: The anticoccidial effect of a natural plant product combination formulation (eucalyptus oil + apigenin + eugenol essential oil) was tested against Eimeria tenella in broilers. To search for the optimal concentration of the combination formulation, we screened 120 broilers in a chicken cage trial in which 100 broilers were infected with 5 × 104 sporulated Eimeria tenella oocysts; broilers receiving a decoquinate solution was set up as a chemical control. The optimal anticoccidial concentration was determined by calculating the anticoccidial index (ACI), and the suitable concentration was used as the recommended dose for a series of safety dose assessment tests, such as feed conversion ratio (FCR), hematological indices and serum biochemical indices, as well as liver and kidney sections, at onefold (low dose), threefold (medium dose) and sixfold (high dose) the recommended dose (RD). RESULTS: The results showed that this combination formulation of three plant natural products had a better anticoccidial effect than formulations containing two plant natural products or a single one, with an ACI of 169.3. The dose gradient anticoccidial test revealed that the high-dose formulation group had a better anticoccidial effect (ACI = 169.2) than the medium- and low-dose groups. The safety evaluation test showed that concentrations of the formulation at one-, three- and sixfold the RD were non-toxic to Arbor Acres broilers, indicating the high safety of the combination formulation. CONCLUSIONS: The combination formulation showed not only a moderate anticoccidial effect but also had a high safety profile for broilers. The results of this study indicate a new alternative for the prevention and control of coccidiosis in broilers.


Subject(s)
Chickens , Coccidiosis , Coccidiostats , Eimeria tenella , Eucalyptus , Eugenol , Poultry Diseases , Animals , Chickens/parasitology , Eimeria tenella/drug effects , Coccidiosis/drug therapy , Coccidiosis/veterinary , Coccidiosis/parasitology , Poultry Diseases/drug therapy , Poultry Diseases/parasitology , Coccidiostats/pharmacology , Coccidiostats/therapeutic use , Coccidiostats/administration & dosage , Eugenol/pharmacology , Eugenol/administration & dosage , Eucalyptus/chemistry , Biological Products/pharmacology , Biological Products/administration & dosage , Oocysts/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/administration & dosage , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/administration & dosage
9.
bioRxiv ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39091741

ABSTRACT

Preferentially Expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells. Analysis of TCGA and GTEx databases confirmed a negative relationship between TET2 and PRAME mRNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5' promoter in melanoma compared to nevi, suggesting a role for 5hmC in PRAME transcription. Restoring 5hmC levels via TET2 overexpression notably reduced PRAME expression in melanoma cell lines. These findings establish a function of TET2-mediated DNA hydroxymethylation in regulating PRAME expression and demonstrate epigenetic reprogramming as pivotal in melanoma tumorigenesis. Teaser: Melanoma biomarker PRAME expression is negatively regulated epigenetically by TET2-mediated DNA hydroxymethylation.

10.
Contemp Clin Trials Commun ; 39: 101317, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38948333

ABSTRACT

Introduction: Post-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without timely treatment. Sangdantongluo granule, a modern traditional Chinese patent medicine, has significant clinical efficacy in treating PSS. However, the mechanism of Sangdantongluo granule in treating PSS is still unknown. We designed this study to explore the mechanism of Sangdantongluo granule in treating PSS through multimodal functional magnetic resonance imaging (fMRI) combined with transcranial magnetic stimulation (TMS). Methods and analysis: In a single-center, randomized, double-blind, parallel placebo-controlled study, 60 PSS patients will be recruited in China and randomly assigned to either the experimental or control groups at a ratio of 1:1. For eight weeks, Sangdantongluo granule or placebo will be utilized for intervention. The main outcome is the Modified Ashworth Scale (MAS), the secondary outcome includes the Fugl-Meyer Assessment Scale-upper Extremity (FMA-UE), National Institute of Health Stroke Scale (NIHSS), and Modified Rankin Scale (mRS), the mechanism measure is the changes in cortical excitability and multimodal fMRI at baseline and after eight weeks. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine (approval number: [202364]). Clinical trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300074793. Registered on 16 August 2023.

11.
Lasers Surg Med ; 56(7): 657-663, 2024 09.
Article in English | MEDLINE | ID: mdl-38992905

ABSTRACT

OBJECTIVES: The aim of this study was to assess the value of CO2 laser vaporization in treating huge adult laryngeal vascular anomalies (HALVAs) by combining it with bleomycin injection. MATERIALS AND METHODS: This study retrospectively reviewed the records of 13 adult patients who underwent 18 different procedures. Methods to treat HALVAs include traditional bleomycin injection and CO2 laser vaporization combined with bleomycin injection between September 2009 and January 2023. Treatment results were evaluated by the grade of lumen constriction. RESULTS: A total of five males and eight females, with an average age of 46.3 years (range, 22-66 years), were included in the study. The huge adult laryngeal vascular anomalies in our study were greater than 1633.71 mm3, and the long diameters of the bases were longer than 15 mm. Compared with the bleomycin injection-only group, the results with the CO2 laser vaporization and bleomycin injection combined were better. CONCLUSIONS: Both bleomycin injection and CO2 laser vaporization are safe treatment methods. Their combination may produce better results for huge adult laryngeal vascular anomalies.


Subject(s)
Bleomycin , Lasers, Gas , Humans , Male , Middle Aged , Adult , Bleomycin/administration & dosage , Bleomycin/therapeutic use , Bleomycin/analogs & derivatives , Female , Lasers, Gas/therapeutic use , Retrospective Studies , Aged , Young Adult , Vascular Malformations/surgery , Vascular Malformations/therapy , Combined Modality Therapy , Larynx/surgery , Laser Therapy/methods , Treatment Outcome
12.
Sheng Li Xue Bao ; 76(3): 394-406, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38939934

ABSTRACT

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.


Subject(s)
MicroRNAs , Spinal Cord Injuries , Spinal Cord Injuries/genetics , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/physiopathology , MicroRNAs/genetics , MicroRNAs/metabolism , MicroRNAs/physiology , Humans , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Long Noncoding/physiology , RNA, Circular/genetics , RNA, Circular/physiology , RNA, Circular/metabolism , Oxidative Stress , Apoptosis/genetics
13.
Int J Cosmet Sci ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38922913

ABSTRACT

OBJECTIVE: The objective of this work was to understand how triglyceride plant oils can deliver strength and softness benefits to hair by their penetration. These plant oils are complex mixtures of TAGs, so the initial studies performed were with pure TAGs and then these data compared to plant oils and their measured TAG compositions. METHODS: LC-MS was used to identify the di and triglycerides in coconut oil, Camellia oleifera oil and safflower seed oil. Penetration of these plant oils and pure individual triglycerides was measured by a differential extraction method. Cross-sections of oils treated with 13C-labelled triolein were studied by NanoSIMS to visualize location of triglyceride inside hair. Fatigue strength was measured using constant stress to generate a survival distribution. Models of the lipid-rich cell membrane complex (CMC) were created with the equimolar ratio of 18-methyl-eicosanoic acid (MEAS), palmitic acid (C16:0) and oleic acid (C18:1). RESULTS: Penetration of the individual pure TAGs was confirmed for all chain lengths and degree of unsaturation tested with higher penetration for shorter chain lengths and unsaturated fatty acids. Detailed compositional analysis of selected plant oils showed a wide variety of TAGs and penetration was also demonstrated for these oils. NanoSIMS and modelling confirmed these TAGs are penetrating the lipid-rich CMC of hair and are interacting with the fatty acids that make up the CMC. All plant oils delivered a fatigue strength improvement by penetration into the CMC and it is proposed that these oils prevent formation and/or propagation of flaws in the CMC network that leads to breakage. CONCLUSIONS: Many plant oils with a wide range of triglyceride compositions can penetrate into hair and NanoSIMS data confirmed these oils partition into the lipid-rich cell membrane complex. Penetration studies of individual TAGs shown to be present in these oils confirmed TAGs of varying chain length can penetrate and there is a correlation between increased penetration efficacy and shorter chain lengths and presence of unsaturation in the fatty acid chains. All the oils studied delivered single fibre fatigue strength benefits.


OBJECTIF: L'objectif de ce travail était de comprendre comment les huiles végétales à base de triglycérides peuvent apporter aux cheveux des bienfaits en termes de résistance et de douceur grâce à leur pénétration. Ces huiles végétales sont des mélanges complexes de TAG, donc les études réalisées initiales ont porté sur des TAG purs et ces données ont été comparées à des huiles végétales et leurs compositions en TAG mesurées. MÉTHODES: La LC­MS a été utilisée pour identifier les di­ et triglycérides dans l'huile de noix de coco, l'huile de Camellia oleifera et l'huile de graines de carthame. La pénétration de ces huiles végétales et des triglycérides individuels purs a été mesurée par une méthode d'extraction différentielle. Des coupes transversales d'huiles traitées avec de la trioléine marquée au C13 ont été étudiées par NanoSIMS pour visualiser l'emplacement des triglycérides à l'intérieur des cheveux. La résistance à la fatigue a été mesurée à l'aide d'une sollicitation constante pour générer une distribution de la survie. Des modèles du complexe de membrane cellulaire riche en lipides (CMC) ont été créés avec le rapport équimolaire en acide 18­méthyleicosanoïque (MEAS), acide palmitique (C16:0) et acide oléique (C18:1). RÉSULTATS: La pénétration des TAG purs individuels a été confirmée pour toutes les longueurs de chaîne et le degré d'insaturation a été testé avec une pénétration plus élevée pour les chaînes plus courtes et les acides gras insaturés. Une analyse détaillée de la composition de certaines huiles végétales a montré une grande variété de TAG et la pénétration a également été démontrée pour ces huiles. Le NanoSIMS et la modélisation ont confirmé que ces TAG pénètrent dans la CMC riche en lipides des cheveux et interagissent avec les acides gras qui composent le CMC. Toutes les huiles végétales ont produit une amélioration de la résistance à la fatigue par pénétration dans le CMC et il est proposé que ces huiles préviennent la formation et/ou la propagation de défauts dans le réseau CMC qui entraînent une rupture. CONCLUSIONS: De nombreuses huiles végétales avec un large éventail de compositions de triglycérides peuvent pénétrer dans les cheveux et les données du NanoSIMS ont confirmé que ces huiles se divisent en complexe de membrane cellulaire riche en lipides. Les études de pénétration des TAG individuels qui se sont avérés présents dans ces huiles ont confirmé que les TAG de longueur de chaîne variable peuvent pénétrer et il existe une corrélation entre l'augmentation de l'efficacité de pénétration et les longueurs de chaîne plus courtes et la présence d'une insaturation dans les chaînes d'acides gras. Toutes les huiles étudiées ont montré des bienfaits en matière de résistance à la fatigue pour une seule fibre.

14.
J Invest Dermatol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38848988

ABSTRACT

Cancer-associated fibroblasts (CAFs) interact reciprocally with tumor cells through various signaling pathways in many cancer types, including cutaneous squamous cell carcinoma. Among normal fibroblast subtypes, papillary fibroblasts (PFs) and reticular fibroblasts (RFs) respond distinctly to tumor cell signaling, eventuating the differentiation of RFs rather than PFs into CAFs. The regulation of subtype differentiation in fibroblasts remains poorly explored. In this study, we assessed the differences between PFs, RFs, and CAFs and examined the effects of small-molecule inhibitors targeting the TGFß, phosphoinositide 3-kinase/protein kinase B/mTOR, and NOTCH pathways on the tumor-promoting property of CAFs and CAF reprogramming in 2-dimensional and 3-dimensional cultures. Blocking TGFß and phosphoinositide 3-kinase strongly deactivated and concurrently induced a PF phenotype in RFs and CAFs. Three-dimensional coculturing of a cutaneous squamous cell carcinoma cell line MET2 with RFs or CAFs led to enhanced tumor invasion, RF-CAF transition, and cytokine production, which were further repressed by blocking TGFß and phosphoinositide 3-kinase/mTOR pathways but not NOTCH pathway. In conclusion, the study identified biomarkers for PFs, RFs, and CAFs and displayed different effects of blocking key signaling pathways in CAFs and tumor cell-CAF interplay. These findings prompted a CAF-to-PF therapeutic strategy and provided perspectives of using included inhibitors in CAF-based cancer therapy.

15.
Hypertens Res ; 47(8): 2195-2210, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38872026

ABSTRACT

Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment and functional loss in elderly patients. Progressive remodeling of cerebral microvessels due to arterial hypertension or other vascular risk factors, such as aging, can cause dementia or stroke. Typical imaging characteristics of CSVD include cerebral microbleeds (CMB), brain atrophy, small subcortical infarctions, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). Nevertheless, no animal models that reflect all the different aspects of CSVD have been identified. Here, we generated a new CSVD animal model using D-galactose (D-gal) combined with cerebral hypoperfusion in spontaneously hypertensive rats (SHR), which showed all the hallmark pathological features of CSVD and was based on vascular risk factors. SHR were hypodermically injected with D-gal (400 mg/kg/d) and underwent modified microcoil bilateral common carotid artery stenosis surgery. Subsequently, neurological assessments and behavioral tests were performed, followed by vascular ultrasonography, electron microscopy, flow cytometry, and histological analyses. Our rat model showed multiple cerebrovascular pathologies, such as CMB, brain atrophy, subcortical small infarction, WMH, and EPVS, as well as the underlying causes of CSVD pathology, including oxidative stress injury, decreased cerebral blood flow, structural and functional damage to endothelial cells, increased blood-brain barrier permeability, and inflammation. The use of this animal model will help identify new therapeutic targets and subsequently aid the development and testing of novel therapeutic interventions. Main process of the study: Firstly, we screened for optimal conditions for mimicking aging by injecting D-gal into rats for 4 and 8 weeks. Subsequently, we performed modified microcoil BCAS intervention for 4 and 8 weeks in rats to screen for optimal hypoperfusion conditions. Finally, based on these results, we combined D-gal for 8 weeks and modified microcoil BCAS for 4 weeks to explore the changes in SHR.


Subject(s)
Aging , Cerebral Small Vessel Diseases , Disease Models, Animal , Galactose , Hypertension , Rats, Inbred SHR , Animals , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/pathology , Aging/pathology , Male , Rats , Hypertension/complications , Risk Factors , Cerebrovascular Circulation , Brain/pathology , Brain/diagnostic imaging
16.
J Am Chem Soc ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858162

ABSTRACT

Understanding how life's essential homochiral biopolymers arose from racemic precursors is a challenging quest. Herein, we present a groundbreaking approach involving hierarchical chiral assembly-driven stereoselective ring-opening polymerization of ε-benzyloxycarbonyl-l/d-lysine N-carboxyanhydrides assisted by ultrasonication in an aqueous medium. This method enabled a narrow dispersity within a few minutes and the achievement of high molecular weight for polypeptides, employing a living polymerization mechanism. The polymerization of l and d enantiomers yielded predominantly right- and left-handed superhelical assemblies in a one-pot preparation, respectively. Notably, stereoselective polypeptide segments were efficiently prepared through hierarchical assembly-driven polymerization of racemic monomers in the absence of a catalyst. This research offers an innovative strategy for the convenient preparations of stereoenriched polypeptides and, more importantly, sheds light on the plausible emergence of homochiral peptides in the origin of life.

17.
iScience ; 27(5): 109721, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38706853

ABSTRACT

This article designs and implements a fast and high-precision multi-robot environment modeling method based on bidirectional filtering and scene identification. To solve the problem of feature tracking failure caused by large angle rotation, a bidirectional filtering mechanism is introduced to improve the error-matching elimination algorithm. A global key frame database for multiple robots is proposed based on a pretraining dictionary to convert images into a bag of words vectors. The images captured by different sub-robots are compared with the database for similarity score calculation, so as to realize fast identification and search of similar scenes. The coordinate transformation from local map to global map and the cooperative SLAM exploration of multiple robots is completed by the best matching image and the transformation matrix. The experimental results show that the proposed algorithm can effectively close the predicted trajectory of the sub-robot, thus achieving high-precision collaborative environment modeling.

18.
Microorganisms ; 12(5)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38792744

ABSTRACT

Streptococcus suis (S. suis) is a zoonotic pathogen capable of causing severe diseases in humans and pigs, including meningitis, sepsis, polyserositis, arthritis, and endocarditis. This study aimed to investigate the biological characteristics of 19 strains of S. suis isolated from diseased pigs in Hubei Province between 2021 and 2023. Through bioinformatics analysis, we investigated the serotype, MLST, pan-genome characteristics, SNP, AMR, and ICE of the 19 S. suis isolates. Among the 19 S. suis strains, ten serotypes were identified, and serotype 9 was the most prevalent (21.05%). Ten new alleles and nine new sequence types (STs) were discovered, with ST28 and ST243 emerging as the predominant STs. The results of the pan-genomic analysis of S. suis indicate that there are 943 core genes, 2259 shell genes, and 5663 cloud genes. Through SNP evolutionary analysis, we identified a strong genetic similarity between SS31 and the reference genome P1/7. The analysis of antibiotic resistance genes revealed widespread presence of erm(B) and tet(O) genes among 19 strains of S. suis. This association may be linked to the high resistance of S. suis to lincosamides, macrolides, and tetracyclines. Integrative and conjugative elements (ICEs) and integrative and mobilizable elements (IMEs) were identified in 16 strains, with a carriage rate of 84.21%, and resistance genes were identified within the ICE/IME elements of 8 strains. Antimicrobial susceptibility testing revealed that all strains showed sensitivity to vancomycin and lincomycin but resistance to tilmicosin, tiamulin, amoxicillin, and doxycycline. This study contributes to our understanding of the genomic diversity of S. suis in Hubei Province of China, providing essential data for the comprehensive prevention and control of S. suis infections in China.

19.
AMB Express ; 14(1): 55, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730054

ABSTRACT

African swine fever virus (ASFV) is a highly pathogenic and rapidly disseminated virus with strong viability in the environment, suggesting the importance of environmental detection for prevention and control in all the pig industry. However, the detection results of environmental swabs cannot always reflect the accurate status of viral pollution, leading to persistent ASFV environmental contamination. In this study, we developed an ASFV eluant with higher environmental ASFV detection efficiency relative to 0.85% saline solution, which obtains the patent certificate issued by the China Intellectual Property Office (patent number:202010976050.9). qPCR analysis showed that in the environmental swab samples, the number of viral copies was 100 times higher for the ASFV eluant treatment than the traditional eluant treatment (0.85% saline solution). And besides, the high sensitivity of the ASFV eluant had be verified in a slaughterhouse environmental sampling detection. In soil samples, the ASFV eluent showed the same extraction effect as the TIANamp Soil DNA Kit, in contrast to no extraction effect for 0.85% saline solution. Simultaneously, this eluent could protect ASFV from degradation and allow the transportation of samples at ambient temperature without refrigeration. In clinical practice, we monitored the environmental contamination condition of the ASFV in a large-scale pig farm. The results shown that the ASFV load decreased after every disinfection in environment. This study provides an effective solution for surveilling the potential threat of ASFV in environment.

20.
Eur J Pharmacol ; 975: 176646, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38762157

ABSTRACT

Severe acute pancreatitis (SAP) is a complicated inflammatory reaction that impacts the pancreas, often resulting in damage to numerous organs. This disorder encompasses a range of processes such as inflammation, oxidative stress, and pancreatitis. The hormone melatonin (MT) is primarily secreted by the pineal gland and plays a crucial role in mitigating inflammation, countering the harmful effects of free radicals, and regulating oxidative stress. The aim of this research was to investigate the potential protective impact and the underlying mechanism of melatonin in mice afflicted with SAP. The biochemical and histological assessments unequivocally demonstrated that melatonin effectively inhibited necrosis, infiltration, edema and cell death in pancreatic tissues, thereby suppressing acute pancreatitis. Notably, melatonin also alleviated the consequent harm to distant organs, notably the lungs, liver, and kidneys. Furthermore, both preventive and therapeutic administration of melatonin prompted nuclear factor E2-related factor 2 (Nrf2) activation followed by Nrf2 target gene expression. Nrf2 initiates the activation of antioxidant genes, thereby providing defense against oxidative stress. Conversely, Nrf2 reduction may contribute to impaired antioxidant protection in SAP. The beneficial impact of Nrf2 on antioxidants was absent in Nrf2-knockout mice, leading to the accumulation of LDH and exacerbation of cell death. This deterioration in both pancreatitis and injuries in distant organs intensified significantly. The results indicate that melatonin has an enhanced ability to protect against multiorgan damage caused by SAP, which is accomplished through the increase in Nrf2 expression. Additionally, Nrf2 initiates the activation of antioxidant genes that offer defense against cell death.


Subject(s)
Melatonin , NF-E2-Related Factor 2 , Oxidative Stress , Pancreatitis , Signal Transduction , Animals , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Melatonin/pharmacology , Melatonin/therapeutic use , Signal Transduction/drug effects , Pancreatitis/drug therapy , Pancreatitis/pathology , Pancreatitis/metabolism , Mice , Oxidative Stress/drug effects , Male , Antioxidants/pharmacology , Antioxidants/therapeutic use , Mice, Knockout , Pancreas/drug effects , Pancreas/pathology , Pancreas/metabolism , Mice, Inbred C57BL , Acute Disease
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