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1.
J Control Release ; 370: 501-515, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38703950

ABSTRACT

Although nanomaterial-based nanomedicine provides many powerful tools to treat cancer, most focus on the "immunosilent" apoptosis process. In contrast, ferroptosis and immunogenic cell death, two non-apoptotic forms of programmed cell death (PCD), have been shown to enhance or alter the activity of the immune system. Therefore, there is a need to design and develop nanoplatforms that can induce multiple modes of cell death other than apoptosis to stimulate antitumor immunity and remodel the immunosuppressive tumor microenvironment for cancer therapy. In this study, a new type of multifunctional nanocomposite mainly consisting of HMME, Fe3+ and Tannic acid, denoted HFT NPs, was designed and synthesized to induce multiple modes of cell death and prime the tumor microenvironment (TME). The HFT NPs consolidate two functions into one nano-system: HMME as a sonosensitizer for the generation of reactive oxygen species (ROS) 1O2 upon ultrasound irradiation, and Fe3+ as a GSH scavenger for the induction of ferroptosis and the production of ROS ·OH through inorganic catalytic reactions. The administration of HFT NPs and subsequent ultrasound treatment caused cell death through the consumption of GSH, the generation of ROS, ultimately inducing apoptosis, ferroptosis, and immunogenic cell death (ICD). More importantly, the combination of HFT NPs and ultrasound irradiation could reshape the TME and recruit more T cell infiltration, and its combination with immune checkpoint blockade anti-PD-1 antibody could eradicate tumors with low immunogenicity and a cold TME. This new nano-system integrates sonodynamic and chemodynamic properties to achieve outstanding therapeutic outcomes when combined with immunotherapy. Collectively, this study demonstrates that it is possible to potentiate cancer immunotherapy through the rational and innovative design of relatively simple materials.

2.
J Colloid Interface Sci ; 670: 449-459, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38772261

ABSTRACT

Aqueous zinc ion batteries (ZIBs) have been considered promising energy storage systems due to their excellent electrochemical performance, environmental toxicity, high safety and low cost. However, uncontrolled dendrite growth and side reactions at the zinc anode have seriously hindered the development of ZIBs. Herein, we prepared the carbon nanoparticles layer coated zinc anode with (103) crystal plane preferential oriented crystal structure (denoted as C@RZn) by a facile one-step vapor deposition method. The preferential crystallographic orientation of (103) crystal plane promotes zinc deposition at a slight angle, effectively preventing the formation of Zn dendrites on the surface. In addition, the hydrophobic layer of carbon layer used as an inert physical barrier to prevent corrosion reaction and a buffer during volume changes, thus improving the reversibility of the zinc anode. As a result. the C@RZn anode achieves a stable cycle performance of more than 3000 h at 1 mA cm-2 with CE of 99.77 % at 5 mA cm-2. The full battery with C@RZn anode and Mn-doped V6O13 (MVO) cathode show stability for 5000 cycles at the current density of 5 A g-1. This work provides a new approach for the design of multifunctional interfaces for Zn anode.

3.
Exp Eye Res ; 243: 109907, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38649019

ABSTRACT

Sleep loss is common in modern society and is increasingly associated with eye diseases. However, the precise effects of sleep loss on retinal structure and function, particularly on the retinal circadian system, remain largely unexplored. This study investigates these effects using a chronic sleep deprivation (CSD) model in mice. Our investigation reveals that CSD significantly alters the retinal circadian transcriptome, leading to remarkable changes in the temporal patterns of enriched pathways. This perturbation extends to metabolic and immune-related transcriptomes, coupled with an accumulation of reactive oxygen species in the retina. Notably, CSD rhythmically affects the thickness of the ganglion cell complex, along with diurnal shifts in microglial migration and morphology within the retina. Most critically, we observe a marked decrease in both scotopic and photopic retinal function under CSD conditions. These findings underscore the broad impact of sleep deprivation on retinal health, highlighting its role in altering circadian gene expression, metabolism, immune response, and structural integrity. Our study provides new insights into the broader impact of sleep loss on retinal health.


Subject(s)
Circadian Rhythm , Mice, Inbred C57BL , Retina , Sleep Deprivation , Transcriptome , Animals , Sleep Deprivation/physiopathology , Sleep Deprivation/metabolism , Sleep Deprivation/genetics , Mice , Circadian Rhythm/physiology , Male , Retina/metabolism , Retina/physiopathology , Disease Models, Animal , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/metabolism , Electroretinography , Gene Expression Regulation , Chronic Disease
4.
Biomed Pharmacother ; 174: 116562, 2024 May.
Article in English | MEDLINE | ID: mdl-38626518

ABSTRACT

Rhabdomyosarcoma (RMS), a mesenchymal tumor occurring in the soft tissue of children, is associated with a defect in differentiation. This study unveils a novel anti-tumor mechanism of dimethylaminomicheliolide (DMAMCL), which is a water-soluble derivative of Micheliolide. First, we demonstrate that DMAMCL inhibits RMS cell growth without obvious cell death, leading to morphological alterations, enhanced expression of muscle differentiation markers, and a shift from a malignant to a more benign metabolic phenotype. Second, we detected decreased expression of DLL1 in RMS cells after DMAMCL treatment, known as a pivotal ligand in the Notch signaling pathway. Downregulation of DLL1 inhibits RMS cell growth and induces morphological changes similar to the effects of DMAMCL. Furthermore, DMAMCL treatment or loss of DLL1 expression also inhibits RMS xenograft tumor growth and augmented the expression of differentiation markers. Surprisingly, in C2C12 cells DMAMCL treatment or DLL1 downregulation also induces cell growth inhibition and an elevation in muscle differentiation marker expression. These data indicated that DMAMCL induced RMS differentiation and DLL1 is an important factor for RMS differentiation, opening a new window for the clinical use of DMAMCL as an agent for differentiation-inducing therapy for RMS treatment.


Subject(s)
Calcium-Binding Proteins , Cell Differentiation , Cell Proliferation , Down-Regulation , Rhabdomyosarcoma , Cell Differentiation/drug effects , Rhabdomyosarcoma/pathology , Rhabdomyosarcoma/drug therapy , Rhabdomyosarcoma/metabolism , Animals , Down-Regulation/drug effects , Humans , Cell Line, Tumor , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/genetics , Cell Proliferation/drug effects , Mice , Xenograft Model Antitumor Assays , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice, Nude , Intercellular Signaling Peptides and Proteins/metabolism , Signal Transduction/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Antineoplastic Agents/pharmacology
5.
Sci Total Environ ; 930: 172508, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38642752

ABSTRACT

Water-soluble organic aerosol (WSOA) plays a crucial role in altering radiative forcing and impacting human health. However, our understanding of the seasonal variations of WSOA in Chinese megacities after the three-year clean air action plan is limited. In this study, we analyzed PM2.5 filter samples collected over one year (2020-2021) in Beijing to characterize the seasonal changes in the chemical and optical properties of WSOA using an offline aerosol mass spectrometer along with spectroscopy techniques. The mean mass concentration of WSOA during the observation period was 8.84 ± 7.12 µg m-3, constituting approximately 64-67 % of OA. Our results indicate the contribution of secondary OA (SOA) increased by 13-28 % due to a substantial reduction in primary emissions after the clean air action plan. The composition of WSOA exhibited pronounced seasonal variations, with a predominant contribution from less oxidized SOA in summer (61 %) and primary OA originating from coal combustion and biomass burning during the heating season (34 %). The mass absorption efficiency of WSOA at 365 nm in winter was nearly twice that in summer, suggesting that WSOA from primary emissions possesses a stronger light-absorbing capability than SOA. On average, water-soluble brown carbon accounted for 33-48 % of total brown carbon absorption. Fluorescence analysis revealed humic-like substances as the most significant fluorescence component of WSOA, constituting 82 %. Furthermore, both absorption and fluorescence chromophores were associated with nitrogen-containing compounds, highlighting the role of nitrogen-containing species in influencing the optical properties of WSOA. The results are important for chemical transport models to accurately simulate the WSOA and its climate effects.

6.
Sci Total Environ ; 929: 172497, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38636875

ABSTRACT

Silicon (Si) biogeochemical cycling is beneficial for crop productivity and carbon (C) sequestration in agricultural ecosystem, thus offering a nonnegligible role in alleviating global warming and food crisis. Compared with other crops, rice plants have a greater quantity of phytolith production, because they are able to take up a lot of Si. However, it remains unclear on Si supply capacity of paddy soils across the world, general rice yield-increasing effect after Si fertilizer addition, and factors affecting phytolith production and potential of phytolith C sequestration in paddy fields. This study used a meta-analysis of >3500 data from 87 studies to investigate Si supply capacity of global paddy soils and elaborate the benefits of Si regarding rice productivity and phytolith C sequestration in paddy fields. Analytical results showed that the Si supply capacity of paddy soils was insufficient in the major rice producing countries/regions. Dealing with this predicament, Si fertilization was an effective strategy to supply plant-available Si to improve rice productivity. Our meta-analysis results further revealed that Si fertilization led to the average increasing rate of 36 % and 39 % in rice yield and biomass, which could reach up to 52 % and 46 % with the increasing doses of Si fertilizer, respectively. Especially, this strategy also improved the potential of phytolith C sequestration through the increased phytolith content and rice biomass, despite that this potential might have a decline in old paddy soils (≥ 7000 year) compared to in young paddy soils (≤ 1000 year) due to the slow migration and dissolution of phytoliths at millennial scale. Our findings thus indicate that a deep investigation on the benefits of Si in agroecosystem will further improve our understanding on regulating crop production and the potential of biogeochemical C sequestration within phytoliths in global cropland.


Subject(s)
Agriculture , Carbon Sequestration , Fertilizers , Oryza , Silicon , Agriculture/methods , Soil/chemistry , Crops, Agricultural
7.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1211-1224, 2024 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-38658158

ABSTRACT

To study the genetic background of lily (Lilium spp.) germplasm resources, and accurately evaluate and select excellent germplasm for genetic improvement of lily, we analyzed the genetic background of 62 lily germplasm accessions from 11 provinces of China by using simple sequence repeat (SSR) molecular markers. The results showed that 15 out of 83 pairs of lily SSR primers were polymorphic. A total of 157 allelic loci were amplified, with the number of alleles per locus ranging from 5 to 19 and the average number of effective alleles per locus being 4.162 8. The average observed heterozygosity and expected heterozygosity were 0.228 2 and 0.694 1, respectively. The average polymorphic information content was 0.678 8. The average Nei's diversity index and Shannon's information index were 0.694 1 and 1.594 9, respectively, indicating that the tested lily germplasm had high genetic diversity. The 62 germplasm accessions were classified into 5 groups by the unweighted pair group method with arithmetic mean (UPGMA) and into 3 groups by the principal component analysis. The two analyses revealed a geographic correlation among different groups. The majority of lily germplasm accessions from the same source tended to cluster together. The population structure analysis classified the lily accessions into 4 populations and 1 mixed population. The above results provide a theoretical basis and genetic resources for the precise identification and breeding of lily germplasm resources.


Subject(s)
Genetic Variation , Lilium , Microsatellite Repeats , Polymorphism, Genetic , Lilium/genetics , Lilium/classification , Microsatellite Repeats/genetics , China , Genetic Markers , Alleles , DNA, Plant/genetics
8.
Nano Lett ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597670

ABSTRACT

We report experimental and theoretical studies of MoTe2-MoSe2 heterobilayers with rigid moiré superlattices controlled by the twist angle. Using an effective continuum model that combines resonant interlayer electron tunneling with stacking-dependent moiré potentials, we identify the nature of moiré excitons and the dependence of their energies, oscillator strengths, and Landé g-factors on the twist angle. Within the same framework, we interpret distinct signatures of bound complexes among electrons and moiré excitons in nearly collinear heterostacks. Our work provides a fundamental understanding of hybrid moiré excitons and trions in MoTe2-MoSe2 heterobilayers and establishes the material system as a prime candidate for optical studies of correlated phenomena in moiré lattices.

9.
Front Vet Sci ; 11: 1360504, 2024.
Article in English | MEDLINE | ID: mdl-38601910

ABSTRACT

Bovine Viral Diarrhea Virus (BVDV) and Infectious Bovine Rhinotracheitis Virus (IBRV) are the two most prevalent infectious diseases in cattle. They both can cause persistent infection and immunosuppression, resulting in significant economic losses in the livestock industry. Therefore, rapid detection of early BVDV and IBRV infections is crucial. In this study, a method for the rapid detection of BVDV and IBRV was established by using recombinase polymerase amplification (RPA) combined with lateral flow device (LFD). By optimizing the temperature and time conditions of the RPA reaction, the sensitivity, specificity, and clinical performance were evaluated. The results indicated that the RPA reaction could be completed at 40°C within 25 min. The LOD for BVDV and IBRV by RPA-LFD were 5.1 × 101 copies/µL and 6.65 × 101 copies/µL, respectively, with no cross-reactivity observed with other viruses such as CSFV, BRSV, BPIV3, BRV, and BCoV. Testing of 32 clinical samples showed consistent results between RPA-LFD and qPCR. The RPA-LFD method established in this study can be used for the rapid clinical detection of BVDV and IBRV, which providing a rapid and convenient molecular biology approach for on-site rapid detection and epidemiological investigations. Simultaneously, it offers technical support for the prevention and control of these viruses.

10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 331-334, 2024 Mar 10.
Article in Chinese | MEDLINE | ID: mdl-38448024

ABSTRACT

OBJECTIVE: To explore the genetic etiology of two patients with Gitelman syndrome (GS). METHODS: Two patients who had presented at the Linyi People's Hospital in January and June 2022 respectively were selected as the study subjects. Peripheral blood samples of them were collected and subjected to whole exome sequencing (WES). Electrolyte levels in their serum and urine were detected. Candidate variants were verified by Sanger sequencing. PyMOL software was used to predict the impact of the variants on the protein structure. RESULTS: Patient 1 was a 27-year-old female with decreased serum levels of sodium, potassium, chloride and magnesium, along with decreased urine chloride and calcium. WES revealed that she has harbored compound heterozygous variants of the SLC12A3 gene, namely c.1456G>A (p.D486N) and c.179C>T (p.T60M). The former was inherited from her mother and known to be pathogenic. Patient 2 was a 4-year-old male with lower serum sodium, chloride and magnesium levels, and his serum potassium level was found to be critically low. He was found to harbor compound heterozygous variants of c.602-16G>A and c.805_806insTTGGCGTGGTCTCGGTCA (p.V268_T269insIGVVSV) of the SLC12A3 gene, which were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2_Supporting+PP3; PVS1+PM2_Supporting+PM4). CONCLUSION: The above heterozygous variants of the SLC12A3 gene probably underlay the GS in these patients.


Subject(s)
Gitelman Syndrome , Humans , Female , Male , Adult , Child, Preschool , Gitelman Syndrome/genetics , Chlorides , Magnesium , Potassium , Sodium , Solute Carrier Family 12, Member 3/genetics
11.
J Med Virol ; 96(3): e29528, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38501378

ABSTRACT

The emerging Omicron subvariants have a remarkable ability to spread and escape nearly all current monoclonal antibody (mAb) treatments. Although the virulence of SARS-CoV-2 has now diminished, it remains a significant threat to public health due to its high transmissibility and susceptibility to mutation. Therefore, it is urgent to develop broad-acting and potent therapeutics targeting current and emerging Omicron variants. Here, we identified a panel of Omicron BA.1 spike receptor-binding domain (RBD)-targeted nanobodies (Nbs) from a naive alpaca VHH library. This panel of Nbs exhibited high binding affinity to the spike RBD of wild-type, Alpha B.1.1.7, Beta B.1.351, Delta plus, Omicron BA.1, and BA.2. Through multivalent Nb construction, we obtained a subpanel of ultrapotent neutralizing Nbs against Omicron BA.1, BA.2, BF.7 and even emerging XBB.1.5, and XBB.1.16 pseudoviruses. Protein structure prediction and docking analysis showed that Nb trimer 2F2E5 targets two independent RBD epitopes, thus minimizing viral escape. Taken together, we obtained a panel of broad and ultrapotent neutralizing Nbs against Omicron BA.1, Omicron BA.2, BF.7, XBB.1.5, and XBB.1.16. These multivalent Nbs hold great promise for the treatment against SARS-CoV-2 infection and could possess a superwide neutralizing breadth against novel omicron mutants or recombinants.


Subject(s)
COVID-19 , SARS-CoV-2 , Single-Domain Antibodies , Humans , Single-Domain Antibodies/genetics , Antibodies, Monoclonal , Epitopes , Antibodies, Neutralizing , Antibodies, Viral
12.
Funct Integr Genomics ; 24(2): 58, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489049

ABSTRACT

Recent studies have shown that NOP2, a nucleolar protein, is up-regulated in various cancers, suggesting a potential link to tumor aggressiveness and unfavorable outcomes. This study examines NOP2's role in lung adenocarcinoma (LUAD), a context where its implications remain unclear. Utilizing bioinformatics, we assessed 513 LUAD and 59 normal tissue samples from The Cancer Genome Atlas (TCGA) to explore NOP2's diagnostic and prognostic significance in LUAD. Additionally, in vitro experiments compared NOP2 expression between Beas-2b and A549 cells. Advanced databases and analytical tools, including LINKEDOMICS, STRING, and TISIDB, were employed to further elucidate NOP2's association with LUAD. Our findings indicate a significantly higher expression of NOP2 mRNA and protein in A549 cells compared to Beas-2b cells (P < 0.001). In LUAD, elevated NOP2 levels were linked to decreased Overall Survival (OS) and advanced clinical stages. Univariate Cox analysis revealed that high NOP2 expression correlated with poorer OS in LUAD (P < 0.01), a finding independently supported by multivariate Cox analysis (P < 0.05). The relationship between NOP2 expression and LUAD risk was presented via a Nomogram. Additionally, Gene Set Enrichment Analysis (GSEA) identified seven NOP2-related signaling pathways. A focal point of our research was the interplay between NOP2 and tumor-immune interactions. Notably, a negative correlation was observed between NOP2 expression and the immune infiltration levels of macrophages, neutrophils, mast cells, Natural Killer (NK) cells, and CD8 + T cells in LUAD. Moreover, the expression of NOP2 was related to the sensitivity of various chemotherapeutic drugs. In vitro, we found that downregulating NOP2 can decrease the proliferation, migration and invasion of A549 cells. Furthermore, NOP2 can regulate Caspase3-mediated apoptosis. Collectively, particularly regarding prognosis, immune infiltration and vitro experiments, these findings suggest NOP2's potential of serving as a poor-prognostic biomarker for LUAD and aggravating the malignancy of lung adenocarcinoma cells.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Nuclear Proteins , Adenocarcinoma of Lung/genetics , Apoptosis , Computational Biology , Lung Neoplasms/genetics , tRNA Methyltransferases
13.
CNS Neurosci Ther ; 30(3): e14664, 2024 03.
Article in English | MEDLINE | ID: mdl-38516781

ABSTRACT

AIMS: Neuroblastoma (NB) is the most common extracranial solid tumor in children, with a 5-year survival rate of <50% in high-risk patients. MYCN amplification is an important factor that influences the survival rate of high-risk patients. Our results indicated MYCN regulates the expression of SESN1. Therefore, this study aimed to investigate the role and mechanisms of SESN1 in NB. METHODS: siRNAs or overexpression plasmids were used to change MYCN, SESN1, or MyD88's expression. The role of SESN1 in NB cell proliferation, migration, and invasion was elucidated. Xenograft mice models were built to evaluate SESN1's effect in vivo. The correlation between SESN1 expression and clinicopathological data of patients with NB was analyzed. RNA-Seq was done to explore SESN1's downstream targets. RESULTS: SESN1 was regulated by MYCN in NB cells. Knockdown SESN1 promoted NB cell proliferation, cell migration, and cell invasion, and overexpressing SESN1 had opposite functions. Knockdown SESN1 promoted tumor growth and shortened tumor-bearing mice survival time. Low expression of SESN1 had a positive correlation with poor prognosis in patients with NB. RNA-Seq showed that Toll-like receptor (TLR) signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway in cancer were potential downstream targets of SESN1. Knockdown MyD88 or TLRs inhibitor HCQ reversed the effect of knockdown SESN1 in NB cells. High expression of SESN1 was significantly associated with a higher immune score and indicated an active immune microenvironment for patients with NB. CONCLUSIONS: SESN1 functions as a new tumor suppressor gene via TLR signaling pathway in NB.


Subject(s)
Myeloid Differentiation Factor 88 , Neuroblastoma , Child , Humans , Animals , Mice , N-Myc Proto-Oncogene Protein/genetics , N-Myc Proto-Oncogene Protein/metabolism , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Transcription Factors/genetics , Signal Transduction/genetics , Neuroblastoma/pathology , Genes, Tumor Suppressor , Toll-Like Receptors/genetics , Toll-Like Receptors/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Tumor Microenvironment , Sestrins/genetics , Sestrins/metabolism
14.
Phys Rev Lett ; 132(7): 076902, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38427888

ABSTRACT

We study experimentally and theoretically the hybridization among intralayer and interlayer moiré excitons in a MoSe_{2}/WS_{2} heterostructure with antiparallel alignment. Using a dual-gate device and cryogenic white light reflectance and narrow-band laser modulation spectroscopy, we subject the moiré excitons in the MoSe_{2}/WS_{2} heterostack to a perpendicular electric field, monitor the field-induced dispersion and hybridization of intralayer and interlayer moiré exciton states, and induce a crossover from type I to type II band alignment. Moreover, we employ perpendicular magnetic fields to map out the dependence of the corresponding exciton Landé g factors on the electric field. Finally, we develop an effective theoretical model combining resonant and nonresonant contributions to moiré potentials to explain the observed phenomenology, and highlight the relevance of interlayer coupling for structures with close energetic band alignment as in MoSe_{2}/WS_{2}.

16.
Mucosal Immunol ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38428739

ABSTRACT

Sleep deprivation (SD) has a wide range of adverse health effects. However, the mechanisms by which SD influences corneal pathophysiology and its post-wound healing remain unclear. This study aimed to examine the basic physiological characteristics of the cornea in mice subjected to SD and determine the pathophysiological response to injury after corneal abrasion. Using a multi-platform water environment method as an SD model, we found that SD leads to disturbances of corneal proliferative, sensory, and immune homeostasis as well as excessive inflammatory response and delayed repair after corneal abrasion by inducing hyperactivation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Pathophysiological changes in the cornea mainly occurred through the activation of the IL-17 signaling pathway. Blocking both adrenergic and glucocorticoid synthesis and locally neutralizing IL-17A significantly improved corneal homeostasis and the excessive inflammatory response and delay in wound repair following corneal injury in SD-treated mice. These results indicate that optimal sleep quality is essential for the physiological homeostasis of the cornea and its well-established repair process after injury. Additionally, these observations provide potential therapeutic targets to ameliorate SD-induced delays in corneal wound repair by inhibiting or blocking the activation of the stress system and its associated IL-17 signaling pathway.

17.
iScience ; 27(3): 109165, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38420589

ABSTRACT

Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality, and its severity is closely related to the short-term prognosis of SAH patients. S100 calcium-binding protein A9 (S100A9) has been shown to be associated with some neurological diseases. In this study, the concentration of S100A9 in clinical cerebrospinal fluid samples was detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between S100A9 and the prognosis of patients was explored. In addition, WT mice and S100A9 knockout mice were used to establish an in vivo SAH model. Neurological scores, brain water content, and histopathological staining were performed after a specified time. A co-culture model of BV2 and HT22 cells was treated with heme chloride to establish an in vitro SAH model. Our study confirmed that the expression of S100A9 protein in the CSF of SAH patients is increased, and it is related to the short-term prognosis of SAH patients. S100A9 protein is highly expressed in microglia in the central nervous system. S100A9 gene knockout significantly improved neurological function scores and reduced neuronal apoptosis. S100A9 protein can activate TLR4 receptor, promote nuclear transcription of NF-κB, increase the activation of inflammatory body, and ultimately aggravate nerve injury.

18.
Zhongguo Zhong Yao Za Zhi ; 49(1): 216-223, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403354

ABSTRACT

This study aims to investigate the effect of Buyang Huanwu Decoction on blood flow recovery and arteriogenesis after hindlimb ischemia in mice via the platelet-derived growth factor(PDGF) signaling pathway. Forty C57BL/6 mice were randomized into model(clean water, 10 mL·kg~(-1)·d~(-1)), beraprost sodium(positive control, 18 µg·kg~(-1)·d~(-1)), and low-, medium-, and high-dose(10, 20, and 40 g·kg~(-1)·d~(-1), respectively) Buyang Huanwu Decoction groups(n=8). The hindlimb ischemia model was established by femoral artery ligation. The mice were administrated with corresponding agents by gavage daily for 14 days after ligation. For laser Doppler perfusion imaging, the mice were anesthetized and measured under a Periscan PSI imager. The density of capillary and arterio-le in the ischemic gastrocnemius was measured using immunofluorescence staining of the frozen tissue sections. Western blot was employed to determine the expression of PDGF subunit B(PDGFB), phosphorylated mitogen extracellular kinase(p-MEK), MEK, phosphorylated extracellular signal-regulated kinase(p-ERK), and ERK. Real-time PCR was employed to determine the mRNA level of PDGFB. The Buyang Huanwu Decoction-containing serum was used to treat the vascular smooth muscle cells(VSMCs) in hypoxia at doses of 10% and 20%. The proliferation and migration of VSMCs was assessed in vitro. The results showed that compared with the model group, beraprost sodium and Buyang Huanwu Decoction enhanced the blood flow recovery, increased the capillary and arteriole density, and up-regulated the protein levels of PDGFB, p-MEK, p-ERK, and mRNA levels of PDGFB, with the medium-dose Buyang Huanwu Decoction demonstrating the most significant effect. The 10% Buyang Huanwu Decoction-containing serum enhanced the proliferation and migration of VSMCs. Our findings demonstrate that Buyang Huanwu Decoction up-regulates PDGFB transcription and activates PDGF signaling pathway to promote arteriogenesis and blood flow recovery in ischemic gastrocnemius.


Subject(s)
Drugs, Chinese Herbal , Rats , Mice , Animals , Rats, Sprague-Dawley , Proto-Oncogene Proteins c-sis , Mice, Inbred C57BL , Drugs, Chinese Herbal/therapeutic use , Signal Transduction , Ischemia/drug therapy , Hindlimb/metabolism , RNA, Messenger/metabolism , Mitogen-Activated Protein Kinase Kinases/metabolism
19.
Pigment Cell Melanoma Res ; 37(3): 411-425, 2024 May.
Article in English | MEDLINE | ID: mdl-38411373

ABSTRACT

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.


Subject(s)
Melanoma , Mutation , Uveal Neoplasms , Uveal Neoplasms/genetics , Uveal Neoplasms/pathology , Uveal Neoplasms/therapy , Humans , Melanoma/genetics , Melanoma/pathology , Melanoma/therapy , Mutation/genetics , Molecular Targeted Therapy , Neoplasm Metastasis , Animals , Immunotherapy
20.
Mucosal Immunol ; 17(2): 211-225, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38331094

ABSTRACT

Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl] (AMG-517)) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, tumor necrosis factor-α production by MCs, eosinophil infiltration and activation, and C-C motif chemokine 11 (CCL11) (eotaxin-1) expression in fibroblasts. Subsequent findings demonstrated that TRPV1+ sensory nerves secrete somatostatin (SST), which binds to SST receptor 5 (SSTR5) on MCs and conjunctival fibroblasts. SST effectively inhibited tumor necrosis factor-α production in MCs and CCL11 expression in fibroblasts, thereby reducing eosinophil infiltration and alleviating AC symptoms, including eyelid swelling, lacrimation, conjunctival chemosis, and redness. These findings suggest that targeting TRPV1+ sensory nerve-mediated SST-SSTR5 signaling could be a promising therapeutic strategy for AC, offering insights into neuroimmune mechanisms and potential targeted treatments.


Subject(s)
Antineoplastic Agents , Conjunctivitis, Allergic , Mice , Animals , Tumor Necrosis Factor-alpha/metabolism , Conjunctiva/metabolism , Conjunctiva/pathology , Eosinophils , Antineoplastic Agents/adverse effects , Inflammation/metabolism , TRPV Cation Channels/genetics , TRPV Cation Channels/metabolism
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