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1.
J Cell Mol Med ; 28(14): e18575, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39048916

ABSTRACT

In recent years, in the development of emerging immunotherapy, B7-H3 is also termed as CD276 and has become a novel chimeric antigen receptor (CAR)-T target against glioma and other tumours, and aroused extensive attention. However, B7-H3 has three isoforms (2, 3 and 4Ig) with the controversial expression and elusive function in tumour especially glioma. The current study mainly focuses on the regulatory factors and related mechanisms of generation of different B7-H3 isoforms. First, we have determined that 2Ig is dominant in glioma with high malignancy, and 4Ig is widely expressed, whereas 3Ig shows negative expression in all glioma. Next, we have further found that RNA binding protein annexin A2 (ANXA2) is essential for B7-H3 isoform maintenance, but fail to determine the choice of 4Ig or 2Ig. RNA methyltransferase NOP2/Sun RNA methyltransferase 2 (NSUN2) and 5-methylcytosine reader Y-box binding protein 1 (YBX1) facilitate the production of 2Ig. Our findings have uncovered a series of factors (ANXA2/NSUN2/YBX1) that can determine the alternative generation of different isoforms of B7-H3 in glioma. Our result aims to help peers gain a clearer understanding of the expression and regulatory mechanisms of B7H3 in tumour patients, and to provide better strategies for designing B7H3 as a target in immunotherapy.


Subject(s)
Annexin A2 , B7 Antigens , Gene Expression Regulation, Neoplastic , Glioma , Protein Isoforms , Humans , Glioma/genetics , Glioma/metabolism , Glioma/pathology , B7 Antigens/metabolism , B7 Antigens/genetics , Protein Isoforms/metabolism , Protein Isoforms/genetics , Annexin A2/metabolism , Annexin A2/genetics , Cell Line, Tumor , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/pathology
2.
Clin Immunol ; 265: 110296, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38914361

ABSTRACT

Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895-0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796-0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Nomograms , Humans , Female , Male , Adult , Lupus Erythematosus, Systemic/complications , Kidney/pathology , ROC Curve , Middle Aged , Prognosis , Young Adult , Cohort Studies , Risk Factors
3.
J Transl Med ; 22(1): 408, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689293

ABSTRACT

Cancer-related cachexia is a metabolic syndrome characterized by weight loss, adipose tissue decomposition, and progressive skeletal muscle atrophy. It is a major complication of many advanced cancers and seriously affects the quality of life and survival of cancer patients. However, the specific molecules that mediate cancer-related cachexia remain elusive, and the fundamental cellular and molecular mechanisms associated with muscle atrophy and lipidolysis in cancer patients still need to be investigated. Exosomes, a newly discovered class of small extracellular vesicles that facilitate intercellular communication, have a significant role in the onset and development of various cancers. Studies have shown that exosomes play a role in the onset and progression of cancer-related cachexia by transporting active molecules such as nucleic acids and proteins. This review aimed to provide an overview of exosome developments in cancer-induced skeletal muscle atrophy and adipose tissue degradation. More importantly, exosomes were shown to have potential as diagnostic markers or therapeutic strategies for cachexia and were prospected, providing novel strategies for the diagnosis and treatment of cancer-related cachexia.


Subject(s)
Cachexia , Exosomes , Neoplasms , Cachexia/etiology , Cachexia/pathology , Cachexia/therapy , Cachexia/metabolism , Humans , Exosomes/metabolism , Neoplasms/complications , Neoplasms/pathology , Animals , Adipose Tissue/pathology , Adipose Tissue/metabolism , Muscular Atrophy/pathology , Muscular Atrophy/metabolism , Muscular Atrophy/etiology
4.
Microb Pathog ; 191: 106669, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38697231

ABSTRACT

African swine fever (ASF) is a lethal disease caused by ASF virus (ASFV), severely impacting the global swine industry. Though nuclear acid-based detection methods are reliable, they are laboratory-dependent. In this study, we developed a device-independent, user friendly and cost-effective quantum dots based immunochromatographic strip (QDs-ICS) with high specificity and sensitivity for the rapid and on-site detection of ASFV antigen. For the preparation of the QDs-ICS, we generated a monoclonal antibody (mAb) mAb-8G8 and polyclonal antibody (pAb) against ASFV-p72 protein. The pAb was labelled with QDs to be used as the detection probe and the mAb-8G8 was coated on the nitrocellulose membrane as the test line. Our results proved that the strip displayed no cross-reactivity with other swine viruses and detection limit of the QDs-ICS was down to 1 ng/mL for the ASFV-p72 protein with great reproducibility. The strip also exhibited high stability with a storage period up to 12 months under room temperature. Twenty blind samples and one hundred clinical samples were examined by the QDs-ICS, conventional PCR and real-time PCR method, respectively. Results showed that the agreement rate between the QDs-ICS and PCR method was 100%, and the agreement rate between the strip and real-time PCR was 94%. The novel QDs-ICS developed here would be an effective tool for on-site detection of ASFV.


Subject(s)
African Swine Fever Virus , African Swine Fever , Antibodies, Monoclonal , Antibodies, Viral , Antigens, Viral , Chromatography, Affinity , Quantum Dots , Sensitivity and Specificity , African Swine Fever Virus/isolation & purification , African Swine Fever Virus/immunology , African Swine Fever Virus/genetics , Animals , African Swine Fever/diagnosis , African Swine Fever/virology , African Swine Fever/immunology , Swine , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Chromatography, Affinity/methods , Antigens, Viral/analysis , Antigens, Viral/immunology , Reproducibility of Results , Reagent Strips
5.
Clin Exp Rheumatol ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38910583

ABSTRACT

OBJECTIVES: To investigate the expression and function of WNT16, a member of the WNT family protein, in the context of systemic lupus erythematosus (SLE). METHODS: WNT16 expression was assessed in peripheral blood mononuclear cells (PBMCs) from 35 SLE patients and 25 healthy individuals using quantitative polymerase chain reaction. Additionally, serum WNT16 protein levels were quantified via enzyme-linked immunosorbent assay in 162 SLE patients, 96 healthy controls (HC), and disease controls comprised 154 individuals with rheumatoid arthritis (RA) and Sjögren's syndrome (SS). We investigated the associations between WNT16 protein levels and clinical manifestations, laboratory indices, and disease activity in SLE patients. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of serum WNT16 for SLE. Furthermore, we performed a knockdown assay on Jeko-1 cells and assessed cell proliferation and apoptosis using Cell Counting Kit-8 and flow cytometry. RESULTS: WNT16 mRNA in SLE patients' PBMCs were significantly lower than those in HC. Furthermore, serum WNT16 in SLE patients were markedly reduced compared to HC, RA, and SS cohorts. ROC curve analysis indicated that plasma WNT16 levels could serve as a potential biomarker for SLE identification (AUC=0.809, SLE vs. HC; AUC=0.760, SLE vs. RA; AUC=0.710, SLE vs. SS). Notably, a weak positive correlation was observed between WNT16 protein and both alkaline phosphatase and lymphocyte percentages. Conversely, a weak negative correlation existed between WNT16 and low-density lipoprotein, neutrophil percentage, and the incidence of pleurisy and disease activity. Additionally, our study confirmed that WNT16 knockdown impairs cell proliferation and enhances apoptosis. CONCLUSIONS: Serum WNT16 levels effectively differentiate SLE patients from healthy controls and individuals with other autoimmune disorders. WNT16 serves as a potential biomarker with high sensitivity. The diminished expression of WNT16 in SLE may have a significant role in its pathogenesis through the regulation of cell proliferation and apoptosis.

6.
Plant Dis ; 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38173267

ABSTRACT

Pear is popular among people, which is an important pillar industry in China. In March of 2023, dark brown necrotic lesions were discovered on the trunks of Pyrus pyrofolia cv. Osmanthus pear in orchard, Liuzhou City, Guangxi Zhuang Autonomous Region. In August, field investigation and sample collection were conducted in orchard. Forty pear trees were selected for symptomatic observation, which of 21 had lesions ranging from 10 to 24 per tree, and 19 with 1 to 8 lesions, respectively. To isolate the pathogen, small tissue pieces of 3 diseased pear trunk samples were disinfected with 75% ethanol for 1 minute, rinsed with sterile water, and dried with filter paper. The tissue pieces were placed on potato dextrose agar (PDA) plates and cultured in a dark incubator at 25℃. Six isolates with the similar morphology were obtained. One of the six isolates was randomly selected as the representative strain and named as GX-3. Mycelium grows with an average rate of 4.26 cm/d. The hypha is highly aerial, and is initially white and then turns black. Subsequently, pycnidia formed and secreted black mucus on the PDA medium after 28 days. The immature conidia were ellipsoid, colorless, hyaline, and unicellular, mostly becoming brown bicellular with longitudinal stripes at maturity. The conidial size was 22.5 to 32.6×12.1 to 19.7µm, and the average size was 28.4±2.3×16.7±2.0 µm (n=50), respectively. GX-3 colony morphology was consistent with that of Lasiodiplodia pseudotheobromae (Alves et al.2008). For molecular identification, the internal transcribed spacer of rDNA (ITS), translation elongation factor 1-α (TEF1-α), and ß-tubulin regions were amplified using the primers ITS1/4, EF1-728F/986R, and Bt2a/Bt2b, respectively (White et al.1990; Carbone and Kohn 1999; Glass and Donaldson 1995). The obtained sequences of GX-3 were deposited in NCBI with Accession numbers OR655421, OR661231, and OR661230, respectively. The sequences of ITS, TEF1-α, and ß-tubulin from GX-3 are 99.44%、99.67% and 99.78% identities with those of L. pseudotheobromae CBS 447.62, respectively. The phylogenetic analysis was performed by maximum likelihood method, revealing that GX-3 is closely clustered with the isolates of L. pseudotheobromae. Therefore, the GX-3 strain was identified as L. pseudotheobromae. GX-3 was further analyzed for its pathogenicity on pear. Firstly, the GX-3 mycelium plugs and spraying spore suspension with the concentration of 1×107 conidia/ml were applied on the stems of 4-month-old healthy birch-leaf pear (Pyrus betulifolia Bunge) potted seedlings by acupuncture needle method, meanwhile PDA and sterile water were used as controls. After 3 days of inoculation, stem surface of the birch-leaf pear exhibited dark brown lesions with slight surface depression, obvious dryness, and canker symptoms, while the control treatment showed no symptoms. The GX-3 was also inoculated on in vitro branches of 'Hosui', 'Hongxiangsu', 'Bodoqing' and 'Xuehua', showing dark brown canker lesions. The same pathogen can be successfully isolated from diseased stems and branches but not from the controls, which accomplishes Koch's postulates. L. pseudotheobromae has been widely reported that it can cause rot and canker on apple, walnut, hackberry, and so on (Xue et al. 2019; Wang et al. 2023; Liang et al. 2020). This is the first report of necrosis and canker disease caused by L. pseudotheobromae on pear in China, which is a potential threat to pear industry.

7.
PLoS Comput Biol ; 18(10): e1010594, 2022 10.
Article in English | MEDLINE | ID: mdl-36215325

ABSTRACT

Advanced volumetric imaging methods and genetically encoded activity indicators have permitted a comprehensive characterization of whole brain activity at single neuron resolution in Caenorhabditis elegans. The constant motion and deformation of the nematode nervous system, however, impose a great challenge for consistent identification of densely packed neurons in a behaving animal. Here, we propose a cascade solution for long-term and rapid recognition of head ganglion neurons in a freely moving C. elegans. First, potential neuronal regions from a stack of fluorescence images are detected by a deep learning algorithm. Second, 2-dimensional neuronal regions are fused into 3-dimensional neuron entities. Third, by exploiting the neuronal density distribution surrounding a neuron and relative positional information between neurons, a multi-class artificial neural network transforms engineered neuronal feature vectors into digital neuronal identities. With a small number of training samples, our bottom-up approach is able to process each volume-1024 × 1024 × 18 in voxels-in less than 1 second and achieves an accuracy of 91% in neuronal detection and above 80% in neuronal tracking over a long video recording. Our work represents a step towards rapid and fully automated algorithms for decoding whole brain activity underlying naturalistic behaviors.


Subject(s)
Brain , Caenorhabditis elegans , Animals , Caenorhabditis elegans/physiology , Brain/physiology , Neurons/physiology
8.
Biometrics ; 79(4): 3082-3095, 2023 12.
Article in English | MEDLINE | ID: mdl-37211860

ABSTRACT

Group variable selection is often required in many areas, and for this many methods have been developed under various situations. Unlike the individual variable selection, the group variable selection can select the variables in groups, and it is more efficient to identify both important and unimportant variables or factors by taking into account the existing group structure. In this paper, we consider the situation where one only observes interval-censored failure time data arising from the Cox model, for which there does not seem to exist an established method. More specifically, a penalized sieve maximum likelihood variable selection and estimation procedure is proposed and the oracle property of the proposed method is established. Also, an extensive simulation study is performed and suggests that the proposed approach works well in practical situations. An application of the method to a set of real data is provided.


Subject(s)
Proportional Hazards Models , Likelihood Functions , Regression Analysis , Computer Simulation
9.
Theor Appl Genet ; 135(12): 4289-4302, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36136127

ABSTRACT

KEY MESSAGE: GWAS identified 347 QTLs associated with eight traits related to nitrogen use efficiency in a 389-count wheat panel. Four novel candidate transcription factor genes were verified using qRT-PCR. Nitrogen is an essential nutrient for plants that determines crop yield. Improving nitrogen use efficiency (NUE) should considerably increase wheat yield and reduce the use of nitrogen fertilisers. However, knowledge on the genetic basis of NUE during wheat maturity is limited. In this study, a diversity panel incorporating 389 wheat accessions was phenotyped for eight NUE-related agronomic traits across five different environments. A total of 347 quantitative trait loci (QTLs) for low nitrogen tolerance indices (ratio of agronomic characters under low and high nitrogen conditions) were identified through a genome-wide association study utilising 397,384 single nucleotide polymorphisms (SNPs) within the MLM (Q + K) model, including 11 stable QTLs. Furthermore, 69 candidate genes were predicted for low nitrogen tolerance indices of best linear unbiased predictions values of the eight studied agronomic traits, and four novel candidate transcription factors (TraesCS5A02G237500 for qFsnR5A.2, TraesCS5B02G384500 and TraesCS5B02G384600 for qSLR5B.1, and TraesCS3B02G068800 for qTKWR3B.1) showed differing expression patterns in contrasting low-nitrogen-tolerant wheat genotypes. Moreover, the number of favourable marker alleles calculated using NUE that were significantly related to SNP in accessions decreased over the decades, indicating a decline in the NUE of the 389 wheat varieties. These findings denote promising NUE markers that could be useful in breeding high-NUE wheat varieties, and the candidate genes could further detail the NUE-related regulation network in wheat.


Subject(s)
Genome-Wide Association Study , Triticum , Triticum/genetics , Triticum/metabolism , Nitrogen/metabolism , Plant Breeding , Quantitative Trait Loci , Phenotype , Polymorphism, Single Nucleotide
10.
Anal Bioanal Chem ; 413(6): 1629-1637, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33495847

ABSTRACT

Total aflatoxins (AFTs) are an important safety indicator for botanical materials, but at present, rapid detection technology for AFTs is seldom reported. In this study, the monoclonal antibody with similar reactivity to total aflatoxins was produced, and the quantum dot-based lateral flow immunoassay (QD-LFIA) coupled with a portable device was developed to rapidly determine AFT residues in botanical materials. The half maximal inhibitory concentrations (IC50) of the QD-LFIA for AFB1, AFB2, AFG1, AFG2, AFM1, and AFM2 were 10.57, 12.64, 11.34, 12.67, 10.13, and 12.75 µg kg-1, respectively, which show high reaction consistency to total aflatoxins. For different botanical materials, the sample was simply extracted with methanol-water and diluted with PBS, and the sample solution was directly loaded onto the QD-LFIA strip for determination. To overcome interference from the matrix effects, specific standard curves were established for each kind of botanical material. The detection limit of AFTs in 6 different botanical materials was 0.95~2.03 µg kg-1 with a linear range of 2~120 µg kg-1. The spiked recoveries of AFTs in botanical materials of different species and localities of growth were 75~105% with a coefficient of variation below 15%. The test results of the actual samples are consistent with the Chinese national standard test method. This study provides an easy-to-use method to rapidly determine AFTs in different botanical materials. Graphical abstract.


Subject(s)
Aflatoxins/analysis , Food Contamination/analysis , Immunoassay/methods , Quantum Dots , Antibodies, Monoclonal/chemistry , Antigens/analysis , Chromatography, High Pressure Liquid , Inhibitory Concentration 50 , Limit of Detection , Materials Testing , Reproducibility of Results , Software , Temperature
11.
Can J Physiol Pharmacol ; 95(5): 580-585, 2017 May.
Article in English | MEDLINE | ID: mdl-28177682

ABSTRACT

Multidrug resistance (MDR) is one of the major obstacles confronted in cancer chemotherapy; this obstacle is mainly due to the overexpression of P-glycoprotein (P-gp). Co-administration of anticancer drugs and P-gp inhibitors is a promising approach to overcome MDR. WYX-5, a novel P-gp inhibitor, shows a notable reversal effect with low cytotoxicity in vitro. In this paper, the reversal mechanism and safety of the MDR modulator WYX-5 were explored in vitro, and evaluated for its pharmacokinetics and effects on adriamycin (ADM) metabolism in vivo. The results suggest that WYX-5 is a potent P-gp inhibitor with EC50 in nanomole range (EC50 = 204.3 ± 20.2 nmol·L-1), relative safety (therapeutic index = 446.4), which performs as a substrate of P-gp and retrains its function. Further, WYX-5 (5 mg·kg-1) had relatively ideal pharmacokinetic properties (T1/2 = 6.448 h, F = 96.05%) without interactions with ADM metabolism in vivo. In conclusion, WYX-5 may be a promising candidate for MDR cancer combined-chemotherapy research.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/pharmacokinetics , Drug Resistance, Multiple/drug effects , Isoquinolines/pharmacology , Isoquinolines/pharmacokinetics , Triazoles/pharmacology , Triazoles/pharmacokinetics , Animals , Doxorubicin/metabolism , Doxorubicin/pharmacology , Drug Interactions , Humans , K562 Cells , Male , Rats , Xenograft Model Antitumor Assays
12.
Bioorg Med Chem ; 24(10): 2287-97, 2016 05 15.
Article in English | MEDLINE | ID: mdl-27073052

ABSTRACT

A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100µM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Drug Design , Drug Resistance, Multiple/drug effects , Tetrahydroisoquinolines/chemistry , Tetrahydroisoquinolines/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antibiotics, Antineoplastic/pharmacokinetics , Antibiotics, Antineoplastic/pharmacology , Benzamides/pharmacology , Click Chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/drug effects , Humans , K562 Cells , Neoplasms/drug therapy , Structure-Activity Relationship , Tetrahydroisoquinolines/chemical synthesis
13.
Biochem Biophys Res Commun ; 458(3): 596-600, 2015 Mar 13.
Article in English | MEDLINE | ID: mdl-25680470

ABSTRACT

To explore the association of the phenotype of ATP-activated current with the genotype of P2X1-6 subunits in nociceptors, we developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion (TG) neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons, and then to conduct single cell immunohistochemical staining for P2X1-6 subunits in the same neuron. We found that fast application of 100 µM ATP to fluorescence-traced TG neurons produced robust inward current in 87% (96/110) of cells tested. The diameter of cells varied from 16 to 56 µm. Three types of ATP-activated current (F, I and S) were recorded with distinct rise times of the current (R10-90, P < 0.05). There was a positive correlation between the cell diameter and the value of R10-90 (P < 0.05): the value of R10-90 increased with increases in the cell diameter. Cells responsive to ATP with the type F current mainly showed positive staining for P2X3 and P2X5, but negative staining for P2X2; cells responsive to ATP with the type I current showed positive staining for P2X1-3 and P2X5, but negative staining for P2X4; and cells responsive to ATP with the type S current showed positive staining for P2X1-5, but negative staining for P2X6. The present findings suggest that in addition to P2X3 subunits, P2X5 subunits are also involved in the generation of the F type of ATP-activated current in small-sized nociceptive neurons. In addition to the P2X2/3 subunit-containing channels, more complex uncharacterized combinations of P2X1-5 subunits exist in native medium-sized nociceptive neurons exhibiting the I and S types of ATP-activated current. In addition, the P2X6 subunit is not a main subunit involved in the nociceptive signal in rat TG neurons innervating tooth-pulp.


Subject(s)
Adenosine Triphosphate/metabolism , Dental Pulp/innervation , Neurons/cytology , Receptors, Purinergic P2X/metabolism , Receptors, Purinergic P2/metabolism , Animals , Cells, Cultured , Genotype , Immunohistochemistry , Neurons/metabolism , Patch-Clamp Techniques , Protein Subunits/genetics , Protein Subunits/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Purinergic P2/genetics , Receptors, Purinergic P2X/genetics , Trigeminal Ganglion/cytology
14.
Brain Res Bull ; 215: 111024, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38969066

ABSTRACT

Parkinson's disease is a complex neurodegenerative disease characterized by progressive movement impairments. Predominant symptoms encompass resting tremor, bradykinesia, limb rigidity, and postural instability. In addition, it also includes a series of non-motor symptoms such as sleep disorders, hyposmia, gastrointestinal dysfunction, autonomic dysfunction and cognitive impairment. Pathologically, the disease manifests through dopaminergic neuronal loss and the presence of Lewy bodies. At present, no significant breakthrough has been achieved in clinical Parkinson's disease treatment. Exploring treatment modalities necessitate the establishment of scientifically sound animal models. In recent years, researchers have focused on replicating the symptoms of human Parkinson's disease, resulting in the establishment of various experimental animal models primarily through drugs and transgenic methods to mimic relevant pathologies and identify more effective treatments. This review examines traditional neurotoxin and transgenic animal models as well as α-synuclein pre-formed fibrils models, non-human primate models and non-mammalian specie models. Additionally, it introduces emerging models, including models based on optogenetics, induced pluripotent stem cells, and gene editing, aiming to provide a reference for the utilization of experimental animal models and clinical research for researchers in this field.


Subject(s)
Disease Models, Animal , Parkinson Disease , Animals , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Parkinson Disease/pathology , Humans , Animals, Genetically Modified , alpha-Synuclein/metabolism , alpha-Synuclein/genetics
15.
Adv Sci (Weinh) ; : e2404190, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39115981

ABSTRACT

Piezoelectric effect produces an electrical signal when stress is applied to the bone. When the integrity of the bone is destroyed, the biopotential within the defect site is reduced and several physiological responses are initiated to facilitate healing. During the healing of the bone defect, the bioelectric potential returns to normal levels. Treatment of fractures that exceed innate regenerative capacity or exhibit delayed healing requires surgical intervention for bone reconstruction. For bone defects that cannot heal on their own, exogenous electric fields are used to assist in treatment. This paper reviews the effects of exogenous electrical stimulation on bone healing, including osteogenesis, angiogenesis, reduction in inflammation and effects on the peripheral nervous system. This paper also reviews novel electrical stimulation methods, such as small power supplies and nanogenerators, that have emerged in recent years. Finally, the challenges and future trends of using electrical stimulation therapy for accelerating bone healing are discussed.

16.
Genes Dis ; 11(6): 101180, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39281838

ABSTRACT

The NRF2 pathway is a metabolic- and redox-sensitive signaling axis in which the transcription factor controls the expression of a multitude of genes that enable cells to survive environmental stressors, such as oxidative stress, mainly by inducing the expression of cytoprotective genes. Basal NRF2 levels are maintained under normal physiological conditions, but when exposed to oxidative stress, cells activate the NRF2 pathway, which is crucial for supporting cell survival. Recently, the NRF2 pathway has been found to have novel functions in metabolic regulation and interplay with other signaling pathways, offering novel insights into the treatment of various diseases. Numerous studies have shown that targeting its pathway can effectively investigate the development and progression of age-related musculoskeletal diseases, such as sarcopenia, osteoporosis, osteoarthritis, and intervertebral disc degeneration. Appropriate regulation of the NRF2 pathway flux holds promise as a means to improve musculoskeletal function, thereby providing a new avenue for drug treatment of age-related musculoskeletal diseases in clinical settings. The review summarized an overview of the relationship between NRF2 and cellular processes such as oxidative stress, apoptosis, inflammation, mitochondrial dysfunction, ferroptosis, and autophagy, and explores the potential of targeted NRF2 regulation in the treatment of age-related musculoskeletal diseases.

17.
Medicine (Baltimore) ; 103(2): e36817, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38215116

ABSTRACT

BACKGROUND: Recurrent aphthous stomatitis (RAS) is common in clinical practice and imposes both physical and psychological distress on patients. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of fire needle therapy for the treatment of RAS, providing a basis for clinical decision-making. METHODS: Eight databases, in both Chinese and English, were searched from their inception until December 2022. All randomized controlled trials (RCTs) that utilized fire needle therapy, either alone or combined with other treatments for RAS, were considered. Data evaluation and extraction were conducted independently by 2 authors. RESULTS: The revised Cochrane Risk of Bias Version 2 tool was employed to assess the risk of bias in the included RCTs. A meta-analysis was conducted using Review Manager 5.4 and Stata 15.0. Nine RCTs involving 1469 patients were selected for inclusion. The meta-analysis revealed that, compared to a non-fire-needle control group (primarily utilizing vitamin and transfer factor treatments), fire needle therapy for RAS significantly improved the total effective rate (relative risk = 1.25, 95% confidence interval [CI] [1.14, 1.36], P < .00001), reduced the visual analogue scale score (mean difference = -1.68, 95% CI [-1.82, -1.53], P < .0001), diminished the Traditional Chinese Medicine symptom score (standardized mean difference = -1.20, 95% CI [-1.76, -0.65], P < .0001), and shortened the healing time (mean difference = -1.66, 95% CI [-2.73, -0.59], P = .002). Notably, there was no significant difference in the recurrence rate between the groups (relative risk = -0.18, 95% CI [-0.36, 0.01], P = .06). Further subgroup analysis on total efficacy rate was performed based on variables such as experimental group intervention, control group intervention, and duration of therapy to explore potential sources of heterogeneity. CONCLUSION: Fire needle therapy appears to be a clinically effective treatment for RAS, offering benefits such as pain alleviation, symptom improvement based on the Traditional Chinese Medicine parameters, and faster recovery. Nonetheless, the overall quality of the RCTs available raises concerns. Future research, involving high-quality RCTs, is essential to confirm the clinical efficacy and safety of this treatment. Registration number: PROSPERO (CRD42023387973).


Subject(s)
Stomatitis, Aphthous , Humans , Medicine, Chinese Traditional , Needles , Stomatitis, Aphthous/therapy
18.
Sci Rep ; 14(1): 8893, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632459

ABSTRACT

Here, this study reports single-band red upconversion emission in ß-Ba2ScAlO5: Yb3+/Er3+ phosphor by doping Mn2+. The optimum concentration of Mn2+ ions in ß-Ba2ScAlO5: Yb3+/Er3+ phosphor was 0.20. The intensity of red and green emissions is increased by 27.4 and 19.3 times, respectively. Compared with the samples without Mn2+ ions, the red-green integral strength ratio of ß-Ba2ScAlO5: Yb3+/Er3+/Mn2+ sample was significantly increased by 28.4 times, reaching 110.9. The UCL mechanism was explored by analyzing the down-conversion luminescence spectra, absorption spectra, UCL spectra, and upconversion fluorescence lifetime decay curves of Yb3+/Er3+/Mn2+ co-doped ß-Ba2ScAlO5. The enhancement of upconversion red light is achieved through energy transfer between defect bands and Er3+ ions, as well as energy transfer between Mn2+ ions and Er3+ ions. In addition, the Mn2+ doped ß-Ba2ScAlO5: Yb3+/Er3+ red UCL phosphors have great potential for ambient temperature sensing in the 298-523 K temperature range. The maximum sensitivity of ß-Ba2ScAlO5: Yb3+/Er3+/Mn2+ phosphor as a temperature sensor at 523 K is 0.0247 K-1.

19.
PLoS One ; 19(1): e0296416, 2024.
Article in English | MEDLINE | ID: mdl-38166022

ABSTRACT

In sorghum [Sorghum bicolor (L.) Moench], combining ability and heterosis analysis are commonly used to evaluate superior parental lines and to screen for strongly heterotic hybrids, which helps in sorghum variety selection and breeding. In this context, combining ability and heterosis analysis were assessed using 14 restorer lines and seven cytoplasmic male sterile (CMS) lines in 2019 and 2020. The analysis of variance of all cross combinations had highly significant differences for all characters studied, which indicated a wide variation across the parents, lines, testers, and crosses. Combining ability analysis showed that the general combining ability (GCA) and specific combining ability (SCA) of the different parents were differed significantly among different traits. Most combinations with high SCA also showed high GCA in their parent lines. The heritability in the narrow sense of grain weight per panicle and grain yield was relatively low, indicating that the ability of these traits to be directly inherited by offspring was weak, that they were greatly affected by the environment. The better-parent heterosis for plant height, grain weight per panicle, panicle length, and 1000-grain weight was consistent with the order of mid-parent heterosis from strong to weak. The GCA effects of two lines 10480A, 3765A and three testers 0-30R, R111, and JY15R were significant for the majority of the agronomic traits including grain yield and might be used for improving the yield of grains in sorghum as parents of excellent specific combining ability. Seven strongly heterotic F1 hybrids were screened; of these, hybrids 3765A × R111, 1102A × L2R, and 3765A × JY15R showed significant increases in seed iristectorigenin A content and will feature into the creation of new sorghum varieties rich in iristectorigenin A.


Subject(s)
Hybrid Vigor , Sorghum , Hybrid Vigor/genetics , Sorghum/genetics , Plant Breeding , Phenotype , Edible Grain
20.
Int Immunopharmacol ; 132: 112026, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38583240

ABSTRACT

Ubiquitination (Ub) and deubiquitination are crucial post-translational modifications (PTMs) that precisely regulate protein degradation. Under the catalysis of a cascade of E1-E2-E3 ubiquitin enzymes, ubiquitination extensively regulates protein degradation exerting direct impact on various cellular processes, while deubiquitination opposes the effect of ubiquitination and prevents proteins from degradation. Notably, such dynamic modifications have been widely investigated to be implicated in cell cycle, transcriptional regulation, apoptosis and so on. Therefore, dysregulation of ubiquitination and deubiquitination could lead to certain diseases through abnormal protein accumulation and clearance. Increasing researches have revealed that the dysregulation of catalytic regulators of ubiquitination and deubiquitination triggers imbalance of cartilage homeostasis that promotes osteoarthritis (OA) progression. Hence, it is now believed that targeting on Ub enzymes and deubiquitinating enzymes (DUBs) would provide potential therapeutic pathways. In the following sections, we will summarize the biological role of Ub enzymes and DUBs in the development and progression of OA by focusing on the updating researches, with the aim of deepening our understanding of the underlying molecular mechanism of OA pathogenesis concerning ubiquitination and deubiquitination, so as to explore novel potential therapeutic targets of OA treatment.


Subject(s)
Osteoarthritis , Ubiquitination , Humans , Osteoarthritis/metabolism , Animals , Deubiquitinating Enzymes/metabolism , Protein Processing, Post-Translational
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