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1.
Shanghai Kou Qiang Yi Xue ; 33(2): 113-116, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-39005084

ABSTRACT

PURPOSE: To study the damage and the expression of LC3 and p62 of condylar cartilage in fluorosis mouse. METHODS: Thirty 4-week-old male C57BL/6 mice were randomly divided into control group and the experimental group with 15 animals in each group. The control group received regular drinking water and the experimental group received a fluoride concentration of 75 mg/L drinking water for 8 weeks. The structure of condylar cartilage was observed through modified safranine O-fast green FCF cartilage stain kit. Immunohistochemistry was used to detect the expression of MMP-13, type Ⅱ collagen and LC3 and p62. Two-way analysis of variance test was conducted for analysis of semi-quantitative results of immunohistochemistry using SPSS 22.0 software package. RESULTS: Compared with the control group, the fibrocartilage layer of the experimental group became thinner, the condrocytes were smaller, and the staining became deeper.Immunohistochemistry results showed that the expression of MMP-13 and LC3 increased; the expression of type Ⅱ collagen and p62 decreased in the experimental group. CONCLUSIONS: There was degeneration of the condylar cartilage and autophagy in mice with drinking water containing 75 mg/L fluoride.


Subject(s)
Autophagy , Fluorosis, Dental , Matrix Metalloproteinase 13 , Mice, Inbred C57BL , Microtubule-Associated Proteins , Animals , Mice , Autophagy/drug effects , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 13/genetics , Male , Microtubule-Associated Proteins/metabolism , Fluorosis, Dental/metabolism , Collagen Type II/metabolism , Mandibular Condyle/metabolism , Mandibular Condyle/pathology , Fluorides/toxicity , Cartilage, Articular/metabolism , Immunohistochemistry
2.
World J Gastroenterol ; 30(24): 3076-3085, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38983956

ABSTRACT

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU). AIM: To investigate the contributions of H. pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases. METHODS: Patients with H. pylori infection and either GU or DU, and healthy individuals without H. pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed. RESULTS: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H. pylori-positive patients with GU was dominated by H. pylori, with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H. pylori-positive GU patients, were all derived from H. pylori, particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori-positive DU patients and healthy controls. CONCLUSION: H. pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU.


Subject(s)
Duodenal Ulcer , Gastric Mucosa , Gastrointestinal Microbiome , Helicobacter Infections , Helicobacter pylori , Stomach Ulcer , Humans , Helicobacter Infections/microbiology , Helicobacter pylori/isolation & purification , Helicobacter pylori/genetics , Duodenal Ulcer/microbiology , Duodenal Ulcer/diagnosis , Male , Female , Middle Aged , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Stomach Ulcer/microbiology , Adult , Case-Control Studies , Aged , Metagenomics/methods , Duodenum/microbiology , Dysbiosis/microbiology
3.
J Chem Phys ; 161(3)2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39007369

ABSTRACT

We propose a scheme for achieving basic quantum gates using ultracold polar molecules in pendular states. The qubits are encoded in the YbF molecules trapped in an electric field with a certain gradient and coupled by the dipole-dipole interaction. The time-dependent control sequences consisting of multiple pulses are considered to interact with the pendular qubits. To achieve high-fidelity quantum gates, we map the control problem for the coupled molecular system into a Markov decision process and deal with it using the techniques of deep reinforcement learning (DRL). By training the agents over multiple episodes, the optimal control pulse sequences for the two-qubit gates of NOT, controlled NOT, and Hadamard are discovered with high fidelities. Moreover, the population dynamics of YbF molecules driven by the discovered gate sequences are analyzed in detail. Furthermore, by combining the optimal gate sequences, we successfully simulate the quantum circuit for entanglement. Our findings could offer new insights into efficiently controlling molecular systems for practical molecule-based quantum computing using DRL.

4.
Nat Commun ; 15(1): 5912, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003287

ABSTRACT

Previous studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.


Subject(s)
Acute Kidney Injury , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Glucagon-Like Peptide-1 Receptor/agonists , Male , Female , Middle Aged , Aged , Acute Kidney Injury/mortality , Acute Kidney Injury/drug therapy , Hypoglycemic Agents/therapeutic use , Cardio-Renal Syndrome/drug therapy , Cardio-Renal Syndrome/mortality , Cardiovascular Diseases/mortality , Cardiovascular Diseases/drug therapy , Treatment Outcome , Glucagon-Like Peptide-1 Receptor Agonists
5.
Neurospine ; 21(2): 665-675, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38955536

ABSTRACT

OBJECTIVE: This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans. METHODS: Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net's segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness. RESULTS: The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements. CONCLUSION: Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124735, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38955066

ABSTRACT

Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.

7.
Bot Stud ; 65(1): 18, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38992189

ABSTRACT

BACKGROUND: The emergence of Spodoptera frugiperda (fall armyworm; FAW) in the world has raised concerns regarding its impact on crop production, particularly on corn and sorghum. While chemical control and Bt crops have been effective in managing FAW damage, the development of pesticide-resistant and Bt-resistant strains necessitates alternative control methods. The push-pull farming system has gained attention, but direct utilization of African plant species in Taiwan faces challenges due to invasive potential and climatic disparities. Therefore, identifying and evaluating suitable local plant species, such as Napier grass (Pennisetum purpureum), Desmodium species, and signal grass (Brachiaria brizantha), is crucial for implementing effective FAW management strategies in Taiwan. RESULTS: In screening fifty Napier grass germplasms, all demonstrated an antibiotic effect, reducing leaf consumption compared to corn. Notably, thirty-five germplasms exhibited robust antibiotic traits, decreasing FAW consumption and increasing mortality rates. Three Napier grass germplasms also attracted more female moths for oviposition. Further evaluation of selected Napier grass germplasms and signal grass demonstrated efficacy in reducing FAW larval weight and survival duration. Additionally, Desmodium species, particularly D. uncinatum, showed promising toxicity against FAW larvae. CONCLUSION: Our findings support the effectiveness of selected Napier grass germplasms and signal grass as pull plants, and highlight the potential of D. uncinatum as a push plant in FAW management strategies in Taiwan.

8.
Heliyon ; 10(12): e32743, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975171

ABSTRACT

The pathogenesis of schizophrenia (SCZ) is heavily influenced by genetic factors. Ring finger protein 4 (RNF4) and squamous cell carcinoma antigen recognized by T cells 3 (SART3) are thought to be involved in nervous system growth and development via oxidative stress pathways. Moreover, they have previously been linked to SCZ. Yet the role of RNF4 and SART3 in SCZ remains unclear. Here, we investigated how these two genes are involved in SCZ by studying their variants observed in patients. We first observed significantly elevated mRNA levels of RNF4 and SART3 in the peripheral blood in both first-episode (n = 30) and chronic (n = 30) SCZ patients compared to controls (n = 60). Next, we targeted-sequenced three single nucleotide polymorphisms (SNPs) in SART3 and six SNPs in RNF4 for association with SCZ using the genomic DNA extracted from peripheral blood leukocytes from SCZ participants (n = 392) and controls (n = 572). We observed a combination of SNPs that included rs1203860, rs2282765 (both in RNF4), and rs2287550 (in SART3) was associated with increased risk of SCZ, suggesting common pathogenic mechanisms between these two genes. We then conducted experiments in HEK293T cells to better understand the interaction between RNF4 and SART3. We observed that SART3 lowered the expression of RNF4 through ubiquitination and downregulated the expression of nuclear factor E2-related factor 2 (NRF2), a downstream factor of RNF4, implicating the existence of a possible shared regulatory mechanism for RNF4 and SART3. In conclusion, our study provides evidence that the interaction between RNF4 and SART3 contributes to the risk of SCZ. The findings shed light on the underlying molecular mechanisms of SCZ and may lead to the development of new therapies and interventions for this disorder.

9.
Chem Soc Rev ; 53(13): 6960-6991, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38836431

ABSTRACT

The past few decades have witnessed encouraging progress in the development of high-performance film-based fluorescent sensors (FFSs) for detecting explosives, illicit drugs, chemical warfare agents (CWAs), and hazardous volatile organic chemicals (VOCs), among others. Several FFSs have transitioned from laboratory research to real-world applications, demonstrating their practical relevance. At the heart of FFS technology lies the sensing films, which play a crucial role in determining the analytes and the resulting signals. The selection of sensing fluorophores and the fabrication strategies employed in film construction are key factors that influence the fluorescence properties, active-layer structures, and overall sensing behaviors of these films. This review examines the progress and innovations in the research field of FFSs over the past two decades, focusing on advancements in fluorophore design and active-layer structural engineering. It underscores popular sensing fluorophore scaffolds and the dynamics of excited state processes. Additionally, it delves into six distinct categories of film fabrication technologies and strategies, providing insights into their advantages and limitations. This review further addresses important considerations such as photostability and substrate effects. Concluding with an overview of the field's challenges and prospects, it sheds light on the potential for further development in this burgeoning area.

10.
J Formos Med Assoc ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38910095

ABSTRACT

INTRODUCTION: Fluid resuscitation reduces mortality and morbidity in acute pancreatitis (AP); however, whether glucose-containing fluids negatively impact AP remains uncertain. We aimed to examine the association between glucose-containing fluids and AP outcomes. METHODS: This multicenter retrospective cohort study included patients diagnosed with AP between January 2015 and December 2018. Glucose density was defined as total glucose content divided by total fluid volume (g/dl) on day 1, and was considered high if the level exceeded the median. Endpoints were early organ failure (OF), including cardiovascular, renal, or respiratory system failure within 7 days; 30-day OF; ICU admission; and AP-related 90-day mortality. Logistic regression models, restricted cubic spline curves, and Cox proportional hazards models were used for statistical analysis. RESULTS: From the database, 1,146 patients with AP were included. Early OF occurred in 8.8% of patients within 7 days. The high glucose-density group (>5 g/dl) had increased risk of early OF (9.7% vs. 8.2%; adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.03-2.80; P = 0.039), respiratory failure (8.0% vs. 6.2%; aOR, 1.88; 95% CI, 1.09-3.24; P = 0.024), cardiovascular failure (3.4% vs. 2.4%; aOR, 3.59; 95% CI, 1.28-10.0; P = 0.015), and ICU admission (6.8% vs. 5.8%; aOR, 2.06; 95% CI, 1.08-3.94; P = 0.029), with a dose-response effect observed for cardiovascular failure and ICU admission. A significant increase 30-day OF risk (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.19-2.45) was also noted. CONCLUSION: Excess glucose-containing fluid was associated with increased risks of overall, respiratory, and cardiovascular OF and ICU admission in AP.

11.
Nat Commun ; 15(1): 4972, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862491

ABSTRACT

Molecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm-1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.

12.
Science ; 384(6700): 1134-1142, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38843324

ABSTRACT

The ability to genetically encode noncanonical amino acids (ncAAs) has empowered proteins with improved or previously unknown properties. However, existing strategies in mammalian cells rely on the introduction of a blank codon to incorporate ncAAs, which is inefficient and limits their widespread applications. In this study, we developed a rare codon recoding strategy that takes advantage of the relative rarity of the TCG codon to achieve highly selective and efficient ncAA incorporation through systematic engineering and big data-model predictions. We highlight the broad utility of this strategy for the incorporation of dozens of ncAAs into various functional proteins at the wild-type protein expression levels, as well as the synthesis of proteins with up to six-site ncAAs or four distinct ncAAs in mammalian cells for downstream applications.


Subject(s)
Amino Acids , Codon , Genetic Code , Protein Biosynthesis , Animals , Humans , Amino Acids/genetics , HEK293 Cells , Protein Biosynthesis/genetics , Protein Engineering
13.
Phytomedicine ; 132: 155823, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38941815

ABSTRACT

BACKGROUND: Neuropathic pain (NP) due to nerve injury, disrupts neural plasticity by triggering the release of inflammatory mediators. Alongside the hypothesis that neuro-inflammation contributes to this disruption, Andrographolide (Andro), a traditional bioactive compound derived from Andrographis paniculata, has garnered attention for its potent anti-inflammatory properties. However, whether Andro could ameliorate NP by regulating neuroinflammation remains unknown. PURPOSE: This study aimed to investigate whether and how Andro regulates neuroinflammation and alleviates NP. METHODS: The analgesic effects of Andro on NP were evaluated using both the spinal nerve ligation (SNL) and formalin rat models. A combination of network pharmacology, RNA sequencing, and experimental validation was employed to elucidate the underlying mechanism behind Andro's analgesic effects. Additionally, various techniques such as functional ultrasound, immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), patch clamp, and electron microscopy were employed to investigate the specific neural cell types, neural functions, and changes in neural plasticity influenced by Andro. RESULTS: Network pharmacology analysis unveiled the crucial roles played by shared targets of Andro and pain in regulating pain-related inflammation, including microglia activation, neuroinflammation, immune modulation, and synaptic transmission. Furthermore, we confirmed Andro's superior efficacy in pain relief compared to the traditional analgesic drug, Gabapentin. In these models, Andro was observed to modulate the haemodynamic response triggered by SNL. Transcriptome analysis and molecular docking studies indicated the involvement of major histocompatibility complex class II (MHCII) genes (Db1, Da, and Bb). Electron microscopy revealed improvements in synaptic ultrastructure, and electrophysiological investigations showed a selective reduction in glutamatergic transmission in neuropathic rats after following Andro treatment. The integration of systems pharmacology analysis and biological validation collectively demonstrated that the mechanism of pain relief involves immune modulation, enhancement of synaptic plasticity, and precise regulation of excitatory neurotransmission. CONCLUSION: In conclusion, this study has demonstrated that Andro, by targeting MHCII genes, may serve as a promising therapeutic candidate for neuropathic pain.

14.
Article in English | MEDLINE | ID: mdl-38937186

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) infection imposes substantial health burden and disproportionally affects young infants, elderly, and immunocompromised hosts. RSV harbors key surface glycoproteins F and G, both crucial for viral infection and evolution. METHODS: In this study, we examined the genetic characteaistics of 179 RSV isolates collected between 2017 and 2021 in Taiwan. G ectodomain and whole F gene were sequenced and aligned with available references from GenBank. RESULTS: RSV ON1 and BA9 were two predominant genotypes throughout the study period. Genetic variations of G protein accumulated over time. New ON1 strains containing E257K and K204R-V225A-T238I-Y280H in combination emerged in 2019 and contributed to a local endemic in 2020. RSV-B strain with A131T and T137I substitution in G protein emerged in 2018. On the other hand, F protein of both RSV genotypes was generally conserved but some feature changes should be noted: RSV-B in Taiwan harbored 100% of I206M and Q209R in site Ø, and L172Q and S173L in site V. These amino acid changes do not affect the susceptibility of Nirsevimab but imply no effectiveness of Suptavumab. CONCLUSION: RSV continuously evolves in Taiwan and accumulated signature genetic changes over time. Vigilant RSV genomic surveillance is important to monitor the viral evolution in the upcoming future of new RSV vaccines and prophylaxis.

15.
Molecules ; 29(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38930958

ABSTRACT

The phosphoenol pyruvate-oxaloacetate-pyruvate-derived amino acids (POP-AAs) comprise native intermediates in cellular metabolism, within which the phosphoenol pyruvate-oxaloacetate-pyruvate (POP) node is the switch point among the major metabolic pathways existing in most living organisms. POP-AAs have widespread applications in the nutrition, food, and pharmaceutical industries. These amino acids have been predominantly produced in Escherichia coli and Corynebacterium glutamicum through microbial fermentation. With the rapid increase in market requirements, along with the global food shortage situation, the industrial production capacity of these two bacteria has encountered two bottlenecks: low product conversion efficiency and high cost of raw materials. Aiming to push forward the update and upgrade of engineered strains with higher yield and productivity, this paper presents a comprehensive summarization of the fundamental strategy of metabolic engineering techniques around phosphoenol pyruvate-oxaloacetate-pyruvate node for POP-AA production, including L-tryptophan, L-tyrosine, L-phenylalanine, L-valine, L-lysine, L-threonine, and L-isoleucine. Novel heterologous routes and regulation methods regarding the carbon flux redistribution in the POP node and the formation of amino acids should be taken into consideration to improve POP-AA production to approach maximum theoretical values. Furthermore, an outlook for future strategies of low-cost feedstock and energy utilization for developing amino acid overproducers is proposed.


Subject(s)
Amino Acids , Metabolic Engineering , Metabolic Engineering/methods , Amino Acids/metabolism , Oxaloacetic Acid/metabolism , Escherichia coli/metabolism , Escherichia coli/genetics , Phosphoenolpyruvate/metabolism , Corynebacterium glutamicum/metabolism , Corynebacterium glutamicum/genetics , Pyruvic Acid/metabolism , Metabolic Networks and Pathways , Fermentation
16.
Alzheimers Dement (Amst) ; 16(2): e12612, 2024.
Article in English | MEDLINE | ID: mdl-38912304

ABSTRACT

INTRODUCTION: Vascular pathology is known to contribute to dementia and vascular endothelial growth factor (VEGF) is a well-established biomarker associated with vascular alterations. Nonetheless, research findings on VEGF in Alzheimer's disease (AD) and vascular dementia (VaD) are inconsistent across various studies. METHODS: We conducted a meta-analysis to elucidate relationships between VEGF and AD/VaD. RESULTS: Twenty-four studies were included. Pooled data showed that both blood and cerebrospinal fluid (CSF) VEGF levels were higher in VaD patients, whereas no significant difference was found between AD patients and healthy controls. However, the correlation between blood VEGF and AD was found among studies with AD pathology verification. And blood VEGF levels were higher in AD patients than controls in "age difference < 5 years" subgroup and CSF samples for European cohorts. DISCUSSION: This study highlights that VEGF is more effective for the diagnosis of VaD and vascular factors are also an important contributor in AD. Highlights: Vascular endothelial growth factor (VEGF) levels were higher in the vascular dementia group, but not in the overall Alzheimer's disease (AD) group.Correlation between VEGF and AD was found among studies with clear AD pathological verification.Elevated VEGF in the cerebrospinal fluid might be a diagnostic marker for AD in European populations.

17.
Curr Med Chem ; 31(20): 2900-2920, 2024.
Article in English | MEDLINE | ID: mdl-38904160

ABSTRACT

TYK2 (tyrosine-protein kinase 2) is a non-receptor protein kinase belonging to the JAK family and is closely associated with various diseases, such as psoriasis, inflammatory bowel disease, systemic lupus erythematosus. TYK2 activates the downstream proteins STAT1-5 by participating in the signal transduction of immune factors such as IL-12, IL-23, and IL-10, resulting in immune expression. The activity of the inhibitor TYK2 can effectively block the transduction of excessive immune signals and treat diseases. TYK2 inhibitors are divided into two types of inhibitors according to the different binding sites. One is a TYK2 inhibitor that binds to JH2 and inhibits its activity through an allosteric mechanism. The representative inhibitor is BMS-986165, developed by Bristol-Myers Squibb. The other class binds to the JH1 adenosine triphosphate (ATP) site and prevents the catalytic activity of the kinase by blocking ATP and downstream phosphorylation. This paper mainly introduces the protein structure, signaling pathway, synthesis, structure-activity relationship and clinical research of TYK2 inhibitors.


Subject(s)
Protein Kinase Inhibitors , TYK2 Kinase , TYK2 Kinase/antagonists & inhibitors , TYK2 Kinase/metabolism , Humans , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Structure-Activity Relationship , Signal Transduction/drug effects , Animals , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/metabolism , Psoriasis/drug therapy , Psoriasis/metabolism
18.
Int Immunopharmacol ; 136: 112372, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38850784

ABSTRACT

Hypoxic ischemic encephalopathy (HIE) is a primary cause of neonatal death and disabilities. The pathogenetic process of HIE is closely associated with neuroinflammation. Therefore, targeting and suppressing inflammatory pathways presents a promising therapeutic strategy for the treatment of HIE. Echinatin is an active component of glycyrrhiza, with anti-inflammatory and anti-oxidative properties. It is commonly combined with other traditional Chinese herbs to exert heat-clearing and detoxifying effects. This study aimed to investigate the anti-inflammatory and neuroprotective effects of Echinatin in neonatal rats with hypoxic-ischemic brain damage, as well as in PC12 cells exposed to oxygen-glucose deprivation (OGD). In vivo, Echinatin effectively reduced cerebral edema and infarct volume, protected brain tissue morphology, improved long-term behavioral functions, and inhibited microglia activation. These effects were accompanied by the downregulation of inflammatory factors and pyroptosis markers. The RNA sequencing analysis revealed an enrichment of inflammatory genes in rats with hypoxic-ischemic brain damage, and Protein-protein interaction (PPI) network analysis identified TLR4, MyD88, and NF-κB as the key regulators. In vitro, Echinatin reduced the levels of TLR4 relevant proteins, inhibited nuclear translocation of NF-κB, reduced the expression of downstreams inflammatory cytokines and pyroptosis proteins, and prevented cell membrane destructions. These findings demonstrated that Echinatin could inhibit the TLR4/NF-κB pathway, thereby alleviating neuroinflammation and pyroptosis. This suggests that Echinatin could be a potential candidate for the treatment of HIE.


Subject(s)
Hypoxia-Ischemia, Brain , NF-kappa B , Neuroprotective Agents , Pyroptosis , Rats, Sprague-Dawley , Signal Transduction , Toll-Like Receptor 4 , Animals , Male , Rats , Animals, Newborn , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Brain/drug effects , Brain/pathology , Brain/metabolism , Disease Models, Animal , Hypoxia-Ischemia, Brain/drug therapy , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/pathology , Inflammation/drug therapy , Microglia/drug effects , Microglia/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , NF-kappa B/metabolism , PC12 Cells , Pyroptosis/drug effects , Signal Transduction/drug effects , Toll-Like Receptor 4/metabolism , NF-kappa B p50 Subunit/metabolism
19.
J Thorac Dis ; 16(5): 3042-3050, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38883685

ABSTRACT

Background: Anesthesia remains challenging for bronchoscopic tracheobronchial surgeries (BTS) involving surgical manipulations for central airway obstruction within shared airways. To provide complete airway use through intervention with spontaneous breathing without endotracheal tubes, monitored non-intubated anesthesia has been successfully applied with electroencephalogram-derived monitored total intravenous anesthesia. This study evaluated the feasibility and the outcomes of BTS with monitored non-intubated anesthesia. The factors associated with desaturation and complications were also analyzed. Methods: Data from patients receiving non-intubated BTS performed between October 2019 and August 2022 were retrospectively collected. Intraoperative results and postoperative outcomes were analyzed. Results: Data of 92 patients were collected. Supraglottic airways devices and high-flow nasal oxygen were used in 68 and 24 patients respectively. Surgery was successfully completed in 87 patients (94.6%), whereas three patients required conversion to intubation because of substantial bleeding. In total, 11% of patients experienced desaturation [oxygen saturation (SpO2) <90%] for an average of 9 minutes. Unexpected admission to the intensive care unit (ICU) occurred in 12.2% (5/41) of patients from outpatient department and 7.8% (4/51) of hospitalization settings because of high-grade surgical bleeding. With comparable desaturation incidence, tracheal surgery had significantly longer desaturation times (14.5±6.9 min) than bronchial surgeries (5.8±2.6 min) did. Conclusions: Monitored non-intubated anesthesia with spontaneous breathing is feasible for BTS, with high success rate, few complications, and rapid recovery. High-grade bleeding remains the most unpredictable risk for intraoperative desaturation and postoperative ICU admission, especially in tracheal obstruction cases.

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