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1.
ACS Omega ; 9(13): 15709-15717, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38585099

RESUMO

In order to study the effect of the venting direction on explosion pressure in liquefied petroleum gas pipelines, explosion accident scenarios are experimentally tested and numerically simulated in a pipeline model with different explosion venting directions. In addition, the effect characteristic is analyzed through the pressure field varying with time and peak pressure varying with the distance. Results show that the pressure in the vertical branch decreases sharply, while the pressure in the horizontal branch does not show an obvious decrease with explosion venting of the vertical branch. However, the pressure decreases obviously in both branches with explosion venting of the horizontal branch, and the biggest reduction of peak pressure of monitoring points is 73.55% compared with that without venting. In addition, large areas of negative pressure appear in both branches with explosion venting of the vertical branch; however, a large area of negative pressure area appears in the horizontal branch with explosion venting of the horizontal branch. What is more, the arrival time of peak pressure in the main pipe of the explosion pipeline is significantly reduced with explosion venting, which is caused by the different generation ways of peak pressure. The effect analysis result of the venting direction on explosion pressure could aid the optimal layout design of LPG pipelines with the location of venting and important facilities as well as with the selection of negative-pressure-resistant material and higher-accuracy sensors.

2.
Mov Disord ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477228

RESUMO

BACKGROUND: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18 F-9-fluoropropyldihydrotetrabenazine (18 F-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). OBJECTIVE: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using 18 F-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. METHODS: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using 18 F-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. RESULTS: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. CONCLUSIONS: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. © 2024 International Parkinson and Movement Disorder Society.

3.
Biomater Sci ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517138

RESUMO

Shape memory polymers (SMPs), which initiate shape transformation in response to environmental stimuli, have attracted significant attention in both academic research and technological innovation. The combination of functional nanomaterials and SMPs has led to the emergence of a variety of shape memory polymeric nanocomposites (SMPNs) with multifunctional properties. This has injected new vitality and vigor into fields such as tissue engineering, biomedicine, optical sensing, aerospace and mechanical engineering. In this review article, we present a brief introduction to the fundamentals of SMPs and SMPNs, followed by a discussion of the recent advances in their multifunctional applications in biomedical manufacturing, drug delivery devices, mechanical sensing, micro-engines, etc. The opportunities and challenges in the future development of SMPs are also discussed.

4.
Microbiol Spectr ; : e0375623, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534119

RESUMO

Zur (zinc uptake regulator) is a significant member of the Fur (ferric uptake regulator) superfamily, which is widely distributed in bacteria. Zur plays crucial roles in zinc homeostasis and influences cell development and environmental adaptation in various species. Yersinia pseudotuberculosis is a Gram-negative enteric that pathogen usually serves as a model organism in pathogenicity studies. The regulatory effects of Zur on the zinc transporter ZnuABC and the protein secretion system T6SS have been documented in Y. pseudotuberculosis. In this study, a comparative transcriptomics analysis between a ∆zur mutant and the wild-type (WT) strain of Y. pseudotuberculosis was conducted using RNA-seq. This analysis revealed global regulation by Zur across multiple functional categories, including membrane transport, cell motility, and molecular and energy metabolism. Additionally, Zur mediates the homeostasis not only of zinc but also ferric and magnesium in vivo. There was a notable decrease in 35 flagellar biosynthesis and assembly-related genes, leading to reduced swimming motility in the ∆zur mutant strain. Furthermore, Zur upregulated multiple simple sugar and oligopeptide transport system genes by directly binding to their promoters. The absence of Zur inhibited biofilm formation as well as reduced resistance to chloramphenicol and acidic stress. This study illustrates the comprehensive regulatory functions of Zur, emphasizing its importance in stress resistance and pathogenicity in Y. pseudotuberculosis. IMPORTANCE: Bacteria encounter diverse stresses in the environment and possess essential regulators to modulate the expression of genes in responding to the stresses for better fitness and survival. Zur (zinc uptake regulator) plays a vital role in zinc homeostasis. Studies of Zur from multiple species reviewed that it influences cell development, stress resistance, and virulence of bacteria. Y. pseudotuberculosis is an enteric pathogen that serves a model organism in the study of pathogenicity, virulence factors, and mechanism of environmental adaptation. In this study, transcriptomics analysis of Zur's regulons was conducted in Y. pseudotuberculosis. The functions of Zur as a global regulator in metal homeostasis, motility, nutrient acquisition, glycan metabolism, and nucleotide metabolism, in turn, increasing the biofilm formation, stress resistance, and virulence were reviewed. The importance of Zur in environmental adaptation and pathogenicity of Y. pseudotuberculosis was emphasized.

5.
Chem Commun (Camb) ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38535993

RESUMO

Here, we synthesized a series of cholesteryl-based compounds, whose phases and their transformation can be modulated by temperature and the chain length of the fluoroalkyl moieties. To our knowledge, this is the first time that the phase transition could be modulated with perfluoroalkyl tail engineering in organic single-component ferroelectric crystals.

7.
Mol Clin Oncol ; 20(4): 31, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476334

RESUMO

Tumor hyperthermia is the fifth tumor treatment method after surgery, chemotherapy, radiotherapy and biological therapy, and is also one of the important adjuvant treatment methods for tumors. Hyperthermia can not only directly eliminate tumor cells, but also stimulate the antitumor immune response of the body, and improve the sensitivity of tumor tissues to radiotherapy and chemotherapy. An organoid is a tissue-specific cell cluster formed by 3D culture of various types of cells derived from target organ stem cells, which can reproduce the functions of target organs in vivo. At present, the research models of hepatocellular carcinoma (HCC) in vitro are mainly 2D culture cell line models, and there is no clinical report on tumor hyperthermia using HCC tumoroids. It was hypothesized that this will be a promising research direction.

8.
Biochem Genet ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530576

RESUMO

Age-related cataract (ARC) is the prevalent cause of useful vision loss. Circular RNAs are related to ARC pathogenesis partly through their competing endogenous RNA (ceRNA) activity. Herein, we defined the action of hsa_circ_0105558 in hydrogen peroxide (H2O2)-driven apoptosis and oxidative damage in human lens epithelial SRA01/04 cells. Hsa_circ_0105558, microRNA (miR)-182-5p and activating transcription factor 6 (ATF6) were evaluated by a qRT-PCR or immunoblotting method. The hsa_circ_0105558/miR-182-5p and miR-182-5p/ATF6 relationships were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assay. Reactive oxygen species level, glutathione peroxidase level, superoxide dismutase activity, and malondialdehyde level were measured using the matched assay kits. Hsa_circ_0105558 was upregulated in human ARC lens and H2O2-exposed SRA01/04 cells. Suppression of hsa_circ_0105558 attenuated H2O2-driven SRA01/04 cell apoptosis and oxidative damage. Hsa_circ_0105558 targeted miR-182-5p, and reduced miR-182-5p expression reversed the influence of hsa_circ_0105558 depletion on H2O2-driven oxidative damage and apoptosis. ATF6 was a target of miR-182-5p, and miR-182-5p-driven downregulation of ATF6 regulated cell oxidative damage and apoptosis under H2O2 insult. Moreover, hsa_circ_0105558 functioned as a ceRNA to post-transcriptionally control ATF6 expression through miR-182-5p competition. Our study demonstrates that hsa_circ_0105558 modulates SRA01/04 cell oxidative damage and apoptosis under H2O2 insult through the miR-182-5p/ATF6 cascade.

9.
J Neurol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528162

RESUMO

BACKGROUND: Orthostatic hypotension (OH) is one of the most common symptoms in patients with multiple system atrophy (MSA). Vestibular system plays an important role in blood pressure regulation during orthostatic challenges through vestibular-sympathetic reflex. The current study aimed to investigate the relationship between vestibular function and OH in patients with MSA. METHODS: Participants with MSA, including 20 with OH (mean age, 57.55 ± 8.44 years; 7 females) and 15 without OH (mean age, 59.00 ± 8.12 years; 2 females) and 18 healthy controls (mean age, 59.03 ± 6.44 years; 8 females) were enrolled. Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) tests were conducted to evaluate vestibular function. RESULTS: Patients with MSA presented with significantly higher rate of absent cVEMPs (57.1% vs 11.1%, p = 0.001) and oVEMPs (25.7% vs 0, p = 0.021) than controls. MSA patients with OH showed more absent cVEMPs (75.0% vs 11.1%, Bonferroni corrected p < 0.001) and oVEMPs (40.0% vs 0, Bonferroni corrected p = 0.003) than controls. Patients with OH also showed higher rate of absent cVEMPs than those without OH (33.3%, Bonferroni corrected p = 0.014). CONCLUSIONS: Our results demonstrated that impairment of vestibular function was associated with MSA, particularly in those with OH. Absent VEMPs may be a potential marker for MSA severity. Our findings suggest that impaired vestibular function is involved in OH development and may serve as an intervention target.

10.
Health Sci Rep ; 7(3): e1947, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38440261

RESUMO

Background and Aims: It is demonstrated that lipid metabolism disorders are associated with the reproductive performances of assisted reproductive technology. However, it is little known whether hyperlipidemia is associated with the endometrial receptivity and pregnancy outcomes of patients undergoing frozen-thawed embryo transfer (FET). Methods: This was a retrospective analysis involving 554 infertile women undergoing FET. The patients were divided into the hyperlipidemia group (n = 224) and control group (n = 320) based on the levels of serum lipids. The clinical and laboratory indexes between the two groups were compared. Meanwhile, the stratified analysis based on body mass index (BMI) and endometrial preparation protocols was performed. The independent samples t-test, Mann-Whitney U test, χ2 test and multiple logistic regression analysis were used to compare and analyze the data. Results: The patients with hyperlipidemia had significantly higher serum lipids levels and BMI and lower clinical pregnancy and implantation rates than those with normal blood lipids (p < 0.05). The impact of hyperlipidemia on pregnancy outcomes was independent of BMI. The multiple logistic regression analysis showed that higher cholesterol was associated with lower pregnancy rate and implantation rate (p < 0.05). Regardless of blood lipid levels, the patients undergoing the hormone replacement therapy (HRT) protocol had higher estradiol levels and lower progesterone levels compared with the stimulated cycles (STC) (p < 0.05). Moreover, the clinical pregnancy rate and implantation rate of the HRT protocol were higher than those of the STC, although there was no significant difference between the two. Conclusion: Hyperlipidemia especially higher cholesterol has a negative effect on the pregnancy outcomes of the patients undergoing FET. Actively implementing lipid-lowering treatment and the HRT protocol seem more friendly for these patients.

11.
Dev Comp Immunol ; 154: 105144, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38316232

RESUMO

Antimicrobial peptides (AMPs) are an essential part of the vertebrate innate immune system. Piscidins are a family of AMPs specific in fish. In our previous investigation, we identified four paralogous genes of piscidins in the orange-spotted grouper (Epinephelus coicodes), which exhibited distinct activities against bacteria, fungi, and parasitic ciliated protozoa. Piscidins demonstrated their capability to modulate the expression of diverse immune-related genes; however, their precise immunoregulatory functions remain largely unexplored. In this study, we examined the immunomodulatory properties of putative mature peptides derived from four E. coicodes piscidins (ecPis1S, ecPis2S, ecPis3S, and ecPis4S) in head kidney leukocytes (HKLs) or monocytes/macrophages (MO/MΦ)-like cells isolated from E. coicodes. Our data demonstrate that E. coicodes piscidins exhibit immunomodulatory activities supported by multiple lines of evidence. Firstly, all four piscidins displayed chemotactic activities towards HKLs, with the most potent chemotactic activity observed in ecPis2S. Secondly, stimulation with E. coicodes piscidins enhanced respiratory burst and phagocytic activity in MO/MФ-like cells, with ecPis3S showing the highest efficacy in increasing phagocytosis of MO/MΦ-like cells. Thirdly, mRNA expression levels of chemokine receptors, Toll-like receptors, T cell receptors, and proinflammatory cytokines were modulated to varying extents by the four piscidins in E. coicodes HKLs. Overall, our findings indicate that the immunological activities of these four paralogous piscidins from E. coicodes are exhibited in a paralog-specific and concentration-dependent manner, highlighting their distinct and versatile immunomodulatory properties. This study makes a significant contribution to the field of fish AMPs immunology by elucidating the novel mechanisms through which members of the piscidin family exert their immunomodulatory effects. Moreover, it provides valuable insights for further exploration of fish immunomodulating agents.


Assuntos
Bass , Animais , Bass/genética , Bass/metabolismo , Sequência de Aminoácidos , Peptídeos Antimicrobianos , Quimiotaxia , Explosão Respiratória , Peptídeos Catiônicos Antimicrobianos/metabolismo , Alinhamento de Sequência , Proteínas de Peixes/metabolismo , Macrófagos/metabolismo , Fagocitose
12.
Neurochem Res ; 49(5): 1359-1372, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38366208

RESUMO

Spinal cord injury (SCI) encompasses various pathological processes, notably neuroinflammation and apoptosis, both of which play significant roles. CTLA-4, a well-known immune molecule that suppresses T cell-mediated immune responses, is a key area of research and a focal point for targeted therapy development in treating tumors and autoimmune disorders. Despite its prominence, the impact of CTLA-4 inhibition on inflammation and apoptosis subsequent to SCI remains unexplored. This study aimed to investigate the influence of CTLA-4 on SCI. A weight-drop technique was used to establish a rat model of SCI. To examine the safeguarding effect of CTLA-4 on the restoration of motor function in rats with SCI, the Basso-Beattie-Bresnahan (BBB) scale and inclined plane test were employed to assess locomotion. Neuronal degeneration and apoptosis were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and Fluoro-Jade B labeling, respectively, and the activity of microglial cells was examined by immunofluorescence. To evaluate the impact of CTLA4 on SCI, the levels of inflammatory markers were measured. After treatment with the CTLA-4 inhibitor ipilimumab, the rats showed worse neurological impairment and more severe neuroinflammation after SCI. Furthermore, the combination therapy with ipilimumab and durvalumab after SCI had more pronounced effects than treatment with either inhibitor alone. These findings indicate that CTLA-4 contributes to neuroinflammation and apoptosis after SCI, presenting a promising new therapeutic target for this traumatic condition.


Assuntos
Doenças Neuroinflamatórias , Traumatismos da Medula Espinal , Ratos , Animais , Ratos Sprague-Dawley , Antígeno CTLA-4/uso terapêutico , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Traumatismos da Medula Espinal/patologia , Apoptose , Inflamação/patologia , Medula Espinal , Recuperação de Função Fisiológica
13.
Plants (Basel) ; 13(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38337943

RESUMO

To explore the regulation mechanism of endogenous phytohormones on rhizome bud germination in Cephalostachyum pingbianense, the contents of IAA, ABA, GA, and CTK in seven above- and under-ground bamboo structure components were determined using enzyme-linked immunosorbent assays (ELISA). The results showed that a higher content of IAA, GA, and CTK all year was found in above-ground components and dormant rhizome buds. Meanwhile, a higher ABA content in young shoots and a lower ABA content in the culm base and dormant rhizome buds were detected during the peak period of shooting. The amounts of emerging shoots and the grown bamboo culms were positively correlated with the content of IAA and the ratio of IAA/ABA and (IAA + CTK + GA)/ABA, while they were negatively correlated with the ratio of CTK/IAA in dormant rhizome buds. The all-year high contents of IAA (19-31 ng/g) and ABA (114-144 ng/g) in rhizome buds, as well as interactions among four hormones, may be the key physiological mechanisms to maintain rhizome bud germination throughout the year in C. pingbianense. As C. pingbianense is a special bamboo species of multi-season shoot sprouting, the above results may supplement scientific data for a comprehensive understanding of physiological mechanisms within the bamboo subfamily.

14.
Zhongguo Zhong Yao Za Zhi ; 49(1): 151-161, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403348

RESUMO

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.


Assuntos
Injúria Renal Aguda , Ferroptose , Camundongos , Masculino , Animais , Cisplatino/efeitos adversos , Camundongos Endogâmicos C57BL , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/genética , Glicogênio , Superóxido Dismutase , Ferro , 1-Acilglicerofosfocolina O-Aciltransferase
15.
Arch Bone Jt Surg ; 12(2): 144-147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420523

RESUMO

We present a unique case of a 59-year-old shipyard worker who sustained an avulsion fracture of the tibialis anterior tendon, concurrently with a comminuted fracture at the base of the first metatarsal. This is the first reported case highlighting this concomitant presentation, which underlines the possibility of avulsion fractures accompanying comminuted fractures. Importantly, such avulsion fractures could lead to skin tenting and potential necrosis, necessitating early identification and prompt intervention. The patient underwent successful surgical intervention and displayed good functional restoration 15 months postoperatively.

16.
Cytokine ; 175: 156498, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38176086

RESUMO

S. aureus isolated from bacterial bovine endometritis is common in epidemiological reports, but is often ignored as a subclinical pathogenic microorganism. In a previous study, we showed that live S. aureus (LSA) and heat killed S. aureus (HK-SA) induce different inflammatory responses in bovine endometrial tissue, and possibly being associated with the accumulation of prostaglandin E2 (PGE2). Thus, in this study, we varied PGE2 concentrations using inhibitors or agonists in HK-SA-treated bovine endometrial tissues. The results demonstrated that PGE2 has a positive relationship with IL-6, TNF-α, and damage-associated molecular patterns (DAMPs; e.g., HMGB-1 and HABP-1) expression and tissues damage, and is regulated by the EP4-p38 MAPK pathway. We concluded that lipoproteins of S. aureus are associated with PGE2 generation. To further explore the relationship between LSA and PGE2 accumulation, we used the S. aureus strain SA113 lipoprotein knockout (SA113Δlpl) to infect bovine endometrial epithelial cells (BECs). LSA decreased PGE2, cAMP, EP4, IL-6, IL-8, cAMP secretion, and the MAPK and PKA signaling pathways when infected with SA113Δlpl, as compared with SA113-infected groups. Moreover, the adhesion and invasion of BECs were similarly downregulated when lipoproteins in S. aureus were knocked out. The results of this study show that PGE2 is involved in both HK-SA- and LSA-induced inflammatory responses in the bovine endometrium. We suggest that S. aureus infection is associated with bovine endometritis, and although HK-SA and LSA induce different inflammatory responses, the strategy of decreasing PGE2 accumulation is helpful in reducing the inflammation stage caused by S. aureus.


Assuntos
Endometrite , Staphylococcus aureus Resistente à Meticilina , Feminino , Humanos , Animais , Bovinos , Dinoprostona/metabolismo , Staphylococcus aureus Resistente à Meticilina/metabolismo , Staphylococcus aureus/metabolismo , Interleucina-6 , Lipoproteínas , Receptores de Prostaglandina E Subtipo EP4/metabolismo
17.
Int Immunopharmacol ; 129: 111526, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38295545

RESUMO

Staphylococcus aureus (S. aureus) is one of the most infamous and widespread bacterial pathogens, causing a hard-to-estimate number of uncomplicated skin infections and probably hundreds of thousands to millions of more severe, invasive infections globally per year. S. aureus may also be acquired from animals, especially in the livestock industry. The interaction mechanism of host and S. aureus has significance for finding ways to against S. aureus infection and control inflammatory response of host, while the molecular biological activities after S. aureus infection, particular in inflammatory and immune cells are not fully clear. The present study aimed to explore whether pattern recognition receptors (PRRs) mediate prostaglandin D2 (PGD2) synthesis and PGD2 participates in the regulation of inflammatory response in macrophages during S. aureus infection or synthetic bacterial lipopeptide (Pam2CSK4) stimulation. PGD2 secretion level was enhanced by mice peritoneal macrophages infected with the S. aureus. The results indicated that PGD2 secretion was impaired in S. aureus infected-macrophages from toll-like receptors 2 (TLR2)-deficient and NLR pyrin domain-containing 3 (NLRP3)-deficient mice. PGD2 synthetase (hematopoietic PGD synthase, HPGDS) inhibitors could reduce the activation of macrophage mitogen-activated protein kinase (MAPK)/nuclear factor-κ-gene binding (NF-κB) signaling pathways. HPGDS inhibition impaired cytokines (TNF-α, IL-1ß, IL-10 and RANTES) secretion and macrophage phagocytosis during S. aureus infection. In addition, inhibition of endogenous PGD2 synthesis was unable to affect the TLR2 and NLRP3 expression in S. aureus-infected macrophages. Taken together, macrophage PGD2 secretion after S. aureus infection depended on receptors TLR2 and NLRP3, and the induced PGD2 participated in the regulation of inflammatory response in S. aureus-infected macrophages. Interestingly, it was found that exogenous PGD2 down-regulated the cytokines secretion and had no effect on phagocytosis in the S. aureus-infected macrophages.


Assuntos
Staphylococcus aureus , Receptor 2 Toll-Like , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Macrófagos , NF-kappa B/metabolismo , Citocinas/metabolismo
18.
IEEE J Biomed Health Inform ; 28(4): 2223-2234, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38285570

RESUMO

Preterm birth is the leading cause of death in children under five years old, and is associated with a wide sequence of complications in both short and long term. In view of rapid neurodevelopment during the neonatal period, preterm neonates may exhibit considerable functional alterations compared to term ones. However, the identified functional alterations in previous studies merely achieve moderate classification performance, while more accurate functional characteristics with satisfying discrimination ability for better diagnosis and therapeutic treatment is underexplored. To address this problem, we propose a novel brain structural connectivity (SC) guided Vision Transformer (SCG-ViT) to identify functional connectivity (FC) differences among three neonatal groups: preterm, preterm with early postnatal experience, and term. Particularly, inspired by the neuroscience-derived information, a novel patch token of SC/FC matrix is defined, and the SC matrix is then adopted as an effective mask into the ViT model to screen out input FC patch embeddings with weaker SC, and to focus on stronger ones for better classification and identification of FC differences among the three groups. The experimental results on multi-modal MRI data of 437 neonatal brains from publicly released Developing Human Connectome Project (dHCP) demonstrate that SCG-ViT achieves superior classification ability compared to baseline models, and successfully identifies holistically different FC patterns among the three groups. Moreover, these different FCs are significantly correlated with the differential gene expressions of the three groups. In summary, SCG-ViT provides a powerfully brain-guided pipeline of adopting large-scale and data-intensive deep learning models for medical imaging-based diagnosis.


Assuntos
Conectoma , Nascimento Prematuro , Feminino , Criança , Humanos , Recém-Nascido , Pré-Escolar , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Conectoma/métodos , Fontes de Energia Elétrica
19.
Int J Pharm ; 652: 123865, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38286195

RESUMO

Clinical treatment for osteosarcoma (OS) is still lacking effective means, and no significant progress in OS treatment have been made in recent years. Single chemotherapy has serious side effects and can produce drug resistance easily, resulting poor therapeutic effect. As a modern and non-invasive treatment form, photodynamic therapy (PDT) is widely used to treat diverse cancers. Chemotherapy in combination with PDT is a particularly efficient antitumor method that could overcome the defects of monotherapies. Since mitochondria is a key subcellular organelle involved in cell apoptosis regulation, targeting tumor cells mitochondria for drug delivery has become an important entry point for anti-tumor therapy. Herein, we rationally designed a core-shell structured biomimetic nanoplatform, i.e., D@SLNP@OSM-IR780, to achieve tumor homologous targeting and mitochondria targeted drug release for chemotherapy combined with PDT against OS. Upon 808 nm laser irradiation, D@SLNP@OSM-IR780 exhibited excellent photo-cytotoxicity in vitro. The excellent targeting effect of D@SLNP@OSM-IR780 in tumor tissues produced a tumor inhibition rate of 98.9% in vivo. We further indicated that synergistic chemo-photodynamic effect induced by D@SLNP@OSM-IR780 could activate mitochondria-mediated apoptosis pathway, along with host immune response and potential photothermal effect. On the whole, D@SLNP@OSM-IR780 is revealed to be a promising platform for OS targeted combination therapeutics.


Assuntos
Neoplasias Ósseas , Nanopartículas , Osteossarcoma , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Biomimética , Nanopartículas/uso terapêutico , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Mitocôndrias , Linhagem Celular Tumoral
20.
Nat Commun ; 15(1): 244, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38172120

RESUMO

Viruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected to host-mediated post-translational modifications. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on the lysine 65 residue, which efficiently mediates SARS2-NP's ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS). Thereby the innate antiviral immune response is suppressed robustly. These roles can be achieved through intermolecular association between SUMO conjugation and a newly identified SUMO-interacting motif in SARS2-NP. Importantly, the widespread SARS2-NP R203K mutation gains a novel site of SUMOylation which further increases SARS2-NP's LLPS and immunosuppression. Notably, the SUMO E3 ligase TRIM28 is responsible for catalyzing SARS2-NP SUMOylation. An interfering peptide targeting the TRIM28 and SARS2-NP interaction was screened out to block SARS2-NP SUMOylation and LLPS, and consequently inhibit SARS-CoV-2 replication and rescue innate antiviral immunity. Collectively, these data support SARS2-NP SUMOylation is critical for SARS-CoV-2 virulence, and therefore provide a strategy to antagonize SARS-CoV-2.


Assuntos
COVID-19 , Sumoilação , Humanos , SARS-CoV-2/genética , Proteínas do Nucleocapsídeo , Virulência/genética , Replicação Viral , Proteína 28 com Motivo Tripartido
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