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1.
Front Immunol ; 15: 1345625, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370420

RESUMO

The P2X7 receptor (P2X7R), a non-selective cation channel modulated by adenosine triphosphate (ATP), localizes to microglia, astrocytes, oligodendrocytes, and neurons in the central nervous system, with the most incredible abundance in microglia. P2X7R partake in various signaling pathways, engaging in the immune response, the release of neurotransmitters, oxidative stress, cell division, and programmed cell death. When neurodegenerative diseases result in neuronal apoptosis and necrosis, ATP activates the P2X7R. This activation induces the release of biologically active molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen species, and excitotoxic glutamate/ATP. Subsequently, this leads to neuroinflammation, which exacerbates neuronal involvement. The P2X7R is essential in the development of neurodegenerative diseases. This implies that it has potential as a drug target and could be treated using P2X7R antagonists that are able to cross the blood-brain barrier. This review will comprehensively and objectively discuss recent research breakthroughs on P2X7R genes, their structural features, functional properties, signaling pathways, and their roles in neurodegenerative diseases and possible therapies.


Assuntos
Doenças Neurodegenerativas , Receptores Purinérgicos P2X7 , Humanos , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/metabolismo , Doenças Neurodegenerativas/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Trifosfato de Adenosina/metabolismo
2.
J Environ Manage ; 354: 120329, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38373375

RESUMO

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants in combination with other environmental pollutants, such as levofloxacin (LVFX). After a 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, LVFX was neurotoxic to Rana nigromaculata tadpoles. The order of the effects of the exposure treatment on tadpole behavior was: LVFX-MP3>LVFX-MP1>LVFX-MP2 ≥ LVFX. Results of transcriptome analysis of tadpole brain tissue showed that LVFX in combination with 0.10 and 10.00 µm MP interferes with the nervous system through the cell adhesion molecules pathway. Interestingly, the order of effects of the co-exposure on oxidative stress in the intestine was inconsistent with that of tadpole behavior. We found that Paraacteroides might be a microplastic indicator species for the gut microbiota of aquatic organisms. The results of the targeted metabolism of neurotransmitters in the intestine suggest that in the LVFX-MP2 treatment, LVFX alleviated the intestinal microbiota disorder caused by 1.00 µm MP, by regulating intestinal microbiota participating in the TCA cycle VI and gluconeogenesis and tetrapyrrole biosynthesis I, while downregulating Met and Orn, and upregulating 5HIAA, thereby easing the neurotoxicity to tadpoles exposed to LVFX-MP2. This work is of great significance for the comprehensive assessment of the aquatic ecological risks of microplastics-antibiotic compound pollutants.

3.
Food Chem X ; 21: 101189, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38357376

RESUMO

Flavor profiles of various Pyrus spp. cultivars exhibit significant variations, yet the underlying flavor-contributing factors remain elusive. In this investigation, a comprehensive approach encompassing metabolomics analysis, volatile fingerprint analysis, and descriptive sensory analysis was employed to elucidate the flavor disparities among Nanguoli, Korla fragrant pear, and Qiuyueli cultivars and uncover potential flavor contributor. The study comprehensively characterized the categories and concentrations of nonvolatile and volatile metabolites, and 925 metabolites were identified. Flavonoids and esters dominated the highest cumulative response, respectively. Utilizing weighted correlation network analysis (WGCNA), seven highly correlated modules were identified, yielding 407 pivotal metabolites. Further correlation analysis of the differential substances provided potential flavor constituents strongly associated with various sensory attributes; taste factors had a certain association with olfactory characteristics. Our findings demonstrated the manifestation of flavor was a result of the synergistic effect of various compounds; evaluation olfactory flavor necessitated a comprehensive consideration of taste substances.

4.
J Transl Med ; 22(1): 164, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365806

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model. METHODS: We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously. RESULTS: C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Besides, C3a enhanced IL-1ß activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro. CONCLUSION: Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Ratos , Humanos , Animais , Hipertensão Arterial Pulmonar/tratamento farmacológico , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Complemento C3/metabolismo , Inativadores do Complemento/efeitos adversos , Inativadores do Complemento/metabolismo , Artéria Pulmonar/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças
5.
Bioengineering (Basel) ; 11(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38391594

RESUMO

Prosthetic technology has witnessed remarkable advancements, yet challenges persist in achieving autonomous grasping control while ensuring the user's experience is not compromised. Current electronic prosthetics often require extensive training for users to gain fine motor control over the prosthetic fingers, hindering their usability and acceptance. To address this challenge and improve the autonomy of prosthetics, this paper proposes an automated method that leverages computer vision-based techniques and machine learning algorithms. In this study, three reinforcement learning algorithms, namely Soft Actor-Critic (SAC), Deep Q-Network (DQN), and Proximal Policy Optimization (PPO), are employed to train agents for automated grasping tasks. The results indicate that the SAC algorithm achieves the highest success rate of 99% among the three algorithms at just under 200,000 timesteps. This research also shows that an object's physical characteristics can affect the agent's ability to learn an optimal policy. Moreover, the findings highlight the potential of the SAC algorithm in developing intelligent prosthetic hands with automatic object-gripping capabilities.

6.
Dalton Trans ; 53(9): 4243-4250, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38334482

RESUMO

At present, tuning the luminescence characteristics of phosphors by external physical stimuli such as temperature and pressure has attracted the interest of researchers. However, the emission-tunable luminescence processes by temperature or pressure in lead-free perovskite with ordered vacancy materials have not been systematically studied. In this study, Bi3+-doped Rb2SnCl6 crystals were successfully synthesized using a simple precipitation method, and these crystals demonstrated a remarkable enhancement of luminescence intensity compared with the unannealed ones at 140-200 °C, and with a red-shift in the emission peak from 450 to 500 nm. It was found that the annealing treatment increased the Bi-Cl bond length leading to emission red-shift and achieved the change in the emission intensity due to the band gap modulation of the material. Furthermore, a candidate material for the color-changing optical security strategies was obtained by combining the Bi3+-doped Rb2SnCl6 phosphor and printing ink. This work is a valuable reference for the rational design of luminescent perovskites with promising new functionalities and stimulates the great potential of luminescent perovskites in developing promising phosphors for advanced anticounterfeiting.

7.
ISME J ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38366029

RESUMO

Wildfires affect soils in multiple ways, leading to numerous challenges for colonizing microorganisms. While it is thought that fire-adapted microorganisms lie at the forefront of postfire ecosystem recovery, the specific strategies that these organisms use to thrive in burned soils remain largely unknown. Through bioactivity screening of bacterial isolates from burned soils, we discovered that several Paraburkholderia spp. isolates produced a set of unusual rhamnolipid surfactants with a natural methyl ester modification. These rhamnolipid methyl esters (RLMEs) exhibited enhanced antimicrobial activity against other postfire microbial isolates, including pyrophilous Pyronema fungi and Amycolatopsis bacteria, compared to the typical rhamnolipids made by organisms such as Pseudomonas spp. RLMEs also showed enhanced surfactant properties and facilitated bacterial motility on agar surfaces. In vitro assays further demonstrated that RLMEs improved aqueous solubilization of polycyclic aromatic hydrocarbons, which are potential carbon sources found in char. Identification of the rhamnolipid biosynthesis genes in the postfire isolate, Paraburkholderia kirstenboschensis str. F3, led to the discovery of rhlM, whose gene product is responsible for the unique methylation of rhamnolipid substrates. RhlM is the first characterized bacterial representative of a large class of integral membrane methyltransferases that are widespread in bacteria. These results indicate multiple roles for RLMEs in the postfire lifestyle of Paraburkholderia isolates, including enhanced dispersal, solubilization of potential nutrients, and inhibition of competitors. Our findings shed new light on the chemical adaptations that bacteria employ to navigate, grow, and outcompete other soil community members in postfire environments.

8.
J Nat Prod ; 87(2): 371-380, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38301035

RESUMO

Thiazole scaffold-based small molecules exhibit a range of biological activities and play important roles in drug discovery. Based on bioinformatics analysis, a putative biosynthetic gene cluster (BGC) for thiazole-containing compounds was identified from Streptomyces sp. SCSIO 40020. Heterologous expression of this BGC led to the production of eight new thiazole-containing compounds, grisechelins E, F, and I-N (1, 2, 5-10), and two quinoline derivatives, grisechelins G and H (3 and 4). The structures of 1-10, including their absolute configurations, were elucidated by HRESIMS, NMR spectroscopic data, ECD calculations, and single-crystal X-ray diffraction analysis. Grisechelin F (2) is a unique derivative, distinguished by the presence of a salicylic acid moiety. The biosynthetic pathway for 2 was proposed based on bioinformatics analysis and in vivo gene knockout experiments. Grisechelin E (1) displayed moderate antimycobacterial activity against Mycobacterium tuberculosis H37Ra (MIC of 8 µg mL-1).


Assuntos
Streptomyces , Streptomyces/genética , Streptomyces/química , Antibacterianos/farmacologia , Espectroscopia de Ressonância Magnética , Ácido Salicílico , Tiazóis
9.
Org Lett ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363662

RESUMO

A known polycyclic tetramate macrolactam (aburatubolactam C, 3) and three new ones (aburatubolactams D-F, 4-6, respectively) were isolated from the marine-derived Streptomyces sp. SCSIO 40070. The absolute configuration of 3 was established by X-ray analysis. A combinatorial biosynthetic approach unveiled biosynthetic enzymes dictating the formation of distinct 5/5-type ring systems (such as C7-C14 cyclization by AtlB1 in 5 and C6-C13 cyclization by AtlB2 in 6) in aburatubolactams.

10.
Int J Equity Health ; 23(1): 40, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409009

RESUMO

BACKGROUND: Patient satisfaction is an important outcome domain of patient-centered care. Medical humanization follows the patient-centered principle and provides a more holistic view to treat patients. The COVID-19 pandemic posed significant barriers to maintaining medical humanization. However, empirical study on the relationship between medical humanization and patient satisfaction is clearly absent. OBJECTIVES: We examined the mediation effects of communication on the relationship between medical humanization and patient satisfaction when faced with a huge public health crisis like the COVID-19 pandemic, and the moderation effect of medical institutional trust on the mediation models. METHODS: A cross-sectional survey study was performed. A final sample size of 1445 patients was surveyed on medical humanization, communication, patient satisfaction and medical institutional trust. RESULTS: All correlations were significantly positive across the main variables (r = 0.35-0.67, p < 0.001 for all) except for medical institutional trust, which was negatively correlated with the medical humanization (r=-0.14, p < 0.001). Moderated mediation analysis showed that the indirect effect of medical humanization on patient satisfaction through communication was significant (b = 0.22, 95% CI: 0.18 ~ 0.25). Medical institutional trust significantly moderated the effect of medical humanization on patient satisfaction (b=-0.09, p < 0.001) and the effect of medical humanization on communication (b= -0.14, p < 0.001). CONCLUSION: Medical humanization positively influence patient satisfaction, communication mediated the association between medical humanization and patient satisfaction, and medical institutional trust negatively moderated the effects of medical humanization on patient satisfaction and communication. These findings suggest that humanistic communication contributes to patient satisfaction in the face of a huge public health crisis, and patients' evaluation of satisfaction is also regulated by rational cognition.


Assuntos
COVID-19 , Saúde Pública , Humanos , Estudos Transversais , Pandemias , Comunicação , Satisfação do Paciente , Confiança , Relações Médico-Paciente
11.
J Exp Bot ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38243384

RESUMO

Needle-like calcium oxalate crystals, called raphides, are unique structures in the plant kingdom. Multiple biomacromolecules work together in the regulatory and transportation pathways to form raphides; however, how this occurs remains unknown. This study combined in vivo biological methods, including confocal microscopy, transmission electron microscopy, and Q Exactive mass spectrometry, to identify the main biomolecules, such as: vesicles, alongside lipid and protein compositions from the crystal chamber. Simulations of the vesicle transportation process and the synthesis of elongated calcium oxalate crystals in vitro were then conducted. These results suggest that vesicles carrying amorphous calcium oxalate and proteins embedded in raphides are transported along actin filaments. Subsequently, these vesicles fuse with the crystal chamber, utilizing the proteins embedded in raphides as a template for the final formation of raphides. These findings contribute to our fundamental understanding of the regulation of diverse biomacromolecules that are crucial for raphide formation. Moreover, the implications of these findings extend to other fields, such as materials science, particularly the synthesis of functionalized materials.

12.
ACS Appl Mater Interfaces ; 16(4): 4618-4627, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38232233

RESUMO

The ternary strategy has been widely applied and recognized to be a valid strategy to enhance the organic photovoltaics' (OPVs) performance. Here, a new fused-ring electron acceptor, BTP-PIO, is designed and synthesized, whose ending groups were replaced by a phthalimide-based group (2-butylcyclopenta[f]isoindole-1,3,5,7(2H,6H)-tetraone) from traditional 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile. The phthalimide-based ending groups endow BTP-PIO with the highest lowest unoccupied molecular orbital (LUMO) level and wider band gap than those of Y6. The ternary device based on PM6:Y6 with BTP-PIO as a guest electron acceptor achieved an elevated open-circuit voltage (VOC) of 0.848 V, a short-circuit current density (JSC) of 27.31 mA cm-2, and a fill factor (FF) of 73.9%, generating a remarkable power conversion efficiency (PCE) of 17.10%, which is superior to the PM6:Y6 binary device of 16.08%. The ternary device exhibited improved charge transfer, suppressed carrier recombination, and lower energy loss. BTP-PIO exhibited a good miscibility with Y6, and an alloy phase between BTP-PIO and Y6 was formed in the ternary bulk heterojunction, leading to better phase separation and molecular packing. This research reveals that ending group modification of Y6 derivatives is a feasible way to produce highly efficient ternary devices.

13.
Environ Sci Technol ; 58(4): 2078-2088, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38235676

RESUMO

Lake sediments connection to the biogeochemical cycling of phosphorus (P) and carbon (C) influences streamwater quality. However, it is unclear whether and how the type of sediment controls P and C cycling in water. Here, the adsorption behavior of montmorillonite (Mt) with different interlayer cations (Na+, Ca2+, or Fe3+) on dissolved organic matter (DOM) and P was investigated to understand the role of Mt in regulating the organic carbon-to-phosphate (OC/P) ratio within freshwater systems. The adsorption capacity of Fe-Mt for P was 3.2-fold higher than that of Ca-Mt, while it was 1/3 lower for DOM. This dissimilarity in adsorption led to an increased OC/P in Fe-Mt-dominated water and a decreased OC/P in Ca-Mt-dominated water. Moreover, an in situ atomic force microscope and high-resolution mass spectrometry revealed molecular fractionation mechanisms and adsorptive processes. It was observed that DOM inhibited the nucleation and crystallization processes of P on the Mt surface, and P affected the binding energy of DOM on Mt through competitive adsorption, thereby governing the interfacial P/DOM dynamics on Mt substrates at a molecular level. These findings have important implications for water quality management, by highlighting the role of clay minerals as nutrient sinks and providing new strategies for controlling P and C dynamics in freshwater systems.


Assuntos
Matéria Orgânica Dissolvida , Fósforo , Argila , Adsorção , Minerais/química , Lagos/química , Carbono
14.
Nat Microbiol ; 9(2): 502-513, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38228859

RESUMO

Probiotic supplements are suggested to promote human health by preventing pathogen colonization. However, the mechanistic bases for their efficacy in vivo are largely uncharacterized. Here using metabolomics and bacterial genetics, we show that the human oral probiotic Streptococcus salivarius K12 (SAL) produces salivabactin, an antibiotic that effectively inhibits pathogenic Streptococcus pyogenes (GAS) in vitro and in mice. However, prophylactic dosing with SAL enhanced GAS colonization in mice and ex vivo in human saliva. We showed that, on co-colonization, GAS responds to a SAL intercellular peptide signal that controls SAL salivabactin production. GAS produces a secreted protease, SpeB, that targets SAL-derived salivaricins and enhances GAS survival. Using this knowledge, we re-engineered probiotic SAL to prevent signal eavesdropping by GAS and potentiate SAL antimicrobials. This engineered probiotic demonstrated superior efficacy in preventing GAS colonization in vivo. Our findings show that knowledge of interspecies interactions can identify antibiotic- and probiotic-based strategies to combat infection.


Assuntos
Probióticos , Infecções Estreptocócicas , Animais , Humanos , Camundongos , Antibacterianos , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes , Saliva
15.
Org Biomol Chem ; 22(6): 1152-1156, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38214554

RESUMO

Two C-methylated fluostatins (FSTs) B3 (1) and B4 (2) were synthesized from flavin-mediated nonenzymatic epoxide ring-opening reactions of FST C. The structures of 1 and 2 were elucidated by HRESIMS, NMR, and ECD spectroscopic analyses. A subsequent 13C labeling study demonstrated that the C-methyl groups of 1 and 2 were derived from DMSO and enabled the mechanistic proposal of a nonenzymatic C-methylation.


Assuntos
Metilação , Espectroscopia de Ressonância Magnética
16.
Eur J Pharmacol ; 966: 176346, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38246329

RESUMO

Cell transplantation has brought about a breakthrough in the treatment of nerve injuries, and the efficacy of cell transplantation compared to drug and surgical therapies is very exciting. In terms of transplantation targets, the classic cells include neural stem cells (NSCs) and Schwann cells, while a class of cells that can exist and renew throughout the life of the nervous system - olfactory ensheathing cells (OECs) - has recently been discovered in the olfactory system. OECs not only encircle the olfactory nerves but also act as macrophages and play an innate immune role. OECs can also undergo reprogramming to transform into neurons and survive and mature after transplantation. Currently, many studies have confirmed the repairing effect of OECs after transplantation into injured nerves, and safe and effective results have been obtained in clinical trials. However, the specific repair mechanism of OECs among them is not quite clear. For this purpose, we focus here on the repair mechanisms of OECs, which are summarized as follows: neuroprotection, secretion of bioactive factors, limitation of inflammation and immune regulation, promotion of myelin and axonal regeneration, and promotion of vascular proliferation. In addition, integrating the aspects of harvesting, purification, and prognosis, we found that OECs may be more suitable for transplantation than NSCs and Schwann cells, but this does not completely discard the value of these classical cells. Overall, OECs are considered to be one of the most promising transplantation targets for the treatment of nerve injury disorders.


Assuntos
Células-Tronco Neurais , Traumatismos da Medula Espinal , Humanos , Bulbo Olfatório , Bainha de Mielina , Neurônios , Transplante de Células/métodos , Regeneração Nervosa , Neuroglia
18.
Oncogene ; 43(9): 682-692, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216672

RESUMO

Hepatocellular carcinoma (HCC) stands as the fifth most prevalent malignant tumor on a global scale and presents as the second leading cause of cancer-related mortality. DNA damage-based radiotherapy (RT) plays a pivotal role in the treatment of HCC. Nevertheless, radioresistance remains a primary factor contributing to the failure of radiation therapy in HCC patients. In this study, we investigated the functional role of transketolase (TKT) in the repair of DNA double-strand breaks (DSBs) in HCC. Our research unveiled that TKT is involved in DSB repair, and its depletion significantly reduces both non-homologous end joining (NHEJ) and homologous recombination (HR)-mediated DSB repair. Mechanistically, TKT interacts with PARP1 in a DNA damage-dependent manner. Furthermore, TKT undergoes PARylation by PARP1, resulting in the inhibition of its enzymatic activity, and TKT can enhance the auto-PARylation of PARP1 in response to DSBs in HCC. The depletion of TKT effectively mitigates the radioresistance of HCC, both in vitro and in mouse xenograft models. Moreover, high TKT expression confers resistance of RT in clinical HCC patients, establishing TKT as a marker for assessing the response of HCC patients who received cancer RT. In summary, our findings reveal a novel mechanism by which TKT contributes to the radioresistance of HCC. Overall, we identify the TKT-PARP1 axis as a promising potential therapeutic target for improving RT outcomes in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Quebras de DNA de Cadeia Dupla , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Transcetolase/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Reparo do DNA , DNA , Reparo do DNA por Junção de Extremidades , Reparo de DNA por Recombinação , Poli(ADP-Ribose) Polimerase-1/genética
19.
Brain Res ; 1825: 148732, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38104922

RESUMO

Trigeminal neuralgia (TN) is a common form of facial pain, which primarily manifests as severe pain similar to facial acupuncture and electric shock. Olfactory ensheathing cells (OECs) are glial cells with high bioactivity; these cells are essential for the periodic regeneration of the olfactory nerve and have been utilized for the repair of nerve injuries. A member of the P2X receptor family, P2X7R, is an ion channel type receptor that has been confirmed to participate in various pain response processes. In this study, we transplanted OECs into trigeminal nerve-model rats with distal infraorbital nerve ligation to observe the therapeutic effect of transplanted OECs in rats. Additionally, we utilized the P2X7R-specific inhibitor brilliant blue G (BBG) to study the therapeutic mechanisms of cell transplantation. The facial mechanical pain threshold of these rats significantly increased following cell transplantation. The immunohistochemistry, immunoblotting, and RT-qPCR results demonstrated that the levels of P2X7R, (NOD)-like receptor protein-3 (NLRP3), nuclear factor-κB (NF-κB), interleukin (IL)-1ß, and IL-18 in the trigeminal ganglion of rats treated with OEC transplantation or BBG treatment were significantly lower than those in the injured group without treatment. Overall, our results demonstrate that OEC transplantation can alleviate TN in rats, and it can reduce the expression of P2X7R related inflammatory factors in TN rats, reducing neuroinflammatory response in TG.


Assuntos
Neuralgia do Trigêmeo , Ratos , Animais , Neuralgia do Trigêmeo/tratamento farmacológico , Neuralgia do Trigêmeo/metabolismo , Ratos Sprague-Dawley , Dor Facial/metabolismo , Limiar da Dor/fisiologia , Transplante de Células/métodos , Bulbo Olfatório/metabolismo
20.
Int J Antimicrob Agents ; 63(2): 107062, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104947

RESUMO

BACKGROUND: Tigecycline has been widely used for multi-drug-resistant bacterial infections in China. Although many studies have reported the risk factors for tigecycline-induced hypofibrinogenaemia, it remains unknown whether valproic acid or voriconazole in combination with tigecycline is associated with the decrease in fibrinogen, as both drugs could lead to coagulation disorders. The aim of this study was to develop a nomogram for the prediction of tigecycline-induced hypofibrinogenaemia. METHODS: This was a multi-centre retrospective case-control study. The primary outcome was the accurate prediction of tigecycline-induced hypofibrinogenaemia. Nomograms were developed from logistic regression models with least absolute shrinkage and selection operator regression for variable selection. Model performance was assessed via calibration plots, and models were validated internally using bootstrapping on a validation cohort. RESULTS: In total, 2362 patients were screened, of which 611 were eligible for inclusion in this study. These 611 patients were divided into the training cohort (n=488) and the validation cohort (n=123). Predictors included in the nomogram for the total population were total dose, age, fibrinogen, prothrombin time (PT), comorbidity, and concomitant use of voriconazole. Total dose, fibrinogen, PT, activated partial thromboplastin time, white blood cell count, and concomitant use of voriconazole were selected to predict hypofibrinogenaemia in patients with malignant haematologic diseases. Both models were calibrated adequately, and their predictions were correlated with the observed outcome. The cut-offs for treatment duration in the total population and the subgroup were 10 and 6 days, respectively. CONCLUSIONS: Tigecycline in combination with voriconazole could increase the risk of hypofibrinogenaemia, and tigecycline-induced hypofibrinogenaemia is more likely to occur in patients with malignant haematologic diseases.


Assuntos
Afibrinogenemia , Nomogramas , Humanos , Tigeciclina/uso terapêutico , Afibrinogenemia/tratamento farmacológico , Estudos Retrospectivos , Estudos de Casos e Controles , Voriconazol , Fibrinogênio
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