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1.
J Am Chem Soc ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949127

RESUMO

Intercalation of hydrogen into the palladium atomic layers during the growth of Pd nanoparticles can lead to the synthesis of unique palladium hydride phases. Here, we discover an unusual nonfcc palladium hydride nanoparticle, a structure that is not face-centered cubic (fcc), formed through coreduction of water molecules and Pd ions in solution. Crystal structure determination based on atomic electron tomography points to potential triclinic unit cells, indicating the presence of more than one nonfcc phase, with some of those being a stack of loosened and distorted close-packed layer of atoms. The probability of finding the nonfcc phase in single-crystalline particles varies depending on the number and distribution of contact area with other particles. Roughly half of the isolated and one side-coalesced single-crystal particles exhibit a nonfcc structure, while fcc dominates multiple side-coalesced single crystals as well as polycrystal particles. These observations suggest a coalescence-induced phase transition from a nonfcc to a stable fcc structure, due to the metastable nature of the nonfcc phases. While hydrogen is proven to be a key component for the synthesis of the nonfcc structure, there was limited formation of the unusual phase in a H2 gas bubbling system. Thus, electrochemical pathways can be promising for the in situ creation and study of unique metastable nanomaterials.

2.
Endosc Ultrasound ; 13(2): 100-106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947749

RESUMO

Background and Objective: To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (125I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer. Methods: We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-125I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups. Results: EUS-CPN and 125I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-125I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-125I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure. Conclusions: Both EUS-CPN and EUS-125I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-125I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.

3.
Eur Respir Rev ; 33(172)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38925790

RESUMO

Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune systems to detect and respond to pathogens, pollutants and other potential hazards in the respiratory tract. This interaction helps maintain the health and integrity of the respiratory system. Therefore, understanding the complex interactions between the respiratory nervous system and immune system is critical to maintaining lung health and developing treatments for respiratory diseases. In this review, we summarise the projection distribution of different types of neurons (trigeminal nerve, glossopharyngeal nerve, vagus nerve, spinal dorsal root nerve, sympathetic nerve) in the respiratory tract. We also introduce several types of cells in the respiratory epithelium that closely interact with nerves (pulmonary neuroendocrine cells, brush cells, solitary chemosensory cells and tastebuds). These cells are primarily located at key positions in the respiratory tract, where nerves project to them, forming neuroepithelial recognition units, thus enhancing the ability of neural recognition. Furthermore, we summarise the roles played by these different neurons in sensing or responding to specific pathogens (influenza, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, human metapneumovirus, herpes viruses, Sendai parainfluenza virus, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, amoebae), allergens, atmospheric pollutants (smoking, exhaust pollution), and their potential roles in regulating interactions among different pathogens. We also summarise the prospects of bioelectronic medicine as a third therapeutic approach following drugs and surgery, as well as the potential mechanisms of meditation breathing as an adjunct therapy.


Assuntos
Neuroimunomodulação , Sistema Respiratório , Humanos , Animais , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , Interações Hospedeiro-Patógeno , Doenças Respiratórias/imunologia , Doenças Respiratórias/terapia , Doenças Respiratórias/fisiopatologia , Doenças Respiratórias/virologia , Transdução de Sinais
4.
Mol Ther ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822526

RESUMO

Vagus nerve regulates viral infection and inflammation via the alpha 7 nicotinic acetylcholine receptor (α7 nAChR); however, the role of α7 nAChR in ZIKA virus (ZIKV) infection, which can cause severe neurological diseases such as microcephaly and Guillain-Barré syndrome, remains unknown. Here, we first examined the role of α7 nAChR in ZIKV infection in vitro. A broad effect of α7 nAChR activation was identified in limiting ZIKV infection in multiple cell lines. Combined with transcriptomics analysis, we further demonstrated that α7 nAChR activation promoted autophagy and ferroptosis pathways to limit cellular ZIKV viral loads. Additionally, activation of α7 nAChR prevented ZIKV-induced p62 nucleus accumulation, which mediated an enhanced autophagy pathway. By regulating proteasome complex and an E3 ligase NEDD4, activation of α7 nAChR resulted in increased amount of cellular p62, which further enhanced the ferroptosis pathway to reduce ZIKV infection. Moreover, utilizing in vivo neonatal mouse models, we showed that α7 nAChR is essential in controlling the disease severity of ZIKV infection. Taken together, our findings identify an α7 nAChR-mediated effect that critically contributes to limiting ZIKV infection, and α7 nAChR activation offers a novel strategy for combating ZIKV infection and its complications.

5.
Surg Endosc ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898340

RESUMO

BACKGROUND: Endoscopic ultrasound-guided pancreatic duct (PD) drainage (EUS-PDD) is being increasingly performed as an alternative method to surgical drainage to achieve PD decompression after failed endoscopic retrograde pancreatography (ERP). However, no directly study has compared EUS-PDD with surgical PD drainage after failed ERP in patients with chronic pancreatitis. METHODS: Consecutive patients who underwent EUS-PDD or longitudinal pancreaticojejunostomy after failed ERP were retrospectively identified from our endoscopy and medical information systems. The primary end point was the Izbicki pain score. The secondary end points were pain relief at the end of follow-up, procedure outcomes, adverse events, readmission, and reintervention. RESULTS: A total of 21 patients (11 EUS-PDD, 10 surgical drainages) were analyzed. There were no significant differences in mean Izbicki pain score (EUS-PDD, 13.6 ± 10.1 vs. surgical drainage 10.7 ± 7.9, p = 0.483) or complete/partial pain relief (60%/30% vs. 70%/30%, p = 0.752) at the end of follow-up of the two groups. The rates of overall adverse events (27.3% vs. 30.0%, p = 0.893) and readmission (63.6% vs. 40.0%, p = 0.290) were similar in the two treatment groups, while patients in EUS-PDD group required more reinterventions (45.5% vs. 0%, p = 0.039) compared with patients in the surgery group. CONCLUSION: EUS-PDD showed comparable pain relief and safety to surgical PD drainage after failed ERP, with a higher rate of reintervention. The selection of EUS-PDD or surgical drainage may be appropriate based on an individualized strategy.

6.
Brain Behav Immun ; 120: 499-512, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944162

RESUMO

The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.

7.
Parasite ; 31: 32, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912916

RESUMO

The plerocercoid larvae of Spirometra mansoni are etiological agents of human and animal sparganosis. Annexins are proteins with important roles in parasites. However, our knowledge of annexins in S. mansoni is still inadequate. In this study, 18 new members of the Annexin (ANX) family were characterized in S. mansoni. The clustering analysis demonstrated that all the SmANXs were divided into two main classes, consistent with the patterns of conserved motif organization. The 18 SmANXs were detected at all developmental stages (plerocercoid, adult, and egg) and displayed ubiquitous but highly variable expression patterns in all tissues/organs studied. The representative member rSmANX18 was successfully cloned and expressed. The protein was immunolocalized in the tegument and parenchyma of the plerocercoid and in the tegument, parenchyma, uterus and egg shell of adult worms. The recombinant protein can bind phospholipids with high affinity in a Ca2+-dependent manner, shows high anticoagulant activity and combines with FITC to recognize apoptotic cells. Annexin gene polymorphism and conservative core motif permutation were found in both cestodes and trematodes. SmANXs also revealed high genetic diversity among Platyhelminthes of medical interest. Our findings lay a foundation for further studies on the biological functions of ANXs in S. mansoni as well as other taxa in which ANXs occur.


Title: La famille des gènes des annexines chez Spirometra mansoni (Cestoda : Diphyllobothriidae) et son schéma phylogénétique parmi les Plathelminthes d'intérêt médical. Abstract: Les larves plérocercoïdes de Spirometra mansoni sont des agents étiologiques de la sparganose humaine et animale. Les annexines sont des protéines jouant un rôle important chez les parasites. Cependant, nos connaissances sur les annexines chez S. mansoni sont encore insuffisantes. Dans cette étude, 18 nouveaux membres de la famille des annexines (ANX) ont été caractérisés chez S. mansoni. L'analyse de regroupement a démontré que tous les SmANX étaient divisées en deux classes principales, ce qui correspond aux modèles d'organisation des motifs conservés. Les 18 SmANX ont été détectées à tous les stades de développement (plérocercoïde, adulte et œuf) et présentaient des modèles d'expression omniprésents mais très variables dans tous les tissus/organes étudiés. Le membre représentatif rSmANX18 a été cloné et exprimé avec succès. La protéine a été immunolocalisée dans le tégument et le parenchyme du plérocercoïde ainsi que dans le tégument, le parenchyme, l'utérus et la coquille d'œuf des vers adultes. La protéine recombinante peut se lier aux phospholipides avec une affinité élevée de manière dépendante du Ca2+, présente une activité anticoagulante élevée et se combine avec le FITC pour reconnaître les cellules apoptotiques. Un polymorphisme du gène de l'annexine et une permutation conservatrice du motif central ont été trouvés chez les cestodes et les trématodes. Les SmANX ont également révélé une grande diversité génétique parmi les Plathelminthes d'intérêt médical. Nos résultats jettent les bases pour des études plus approfondies sur les fonctions biologiques des ANX chez S. mansoni ainsi que dans d'autres taxons dans lesquels les ANX sont présents.


Assuntos
Anexinas , Filogenia , Spirometra , Animais , Spirometra/genética , Anexinas/genética , Anexinas/química , Sequência de Aminoácidos , Proteínas de Helminto/genética , Proteínas de Helminto/química , Família Multigênica , Humanos , Feminino , Variação Genética , Proteínas Recombinantes/genética
8.
J Psychiatry Neurosci ; 49(3): E192-E207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38816029

RESUMO

BACKGROUND: Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocin-oxytocin receptor system in fear empathy. METHODS: We used C57BL mice to establish 2 models of fear empathy and pain empathy. We employed immunofluorescence histochemical techniques to observe the expression of c-Fos throughout the entire brain and subsequently quantified the number of c-Fos-positive cells in different brain regions. Furthermore, we employed chemogenetic technology to selectively manipulate these neurons in Oxt-Cre-/+ mice to identify the role of oxytocin in this process. RESULTS: The regions activated by fear empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, paraventricular nucleus (PVN), lateral habenula, and ventral and dorsal hippocampus. The regions activated by pain empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, and lateral habenula. We found that increasing the activity of oxytocin neurons in the PVN region enhanced the response to fear empathy. This enhancement may be mediated through oxytocin receptors. LIMITATIONS: This study included only male animals, which restricts the broader interpretation of the findings. Further investigations on circuit function need to be conducted. CONCLUSION: The brain regions implicated in the regulation of fear and pain empathy exhibit distinctions; the activity of PVN neurons was positively correlated with empathic behaviour in mice. These findings highlight the role of the PVN oxytocin pathway in regulating fear empathy and suggest the importance of oxytocin signalling in mediating empathetic responses.


Assuntos
Empatia , Medo , Camundongos Endogâmicos C57BL , Neurônios , Ocitocina , Núcleo Hipotalâmico Paraventricular , Animais , Ocitocina/metabolismo , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Medo/fisiologia , Empatia/fisiologia , Neurônios/metabolismo , Camundongos , Receptores de Ocitocina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Dor/fisiopatologia , Dor/psicologia , Camundongos Transgênicos
9.
J Am Chem Soc ; 146(21): 14369-14385, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38718351

RESUMO

Supercapacitors (SCs) are some of the most promising energy storage devices, but their low energy density is one main weakness. Over the decades, superior electrode materials and suitable electrolytes have been widely developed to enhance the energy storage ability of SCs. Particularly, constructing asymmetric supercapacitors (ASCs) can extend their electrochemical stable voltage windows (ESVWs) and thus achieve high energy density. However, only full utilization of the electrochemical stable potential windows (ESPWs) of both positive and negative electrodes can endow the ASC devices with a maximum ESVW by using a suitable mass-ratio between two electrodes (the mass-balancing). Nevertheless, insufficient attention is directed to mass-balancing, and even numerous misunderstandings and misuses have appeared. Therefore, in this Perspective, we focus on the mass-balancing: summarize theoretic basis of the mass-balancing, derive relevant relation equations, analyze and discuss the change trends of the specific capacitance and energy density of ASCs with mass-ratios, and finally recommend some guidelines for the normative implementation of the mass-balancing. Especially, the issues related to pseudocapacitive materials, hybrid devices, and different open circuit potentials (OCPs) of the positive and negative electrodes in the mass-balancing are included and emphasized. These analyses and guidelines can be conducive to understanding and performing mass-balancing for developing high-performance SCs.

10.
Nat Genet ; 56(6): 1235-1244, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38714866

RESUMO

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.


Assuntos
Brassica , Domesticação , Genoma de Planta , Estudo de Associação Genômica Ampla , Genômica , Brassica/genética , Genômica/métodos , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Domínio MADS/genética
11.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2326-2335, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812133

RESUMO

Based on the association network of "drug pair-disease", the effect characteristics of Astragali Radix-Chuanxiong Rhizoma drug pair in the treatment of ischemic stroke(IS) with Qi deficiency and blood stasis and the matching mechanism of the two were explored. Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction Database, the effective chemical components of the drug pair were screened, and the candidate targets were predicted. Databa-ses such as GeneCards, DrugBank, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD) were searched to obtain gene targets related to IS. Through STRING and Cytoscape 3.9.1 software, the protein-protein interaction(PPI) network was constructed by using the interaction information of disease syndrome-related genes and candidate targets of drug pairs, and the core targets were screened according to the network topological feature values. Based on the Metascape platform and DAVID database, the biomolecular interaction information was integrated to analyze the Kyoto Encyclopedia of Genes and Genomes(KEGG) and mine biological functions, so as to further explore the mechanism of action and compatibility characteristics of Astragali Radix-Chuan-xiong Rhizoma. The results showed that the candidate biological process was mainly involved in the regulation of functional modules such as immune, blood circulation, neurotransmitter, and oxidative stress, and it was enriched in lipid and atherosclerosis, calcium signaling pathway, and platelet activation. Astragali Radix and Chuanxiong Rhizoma have their own characteristics. Astragali Radix has a regulatory response to growth factors while maintaining the body's immune balance, while Chuanxiong Rhizoma mainly improves the circulatory system and participates in hormone metabolism, so as to indicate the compatibility mechanism of Astragali Radix-Chuanxiong Rhizoma drug pair for multi-target and multi-pathway synergistic treatment of IS. Through further experimental verification, it was found that the Astragali Radix-Chuanxiong Rhizoma drug pair could significantly down-regulate the expression of key targets including TLR4, NF-κB, IL-1ß, F2R, PLCß1, and MYLK. This study preliminarily reveals that the Astragali Radix-Chuanxiong Rhizoma drug pair may play the three replenishing effects of promoting blood circulation, benefiting Qi, and clearing collaterals by correcting immune di-sorders, blood circulation disorders, and inflammation, which provide support for the clinical research on the subsequent improvement of Qi deficiency and blood stasis in the treatment of IS and provide a new idea for the analysis of modern biological connotation of the compatibility of seven emotions of traditional Chinese medicine.


Assuntos
Astragalus propinquus , Medicamentos de Ervas Chinesas , AVC Isquêmico , Mapas de Interação de Proteínas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Astragalus propinquus/química , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , Rizoma/química , Ligusticum/química
12.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2308-2315, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812131

RESUMO

This study aims to decipher the mechanism of tetramethylpyrazine(TMP) in regulating the migration of neural stem cells(NSCs) in the rat model of middle cerebral artery occlusion(MCAO) via the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)/C-X-C motif chemokine receptor 4(CXCR4) pathway. SD rats were randomized into sham, MCAO(model), and tetramethylpyrazine(TMP, 20 mg·kg~(-1) and 40 mg·kg~(-1)) groups. The neurological impairment was assessed by the modified neurological severity score(mNSS). The immunofluorescence assay was employed to detect the cells stained with both 5-bromodeoxyuridine(BrdU) and doublecortin(DCX) in the brain tissue. The effect of TMP on the migration of C17.2 cells was observed. Western blot was employed to determine the protein levels of Nrf2, HO-1, p62, NAD(P)H quinone oxidoreductase 1(NQO1), stromal cell-derived factor 1(SDF-1), and CXCR4 in the brain tissue and C17.2 cells. The results showed that after 7 days and 21 days of mode-ling, the mNSS and BrdU~+/DCX~+ cells were increased, and the expression of Nrf2 and CXCR4 in the brain tissue was up-regulated. Compared with the model group, TMP(40 mg·kg~(-1)) reduced the mNSS, increased the number of BrdU~+/DCX~+ cells, and up-regulated the expression of Nrf2, CXCR4, and SDF-1. In addition, TMP promoted the migration of C17.2 cells and up-regulated the expression of p62, Nrf2, HO-1, and NQO1 in a time-and dose-dependent manner. The expression was the highest at the time point of 12 h in the TMP(50 µg·mL~(-1)) group(P<0.01). In conclusion, TMP activates the Nrf2/HO-1/CXCR4 pathway to promote the migration of NSCs to the ischemic area, thus exerting the therapeutic effect on the ischemia-reperfusion injury. This study provides experimental support for the application of TMP in ischemic stroke.


Assuntos
Movimento Celular , Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Células-Tronco Neurais , Pirazinas , Ratos Sprague-Dawley , Receptores CXCR4 , Animais , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Pirazinas/farmacologia , Ratos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Movimento Celular/efeitos dos fármacos , Masculino , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Proteína Duplacortina , Transdução de Sinais/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Humanos
13.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2316-2325, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812132

RESUMO

This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery occlusion(MCAO) rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior. MCAO rats were randomly divided into a model group, a TMP group, an NSCs transplantation group, and a TMP combined with NSCs transplantation group according to neurological function scores. A sham group was set up at the same time. The neurological function score was used to evaluate the improvement of neurological function in MCAO rats after TMP combined with NSCs transplantation. The proliferation, migration, and differentiation of NSCs were evaluated by BrdU, BrdU/DCX, BrdU/NeuN, and BrdU/GFAP immunofluorescence labeling. The protein expression of stromal cell-derived factor 1(SDF-1), C-X-C motif chemokine receptor 4(CXCR4), as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(KEAP1), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1) was detected by Western blot to study the migration mechanism of TMP combined with NSCs. The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats. Immunofluorescence staining showed a significant increase in the number of BrdU~+, BrdU~+/DCX~+, BrdU~+/NeuN~+, and BrdU~+/GFAP~+ cells in the TMP, NSCs transplantation, and combined treatment groups, with the combined treatment group showing the most significant increase. Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP, NSCs transplantation, and combined treatment groups, along with up-regulated protein expression of Nrf2, HO-1, and NQO1, and decreased KEAP1 protein expression. This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation, migration, and differentiation of NSCs, and the effect of TMP combined with NSCs transplantation is superior. The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.


Assuntos
Isquemia Encefálica , Proteína Duplacortina , Fator 2 Relacionado a NF-E2 , Células-Tronco Neurais , Pirazinas , Ratos Sprague-Dawley , Receptores CXCR4 , Animais , Pirazinas/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/transplante , Células-Tronco Neurais/metabolismo , Ratos , Masculino , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Quimiocina CXCL12/metabolismo , Quimiocina CXCL12/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Transplante de Células-Tronco/métodos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Humanos , Traumatismo por Reperfusão/terapia , Traumatismo por Reperfusão/metabolismo , Infarto da Artéria Cerebral Média/terapia , NAD(P)H Desidrogenase (Quinona)/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética
14.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2336-2344, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812134

RESUMO

This study aims to optimize the conditions for the formation of neutrophil extracellular traps(NETs) in vitro, so as to establish a relatively stable experimental research platform. Different conditions were compared, including commonly used laboratory animals(rats and mice) and a variety of cell sources(bone marrow neutrophils and peripheral blood neutrophils separated by percoll density gradient centrifugation). Different inducers like lipopolysaccharide(LPS) and phorbol 12-myristate 13-acetate(PMA) were used for induction in vitro. Myeloperoxidase(MPO)/citrullinated histone H3(CitH3)/DAPI immunofluorescence and cell free DNA(cf-DNA) content determination were used for comprehensive evaluation to screen the optimal conditions for the formation of NETs induced in vitro. Furthermore, the stability of the selected conditions for inducing the formation of NETs in vitro was evaluated by tetramethylpyrazine(TMP), an active component in Chinese herbal medicines. The results showed that coated poly-D-lysine(PDL) induced the formation of NETs in bone marrow neutrophils of mice to a certain extent. Both LPS and PMA significantly up-regulated the protein levels of MPO and CitH3 in mouse bone marrow neutrophils and elevated the cfDNA level in the supernatant of rat peripheral blood neutrophils. The cfDNA level in the PMA-induced group increased more significantly than that in the LPS-induced group(P<0.05). The results of immunofluorescence staining showed that the expression of MPO and CitH3 in mouse bone marrow neutrophils, rat bone marrow neutrophils, and rat peripheral blood neutrophils were significantly increased after PMA induction, especially in rat peripheral blood neutrophils. TMP significantly down-regulated the protein levels of MPO, CitH3, and neutrophil elastase(NE) in rat peripheral blood neutrophils induced by PMA. In conclusion, treating the peripheral blood neutrophils of rats with PMA is the optimal condition for inducing the formation of NETs in vitro. This study provides an optimal platform for in vitro studies based on NETs and a basis for studying the effects of traditional Chinese medicines targeting NETs.


Assuntos
Armadilhas Extracelulares , Neutrófilos , Peroxidase , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Animais , Neutrófilos/efeitos dos fármacos , Neutrófilos/citologia , Camundongos , Ratos , Peroxidase/metabolismo , Peroxidase/genética , Acetato de Tetradecanoilforbol/farmacologia , Masculino , Lipopolissacarídeos/farmacologia , Ratos Sprague-Dawley , Histonas/metabolismo , Histonas/genética , Humanos
15.
Artigo em Inglês | MEDLINE | ID: mdl-38753528

RESUMO

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

16.
Mol Oral Microbiol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757737

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. METHODS: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot. RESULTS: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6. CONCLUSIONS: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.

17.
Echocardiography ; 41(5): e15828, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38762785

RESUMO

OBJECTIVES: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. METHODS: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. RESULTS: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD-flow combined with STIC than that in the 2D combined with HD-flow. CONCLUSION: HD-flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value.


Assuntos
Aorta Torácica , Ultrassonografia Pré-Natal , Humanos , Feminino , Ultrassonografia Pré-Natal/métodos , Gravidez , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/anormalidades , Aorta Torácica/embriologia , Estudos Retrospectivos , Adulto , Reprodutibilidade dos Testes , Coração Fetal/diagnóstico por imagem
18.
Small ; : e2401159, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716681

RESUMO

Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO3 with inert electrocatalytic behavior can be activated through defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H2 atmosphere, oxygen vacancies will generate in WO3 and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO3 into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate *H adsorption energies on various WOx surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.

19.
Sci Rep ; 14(1): 10740, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729987

RESUMO

Klotho regulates many pathways in the aging process, but it remains unclear how it is physiologically regulated. Because Klotho is synthesized, cleaved, and released from the kidney; activates the chief urinary K+ secretion channel (ROMK) and stimulates urinary K+ secretion, we explored if Klotho protein is regulated by dietary K+ and the potassium-regulatory hormone, Aldosterone. Klotho protein along the nephron was evaluated in humans and in wild-type (WT) mice; and in mice lacking components of Aldosterone signaling, including the Aldosterone-Synthase KO (AS-KO) and the Mineralocorticoid-Receptor KO (MR-KO) mice. We found the specific cells of the distal nephron in humans and mice that are chief sites of regulated K+ secretion have the highest Klotho protein expression along the nephron. WT mice fed K+-rich diets increased Klotho expression in these cells. AS-KO mice exhibit normal Klotho under basal conditions but could not upregulate Klotho in response to high-K+ intake in the K+-secreting cells. Similarly, MR-KO mice exhibit decreased Klotho protein expression. Together, i) Klotho is highly expressed in the key sites of regulated K+ secretion in humans and mice, ii) In mice, K+-rich diets increase Klotho expression specifically in the potassium secretory cells of the distal nephron, iii) Aldosterone signaling is required for Klotho response to high K+ intake.


Assuntos
Aldosterona , Glucuronidase , Proteínas Klotho , Camundongos Knockout , Potássio , Proteínas Klotho/metabolismo , Animais , Humanos , Camundongos , Potássio/metabolismo , Aldosterona/metabolismo , Glucuronidase/metabolismo , Glucuronidase/genética , Masculino , Néfrons/metabolismo , Potássio na Dieta/metabolismo , Potássio na Dieta/administração & dosagem , Feminino , Receptores de Mineralocorticoides/metabolismo , Receptores de Mineralocorticoides/genética , Camundongos Endogâmicos C57BL
20.
Integr Cancer Ther ; 23: 15347354241243024, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708673

RESUMO

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the world. Multiple evidence suggests that there is an association between excess fat consumption and the risk of CRC. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential for human health, and both in vitro and in vivo studies have shown that these fatty acids can prevent CRC development through various molecular mechanisms. These include the modulation of arachidonic acid (AA) derived prostaglandin synthesis, alteration of growth signaling pathways, arrest of the cell cycle, induction of cell apoptosis, suppression of angiogenesis and modulation of inflammatory response. Human clinical studies found that LC n-3 PUFA combined with chemotherapeutic agents can improve the efficacy of treatment and reduce the dosage of chemotherapy and associated side effects. In this review, we discuss comprehensively the anti-cancer effects of LC n-3 PUFA on CRC, with a main focus on the underlying molecular mechanisms.


Assuntos
Neoplasias Colorretais , Ácidos Graxos Ômega-3 , Humanos , Neoplasias Colorretais/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
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