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1.
Proc Natl Acad Sci U S A ; 121(28): e2314320121, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38954540

RÉSUMÉ

Liquid-phase electron microscopy (LP-EM) imaging has revolutionized our understanding of nanosynthesis and assembly. However, the current closed geometry limits its application for open systems. The ubiquitous physical process of the coffee-ring phenomenon that underpins materials and engineering science remains elusive at the nanoscale due to the lack of experimental tools. We introduce a quartz nanopipette liquid cell with a tunable dimension that requires only standard microscopes. Depending on the imaging condition, the open geometry of the nanopipette allows the imaging of evaporation-induced pattern formation, but it can also function as an ordinary closed-geometry liquid cell where evaporation is negligible despite the nano opening. The nano coffee-ring phenomenon was observed by tracking individual nanoparticles in an evaporating nanodroplet created from a thin liquid film by interfacial instability. Nanoflows drive the assembly and disruption of a ring pattern with the absence of particle-particle correlations. With surface effects, nanoflows override thermal fluctuations at tens of nanometers, in which nanoparticles displayed a "drunken man trajectory" and performed work at a value much smaller than kBT.

2.
Surg Endosc ; 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38886229

RÉSUMÉ

BACKGROUND: To compare the clinical outcomes in patients with acute perforated peptic ulcer (PPU) treated with over-the-scope clip (OTSC), non-surgical, and surgical interventions, and to explore the effectiveness and safety of OTSC closure. METHODS: Hospital stay, antibiotic use, diet resumption time, and mortality rate were analyzed retrospectively. Binary Logistic regression analysis was used to identify the risk factors influencing PPU complicated with sepsis. RESULTS: Patients were divided into three treatment groups: OTSC (n = 62), non-surgical (n = 72), and surgical (n = 55) groups. The median time (IQR) from symptom onset to admission was 9.0 (4-23) h. 88.71% (55/62) of the patients in In the OTSC group underwent OTSC closure within 24 h (median [IQR] time: 14.5 [7.00-30.25] h). The perforation diameters in the OTSC and surgical groups were 9.87 mm ± 5.97 mm and 8.55 mm ± 6.17 mm, respectively. The median (IQR) hospital stays in the OTSC (9.50 [7.00-12.25] days) and non-surgical group (9.00[7.00-13.00]days) were similar (p > 0.05), but shorter than that in surgical group (12.00[10.00-16.00]days), (p < 0.05). The median duration of antibiotic use was shorter in the OTSC group (7.00[3.00-10.00]) than in the non-surgical group (9.00[7.00-11.00]) and surgical group (11.00[9.00-13.00]) ( p < 0.05); and the time to resume oral feeding was shorter in the OTSC group (4.00[2.00-5.25]) than in the non-surgical group (7.00[6.13-9.00]) and surgical group (8.00[6.53-10.00]), respectively ( p < 0.05). No mortality difference among groups (p = 0.109) was found. Lower albumin level at admission, older age, and elevated creatinine levels were associated with increased sepsis risk, with OR(95%CI) of 0.826 (0.687-0.993), 1.077 (1.005-1.154), and 1.025 (1.006-1.043), respectively (all p < 0.05). CONCLUSION: OTSC closure improves clinical outcomes of acute PPU patients without sepsis. Age, hypoalbuminemia, and baseline renal dysfunction increase the risk of sepsis, while mortality was associated with sepsis and multiorgan dysfunction.

3.
PLoS Biol ; 22(6): e3002680, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38865309

RÉSUMÉ

CRISPR-Cas12a, often regarded as a precise genome editor, still requires improvements in specificity. In this study, we used a GFP-activation assay to screen 14 new Cas12a nucleases for mammalian genome editing, successfully identifying 9 active ones. Notably, these Cas12a nucleases prefer pyrimidine-rich PAMs. Among these nucleases, we extensively characterized Mb4Cas12a obtained from Moraxella bovis CCUG 2133, which recognizes a YYN PAM (Y = C or T). Our biochemical analysis demonstrates that Mb4Cas12a can cleave double-strand DNA across a wide temperature range. To improve specificity, we constructed a SWISS-MODEL of Mb4Cas12a based on the FnCas12a crystal structure and identified 8 amino acids potentially forming hydrogen bonds at the target DNA-crRNA interface. By replacing these amino acids with alanine to disrupt the hydrogen bond, we tested the influence of each mutation on Mb4Cas12a specificity. Interestingly, the F370A mutation improved specificity with minimal influence on activity. Further study showed that Mb4Cas12a-F370A is capable of discriminating single-nucleotide polymorphisms. These new Cas12a orthologs and high-fidelity variants hold substantial promise for therapeutic applications.


Sujet(s)
Allèles , Protéines associées aux CRISPR , Systèmes CRISPR-Cas , Édition de gène , Édition de gène/méthodes , Protéines associées aux CRISPR/métabolisme , Protéines associées aux CRISPR/génétique , Humains , Endodeoxyribonucleases/métabolisme , Endodeoxyribonucleases/génétique , Endodeoxyribonucleases/composition chimique , Animaux , Ingénierie des protéines/méthodes , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Protéines bactériennes/composition chimique , Polymorphisme de nucléotide simple , Mutation , ADN/métabolisme , ADN/génétique , Cellules HEK293
4.
Sci Bull (Beijing) ; 2024 Jun 10.
Article de Anglais | MEDLINE | ID: mdl-38910106

RÉSUMÉ

Many clustered regularly interspaced short palindromic repeat and CRISPR-associated protein 12b (CRISPR-Cas12b) nucleases have been computationally identified, yet their potential for genome editing remains largely unexplored. In this study, we conducted a GFP-activation assay screening 13 Cas12b nucleases for mammalian genome editing, identifying five active candidates. Candidatus hydrogenedentes Cas12b (ChCas12b) was found to recognize a straightforward WTN (W = T or A) proto-spacer adjacent motif (PAM), thereby dramatically expanding the targeting scope. Upon optimization of the single guide RNA (sgRNA) scaffold, ChCas12b exhibited activity comparable to SpCas9 across a panel of nine endogenous loci. Additionally, we identified nine mutations enhancing ChCas12b specificity. More importantly, we demonstrated that both ChCas12b and its high-fidelity variant, ChCas12b-D496A, enabled allele-specific disruption of genes harboring single nucleotide polymorphisms (SNPs). These data position ChCas12b and its high-fidelity counterparts as promising tools for both fundamental research and therapeutic applications.

5.
Photodiagnosis Photodyn Ther ; 47: 104215, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38735352

RÉSUMÉ

BACKGROUND: Nodulocystic acne is a severe form of acne, which is commonly treated with oral isotretinoin, hormones, or antibiotics. However, drug therapy often has some side effects and poor compliance. Fire needle combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a simple, effective, short-term treatment with few adverse reactions, which is expected to be an effective physiotherapy for nodulocystic acne. Moreover, the combination with isotretinoin can reduce the dosage of the drug, thereby reducing the side effects of isotretinoin. OBJECTIVES: To evaluate the safety and efficacy of fire-needle pretreated ALA-PDT combined with low-dose isotretinoin in the treatment of severe refractory nodulocystic acne. METHODS: This study reported 10 patients with refractory nodulocystic acne who received combined treatment. During the treatment period, all patients received a low dose of oral isotretinoin capsules daily. The acne lesions were pretreated with fire needle before ALA-PDT treatment. The number of acne lesions, including papules, pustules, and nodular cysts, was documented at weeks 0, 2, 4, 8, and 12 to assess the therapeutic efficacy. Concurrently, adverse reactions such as pain, pruritus, and pigmentation changes were recorded and evaluated throughout the treatment course. RESULTS: After combined treatment, all patients achieved good therapeutic effects, with an overall effective rate of 90 % at week 12. After treatment, skin lesions such as nodules, and cysts subsided significantly. The combination therapy has no serious adverse effects and has a favorable safety profile. CONCLUSION: Fire needle pretreatment ALA-PDT combined with low-dose isotretinoin is effective and safe in the treatment of severe refractory nodular cystic acne, which is worthy of clinical promotion and research.


Sujet(s)
Acné juvénile , Acide amino-lévulinique , Isotrétinoïne , Photothérapie dynamique , Photosensibilisants , Humains , Isotrétinoïne/administration et posologie , Isotrétinoïne/usage thérapeutique , Acide amino-lévulinique/administration et posologie , Acide amino-lévulinique/usage thérapeutique , Photothérapie dynamique/méthodes , Acné juvénile/traitement médicamenteux , Photosensibilisants/usage thérapeutique , Photosensibilisants/administration et posologie , Mâle , Femelle , Jeune adulte , Adulte , Adolescent , Association thérapeutique , Produits dermatologiques/administration et posologie , Produits dermatologiques/usage thérapeutique , Relation dose-effet des médicaments
6.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1956-1965, 2024 Apr.
Article de Chinois | MEDLINE | ID: mdl-38812208

RÉSUMÉ

The latent structure model and association rules analysis were employed to explore the compatibility rules of prescriptions for heart failure of dilated cardiomyopathy, with a view to providing theoretical support for the clinical treatment of this disease based on syndrome differentiation and the formulation of guidelines. The articles about the treatment of heart failure of dilated cardiomyopathy were retrieved from CNKI, Wanfang, VIP, and SinoMed. The database was established in Microsoft Excel 2019. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of Chinese medicine with the frequency greater than 4.00%. Furthermore, the frequency structure model was used to mine the rules of prescriptions for heart failure of dilated cardiomyopathy. The study included 175 traditional Chinese medicine(TCM) prescriptions, involving 128 Chinese medicines, with the cumulative frequency of 1 847. High-frequency medicines included Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, with the main effects of tonifying, activating blood, resolving stasis, and releasing exterior. A total of 17 hidden variables, 34 hidden categories, and 6 comprehensive cluster models, along with 15 core prescriptions, were obtained. According to the prescriptions, the patients mainly had the syndromes of heart-Yang and Qi deficiency, Qi deficiency and blood stasis, heart-kidney Yang deficiency or Qi-Yin deficiency. Fifty-four strong association rules were obtained through association rule analysis. The highest degree of support was observed for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix, while the highest degree of confidence was found for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Cinnamomi Ramulus-Ophiopogonis Radix-Astragali Radix. The heart failure of dilated cardiomyopathy, characterized by internal deficiency and excess manifestations, is attributed to deficiency, stasis, and water. These factors are closely associated with the heart, lung, and spleen. The treatment should follow the principle of invigorating Qi and warming Yang, and meanwhile the method of activating blood and resolve stasis or moving Qi and promoting urination can be adopted according to the specific syndrome of patients.


Sujet(s)
Cardiomyopathie dilatée , Médicaments issus de plantes chinoises , Défaillance cardiaque , Cardiomyopathie dilatée/traitement médicamenteux , Cardiomyopathie dilatée/physiopathologie , Humains , Médicaments issus de plantes chinoises/usage thérapeutique , Médicaments issus de plantes chinoises/composition chimique , Défaillance cardiaque/traitement médicamenteux , Défaillance cardiaque/physiopathologie , Médecine traditionnelle chinoise , Ordonnances médicamenteuses/statistiques et données numériques
7.
Clin Cosmet Investig Dermatol ; 17: 925-930, 2024.
Article de Anglais | MEDLINE | ID: mdl-38699408

RÉSUMÉ

Objective: Dermatological consultation plays an important role in diagnosing and treating skin diseases in the Department of Geriatrics. The objective of this study is to provide an analysis of the factors leading geriatric inpatients to seek dermatological consultation, aiming to facilitate accurate diagnosis and effective treatment of skin diseases by healthcare professionals specializing in geriatrics and dermatology. Methods: The electronic health records of hospitalized patients in the Department of Geriatrics who applied for dermatological consultation at the Second Hospital of Shandong University from June 1, 2022, to June 1, 2023, were retrieved. Sex, age, number of consultations, reason for dermatology consultation, and final diagnosis by dermatologists were reviewed. Results: A total of 216 consultations of 178 patients (n=178, 95 men and 83 women) were collected in this study, of whom 153 (86.0%) required only one consultation, 19 (10.7%) required two consultations, and 4 (2.2%) required three consultations. The reasons for dermatology consultations were divided into three categories: the first was for the definitive diagnosis of a new skin condition that developed during the patient's hospitalization (n=165, 76.4%), the second was for the follow-up of the condition and adjustment of medication (n=40, 18.5%), and the third was for the evaluation of the patient's disease that existed before admission to the hospital (n=11, 5.1%). In 165 consultations, most of these diseases (n=131, 79.4%) can be diagnosed by patients' conscious symptoms and clinical manifestations. Some of them need to be diagnosed or differentially diagnosed with the help of supplementary examinations, such as microscopic examination of scabies or fungi, and pathological examination. Conclusion: This study summarized the reasons for dermatology consultations for geriatric inpatients and found that dermatitis/eczema and infectious diseases were the common types of diseases consulted. The findings of this study contribute to the enhanced comprehension and management of dermatological conditions in hospitalized patients by geriatricians, as well as facilitating more efficient diagnosis and treatment by dermatologists.

8.
Sci Rep ; 14(1): 11947, 2024 05 25.
Article de Anglais | MEDLINE | ID: mdl-38789486

RÉSUMÉ

A research model combining a disease and syndrome can provide new ideas for the treatment of ischemic stroke. In the field of traditional Chinese medicine, blood stasis and toxin (BST) syndrome is considered an important syndrome seen in patients with ischemic stroke (IS). However, the biological basis of IS-BST syndrome is currently not well understood. Therefore, this study aimed to explore the biological mechanism of IS-BST syndrome. This study is divided into two parts: (1) establishment of an animal model of ischemic stroke disease and an animal model of BST syndrome in ischemic stroke; (2) use of omics methods to identify differentially expressed genes and metabolites in the models. We used middle cerebral artery occlusion (MCAO) surgery to establish the disease model, and utilized carrageenan combined with active dry yeast and MCAO surgery to construct the IS-BST syndrome model. Next, we used transcriptomics and metabolomics methods to explore the differential genes and metabolites in the disease model and IS-BST syndrome model. It is found that the IS-BST syndrome model exhibited more prominent characteristics of IS disease and syndrome features. Both the disease model and the IS-BST syndrome model share some common biological processes, such as thrombus formation, inflammatory response, purine metabolism, sphingolipid metabolism, and so on. Results of the "gene-metabolite" network revealed that the IS-BST syndrome model exhibited more pronounced features of complement-coagulation cascade reactions and amino acid metabolism disorders. Additionally, the "F2 (thrombin)-NMDAR/glutamate" pathway was coupled with the formation process of the blood stasis and toxin syndrome. This study reveals the intricate mechanism of IS-BST syndrome, offering a successful model for investigating the combination of disease and syndrome.


Sujet(s)
Modèles animaux de maladie humaine , Accident vasculaire cérébral ischémique , Médecine traditionnelle chinoise , Métabolomique , Transcriptome , Animaux , Métabolomique/méthodes , Accident vasculaire cérébral ischémique/métabolisme , Accident vasculaire cérébral ischémique/génétique , Médecine traditionnelle chinoise/méthodes , Mâle , Réseaux de régulation génique , Rats , Analyse de profil d'expression de gènes , Infarctus du territoire de l'artère cérébrale moyenne/métabolisme , Infarctus du territoire de l'artère cérébrale moyenne/génétique , Syndrome , Rat Sprague-Dawley
10.
J Inflamm Res ; 17: 2939-2949, 2024.
Article de Anglais | MEDLINE | ID: mdl-38764498

RÉSUMÉ

Background: To date, there are no studies regarding the Mrp 8/14 in predicting the occurrence of acute respiratory distress syndrome (ARDS) induced by sepsis. Thus, the objective of this study was to investigate the expression of Myeloid-related proteins 8 and 14 (Mrp 8/14) and its role in ARDS induced by sepsis. Methods: A total of 168 septic patients were enrolled in the observational study. The baseline information and clinical outcomes were obtained retrospectively. Serum Mrp 8/14 level was determined by enzyme linked immunosorbent assay (ELISA). The patients were categorized into sepsis and ARDS group based on whether they developed ARDS during the intensive care unit (ICU) hospitalization. Results: There was significant difference in the level of Mrp 8/14 between the sepsis group and ARDS groups (P < 0.05). Mrp 8/14 correlated positively with procalcitonin (PCT), interleukin-6 (IL-6), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score on day 1, mechanical ventilation time, length of ICU stay and hospitalization expenses in ICU (all P < 0.05). Logistic regression analysis showed Mrp 8/14 was the independent factor for forecasting the occurrence of sepsis- induced ARDS (P < 0.05). The areas under receiver operating characteristic curves for Mrp 8/14 were higher than that of PCT, APACHE II score and SOFA score on day 1 (P < 0.05). Conclusion: The serum Mrp 8/14 level at admission may be a potential marker for predicting the occurrence of ARDS induced by sepsis. Early detection of serum Mrp 8/14 could help clinicians to identify and evaluate the severity of ARDS induced by sepsis.

11.
Molecules ; 29(10)2024 May 15.
Article de Anglais | MEDLINE | ID: mdl-38792186

RÉSUMÉ

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.


Sujet(s)
Systèmes de délivrance de médicaments , Fibrinolytiques , Thrombose , Humains , Fibrinolytiques/composition chimique , Fibrinolytiques/usage thérapeutique , Fibrinolytiques/administration et posologie , Thrombose/traitement médicamenteux , Nanostructures/composition chimique , Nanostructures/usage thérapeutique , Traitement thrombolytique/méthodes , Animaux
12.
Clin Cosmet Investig Dermatol ; 17: 1193-1202, 2024.
Article de Anglais | MEDLINE | ID: mdl-38800354

RÉSUMÉ

Objective and Design: The treatment of recurrent rosacea has always been a problem. Oral minocycline has been widely used in the treatment of rosacea. However, the efficacy and safety of ozonated hydrotherapy combined with LED yellow light irradiation and oral minocycline for mild to moderate papulopustular rosacea (PPR) has not been thoroughly studied. Methods: Patients with rosacea who met the criteria and had complete clinical statistic admitted to our hospital from April 2021 to September 2022 were retrospectively collected and divided into combined therapy group and oral only group. The patients in the two groups were treated with minocycline for 8 weeks. In addition, the patients in combined therapy group were treated with ozone hydrotherapy once a week, followed by LED yellow light irradiation for a total of 4 weeks. The Investigator' s global assessment (IGA) score was used to assess the condition. The efficacy was evaluated using the patients' subjective symptom scores. Skin lesion images and adverse reactions were recorded. The recurrence rate was observed after 24 weeks of follow-up. Results: A total of 39 patients included in the study. After 4 weeks of treatment, the effective rate was 90% in combined therapy group and 52.63% in oral only group (p<0.05). After 8 weeks of treatment, the total score of the patients' subjective symptom scores and the scores of itching and burning sensation in combined therapy group were lower than those in oral only group (p<0.05). After 24 weeks of follow-up, the recurrence rate of combined therapy group was 5%, and that of oral only group was 26.32%. The mild adverse reactions experienced by both groups disappeared during follow-up. Conclusion: This combination therapy has a significant, rapid and safe therapeutic effect, especially in relieving itching and burning sensations, and may reduce the recurrence rate.

13.
Mod Pathol ; 37(6): 100486, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38588882

RÉSUMÉ

The role of artificial intelligence (AI) in pathology offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of the AICyte assistive system for cervical screening, and investigating the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte assistive system, to create an AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides. For validation purposes, 2 pathologists reviewed OOIs from 32,451 cases of ThinPrep Paps independently, and their interpretations were correlated with the original ThinPrep interpretations (OTPI). The analysis was focused on the comparison of reporting rates, correlation between cytological results and histologic follow-up findings, and the assessment of independent AICyte screening utility. Pathologists using the AICyte system had a mean reading time of 55.14 seconds for the first 3000 cases trending down to 12.90 seconds in the last 6000 cases. Overall average reading time was 22.23 seconds per case compared with a manual reading time approximation of 180 seconds. Usage of AICyte compared with OTPI had similar sensitivity (97.89% vs 97.89%) and a statistically significant increase in specificity (16.19% vs 6.77%) for the detection of cervical intraepithelial neoplsia 2 and above lesions. When AICyte was run alone at a 50% negative cutoff value, it was able to read slides with a sensitivity of 99.30% and a specificity of 9.87%. When AICyte was run independently at this cutoff value, no sole case of high-grade squamous intraepithelial lesions/squamous cell carcinoma squamous lesion was missed. AICyte can provide a potential tool to help pathologists in both diagnostic capability and efficiency, which remained reliable compared with the baseline standard. Also unique for AICyte is the development of a negative cutoff value for which AICyte can categorize cases as "not needed for review" to triage cases and lower pathologist workload. This is the largest case number study that pathologists reviewed OOI with an AI-assistive system. The study demonstrates that AI-assistive system can be broadly applied for cervical cancer screening.


Sujet(s)
Intelligence artificielle , Tumeurs du col de l'utérus , Frottis vaginaux , Humains , Femelle , Tumeurs du col de l'utérus/diagnostic , Tumeurs du col de l'utérus/anatomopathologie , Frottis vaginaux/méthodes , Dépistage précoce du cancer/méthodes , Test de Papanicolaou/méthodes , Interprétation d'images assistée par ordinateur/méthodes , Reproductibilité des résultats , Dysplasie du col utérin/diagnostic , Dysplasie du col utérin/anatomopathologie , Cytologie
14.
Chem Commun (Camb) ; 60(38): 5026-5029, 2024 May 07.
Article de Anglais | MEDLINE | ID: mdl-38629636

RÉSUMÉ

In the research presented herein, low-valent-tungsten-catalyzed hydroboration of esters and nitriles was investigated. Aromatic and aliphatic substrates were smoothly reduced to corresponding alcohol derivatives and N,N-diborylamines in the presence of W(CO)4(NCMe)2. Valuable derivatives were conveniently accessed by introducing a further functionalization process to crude hydroboration mixtures in one pot.

15.
Curr Pain Headache Rep ; 28(5): 439-451, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38502437

RÉSUMÉ

PURPOSE OF REVIEW: Tension-type headaches (TTH) significantly diminish patients' quality of life and increase absenteeism, thereby imposing a substantial economic burden. Animal models are essential tools for studying disease mechanisms and drug development. However, until now, little focus has been placed on summarizing the animal models of TTH and associated mechanistic studies. This narrative review discusses the current animal models of TTH and related mechanistic studies to provide insights into the pathophysiological mechanisms of and treatments for TTH. RECENT FINDINGS: The primary method for constructing an animal model of TTH involves injecting a solution of pain relievers, such as adenosine triphosphate, nerve growth factor, or a high concentration of salt solution, into the neck to initiate harmful cervical muscle responses. This model enables the examination of the interaction between peripheral muscles and central sensitization, which is crucial for understanding the pathophysiology of TTH. Mechanistic studies based on this model have investigated the effect of the P2X receptor antagonist, P2X7 receptor blockade, the P2Y1 receptor agonist 2-MESADP, P2Y1 receptor antagonist MRS2179, nitric oxide synthase inhibitors, and acetylsalicylic acid. Despite notable advancements, the current model of TTH has limitations, including surgical complexity and the inability to replicate chronic tension-type headache (CTTH). To gain a more comprehensive understanding and develop more effective treatment methods, future studies should focus on simplifying surgical procedures, examining other predisposing factors, and establishing a model for chronic TTH. This will offer a deeper insight into the pathophysiological mechanism of TTH and pave the way for improved treatment approaches.


Sujet(s)
Modèles animaux de maladie humaine , Céphalée de tension , Céphalée de tension/physiopathologie , Céphalée de tension/traitement médicamenteux , Céphalée de tension/thérapie , Animaux , Humains
16.
Free Radic Biol Med ; 216: 60-77, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38479634

RÉSUMÉ

Parkinson's disease (PD) is a prevalent progressive and multifactorial neurodegenerative disorder. Cordycepin is known to exhibit antitumor, anti-inflammatory, antioxidative stress, and neuroprotective effects; however, few studies have explored the neuroprotective mechanism of cordycepin in PD. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, we investigated the impact of cordycepin on PD and its underlying molecular mechanisms. The findings indicated that cordycepin significantly mitigated MPTP-induced behavior disorder and neuroapoptosis, diminished the loss of dopaminergic neurons in the striatum-substantia nigra pathway, elevated striatal monoamine levels and its metabolites, and inhibited the polarization of microglia and the expression of pro-inflammatory factors. Subsequent proteomic and phosphoproteomic analyses revealed the involvement of the MAPK, mTOR, and PI3K/AKT signaling pathways in the protective mechanism of cordycepin. Cordycepin treatment inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the expression of autophagy proteins in the striatum and substantia nigra. We also demonstrated the in vivo inhibition of the ERK/JNK signaling pathway by cordycepin treatment. In summary, our investigation reveals that cordycepin exerts neuroprotective effects against PD by promoting autophagy and suppressing neuroinflammation and neuronal apoptosis by inhibiting the PI3K/AKT/mTOR and ERK/JNK signaling pathways. This finding highlights the favorable characteristics of cordycepin in neuroprotection and provides novel molecular insights into the neuroprotective role of natural products in PD.


Sujet(s)
Désoxyadénosine , Neuroprotecteurs , Maladie de Parkinson , Souris , Animaux , Maladie de Parkinson/traitement médicamenteux , Maladie de Parkinson/génétique , Maladie de Parkinson/métabolisme , Neuroprotecteurs/pharmacologie , Protéines proto-oncogènes c-akt/génétique , Protéines proto-oncogènes c-akt/métabolisme , Phosphatidylinositol 3-kinases/génétique , Phosphatidylinositol 3-kinases/métabolisme , Maladies neuro-inflammatoires , Protéomique , Sérine-thréonine kinases TOR/génétique , Sérine-thréonine kinases TOR/métabolisme , Souris de lignée C57BL , Neurones dopaminergiques/métabolisme , Modèles animaux de maladie humaine , 1-Méthyl-4-phényl-1,2,3,6-tétrahydropyridine/effets indésirables
17.
Neuroreport ; 35(6): 421-430, 2024 04 03.
Article de Anglais | MEDLINE | ID: mdl-38526966

RÉSUMÉ

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The main bioactive component of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) exerts protective effects against diseases such as neurodegenerative diseases and cancer. Therefore, this study investigated the effect of EGCG on the amelioration of neural damage in a chronic PD mouse model induced by α-synuclein preformed fibrils (α-syn-PFFs). A total of 20 C57BL/6J female mice were randomly divided into 3 groups: control group (saline, n = 6), model group (PFFs, n = 7), and prevention group (EGCG+PFFs, n = 7). A chronic PD mouse model was obtained by the administration of α-syn-PFFs by stereotaxic localization in the striatum. Behavioral tests were performed to evaluate PD-related anxiety-like behavior and motor impairments in the long-term PD progression. Tyrosine hydroxylase (TH) immuno-positive neurons and Ser129-phosphorylated α-syn (p-α-syn) were identified by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokines were measured by real-time quantitative PCR. EGCG pretreatment reduced anxiety-like behavior and motor impairments as revealed by the long-term behavioral test (2 weeks, 1 month, 3 months, and 6 months) on PD mice. EGCG also ameliorated PFF-induced degeneration of TH immuno-positive neurons and accumulation of p-α-syn in the SN and striatum at 6 months. Additionally, EGCG reduced the expression of pro-inflammatory cytokines while promoting the release of anti-inflammatory cytokines. EGCG exerts a neuroprotective effect on long-term progression of the PD model.


Sujet(s)
Catéchine/analogues et dérivés , Maladies neurodégénératives , Neuroprotecteurs , Maladie de Parkinson , Souris , Femelle , Animaux , Maladie de Parkinson/traitement médicamenteux , Maladie de Parkinson/métabolisme , Neuroprotecteurs/pharmacologie , Maladies neurodégénératives/métabolisme , Souris de lignée C57BL , alpha-Synucléine/métabolisme , Substantia nigra , Neurones dopaminergiques , Thé , Anti-inflammatoires/pharmacologie , Cytokines/métabolisme , Modèles animaux de maladie humaine
18.
Hortic Res ; 11(3): uhae032, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38544550

RÉSUMÉ

Jasmonates, such as jasmonic acid (JA) and methyl jasmonate (MeJA), are crucial aspect of black tea quality. However, lipids species, hormones, and genes regulated mechanism in the jasmonate biosynthesis during black tea processing are lacking. In this study, we employed lipidomics, hormone metabolism analysis, and transcriptome profiling of genes associated with the MeJA biosynthesis pathway to investigate these factors. The contents of lipids GLs, PLs, and TAG are decreased, accompanied by the main lipids species reduced during black tea processing. Galactolipids, primarily 34:3/36:6/36:3 DGDG and 36:6/36:5/36:4 MGDG, are transformed into massive MeJA and JA in black tea processing, accompanied by the decreased SA, MeSA, IAA, and BA and increased zeatin. Additionally, the transcriptional activity of the primary genes in MeJA biosynthesis pathway exhibited downregulated trends except for AOS and OPR and non-primary genes tend to be a little high or have fluctuation of expression. Coordinated expression of main CsHPL (TEA008699), CsAOS (TEA001041), and CsJMT (TEA015791) control the flow of lipids degradation and MeJA production. A strong infected reduction of a key lipoxygenase gene, CsLOX6 (TEA009423), in tea buds significantly reduced the level of jasmonates and expression of downstream genes, accompanied by SA, MeSA level rising, and ABA declining. We have identified a key CsLOX6, as well as established galactolipids, mainly 34:3/36:6/36:3 DGDG and 36:6/36:5/36:4 MGDG, sources for MeJA biosynthesis regulated by dynamics hormone and controlled by coordinated expressed CsHPL (TEA008699), CsAOS (TEA001041), and CsJMT (TEA015791). Our findings provide a theoretical basis for breeding high-quality black tea and offer valuable insights for improving processing methods.

19.
J Phys Chem Lett ; 15(11): 3127-3134, 2024 Mar 21.
Article de Anglais | MEDLINE | ID: mdl-38471101

RÉSUMÉ

Here, we showed that supramolecular assemblies based on perylene diimides (PDIs) are able to activate molecular oxygen through both the electron transfer and energy transfer pathways, which consequently leads to the formation of superoxide radicals (·O2-) and singlet oxygen species (1O2), respectively. These reactive oxygen species (ROS) can effectively lead to oxidative coupling of benzylamine and oxidation of 2-chloroethyl sulfide (CEES). We have designed and synthesized PDIs with similar molecular structures yet differing by the molecular stacking modes. We found that the photooxidation activities of the PDI supramolecular assemblies are inversely associated with the photoluminescence wavelength difference between the assemblies and the monomers (Δλ) quantitatively, and a smaller Δλ results in a higher catalytic efficiency accordingly. Overall, this work contributes to the design and fabrication of high performance photocatalysts based on metal-free organic materials.

20.
Ecol Evol ; 14(3): e10919, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38476707

RÉSUMÉ

The rapid loss of global biodiversity can greatly affect the normal functioning of ecosystems. However, how biodiversity losses affect plant community structure and soil nutrients is unclear. We conducted a field experiment to examine the short- and long-term effects of removing plant functional groups (Gramineae, Cyperaceae, legumes, and forbs) on the interrelationships among the species diversity, productivity, community structure, and soil nutrients in an alpine meadow ecosystem at Menyuan County, Qinghai Province. The variations in the species richness, above- and belowground biomass of the community gradually decreased over time. Species richness and productivity were positively correlated, and this correlation tended to be increasingly significant over time. Removal of the Cyperaceae, legumes, and other forbs resulted in fewer Gramineae species in the community. Soil total nitrogen, phosphorus, organic matter, and moisture contents increased significantly in the legume removal treatment. The removal of other forbs led to the lowest negative cohesion values, suggesting that this community may have difficulty recovering its previous equilibrium state within a short time. The effects of species removal on the ecosystem were likely influenced by the species structure and composition within the community. Changes in the number of Gramineae species indicated that they were more sensitive and less resistant to plant functional group removal. Legume removal may also indirectly cause distinct community responses through starvation and compensation effects. In summary, species loss at the community level led to extensive species niche shifts, which caused community resource redistribution and significant changes in community structure.

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