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1.
Clin Cosmet Investig Dermatol ; 17: 925-930, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699408

RESUMEN

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.

3.
Photodiagnosis Photodyn Ther ; : 104215, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38735352

RESUMEN

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 method 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.

4.
J Inflamm Res ; 17: 2939-2949, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38764498

RESUMEN

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.

5.
Mod Pathol ; 37(6): 100486, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38588882

RESUMEN

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.

6.
Chem Commun (Camb) ; 60(38): 5026-5029, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38629636

RESUMEN

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.

7.
Hortic Res ; 11(3): uhae032, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38544550

RESUMEN

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.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38502437

RESUMEN

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.

9.
J Phys Chem Lett ; 15(11): 3127-3134, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38471101

RESUMEN

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.

10.
Free Radic Biol Med ; 216: 60-77, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38479634

RESUMEN

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.


Asunto(s)
Desoxiadenosinas , Fármacos Neuroprotectores , Enfermedad de Parkinson , Ratones , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Fármacos Neuroprotectores/farmacología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Enfermedades Neuroinflamatorias , Proteómica , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Ratones Endogámicos C57BL , Neuronas Dopaminérgicas/metabolismo , Modelos Animales de Enfermedad , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/efectos adversos
11.
Ecol Evol ; 14(3): e10919, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38476707

RESUMEN

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.

12.
Neuroreport ; 35(6): 421-430, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38526966

RESUMEN

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.


Asunto(s)
Catequina/análogos & derivados , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Enfermedad de Parkinson , Ratones , Femenino , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Fármacos Neuroprotectores/farmacología , Enfermedades Neurodegenerativas/metabolismo , Ratones Endogámicos C57BL , alfa-Sinucleína/metabolismo , Sustancia Negra , Neuronas Dopaminérgicas , , Antiinflamatorios/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad
13.
Zhongguo Zhong Yao Za Zhi ; 49(2): 518-533, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403327

RESUMEN

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.


Asunto(s)
Enfermedad Coronaria , Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Humanos , Metaanálisis en Red , Medicamentos sin Prescripción/uso terapéutico , Proteína C-Reactiva , Volumen Sistólico , Función Ventricular Izquierda , Medicamentos Herbarios Chinos/uso terapéutico , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico
14.
J Hazard Mater ; 465: 133172, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38071777

RESUMEN

Although antibiotic alternatives are widely used in livestock and poultry breeding industry after in-feed antibiotics ban, their intervention effects on antibiotic resistance genes (ARGs) in these food animals' feces remain poorly understood. Here effects of fructooligosaccharide (FOS) and astragalus polysaccharide (APS), as typical antibiotic alternatives in China, on ARGs in layer feces were estimated by performing metagenomic sequencings and fluorescence quantitative PCR. Fructooligosaccharide significantly reduced sum abundance of ARGs and mobile genetic elements (MGEs) by increasing Lactobacillus clones and reducing Escherichia clones which had relatively higher abundances of ARG subtypes and MGE subtypes in layer feces. However, at least parts of core ARGs and MGEs categories were not reduced by FOS, such as aminoglycosides- and tetracyclines-resistant genes, Tn916, Integrase, and so on. MGEs and microbiome, especially Escherichia genus and Lactobacillus genus, were the key factors affecting ARGs' sum abundance. MGEs had a higher correlation coefficient with ARGs' sum abundance than Escherichia genus and Lactobacillus genus. These findings firstly reveal the defects of antibiotic alternatives in controlling bacterial resistance in livestock and poultry breeding after in-feed antibiotics ban, and more strategies are needed to control pollutions and risks of core ARGs and MGEs in food animals' feces under a special environment.


Asunto(s)
Antibacterianos , Genes Bacterianos , Oligosacáridos , Animales , Antibacterianos/farmacología , Farmacorresistencia Microbiana/genética , Heces , Polisacáridos
15.
Nanomedicine ; 56: 102726, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38052371

RESUMEN

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.


Asunto(s)
Biomimética , Nanopartículas , Preparaciones Farmacéuticas , Simvastatina/farmacología , Nanopartículas/química , Sistemas de Liberación de Medicamentos
16.
Circulation ; 149(4): 317-329, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-37965733

RESUMEN

BACKGROUND: Pathogenic variants in SCN5A can result in long QT syndrome type 3, a life-threatening genetic disease. Adenine base editors can convert targeted A T base pairs to G C base pairs, offering a promising tool to correct pathogenic variants. METHODS: We generated a long QT syndrome type 3 mouse model by introducing the T1307M pathogenic variant into the Scn5a gene. The adenine base editor was split into 2 smaller parts and delivered into the heart by adeno-associated virus serotype 9 (AAV9-ABEmax) to correct the T1307M pathogenic variant. RESULTS: Both homozygous and heterozygous T1307M mice showed significant QT prolongation. Carbachol administration induced Torsades de Pointes or ventricular tachycardia for homozygous T1307M mice (20%) but not for heterozygous or wild-type mice. A single intraperitoneal injection of AAV9-ABEmax at postnatal day 14 resulted in up to 99.20% Scn5a transcripts corrected in T1307M mice. Scn5a mRNA correction rate >60% eliminated QT prolongation; Scn5a mRNA correction rate <60% alleviated QT prolongation. Partial Scn5a correction resulted in cardiomyocytes heterogeneity, which did not induce severe arrhythmias. We did not detect off-target DNA or RNA editing events in ABEmax-treated mouse hearts. CONCLUSIONS: These findings show that in vivo AAV9-ABEmax editing can correct the variant Scn5a allele, effectively ameliorating arrhythmia phenotypes. Our results offer a proof of concept for the treatment of hereditary arrhythmias.


Asunto(s)
Trastorno del Sistema de Conducción Cardíaco , Edición Génica , Síndrome de QT Prolongado , Ratones , Animales , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/terapia , Síndrome de QT Prolongado/diagnóstico , Arritmias Cardíacas , Miocitos Cardíacos , Adenina , ARN Mensajero , Canal de Sodio Activado por Voltaje NAV1.5/genética , Mutación
17.
Artículo en Inglés | MEDLINE | ID: mdl-38083122

RESUMEN

BACKGROUND: Our previous study has shown that stimulation of the vagus nerve with low-intensity focused ultrasound could modulate blood pressure (BP), but the underlying mechanisms remain unclear. This study investigated the changes of cardiovascular neurotransmitter levels to indirectly evaluate the responses of the autonomic nervous system and renin-angiotensin system under low-intensity focused ultrasound stimulation (FUS) of the vagus nerve. METHODS: Cardiovascular neurotransmitter levels of epinephrine (EPI), norepinephrine (NE), and angiotensin II (ANGII) were measured and compared before and after the FUS in seven spontaneously hypertensive rats; and were also measured and compared between a target stimulation group (FUS, n = 6) and non-target stimulation group (Control, n = 5) after stimulation to exclude the influence of potential confounding factors. RESULTS: The t-test results showed that the levels of EPI, NE, and ANGII were significantly decreased (P < 0.05) after stimulation compared to before stimulation. Additionally, the levels of NE and EPI were significantly lower (P < 0.05) in the FUS group than in the Control group after stimulation, indicating that the activities of the sympathetic nervous system and renin-angiotensin system of the vagus nerve might be inhibited by FUS of the vagus nerve. CONCLUSION: These findings reveal the mechanism of BP lowing in response to FUS of the vagus nerve.Clinical Relevance-This study revealed the mechanism of BP lowering in response to focused ultrasound stimulation of the vagus nerve through analyzing the changes of cardiovascular neurotransmitter levels.


Asunto(s)
Corazón , Nervio Vago , Ratas , Animales , Nervio Vago/fisiología , Presión Sanguínea/fisiología , Sistema Nervioso Autónomo , Sistema Nervioso Simpático/fisiología
18.
ACS Sens ; 8(12): 4442-4467, 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38091479

RESUMEN

In recent years, there has been a notable increase in interest surrounding nanozymes due to their ability to imitate the functions and address the limitations of natural enzymes. The scientific community has been greatly intrigued by the study of nanoceria, primarily because of their distinctive physicochemical characteristics, which include a variety of enzyme-like activities, affordability, exceptional stability, and the ability to easily modify their surfaces. Consequently, nanoceria have found extensive use in various biosensing applications. However, the impact of its redox activity on the enzymatic catalytic mechanism remains a subject of debate, as conflicting findings in the literature have presented both pro-oxidant and antioxidant effects. Herein, we creatively propose a seesaw model to clarify the regulatory mechanism on redox balance and survey possible mechanisms of multienzyme mimetic properties of nanoceria. In addition, this review aims to showcase the latest advancements in this field by systematically discussing over 180 research articles elucidating the significance of ceria-based nanozymes in enhancing, downsizing, and enhancing the efficacy of point-of-care (POC) diagnostics. These advancements align with the ASSURED criteria established by the World Health Organization (WHO). Furthermore, this review also examines potential constraints in order to offer readers a concise overview of the emerging role of nanoceria in the advancement of POC diagnostic systems for future biosensing applications.


Asunto(s)
Cerio , Sistemas de Atención de Punto , Oxidación-Reducción , Cerio/química , Antioxidantes
19.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5932-5945, 2023 Nov.
Artículo en Chino | MEDLINE | ID: mdl-38114189

RESUMEN

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) > Yiqi Fumai Injection+conventional treatment(57.1%) > Xuebijing Injection+conventional treatment(56.6%) > Shenmai Injection+conventional treatment(53.1%) > Shenfu Injection+conventional treatment(45.3%) > conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) > Shenmai Injection+conventional treatment(69.6%) > Shenfu Injection+conventional treatment(62.7%) > Xinmailong Injection+conventional treatment(61.6%) > Shuxuening Injection+conventional treatment(54.8%) > Shenqi Fuzheng Injection+conventional treatment(46.7%) > Shengmai Injection+conventional treatment(45.9%) > Breviscapine Injection+conventional treatment(39.9%) > Danhong Injection+conventional treatment(38.8%) > Huangqi Injection+conventional treatment(38.7%) > conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) > Shenmai Injection+conventional treatment(57.7%) > Shenfu Injection+conventional treatment(52.5%) > Shengmai Injection+conventional treatment(30.1%) > conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) > Yiqi Fumai Injection+conventional treatment(61.5%) > Shenfu Injection+conventional treatment(51.2%) > Shengmai Injection+conventional treatment(48.1%) > Xinmailong Injection+conventional treatment(26.6%) > conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) > Xinmailong Injection+conventional treatment(68.1%) > Shenfu Injection+conventional treatment(63.1%) > Xuebijing Injection+conventional treatment(56.7%) > Shengmai Injection+conventional treatment(51.1%) > Shenqi Fuzheng Injection+conventional treatment(42.8%) > Huangqi Injection+conventional treatment(34.7%) > conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.


Asunto(s)
Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Medicina Tradicional China , Volumen Sistólico , Metaanálisis en Red , Proteína C-Reactiva , Función Ventricular Izquierda , Medicamentos Herbarios Chinos/efectos adversos , Infarto del Miocardio/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico
20.
Zhongguo Zhong Yao Za Zhi ; 48(22): 6225-6233, 2023 Nov.
Artículo en Chino | MEDLINE | ID: mdl-38114229

RESUMEN

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.


Asunto(s)
Aconitum , Medicamentos Herbarios Chinos , Panax , Humanos , Síndrome del Seno Enfermo/tratamiento farmacológico , Deficiencia Yang/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China , Prescripciones , Rizoma/química
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