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1.
IEEE Trans Med Imaging ; PP2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292579

RESUMEN

Recently, diffusion models have shown considerable promise for MRI reconstruction. However, extensive experimentation has revealed that these models are prone to generating artifacts due to the inherent randomness involved in generating images from pure noise. To achieve more controlled image reconstruction, we reexamine the concept of interpolatable physical priors in k-space data, focusing specifically on the interpolation of high-frequency (HF) k-space data from low-frequency (LF) k-space data. Broadly, this insight drives a shift in the generation paradigm from random noise to a more deterministic approach grounded in the existing LF k-space data. Building on this, we first establish a relationship between the interpolation of HF k-space data from LF k-space data and the reverse heat diffusion process, providing a fundamental framework for designing diffusion models that generate missing HF data. To further improve reconstruction accuracy, we integrate a traditional physics-informed k-space interpolation model into our diffusion framework as a data fidelity term. Experimental validation using publicly available datasets demonstrates that our approach significantly surpasses traditional k-space interpolation methods, deep learning-based k-space interpolation techniques, and conventional diffusion models, particularly in HF regions. Finally, we assess the generalization performance of our model across various out-of-distribution datasets. Our code are available at https://github.com/ZhuoxuCui/Heat-Diffusion.

2.
Heliyon ; 10(17): e37249, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39286188

RESUMEN

Objective: Glucocorticoid-induced osteoporosis (GIOP) represents a major complication arising from the long-term use of glucocorticoids, which are widely prescribed for various inflammatory and autoimmune conditions. Despite its prevalence, the current therapeutic options for GIOP are limited in terms of efficacy, safety profiles, and patient compliance. The Modified Danggui Buxue Decoction (DGBXD), a traditional Chinese herbal formulation, has shown promise in preliminary studies for its potential osteoprotective effects. The present study aimed to explore the mechanistic underpinnings of DGBXD's action on GIOP using network pharmacology and molecular docking approaches, bridging traditional medicine with modern pharmacological insights. Method: Network pharmacology is applied to screen drug-active compounds and potential core target proteins for disease treatment and to explore the drugs' therapeutic mechanisms. Result: Altogether, 78 DGBXD active compounds and 223 DGBXD-related, 146 component-disease common, and 2168 GIOP-associated target genes were obtained. The PPI network had 43 nodes and 462 edges, and a total of 10 core target genes, including TP53, JUN and MAPK3, were identified. The results of the GO enrichment analysis implied that DGBXD might participate in biological activities, including responses to oxidative stress and nutrient levels. The outcomes of the KEGG pathway enrichment analysis showed that DGBXD may treat GIOP through TNF, IL-17, and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways. Based on to the molecular docking results, biologically active compounds (beta-carotene, formononetin, luteolin, and isorhamnetin) exhibited good binding to AKT1 and ESR1. Conclusion: DGBXD may aid in GIOP treatment by modulating multiple therapeutic targets and signaling pathways.

3.
Nutrients ; 16(15)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39125342

RESUMEN

BACKGROUND: Dietary acid load (DAL) is closely related to several chronic diseases. However, the link between DAL and chronic kidney disease (CKD) remains scarce and without data from the Chinese populations whose diet is quite different from people in Western countries. METHODS: This study evaluated DAL by potential renal acid load (PRAL) and net endogenous acid production (NEAP). We clarified the relationship between DAL and CKD by logistic regression analysis based on data from the China Health and Nutrition Survey (CHNS). RESULTS: The final analysis included 7699 individuals, of whom 811 (11.44%) were CKD patients. Although there was no notable link between PRAL and CKD, higher NEAP levels were independently correlated with CKD. As NEAP values rise, so does CKD prevalence. This trend remains highly significant even after adjustments. In subgroup analyses, the relationship between NEAP and CKD was more consistent in the elderly and subjects with a waistline of less than 82 cm and those without diabetes and heart disease. RCS analysis further confirmed the clear linear relationship between the OR of CKD and NEAP score. CONCLUSIONS: This study highlighted that higher NEAP was positively correlated with the risk of CKD.


Asunto(s)
Dieta , Encuestas Nutricionales , Insuficiencia Renal Crónica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácidos/efectos adversos , China/epidemiología , Estudios Transversales , Dieta/efectos adversos , Pueblos del Este de Asia , Riñón/fisiopatología , Modelos Logísticos , Prevalencia , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo
5.
Chem Commun (Camb) ; 60(59): 7638-7641, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38963238

RESUMEN

The versatile reactivity of isothiocyanate intermediates enabled the diversity-oriented synthesis (DOS) of N-heterocycles in a DNA-compatible manner. We first reported a mild in situ conversion of DNA-conjugated amines to isothiocyanates. Subsequently, a set of diverse transformations was successfully developed to construct 2-thioxo-quinazolinones, 1,2,4-thiadiazoles, and 2-imino thiazolines. Finally, the feasibility of these approaches in constructing DELs was further demonstrated through enzymatic ligation and mock pool preparation. This study demonstrated the advantages of combining in situ conversion strategies with DOS, which effectively broadened the chemical and structural diversity of DELs.


Asunto(s)
ADN , Compuestos Heterocíclicos , Isotiocianatos , Isotiocianatos/química , ADN/química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/síntesis química , Estructura Molecular , Aminas/química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis química
6.
Materials (Basel) ; 17(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38998178

RESUMEN

Replacing the flammable liquid electrolytes with solid ones has been considered to be the most effective way to improve the safety of the lithium batteries. However, the solid electrolytes often suffer from low ionic conductivity and poor rate capability due to their relatively stable molecular/atomic architectures. In this study, we report a composite solid electrolyte, in which polyethylene oxide (PEO) is the matrix and Li6.4La3Zr1.45Ta0.5Mo0.05O12 (LLZTMO) and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) are the fillers. Ta/Mo co-doping can further promote the ion transport capacity in the electrolyte. The synthesized composite electrolytes exhibit high thermal stability (up to 413 °C) and good ionic conductivity (LLZTMO-PEO 2.00 × 10-4 S·cm-1, LLZTO-PEO 1.53 × 10-4 S·cm-1) at 35 °C. Compared with a pure PEO electrolyte, whose ionic conductivity is in the range of 10-7~10-6 S·cm-1, the ionic conductivity of composite solid electrolytes is greatly improved. The full cell assembled with LiFePO4 as the positive electrode exhibits excellent rate performance and good cycling stability, indicating that prepared solid electrolytes have great potential applications in lithium batteries.

7.
Clin Interv Aging ; 19: 1103-1116, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915432

RESUMEN

Background: Rivaroxaban, a non-vitamin K antagonist oral anticoagulant, has become widely used for the management of venous thromboembolism (VTE) in adult patients. However, few trials have explored the efficacy and safety of rivaroxaban in VTE patients over 80 years of age. This necessitates further real-world studies of rivaroxaban across elderly populations. Methods: We performed a retrospective single center study involving extremely aged VTE sufferers treated with rivaroxaban. The sample comprised 121 patients newly initiated on rivaroxaban diagnosed between January 2018 and January 2020. Patients were followed up for no less than 2 years. The effectiveness outcome was the disappearance of thromboembolism. The safety outcome was the incidence of major bleeding events. Comorbidities and complications were recorded throughout the entire study. Results: The efficacy outcome occurred in 114 of 121 patients (94.21%) and the safety outcome occurred in 12 of 121 patients (9.91%). Increased hemorrhages were observed in patients with infection (15.15% vs 7.80%), but no significant difference was observed due to limited sample size (P=0.3053). Patients with an age-adjusted Charlson comorbidity index score higher than 6 points exhibited higher bleeding rates (14.08% vs 4.00%; P=0.0676) and lower thrombus cure rates (88.73% vs 100%; P=0.0203). Key conclusions: Patients with infection should be more careful of bleeding events during rivaroxaban therapy. An age-adjusted Charlson comorbidity index score higher than 6, which predicted poor survival, indicated inferior safety and efficacy of rivaroxaban. Aim: To investigate the efficacy and safety of Rivaroxaban in an aged venous thromboembolism patient population under real-world conditions.


Asunto(s)
Inhibidores del Factor Xa , Hemorragia , Rivaroxabán , Tromboembolia Venosa , Humanos , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Tromboembolia Venosa/tratamiento farmacológico , Anciano de 80 o más Años , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Hemorragia/inducido químicamente , Estudios Transversales , Resultado del Tratamiento , Comorbilidad
8.
Acad Radiol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38876841

RESUMEN

RATIONALE AND OBJECTIVES: Accurate assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) plays a pivotal role in tailoring personalized treatment plans. This study aimed to investigate habitats-based spatial distributions to quantitatively measure tumor heterogeneity on multiparametric magnetic resonance imaging (MRI) scans and assess their predictive capability for LVI in patients with IBC. MATERIALS AND METHODS: In this retrospective cohort study, we consecutively enrolled 241 women diagnosed with IBC between July 2020 and July 2023 and who had 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, and dynamic contrast-enhanced MRI. Habitats-based spatial distributions were derived from the gross tumor volume (GTV) and gross tumor volume plus peritumoral volume (GPTV). GTV_habitats and GPTV_habitats were generated through sub-region segmentation, and their performances were compared. Subsequently, a combined nomogram was developed by integrating relevant spatial distributions with the identified MR morphological characteristics. Diagnostic performance was compared using receiver operating characteristic curve analysis and decision curve analysis. Statistical significance was set at p < 0.05. RESULTS: GPTV_habitats exhibited superior performance compared to GTV_habitats. Consequently, the GPTV_habitats, diffusion-weighted imaging rim signs, and peritumoral edema were integrated to formulate the combined nomogram. This combined nomogram outperformed individual MR morphological characteristics and the GPTV_habitats index, achieving area under the curve values of 0.903 (0.847 -0.959), 0.770 (0.689 -0.852), and 0.843 (0.776 -0.910) in the training set and 0.931 (0.863 -0.999), 0.747 (0.613 -0.880), and 0.849 (0.759 -0.938) in the validation set. CONCLUSION: The combined nomogram incorporating the GPTV_habitats and identified MR morphological characteristics can effectively predict LVI in patients with IBC.

9.
Discov Oncol ; 15(1): 215, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850433

RESUMEN

BACKGROUND: Multiple myeloma (MM) is a prevalent hematologic malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow and excessive monoclonal immunoglobulin production, leading to organ damage. Despite therapeutic advancements, recurrence and drug resistance remain significant challenges. OBJECTIVE: This study investigates the effects of dandelion flavone (DF) on MM cell proliferation, migration, and invasion, aiming to elucidate the mechanisms involved in MM metastasis and to explore the potential of traditional Chinese medicine in MM therapy. METHODS: DF's impact on myeloma cell viability was evaluated using the CCK-8 and colony formation assays. Cell mobility and invasiveness were assessed through wound healing and transwell assays, respectively. RT-PCR was employed to quantify mRNA levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Apoptotic rates and molecular markers were analyzed via flow cytometry and RT-PCR. The PI3K/AKT signaling pathway was studied using Western blot and ELISA, with IGF-1 and the PI3K inhibitor LY294002 used to validate the findings. RESULTS: DF demonstrated dose-dependent inhibitory effects on MM cell proliferation, migration, and invasion. It reduced mRNA levels of MMP-2 and MMP-9 while increasing those of TIMP-1 and TIMP-2. Furthermore, DF enhanced the expression of pro-apoptotic proteins and inhibited M2 macrophage polarization by targeting key molecules and enzymes. The anti-myeloma activity of DF was mediated through the inhibition of the PI3K/AKT pathway, as evidenced by diminished phosphorylation and differential effects in the presence of IGF-1 and LY294002. CONCLUSION: By modulating the PI3K/AKT pathway, DF effectively inhibits MM cell proliferation, migration, and invasion, and induces apoptosis, establishing a novel therapeutic strategy for MM based on traditional Chinese medicine.

10.
J Colloid Interface Sci ; 668: 448-458, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38691955

RESUMEN

People have been focusing on how to improve the specific capacity and cycling stability of lithium-sulfur batteries at room temperature, however, on some special occasions such as cold cities and aerospace fields, the operating temperature is low, which dramatically hinders the performance of batteries. Here, we report an iron carbide (Fe3C)/rGO composite as electrode host, the Fe3C nanoparticles in the composite have strong adsorption and high catalytic ability for polysulfide. The rGO makes the distribution of Fe3C nanoparticles more disperse, and this specific structure makes the deposition of Li2S more uniform. Therefore, it realizes the rapid transformation and high performance of lithium-sulfur batteries at both room and low temperatures. At room temperature, after 100 cycles at 1C current density, the reversible specific capacity of the battery can be stabilized at 889 ± 7.1 mAh/g. Even at -40 °C, in the first cycle battery still emits 542.9 ± 3.7 mAh/g specific capacity. This broadens the operating temperature for lithium-sulfur batteries and also provides a new idea for the selection of host materials for sulfur in low-temperature lithium-sulfur batteries.

11.
BMJ Open ; 14(4): e079354, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38569706

RESUMEN

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.


Asunto(s)
Terapia por Acupuntura , Diabetes Mellitus , Neuropatías Diabéticas , Electroacupuntura , Humanos , Neuropatías Diabéticas/terapia , Dolor , China , Beijing , Resultado del Tratamiento , Electroacupuntura/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
12.
J Orthop Surg Res ; 19(1): 194, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38509573

RESUMEN

PURPOSE: To evaluate the learning curve and complications in unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF) using the Cumulative Sum (CUSUM) analysis and Risk-adjusted Cumulative Sum (RA-CUSUM) analysis. METHODS: This study retrospectively analyzed 184 consecutive patients who received ULIF in our hospital, including 104 males and 80 females. CUSUM analysis and RA-CUSUM analysis were used to evaluate the learning curve of ULIF based on the operation time and surgical failure rate, respectively. All postoperative complications were defined as surgical failure. Variables of different phases were compared based on the learning curve. RESULTS: The CUSUM analysis showed the cutoff point for ULIF was 29 cases, and the RA-CUSUM analysis showed the cutoff point for ULIF was 41 cases. Operating time and hospital stay were significantly decreased as the learning curve progressed (P < 0.05). Visual analogue score (VAS) and Oswestry disability index (ODI) at the last follow-up were significantly lower than preoperatively. At the last follow-up, a total of 171 patients reached intervertebral fusion, with a fusion rate of 92.9% (171/184). A total of eleven complications were observed, and RA-CUSUM analysis showed that the incidence of complications in the early phase was 17.07% and in the late phase was 2.6%, with a significant difference (P < 0.05). CONCLUSION: ULIF is an effective minimally invasive lumbar fusion surgical technique. But a learning curve of at least 29 cases will be required to master ULIF, while 41 cases will be required to achieve a stable surgical success rate.


Asunto(s)
Curva de Aprendizaje , Fusión Vertebral , Masculino , Femenino , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Endoscopía/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía
13.
J Clin Immunol ; 44(3): 80, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38462559

RESUMEN

OBJECTIVE: We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2. METHODS: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted. RESULTS: In this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts. CONCLUSION: The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population.


Asunto(s)
COVID-19 , Interferón Tipo I , Anciano , Humanos , Masculino , Autoanticuerpos , COVID-19/epidemiología , SARS-CoV-2 , Prevalencia , China/epidemiología , Anticuerpos Neutralizantes , Antivirales
14.
ACS Appl Mater Interfaces ; 16(6): 7576-7592, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38316581

RESUMEN

The low targeted drug delivery efficiency, including poor tumor accumulation and penetration and uncontrolled drug release, leads to the failure of cancer therapy. Herein, a multifunctional supramolecular nanoplatform loading triptolide (TPL/PBAETK@GA NPs) was fabricated via the host-guest interaction between glycyrrhetinic-acid-modified poly(ethylene glycol)-adamantanecarboxylic acid moiety and reactive oxygen species (ROS)/pH cascade-responsive copolymer poly(ß-amino esters)-thioketal (TK)-ß-cyclodextrin. TPL/PBAETK@GA NPs could accumulate in hepatocellular carcinoma (HCC) tissue effectively, mediated by nanoscale advantage and GA' recognition to specific receptors. The elevated concentration of ROS in tumor microenvironment (TME) quickly breaks the TK linkages, causing the detachment of shell (cyclodextrin) CD layer. Then, the accompanying negative-to-positive charge-reversal of NPs was realized via the PBAE moiety protonation under the slightly acidic TME, significantly enhancing the NPs' cellular internalization. Remarkably, the pH-responsive endo/lysosome escape of PBAE core triggered intracellular TPL burst release, promoting the cancer cell apoptosis, autophagy, and intracellular ROS generation, leading to the self-amplification of ROS in TME. Afterward, the ROS positive-feedback loop was generated to further promote size-shrinkage and charge-reversal of NPs. Both in vitro and in vivo tests verified that TPL/PBAETK@GA NPs produced a satisfactory anti-HCC therapy outcome. Collectively, this study offers a potential appealing paradigm to enhance TPL-based HCC therapy outcomes via multifunctionalized supramolecular nanodrugs.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Especies Reactivas de Oxígeno , Microambiente Tumoral , Neoplasias Hepáticas/tratamiento farmacológico , Concentración de Iones de Hidrógeno , Regeneración , Nanopartículas/química , Línea Celular Tumoral
15.
Front Endocrinol (Lausanne) ; 15: 1328404, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38370360

RESUMEN

Background: The burden of metabolic syndrome (MetS) continues to rise globally and is associated with complications of multiple organ systems. We aimed to identify the association between changes in MetS status and accelerated renal function progression through a regional epidemiological survey in China, thus discovering influence factors with treatable potential. Methods: This study was a population-based survey conducted in 2008 and 2014, assessing a representative sample of 5,225 individuals from rural areas of China. They were divided into four subgroups according to their MetS status in 2008 and 2014 (Never, Previously abnormal, New-onset, and Consistent). Multivariate logistic regression and stratification analysis evaluated the relationship between clinical factors and renal function decline under different MetS statuses. Smooth curve fitting further addressed the role of serum uric acid, illustrating the vital turning point of uric acid levels in the background of renal function deterioration. Results: Of all groups of MetS states, the new-onset MetS showed the most significant eGFR decline, with a 6.66 ± 8.21 mL/min/1.73 m2 decrease over 6 years. The population with newly-onset MetS showed a considerable risk increase in delta eGFR with a beta coefficient of 1.66 (95%CI=1.09-2.23) after necessary correction. In searching for the drivers, the strength of the association was significantly reduced after additional adjustment for uric acid levels (ß=0.91, 95%CI=0.35-1.45). Regarding the turning point, uric acid levels exceeding 426 µmol/L were more significantly associated with the stepped-up deterioration of kidney function for those with new-onset MetS. Conclusion: Metabolic syndrome demonstrated a solid correlation with the progression of renal function, particularly in those with newly-onset MetS status. In addition to the diagnostic components of MetS, hyperuricemia could be used as a marker to identify the high risk of accelerating eGFR decline early. Furthermore, we suggested a potential renal benefit for the newly-onset MetS population when maintaining their serum uric acid level below the criteria for asymptomatic hyperuricemia.


Asunto(s)
Hiperuricemia , Síndrome Metabólico , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Estudios de Cohortes , Ácido Úrico , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Riñón
17.
Org Lett ; 26(5): 1094-1099, 2024 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-38277138

RESUMEN

Utilizing already existing DNA-encoded libraries (DELs) for the generation of a distinct DEL represents an expedited strategy for expanding the chemical space. Herein, we leverage the unique photoreactivity of tetrazoles to synthesize diacylhydrazines on DNA. Widely available carboxylic acids serving as building blocks were employed under the mild photomediated reaction conditions, affording diverse DNA-conjugated diacylhydrazines. This methodology also demonstrates robustness in DEL-compatible synthesis and facilitates the preparation of oligonucleotide-based chemical probes.


Asunto(s)
ADN , Biblioteca de Genes , Ácidos Carboxílicos , Bibliotecas de Moléculas Pequeñas/síntesis química
18.
PLoS One ; 19(1): e0290925, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38166086

RESUMEN

BACKGROUND: Articular cartilage and cartilage matrix degradation are key pathological changes occurring in the early stage of knee osteoarthritis (KOA). However, currently, there are limited strategies for early prevention and treatment of KOA. Duhuo Jisheng Decoction (DHJSD) is a formula quoted in Bei Ji Qian jin Yao Fang, which was compiled by Sun Simiao in the Tang Dynasty of China. As a complementary therapy, it is widely used to treat early-stage KOA in China; however, its mechanism has not been completely elucidated. OBJECTIVE: This study investigated the potential role of DHJSD in preventing cartilage degradation and the underlying mechanism. METHODS: A rat model of KOA model was established via the Hulth method. Subsequently, 25 rats were randomized into sham (saline), model control (saline), high-DHJSD (1.9g/mL of DHJSD), medium-DHJSD (1.2g/mL of DHJSD), and low-DHJSD groups (0.6g/mL of DHJSD). After 4 weeks of treatment, all rats were sacrificed and the severity of the cartilage degeneration was evaluated by a series of histological methods. The autophagosome was observed using transmission electron microscopy, and the related functional proteins were detected by the western blotting and real-time polymerase chain reaction. Next, the mechanism by which DHJSD improves knee cartilage degeneration was further clarified the in vitro by gene silencing technology combined with a series of functional experiments. The proteins levels of PTEN, Akt, p-Akt, mTOR, and p-mTOR, as well as the marker proteins of autophagy and apoptosis were determined. Zinc levels in chondrocytes were determined using inductively coupled plasma mass spectrometry. RESULTS: Histopathological staining revealed that DHJSD had a protective effect on the cartilage. DHJSD increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in chondrocytes. Moreover, it reduced the phosphorylation levels of Akt and mTOR and the levels of zinc, MMP-13, Bax, and Bcl-2. Following PTEN silencing, this DHJSD-mediated reduction in Akt and mTOR phosphorylation and Bax, Bcl-2, and zinc levels were further decreased; in addition, DHJSD-mediated increase in LC3 and Beclin-1 levels was decreased. CONCLUSION: DHJSD inhibits the Akt/mTOR signaling pathway by targeting PTEN to promote autophagy in chondrocytes, which may help reduce MMP-13 production by regulating zinc levels in chondrocytes.


Asunto(s)
Cartílago Articular , Osteoartritis de la Rodilla , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/metabolismo , Beclina-1/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Condrocitos/metabolismo , Osteoartritis de la Rodilla/patología , Cartílago Articular/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Autofagia , Homeostasis
19.
BMC Public Health ; 24(1): 147, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200420

RESUMEN

BACKGROUND: Low back pain is the leading cause of productivity loss, imposes a significant economic burden on the patients and society. Oxidative stress is considered a critical factor in the complex pathophysiological process and pathogenic mechanism of low back pain. Adjustment dietary pattern can effectively increase antioxidant biomarkers levels within the body to reduce oxidative stress. The composite dietary antioxidant index (CDAI) serves a reliable scoring system for quantifying the potential dietary antioxidant capacity of daily diets. OBJECTIVE: We aim to investigate the potential association between CDAI and low back pain, in order to enhance the management of low back pain through dietary guidance. METHODS: This study included 17,682 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2000, 2001-2002, 2003-2004 and 2009-2010. The weighted logistic regression model was used to investigate the association between CDAI and low back pain, while restricted cubic spline (RCS) was employed to examine non-linear trend and cutoffs. RESULTS: After adjusting for all confounders, the results showed that there was no significant association between CDAI and low back pain. However, individuals in the highest quartile of CDAI exhibited an 11.7% less likelihood of experiencing a low back pain than those in the lowest quartile (OR = 0.883; 95% CI [0.787,0.991], P = 0.034), and the trend test was also significant (P for trend < 0.001). RCS indicated a linear relationship between CDAI and low back pain (P for non-linear = 0.876). Gender subgroup analysis showed that this negative association was significant in the female population (OR = 0.983; 95% CI [0.968, 0.998], P = 0.027), and females in the highest quartile of CDAI were 19.7% less likely to suffer low back pain than those in the lowest quartile (OR = 0.803; 95% CI [0.682,0.945], P = 0.008). Additionally, the changes in zinc (OR = 1.009; 95% CI [1.002, 1.016], P = 0.015) and selenium (OR = 0.379; 95% CI [0.164, 0.875], P = 0.023) per milligram were independently associated with low back pain. CONCLUSION: The fully adjusted model showed no significant association between CDAI and low back pain, but it was significant in quartiles. Meanwhile, subgroup analysis by gender revealed a negative association between CDAI and low back pain in the female population. Additionally, the findings of this study also suggested that the antioxidant diets should be studied in a dietary pattern context.


Asunto(s)
Antioxidantes , Dolor de la Región Lumbar , Adulto , Femenino , Humanos , Estudios Transversales , Encuestas Nutricionales , Dolor de la Región Lumbar/epidemiología , Dieta
20.
Heliyon ; 10(1): e24229, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38234920

RESUMEN

Background: Plantar fasciitis (PF) is the most common cause of chronic heel pain among adults. Extracorporeal shock wave therapy (ESWT) is the recommended in the current guidelines, and the small needle-knife yields acceptable clinical effects for musculoskeletal pain. Objective: To systematically compare the efficacy of the small needle-knife versus ESWT for the treatment of PF. Methods: The present review was registered in the International Prospective Register of Systematic Reviews (i.e., "PROSPERO", CRD42023448813). Two of the authors searched electronic databases for randomized controlled trials (RCTs) comparing the small needle-knife versus ESWT for the treatment of PF, and collected outcomes including curative effect, pain intensity, and function. Risk of bias was assessed using the Cochrane Handbook Risk of Bias tool and the quality of the RCTs was evaluated according to the Jadad Scale. The same authors independently performed data extraction from the included studies, which were imported into Review Manager version 5.4.1(Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2020) for meta-analysis. Results: The initial literature search retrieved 886 studies, of which 6 were eventually included in this study. Meta-analysis revealed no significant difference in curative effect (OR = 1.87; 95 % CI [0.80, 4.37], p = .15) nor short-term pain improvement (MD = 2.20; 95 % CI [-2.77, 7.16], p = .39) between the small needle-knife and ESWT. However, the small needle-knife may be more effective than ESWT for pain improvement in mid-term (MD = 9.11; 95 % CI [5.08, 13.15], p< .00001) and long-term follow-ups (MD = 10.71; 95 % CI [2.18, 19.25], p< .00001). Subgroup analysis revealed that the small needle-knife combined with a corticosteroid injection yielded a statistically significant difference in reduction of pain intensity at all follow-ups (MD = 4.84; 95 % CI [1.33, 8.36], p = .007; MD = 10.99; 95 % CI [8.30, 13.69], p< .00001; MD = 17.87; 95 % CI [15.26, 20.48], p< .00001). Meta-analysis revealed no statistical differences in short-term (MD = 1.34; 95 % CI [-3.19, 5.86], p = .56) and mid-term (MD = 2.75; 95 % CI [-1.21, 6.72], p = . 17) functional improvement between the needle-knife and ESWT groups. In a subgroup analysis of moderate-quality studies, the small needle-knife demonstrated a favorable effect on mid-term functional improvement (MD = 1.58; 95 % CI [0.52, 2.65], p = .004), with low heterogeneity (χ2 = 0.77, p = .038, I2 = 0 %). Conclusion: Pain reduction and functional improvement are essential for the treatment of PF. Therefore, treatment using the small needle-knife may be superior to ESWT. Results of this systematic review and meta-analysis may provide alternative treatment options for patients with PF as well as more reliable, evidence-based recommendations supporting use of the small needle-knife.

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