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1.
Biochem Genet ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839646

RESUMO

Thyroid cancer (THCA) is one of the most common malignancies of the endocrine system. Exosomes have significant value in performing molecular treatments, evaluating the diagnosis and determining tumor prognosis. Thus, the identification of exosome-related genes could be valuable for the diagnosis and potential treatment of THCA. In this study, we examined a set of exosome-related differentially expressed genes (DEGs) (BIRC5, POSTN, TGFBR1, DUSP1, BID, and FGFR2) by taking the intersection between the DEGs of the TCGA-THCA and GeneCards datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the exosome-related DEGs indicated that these genes were involved in certain biological functions and pathways. Protein‒protein interaction (PPI), mRNA‒miRNA, and mRNA-TF interaction networks were constructed using the 6 exosome-related DEGs as hub genes. Furthermore, we analyzed the correlation between the 6 exosome-related DEGs and immune infiltration. The Genomics of Drug Sensitivity in Cancer (GDSC), the Cancer Cell Line Encyclopedia (CCLE), and the CellMiner database were used to elucidate the relationship between the exosome-related DEGs and drug sensitivity. In addition, we verified that both POSTN and BID were upregulated in papillary thyroid cancer (PTC) patients and that their expression was correlated with cancer progression. The POSTN and BID protein expression levels were further examined in THCA cell lines. These findings provide insights into exosome-related clinical trials and drug development.

2.
Molecules ; 29(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38731569

RESUMO

Skin wounds, leading to infections and death, have a huge negative impact on healthcare systems around the world. Antibacterial therapy and the suppression of excessive inflammation help wounds heal. To date, the application of wound dressings, biologics and biomaterials (hydrogels, epidermal growth factor, stem cells, etc.) is limited due to their difficult and expensive preparation process. Cinnamomum burmannii (Nees & T. Nees) Blume is an herb in traditional medicine, and its essential oil is rich in D-borneol, with antibacterial and anti-inflammatory effects. However, it is not clear whether Cinnamomum burmannii essential oil has the function of promoting wound healing. This study analyzed 32 main components and their relative contents of essential oil using GC-MS. Then, network pharmacology was used to predict the possible targets of this essential oil in wound healing. We first proved this essential oil's effects in vitro and in vivo. Cinnamomum burmannii essential oil could not only promote the proliferation and migration of skin stromal cells, but also promote M2-type polarization of macrophages while inhibiting the expression of pro-inflammatory cytokines. This study explored the possible mechanism by which Cinnamomum burmannii essential oil promotes wound healing, providing a cheap and effective strategy for promoting wound healing.


Assuntos
Cinnamomum , Óleos Voláteis , Cicatrização , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Cicatrização/efeitos dos fármacos , Cinnamomum/química , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Movimento Celular/efeitos dos fármacos , Pele/efeitos dos fármacos , Humanos
3.
Sci Rep ; 14(1): 10959, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745034

RESUMO

Molecular hydrogen is an emerging broad-spectrum antioxidant molecule that can be used to treat myocardial infarction (MI). However, with hydrogen inhalation, the concentration that can be reached within target organs is low and the duration of action is short, which makes it difficult to achieve high dose targeted delivery of hydrogen to the heart, seriously limiting the therapeutic potential of hydrogen for MI. As a result of reactions with the internal environment of the body, subcutaneous implantation of magnesium slices leads to continuous endogenous hydrogen production, leading to a higher hydrogen concentration and a longer duration of action in target organs. In this study, we propose magnesium implant-based hydrogen therapy for MI. After subcutaneous implantation of magnesium slices in the dorsum of rats, we measured hydrogen production and efficiency, and evaluated the safety of this approach. Compared with hydrogen inhalation, it significantly improved cardiac function in rats with MI. Magnesium implantation also cleared free radicals that were released as a result of mitochondrial dysfunction, as well as suppressing cardiomyocyte apoptosis.


Assuntos
Hidrogênio , Magnésio , Infarto do Miocárdio , Animais , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Magnésio/metabolismo , Ratos , Masculino , Ratos Sprague-Dawley , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Modelos Animais de Doenças
4.
J Chem Phys ; 160(19)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38752536

RESUMO

The proton transport in one-dimensional (1D) confined water chains has been extensively studied as a model for ion channels in cell membrane and fuel cell. However, the mechanistic understanding of the proton transfer (PT) process in 1D water chains remains incomplete. In this study, we demonstrate that the two limiting structures of the hydrated excess proton, H5O2+ (Zundel) and H3O+ (linear H7O3+), undergo a change in dominance as the water chain grows, causing two co-existing and opposing PT mechanisms. Specifically, H5O2+ is stable in the middle of the chain, whereas H3O+ serves as a transition state (TS). Except for this region, H3O+ is stabilized while H5O2+ serves as a TS. The interaction analysis shows that the electrostatic interaction plays a crucial role in the difference in PT mechanisms. Our work fills a knowledge gap between the various PT mechanisms reported in bulk water and long 1D water chains, contributing to a deeper understanding of biological ion channels at the atomic level.

5.
J Chem Phys ; 160(16)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38647312

RESUMO

Understanding and further regulating the degradation of mandrel materials is a key aspect of target fabrication in inertial confinement fusion (ICF). Here, a quasi-one-dimensional confinement model is developed using a series of single-walled carbon nanotubes with varying diameters (Dm), and the degradation of poly-α-methylstyrene (PAMS) as a typical mandrel material is investigated under such confined conditions by using the combined method of quantum mechanics and molecular mechanics. In comparison to the isolated system, the calculations show that confinement can decrease or increase the energy barriers of PAMS degradation, which directly depends on Dm. Following which a clear exponential relationship between the degradation rate of PAMS and its own density is derived, indicating that the density of PAMS can be used to regulate mandrel degradation. This work highlights the important effects of confinement on degradation and provides a valuable reference for further development of polymer degradation technologies in ICF target fabrication and other fields.

6.
Colloids Surf B Biointerfaces ; 238: 113904, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603845

RESUMO

Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.


Assuntos
Apoptose , Colestase , Grafite , Hepatócitos , Nanocompostos , Ácido Ursodesoxicólico , Grafite/química , Grafite/farmacologia , Ácido Ursodesoxicólico/farmacologia , Ácido Ursodesoxicólico/química , Animais , Apoptose/efeitos dos fármacos , Nanocompostos/química , Camundongos , Colestase/tratamento farmacológico , Colestase/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Polietilenoimina/química , Polietilenoimina/farmacologia , Humanos
7.
Vascular ; : 17085381241249288, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38670962

RESUMO

BACKGROUND: Endovenous interventions and minimally invasive procedures are effective in the management of varicose veins. However, they can cause postoperative discomfort. OBJECTIVE: To evaluate the clinical efficacy of sodium aescinate (SA) in improving edema, pain, vein-specific symptoms, and quality of life in patients following endovenous laser ablation (EVLA) for varicose veins. METHODS: In this single-center randomized controlled trial (RCT), patients were allocated into two groups: in Group A, 60 mg SA was administered twice daily for 20 days, and in Group B (control), no venoactive drug was prescribed. The Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system for chronic venous disorders was used to assess the varicose veins. The circumferences of the calf and ankle were recorded for evaluating edema. The 10-point Visual Analog Scale (VAS), Venous Clinical Severity Score (VCSS), and Aberdeen Varicose Veins Questionnaire (AVVQ) were used to measure the pain intensity, overall varicose vein severity, and patient's quality of life, respectively. RESULTS: The study included 87 patients (mean age, 59.9 ± 10.7 years; 54 men) with CEAP class C2-C5 varicose veins who underwent EVLA and phlebectomy or foam sclerotherapy. The calf circumference recovered quicker in Group A than in Group B by days 10, 21, and 30 (difference from baseline was 1.04 ± 0.35 vs 2.39 ± 1.15 [p < .001], 0.48 ± 0.42 vs1.73 ± 1.00 [p < .001], and 0.18 ± 0.64 vs 0.82 ± 0.96 [p < .001], respectively). The ankle circumference recovered quicker in Group A than in Group B by days 10 and 21 (the difference from baseline was 1.37 ± 0.52 vs 2.36 ± 0.93 [p < .001] and 0.58 ± 0.60 vs 1.14 ± 0.88 [p = .002], respectively). Pain relief was achieved quicker in Group A than in Group B (0.257 ± 1.097 [p = .0863] vs 0.506 ± 1.250 [p = .0168] by day 21). There were no significant differences in the VCSS and AVVQ scores between both groups. There were no drug-related adverse effects. CONCLUSIONS: SA, in combination with compression therapy, can relieve edema and alleviate pain in patients following EVLA for varicose veins.

8.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474182

RESUMO

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.


Assuntos
COVID-19 , Flavonas , Humanos , SARS-CoV-2 , Scutellaria baicalensis , Glicoproteína da Espícula de Coronavírus , Angiotensinas , Ligação Proteica
9.
Dalton Trans ; 53(11): 5284-5290, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38410928

RESUMO

Herein we report electrochemiluminescence (ECL) generation from three new iridium(III)/ruthenium(II) (Ir(III)/Ru(II)) complexes with naphthyl (nap) tags in solutions and host-guest thin films. In comparison with its parent structure, the addition of a nap tag to [4-(2-naphthalenyl)-1,10-phenanthroline]bis(2,2'-bipyridine)ruthenium(II) results in a 6.1-fold enhancement in the ECL efficiency. Moreover, the nap tag enables the non-covalent immobilization of Ir(III)/Ru(II) complexes via host-guest interactions. Therefore, a molecular thin film was constructed by hydrophobic effects between the cavity of ß-cyclodextrin and the nap tags, which emits stable and strong ECL emission in the presence of tri-n-propylamine (TPrA). These results give a mechanistic insight into ECL generation from (Ir(III)/Ru(II)) complexes with host-guest recognition tags and may help in the development of host-guest thin film-based ECL sensors.

10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 6-12, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322525

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Due to the insidious onset and rapid progression and a lack of effective treatments, the prognosis of patients with HCC is extremely poor, with the average 5-year survival rate being less than 10%. The tumor microenvironment (TME), the internal environment in which HCC develops, can regulate the oncogenesis, development, invasion, and metastasis of HCC. During the process of cancer progression, HCC cells can regulate the biological behaviors of tumor cells, cancer-associated fibroblasts, cancer-associated immune cells, and other cells in the TME by releasing exosomes containing specific signals, thereby promoting cancer progression. However, the exact molecular mechanisms and the roles of exosomes in the specific cellular regulation of these processes are not fully understood. Herein, we summarized the TME components of HCC, the sources and the biological traits of exosomes in the TME, and the impact of mechanical factors on exosomes. In addition, special attention was given to the discussion of the effects of HCC-exosomes on different types of cells in the microenvironment. There are still many difficulties to be overcome before exosomes can be applied as carriers in clinical cancer treatment. First of all, the homogeneity of exosomes is difficult to ensure. Secondly, exosomes are mainly administered through subcutaneous injection. Although this method is simple and easy to implement, the absorption efficiency is not ideal. Thirdly, exosome extraction methods are limited in number and inefficient, making it difficult to prepare exosomes in large quantities. It is important to ensure that exosomes are used in sufficient quantities to trigger an effective tumor immune response, especially for exosome-mediated tumor immunotherapy. With the improvement in identification, isolation, and purification technology, exosomes are expected to be successfully used in the clinical diagnosis of early-stage HCC and the clinical treatment of liver cancer.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Microambiente Tumoral , Comunicação Celular
11.
Ann Hum Biol ; 51(1): 1-6, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38251837

RESUMO

BACKGROUND: At present, there are no available genetic data on the AGCU EX22 Kit from the Wuhu Han population. AIM: This study investigates the applicability of the AGCU EX22 kit, designed for the Chinese population for forensic analysis and population genetics of the Wuhu Han population. SUBJECTS AND METHODS: Bloodstains from 1565 unrelated healthy individuals in Wuhu city, Anhui Province, were collected for analysis. The AGCU EX22 kit was used for amplification, and capillary electrophoresis was used to separate the amplification products. Allele frequencies and forensic parameters were determined. The Wuhu Han population was compared to 10 reference populations through genetic distance, a phylogenetic neighbor-joining tree and principal component analysis. RESULTS: In total, 281 alleles and 1187 genotypes were observed. No significant deviations from Hardy-Weinberg equilibrium at any locus were found after Bonferroni's correction. The 21 autosomal short tandem repeat (STR) genetic markers exhibited high informativeness and polymorphism. The cumulative power of discrimination and power of exclusion were 0.999999999999999999999999913380 and 0.999999996752339, respectively. Population comparisons revealed a genetic affinity between Wuhu Han and southern Han populations, except for the Guangdong Han population, which aligned with the traditional geographical division in China. CONCLUSION: The AGCU EX22 Kit, containing 21 STR loci, is suitable for forensic application and population genetics studies in the Wuhu Han population.


Assuntos
População do Leste Asiático , Repetições de Microssatélites , Humanos , Alelos , China , População do Leste Asiático/genética , Genética Forense , Frequência do Gene , Genética Populacional , Voluntários Saudáveis , Filogenia , Sangue
12.
Environ Sci Pollut Res Int ; 31(5): 7959-7976, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38175505

RESUMO

Sulfur-containing gases are main sources of landfill odors, which has become a big issue for pollution to environment and human health. Biocover is promising for treating landfill odors, with advantages of durability and environmental friendliness. In this study, charcoal sludge compost was utilized as the main effective component of a novel alternative landfill cover and the in situ control of sulfur-containing odors from municipal solid waste landfilling process was simulated under nine different operating conditions. Results showed that five sulfur-containing odors (hydrogen sulfide, H2S; methyl mercaptan, CH3SH; dimethyl sulfide, CH3SCH3; ethylmercaptan, CH3CH2SH; carbon disulfide, CS2) were monitored and removed by the biocover, with the highest removal efficiencies of 77.18% for H2S, 87.36% for CH3SH, and 92.19% for CH3SCH3 in reactor 8#, and 95.94% for CH3CH2SH and 94.44% for CS2 in reactor 3#. The orthogonal experiment showed that the factors influencing the removal efficiencies of sulfur-containing odors were ranked from high to low as follows: temperature > weight ratio > humidity content. The combination of parameters of 20% weight ratio, 25°C temperature, and 30% water content was more recommended based on the consideration of the removal efficiencies and economic benefits. The mechanisms of sulfur conversion inside biocover were analyzed. Most organic sulfur was firstly degraded to reduced sulfides or element sulfur, and then oxidized to sulfate which could be stable in the layer as the final state. In this process, sulfur-oxidizing bacteria play a great role, and the distribution of them in reactor 1#, 5#, and 8# was specifically monitored. Bradyrhizobiaceae and Rhodospirillaceae were the dominant species which can utilize sulfide as substance to produce sulfate and element sulfur, respectively. Based on the results of OUTs, the biodiversity of these sulfur-oxidizing bacteria, these microorganisms, was demonstrated to be affected by the different parameters. These results indicate that the novel alternative landfill cover modified with bamboo charcoal compost is effective in removing sulfur odors from landfills. Meanwhile, the findings have direct implications for addressing landfill odor problems through parameter adjustment.


Assuntos
Sulfeto de Hidrogênio , Odorantes , Humanos , Carvão Vegetal/metabolismo , Sulfeto de Hidrogênio/metabolismo , Enxofre/metabolismo , Instalações de Eliminação de Resíduos , Óxidos de Enxofre , Bactérias/metabolismo , Sulfatos/metabolismo
13.
Adv Healthc Mater ; 13(7): e2302443, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37962054

RESUMO

Although immunosuppressive drugs for targeting T cells are the standard of care in acute transplantation rejection, the role of innate immune cells should not be ignored. Here, single-cell RNA sequencing (scRNA-seq) and flow cytometry are performed to reveal the dynamic changes of innate immune cells within the acute rejection time and find a significantly-increased presence of Ly6G- Ly6C+ inflammatory macrophages and decreased presence of neutrophils among all types of immune cells. Next, to further explore potential targets regulating Ly6G- Ly6C+ inflammatory macrophages, scRNA-seq is used to analyze the reciprocal signaling of both neutrophils and macrophages, along with the surface genes of macrophages. It is found that activating colony-stimulating factor 1/ colony-stimulating factor 1 receptor (CSF1/CSF1R) andcluster of differentiation 47/signal regulatory protein α (CD47/SIRPα) signaling may serve as a strategy to relieve Ly6G- Ly6C+ inflammatory macrophage-mediated early graft rejection. To investigate this hypothesis, CSF1/CD47 dual-targeting nanovesicles (NVs) derived from IFN-γ-stimulated induced pluripotent stem cell-derived mesenchymal stem cells ( iPSC-MSCs )are designed and constructed. It is confirmed that CSF1/CD47 NVs synergistically induce the differentiation of Ly6G- Ly6C- M2 inhibitory macrophages by the CSF1/CSF1R pathway, and inhibit the phagocytosis of inflammatory macrophages and inflammatory response by the CD47/SIRPα pathway, ultimately relieving immune rejection. This study highlights the power of dual-targeting CSF1/CD47 NVs as an immunosuppressant against early innate immune responses with the potential for broad clinical applications.


Assuntos
Transplante de Coração , Fator Estimulador de Colônias de Macrófagos , Fator Estimulador de Colônias de Macrófagos/genética , Antígeno CD47 , Fagocitose , Imunidade Inata , Perfilação da Expressão Gênica
14.
Arch. esp. urol. (Ed. impr.) ; 76(10): 802-809, diciembre 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-229541

RESUMO

Background: This study aimed to explore technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) renal dynamicimaging to evaluate duplex kidney function in adult patients.Subjects and Methods: We retrospectively analyzed the clinical data of 25 patients with duplex kidneys who underwent 99mTc-DTPA renal dynamic imaging between June 2011 and March 2023 at our hospital. Patients in the duplex kidney group (n = 25)were divided into renogram normal (n = 9) and abnormal (n = 16) groups according to the imaging data. Additionally, normalpatients were selected as the control group (n = 25). After imaging, the region of interest of the kidneys was delineated, andrenography was performed. Renography can provide renal function parameters, including glomerular filtration rate (GFR),Tmax, T1/2, renal clearance, and the GFR ratio of the duplex renal segment (upper renal moiety).Results: Compared with the control group, the serum creatinine level in the duplex kidney group was higher (p = 0.025), GFRwas lower (p = 0.001), and patients with impaired renal function were mainly in the abnormal renography group (p = 0.001). Inthe duplex kidney group, the GFR (p = 0.026) and renal clearance (p = 0.006) of the affected kidneys were lower than those of thecontralateral kidneys, and Tmax (p = 0.025) was higher than that of the contralateral kidneys. There were no differences in renalfunction indicators of duplex renal segments with different GFR ratios. However, when the GFR ratio exceeded 50%, the renalfunction tended to decline.Conclusions: 99mTc-DTPA renal dynamic imaging was found useful to evaluate the total renal function, split renal function,and upper urinary tract patency in patients with duplex kidneys. Patients with abnormal renography results had worse renalfunction, and those with poor renal clearance in the affected renal moiety required surgical treatment. (AU)


Assuntos
Humanos , Rim/diagnóstico por imagem , Ácido Pentético , Pentetato de Tecnécio Tc 99m , Sistema Urinário , Tecnécio , Estudos Retrospectivos
15.
J Phys Chem Lett ; 14(47): 10592-10598, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37976462

RESUMO

Quantum mechanical tunneling (QMT) can play an important role in light element-related chemical reactions; however, its influence on racemization is not fully understood. Herein, we demonstrate that the role of QMT is decisive for rapid racemization of the well-known thalidomide molecule in aqueous environments, increasing the reaction rate constants of the most likely racemization pathways by 87-149 times at approximately body temperature and achieving good agreement between theoretical calculations and experimental observations. In addition, the kinetic isotope effect values fit well with those of previous experiments. These results are attributed to enhanced tunneling probability due to the alteration of potential barriers for proton transfer reactions via water bridges. This work highlights the significance of the QMT effect in racemization and its potential impact on drug safety, providing a fundamental perspective for understanding chirality-related issues in biological systems.

16.
Bone Res ; 11(1): 60, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37940665

RESUMO

Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content. However, the role of MVs in the progression of osteoporosis is poorly understood. Here, we report that annexin A5, an important component of the matrix vesicle membrane, plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis. We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice. We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type I to achieve MV adhesion and the subsequent activation of cellular autophagy. Finally, we proved its protective role in resisting bone loss by applying it to osteoporotic mice. Taken together, these data revealed the importance of annexin A5, originating from adherent MVs of osteoblasts, in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Calcificação Vascular , Animais , Camundongos , Anexina A5/metabolismo , Calcificação Fisiológica/fisiologia , Matriz Óssea/metabolismo
17.
J Phys Chem Lett ; 14(41): 9351-9356, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37820388

RESUMO

Roaming bypasses the conventional transition state and is a significant reaction pathway due to the unusual energy distributions of its products; however, its reaction pathway under external environmental interactions remains unclear. Herein, we report for the first time the roaming process of nitrobenzene, which is influenced by the hydrogen bonds (H-bonds) between nitro- and phenyl radicals and water molecules in the gas phase. Notably, despite the fact that the single water structure produces a higher but narrower barrier, whereas the double water structure leads to a lower but wider barrier, the roaming reaction still occurs. The underlying mechanism responsible for these influences of H-bonds is ascribed to the dramatically changed polarization and correlation interactions between the roaming radicals. The reaction rates and thermal perturbation probabilities are also remarkably influenced due to the presence of the H-bonds, by approximately 2 orders of magnitude. It is anticipated that this work will encourage the promising feasibility of introducing environmental molecules to modulate the roaming reaction.

18.
Front Cardiovasc Med ; 10: 1128294, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37705686

RESUMO

Objective: Contrast-associated acute kidney injury (CA-AKI) is a critical complication when applying contrast medium, and the risk factors of CA-AKI have not been fully clarified. This study aimed to explore the relationships of CA-AKI with erythrocyte parameters, anemia conditions, and sex differences in patients after coronary angiography (CAG). Methods: In this retrospective study, 4,269 patients who underwent CAG were enrolled. CA-AKI was defined as an increase in plasma creatinine of at least 0.5 mg/dl (44 µmol/L) or 25% within 72 h after exposure to the contrast medium. Three erythrocyte parameters, including hemoglobin, hematocrit, and red blood cell (RBC) count, were collected on admission. Logistic regression analyses were used to examine the associations of sex differences and erythrocyte parameters with CA-AKI in the overall population, restricted cubic splines to visualize these associations flexibly. Moreover, stratified and sensitivity analyses were conducted to assess the robustness of the findings. Results: Overall, the mean (± standard deviations) age of patients was 67.05 ± 10.77 years, and 759 subjects (17.8%) developed CA-AKI. The results showed L-shaped relationships between erythrocyte parameters and CA-AKI incidence in each model (all P < 0.001). The incidence of CA-AKI was positively associated with the severity of anemia, while it showed no significant differences among the types of anemia. Moreover, female patients undergoing CAG had a higher risk of CA-AKI than male patients. Mediation analysis verified that erythrocyte parameters exerted an indirect effect on the sex differences of CA-AKI incidences. Conclusion: In conclusion, females, perioperative anemia conditions, and lower erythrocyte parameters (hemoglobin, hematocrit, and RBC count) were verified as risk factors of CA-AKI in patients undergoing CAG. Furthermore, lower erythrocyte parameters among females exerted indirect effects on the sex differences in CA-AKI incidence.

19.
J Nanobiotechnology ; 21(1): 320, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679841

RESUMO

The utilization of nanomaterials in the biosensor field has garnered substantial attention in recent years. Initially, the emphasis was on enhancing the sensor current rather than material interactions. However, carbon nanotubes (CNTs) have gained prominence in glucose sensors due to their high aspect ratio, remarkable chemical stability, and notable optical and electronic attributes. The diverse nanostructures and metal surface designs of CNTs, coupled with their exceptional physical and chemical properties, have led to diverse applications in electrochemical glucose sensor research. Substantial progress has been achieved, particularly in constructing flexible interfaces based on CNTs. This review focuses on CNT-based sensor design, manufacturing advancements, material synergy effects, and minimally invasive/noninvasive glucose monitoring devices. The review also discusses the trend toward simultaneous detection of multiple markers in glucose sensors and the pivotal role played by CNTs in this trend. Furthermore, the latest applications of CNTs in electrochemical glucose sensors are explored, accompanied by an overview of the current status, challenges, and future prospects of CNT-based sensors and their potential applications.


Assuntos
Nanoestruturas , Nanotubos de Carbono , Glicemia , Automonitorização da Glicemia , Condutividade Elétrica
20.
Medicina (Kaunas) ; 59(9)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37763673

RESUMO

COVID-19 is a highly transmittable respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major complication of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6 and TNF-α) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

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