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1.
Fitoterapia ; : 105440, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36736596

RESUMO

Six new flavonols, including four glucosylated flavonols (dysosmaflavonoid A-D), one phenylpropanoid-substituted flavonol (dysosmaflavonoid E), and one phenyl-substituted flavonol (dysosmaflavonoid F), together with five known analogues, were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HRESIMS, and HPLC data. The antioxidant activities of all isolated compounds were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 2, 3, 5-8, and 12 exhibited significant DPPH scavenging capacity with IC50 values of 33.95, 39.02, 31.17, 32.79, 31.85, 30.48, and 23.75 µM, respectively, in comparison with Trolox (IC50, 15.80 µM). Compound 12 displayed more potent DPPH radical scavenging activity than prenylated and (or) glucosided derivatives (2-4, or 10). The preliminary structure-activity relationship showed that the catechol structure in flavonol is essential for DPPH radical scavenging effect.

2.
Zhongguo Zhong Yao Za Zhi ; 48(2): 443-454, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725234

RESUMO

To improve the quality control methods of Poria and develop and utilize its resources fully, alkaline extraction was used in this study to determine the yield and content of alkali-soluble polysaccharides of Poria. The alkali-soluble extracts of Poria were obtained according to the optimum extraction conditions on the basis of single-factor test, and 30 batches of samples were determined. The structure and chemical composition of the alkali-soluble extracts was characterized by high-performance gel permeation chromatography(HPGPC), Fourier transform infrared spectrometry(FT-IR), nuclear magnetic resonance(NMR) spectroscopy and high-performance liquid chromatography(HPLC) with 1-phenyl-3-methyl-5-pyrazolone(PMP-HPLC). The results showed that the content of the alkali-soluble extracts was in the range of 46.98%-73.86%. The main component was ß-(1→3)-glucan, and its molecular mass was about 1.093×10~5. Further, the content of alkali-soluble polysaccharides of Poria was measured by UV-Vis spectrophotometry and HPLC coupled with the evaporative light scattering detector(HPLC-ELSD), and 30 batches of samples were measured. The results indicated that the content of alkali-soluble polysaccharides determined by UV-Vis spectrophotometry was in the range of 73.70%-92.57%, and the content of samples from Hubei province was slightly higher than that from Yunnan province, Anhui province and Hunan province. The content of alkali-soluble polysaccharides determined by HPLC-ELSD was in the range of 51.42%-76.69%, and the samples from Hunan province had slightly higher content than that from the other three provinces. The content determined by UV-Vis spectrophotometry was higher than that by HPLC-ELSD. However, the content determined by HPLC-ELSD was close to that of alkali-soluble extract, which could accurately characterize the content of alkali-soluble polysaccharides in Poria, and the method was simple and repeatable. Therefore, it is recommended that the quantitative analysis method for alkali-soluble extract and alkali-soluble polysaccharides by HPLC-ELSD be used in the quality standards of Poria in Chinese Pharmacopeia.


Assuntos
Poria , Poria/química , Espectroscopia de Infravermelho com Transformada de Fourier , China , Polissacarídeos/química , Padrões de Referência , Cromatografia Líquida de Alta Pressão/métodos
3.
Zhongguo Zhong Yao Za Zhi ; 48(1): 114-125, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725264

RESUMO

Galli Gigerii Endothelium Corneum(GGEC), the dried gizzard membrane of Gallus gallus domesticus is a Chinese medicinal material commonly used for digestion. However, due to the particularity of texture and composition, its active ingre-dients have not been clarified so far, and there is also a lack of quality evaluation indicators. In this study, UPLC-Q-TOF-MS was used to analyze the chemical components from the water extract of GGEC, and ten nucleosides were identified for the first time. HPLC fingerprints of the water extracts of GGEC were established and the content of seven nucleosides was determined. The fingerprint similarities of 40 batches of GGEC samples ranged from 0.765 to 0.959, indicating that there were great differences among the GGEC products processed with different methods. In addition, SPSS 22.0 and SIMCA 14.1 were used for hierarchical cluster analysis(HCA) and principal component analysis(PCA) on the 19 common peaks of the HPLC fingerprints of GGEC, and the 40 batches of samples were divided into three categories: raw GGEC, fried GGEC and vinegar-processed GGEC. Eight differential components in GGEC were marked by orthogonal partial least squares discrimination analysis(OPLS-DA), two of which were adenine and thymine. The results of content determination showed that the total content of the seven nucleosides in raw GGEC, fried GGEC and vinegar-processed GGEC were 182.5-416.8, 205.3-368.7, and 194.2-283.0 µg·g~(-1), respectively. There were significant differences in the content of hypoxanthine, thymine and thymidine among the GGEC products processed with different methods(P<0.05), which were graded in the order of fried GGEC>vinegar-processed GGEC>raw GGEC. This suggested that the content of hypoxanthine, thymine and thymidine tended to increase during the frying process, and the variation range might be related to the degree of heat exposure. The established methods in this study were simple and reproducible, and could be used for qualitative and quantitative analysis of GGEC and its processed pro-ducts. This study also provided reference for the establishment of quality standards of GGEC with chemical components as control index.


Assuntos
Medicamentos de Ervas Chinesas , Nucleosídeos , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão , Ácido Acético , Timina , Timidina , Água , Hipoxantinas
4.
Inorg Chem ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721875

RESUMO

Class Id ribonucleotide reductase (RNR) is a newly discovered enzyme, which employs the dimanganese cofactor in the superoxidized state (MnIII/MnIV) as the radical initiator. The dimanganese cofactor of class Id RNR in the reduced state (inactive) is clearly based on the crystal structure of the Fj-ß subunit. However, the state of the dimanganese cofactor of class Id RNR in the oxidized state (active) is not known. The X-band EPR spectra have shown that the activated Fj-ß subunit exists in two distinct complexes, 1 and 2. In this work, quantum mechanical/molecular mechanical calculations were carried out to study class Id RNR. First, we have determined that complex 2 contains a MnIII-(µ-oxo)2-MnIV cluster, and complex 1 contains a MnIII-(µ-hydroxo/µ-oxo)-MnIV cluster. Then, based on the determined dimanganese cofactors, the mechanism of radical initiation and transfer in class Id RNR is revealed. The MnIII-(µ-oxo)2-MnIV cluster in complex 2 has not enough reduction potential to initiate radical transfer directly. Instead, it needs to be monoprotonated into MnIII-(µ-hydroxo/µ-oxo)-MnIV (complex 1) before the radical transfer. The protonation state of µ-oxo can be regulated by changing the protein microenvironment, which is induced by the protein aggregation and separation of ß subunits with α subunits. The radical transfer between the cluster of MnIII-(µ-hydroxo/µ-oxo)-MnIV and Trp30 in the radical-transfer chain of the Fj-ß subunit (MnIII/MnIV ↔ His100 ↔ Asp194 ↔ Trp30 ↔ Arg99) is a water-mediated tri-proton-coupled electron transfer, which transfers proton from the ε-amino group of Lys71 to the carboxyl group of Glu97 via the water molecule Wat551 and the bridging µ-hydroxo ligand through a three-step reaction. This newly discovered proton-coupled electron-transfer mechanism in class Id RNR is different from those reported in the known Ia-Ic RNRs. The ε-amino group of Lys71, which serves as a proton donor, plays an important role in the radical transfer.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36723229

RESUMO

Photochemical afterglow systems have drawn considerable attention in recent years due to their regulable photophysical properties and charming application potential. However, conventional photochemical afterglow suffered from its unrepeatability due to the consumption of energy cache units as afterglow photons are emitted. Here we report a novel strategy to realize repeatable photochemical afterglow (RPA) through the reversible storage of 1O2 by 2-pyridones. Near-infrared afterglow with a lifetime over 10 s is achieved, and its initial intensity shows no significant reduction over 50 excitation cycles. A detailed mechanism study was conducted and confirmed the RPA is realized through the singlet oxygen-sensitized fluorescence emission. Furthermore, the generality of this strategy is demonstrated and tunable afterglow lifetimes and colors are achieved by rational design. The developed RPA is further applied for attacker-misleading information encryption, presenting a repeatable-readout.

6.
Plants (Basel) ; 12(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36678936

RESUMO

The ability of plants to absorb unsaturated atmospheric water vapor is a controversial topic. To study how vegetation in arid areas survives under limited water resources, this study uses Tamarisk in the Ulan Buh Desert of China as an example. The in-situ observation of a newly designed Lysimeter and sap flow meter system were used to monitor the precipitation infiltration and the utilization efficiency of Tamarisk of atmospheric vapor. The results show that the annual precipitation of 84 mm in arid areas could still result in deep soil recharge (DSR) with a recharge rate of 5 mm/year. Furthermore, DSR is detectable even in the winter, and the 5-year average DSR was 5.77% of the annual precipitation. It appears that the small precipitation events are critically important for the survival of Tamarisk. When the atmospheric relative humidity reaches 70%, Tamarisk leaves can absorb the unsaturated atmospheric vapor, which accounts for 13.2% of the annual precipitation amount. To adapt to the arid environment, Tamarisk can harvest its water supply from several sources including atmospheric vapor and micro-precipitation events (whose precipitation is below the measurement limit of 0.2 mm of the precipitation gauge) and can still permit a certain amount of recharge to replenish the deep soil moisture. Such an ecohydrological dynamic is of great significance to desert vegetation.

7.
Sci Bull (Beijing) ; 68(1): 77-94, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36621435

RESUMO

Iron accumulation and lipid peroxidation form the basis of ferroptosis, potentially circumventing the limitations of apoptosis in cancer treatment. Owing to the lack of potent ferroptosis inducers, the development of efficient ferroptosis-based therapeutic agents and protocols against cancers is highly challenging. Inspired by the topological effect of nanoparticles in modulating cellular function/status, a specific tetrapod ferroptosis-inducer iron-palladium (FePd) nanocrystal was rationally engineered for physically activated autophagy-augmented ferroptosis and enhanced cancer immunotherapy. Specifically, the tetrapod FePd nanocrystal featured strong peroxidase-/glutathione oxidase-mimicking bioactivities, which promoted cancer cell ferroptosis. The special spiky morphology and nanostructure of the FePd nanocrystal simultaneously induced autophagy, which augmented ferroptosis in cancer cells and triggered the release of inflammatory cytokines in macrophages for strengthening anti-PD-L1-antibody mediated immunotherapy, synergistically achieving the maximal antineoplastic effect in three tumor-bearing animal models. This unique physical activation strategy for efficient cancer treatment via precise morphological tuning represents a paradigm for nanomedicine design for efficient tumor treatment.


Assuntos
Ferroptose , Neoplasias , Animais , Nanomedicina , Neoplasias/tratamento farmacológico , Ferro/farmacologia , Imunoterapia , Autofagia
8.
Sci Total Environ ; 870: 161841, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36720395

RESUMO

Phosphorus imbalance for cropland can greatly influence environmental quality and productivity of agricultural systems. Resolving cropland phosphorus imbalance may be possible with more efficient multilateral crop trade within the involved trading countries; however, the driving mechanisms are unclear. This study calculates phosphorus budgets in China and five central Asian countries and proposes two optimal multilateral crop trade models to mitigate the phosphorus imbalance. Results show that the current trading pattern between China and Central Asia is causing a phosphorus imbalance intensification. Phosphorus surpluses in China and Uzbekistan are 41.7 and 8.9 kg/ha, while Kazakhstan, Kyrgyzstan, Tajikistan, and Turkmenistan exhibit phosphorus deficits with the negative value of -0.7, -1.2, -0.8, and -0.8 kg/ha, respectively. However, under the optimal multilateral crop trade patterns, phosphorus budget of China and Central Asia will become balanced. Phosphorus imbalance intensification for China is reduced to -2525 and -2472 kt under the single- and bilevel-objective-based crop trades. In Kyrgyzstan, it will drop 61.5 % and 50.0 % and change to 321 and 417 kt under the two optimal crop trades. Moreover, changes of phosphorus imbalance mitigations for other central Asian countries range from 11.9 % to 28.2 %. This provides a scientific basis when establishing policies for strengthening optimal multilateral crop trading across the world to promote global phosphorus management.

9.
Structure ; 31(1): 68-77.e5, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36608665

RESUMO

As the prototype of Sec1/Munc18 (SM) family proteins, Munc18-1 can manipulate the distinct conformations of syntaxin-1 for controlling intracellular membrane fusion. The Munc18-1-interacting domain of Mint1 (Mint1-MID) binds to Munc18-1 together with syntaxin-1 to form a Mint1-Munc18-1-syntaxin-1 complex, but the mechanism underlying the complex assembly remains unclear. Here, we determine the structure of the Mint1-MID-Munc18-1-syntaxin-1 complex. Unexpectedly, Munc18-1 recognizes Mint1-MID and syntaxin-1 simultaneously via two opposite sites. The canonical central cavity between domains 1 and 3a of Munc18-1 embraces closed syntaxin-1, whereas the non-canonical basic pocket in domain 3b captures the acidic Mint1-MID helix. The domain 3b-mediated recognition of an acidic-helical motif is distinct from other target-recognition modes of Munc18-1. Mutations in the interface between domain 3b and Mint1-MID disrupt the assembly of the Mint1-Munc18-1-syntaxin-1 complex. This work reveals a non-canonical target-binding site in Munc18-1 domain 3b for assembling the Mint1-Munc18-1-syntaxin-1 complex.


Assuntos
Proteínas Munc18 , Proteínas SNARE , Proteínas Qa-SNARE/metabolismo , Sítios de Ligação , Proteínas Munc18/genética , Proteínas Munc18/química , Proteínas Munc18/metabolismo , Sintaxina 1/química , Domínios Proteicos , Ligação Proteica , Proteínas SNARE/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-36718610

RESUMO

Interface fusion plays a key role in constructing Ni-based single-crystal cathodes, and is governed by the atomic migration related to kinetics. However, the interfacial atom migration path and its control factors are lack of clearly understanding. Herein, we systematically probe the solid-state synthesis mechanism of single-crystal LiNi0.92Co0.04Mn0.04O2, including the effects of precursor size, Li/transition metal (TM) ratio and sintering temperature on the structure. Multi-dimensional analysis unravels that thermodynamics drives interface atoms migration through intermediate state (i.e., cation mixing phase) to induce grain boundary fusion. Moreover, we demonstrate that smaller precursor size (< 6 µm), lager Li/TM ratio (> 1.0) and higher temperature (≥ 810 ℃) are conducive to promote the growth of the intermediate state due to reaction kinetics enhancement, and ultimately strengthen the atomic migration-induced interface fusion.

11.
Nat Commun ; 14(1): 20, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596764

RESUMO

Miniaturized rotors based on Marangoni effect have attracted great attentions due to their promising applications in propulsion and power generation. Despite intensive studies, the development of Marangoni rotors with high rotation output and fuel economy remains challenging. To address this challenge, we introduce an asymmetric porosity strategy to fabricate Marangoni rotor composed of thermoresponsive hydrogel and low surface tension anesthetic metabolite. Combining enhanced Marangoni propulsion of asymmetric porosity with drag reduction of well-designed profile, our rotor precedes previous studies in rotation output (~15 times) and fuel economy (~34% higher). Utilizing thermoresponsive hydrogel, the rotor realizes rapid refueling within 33 s. Moreover, iron-powder dopant further imparts the rotors with individual-specific locomotion in group under magnetic stimuli. Significantly, diverse functionalities including kinetic energy transmission, mini-generator and environmental remediation are demonstrated, which open new perspectives for designing miniaturized rotating machineries and inspire researchers in robotics, energy, and environment.


Assuntos
Hidrogéis , Porosidade , Fenômenos Físicos , Tempo , Tensão Superficial
12.
Adv Sci (Weinh) ; : e2205962, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627131

RESUMO

The controllability of the microstructure of a compressed hierarchical building block is essential for optimizing a variety of performance parameters, such as thermal management. However, owing to the strong orientation effect during compression molding, optimizing the alignment of materials perpendicular to the direction of pressure is challenging. Herein, to illustrate the effect of the ordered microstructure on heat dissipation, thermally conductive carbon-based materials are fabricated by tailoring dense, orientation-tunable, and interleaved structures. Vertically aligned carbon nanotube arrays (VACNTs) interconnected with graphene films (GF) are prepared as a 3D core-ordered material to fabricate compressed building blocks of O-VA-GF and S-VA-GF. Leveraging the densified interleaved structure offered by VACNTs, the hierarchical O-VA-GF achieves excellent through-plane (41.7 W m-1 K-1 ) and in-plane (397.9 W m-1 K-1 ) thermal conductivities, outperforming similar composites of S-VA-GF (through-plane: 10.3 W m-1 K-1 and in-plane: 240.9 W m-1 K-1 ) with horizontally collapsed carbon nanotubes. As heat dissipation plates, these orderly assembled composites yield a 144% and 44% enhancement in the cooling coefficient compared with conventional Si3 N4 for cooling high-power light-emitting diode chips.

13.
Methods Mol Biol ; 2608: 97-114, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36653704

RESUMO

Fibrillar collagen is an abundant extracellular matrix (ECM) component of interstitial tissues which supports the structure of many organs, including the skin and breast. Many different physiological processes, but also pathological processes such as metastatic cancer invasion, involve interstitial cell migration. Often, cell movement takes place through small ECM gaps and pores and depends upon the ability of the cell and its stiff nucleus to deform. Such nuclear deformation during cell migration may impact nuclear integrity, such as of chromatin or the nuclear envelope, and therefore the morphometric analysis of nuclear shapes can provide valuable insight into a broad variety of biological processes. Here, we describe a protocol on how to generate a cell-collagen model in vitro and how to use confocal microscopy for the static and dynamic visualization of labeled nuclei in single migratory cells. We developed, and here provide, two scripts that (Fidler, Nat Rev Cancer 3(6):453-458, 2003) enable the semi-automated and fast quantification of static single nuclear shape descriptors, such as aspect ratio or circularity, and the nuclear irregularity index that forms a combination of four distinct shape descriptors, as well as (Frantz et al., J Cell Sci 123 (Pt 24):4195-4200, 2010) a quantification of their changes over time. Finally, we provide quantitative measurements on nuclear shapes from cells that migrated through collagen either in the presence or the absence of an inhibitor of collagen degradation, showing the distinctive power of this approach. This pipeline can also be applied to cell migration studied in different assays, ranging from 3D microfluidics to migration in the living organism.


Assuntos
Colágeno , Matriz Extracelular , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Movimento Celular/fisiologia , Núcleo Celular/metabolismo , Cromatina/metabolismo , Linhagem Celular Tumoral
14.
J Neurointerv Surg ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690440

RESUMO

BACKGROUND: Flow diverters have revolutionized the treatment of intracranial aneurysms. However, the delayed complications associated with flow diverter use are unknown. OBJECTIVE: To evaluate the incidence, severity, clinical outcomes, risk factors, and dynamic changes associated with in-stent stenosis (ISS) after treatment with a Pipeline embolization device (PED). METHODS: Patients who underwent PED treatment between 2015 and 2020 were enrolled. The angiographic, clinical, and follow-up data of 459 patients were independently reviewed by four neuroradiologists to identify ISS. Binary logistic regression was conducted to determine ISS risk factors, and an ISS-time curve was established to demonstrate dynamic changes in ISS after PED implantation. RESULTS: Of the 459 treated patients, 69 (15.0%) developed ISS. At follow-up, nine patients (2.0%) with ISS demonstrated reversal, while 18 (3.9%) developed parental artery occlusion. A total of 380 patients (82.8%) achieved complete aneurysm occlusion (O'Kelly-Marotta grade D). Patients with posterior-circulation aneurysm (OR=2.895, 95% CI (1.732 to 4.838; P<0.001) or balloon angioplasty (OR=1.992, 95% CI 1.162 to 3.414; P=0.037) were more likely to develop ISS. Patients aged >54 years (OR=0.464, 95% CI 0.274 to 0.785; P=0.006) or with a body mass index of >28 kg/m2 (OR=0.427, 95% CI 0.184 to 0.991; P=0.026) had a lower ISS risk. Intimal hyperplasia initiated by PED placement peaked within 1 year after the procedure, rarely progressed after 12 months, and tended to reverse within 24 months. CONCLUSIONS: ISS is a common, benign, and self-limiting complication of PED implantation in the Chinese population.

15.
J Nat Med ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36689084

RESUMO

Two new ß-carboline alkaloids, anemonilins A and B (1-2), and two known ß-carboline alkaloids, flazine (3) and 4-(9H-ß-carbolin-l-yl)-4-oxo-butyric acid (4), were isolated from the roots of Anemone altaica. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods (1D and 2DNMR, HRESIMS). Compounds 2 and 4 significantly attenuated the growth inhibition induced by lipopolysaccharide (LPS) in normal rat kidney tubule epithelioid (NRK52e) cells (p < 0.05 or p < 0.01). Furthermore, compound 2 significantly reduced the apoptosis (p < 0.05) and the caspase-3/9 expression of NRK52e cells induced by LPS.

17.
Anal Chem ; 95(4): 2478-2486, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36649320

RESUMO

Hypoxia is a common feature of many diseases such as solid tumors. The measurement and imaging of oxygen (O2) are extremely important for disease diagnosis and therapy evaluation. In this work, the afterglow/fluorescence dual-emissive ratiometric O2 probe based on a photochemical reaction-based afterglow system is reported. The afterglow is highly sensitive to O2 because the O2 content is directly related to the 1O2 yield and eventually affects the afterglow intensity. The O2-insensitive fluorescence of an emitter can serve as an internal reference. As the O2 concentration changes from 0.08 to 18.5 mg L-1, the ratio value shows a remarkable 53-fold increase. Compared with the intensity of a single peak, the ratiometric signal can eliminate the interference of the probe concentration to achieve higher accuracy. This afterglow/fluorescence dual-emissive ratiometric O2 probe is successfully applied to hypoxia imaging in tumor-bearing mice, which may further promote the development of O2 sensing in the biomedical field.


Assuntos
Neoplasias , Oxigênio , Animais , Camundongos , Corantes Fluorescentes/química , Fluorescência , Hipóxia Tumoral , Hipóxia , Neoplasias/diagnóstico por imagem
18.
J Exp Clin Cancer Res ; 42(1): 22, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639681

RESUMO

BACKGROUND: Nitric oxide-releasing drugs are used for cardiovascular diseases; however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice. METHODS: The effects of three different nitric oxide-releasing compounds (SNAP, SNP, and ISMN) on tumor growth were studied in tumor-bearing mouse models. Three mouse tumor models were used: B16F1 melanoma and LL2 lung carcinoma in C57BL/6 mice, CT26 colon cancer in BALB/c mice, and LL2 lung carcinoma in NOD/SCID mice. After nitric oxide treatment, splenic cytokines and lymphocytes were analyzed by cytokine array and flow cytometry, and tumor-infiltrating lymphocytes in the TME were analyzed using flow cytometry and single-cell RNA sequencing. RESULTS: Low doses of three exogenous nitric oxide donors inhibited tumor growth in two immunocompetent mouse models but not in NOD/SCID immunodeficient mice. Low-dose nitric oxide donors increase the levels of splenic cytokines IFN-γ and TNF-α but decrease the levels of cytokines IL-6 and IL-10, suggesting an alteration in Th2 cells. Nitric oxide donors increased the number of CD8+ T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8+ T cells and dendritic cells. The antitumor effect of nitric oxide donors was abolished by depletion of CD8+ T cells, indicating the requirement for CD8+ T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic effect was accompanied by an increase in the cells expressing the gene signature of NK cell. CONCLUSIONS: Low concentrations of exogenous nitric oxide donors inhibit tumor growth in vivo by regulating T cells and macrophages. CD8+ T cells are essential for antitumor effects. In addition, low-dose nitric oxide donors may be combined with chemotherapeutic drugs in cancer therapy in the future.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma , Animais , Camundongos , Óxido Nítrico , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêutico , Reposicionamento de Medicamentos , Camundongos Endogâmicos C57BL , Camundongos SCID , Citocinas , Microambiente Tumoral
19.
Int Orthop ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646902

RESUMO

PURPOSES: Temporary hemiepiphysiodesis (TH) using eight-plates is one of the most frequently performed surgeries for correcting angular deformities of the lower extremities in adolescents. Rarely have studies examined children with X-linked hypophosphataemic rickets (X-LHPR) treated with TH using eight-plates. This study was conducted to investigate the efficacy, the endpoint, and the complications of TH using eight-plates to correct angular deformities of the lower extremities in skeletally immature children. METHODS: We reviewed a total of 26 children (86 physes, 52 knees) with X-LHPR (mean age of 6.2 years, range from 2 to 13 years) who underwent TH using eight-plate to correct angular deformities of the lower extremities. Radiographs and clinical records of these patients were evaluated for demographic data and related clinical factors. RESULTS: The average correction of the mechanical lateral distal femoral angle (mLDFA) was 11.7 ± 8.7° (range from 1.0 to 29.7°), and the average correction of the mechanical medial proximal tibial angle (mMPTA) was 8.4 ± 5.0° (range from 0.3 to 16.7°). The mean deformity correction time was 22.7 months (range from 7 to 60 months), and the mean follow-up after eight-plate removal was 43.9 months (range from 24 to 101 months). Overall, 76.9% (20/26 patients) of the angular deformities of the knee were completely corrected and 15.4% (4/26) of the patients received osteotomy surgery. The femoral correction velocity (0.9° per month) was significantly higher than the proximal tibial (0.6° per month) (p = 0.02). The correction velocity of the mLDFA and mMPTA with the TH procedure was faster than that in the absence of intervention (0.9° vs. 0.2°, 0.7° vs. 0.4° per month, p < 0.05). The correction velocity of the mLDFA (1.2° vs. 0.5° per month, [Formula: see text]) and mMPTA (0.7° vs. 0.5° per month, p = 0.04) of patients whose age ≤ five years old was faster than that of patients whose age > five years old. A total of 69.2% (18/26) patients experienced one TH procedure using eight-plates only. Two patients had screw loosening (2/26, 7.7%). One patient (1/26, 3.8%) had a rebound phenomenon after the removal of eight-plate and had the TH procedure again. There was no breakage, infection, physis preclosure, or limited range of movement found in the follow-up. CONCLUSION: TH using eight-plates is a safe and effective procedure with a relatively low incidence of complication and rebound, and it could be used as part of a streamlined treatment for younger X-LHPR patients with resistant or progressive lower limb deformity despite optimal medical treatment. Early intervention can achieve better results.

20.
Anal Chem ; 95(2): 1755-1763, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36596643

RESUMO

Mustard gas [sulfur mustard (SM)] and phosgene are the most frequently used chemical warfare agents (CWAs), which pose a serious threat to human health and national security, and their rapid and accurate detection is essential to respond to terrorist attacks and industrial accidents. Herein, we developed a fluorescent probe with o-hydroxythioketone as two sensing sites, AQso, which can detect and distinguish mustard gas and phosgene. The dual-sensing-site probe AQso reacts with mustard gas to form a cyclic product with high sensitivity [limit of detection (LOD) = 70 nM] and is highly selective to SM over phosgene, SM analogues, active alkylhalides, acylhalides, and nerve agent mimics, in ethanol solutions. When encountering phosgene, AQso rapidly converts to cyclic carbonate, which is sensitive (LOD = 14 nM) and highly selective. Their sensing mechanisms of AQso to mustard gas and phosgene were well demonstrated by separation and characterization of the sensing products. Furthermore, a facile test strip with the probe was prepared to distinguish 2-chloroethyl ethyl sulfide (CEES) and phosgene in the gas phase by different fluorescence colors and response rates. Not using the complicated instrument, the qualitative and quantitative detection of CEES or phosgene can be achieved only by measuring the red-green-blue (RGB) channel intensity of the test strip after being exposed to CEES or phosgene gas by the smartphone with an RGB color application.


Assuntos
Substâncias para a Guerra Química , Gás de Mostarda , Fosgênio , Humanos , Fosgênio/química , Corantes Fluorescentes/química
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