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1.
World J Gastroenterol ; 30(15): 2143-2154, 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38681990

RESUMEN

BACKGROUND: Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to liver cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells (HSCs), which can transdifferentiate into myofibroblasts to produce an excess of the extracellular matrix (ECM). Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis. Therefore, activated hepatic stellate cells (aHSCs), the principal ECM producing cells in the injured liver, are a promising therapeutic target for the treatment of hepatic fibrosis. AIM: To explore the effect of taurine on aHSC proliferation and the mechanisms involved. METHODS: Human HSCs (LX-2) were randomly divided into five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated group, and low, medium, and high dosage of taurine (10 mmol/L, 50 mmol/L, and 100 mmol/L, respectively) with PDGF-BB (20 ng/mL) treated group. Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs. Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species (ROS), malondialdehyde, glutathione, and iron concentration. Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression of α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin 1, PTGS2, SLC7A11, and p62. RESULTS: Taurine promoted the death of aHSCs and reduced the deposition of the ECM. Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation, by decreasing autophagosome formation, downregulating LC3B and Beclin 1 protein expression, and upregulating p62 protein expression. Meanwhile, treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Furthermore, bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4, exhibiting the best average binding affinity of -20.99 kcal/mol. CONCLUSION: Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.


Asunto(s)
Autofagia , Proliferación Celular , Ferroptosis , Células Estrelladas Hepáticas , Cirrosis Hepática , Especies Reactivas de Oxígeno , Taurina , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Humanos , Autofagia/efectos de los fármacos , Taurina/farmacología , Ferroptosis/efectos de los fármacos , Cirrosis Hepática/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Proliferación Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Becaplermina/farmacología , Becaplermina/metabolismo , Línea Celular , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Supervivencia Celular/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
2.
Synth Syst Biotechnol ; 9(3): 522-530, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38645975

RESUMEN

The morphology is the consequence of evolution and adaptation. Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5 µm long and 0.5 µm wide. Many shape-related genes have been identified and used in morphology engineering of this bacteria. However, little is known about if specific metabolism and metal irons could modulate bacteria morphology. Here in this study, we discovered filamentous shape change of E. coli cells overexpressing pigeon MagR, a putative magnetoreceptor and extremely conserved iron-sulfur protein. Comparative transcriptomic analysis strongly suggested that the iron metabolism change and iron accumulation due to the overproduction of MagR was the key to the morphological change. This model was further validated, and filamentous morphological change was also achieved by supplement E. coli cells with iron in culture medium or by increase the iron uptake genes such as entB and fepA. Our study extended our understanding of morphology regulation of bacteria, and may also serves as a prototype of morphology engineering by modulating the iron metabolism.

3.
Anal Chem ; 96(12): 5006-5013, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38484040

RESUMEN

The development of new imaging and treatment nanoprodrug systems is highly demanded for diagnosis and therapy of liver cancer, a severe disease characterized by a high recurrence rate. Currently, available small molecule drugs are not possible for cancer diagnosis because of the fast diffusion of imaging agents and low efficacy in treatment due to poor water solubility and significant toxic side effects. In this study, we report the development of a tumor microenvironment activatable nanoprodrug system for the diagnosis and treatment of liver cancer. This nanoprodrug system can accumulate in the tumor site and be selectively activated by an excess of hydrogen peroxide (H2O2) in the tumor microenvironment, releasing near-infrared solid-state organic fluorescent probe (HPQCY-1) and phenylboronic acid-modified camptothecin (CPT) prodrug. Both HPQCY-1 and CPT prodrugs can be further activated in tumor sites for achieving more precise in situ near-infrared (NIR) fluorescence imaging and treatment while reducing the toxic effects of drugs on normal tissues. Additionally, the incorporation of hydrophilic multivalent chitosan as a carrier effectively improved the water solubility of the system. This research thus provides a practical new approach for the diagnosis and treatment of liver cancer.


Asunto(s)
Neoplasias Hepáticas , Nanopartículas , Profármacos , Humanos , Microambiente Tumoral , Peróxido de Hidrógeno , Profármacos/farmacología , Profármacos/uso terapéutico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Imagen Óptica , Agua , Línea Celular Tumoral , Camptotecina/farmacología
4.
Water Res ; 253: 121326, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38377928

RESUMEN

Cadmium (Cd) is a widespread and highly toxic environmental pollutant, seriously threatening animal and plant growth. Therefore, monitoring and employing robust tools to enrich and remove Cd from the environment is a major challenge. In this work, by conjugating a fluorescent indicator (CCP) with a functionalized glass slide, a special composite material (CCPB) was constructed to enrich, remove, and monitor Cd2+ in water rapidly. Then Cd2+ could be effectively eluted by immersing the Cd-enriched CCPB in an ethylenediaminetetraacetic acid (EDTA) solution. With this, the CCPB was continuously reused. Its recovery of Cd2+was above and below 100 % after multiple uses by flame atomic absorption spectrometry (FAAS), which was excellent for practical use in enriching and removing Cd2+ in real aqueous samples. Therefore, CCPB is an ideal material for monitoring, enriching, and removing Cd2+ in wastewater, providing a robust tool for future practical applications of Cd enrichment and removal in the environment.


Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Cadmio/análisis , Agua/química , Ácido Edético/química , Aguas Residuales , Contaminantes Ambientales/análisis , Contaminantes Químicos del Agua/análisis , Espectrofotometría Atómica/métodos , Adsorción
5.
J Hazard Mater ; 466: 133653, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38301443

RESUMEN

Cadmium-contaminated water and food are seriously hazardous to the human health, especially liver injury. To understand the entanglement relationship between cadmium ion (Cd2+)-induced liver injury and the biomarker sulfur dioxide (SO2), a reliable bioanalytical tool is urgently needed, detecting SO2 to diagnose and evaluate the extent of liver injury in vivo. Herein, based on the Förster resonance energy transfer (FRET) mechanism, a novel SO2-tunable NIR ratiometric fluorescent probe (SMP) was developed, it was used to diagnose and treat liver injury induced by Cd2+ in biosystems. Specifically, it was constructed by conjugating a NIR dicyanoisophorone with a NIR benzopyranate as the donor and acceptor, respectively, and the ratiometric response of SO2- regulated by the Michael addition reaction. In addition, SMP exhibits rapid reaction time (<15 s), two well-resolved emission peaks (68 nm) with less cross-talk between channels for high imaging resolution, superior selectivity, and low limit of detection (LOD=80.3 nM) for SO2 detection. Impressively, SMP has been successfully used for intracellular ratiometric imaging of Cd2+-induced SO2 and diagnostic and therapeutic evaluation in liver injury mice models with satisfactory results. Therefore, SMP may provide a powerful molecular tool for revealing the occurrence and development relationship between SO2 and Cd2+-induced liver injury. ENVIRONMENTAL IMPLICATION: Cadmium ions are one of the well-known toxic environmental pollutants, which are enriched in the human body through inhalation of cadmium-contaminated air or from the food chain, leading to damage in various organs, especially liver injury. Therefore, we developed a novel fluorescent probe that can specifically detect SO2 in Cd2+-induced liver injury, which is critically important for the diagnosis and evaluation of Cd2+-induced liver injury diseases. The specific detection of SO2 of this probe has been successfully demonstrated in live HepG2 cells and Cd2+-induced liver injury mice.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Colorantes Fluorescentes , Ratones , Humanos , Animales , Cadmio/toxicidad , Células Hep G2 , Dióxido de Azufre/toxicidad , Células HeLa
6.
Acta Pharmacol Sin ; 45(1): 166-179, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37605050

RESUMEN

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.


Asunto(s)
Neovascularización de la Córnea , Síndromes de Ojo Seco , Ratas , Humanos , Ratones , Animales , Femenino , Neovascularización de la Córnea/tratamiento farmacológico , Neovascularización de la Córnea/metabolismo , Neovascularización de la Córnea/patología , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Roedores/metabolismo , Células Endoteliales/metabolismo , Angiogénesis , Inflamación/tratamiento farmacológico , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/inducido químicamente , Factor de Transcripción STAT3/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 48(16): 4421-4428, 2023 Aug.
Artículo en Chino | MEDLINE | ID: mdl-37802868

RESUMEN

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.


Asunto(s)
Asteraceae , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Humanos , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Asteraceae/química , Neoplasias Pulmonares/tratamiento farmacológico
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 303: 123178, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37499473

RESUMEN

Abiotic stress and oxidative stress are closely related to the health status of plants. Plants will produce oxidative stress under abiotic stress, induce mitochondrial dysfunction, cause programmed cell death, and decrease plant survival rate. It is well known that rice is an essential crop for humans, but its cadmium tolerance is poor. Therefore, it is crucial to determine whether cadmium stress causes oxidative stress in rice in order to guide rice cultivation. Hydrogen peroxide (H2O2), a highly reactive oxygen species (ROS), is one of the most critical signals in corps under oxidative stress. In this work, we adopted a near-infrared (NIR) H2O2 fluorescent probe YFE-1 and a cadmium ion (Cd2+) fluorescent probe SCP to observe the fluctuation of H2O2 in rice roots under Cd2+ co-incubation conditions. Due to the advantages of fast response (within 2 min), a large Stokes shift (181 nm), good selectivity, and a low detection limit (LOD:26.4 nM), YFE-1 achieved the visualization of H2O2 produced by Cd2+ stress in rice roots. This study provides a new idea for assessing the risk of oxidative stress of Cd2+ in rice roots. It is expected to guide the control of Cd2+ in the rice planting industry to improve rice yield.


Asunto(s)
Cadmio , Oryza , Humanos , Cadmio/metabolismo , Peróxido de Hidrógeno/metabolismo , Oryza/metabolismo , Colorantes Fluorescentes/metabolismo , Fluorescencia , Estrés Oxidativo , Antioxidantes/metabolismo , Plantas/metabolismo , Raíces de Plantas/metabolismo
9.
J Hazard Mater ; 457: 131748, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37267647

RESUMEN

Cadmium (Cd), a widespread and highly toxic environmental contaminant, has seriously impacted the growth of rice and the quality of its products. Hence, it is crucial to monitor and employ robust means to reduce Cd levels in rice, and selenium (Se) has been proven to chelate cadmium ion (Cd2+) in rice with rational use. Herein, for the first time, the reported selenocysteine (Sec) probe NN-Sec and the newly designed Cd2+ probe SCP were chosen as visualization tools to monitor Sec-inhibited Cd2+ uptake in rice. Specifically, reduced fluorescence of rice precultured with Cd2+ was observed by SCP after Se application, while similarly decreased fluorescence of rice pretreated with Se was observed by NN-Sec after Cd2+ addition. The diminished fluorescence indicated the formation of Cd-Se complexes reduced the Cd2+ content in rice. Additionally, it was Cd2+ and Se that entered the rice causing the fluorescence generation, as demonstrated by inductively coupled plasma mass spectrometry (ICP-MS). To conclude, the two probes successfully visualized Se inhibited Cd2+ uptake in rice, which could provide a robust tool for supporting the development of novel organic fertilizers and reagents to reduce Cd2+ content in rice and the environment.


Asunto(s)
Oryza , Selenio , Contaminantes del Suelo , Selenio/química , Cadmio/toxicidad , Cadmio/análisis , Oryza/química , Colorantes Fluorescentes , Contaminantes del Suelo/análisis
11.
Artículo en Inglés | MEDLINE | ID: mdl-36780508

RESUMEN

Cyclic ethers are promising solvents for low-temperature electrolytes, but they still suffer from intrinsic poor antioxidant abilities. Until now, ether-based electrolytes have been rarely reported for high-voltage sodium-ion batteries (SIBs) operated under a low-temperature range. Herein, a novel ether-based electrolyte consisting of tetrahydrofuran as the main solvent is proposed and it could be utilized for a high-voltage Na2/3Mn2/3Ni1/3O2 (MN) cathode in a wide-temperature range from -40 to 25 °C. Meanwhile, a thin and robust inorganic component-rich cathode electrolyte interface layer is elaborately introduced on the MN cathode by this tailored electrolyte, resulting in excellent cycle life of MN cathode. Specifically, a capacity retention of 97.2% after 140 cycles could be delivered by MN at 0.3 C at room temperature (RT). Especially at an ultra-low temperature of -40 °C, the initial discharge capacity of MN could still approach 89.3% of that at RT, and the capacity retention is 94.1% at 0.2 C after 100 cycles. This work provides a new insight into the rational design of ether-based electrolytes for high-voltage and stable SIBs operated in a wide-temperature range.

12.
Food Chem ; 405(Pt B): 134949, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36403471

RESUMEN

Nitrite (NO2-) and formaldehyde (FA) are practice common food hazards, seriously threatening human health. Herein, for the first time a de novo nanoprobe, named MTB, with a single response group exhibiting different optical signals for NO2-/FA was reported, which had the following characteristics: i) An adamantane-labeled small molecule NI-adH grafted with polycyclodextrin (Poly-ß-CD) to form MTB with excellent water-solubility and biocompatibility. ii) O-phenylenediamine (OPD) with photoinduced electron transfer (PET) played both a fluorescence quencher and as NO2-/FA trappers. Interestingly, fixed on pH6.0, OPD rapidly reacted with NO2- forming triazoles, inhibiting the PET effect and releasing bright fluorescence at 530 nm. While adding FA, OPD ultrafast formed Schiff-base, and MTB absorption red-shifted from 452 nm to 545 nm. Moreover, MTB exhibited excellent selectivity, high sensitivity (21.8 nM/17.1 nM), and rapid response towards (60 s/65 s) NO2-/FA. Impressively, MTB has been successfully adopted to detect NO2-/FA in real foods with satisfactory results.


Asunto(s)
Nitritos , Dióxido de Nitrógeno , Humanos , Alimentos , Formaldehído
13.
Zool Res ; 44(1): 142-152, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36484226

RESUMEN

The ability to navigate long distances is essential for many animals to locate shelter, food, and breeding grounds. Magnetic sense has evolved in various migratory and homing species to orient them based on the geomagnetic field. A highly conserved iron-sulfur cluster assembly protein IscA is proposed as an animal magnetoreceptor (MagR). Iron-sulfur cluster binding is also suggested to play an essential role in MagR magnetism and is thus critical in animal magnetoreception. In the current study, we provide evidence for distinct iron binding and iron-sulfur cluster binding in MagR in pigeons, an avian species that relies on the geomagnetic field for navigation and homing. Pigeon MagR showed significantly higher total iron content from both iron- and iron-sulfur binding. Y65 in pigeon MagR was shown to directly mediate mononuclear iron binding, and its mutation abolished iron-binding capacity of the protein. Surprisingly, both iron binding and iron-sulfur binding demonstrated synergistic effects, and thus appear to be integral and indispensable to pigeon MagR magnetism. These results not only extend our current understanding of the origin and complexity of MagR magnetism, but also imply a possible molecular explanation for the huge diversity in animal magnetoreception.


Asunto(s)
Columbidae , Hierro , Animales , Azufre
14.
BMC Infect Dis ; 22(1): 903, 2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36460998

RESUMEN

BACKGROUND: Kodamaea ohmeri is a rare pathogen with high mortality and is found among blood samples in a considerable proportion; however, gastrointestinal infection of K. ohmeri is extremely rare. Invasive pulmonary aspergillosis is also an uncommon fungal; these two fungal infections reported concomitantly are unprecedented. CASE PRESENTATION: We described a case of a 37-year-old male who got infected with K. ohmeri and invasive pulmonary aspergillosis. We used the mass spectrometry and histopathology to identify these two fungal infections separately. For the treatment of K. ohmeri, we chose caspofungin. As for invasive pulmonary aspergillosis, we used voriconazole, amphotericin B, and then surgery. The patient was treated successfully through the collaboration of multiple disciplines. CONCLUSIONS: We speculate that the destruction of the intestinal mucosa barrier can make the intestine one of the ways for certain fungi to infect the human body.


Asunto(s)
Fungemia , Aspergilosis Pulmonar Invasiva , Saccharomycetales , Adulto , Humanos , Masculino , Caspofungina/uso terapéutico , Fungemia/microbiología , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico
15.
Front Mol Biosci ; 9: 1051943, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36438652

RESUMEN

Iron-sulfur proteins play essential roles in a wide variety of cellular processes such as respiration, photosynthesis, nitrogen fixation and magnetoreception. The stability of iron-sulfur clusters varies significantly between anaerobic and aerobic conditions due to their intrinsic sensitivity to oxygen. Iron-sulfur proteins are well suited to various practical applications as molecular redox sensors or molecular "wires" for electron transfer. Various technologies have been developed recently using one particular iron-sulfur protein, MagR, as a magnetic tag. However, the limited protein stability and low magnetic sensitivity of MagR hindered its wide application. Here in this study, the iron-sulfur binding site of pigeon clMagR was rationally re-designed. One such mutation, T57C in pigeon MagR, showed improved iron-sulfur binding efficiency and higher iron content, as well as prolonged thermostability. Thus, clMagRT57C can serve as a prototype for further design of more stable and sensitive magnetic toolbox for magnetogenetics in the future.

16.
Proc Natl Acad Sci U S A ; 119(45): e2211228119, 2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36322742

RESUMEN

Magnetic targeting is one of the most promising approaches for improving the targeting efficiency by which magnetic drug carriers are directed using external magnetic fields to reach their targets. As a natural magnetic nanoparticle (MNP) of biological origin, the magnetosome is a special "organelle" formed by biomineralization in magnetotactic bacteria (MTB) and is essential for MTB magnetic navigation to respond to geomagnetic fields. The magnetic targeting of magnetosomes, however, can be hindered by the aggregation and precipitation of magnetosomes in water and biological fluid environments due to the strong magnetic attraction between particles. In this study, we constructed a magnetosome-like nanoreactor by introducing MTB Mms6 protein into a reverse micelle system. MNPs synthesized by thermal decomposition exhibit the same crystal morphology and magnetism (high saturation magnetization and low coercivity) as natural magnetosomes but have a smaller particle size. The DSPE-mPEG-coated magnetosome-like MNPs exhibit good monodispersion, penetrating the lesion area of a tumor mouse model to achieve magnetic enrichment by an order of magnitude more than in the control groups, demonstrating great prospects for biomedical magnetic targeting applications.


Asunto(s)
Magnetosomas , Magnetospirillum , Nanopartículas , Neoplasias , Ratones , Animales , Proteínas Bacterianas/metabolismo , Magnetosomas/química , Bacterias Gramnegativas/metabolismo , Nanopartículas/química , Campos Magnéticos , Neoplasias/metabolismo , Magnetospirillum/metabolismo
17.
Stat Med ; 41(29): 5698-5714, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36165535

RESUMEN

In medical research, it is often of great interest to have an accurate estimation of cure rates by different treatment options and for different patient groups. If the follow-up time is sufficiently long and the sample size is large, the proportion of cured patients will make the Kaplan-Meier estimator of survival function have a flat plateau at its tail, whose value indicates the overall cure rate. However, it may be difficult to estimate and compare the cure rates for all the subsets of interest in this way, due to the limit of sample sizes and curse of dimensionality. In the current literature, most regression models for estimating cure rates assume proportional hazards (PH) between different subgroups. It turns out that the estimation of cure rates for subgroups is highly sensitive to this assumption, so more flexible models are needed, especially when this PH assumption is clearly violated. We propose a new cure model to simultaneously incorporate both PH and non-PH scenarios for different covariates. We develop a stable and easily implementable iterative procedure for parameter estimation through maximization of the nonparametric likelihood function. The covariance matrix is estimated by adding perturbation weights to the estimation procedure. In simulation studies, the proposed method provides unbiased estimation for the regression coefficients, survival curves, and cure rates given covariates, while existing models are biased. Our model is applied to a study of stage III soft tissue sarcoma and provides trustworthy estimation of cure rates for different treatment and demographic groups.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Modelos de Riesgos Proporcionales , Modelos Estadísticos , Análisis de Supervivencia , Funciones de Verosimilitud , Sarcoma/terapia , Simulación por Computador
18.
Clin Lymphoma Myeloma Leuk ; 22(10): e938-e946, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35871217

RESUMEN

BACKGROUND: One key clinical challenge remains in how to sequence treatments in follicular lymphoma (FL). The chemoimmunotherapy rituximab cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (R-CHOP) has been a standard treatment option for two decades. However, there are limited data to suggest in which line R-CHOP should be used for older patients. PATIENTS AND METHODS: We leveraged population-based surveillance, epidemiology, and end results-medicare data and identified 675 patients aged ≥65 years newly diagnosed with FL from 2000 to 2009 who received R-CHOP in either the first or second line. We estimated restricted mean survival time using Kaplan-Meier curves, propensity scores (PS), and regression models comparing patients who received R-CHOP as a first versus second line. RESULTS: We found that patients who received R-CHOP as first line had significantly longer 9-year RMST than those who received R-CHOP in the second line using Kaplan-Meier curves (P = .01), PS stratification (P = .002), PS matching (P = .005), and the inverse of PS as the treatment weight (P < .0001). The subgroup analyses using linear regression models showed that the 9-year restricted mean survival time of patients who received R-CHOP as the first line was longer in patients aged ≥80 years (P = .002) and with histological grade 1 or 2 (P = .02), compared to those who received R-CHOP as second line. CONCLUSION: R-CHOP given in the first line was associated with longer overall survival compared to R-CHOP given as second line for older patients with FL.


Asunto(s)
Linfoma Folicular , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida , Doxorrubicina , Humanos , Medicare , Prednisona/efectos adversos , Rituximab/uso terapéutico , Estados Unidos/epidemiología , Vincristina/efectos adversos
19.
J Asthma Allergy ; 15: 133-144, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35140475

RESUMEN

PURPOSE: PTPRH inhibits EGFR activity directly in cancer patients and activated EGFR induces goblet cell hyperplasia and mucus hypersecretion in asthma. However, the function of PTPRH in asthma remains unknown. The purpose of this study was to access the association of PTPRH with asthma and its underlying mechanism. PATIENTS AND METHODS: We examined the PTPRH level in asthma patients (n = 108) and healthy controls (n = 35), and analyzed the correlations between PTPRH and asthma-related indicators. Human bronchial epithelial cell (HBECs) transfected with PTPRH and asthma mouse model were set up to investigate the function of PTPRH. RESULTS: The expression of PTPRH was significantly increased and correlated with pulmonary function parameters, including airway obstruction, and T-helper2 (Th2) associated markers in asthma patients. PTPRH increased in the house dust mite (HDM)-induced asthmatic mice, while Th2 airway inflammation and Muc5ac suppressed when treated with PTPRH. Accordingly, PTPRH expression was markedly increased in IL-13-stimulated HBECs but PTPRH over-expression suppressed MUC5AC. Moreover, HBECs transfected with over-expressed PTPRH inhibited the phosphorylation of EGFR, ERK1/2 and AKT, while induced against PTPRH in HBECs dephosphorylated of EGFR, ERK1/2 and AKT. CONCLUSION: PTPRH reduces MUC5AC secretion to alleviate airway obstruction in asthma via potential phosphorylating of EGFR/ERK1/2/AKT signaling pathway, which may provide possible therapeutic implications for asthma.

20.
J Hazard Mater ; 422: 126936, 2022 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-34463272

RESUMEN

Cadmium (Cd) and dichlorodiphenyltrichloroethane (DDT) are frequently detected in agricultural soils, which poses a threat to public health. This study investigated the effects of inoculation of king grass with Piriformospora indica on the remediation of soils co-contaminated with Cd and DDTs. After treatment for 90 days, the dry shoot and root biomass of king grass inoculated with P. indica markedly increased by 13.0-15.8% and 24.1-46.4%, respectively, compared with those of uninoculated plants. Inoculation with P. indica also increased the uptake of Cd and DDTs by shoots and roots of king grass. The removal efficiency of Cd and DDTs from soils reached 4.88-17.4% and 48.4-51.0%, respectively, in the presence of king grass inoculated with P. indica. Under three Cd-DDTs contamination conditions, root secretion of organic acids, alcohol, and polyamines was distinctively stimulated by P. indica inoculation of king grass compared with planting king grass alone. After phytoremediation, changes in soil bacterial and fungal community composition occurred at different contamination levels. Overall, the results showed that king grass associated with P. indica can be adopted for phytoextraction of Cd and DDTs from moderately contaminated soils by regulating root excretion and reshaping rhizosphere microbial community structure.


Asunto(s)
Microbiota , Contaminantes del Suelo , Basidiomycota , Biodegradación Ambiental , Cadmio/análisis , Raíces de Plantas/química , Poaceae , Rizosfera , Suelo , Contaminantes del Suelo/análisis
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