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1.
J Am Chem Soc ; 2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39099104

RESUMEN

Synthesizing anisotropic polymeric nanoparticles (NPs) with well-defined shapes, dimensions, and molecular orientations is a very challenging task. Herein, we report the synthesis of surprisingly highly uniform shape-anisotropic polymer NPs with uniaxial internal molecular orientation. Keys to our method are synchronized polymerization and self-assembly (SPSA), which can even be realized by regular dispersion polymerization. This is demonstrated using a monomer containing a rigid 4-nitroazobenzene (NAB) side group. The short nucleation period, the completion of microphase separation before molecular motion is frozen, and sufficient low particle/solvent interfacial tension are shown to be the origins of the highly uniform dimensions, single liquid crystal domains, and well-defined anisotropic shape of particles. The liquid crystallization ability of the polymers, control of molecular weight distribution, and the polymerization kinetics are identified as three key factors controlling the NP formation. The uniformity of these NPs facilitates their SA formation into colloidal crystals. The particles exhibit optically anisotropic properties depending on orientations and, in particular, show intriguing photoswitchable LC-glass (order-disorder) transition, which can be used for the detection of ultraviolet (UV) light and allows the fabrication of photoreversible colloidal films.

2.
BMC Genomics ; 24(1): 781, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38102559

RESUMEN

BACKGROUND: Odorant-binding proteins (OBPs) are essential in insect's daily behaviors mediated by olfactory perception. Megachile saussurei Radoszkowski (Hymenoptera, Megachilidae) is a principal insect pollinating alfalfa (Medicago sativa) in Northwestern China. The olfactory function have been less conducted, which provides a lot of possibilities for our research. RESULTS: Our results showed that 20 OBPs were identified in total. Multiple sequence alignment analysis indicated MsauOBPs were highly conserved with a 6-cysteine motif pattern and all belonged to the classic subfamily, coding 113-196 amino acids and sharing 41.32%-99.12% amino acid identity with known OBPs of other bees. Phylogenetic analysis indicated there were certain homologies existed among MsauOBPs and most sequences were clustered with that of Osmia cornuta (Hymenoptera, Megachilidae). Expression analysis showed the identified OBPs were mostly enriched in antennae instead of other four body parts, especially the MsauOBP2, MsauOBP3, MsauOBP4, MsauOBP8, MsauOBP11 and MsauOBP17, in which the MsauOBP2, MsauOBP4 and MsauOBP8 presented obvious tissue-biased expression pattern. Molecular docking results indicated MsauOBP4 might be the most significant protein in recognizing alfalfa flower volatile 3-Octanone, while MsauOBP13 might be the most crucial protein identifying (Z)-3-hexenyl acetate. It was also found the lysine was a momentous hydrophilic amino acid in docking simulations. CONCLUSION: In this study, we identified and analyzed 20 OBPs of M. saussurei. The certain homology existed among these OBPs, while some degree of divergence could also be noticed, indicating the complex functions that different MsauOBPs performed. Besides, the M. saussurei and Osmia cornuta were very likely to share similar physiological functions as most of their OBPs were clustered together. MsauOBP4 might be the key protein in recognizing 3-Octanone, while MsauOBP13 might be the key protein in binding (Z)-3-hexenyl acetate. These two proteins might contribute to the alfalfa-locating during the pollination process. The relevant results may help determine the highly specific and effective attractants for M. saussurei in alfalfa pollination and reveal the molecular mechanism of odor-evoked pollinating behavior between these two species.


Asunto(s)
Himenópteros , Receptores Odorantes , Abejas , Animales , Himenópteros/metabolismo , Odorantes , Secuencia de Aminoácidos , Filogenia , Simulación del Acoplamiento Molecular , Perfilación de la Expresión Génica , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Aminoácidos/metabolismo , Proteínas de Insectos/metabolismo , Antenas de Artrópodos/metabolismo , Transcriptoma
3.
J Am Chem Soc ; 145(50): 27664-27671, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38038486

RESUMEN

The use of carbon materials in porous electrodes has impressive advantages. However, precisely tailoring the multilevel pore structure of carbon electrodes remains an unsolved challenge. Here, we report a highly efficient site-selective growth strategy to synthesize colloidal carbon rings by templating patchy droplets. Carbon rings are used for the direct fabrication of self-standing porous electrodes with hierarchical pores for lithium-oxygen batteries (LOBs). In situ atomic force microscopy reveals that during discharge the discharge products densely nucleate and grow on carbon rings, demonstrating that such rings are a very potential electrode material in LOBs. The hollow carbon ring electrode (HCRE) possesses micrometer-scale channels formed by random packing of rings and nanochannels consisting of ring-shaped hollow cavities connected by nanosized pores in the wall. Both channels contribute to ion transportation and gas diffusion, but the storage of the discharge products mainly lies in micrometer-scale channels, leading to a high discharge capacity of LOBs (20 658 mAh/g). Our work paves a new way to construct hierarchically porous electrodes for application in electrocatalysis and electrochemical energy storage.

4.
Environ Res ; 218: 114937, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36435489

RESUMEN

The use of biochar materials as catalysts to activate persulfate (PS) for the degradation of antibiotics has attracted much attention. In this study, a carbonaceous material (Cu/Zn-SBC) was prepared from sewage sludge by hydrothermal modification. The efficiency of PS activation by Cu/Zn-SBC was investigated using tetracycline (TC) as the model antibiotic. In the Cu/Zn-SBC + PS system, the TC removal rate reached 90.13% at 10 min and exceeded 99% within 4 h. This not only met the requirement of removing large amounts of pollutants in a short time but also achieved the complete removal of pollutants in the subsequent time. Additionally, the Cu/Zn-SBC + PS system was found to be dominated by radical and nonradical pathways. Cu, hydroxyl and carboxyl groups on the surface of Cu/Zn-SBC promoted the production of free radicals and non-free radicals. Under several changes in reaction conditions and water environment factors, the TC removal rate remained above 85% within 10 min. Furthermore, the removal rate of TC was still 85.79% when Cu/Zn-SBC combined with PS was reused twice and 77.14% when reused four times. This study provides an ideal solution for the treatment of sewage sludge, and offers a stable and efficient material for removing antibiotics from wastewater.


Asunto(s)
Antibacterianos , Contaminantes Químicos del Agua , Aguas del Alcantarillado , Contaminantes Químicos del Agua/análisis , Carbón Orgánico , Tetraciclina
5.
Molecules ; 28(4)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36838918

RESUMEN

Confusoside (CF), a major chemical compound in the leaves of Anneslea fragrans Wall., is a dihydrochalcone glycoside with excellent antioxidant and anti-inflammatory effects. However, the hepatoprotective effect of CF has not been described. This study aimed to explore the hepatoprotective effect of CF against acetaminophen (APAP)-induced hepatic injury in HepG2 cells. First, the potential hepatoprotective effect mechanisms of CF were predicted by network pharmacology and were thought to involve reducing inflammation and inhibiting apoptosis. Target proteins (phosphatidylinositol3-kinase (PI3K) and caspase-3 (CASP3)) were found via molecular docking analysis. To verify the predicted results, an analysis of biological indicators was performed using commercial kits and Western blotting. The results showed that CF significantly decreased the levels of liver injury biomarkers (ALT, AST, and LDH), strongly inhibited the production of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and the NO level via inhibiting the activation of the NF-κB signaling pathway, and markedly regulated the expression levels of Bcl2, Bax, and cleaved-CASP3/9 proteins by activating the PI3K-CASP3 apoptosis pathway. The results demonstrated that CF has a therapeutic effect on APAP-induced liver injury by inhibiting intracellular inflammation and cell apoptosis, indicating that CF may be used as a potential reagent for the prevention and treatment of APAP-induced liver injury.


Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Fitoquímicos , Humanos , Acetaminofén/efectos adversos , Caspasa 3/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Inflamación/metabolismo , Hígado , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Células Hep G2 , Fitoquímicos/farmacología
6.
Anal Chem ; 94(46): 16069-16078, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36356236

RESUMEN

Microneedles (MNs) are currently one of the most promising tools for skin interstitial fluid (ISF)-based biosensing, while it is still a challenge to expand the detectable biomarkers in ISF due to limited MNs types and detection techniques. Herein, highly sensitive internal-standard surface-enhanced Raman scattering microneedles (IS-SERS-MNs) were developed, which enabled the reliable detection of bacterial metabolites in ISF as new detectable biomarkers for infection diagnosis. The developed IS-SERS-MNs can not only directly detect pyocyanin (a representative bacterial metabolite) present in mouse dermal ISF but also indirectly detect pyocyanin in the hypodermis via its diffusion into the dermis, revealing a new possible pathway for the source of biomarkers in dermal ISF. Moreover, the SERS signal of pyocyanin was also clearly detected at real mouse wounds, indicating that the developed IS-SERS-MNs have great potential in minimally invasive and painless diagnosis of bacterial infection via a new ISF route. This work not only develops IS-SERS-MNs as a powerful tool for expanding the application of SERS-based MNs but also provides a new chance for ISF-related infection diagnosis.


Asunto(s)
Líquido Extracelular , Espectrometría Raman , Ratones , Animales , Líquido Extracelular/metabolismo , Agujas , Piocianina , Piel/metabolismo , Biomarcadores/metabolismo
7.
Anal Chem ; 94(16): 6347-6354, 2022 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-35427108

RESUMEN

Liquid droplets rectors have been used in clinical diagnosis, high throughput screening and bioassay. However, it is challenging for droplet reactors to be used in practical applications due to the difficulty of uniformly mixing ultrasmall volumes of samples and the lack of rapid and high-precision detection protocols. Here, we have developed an acoustic droplet system for rapid and efficient biological detection and chemical screening. By employing acoustic wave devices, rapid and nondestructive uniform mixing of ∼nL-µL droplets can be achieved. By the acoustophoretic force, the perturbation of the droplets can quickly concentrate the sample and increase the detection limit by five times. Through the color reaction and the coordinated detection of photodiodes, we have developed a biomarker detection protocol with short reaction time and high accuracy. As a proof-of-concept application, we demonstrated that this system can detect ultrasmall or low-abundance samples faster and more accurately, highlighting its wide application in analytical chemistry, basic research, and clinical medicine.


Asunto(s)
Técnicas Analíticas Microfluídicas , Acústica , Bioensayo , Ensayos Analíticos de Alto Rendimiento , Sonido
8.
Opt Express ; 30(2): 1664-1674, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35209322

RESUMEN

Nonlinear Compton scattering is an inelastic scattering process where a photon is emitted due to the interaction between an electron and an intense laser field. With the development of X-ray free-electron lasers, the intensity of X-ray laser is greatly enhanced, and the signal from X-ray nonlinear Compton scattering is no longer weak. Although the nonlinear Compton scattering by an initially free electron has been thoroughly investigated, the mechanism of nonrelativistic nonlinear Compton scattering of X-ray photons by bound electrons is unclear yet. Here, we present a frequency-domain formulation based on the nonperturbative quantum electrodynamics to study nonlinear Compton scattering of two photons by an atom in a strong X-ray laser field. In contrast to previous theoretical works, our results clearly reveal the existence of a redshift phenomenon observed experimentally by Fuchs et al.(Nat. Phys.)11, 964(2015) and suggest its origin as the binding energy of the electron as well as the momentum transfer from incident photons to the electron during the scattering process. Our work builds a bridge between intense-laser atomic physics and Compton scattering processes that can be used to study atomic structure and dynamics at high laser intensities.

9.
J Gastroenterol Hepatol ; 37(9): 1756-1767, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35849493

RESUMEN

BACKGROUND AND AIMS: Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in colorectal cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown. METHODS: We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL) using 16S-rRNA-based next-generation sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal effect between gut microbiota and anastomotic healing. Notably, RNA-seq in the anastomotic tissue of the latter experimental model was utilized to discover the potential molecular mechanism. RESULTS: Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF-ß/Smad signaling pathways were upregulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients is dependent on the TGF-ß/Smad-induced EMT in vitro and in vivo. CONCLUSIONS: Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF-ß/Smad-induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.


Asunto(s)
Microbioma Gastrointestinal , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Animales , Colágeno/metabolismo , Colon/metabolismo , Colon/cirugía , Células Epiteliales/metabolismo , Ratas , Factor de Crecimiento Transformador beta
10.
Neurosurg Rev ; 45(2): 1195-1204, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34716511

RESUMEN

Hypertensive brainstem hemorrhage (HBSH) is of high morbidity and mortality rate. But many clinical studies were written in Chinese and had not been reviewed. A systemic review of Chinese clinical studies for HBSH was performed. A systemic literature search in PubMed, Web of Science, China National Knowledge Infrastructure, and Weipu database and Wanfang database up to March 2020 was performed. Clinical control studies including a surgical evacuation (SE) group and a conservative management (CM) group were included. The clinical outcome and mortality rate were compared. Ten cohort studies were included, involving 944 participants (304 in the SE group and 640 in the CM group). All included patients were comatose, with the average age ranged from 45 to 65 years old. Among five studies using mRS or GOS as outcome score, a total of 16.6% (89/535) of patients achieve self-maintenance with minor disabilities, including 26.8% (34/127) in the SE group and 13.5% (55/408) in the CM group. The overall mortality rate in the SE group was 27.6%, ranged from 9.3 to 60% among different studies. The overall mortality rate in the CM group was 60.6%, ranged from 18.5 to 100.0%. Elder and comatose HBSH patients are not contraindicated for surgery. The review showed that this group of patients obtained a better outcome and lower mortality rate after surgical treatment. The quality of included studies was relatively low, but a high-level clinical study on HBSH is of great difficulty, as both clinicians and patients faced various sociological issues rather than pure medical problems.


Asunto(s)
Tronco Encefálico , Hemorragia Cerebral , Anciano , Tronco Encefálico/cirugía , Hemorragia Cerebral/cirugía , China , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Resultado del Tratamiento
11.
Pak J Med Sci ; 38(8): 2259-2265, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36415226

RESUMEN

Objective: To compare and analyze the clinical effects of ultrasound-guided percutaneous nephrolithotripsy and X-ray-guided percutaneous nephrolithotripsy in the treatment of complex renal calculi without hydronephrosis. Methods: Eighty patients with multiple stones without hydronephrosis were admitted at Department of Ultrasound Diagnosis, The first medical center of Chinese PLA General Hospital from January 21, 2020 to December 21, 2020 randomly divided: into two groups: experimental group and control group, with 40 cases in each group. Patients in the experimental group were treated with ultrasound-guided percutaneous nephrolithotomy, while those in the control group were treated with X-ray-guided percutaneous nephrolithotomy. The differences in operation time, channel establishment time, channel number, blood loss and stone clearance rate between the two groups were compared and analyzed. Venous blood was drawn before surgery and on the first day after surgery, and serum creatinine, urea nitrogen, blood ß2-microglobulin, blood uric acid and other renal indexes were detected. Moreover, renal parenchymal injury was compared between the two groups by renal static imaging, and the incidence of postoperative complications such as pain, fever, urination through incision and injury of surrounding organs were compared and analyzed. Results: The operation time, channel establishment time, channel number and blood loss in the experimental group were significantly lower than those in the control group, with statistically significant differences (p<0.05). The postoperative renal injury score of the experimental group was 1.03±0.37, which was lower than 1.85±0.63 of the control group (p=0.00); Postoperative Cr, BUN, blood ß 2-microglobulin and other indicators in the control group were significantly higher than those in the experimental group, with statistically significant differences (p<0.05). The incidence of peripheral organ injury in experimental group was lower than that in control group, with a statistically significant difference (p=0.04). Conclusion: Ultrasound-guided percutaneous nephrolithotomy is a safe and effective treatment regimen, boasting various advantages such as real-time monitoring of the surgical process, more accurate and clear channel establishment, avoidance of large vessel injury, shortening of surgical time, alleviation of kidney injury and reduction of surgical complications, which is more advantageous for the treatment of complex renal calculi.

12.
Angew Chem Int Ed Engl ; 61(3): e202112507, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-34800076

RESUMEN

The use of simple building blocks to produce hierarchical and porous structured materials is highly desired. Rings are simple colloidal particles but unique for their internal cavities. Here we report the self-assembly (SA) of colloidal rings with tunable asymmetry mediated by a depletion force and demonstrate that a variety of porous colloidal superstructures from microtubes, flexible chains, (plastic) crystals to highly open liquid crystals (LCs) can be formed along the predesigned SA paths. In particular, the SA is staged in binary or ternary systems. Large rings first form complex ring-in-ring and ring-in-ring-in-ring assemblies by capturing smaller rings, which, as new building blocks, can further form multi-walled microtubes and open columnar LCs. Moreover, a plastic columnar LC with alternating intracolumnar stacking is found from asymmetrical rings. The SA with colloidal rings opens a new avenue to construct hierarchical and porous ordered metamaterials.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 786-791, 2022 Jul 15.
Artículo en Zh | MEDLINE | ID: mdl-35894194

RESUMEN

OBJECTIVES: To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome. RESULTS: Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment. CONCLUSIONS: ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Hipertensión Pulmonar , Enfermedades Pulmonares , Síndrome de Circulación Fetal Persistente , Niño , Humanos , Hipertensión Pulmonar/terapia , Recién Nacido , Síndrome de Circulación Fetal Persistente/terapia , Estudios Retrospectivos , Resultado del Tratamiento
14.
Cancer Sci ; 112(9): 3469-3483, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34157192

RESUMEN

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c+ DCs, CD8+ CD11c+ DCs and CD103+ CD11c+ DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8+ T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8+ T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8+ T cells or CD8+ CD11c+ DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8+ DCs and CD103+ DCs mediated CD8+ T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8+ T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8+ DCs and CD103+ DCs mediated tumor-specific multi-functional CD8+ T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.


Asunto(s)
Antígenos CD/metabolismo , Antígenos de Neoplasias/administración & dosificación , Antígenos CD8/metabolismo , Linfocitos T CD8-positivos/inmunología , Anhidrasa Carbónica IX/administración & dosificación , Carcinoma de Células Renales/terapia , Quitosano/química , Células Dendríticas/inmunología , Sistemas de Liberación de Medicamentos/métodos , Inmunidad , Inmunización/métodos , Cadenas alfa de Integrinas/metabolismo , Neoplasias Renales/terapia , Nanopartículas/química , Proteínas Proto-Oncogénicas c-myc/administración & dosificación , Vacunas de ADN/administración & dosificación , Animales , Antígenos de Neoplasias/genética , Anhidrasa Carbónica IX/genética , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Modelos Animales de Enfermedad , Femenino , Células HEK293 , Humanos , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Ratones , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-myc/genética , Resultado del Tratamiento , Vacunas de ADN/inmunología
15.
J Cell Mol Med ; 24(18): 10744-10755, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32725966

RESUMEN

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIXpromotor )-controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIXpromotor -AIM2 adenoviruses (Ad-CAIXpromotor -AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad-CAIXpromotor , Ad-CAIXpromotor -AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786-O cells or OSRC-2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC-2-xenograft mice. The tumour growth was remarkably inhibited in Ad-CAIXpromotor -AIM2-treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD-CMK resulted in the reduction of anti-tumour activity by Ad-CAIXpromotor -AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad-CAIXpromotor -AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour-specific Ad-CAIXpromotor -AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2-based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.


Asunto(s)
Adenovirus Humanos/fisiología , Anhidrasa Carbónica IX/genética , Carcinoma de Células Renales/terapia , Proteínas de Unión al ADN/fisiología , Neoplasias Renales/terapia , Viroterapia Oncolítica , Regiones Promotoras Genéticas/genética , Proteínas E1A de Adenovirus/biosíntesis , Proteínas E1A de Adenovirus/genética , Adenovirus Humanos/genética , Clorometilcetonas de Aminoácidos/farmacología , Animales , Carcinoma de Células Renales/secundario , Caspasa 1/análisis , Línea Celular , Línea Celular Tumoral , Citocinas/análisis , Proteínas de Unión al ADN/genética , Genes Sintéticos , Humanos , Inflamasomas/efectos de los fármacos , Neoplasias Renales/patología , Túbulos Renales/citología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayo de Tumor de Célula Madre , Replicación Viral , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Pharmacol Res ; 159: 104987, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32512044

RESUMEN

In the present study, the concentrations of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) in 2245 batches of Chinese herbal medicines (CHMs) were measured using inductively coupled plasma-mass spectroscopy (ICP-MS). We developed a risk assessment strategy that assessed the heavy metal-associated health risk of CHMs based on our large dataset. Using a combination of the mean and 95th percentile (P95) values of the chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI), and lifetime cancer risk (CR), the health risks of the average exposure population and the high exposure population were estimated, respectively. To obtain a precise and realistic risk assessment, the exposure frequency and exposure duration were determined using questionnaire data from 20,917 randomly selected volunteers. Additionally, given the specific ingestion characteristics of CHMs, the safety factor and the transfer rates of heavy metals were highlighted as well. The concentrations of Pb, Cd, As, Hg, and Cu in 2245 batches of CHMs were 1.566, 0.299, 0.391, 0.074, and 8.386 mg/kg, respectively. The mean HI values indicated that consumption of most CHMs would not pose an unacceptable health risk to the average exposure population, except for argy wormwood leaf (1.326), morinda root (2.095), plantain herb (1.540), chrysanthemum flower (1.146), and Indian madder root (2.826). In addition, CR assessment for Pb and As revealed that, for the average exposure population, the risk of developing cancers was lower than the acceptable levels (1 × 10-4) in the clinic. However, the P95 of the HI and CR values indicated that more attention should be paid to the systemic effects of CHMs in terms of both non-carcinogenic and carcinogenic health risks for the high exposure population. Furthermore, in order to serve population health better, national and international guidelines have now been established. The risk assessment strategy developed in this study is the first of its kind, and contributed to the risk assessment, guidelines, and safety standards for heavy metals in CHMs.


Asunto(s)
Contaminación de Medicamentos , Medicamentos Herbarios Chinos/análisis , Metales Pesados/análisis , Adolescente , Adulto , Seguridad de Productos para el Consumidor , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Masculino , Espectrometría de Masas , Metales Pesados/efectos adversos , Persona de Mediana Edad , Seguridad del Paciente , Control de Calidad , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
17.
Nanotechnology ; 31(49): 495102, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-32990263

RESUMEN

Constructing biological affinity devices is considered as an effective strategy for isolating circulating tumor cells (CTCs), and electrospun nanofibers (ESNFs) have recently received attention. However, the current research focuses on polymer fibers, and fabricating stimuli-responsive inorganic nanofibers for cancer diagnosis and analysis is still challenging. In this work, Zn-Mn oxide nanofibers (ZnMnNFs) are used to capture and purify cancer cells after modification with specific antibodies. Then, the hierarchical nanofibers are degraded by reductive weak acid to release the captured cells efficiently without residues. Fusion of Zn and Mn, two transition metals, enhances the surface activity of oxides so that ZnMnNFs are easier to be degraded and modified. By using MCF-7 cancer cells, the cell capture efficiency of ZnMnNFs is up to 88.2%. Furthermore, by using citric acid, it is discovered that, by comparison with Mn oxide nanofibers, the cell release efficiency of ZnMnNFs is improved to 95.1% from 15.4%. In addition, the viability of released cells exceeds 90%. Lastly, the robustness of ZnMnNFs substrates is tested in peripheral blood from breast cancer patients (BCP) and colorectal cancer patients (CCP). Combined with fluorescence labeling, CTCs are confirmed to be isolated from all the clinical samples. This is the first trial of using ternary inorganic ESNFs for cancer cell capture. It is anticipated that the degradable ESNFs will provide biocompatible theranostic platforms and overcome the current limitations of cell release for high-precision gene analysis.


Asunto(s)
Separación Celular/métodos , Manganeso/química , Nanofibras/química , Células Neoplásicas Circulantes/patología , Óxidos/química , Zinc/química , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Supervivencia Celular , Femenino , Humanos , Células MCF-7
18.
Nano Lett ; 19(4): 2215-2222, 2019 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-30543300

RESUMEN

Zika virus (ZIKV) has emerged as a global health threat due to its unexpected causal link to devastating neurological disorders such as fetal microcephaly; however, to date, no approved vaccine or specific treatment is available for ZIKV infection. Here we develop a biomimetic nanodecoy (ND) that can trap ZIKV, divert ZIKV away from its intended targets, and inhibit ZIKV infection. The ND, which is composed of a gelatin nanoparticle core camouflaged by mosquito medium host cell membranes, effectively adsorbs ZIKV and inhibits ZIKV replication in ZIKV-susceptible cells. Using a mouse model, we demonstrate that NDs significantly attenuate the ZIKV-induced inflammatory responses and degenerative changes and thus improve the survival rate of ZIKV-challenged mice. Moreover, by trapping ZIKV, NDs successfully prevent ZIKV from passing through physiologic barriers into the fetal brain and thereby mitigate ZIKV-induced fetal microcephaly in pregnant mice. We anticipate that this study will provide new insights into the development of safe and effective protection against ZIKV and various other viruses that threaten public health.


Asunto(s)
Microcefalia/prevención & control , Nanopartículas/administración & dosificación , Infección por el Virus Zika/prevención & control , Virus Zika/efectos de los fármacos , Animales , Biomimética/métodos , Membrana Celular/efectos de los fármacos , Membrana Celular/virología , Culicidae/efectos de los fármacos , Culicidae/virología , Modelos Animales de Enfermedad , Femenino , Feto , Gelatina/administración & dosificación , Gelatina/química , Humanos , Ratones , Microcefalia/patología , Microcefalia/virología , Nanopartículas/química , Embarazo , Virus Zika/patogenicidad , Infección por el Virus Zika/patología , Infección por el Virus Zika/virología
19.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3877-3882, 2020 Aug.
Artículo en Zh | MEDLINE | ID: mdl-32893584

RESUMEN

To establish the HPLC-ELSD specific chromatogram analysis method of Rehmanniae Radix and Rehmanniae Radix Prae-parata, and analyze and compare their chemical compositions, so as to reveal the change regularity of compositions during the proces-sing. By HPLC-ELSD method, the chromatographic column for Prevail Carbohydrate ES(4.6 mm ×250 mm, 5 µm) was adopted, with acetonitrile(A)-water(B) as mobile phase for gradient elution, and the evaporative light-scattering detector was used. A total of 23 batches of Rehmannia Radix samples, and 25 batches of Rehmanniae Radix Praeparata samples and processing dynamic samples were compared. The established method had a great repeatability, precision and stability. Eight common chromatographic peaks were extracted from 23 batches of Rehmanniae Radix samples, 8 common peaks were extracted from 25 Rehmanniae Radix Praeparata, and 7 chromatographic peaks were identified. The composition ratio of Rehmannia Radix was changed greatly during the processing. When the simila-rity≥0.95 and the fructose peak area was more than 2 times of stachyose tetrahydrate or more than 20 times of raffinose, the processing degree conformed to the requirements of empirical identification. The three main oligosaccharides of Rehmanniae Radix were sucrose that was heated to generate fructose and glucose, stachyose tetrahydrate that was heated to generate melibiose, sucrose and fructose, and stachyose tetrahydrate that was heated to generate manninotriose. The change in the index of proportion between monosaccharides and oligosaccharides can be used as the quantitative criterion for the processing quality of Rehmanniae Radix Praeparata.


Asunto(s)
Medicamentos Herbarios Chinos , Rehmannia , Cromatografía Líquida de Alta Presión , Monosacáridos , Raíces de Plantas
20.
Nanotechnology ; 30(8): 084001, 2019 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-30523921

RESUMEN

We report a digital acoustofluidic device for on-demand and oil-free droplet generation. By applying a programmed radio frequency signal to a circular interdigital transducer, the dynamic focused acoustic pressure profiles generated rise up and dispense sample liquids from a reservoir to dynamically eject the droplets into the air. Our device allows droplets to be dispensed on demand with precisely controlled generation time and sequence, and accurate droplet volume. Moreover, we also demonstrate the generation of a droplet with a volume of 24 pL within 10 ms, as well as the encapsulation of a single cell into droplets. This acoustofluidic droplet generation technique is simple, biocompatible, and enables the on-demand droplet generation and encapsulation of many different biological materials with precise control, which is promising for single cell sampling and analysis applications.

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