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1.
Microorganisms ; 12(5)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38792792

RESUMO

To gain an in-depth understanding of the diversity and composition of soil Acidobacteria in five different forest types in typical temperate forest ecosystems and to explore their relationship with soil nutrients. The diversity of soil Acidobacteria was determined by high-throughput sequencing technology. Soil Acidobacteria's alpha-diversity index and soil nutrient content differed significantly among different forest types. ß-diversity and the composition of soil Acidobacteria also varied across forest types. Acidobacterial genera, such as Acidobacteria_Gp1, Acidobacteria_Gp4, and Acidobacteria_Gp17, play key roles in different forests. The RDA analyses pointed out that the soil pH, available nitrogen (AN), carbon to nitrogen (C/N) ratio, available phosphorus (AP), total carbon (TC), and total phosphorus (TP) were significant factors affecting soil Acidobacteria in different forest types. In this study, the diversity and composition of soil Acidobacteria under different forest types in a temperate forest ecosystem were analyzed, revealing the complex relationship between them and soil physicochemical properties. These findings not only enhance our understanding of soil microbial ecology but also provide important guidance for ecological conservation and restoration strategies for temperate forest ecosystems.

2.
Cell Mol Biol (Noisy-le-grand) ; 70(1): 239-245, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38372088

RESUMO

UTP23 (UTP23 small subunit processome component) plays a pivotal role in the intricate processing and maturation of the small subunit of ribosomes within the nucleolus. In cases of nucleolar stress, such as those observed in certain tumor cells, the aberrant nucleolar organization and structure can lead to the translocation of nucleolar proteins into the nucleus or cytoplasm, consequently impacting the physiological processes of the tumor cells through non-ribosome-related functions. Our investigation revealed altered localization of UTP23 protein in colorectal cancer clinical tissue samples. Upon analyzing UTP23 expression and its correlation with patient prognosis in a cohort of 143 colorectal cancer patients, the result suggested that high cytoplasmic expression pattern of UTP23 was occured in early-stage metastasis-free colorectal cancer and was significantly associated with poor prognosis. Furthermore, we demonstrated that cytoplasmic expression of UTP23 significantly promoted the metastatic and invasive capabilities of colorectal cancer cells, which was not showed in the nucleollcalised UTP23. Intriguingly, mass spectrometry result suggested that KRT5 bind to UTP23 and showed a regulatory influence on UTP23 metastatic potential in colorectal cancer cells. Conclusively, our study demonstrated that the localization of UTP23 play a key role in colorectal cancer metastatic progression, which may serve as a novel prognostic indicator.


Assuntos
Neoplasias Colorretais , Proteínas Nucleares , Ribossomos , Humanos , Neoplasias Colorretais/patologia , Citosol/metabolismo , Proteínas Nucleares/metabolismo , Ribossomos/metabolismo
3.
Small ; : e2308715, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412419

RESUMO

Biomolecular piezoelectric materials show great potential in the field of wearable and implantable biomedical devices. Here, a self-assemble approach is developed to fabricating flexible ß-glycine piezoelectric nanofibers with interfacial polarization locked aligned crystal domains induced by Nb2 CTx nanosheets. Acted as an effective nucleating agent, Nb2 CTx nanosheets can induce glycine to crystallize from edges toward flat surfaces on its 2D crystal plane and form a distinctive eutectic structure within the nanoconfined space. The interfacial polarization locking formed between O atom on glycine and Nb atom on Nb2 CTx is essential to align the ß-glycine crystal domains with (001) crystal plane intensity extremely improved. This ß-phase glycine/Nb2 CTx nanofibers (Gly-Nb2 C-NFs) exhibit fabulous mechanical flexibility with Young's modulus of 10 MPa, and an enhanced piezoelectric coefficient of 5.0 pC N-1 or piezoelectric voltage coefficient of 129 × 10-3 Vm N-1 . The interface polarization locking greatly improves the thermostability of ß-glycine before melting (≈210°C). A piezoelectric sensor based on this Gly-Nb2 C-NFs is used for micro-vibration sensing in vivo in mice and exhibits excellent sensing ability. This strategy provides an effective approach for the regular crystallization modulation for glycine crystals, opening a new avenue toward the design of piezoelectric biomolecular materials induced by 2D materials.

4.
Foods ; 13(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38338610

RESUMO

Pu-erh tea is a famous tea worldwide, and identification of the geographical origin of Pu-erh tea can not only protect manufacture's interests, but also boost consumers' confidence. However, tree age may also influence the fingerprints of Pu-erh tea. In order to study the effects of the geographical origin and tree age on the interactions of stable isotopes and multi-elements of Pu-erh tea, 53 Pu-erh tea leaves with three different age stages from three different areas in Yunnan were collected in 2023. The δ13C, δ15N values and 25 elements were determined and analyzed. The results showed that δ13C, δ15N, Mg, Mn, Fe, Cu, Zn, Rb, Sr, Y, La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu had significant differences among different geographical origins (p < 0.05). Mn content was significantly influenced by region and tree age interaction. Based on multi-way analysis of variance, principal component analysis and step-wised discriminant analysis, 24 parameters were found to be closely related to the geographical origin rather than tree age, and the geographical origin of Pu-erh tea can be 100.0% discriminated in cross-validation with six parameters (δ13C, δ15N, Mn, Mg, La, and Tb). The study could provide references for the establishment of a database for the traceability of Pu-erh tea, and even the identification of tea sample regions with different tree ages.

5.
Oncogene ; 43(10): 714-728, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38225339

RESUMO

Cisplatin resistance is a major cause of therapeutic failure in patients with high-grade serous ovarian cancer (HGSOC). Long noncoding RNAs (lncRNAs) have emerged as key regulators of human cancers; however, their modes of action in HGSOC remain largely unknown. Here, we provide evidence to demonstrate that lncRNA Platinum sensitivity-related LncRNA from Ascites-Derived Exosomes (PLADE) transmitted by ascites exosomes enhance platinum sensitivity in HGSOC. PLADE exhibited significantly decreased expression in ascites exosomes and tumor tissues, as well as in the corresponding metastatic tumors from patients with HGSOC cisplatin-resistance. Moreover, HGSOC patients with higher PLADE expression levels exhibited longer progression-free survival. Gain- and loss-of-function studies have revealed that PLADE promotes cisplatin sensitivity by suppressing cell proliferation, migration and invasion, and enhancing apoptosis in vitro and in vivo. Furthermore, the functions of PLADE in increasing cisplatin sensitivity were proven to be transferred by exosomes to the cultured recipient cells and to the adjacent tumor tissues in mouse models. Mechanistically, PLADE binds to and downregulates heterogeneous nuclear ribonucleoprotein D (HNRNPD) by VHL-mediated ubiquitination, thus inducing an increased amount of RNA: DNA hybrids (R-loop) and DNA damage, consequently promoting cisplatin sensitivity in HGSOC. Collectively, these results shed light on the understanding of the vital roles of long noncoding RNAs in cancers.


Assuntos
Neoplasias Ovarianas , RNA Longo não Codificante , Animais , Camundongos , Feminino , Humanos , RNA Longo não Codificante/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Ascite/genética , Estruturas R-Loop , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética
6.
Sci Total Environ ; 914: 169835, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190896

RESUMO

Cyanophyta has the potential to produce biocrude via hydrothermal liquefaction (HTL). However, aqueous phase products (APs), as by-products of HTL, pose a risk of eutrophication for the high levels of carbon, nitrogen, and phosphorus. Supercritical water oxidation (SCWO) can efficiently convert organics into small molecules, offering a technique for the harmless treatment of APs. Effects of holding time, pressure, and moisture content on the biocrude yields from isothermal HTL (300 °C) and fast HTL (salt bath temperature of 500 °C) were comprehensively investigated. Biocrude properties were characterized by elemental analysis, FT-IR and GC-MS. Subsequently, the APs obtained under the conditions producing the highest biocrude yield were subjected to SCWO at 550 °C with different oxidation coefficients (n) from 0 to 2. Removal rates of chemical oxygen demand (COD), ammonia nitrogen (NH3-N), and total phosphorus (TP) were further explored. The results show that the highest biocrude yields from isothermal HTL and fast HTL were 24.2 wt% (300 °C, 1800 s, 25 MPa, and 80 wt% moisture content) and 21.9 wt% (500 °C, 40 s, 25 MPa, and 80 wt% moisture content), respectively. The biocrude primarily consisted of N-containing heterocyclic compounds, amides, and acids. SCWO effectively degraded the COD and TP in APs, while the NH3-N required further degradation. At n = 2, the highest removal rates of COD, NH3-N and TP were 98.5 %, 22.6 % and 89.1 %, respectively.

7.
Nat Commun ; 14(1): 8386, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104122

RESUMO

Bioelectronic medicine is a rapidly growing field where targeted electrical signals can act as an adjunct or alternative to drugs to treat neurological disorders and diseases via stimulating the peripheral nervous system on demand. However, current existing strategies are limited by external battery requirements, and the injury and inflammation caused by the mechanical mismatch between rigid electrodes and soft nerves. Here we report a wireless, leadless, and battery-free ferroelectret implant, termed NeuroRing, that wraps around the target peripheral nerve and demonstrates high mechanical conformability to dynamic motion nerve tissue. As-fabricated NeuroRing can act as an ultrasound receiver that converts ultrasound vibrations into electrostimulation pulses, thus stimulating the targeted peripheral nerve on demand. This capability is demonstrated by the precise modulation of the sacral splanchnic nerve to treat colitis, providing a framework for future bioelectronic medicines that offer an alternative to non-specific pharmacological approaches.


Assuntos
Tecido Nervoso , Nervos Periféricos , Nervos Periféricos/fisiologia , Sistema Nervoso Periférico , Eletrodos , Próteses e Implantes
8.
Cell Rep ; 42(9): 113110, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37682704

RESUMO

The crosstalk between ferroptosis and cancer metastasis remains unclear. Here, we identify AMER1 as a key regulator of ferroptosis. AMER1 loss causes resistance to ferroptosis in colorectal cancer (CRC) cells. Interestingly, AMER1-deficient CRC cells preferentially form distant metastases, while AMER1-naive CRC cells mainly invade lymph nodes. Moreover, the ferroptosis inhibitor liproxstatin-1 effectively promotes hematogenous transfer of AMER1-naive cells. Mechanistically, AMER1 binds to SLC7A11 and ferritin light chain (FTL) and recruits ß-TrCP1/2, which degrade SLC7A11 and FTL by ubiquitination. Therefore, AMER1 deficiency increases cellular cystine levels but decreases the pool of labile free iron, thereby enhancing resistance to ferroptosis in CRC cells. Thus, AMER1 deficiency increases the survival of CRC cells in the blood under conditions of high oxidative stress and then promotes hematogenous metastasis of CRC. In conclusion, AMER1 mediates the crosstalk between ferroptosis and cancer metastasis, which provides a window of opportunity for treating metastatic colorectal cancer patients with AMER1 mutations.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Ferroptose , Humanos , Apoferritinas , Reações Cruzadas , Cistina , Neoplasias Colorretais/genética , Sistema y+ de Transporte de Aminoácidos/genética , Proteínas Supressoras de Tumor , Proteínas Adaptadoras de Transdução de Sinal
9.
iScience ; 26(10): 107712, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37701567

RESUMO

High-grade serous ovarian cancer (HGSOC) is a hormone-related cancer with high mortality and poor prognosis. Based on the transcriptome of 57,444 cells in ascites from 10 patients with HGSOC (including 5 pre-menopausal and 5 post-menopausal patients), we identified 14 cell clusters which were further classified into 6 cell types, including T cells, B cells, NK cells, myeloid cells, epithelial cells, and stromal cells. We discovered an increased proportion of epithelial cells and a decreased proportion of T cells in pre-menopausal ascites compared with post-menopausal ascites. GO analysis revealed the pre-menopausal tumor microenvironments (TME) are closely associated with viral infection, while the post-menopausal TME are mostly related to the IL-17 immune pathway. SPP1/CD44-mediated crosstalk between myeloid cells and B cells, NK cells, and stromal cells mainly present in the pre-menopausal group, while SPP1/PTGER4 -mediated crosstalk between myeloid cells and epithelial cells mostly present in the post-menopausal group.

10.
NPJ Precis Oncol ; 7(1): 75, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37567953

RESUMO

Neurotrophic tyrosine kinase (NTRK) fusions involving NTRK1, NTRK2, and NTRK3 were found in a broad range of solid tumors as driver gene variants. However, the prevalence of NTRK fusions in Chinese solid tumor patients is rarely reported. Based on the next-generation sequencing data from 10,194 Chinese solid tumor patients, we identified approximately 0.4% (40/10,194) of Chinese solid tumor patients with NTRK fusion. NTRK fusions were most frequently detected in soft tissue sarcoma (3.0%), especially in the fibrosarcoma subtype (12.7%). A total of 29 NTRK fusion patterns were identified, of which 11 were rarely reported. NTRK fusion mostly co-occurred with TP53 (38%), CDKN2A (23%), and ACVR2A (18%) and rarely with NTRK amplification (5.0%) and single nucleotide variants (2.5%). DNA-based NTRK fusion sequencing exhibited a higher detection rate than pan-TRK immunohistochemistry (100% vs. 87.5%). Two patients with NTRK fusions showed clinical responses to larotrectinib, supporting the effective response of NTRK fusion patients to TRK inhibitors.

11.
Front Oncol ; 13: 1178772, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427134

RESUMO

Microsatellite instability (MSI) is one of the hallmarks of colorectal cancer (CRC). Mismatch repair (MMR) protein expression may reflect MSI status. To analyze the concordance between MSI and MMR expression in CRC and their clinicopathological characteristics, 502 CRC patients were retrospectively collected in this study. Polymerase chain reaction-capillary electrophoresis (PCR-CE) was used to measure MSI, and MMR expression was determined by immunohistochemistry (IHC). The causes of non-concordance were analyzed. Chi-square test was used to find the correlation between MSI and various clinicopathological parameters. PCR-CE results showed 64 (12.7%) patients had high microsatellite instability (MSI-H); low microsatellite instability (MSI-L) and microsatellite stable (MSS) cases were 19 (3.8%)and 419 (83.5%), respectively. With regard to IHC, 430 (85.7%) showed proficient mismatch repair (pMMR) and 72 (14.3%) showed deficient mismatch repair (dMMR). The coincidence rate of MSI and MMR expression in CRC was 98.4% (494/502), with good concordance (Kappa = 0.932). Using PCR-CE as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of IHC were 100%, 98.2%, 88.9%, and 100%, respectively. MSI-H was more common in women, right colon, tumors ≥ 5 cm, ulcerative type, mucinous adenocarcinoma, poor differentiation, T stage I/II, and without lymph node or distant metastasis for CRC patients. In summary, MSI exhibited some typical clinicopathological characteristics. MSI and MMR expression in CRC had good concordance. However, it is still extremely necessary to perform PCR-CE. We recommend that testing packages of different sizes should be developed in clinical practice to create a testing echelon, to facilitate comprehensive selection according to experimental conditions, clinical diagnosis, and treatment needs.

12.
Sci Rep ; 13(1): 7973, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198224

RESUMO

Due to the similarity in the grain and difference in the market value among many rice varieties, deliberate mislabeling and adulteration has become a serious problem. To check the authenticity, we aimed to discriminate rice varieties based on their volatile organic compounds (VOCs) composition by headspace solid phase microextraction (HS-SPME) coupled with gas chromatography mass spectrometry (GC-MS). The VOC profiles of Wuyoudao 4 from nine sites in Wuchang were compared to 11 rice cultivar from other regions. Multivariate analysis and unsupervised clustering showed an unambiguous distinction between Wuchang rice and non-Wuchang rice. Partial least squares discriminant analysis (PLS-DA) demonstrated a goodness of fit of 0.90 and a goodness of prediction of 0.85. The discriminating ability of volatile compounds is also supported by Random forest analysis. Our data revealed eight biomarkers including 2-acetyl-1-pyrroline (2-AP) that can be used for variation identification. Taken together, the current method can readily distinguish Wuchang rice from other varieties which it holds great potential in checking the authenticity of rice.


Assuntos
Oryza , Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas/métodos , Oryza/química , Análise Multivariada , Análise Discriminante , Análise por Conglomerados , Microextração em Fase Sólida/métodos , Compostos Orgânicos Voláteis/análise
13.
Jpn J Infect Dis ; 76(5): 289-294, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37258178

RESUMO

This study examined the management of occupational bloodborne pathogen exposure at a tertiary hospital in China. This prospective study was conducted at the Zhejiang Hospital of Traditional Chinese Medicine between January 2016 and December 2019. Data on bloodborne occupational exposure management were collected. In total, 460 exposures were reported. The majority of exposures (40.2 %) were from hepatitis B virus (HBV)-positive index patients. Of the 460 cases, 453 (98.5%) exposures were reported timeously, and 371 (80.7%) cases received emergency treatment response and management. Sixty-eight personnel (93.2%) received timely prophylaxis treatment. Only 82/113 (72.6%) personnel completed the recommended follow-up period. Outsourced personnel(P = 0.002) and interns (P = 0.011) were independent follow-up factors. Although adequate compliance was achieved with timely reporting and prophylactic medication, there is room for improvement in terms of emergency treatment response and follow-up compliance. Furthermore, HBV vaccination and improved follow-up with outsourced personnel are recommended.


Assuntos
Infecções por HIV , Hepatite B , Exposição Ocupacional , Humanos , Patógenos Transmitidos pelo Sangue , Estudos Prospectivos , Pessoal de Saúde , Exposição Ocupacional/prevenção & controle , Centros de Atenção Terciária , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle
14.
Front Immunol ; 14: 1136652, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936959

RESUMO

Human decidual natural killer (dNK) cells are a unique type of tissue-resident NK cells at the maternal-fetal interface. dNK cells are likely to have pivotal roles during pregnancy, including in maternal-fetal immune tolerance, trophoblast invasion, and fetal development. However, detailed insights into these cells are still lacking. In this study, we performed metabolomic and proteomic analyses on human NK cells derived from decidua and peripheral blood. We found that 77 metabolites were significantly changed in dNK cells. Notably, compared to peripheral blood NK (pNK) cells, 29 metabolites involved in glycerophospholipid and glutathione metabolism were significantly decreased in dNK cells. Moreover, we found that 394 proteins were differentially expressed in dNK cells. Pathway analyses and network enrichment analyses identified 110 differentially expressed proteins involved in focal adhesion, cytoskeleton remodeling, oxidoreductase activity, and fatty acid metabolism in dNK cells. The integrated proteomic and metabolomic analyses revealed significant downregulation in glutathione metabolism in dNK cells compared to pNK cells. Our data indicate that human dNK cells have unique metabolism and protein-expression features, likely regulating their function in pregnancy and immunity.


Assuntos
Células Matadoras Naturais , Proteômica , Gravidez , Feminino , Humanos , Regulação para Baixo , Glutationa/metabolismo
15.
Cancer Sci ; 114(4): 1582-1595, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36632741

RESUMO

Cervical squamous cell carcinoma (CSCC) is one of the leading causes of cancer death in women worldwide. Patients with advanced cervical carcinoma always have a poor prognosis once resistant to cisplatin due to the lack of effective treatment. It is urgent to investigate the molecular mechanisms of cisplatin resistance. Circular RNAs (circRNAs) are known to exert their regulatory functions in a series of malignancies. However, their effects on CSCC remain to be elucidated. Here, we found that cytoplasmic circARHGAP5, derived from second and third exons of the ARHGAP5 gene, was downregulated in cisplatin-resistant tissues compared with normal cervix tissues and untreated cervical cancer tissues. In addition, experiments from overexpression/knockdown cell lines revealed that circARHGAP5 could inhibit cisplatin-mediated cell apoptosis in CSCC cells both in vitro and in vivo. Mechanistically, circARHGAP5 interacted with AU-rich element RNA-binding protein (AUF1) directly. Overexpression of AUF1 could also inhibit cell apoptosis mediated by cisplatin. Furthermore, we detected the potential targets of AUF1 related to the apoptotic pathway and found that bcl-2-like protein 11 (BIM) was not only negatively regulated by AUF1 but positively regulated by circARHGAP5, which indicated that BIM mRNA might be degraded by AUF1 and thereby inhibited tumor cell apoptosis. Collectively, our data indicated that circARHGAP5 directly bound to AUF1 and prevented AUF1 from interacting with BIM mRNA, thereby playing a pivotal role in cisplatin resistance in CSCC. Our study provides insights into overcoming cancer resistance to cisplatin treatment.


Assuntos
Carcinoma de Células Escamosas , Ribonucleoproteína Nuclear Heterogênea D0 , RNA Circular , Neoplasias do Colo do Útero , Feminino , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Proteínas Ativadoras de GTPase/genética , Ribonucleoproteína Nuclear Heterogênea D0/metabolismo , RNA Circular/genética , RNA Mensageiro/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
16.
Sci Total Environ ; 860: 160541, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36464061

RESUMO

The effects of biochemical components and processing variables (e.g., temperatures, solid-liquid ratio, ethanol concentration, and time) during fast hydrothermal liquefaction of a highly CO2-tolerant microalgae (Micractinium sp.) on the product yields and biofuel quality were explored using response surface methodology coupled with central composite design. Results showed that the maximum bio-oil yield (51.4 %) was obtained at 321 °C for 49 min at ethanol concentration of 75 % and solid-liquid ratio of 15.3 %. Among different studied parameters, ethanol concentration showed the highest significant impact on the bio-oil yield due to the low P-value and high F-value in ANOVA analysis. Furthermore, the chemical compositions of bio-oils were determined, which showed that the increase of ethanol concentration in the solvent not only increased the bio-oil yield but also promoted the bio-oil quality by reduction of carboxylic acids and nitrogen-containing compounds with simultaneous enhancement of esters in the bio-oil. The present results show that fast hydrothermal liquefaction is a promising approach to convert the microalgae into high quality biofuels rich in esters.


Assuntos
Biocombustíveis , Microalgas , Dióxido de Carbono , Água/química , Óleos de Plantas , Temperatura , Etanol , Compostos de Nitrogênio , Biomassa
18.
ACS Appl Mater Interfaces ; 14(51): 56454-56470, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36525559

RESUMO

Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G2/M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.


Assuntos
Neoplasias , Pró-Fármacos , Radiossensibilizantes , Humanos , Pró-Fármacos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radiossensibilizantes/farmacologia , Hipóxia , Reparo do DNA , Linhagem Celular Tumoral
19.
J Mater Chem B ; 10(43): 8797-8823, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36278320

RESUMO

Bioelectricity plays a significant role in major biological processes and electrical stimulation is an effective and non-invasive way to promote cellular growth, differentiation and tissue regeneration. In tissue engineering, piezoelectric materials not only act as modulators to regulate behaviors and functions of cells and tissues, but are also used as scaffolds to regulate and guide cell growth and matrix synthesis, thus promoting the formation of new tissue. Piezoelectronic electrons are produced from piezoelectric materials upon mechanical stimuli and have similar effects on cells as an external electrical field. Devices based on piezoelectronics have been widely applied in bioelectronics and biomedical fields. In this review, the effects of piezoelectronic electrons on cells and their possible mechanisms are briefly introduced. Then, we overview the applications of piezoelectronic electrons in cell regulation and tissue regeneration according to the type of cells and tissues. Finally, future perspectives and challenges are also provided.


Assuntos
Elétrons , Alicerces Teciduais , Engenharia Tecidual , Diferenciação Celular , Eletricidade
20.
Nat Commun ; 13(1): 5302, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085331

RESUMO

Invasive electrical stimulation (iES) is prone to cause neural stimulus-inertia owing to its excessive accumulation of exogenous charges, thereby resulting in many side effects and even failure of nerve regeneration and functional recovery. Here, a wearable neural iES system is well designed and built for bionic and long-lasting neural modulation. It can automatically yield biomimetic pulsed electrical signals under the driven of respiratory motion. These electrical signals are full of unique physiological synchronization can give biofeedback to respiratory behaviors, self-adjusting with different physiological states of the living body, and thus realizing a dynamic and biological self-matched modulation of voltage-gated calcium channels on the cell membrane. Abundant cellular and animal experimental evidence confirm an effective elimination of neural stimulus-inertia by these bioelectrical signals. An unprecedented nerve regeneration and motor functional reconstruction are achieved in long-segmental peripheral nerve defects, which is equal to the gold standard of nerve repair -- autograft. The wearable neural iES system provides an advanced platform to overcome the common neural stimulus-inertia and gives a broad avenue for personalized iES therapy of nerve injury and neurodegenerative diseases.


Assuntos
Biônica , Terapia por Estimulação Elétrica , Animais , Biorretroalimentação Psicológica , Estimulação Elétrica , Regeneração Nervosa
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