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1.
Kaohsiung J Med Sci ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34989116

RESUMO

This study is aimed at exploring the biological functions and related mechanism of long noncoding RNA 704 (LINC00704) in the proliferation and cell cycle progression of nasopharyngeal carcinoma (NPC) cells. The expression of LINC00704 in NPC tissues and cells was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). After LINC00704 was overexpressed or knocked down in NPC cell lines, cell counting kit-8 (CCK-8) assay, 5-bromo-2'-deoxyuridine assay, flow cytometry assay, and Transwell assay were adopted to detect the proliferation, cell cycle progression, migration, and invasion of NPC cells. The interaction between LINC00704 and ETS proto-oncogene 1 (ETS1) was verified by bioinformatics analysis, RNA pull-down assay, and RNA immunoprecipitation assay. Dual-luciferase reporter gene assay and chromatin immunoprecipitation followed by qPCR analysis were used to verify the binding status between ETS1 and the promoter region of cyclin-dependent kinase 6 (CDK6). The regulatory effects of LINC00704 and ETS1 on CDK6 expression were detected by Western blot. LINC00704 expression was elevated in NPC tissues and cells, which was significantly correlated with the advanced TNM stage and poor differentiation. LINC00704 overexpression promoted the multiplication, migration, and invasion of NPC cells and blocked the cell cycle progression while knocking down LINC00704 worked oppositely. LINC00704 could bind to ETS1, thus promoting CDK6 transcription. Knocking down LINC00704 inhibited the CDK6 expression in NPC cells. LINC00704 promotes CDK6 transcription by recruiting ETS1 to the promoter region of CDK6, thus promoting the malignant progression of NPC.

2.
J Am Chem Soc ; 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060705

RESUMO

Deciphering the atomic and electronic structures of interfaces is key to developing state-of-the-art perovskite semiconductors. However, conventional characterization techniques have limited previous studies mainly to grain-boundary interfaces, whereas the intragrain-interface microstructures and their electronic properties have been much less revealed. Herein using scanning transmission electron microscopy, we resolved the atomic-scale structural information on three prototypical intragrain interfaces, unraveling intriguing features clearly different from those from previous observations based on standalone films or nanomaterial samples. These intragrain interfaces include composition boundaries formed by heterogeneous ion distribution, stacking faults resulted from wrongly stacked crystal planes, and symmetrical twinning boundaries. The atomic-scale imaging of these intragrain interfaces enables us to build unequivocal models for the ab initio calculation of electronic properties. Our results suggest that these structure interfaces are generally electronically benign, whereas their dynamic interaction with point defects can still evoke detrimental effects. This work paves the way toward a more complete fundamental understanding of the microscopic structure-property-performance relationship in metal halide perovskites.

3.
Sci Total Environ ; : 152834, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34999072

RESUMO

This study was aimed to evaluate the potential of four earthworm species commonly found in South China for the bioremediation of soils contaminated by Cu, Cd, Pb and Zn. Survival rates and metal accumulation of Eisenia fetida, Amynthas morrisi, A. robustus and A. corticis and changes in soil physico-chemical properties were investigated in a 60-day incubation experiment with a metal-polluted soil. At the end of the experiment, the survival rates of E. fetida, A. morrisi and A. robustus were significantly higher than that of A. corticis. Principal component analysis showed that earthworm activity improved soil quality with the averaging soil quality index being 0.66, 0.64, 0.56, 0.53, and 0.12 for the A. corticis, A. morrisi, A. robustus, E. fetida, and control treatments, respectively. The highest total available Cd, Cu, and Pb in casts were found in the treatment with A. morrisi, and this species accumulated the smallest amount of metals. Results indicate that A. morrisi may be the best candidate for earthworm-assisted bioremediation of metal contaminated soils in South China.

4.
Comput Math Methods Med ; 2022: 4312117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35047054

RESUMO

Lung infection seriously affects the effect of chemotherapy in patients with lung cancer and increases pain. The study is aimed at establishing the prediction model of infection in patients with lung cancer during chemotherapy by an artificial neural network (ANN). Based on the data of historical cases in our hospital, the variables were screened, and the prediction model was established. A logistic regression (LR) model was used to screen the data. The indexes with statistical significance were selected, and the LR model and back propagation neural network model were established. A total of 80 cases of advanced lung cancer patients with palliative chemotherapy were predicted, and the prediction performance of different model was evaluated by the receiver operating characteristic curve (ROC). It was found that age≧60 years, length of stay≧14 d, surgery history, combined chemotherapy, myelosuppression, diabetes, and hormone application were risk factors of infection in lung cancer patients during chemotherapy. The area under the ROC curve of the LR model for prediction lung infection was 0.729 ± 0.084, which was less than that of the ANN model (0.897 ± 0.045). The results concluded that the neural network model is better than the LR model in predicting lung infection of lung cancer patients during chemotherapy.

5.
Exp Ther Med ; 23(1): 18, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34815770

RESUMO

Pulmonary thromboembolism (PTE) is a fatal clinical syndrome that usually occurs in elderly individuals. The present study aimed to identify functional and key genes involved in the early diagnosis of PTE using bioinformatics analysis. The GSE84738 dataset was retrieved from the Gene Expression Omnibus database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were subsequently performed. In addition, Cytoscape software v.3.7.2 was used to construct a protein-protein interaction (PPI) network. Serum samples from patients with PTE and healthy individuals were collected and the expression levels of Toll-like receptor (TLR)4, TLR2, IL-1ß, JUN, prostaglandin-endoperoxide synthase 2 (PTGS2), osteopontin (SPP1) and endothelin-1 (ET-1) were analyzed by reverse transcription-quantitative PCR. A total of 160 upregulated and 159 downregulated differentially expressed genes were identified between patients with PTE and healthy individuals. TNF, IL-1ß, JUN, TLR4, PTGS2, vascular cell adhesion molecule 1, SPP1, ryanodine receptor 2, TLR2 and ET-1 were considered as hub genes, which are defined as the genes with the highest degree of interaction in the enrichment and PPI network analyses. The top 10 common genes with the highest degree in the PPI network and the top 10 genes in modules 1 and 2 were TLR4, TLR2, IL-1ß, JUN, PTGS2, SPP1 and ET-1. Taken together, the present study suggested that TLR4, TLR2, IL-1ß and SPP1 were enriched in patients with PTE, thus providing novel potential biomarkers for the diagnosis of PTE.

7.
Phytomedicine ; 95: 153874, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34923232

RESUMO

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) pose a huge threat to human public health, no specific treatment is available. Jinzhen granule (JZ) is a traditional eight ingredients-Chinese medicine with prominent efficacy for treating viral-induced diseases. However, little is known about the antiviral effect and mechanism of JZ against SARS-CoV-2 and HCoV-229E. PURPOSE: This study aimed to reveal the antiviral effects of JZ against SARS-CoV-2 and HCoV-229E, and to further explore the underlying mechanisms regulating the host immune response. METHODS: The chromatographic separation of JZ was performed using a Shimadzu analytical high-performance liquid chromatograph with UV detection and Alltech ELSD 2000ES. We conducted cytopathic effect (CPE) and plaque reduction assays to evaluate the antiviral effect of JZ. A lethal human angiotensin converting enzyme 2 (hACE2) transgenic mouse model of SARS-CoV-2 was established to determine the protective effect of JZ on mortality and lung virus titers. Real-time quantitative PCR assays were used to analyze the expression of proinflammatory cytokines in vitro and in vivo. Western blotting was further performed to determine the activities on regulating the nuclear factor kappa B (NF-κB)/MAPK pathway. Finally, mitochondrial membrane potential assays, flow cytometry analysis and western blotting were used to assess the anti-apoptotic potency toward HCoV-229E infection. RESULTS: The results showed that 13 chemical components were identified and five peaks were determined and quantitated (gallic acid 1.97 mg/g, baicalin 20.69 mg/g, glycyrrhizic acid 4.92 mg/g, hyodeoxycholic acid 4.86 mg/g, cholic acid 4.07 mg/g). We found that JZ exerted inhibitory potency against SARS-CoV-2 and HCoV-229E in vitro by using CPE and plaque reduction assays, and it was further found that JZ protected mice infected by SARS-CoV-2 from death and inhibited lung virus titers. JZ also significantly decreased the induction of inflammatory cytokines (IL-1α, IL-6, CCL-5 and MIP-1ß), similar to the observed in vitro effect. Moreover, JZ suppressed the release of inflammatory cytokines in vitro and it decreased the protein expression of p-p38 MAPK, p-JNK, p-NF-κB p65 and p-IκBα induced by HCoV-229E and increased the expression of IκBα. Notably, JZ significantly protected HCoV-229E-infected Huh-7 cells from mitochondrial damage and decreased apoptotic cells. The activation of the mitochondria-mediated apoptotic pathway was inhibited by JZ, as shown by the reduced expression of cleaved caspase-9, caspase-3 and p-PARP. CONCLUSIONS: In conclusion, JZ (gallic acid 1.97 mg/g, baicalin 20.69 mg/g, glycyrrhizic acid 4.92 mg/g, hyodeoxycholic acid 4.86 mg/g, cholic acid 4.07 mg/g) exhibited antiviral activities against SARS-CoV-2 and HCoV-229E by regulating the NF-κB/MAPK pathway and the mitochondria-mediated apoptotic pathway. These findings demonstrated the efficacy of JZ against CoVs and suggested JZ treatment as a novel clinical therapeutic strategy for COVID-19.


Assuntos
COVID-19 , Coronavirus Humano 229E , Animais , Antivirais/farmacologia , Humanos , Camundongos , NF-kappa B , SARS-CoV-2
8.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5819-5824, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951170

RESUMO

The freeze-drying technique, characterized by low-temperature processing, is especially suitable for sensitive volatile oils with thermal instability. However, there are few studies focusing on the retention of volatile oils in the processing of freeze-dried preparations. This study evaluated the effects of different addition methods(adsorption, emulsification, solid dispersion, and inclusion) on the retention rate of the main components in peppermint oil, aiming to explore the application feasibility of freeze-dried preparations of volatile oils. Firstly, the addition method was determined based on the retention rates of menthol in four freeze-dried preparations. Secondly, an orthogonal test was designed to optimize the preparation process based on the characteristics of the preferred addition method. The results showed that the most suitable preparation form of peppermint oil was inclusion with beta-cyclodextrin(ß-CD), and the retention rate of menthol in freeze-drying was 86.36%. According to the two-step preparation process of inclusion and freeze-drying, we introduced the product of inclusion rate and retention rate, i.e., comprehensive retention rate, to determine the optimum processing parameters. The results showed that ß-CD/oil ratio of 7∶1, inclusion temperature of 40 ℃, and inclusion time of 2 h were the optimum processing parameters. The product prepared with these parameter had the comprehensive retention rate of 68.41%, retention rate of 92.53%, and inclusion rate of 73.93%. The inclusion compound was white powder with significantly increased solubility. The pre-paration process based on cyclodextrin inclusion in this study is stable and reliable and provides a new idea for ensuring the efficacy and stability of volatile components in freeze-dried preparations.


Assuntos
Ciclodextrinas , Óleos Voláteis , Liofilização , Mentha piperita , Óleos Vegetais , Solubilidade , Tecnologia
9.
Chin Med J (Engl) ; 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34958539

RESUMO

Background: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. Methods: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. Results: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. Conclusions: Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.

10.
J AOAC Int ; 2021 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-34954793

RESUMO

Peucedanum praeruptorum Dunn (PPD) is a traditional Chinese medical herb of high medical and economic value. However, PPD is often pretended by inexpensive plants. To establish an integrated methodology using hand-held near-infrared spectroscopy (NIRS) combined with chemical pattern recognition techniques to identify adulterated PPD products. The standard normal variate (SNV) was used to preprocess the original near-infrared spectra. Principal component analysis (PCA), linear discriminant analysis (LDA), and partial least squares regression analysis (PLSDA) were used to construct the recognition models. PCA analysis could not correctly distinguish PPD from non-PPD. However, based on absorbance in the spectral region of 1,405-2,442 nm and SVN pretreatment, the accuracy of the LDA model was above 90% at identifying genuine PPD. Compared with the LDA method, the PLSDA model is more stable and reliable, and its model prediction accuracy was 93.4%. The combination of near-infrared spectroscopy and chemometric methods based on a hand-held near-infrared spectrometer is an efficient, non-destructive, and reliable method for validating traditional Chinese medicine PPD. It can be used for rapid identification and quality evaluation of PPD in the field, medicinal material markets, and points of sale.

11.
ACS Nano ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846125

RESUMO

Synergistic phototherapy provides a promising strategy to conquer the hypoxia and heterogeneity of tumors and realize a better therapeutic effect than monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). The development of efficient multifunctional organic phototheranostic systems still remains a challenging task. Herein, 9,10-phenanthrenequinone (PQ) with strong electron-withdrawing ability is conjugated with the rotor-type electron-donating triphenylamine derivatives to create a series of tailor-made photosensitizers. The highly efficient Type I reactive oxygen species generation and outstanding photothermal conversion capacity are tactfully integrated into these PQ-cored photosensitizers. The underlying photophysical and photochemical mechanisms of the combined photothermal and Type I photodynamic effects are deciphered by experimental and theoretical methods and are closely associated with the active intramolecular bond stretching vibration, facilitated intersystem crossing, and specific redox cycling activity of the PQ core. Both in vitro and in vivo evaluations demonstrate that the nanoagents fabricated by these PQ-based photosensitizers are excellent candidates for Type I photodynamic and photothermal combined antitumor therapy. This study thus broadens the horizon for the development of high-performance PTT/Type I PDT nanoagents for synergistic phototheranostic treatments.

12.
Chem Sci ; 12(42): 14098-14102, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760193

RESUMO

The SARS-CoV-2 3-chymotrypsin-like protease (3CLpro or Mpro) is a key cysteine protease for viral replication and transcription, making it an attractive target for antiviral therapies to combat the COVID-19 disease. Here, we demonstrate that bismuth drug colloidal bismuth subcitrate (CBS) is a potent inhibitor for 3CLpro in vitro and in cellulo. Rather than targeting the cysteine residue at the catalytic site, CBS binds to an allosteric site and results in dissociation of the 3CLpro dimer and proteolytic dysfunction. Our work provides direct evidence that CBS is an allosteric inhibitor of SARS-CoV-2 3CLpro.

13.
Front Med (Lausanne) ; 8: 725298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676225

RESUMO

Background: Population-based data on the risk assessment of newly diagnosed cervical cancer patients' bone metastasis (CCBM) are lacking. This study aimed to develop various predictive models to assess the risk of bone metastasis via machine learning algorithms. Materials and Methods: We retrospectively reviewed the CCBM patients from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to risk factors of the presence of bone metastasis. Clinical usefulness was assessed by Akaike information criteria (AIC) and multiple machine learning algorithms based predictive models. Concordance index (C-index) and receiver operating characteristic (ROC) curve were used to define the predictive and discriminatory capacity of predictive models. Results: A total of 16 candidate variables were included to develop predictive models for bone metastasis by machine learning. The areas under the ROC curve (AUCs) of the random forest model (RF), generalized linear model (GL), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), artificial neutral network (ANN), decision tree (DT), and naive bayesian model (NBM) ranged from 0.85 to 0.93. The RF model with 10 variables was developed as the optimal predictive model. The weight of variables indicated the top seven factors were organ-site metastasis (liver, brain, and lung), TNM stage and age. Conclusions: Multiple machine learning based predictive models were developed to identify risk of bone metastasis in cervical cancer patients. By incorporating clinical characteristics and other candidate variables showed robust risk stratification for CCBM patients, and the RF predictive model performed best among these predictive models.

14.
J Virol ; : JVI0162921, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34705566

RESUMO

The Newcastle disease virus (NDV) matrix (M) protein is the pivotal element for viral assembly, budding and proliferation. It traffics through the cellular nucleus but performs its primary function in the cytoplasm. To investigate the biological importance of M's nuclear-cytoplasmic trafficking and the mechanism involved, the regulatory motif nuclear export signal (NES) and nuclear localization signal (NLS) were deeply analyzed. Here, two types of combined NLS and NES signals were identified within NDV-M. The Herts/33-type M was found to mediate efficient nuclear export and stable virus-like particle (VLP) release, while the LaSota-type M was mostly retained in the nuclei and showed retarded VLP production. Two critical residues, 247 and 263, within the motif were identified and associated with nuclear export efficiency. We identified, for the first time, residue 247 as an important monoubiquitination site, the modification of which regulates the nuclear-cytoplasmic trafficking of NDV-M. Subsequently, mutant LaSota strains were rescued via reverse genetics, which contained either single or double amino acid substitutions that were similar to the M of Herts/33. The rescued rLaSota strains rLaSota-R247K, -S263R, and -DM (double mutation) showed about twofold higher HA titers and 10-fold higher EID50 titers than wild-type (wt) rLaSota. Further, the MDT and ICPI values of those recombinant viruses were slightly higher than that of wt rLaSota probably due to their higher proliferation rates. Our findings contribute to a better understanding of the molecular mechanism of the replication and pathogenicity of NDV, and even those of all other paramyxoviruses. It is beneficial for the development of vaccines and therapies for paramyxoviruses. Importance Newcastle disease virus (NDV) is a pathogen that is lethal to birds and causes heavy losses in the poultry industry worldwide. The World Organization for Animal Health (OIE) ranked ND as the third most significant poultry disease and the eighth most important wildlife disease in the World Livestock Disease Atlas in 2011. The matrix (M) protein of NDV is very important for viral assembly and maturation. It is interesting that M proteins enter the cellular nucleus before performing their primary function in the cytoplasm. We found that NDV-M has a combined nuclear import and export signal. The ubiquitin modification of a lysine residue within this signal is critical for quick, efficient nuclear export and subsequent viral production. Our findings shed new light on viral replication and opens up new possibilities for therapeutics against NDV and other paramyxoviruses; furthermore, we demonstrate a novel approach to improving paramyxovirus vaccines.

16.
Sci Rep ; 11(1): 20930, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686754

RESUMO

The deformation and failure forms of inclined coal seam roadway under the joint action of dip angle and various geological conditions are complex, and there is a lack of targeted support measures, which brings great problems to the stability control of roadway surrounding rock. In order to safely and economically mine inclined coal seams, taking the engineering geology of Shitanjing No. 2 mining area as the background, and the physical similarity model of right-angle trapezoidal roadway in inclined coal seam, in which the non-contact digital image correlation (DIC) technology and the stress sensor is employed to provide full-field displacement and stress measurements. The deformation control technology of the roadway surrounding rock was proposed, verified by numerical simulation and applied to engineering practice. The research results show that the stress and deformation failure of surrounding rock in low sidewall of roadway are greater than those in high sidewall, showing asymmetric characteristics, and the maximum stress concentration coefficients of roadway sidewall, roof and floor are 4.1, 3.4 and 2.8, respectively. A concept of roadway "cyclic failure" mechanism is proposed that is, the cyclic interaction of the two sidewalls, the sharp angles and roof aggravated the failure of roadway, resulting in the overall instability of roadway. The roadway sidewall is serious rib spalling, the roof is asymmetric "Beret" type caving arch failure, and the floor is slightly bulging. On this basis, the principle of roadway deformation control is revealed and asymmetric support design is adopted, and the deformation of roadway is controlled, which support scheme is effective.

17.
Natl Sci Rev ; 8(6): nwaa306, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34691667

RESUMO

Telomerase acts as an important biomarker for tumor identification, and synthesizes telomeric repeats at the end of chromosome telomeres during the replicative phase of the cell cycle; thus, the expression level of telomerase changes as the cell cycle progresses. TERT mRNA expression and telomerase activity were significantly increased in over 80% of human cancers from tissue specimens. Although many efforts have been made in detecting the activity of TERT mRNA and active telomerase, the heterogeneous behavior of the cell cycle was overlooked, which might affect the accuracy of the detection results. Herein, the AIEgen-based biosensing systems of PyTPA-DNA and Silole-R were developed to detect the cellular level of TERT mRNA and telomerase in different cell cycles. As a result, the fluorescence signal of cancer cells gradually increased from G0/G1, G1/S to S phase. In contrast, both cancer cells arrested at G2/M phase and normal cells exhibited negligible fluorescence intensities. Compared to normal tissues, malignant tumor samples demonstrated a significant turn-on fluorescence signal. Furthermore, the transcriptomics profiling revealed that tumor biomarkers changed as the cell cycle progressed and biomarkers of CA9, TK1 and EGFR were more abundantly expressed at early S stage. In this vein, our study presented advanced biosensing tools for more accurate analysis of the cell-cycle-dependent activity of TERT mRNA and active telomerase in clinical tissue samples.

18.
Natl Sci Rev ; 8(6): nwab039, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34691671

RESUMO

Red blood cell (RBC)-mimicking nanoparticles (NPs) offer a promising platform for drug delivery because of their prolonged circulation time, reduced immunogenicity and specific targeting ability. Herein, we report the design and preparation of RBC membrane-bound NPs (M@AP), for tumoral photodynamic-immunotherapy. The M@AP is formed by self-assembly of the positively charged aggregation-induced emission luminogen (AIEgen) (named P2-PPh3) and the negatively charged polyinosinic : polycytidylic acid (Poly(I : C)), followed by RBC membrane encapsulation. P2-PPh3 is an AIE-active conjugated polyelectrolyte with additional photosensitizing ability for photodynamic therapy (PDT), while Poly(I : C) serves as an immune-stimulant to stimulate both tumor and immune cells to activate immunity, and thus reduces tumor cell viability. When applied in tumor-bearing mice, the M@AP NPs are enriched in both the tumor region as a result of an enhanced permeability and retention (EPR) effect, and the spleen because of the homing effect of the RBC-mimicking shell. Upon light irradiation, P2-PPh3 promotes strong ROS generation in tumor cells, inducing the release of tumor antigens (TA). The anti-tumor immunity is further enhanced by the presence of Poly(I : C) in M@AP. Thus, this strategy combines the PDT properties of the AIE-active polyelectrolyte and immunotherapy properties of Poly(I : C) to achieve synergistic activation of the immune system for anti-tumor activity, providing a novel strategy for tumor treatment.

19.
Arch Gynecol Obstet ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34694430

RESUMO

BACKGROUND: Pregnancy complicated with juvenile granulosa cell tumor (JGCT) is very rare; thus, the experience on clinical diagnosis and management is limited. CASES: Two patients presented with abdominal pain, two were incidentally discovered, one by ultrasonography, and one during a caesarian section. One case received an emergency caesarian section because of tumor rupture at 38th week's gestation, the rest were treated at full term and no abnormalities were detected in the newborns. Three cases received further staging surgery, two of which received postoperative adjuvant chemotherapy. No patient had recurrent disease after a follow-up period spanning from 13 to 57 months. CONCLUSION: In the absence of emergency, surgery can be delayed without affecting the fetus. More research is needed to determine the value of chemotherapy in FIGO stage I patients.

20.
FASEB J ; 35(10): e21923, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34551143

RESUMO

Our recent studies have shown that haspin, a protein kinase imperative for mitosis, is engaged in the interphase progression of HeLa and U2OS cancer cells. In this investigation, we employed the Fucci reporter system and time-lapse imaging to examine the impact of haspin gene silencing on cell cycle progressions at a single-cell level. We found that the loss of haspin induced multiple cell cycle defects. Specifically, the S/G2 duration was greatly prolonged by haspin gene depletion or inhibition in synchronous HeLa cells. Haspin gene depletion in asynchronous HeLa and U2OS cells led to a similarly protracted S/G2 phase, followed by mitotic cell death or postmitotic G1 arrest. In addition, haspin deficiency resulted in robust induction of the p21CIP1/WAF1 checkpoint protein, a target of the p53 activation. Also, co-depleting haspin with either p21 or p53 could rescue U2OS cells from postmitotic G1 arrest and partially restore their proliferation. These results substantiate the haspin's capacity to regulate interphase and mitotic progression, offering a broader antiproliferative potential of haspin loss in cancer cells.


Assuntos
Ciclo Celular , Proliferação de Células , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Neoplasias/patologia , /deficiência , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Corantes Fluorescentes , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Humanos , Interfase/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mitose/efeitos dos fármacos , Neoplasias/genética , /genética , Fase S/efeitos dos fármacos , Tubercidina/análogos & derivados , Tubercidina/farmacologia , Proteína Supressora de Tumor p53/genética , Ubiquitinação , Regulação para Cima/efeitos dos fármacos
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