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1.
Huan Jing Ke Xue ; 45(3): 1328-1336, 2024 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-38471849

RESUMEN

The contents of eight carbonaceous subfractions were determined by simultaneously collecting PM2.5 samples from four sites in different functional areas of Tianjin in 2021. The results showed that the organic carbon (OC) concentration was 3.7 µg·m-3 to 4.4 µg·m-3, and the elemental carbon (EC) concentration was 1.6 µg·m-3 to 1.7 µg·m-3, with the highest OC concentration in the central urban area. There was no significant difference in EC concentration. The concentration of PM2.5 showed the distribution characteristics of the surrounding city>central city>peripheral area. The OC/EC minimum ratio method was used to estimate the concentrations of secondary organic carbon (SOC) in PM2.5, and the results showed that the secondary pollution was more prominent in the surrounding city, with SOC accounting for 48.8%. The correlation between carbon subcomponents in each functional area showed the characteristics of the peripheral area>central area>surrounding area, all showing the strongest correlation between EC1 and OC2 and EC1 and OC4. By including the carbon component concentration into the positive definite matrix factorization (PMF) model for source apportionment, the results showed that road dust sources(9.7%-23.5%), coal-combustion sources (10.2%-13.3%), diesel vehicle exhaust (12.6%-20.2%)and gasoline vehicle exhaust (18.9%-38.8%)were the main sources of carbon components in PM2.5 in Tianjin. The pollution sources of carbon components were different in different functional areas, with the central city and peripheral areas mainly affected by gasoline vehicle exhaust; the surrounding city was more prominently affected by the secondary pollution and diesel vehicle exhaust.

2.
Oncogene ; 43(20): 1522-1533, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38532114

RESUMEN

Androgen deprivation therapies (ADT) are the mainstay treatments for castration-resistant prostate cancer (CRPC). ADT suppresses the androgen receptor (AR) signaling by blocking androgen biosynthesis or inhibiting AR with antiandrogens that target AR's ligand-binding domain (LBD). However, the ADT's effect is short-lived, as the AR signaling inevitably arises again, which is frequently coupled with AR-V7 overexpression. AR-V7 is a truncated form of AR that lacks the LBD, thus being constitutively active in the absence of androgens and irresponsive to AR-LBD-targeting inhibitors. Though compelling evidence has tied AR-V7 to drug resistance in CRPC, pharmacological inhibition of AR-V7 is still an unmet need. Here, we discovered a small molecule, SC912, which binds to full-length AR as well as AR-V7 through AR N-terminal domain (AR-NTD). This pan-AR targeting relies on the amino acids 507-531 in the AR-NTD. SC912 also disrupted AR-V7 transcriptional activity, impaired AR-V7 nuclear localization and DNA binding. In the AR-V7 positive CRPC cells, SC912 suppressed proliferation, induced cell-cycle arrest, and apoptosis. In the AR-V7 expressing CRPC xenografts, SC912 attenuated tumor growth and antagonized intratumoral AR signaling. Together, these results suggested the therapeutic potential of SC912 for CRPC.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Animales , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Dominios Proteicos , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/uso terapéutico
3.
Mol Med Rep ; 29(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38426568

RESUMEN

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that two pairs of data panels featured in Figs. 2E and 6D, portraying the results from cell invasion and migration assay experiments, appeared to contain overlapping sections, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. The authors were able to re­examine their original data (which was also presented to the Editorial Office), and realized that errors has been made in the compilation of Fig. 2. The proposed revised version of Fig. 2, now showing the results from the 'field 1' view of the data, is shown on the next page. Note that these errors did not significantly affect either the results or the conclusions reported in this paper,.All the authors agree to the publication of this Corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error; furthermore, they apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 25: 71, 2022; DOI: 10.3892/mmr.2022.12587].

4.
BMC Med Imaging ; 23(1): 215, 2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38110909

RESUMEN

PURPOSE: Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. METHODS: We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. RESULTS: MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). CONCLUSIONS: Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies.


Asunto(s)
Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Estudios Retrospectivos , Pronóstico , Carga Tumoral , Radiofármacos
5.
Cell Rep ; 42(9): 113104, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37703174

RESUMEN

NRF2 (nuclear factor erythroid 2-related factor 2) is a master regulator of protective responses in healthy tissues. However, when it is active in tumor cells, it can result in drug resistance. KEAP1, the endogenous NRF2 inhibitor, binds NRF2 and redirects it to proteasomal degradation, so the KEAP1/NRF2 interaction is critical for maintaining NRF2 at a basal level. A number of clinically relevant KEAP1 mutations were shown to disrupt this critical KEAP1/NRF2 interaction, leading to elevated NRF2 levels and drug resistance. Here, we describe a small-molecule NRF2 inhibitor, R16, that selectively binds KEAP1 mutants and restores their NRF2-inhibitory function by repairing the disrupted KEAP1/NRF2 interactions. R16 substantially sensitizes KEAP1-mutated tumor cells to cisplatin and gefitinib, but does not do so for wild-type KEAP1 cells, and sensitizes KEAP1 G333C-mutated xenograft to cisplatin. We developed a BRET2-based biosensor system to detect the KEAP1/NRF2 interaction and classify KEAP1 mutations. This strategy would identify drug-resistant KEAP1 somatic mutations in clinical molecular profiling of tumors.


Asunto(s)
Cisplatino , Factor 2 Relacionado con NF-E2 , Humanos , Cisplatino/farmacología , Gefitinib/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Línea Celular Tumoral , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Transducción de Señal
6.
Hum Vaccin Immunother ; 19(2): 2240689, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37529904

RESUMEN

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Derrame Pleural , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Derrame Pleural/inducido químicamente , Derrame Pleural/tratamiento farmacológico , Inmunoterapia/efectos adversos
7.
Head Neck ; 45(10): 2700-2709, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37552128

RESUMEN

The low positive predictive value (PPV) of early screening of nasopharyngeal carcinoma (NPC) is the problems that need to be solved urgently. The combination of cell-free DNA (cfDNA) methylation testing and Epstein-Barr virus (EBV) serological testing is the key to solve this problem. This paper reviews recent advances in early screening for NPC and cfDNA methylation, with future perspectives. Pubmed was searched for the literature related to early screening of NPC and cfDNA methylation in the past 5 years. The results of these studies were summarized. Despite these efforts, the PPV is still low (10%). Previous studies have shown that cfDNA methylation analysis has good specificity and accuracy across a variety of tumors. The combination of cfDNA methylation and EBV detection helps to improve the PPV for early screening of NPC. The combination of cfDNA methylation and EBV serological testing is key to addressing the low PPV of NPC early screening.


Asunto(s)
Ácidos Nucleicos Libres de Células , Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Infecciones por Virus de Epstein-Barr/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Herpesvirus Humano 4/genética , ADN Viral/genética
8.
Nat Commun ; 14(1): 4394, 2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37474626

RESUMEN

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Humanos , Ratas , Animales , Proteínas Proto-Oncogénicas c-fos/genética , Inflamación , Factor de Transcripción AP-1/metabolismo
9.
BMC Surg ; 23(1): 189, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37403109

RESUMEN

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Distant metastasis has been detected in approximately 50% of GIST patients at the first diagnosis. The surgical strategy for metastatic GIST with generalized progression (GP) after imatinib therapy remains unclear. METHODS: We recruited 15 patients with imatinib-resistant metastatic GIST. They received cytoreductive surgery (CRS) for tumor rupture, intestinal obstruction and gastrointestinal bleeding. We collected clinical, pathological and prognostic data for analyses. RESULTS: OS and PFS after R0/1 CRS were 56.88 ± 3.47 and 26.7 ± 4.12 months, respectively, when compared with 26 ± 5.35 and 5 ± 2.78 months after R2 CRS (P = 0.002 and P < 0.001, respectively). The OS of patients from the initiation of imatinib in the R0/1 group was 133.90 ± 15.40 months when compared with 59.80 ± 10.98 months in the R2 CRS group. There were two significant grade III complications after 15 operations (13.3%). No patient underwent reoperation. In addition, no perioperative death occurred. CONCLUSIONS: R0/1 CRS is highly probable to provide prognostic benefits for patients with metastatic GIST who experience GP following imatinib treatment. An aggressive surgical strategy for achieving R0/1 CRS can be deemed safe. If applicable, R0/1 CRS should be carefully considered in imatinib-treated patients with GP metastatic GIST.


Asunto(s)
Antineoplásicos , Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Humanos , Mesilato de Imatinib/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Pronóstico , Estudios Retrospectivos , Antineoplásicos/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/cirugía , Neoplasias Gastrointestinales/diagnóstico , Procedimientos Quirúrgicos de Citorreducción
10.
Huan Jing Ke Xue ; 44(5): 2492-2501, 2023 May 08.
Artículo en Chino | MEDLINE | ID: mdl-37177924

RESUMEN

Ambient air pollution is a dominant determinant of health. The health effects and economic losses due to air pollution are very important for decision-making. Since the implementation of the "Air Pollution Prevention and Control Action Plan" and "blue sky defense war" policies, the air quality of Tianjin has changed significantly. Here, the health effects and economic losses attributable to ambient air pollution in Tianjin from 2013 to 2020 wereestimated. For the particulate matter which has complex components, we assessed the inhalation health risks of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in PM2.5. The variation in the concentration of the main components of PM2.5 was also analyzed. The results showed that improved air quality had positive health benefits. The health benefits from SO2 were the highest among the six air pollutants, and 3786 deaths were avoided in 2020 compared to in 2013 due to lower SO2 concentration. The economic losses caused by air pollutants ranged from several billion to ten billion yuan. Among the six air pollutants, particulate matter and ozone had higher health losses in recent years. The health risks of heavy metals and PAHs in PM2.5 showed a decreasing trend. However, Cr(Ⅵ), As, Cd, and Ni in PM2.5in the winter of 2020 still had respiratorysystem carcinogenic risk, whereas there was no health risk of PAHs in PM2.5in 2019-2020. The concentrations of main components of PM2.5 have decreased significantly. In the future, the reduction of health loss caused by air pollution depends on synergy governance of particulate matter and ozone and further research on health effects.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Metales Pesados , Ozono , Hidrocarburos Policíclicos Aromáticos , Monitoreo del Ambiente/métodos , Contaminación del Aire/efectos adversos , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , Metales Pesados/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , China
11.
Mol Cancer Ther ; 22(5): 570-582, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-37139712

RESUMEN

The current mainstay therapeutic strategy for advanced prostate cancer is to suppress androgen receptor (AR) signaling. However, castration-resistant prostate cancer (CRPC) invariably arises with restored AR signaling activity. To date, the AR ligand-binding domain (LBD) is the only targeted region for all clinically available AR signaling antagonists, such as enzalutamide (ENZ). Major resistance mechanisms have been uncovered to sustain the AR signaling in CRPC despite these treatments, including AR amplification, AR LBD mutants, and the emergence of AR splice variants (AR-Vs) such as AR-V7. AR-V7 is a constitutively active truncated form of AR that lacks the LBD; thus, it can not be inhibited by AR LBD-targeting drugs. Therefore, an approach to inhibit AR through the regions outside of LBD is urgently needed. In this study, we have discovered a novel small molecule SC428, which directly binds to the AR N-terminal domain (NTD) and exhibits pan-AR inhibitory effect. SC428 potently decreased the transactivation of AR-V7, ARv567es, as well as full-length AR (AR-FL) and its LBD mutants. SC428 substantially suppressed androgen-stimulated AR-FL nuclear translocation, chromatin binding, and AR-regulated gene transcription. Moreover, SC428 also significantly attenuated AR-V7-mediated AR signaling that does not rely on androgen, hampered AR-V7 nuclear localization, and disrupted AR-V7 homodimerization. SC428 inhibited in vitro proliferation and in vivo tumor growth of cells that expressed a high level of AR-V7 and were unresponsive to ENZ treatment. Together, these results indicated the potential therapeutic benefits of AR-NTD targeting for overcoming drug resistance in CRPC.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Masculino , Humanos , Receptores Androgénicos/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Andrógenos , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/uso terapéutico , Unión Proteica , Línea Celular Tumoral
12.
Huan Jing Ke Xue ; 44(4): 1811-1820, 2023 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-37040932

RESUMEN

Based on the hourly O3 concentration data of 337 prefectural-level divisions and simultaneous surface meteorological data in China, we applied empirical orthogonal function (EOF) analysis to analyze the main spatial patterns, variation trends, and main meteorological driving factors of O3 concentration in China from March to August in 2019-2021. In this study, a KZ (Kolmogorov-Zurbenko) filter was used to decompose the time series of O3 concentration and simultaneous meteorological factors into corresponding short-term, seasonal, and long-term components in 31 provincial capitals.Then, the stepwise regression was used to establish the relationship between O3 and meteorological factors. Ultimately, the long-term component of O3 concentration after "meteorological adjustment" was reconstructed. The results indicated that the first spatial patterns of O3 concentration showed a convergent change, that is, the volatility of O3 concentration was weakened in the high-value region of variability and enhanced in the low-value region.Before and after the meteorological adjustment, the variation trend of O3 concentration in different cities was different to some extent. The adjusted curve was "flatter" in most cities. Among them, Fuzhou, Haikou, Changsha, Taiyuan, Harbin, and Urumqi were greatly affected by emissions. Shijiazhuang, Jinan, and Guangzhou were greatly affected by meteorological conditions. Beijing, Tianjin, Changchun, and Kunming were greatly affected by emissions and meteorological conditions.

13.
Huan Jing Ke Xue ; 44(4): 1962-1973, 2023 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-37040947

RESUMEN

The ambient concentration of ozone is high in Qingdao, and ozone pollution episodes occur frequently in summer. The refined source apportionment of ambient volatile organic compounds (VOCs) and their ozone formation potential (OFP) during ozone pollution episodes and non-ozone pollution periods can play an important role in effectively reducing air ozone pollution in coastal cities and continuously improving ambient air quality. Therefore, this study applied the online VOCs monitoring data with hourly resolution in summer (from June to August) in 2020 in Qingdao to analyze the chemical characteristics of ambient VOCs during the ozone pollution episodes and non-ozone pollution periods and conducted the refined source apportionment of ambient VOCs and their OFP using a positive matrix factorization (PMF) model. The results showed that the average mass concentration of ambient VOCs in Qingdao in summer was 93.8 µg·m-3, and compared with that during the non-ozone pollution period, the mass concentration of ambient VOCs during the ozone pollution episodes increased by 49.3%, and the mass concentration of aromatic hydrocarbons increased by 59.7%. The total OFP of ambient VOCs in summer was 246.3 µg·m-3. Compared with that in the non-ozone pollution period, the total OFP of ambient VOCs in the ozone pollution episodes increased by 43.1%; that of alkanes increased the most, reaching 58.8%. M-ethyltoluene and 2,3-dimethylpentane were the species with the largest increase in OFP and its proportion during the ozone pollution episodes. The main contributors of ambient VOCs in Qingdao in summer were diesel vehicles (11.2%), solvent use (4.7%), liquefied petroleum gas and natural gas (LPG/NG) (27.5%), gasoline vehicles (8.9%), gasoline volatilization (26.6%), emissions of combustion- and petrochemical-related enterprises (16.4%), and plant emissions (4.8%). Compared with that in the non-ozone pollution period, the contribution concentration of LPG/NG in the ozone pollution episodes increased by 16.4 µg·m-3, which was the source category with the largest increase. The contribution concentration of plant emissions increased by 88.6% in the ozone pollution episodes, which was the source category with the highest increase rate. In addition, emissions from combustion- and petrochemical-related enterprises were the largest contributor to the OFP of ambient VOCs in summer in Qingdao, with its OFP and contribution proportion being 38.0 µg·m-3and 24.5%, respectively, followed by that of LPG/NG and gasoline volatilization. Compared with the non-ozone pollution period, the total contributions of LPG/NG, gasoline volatilization, and solvent use to the increase in OFP for ambient VOCs in the ozone pollution episodes were 74.1%, which were the main contribution source categories.

14.
Redox Biol ; 61: 102637, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36821955

RESUMEN

Alzheimer's disease is a neurodegenerative disorder characterized by a decline in cognitive function. The ß-amyloid (Aß) hypothesis suggests that Aß peptides can spontaneously aggregate into ß-fragment-containing oligomers and protofibrils, and this activation of the amyloid pathway alters Ca2+ signaling in neurons, leading to neurotoxicity and thus apoptosis of neuronal cells. In our study, a blood-brain barrier crossing flavonol glycoside hyperoside was identified with anti-Aß aggregation, BACE inhibitory, and neuroprotective effect in cellular or APP/PSEN1 double transgenic Alzheimer's disease mice model. While our pharmacokinetic data confirmed that intranasal administration of hyperoside resulted in a higher bio-availability in mice brain, further in vivo studies revealed that it improved motor deficit, spatial memory and learning ability of APP/PSEN1 mice with reducing level of Aß plaques and GFAP in the cortex and hippocampus. Bioinformatics, computational docking and in vitro assay results suggested that hyperoside bind to Aß and interacted with ryanodine receptors, then regulated cellular apoptosis via endoplasmic reticulum-mitochondrial calcium (Ca2+) signaling pathway. Consistently, it was confirmed that hyperoside increased Bcl2, decreased Bax and cyto-c protein levels, and ameliorated neuronal cell death in both in vitro and in vivo model. By regulating Aß-induced cell death via regulation on Ca2+ signaling cascade and mitochondrial membrane potential, our study suggested that hyperoside may work as a potential therapeutic agent or preventive remedy for Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Ratones Transgénicos , Calcio/metabolismo , Transducción de Señal , Retículo Endoplásmico/metabolismo , Modelos Animales de Enfermedad
15.
Ear Nose Throat J ; : 1455613221140280, 2022 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-36373511

RESUMEN

BACKGROUND: To assess whether specific selective neck dissection (SND) with involved levels is a feasible treatment for isolated regional failure in nasopharyngeal carcinoma (NPC) after radiation. MATERIAL AND METHODS: Between January 2011 and December 2019, a total of 46 patients were assigned to undergo SND in the Department of Head and Neck Surgery at our center. The dissection extent of specific SND usually only involved levels of lymph node sites for isolated regional failure; in addition, lesions of level II or III involved removing both level II and III lymph nodes. The patients' clinical, MRI and pathological characteristics, overall survival (OS), disease-free survival (DFS) and regional-free survival (RFS) were evaluated and analyzed. RESULTS: Level II was the most commonly involved cervical nodal region in 28 neck dissection specimens (54.9%), followed by level III with positive nodes in 11 specimens (21.6%). Eleven patients (34.8%) had post-SND locoregional recurrence without distant metastasis. Of the patients, 7 patients (30.4%) had regional recurrence, and only one patient (2.8%) had lymph node recurrence on the side of SND. In addition, 8 patients (17.4%) had post-SND distant metastasis. The OS, DFS, and RFS of the patients were 76.1%, 58.7%, and 69.6%, respectively, at 3 years. The OS, DFS, and RFS values of patients who underwent SND were similar to those of patients who underwent comprehensive neck dissection (CND) and/or SND in published articles. CONCLUSION: Specific SND was shown to be an effective and feasible treatment for isolated regional failure in NPC.

16.
Front Oncol ; 12: 950418, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36387243

RESUMEN

Background: Peritoneal sarcomatosis (PS) could occur in patients with retroperitoneal sarcomas (RPS). This study aimed to expand the understanding of PS on its characteristics and prognostic role, and develop a nomogram to predict its occurrence preoperatively. Methods: Data of 211 consecutive patients with RPS who underwent surgical treatment between 2011 and 2019 was retrospectively reviewed. First, the clinicopathological characteristics of PS were summarized and analyzed. Second, the disease-specific survival (DSS) and recurrence-free survival (RFS) of patients were analyzed to evaluate the prognostic role of PS. Third, preoperative imaging, nearly the only way to detect PS preoperatively, was combined with other screened risk factors to develop a nomogram. The performance of the nomogram was assessed. Results: Among the 211 patients, 49 (23.2%) patients had PS with an incidence of 13.0% in the primary patients and 35.4% in the recurrent patients. The highest incidence of PS occurred in dedifferentiated liposarcoma (25.3%) and undifferentiated pleomorphic sarcoma (25.0%). The diagnostic sensitivity of the preoperative imaging was 71.4% and its specificity was 92.6%. The maximum standardized uptake value (SUVmax) was elevated in patients with PS (P<0.001). IHC staining for liposarcoma revealed that the expression of VEGFR-2 was significantly higher in the PS group than that in the non-PS group (P = 0.008). Survival analysis (n =196) showed significantly worse DSS in the PS group than in non-PS group (median: 16.0 months vs. not reached, P < 0.001). In addition, PS was proven as one of the most significant prognostic predictors of both DSS and RFS by random survival forest algorithm. A nomogram to predict PS status was developed based on preoperative imaging combined with four risk factors including the presentation status (primary vs. recurrent), ascites, SUVmax, and tumor size. The nomogram significantly improved the diagnostic sensitivity compared to preoperative imaging alone (44/49, 89.8% vs. 35/49, 71.4%). The C-statistics of the nomogram was 0.932, and similar C-statistics (0.886) was achieved at internal cross-validation. Conclusion: PS is a significant prognostic indicator for RPS, and it occurs more often in recurrent RPS and in RPS with higher malignant tendency. The proposed nomogram is effective to predict PS preoperatively.

17.
Front Surg ; 9: 956384, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36157408

RESUMEN

The outcomes of patients with primary retroperitoneal sarcoma (RPS) are significantly superior to those with recurrence. En bloc resection of tumor and adjacent organs is recommended in primary RPS. However, whether en bloc resection of tumor and adjacent organs can benefit recurrent patients or some recurrent patients is unclear. We compared the outcomes of patients with primary RPS, first recurrence (RPS-Rec1), and ≥2 recurrences (≥RPS-Rec2) to evaluate the value and criteria for en bloc resection of tumor and adjacent organs in recurrent cases. We evaluated the safety of en bloc resection of tumor and adjacent organs by assessing operation time, blood loss volume, postoperative morbidities (POM), and efficacy by comparing local recurrence and peritoneal metastasis (LR-PM), distant metastasis, progression-free survival (PFS), and overall survival (OS). A total of 101, 47, and 30 patients with primary RPS, RPS-Rec1, and ≥RPS-Rec2 were included, respectively. Recurrent RPS invaded more adjacent organs and surrounding fat tissue than primary RPS. The operation time, amount of blood loss, incidence of grade III-V POM, LR-PM rate, PFS, and OS in the RPS-Rec1 group were similar to those of the primary group, both of which were significantly superior to those of the ≥RPS-Rec2 group. Macroscopically incomplete resection and high-grade RPS rather than first recurrence were independent risk factors for LR-PM, PFS, and OS. In conclusion, the safety and efficacy of en bloc resection of tumor and adjacent organs in RPS-Rec1 were comparable with those in primary RPS but significantly superior to those of ≥RPS-Rec2. For RPS-Rec1, comparable outcomes to patients with primary RPS can be achieved, particularly in those in whom a macroscopically complete resection is achieved.

18.
Int J Mol Sci ; 23(17)2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36077199

RESUMEN

Ultraviolet-C (UV-C) radiation significantly impacts living organisms. UV-C radiation can also be used as a pest management tool. Therefore, this study was designed to investigate the effect of UV-C radiation on the physiology and gene expression level of Plutella xylostella, a destructive vegetable pest. Results showed that, after exposure to UV-C radiation for 3, 6, 12, and 24 h, the activity of SOD (superoxide dismutase) and CAT (catalase) of P. xylostella increased, while the activity of PPO (polyphenol oxidase), POD (peroxidase), AChE (acetylcholinesterase), CarE (carboxylesterase), and ACP (acid phosphatase) decreased with increased exposure time. Correlation coefficient analyses indicated that the activity of CAT correlated positively, while PPO and CarE correlated negatively, with exposure time. Gene regulation analysis via qRT-PCR confirmed a significant increase in regulation in CAT, CarE, and PPO-related genes. We also investigated the effect of UV-C exposure on the virulence of Cordyceps fumosorosea against P. xylostella. Here, results indicated that when the fungal treatment was applied to larvae before UV-C radiation, the virulence of C. fumosorosea was significantly reduced. However, this decline in virulence of C. fumosorosea due to UV-C exposure remained only for one generation, and no effect was observed on secondary infection. On the other hand, when larvae were exposed to UV-C radiation before fungal application, the mortality rate significantly increased as the exposure time to UV-C radiation increased. From the current study, it could be concluded that UV-C exposure suppressed the immunity to P. xylostella, which later enhanced the virulence of entomopathogenic fungi. Moreover, the study also suggested that UV irradiation is an effective pest management tool that could be incorporated into pest management strategies, which could help reduce pesticide application, be economically beneficial for the farmer, and be environmentally safe.


Asunto(s)
Cordyceps , Mariposas Nocturnas , Acetilcolinesterasa , Animales , Larva/microbiología , Mariposas Nocturnas/microbiología
19.
Huan Jing Ke Xue ; 43(3): 1323-1331, 2022 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-35258196

RESUMEN

Fugitive dust poses an important contribution to urban air particulate matter in China. To further improve the level of dust pollution prevention and control, the emission and contribution characteristics of urban fugitive dust were summarized; the main causes of dust pollution were analyzed; and the key links, key indicators, and main measures for prevention and control were clarified, so as to further improve the concept of "accurate dust control." Among all types of fugitive dust sources, road dust and construction dust were the main emission and contribution sources, among which road dust was more prominent. Production activities, vehicle disturbances, and wind erosion were the main dust-generating links of various dust sources. Silt loading was taken as the key control index for road dust prevention and control, whereas silt loading and bare soil (or material) areas were taken as the key control index for construction and other dust sources. Around the key indicators, three main ways to control the road dust and six main measures to control the construction and other dust sources were defined. In addition, some suggestions on the necessary supporting measures for dust control were put forward, so as to provide a comprehensive and beneficial reference for the practical application of dust control in Chinese cities.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/prevención & control , China , Polvo/análisis , Monitoreo del Ambiente , Material Particulado/análisis
20.
Mol Med Rep ; 25(2)2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35014686

RESUMEN

Long non­coding RNAs can regulate the malignant tumor phenotype either as tumor suppressors or oncogenes. The present study investigated the underlying mechanism of LINC00238 in liver cancer. LINC00238 was identified as a downregulated molecule in The Cancer Genome Atlas liver hepatocellular carcinoma dataset through Gene Expression Profiling Interactive Analysis software. Through gain­ and loss­of­function experiments, LINC00238 was confirmed as a tumor suppressor that could not only decrease cell viability, migration and invasion in vitro, but also tumorigenesis and tumor metastasis in vivo. By cytoplasmic and nuclear RNA isolation, LINC00238 was confirmed to be predominantly cytoplasmic. Mechanistically, RNA pull­down assays showed that LINC00238 sponged microRNA (miR)­522 and then reversed the inhibitory effects on two downstream targets, secreted frizzled related protein 2 and dickkopf1. Collectively, LINC00238 was identified as a tumor suppressor that acts via sponging miR­522 followed by silencing of downstream targets, suggesting that LINC00238 may have a key role in suppressing the malignant phenotype of liver cancer cells.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Línea Celular , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Pollos , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , MicroARNs/genética , Modelos Biológicos , Fenotipo , Pronóstico
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