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1.
J Adv Res ; 35: 279-294, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35024202

RESUMO

Introduction: Perfluorooctanoic acid (PFOA) is a compound used as an industrial surfactant in chemical processes worldwide. Population and cross-sectional studies have demonstrated positive correlations between PFOA levels and human health problems. Objectives: Many studies have focused on the hepatotoxicity and liver problems caused by PFOA, with little attention to remediation of these problems. As an antioxidant, vitamin C is frequently utilized as a supplement for hepatic detoxification. Methods: In this study, we use a mouse model to study the possible role of vitamin C in reducing PFOA-induced liver damage. Based on comparative transcriptomic and metabolomic analysis, we elucidate the mechanisms underlying the protective effect of vitamin C. Results: Our results show that vitamin C supplementation reduces signs of PFOA-induced liver damage including total cholesterol and triglyceride levels increase, liver damage markers aspartate, transaminase, and alanine aminotransferase elevation, and liver enlargement. Further, we show that the protective role of vitamin C is associated with signaling networks control, suppressing linoleic acid metabolism, reducing thiodiglycolic acid, and elevating glutathione in the liver. Conclusion: The findings in this study demonstrate, for the first time, the utility of vitamin C for preventing PFOA-induced hepatotoxicity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35020143

RESUMO

The enantioselective behaviors of chiral pesticides would affect the accuracy of risk assessment. This study evaluated the enantioselectivity of chiral triticonazole (a widely used fungicide) in three kinds of fruits. Firstly, the enantioseparation of triticonazole enantiomers was carried out within 1.2 min utilizing CHIRALPAK OJ-3 column with a mixture of CO2 and methanol (93:7, v/v) using SFC-MS/MS. Secondly, field trials were conducted to clarify the enantioselective degradation and residue of S-( +)-triticonazole and R-(-)-triticonazole in fruits. The initial concentrations of rac-triticonazole were 25.1-93.1 ng/g, and enantioselective degradation was observed in pear, peach, and jujube after 2 h, 10 days, and 3 days, respectively. The degradation of S-( +)-triticonazole was fastest in pear (T1/2, 2.01 days), while the T1/2 of R-(-)-triticonazole was 5.02 days. The residue concentrations of rac-triticonazole were less than the MRL set by EU (10 ng/g) on the 3rd and 21st day in pear and peach, respectively, which were lower than 10 ng/g in jujube on the 30th day (no MRL). Finally, we found that the dietary intake risks of rac-triticonazole in fruits were low for 2-7 age, 20-50 age/female, and 20-50 age/male. The current study could provide complimentary references for the rational usage, MRL formulation, and risk assessment of chiral triticonazole.

3.
Environ Res ; 208: 112692, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34999029

RESUMO

Extracellular polymeric substances (EPS) with high molecular weights, secreted from microorganisms, play a critical functional role in the aerobic granular sludge (AGS). To investigate the level and function of EPS during the granulation of aerobic sludge and in the mature AGS, a sequencing batch reactor (SBR) was operated for 70 days. Aerobic granules with an average diameter of 0.25 mm were obtained with reducing settling time of sludge. Simultaneous removals of COD, nitrogen and phosphorus by the mature AGS exceeded 90, 95 and 95%, respectively. The EPS content increased significantly to above 333 mg/g MLVSS during the initial stage, and after that, it stabilized at about 240 mg/g MLVSS as the mature AGS formed, higher than that of the seed sludge (212 mg/g MLVSS). The increased EPS contents showed a negative correlation with SVI values, while a strong positive relationship with the formation of the AGS. The protein/polysaccharide (PN/PS) ratio in the EPS increased from 1.42 to 4.17, and TP/MLSS increased to about 6%, with the formation of AGS. The proportion of extracellular-P increased with the increase of EPS, and then maintained stable at about 20%, indicating EPS promoted the removal of phosphorus. Furthermore, the results from the Standards, Measurements and Testing (SMT) and X-Ray Diffraction (XRD) showed that phosphorus in the AGS mainly existed in the form of inorganic phosphorus (IP) and the proportion of Ca5(PO4)3(OH) in IP was up to 92%. This investigation demonstrated that EPS had a positive relationship with the sludge granulation and nutrients removal.

4.
Brain Res Bull ; 180: 24-30, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34990732

RESUMO

The main pathological changes that occur in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are extensive demyelination of brain white matter and neuron damage. Previous studies suggested that demyelination and neuron injury are related to activating the Rho/ROCK signaling pathway. Inhibition of the Rho/ROCK signaling pathway can alleviate neuron injury and promote myelin repair. This study utilized a DEACMP model in which rats were prepared by space injection of CO gas intraperitoneally (CO group), and the association between the Rho/ROCK signaling pathway and DEACMP was investigated. The ROCK2 kinase inhibitor Y-27632 was used to prevent the effects of the DEACMP model to elucidate its protective mechanism. The results demonstrated that the cognitive and motor functions were significantly impaired, and the GFAP, NSE, RhoA, and ROCK2 protein levels were significantly increased in the CO group within three weeks after the model was established. After Y-27632 intervention, the cognitive and motor functions of the CO+Y-27632 group were significantly improved within three weeks after the model was established. In the CO+Y-27632 group, the RhoA, ROCK2, GFAP, and NSE (indicating neuron injury) protein levels decreased significantly, and the MBP protein levels (indicating myelin repair) increased significantly within three weeks after the model was established. These results suggested that the pathogenesis of DEACMP was associated with activation of the Rho/ROCK pathway and that Y-27632 inhibited ROCK2 kinase activity in the CO exposed rats, resulting in improved behavioral deficits, reduced neuron damage, and promotion of myelin repair. Therefore, Y-27632 might be a potentially effective drug for the treatment of DEACMP-induced brain damage.

5.
Anal Chem ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35025214

RESUMO

Fluorescence barcoding with multicolor fluorophores is limited by spectral crowding. Herein, we propose a fluorescence encoding method in a single-color channel with photoswitches. The photochromic naphthopyran was used to mediate the fluorescence of polystyrene microspheres through resonance energy transfer. The initial fluorescence intensity (F0) and the fluorescence after UV light activation (F/F0) were combined to generate hundreds of 2-dimensional barcodes. The coding capacity was further expanded with the different chemical kinetics of the photoswitches. The photoswitch-based fluorescence barcodes were applied to simultaneously and selectively detect the DNA sequences of COVID-19 (with related mutations) as a proof-of-concept for real applications. The compatibility with the state-of-the-art fluorescence microscopes and simple encoding and decoding make the method very attractive for multiplexed and high-throughput analyses.

6.
Nanoscale ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029611

RESUMO

Multicolor microbeads are widely used in flow cytometry for various cellular and immunoassays. However, they are limited by their large size of around one to tens of micrometers. Nanomaterials for multiplexed analysis are emerging as valuable tools in high-throughput assays and fluorescence cell barcoding. We present barcoding and related cellular studies based on mass-produced organosilane-derived multifunctional nanospheres with a uniform size. Functional groups including thiols, amines, and azides were integrated in one step from various organosilanes without additional orthosilicates. Fluorescent nanobarcodes (NBs) were achieved through flexible physical adsorption and chemical ligation of spectrally separated fluorescent dyes. Live cells labeled with the NBs were readily distinguished by flow cytometry. The NBs have a small and uniform size (ca. 27 nm in diameter), excellent biocompatibility, rapid cellular uptake, and low dye leakage. The fluorescent nanospheres were applied for long-term cell tracking during multiple rounds of cell division and monitored over 48 hours. While most nanospheres were endolysosome-targeting, modification with fluorescein isothiocyanate (FITC) surprisingly lighted up the cell nucleus. This work lays the foundation of a unique family of functional nanomaterials promising for multiplex detection and other chemical and biological applications.

7.
J Ethnopharmacol ; 283: 114532, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34416296

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qufeng Zhitong capsule (QFZTC) is a traditional Chinese medicine (TCM) clinically used for treating pain. However, the active ingredients of QFZTC and its pharmacological mechanism in the treatment of neuropathic pain (NP) remain unclear. AIM OF THE STUDY: We aimed to identify the active ingredients of QFZTC and reveal its target genes and underlying mechanism of action in NP. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to identify the active ingredients of QFZTC. Network pharmacology analysis was conducted to determine the core targets and pathway enrichment of QFZTC. An NP mice model was established through chronic compression injury (CCI) surgery of the sciatic nerve, while von Frey instrumentation and a thermal stimulator were employed to measure the sensitivity of mice to mechanical and thermal stimuli. Immunofluorescence was used to observe the expression of TLR4 and p-P65 in microglia. Western blotting was used to detect the levels of protein expression of Iba-1, TLR4, MyD88, P65, p-P65, and c-Fos, while ELISA kits were used to detect the release of TNF-α, IL-6, and IL-1ß. RESULTS: Seven active ingredients were identified in QFZTC: gallic acid, loganylic acid, syringin, corilagin, loganin, ellagic acid, and osthole. Network analysis identified TLR4, TNF, IL6, IL1ß, and c-Fos as core targets, and Toll-like receptors and NF-κB as core signaling pathways. Treatment with QFZTC significantly relieved mechanical allodynia and thermal hyperalgesia in CCI mice models. CCI induced an increase in the expression of TLR4 and p-P65 in microglia, whereas QFZTC dose-dependently reduced the expression of Iba-1, TLR4, MyD88, and p-P65 in the spinal cord. QFZTC inhibited the expression of the c-Fos pain marker and reduced the expression of the TNF-α, IL-6, and IL-1ß inflammatory factors. CONCLUSION: We combined the active ingredients of QFZTC with network pharmacology research to clarify its biological mechanism in the treatment of NP. We demonstrated that QFZTC reduced NP in mice probably through regulating the spinal microglia via the TLR4/MyD88/NF-κB signaling pathway. Hence, QFZTC could be regarded as a potential drug for relieving NP.

8.
J Hazard Mater ; 426: 127983, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34923380

RESUMO

The trichomes of Arabidopsis thaliana serve as accumulation sites for heavy metals such as Cd2+, and thereby both help plants cope with heavy metal stress and detoxify the soil. These trichomes are also believed to prime plant defenses against insect herbivores in response to mechanical stimulation. Because Cd2+ in such trichomes may be beneficial for plant defenses, we hypothesized that mechanical stimulation would enhance sequestration of Cd2+ in trichomes. We quantified the distribution and concentration of Cd2+ in leaves of A. thaliana, of the glabrous mutant gl1-1 of A. thaliana, and Brassica rapa L. subsp. pekinensis (Lour.) Hanelt (Chinese cabbage) and examined how these changed following mechanical stimulation of the trichomes or leaves. Light brushing or exposure to caterpillars of Spodoptera exigua led trichomes of both A. thaliana and Chinese cabbage to accumulate Cd2+ complexes more rapidly and to a higher concentration than trichomes in unstimulated controls. Comparison to responses in leaves of gl1-1 mutants suggested that this acceleration and enhancement of Cd2+ storage requires signaling through trichomes. In wild type A. thaliana, Cd2+ was found exclusively in trichomes, whereas in gl1-1 mutants, Cd2+ was found mainly in the - mesophyll cells. Results suggest a mechanobiological pathway for improving heavy metal detoxification of soils through the action of hyperaccumulator plant leaves containing non-glandular trichomes.

9.
Environ Pollut ; 292(Pt B): 118459, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34740732

RESUMO

Fish community manipulation and regulation has been largely overlooked as a mitigation strategy for restoring submerged aquatic vegetation (SAV) in shallow lakes of the middle and lower Yangtze River Basin (MLYRB). An in-situ fish exclusion experiment and a large-scale lake manipulation were conducted to test the hypothesis that the reasonable removal of benthivorous and herbivorous fish would facilitate the restoration and reconstruction of SAV in shallow lakes within the MLYRB. The in-situ exclusion experiment was conducted from April to October in 2017. Electrofishing was used to remove benthivorous and herbivorous fish from the exclosures. SAV were then artificially planted in the same pattern and density in both exclosures and adjacent open sites, and responses were measured for seven consecutive months. The mean percent coverage and biomass of SAV in the exclosures increased quickly and remained significantly higher than those in open sites over the duration of the experiment. Water quality also improved as turbidity, chlorophyll-a, total phosphorus and total nitrogen in the exclosures remained significantly lower than those in the open sites. After the in-situ experiment, a larger scale manipulation of fish in the entire submerged macrophyte zone (SMZ) was implemented from 2017 to 2020. After removing more than 2/3 of the benthivorous and herbivorous fish biomass by October 2020 in the SMZ, both the species richness and spatial coverage of SAV increased from 2 to 9 and from 1.7% to 32.2%, respectively. Our results provided clear evidence that fish are strong regulators of SAV productivity and that their reasonable removal facilitates ecological recovery. Therefore, we propose that fish community manipulation as implemented in this study be given more attention in addition to the reduction of external nutrient loading when designing projects to restore SAV in shallow lakes of the MLYRB.


Assuntos
Ecossistema , Lagos , Animais , Clorofila A , Peixes , Fósforo
10.
Behav Brain Res ; 418: 113652, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758364

RESUMO

Impairments in activities of daily living (ADL) are common clinical symptoms of human Alzheimer's disease (AD). Describing the ADL in AD animal models might provide more insights into the mechanism/treatment of the disease. Here, we demonstrated that the forebrain presenilin 1(Psen1)/presenilin 2 (Psen2) conditional double knockout (DKO) mice exhibited deficits in nest building, marble burying and food burrowing starting at 3 months old and worsening at later ages. At 4 months of age, spontaneous activities in the home cage were also impaired in DKO mice, including physically demanding activities, habituation-like behaviors, and nourishment behaviors during the first two hours in the dark phase. These results indicated that loss of function of Psen1 and Psen2 in mice impaired a series of noncognitive behaviors in the early phase of neurodegeneration. This observation suggests that DKO mice are an ideal model for further mechanistic studies of Psen1 and Psen2 functions in regulating noncognitive behaviors.

11.
Bioact Mater ; 7: 263-274, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34466732

RESUMO

The real physiological environment of human body is complicated with different degrees and forms of dynamic loads applied to implanted medical devices due to the daily activities of the patients, which would have impacts on the degradation behaviors of magnesium alloy implants. In this work, the bio-corrosion behaviors of AZ31B magnesium alloy under alternating cyclic dynamic loads with different low frequencies (0.1-2.5 Hz) were specially investigated. It was found that the bio-degradation performances under external dynamic stressed conditions were much severer than those under unstressed conditions and static loads. The corrosion rates were generally accelerated as the rise of cyclic frequency. Hereby a numerical model for the degradation process of Mg alloy was established. The corrosion current density i corr of Mg alloy and the applied loading frequency f matches a linear relationship of ln i corr ∝ f, which is the result of interactions between the cyclic alternating load and corrosive environment. This work could provide a theoretical reference and an experimental basis for further researches on the biodegradation behaviors of biomedical materials under dynamic conditions.

13.
J Agric Food Chem ; 69(51): 15512-15520, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34927422

RESUMO

Chiral diniconazole is a widely used triazole fungicide, while its enantioselective behaviors in fruits have not been reported. In this article, the absolute configuration was confirmed. A fast supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was developed for the chiral separation and enantioselective study of diniconazole in four kinds of fruits. The residual concentrations gradually decreased with time in four kinds of fruits after applying diniconazole. The dissipation half-lives of R-diniconazole and S-diniconazole were in the range of 5.3-7.9 and 2.5-7.1 days respectively, and S-diniconazole was degraded preferentially. The residue concentrations were lower than the EU's MRL (0.01 mg/kg) on the 40th (harvest time), 30th, and 10th day in pear, jujube, and apple, respectively. But, in peach, residue concentrations were still higher than the MRL after 60 days and the ratio of R/S was 2.2. These results could be helpful for the reasonable use and risk assessment of chiral diniconazole.


Assuntos
Fungicidas Industriais , Espectrometria de Massas em Tandem , Frutas/química , Fungicidas Industriais/análise , Medição de Risco , Estereoisomerismo , Triazóis
14.
Bioengineered ; 12(2): 12461-12469, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34931923

RESUMO

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.


Assuntos
Anticarcinógenos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genisteína/uso terapêutico , Fitoestrógenos/uso terapêutico , Atlas como Assunto , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/virologia , Ciclina D1/genética , Ciclina D1/imunologia , Receptores ErbB/genética , Receptores ErbB/imunologia , Humanos , Interleucina-1alfa/genética , Interleucina-1alfa/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Janus Quinases/genética , Janus Quinases/imunologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Terapia de Alvo Molecular/métodos , Família Multigênica , PPAR gama/genética , PPAR gama/imunologia , Farmacogenética/métodos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/imunologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/patogenicidade , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/imunologia , Transdução de Sinais
15.
Artigo em Chinês | MEDLINE | ID: mdl-34743499

RESUMO

Lung cancer ranks the first cancer-related morbidity and mortality in China. Tumor metastasis always predicts the poor prognosis for patients. Moreover, lymphatic metastasis is one of the most significant predictors of poor prognosis in patients with non-small cell lung cancer (NSCLC) and lymphangiogenesis represents the bridge that functionally facilitates tumor lymphatic metastasis. In this review, we first discussed the molecular mechanisms of tumor-associated lymphangiogenesis and the interaction between tumor microenvironment and lymphatic endothelial cells, then, summarized the role of non-coding RNA in regulating tumor-associated lymphangiogenesis in recent frontier studies, with the aim to provide some novel insights on NSCLC-related lymphangiogenesis research, diagnosis and treatment.
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16.
Am J Epidemiol ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729579

RESUMO

We aimed to examine whether type 2 diabetes prevention diet, a dietary pattern previously developed for reducing type 2 diabetes risk, was associated with mortality in a US population. A population-based cohort of 86633 subjects was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (study period: 1993 to 2015). Dietary information was collected with a food frequency questionnaire. A dietary diabetes risk reduction score was calculated to reflect adherence to this dietary pattern, with higher scores representing better adherence. Hazard ratios (HRs) and absolute risk differences (ARDs) in mortality rates per 10000 person-years were calculated. After a mean follow-up of 13.6 years, 17532 all-cause deaths were observed. The highest versus the lowest quintiles of dietary diabetes risk reduction score was associated with decreased risks of death from all causes (HRquintile 5 versus 1: 0.76; 95% CI: 0.72, 0.80; ARDquintile 5 versus 1: -81.94; 95% CI: -93.76, -71.12), cardiovascular disease (HRquintile 5 versus 1: 0.73; 95% CI: 0.66, 0.81; ARDquintile 5 versus 1: -17.82; 95% CI: -24.81, -11.30), and cancer (HRquintile 5 versus 1: 0.85; 95% CI: 0.78, 0.94; ARDquintile 5 versus 1: -9.92; 95%CI: -15.86, -3.59), which were modified by sex, smoking status, or alcohol consumption in subgroup analyses (all Pinteraction<0.05). In conclusion, type 2 diabetes prevention diet confers reduced risks of death from all causes, cardiovascular disease, and cancer in this US population.

17.
Medicine (Baltimore) ; 100(41): e27535, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731149

RESUMO

ABSTRACT: Enhancer RNAs (eRNAs), a subclass of lncRNAs, are derived from enhancer regions. The function of eRNAs has been reported by many previous studies. However, the role of eRNAs in gastric cancer, especially the prognosis-associated eRNAs, has not been studied yet.In this study, we have used a novel approach to screened key eRNAs in gastric cancer. Kaplan-Meier correlation analysis and Co-expression analysis were used to find the most significant survival-associated eRNAs. Enrichment analysis is applied to explore the key functions and pathways of screened eRNAs. The correlation and survival analysis are used to evaluate targeted genes in the pan-cancer analysisA total of 63 prognostic-associated eRNAs in gastric cancer were identified, the top 6 eRNAs were LINC01714, ZNF192P1, AC079760.2, LINC01645, EMX2OS, and AC114489.2. The correlation analysis demonstrated the top 10 screened eRNAs and their targeted genes. The results demonstrated that EMX2OS was ranked as the top eRNA according to the results of the Kaplan-Meier analysis. The correlation analysis demonstrated that eRNA EMX2OS is correlated with age, grade, stage, and cancer status. The pan-cancer analysis demonstrated that EMX2OS was associated with poor survival outcomes in adrenocortical carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, stomach adenocarcinoma, and uveal melanoma.In this study, survival-related eRNAs were screened and the correlation between survival-related eRNAs and their targeted genes was demonstrated. EMX2OS plays a prognosis-associated eRNA role in gastric cancer, which might be a novel therapeutic target in clinical practice.


Assuntos
Adenocarcinoma/genética , Proteínas de Homeodomínio/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Adenocarcinoma/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Elementos Facilitadores Genéticos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , RNA Antissenso/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida
18.
Thorac Cancer ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34734467

RESUMO

AIM: To further elucidate the prognostic factors of non-small-cell lung cancer (NSCLC) patients with T2aN0M0 (stage IB) who underwent surgical treatment. METHODS: We retrospectively analyzed the data of stage IB NSCLC patients who underwent surgical treatment at our center from October 2013 to September 2016. Eighty patients were enrolled. We analyzed their overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. RESULTS: In univariable analysis, adenosquamous carcinoma (ASC) was significantly associated with inferior DFS (p = 0.036, p = 0.037) and OS (p = 0.001, p = 0.003) in all stage IB patients and those who only accepted surgery. Patients with a number of N2 lymph node dissections of ≥3 regions (N2-LSNDr) exhibited better DFS (p = 0.020, p = 0.005) and OS (p = 0.003, p = 0.001) in all stage IB patients and those who only accepted surgery. In addition, advanced age (≥70 years old) is an adverse factor for DFS (p = 0.049) and OS (p = 0.018) among patients who did not receive adjuvant chemotherapy following surgery. In multivariable analyses, patients with N2-LSNDr exhibited a longer OS (p = 0.045) in all enrolled patients; patients with N2-LSNDr (p = 0.016) and younger age (p = 0.021) demonstrated a superior OS in patients who only received surgery. CONCLUSIONS: We found that N2-LSNDr were independent influencing factors affecting the prognosis in all included stage IB patients and stage IB patients without adjuvant chemotherapy. ASC was associated with worse prognosis of T2aN0M0 NSCLC. Older age is an independent prognostic factor of the worst OS in stage IB patients without adjuvant chemotherapy.

19.
Cancer Manag Res ; 13: 8527-8534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803401

RESUMO

Background: Given the lack of evidence-supported guidance for therapeutic recommendations of primary mediastinal malignant germ cell tumors (PMMGCTs), our study aimed to investigate the clinicopathological features, treatment strategies, and prognostic factors of PMMGCTs. Methods: We carried out a consecutive retrospective evaluation on a series of patients diagnosed with PMMGCTs in Peking Union Medical College Hospital from January 2000 to August 2020. Results: A total of 58 patients were eligible, consisting of 51 males and seven females. There were 15 patients with seminomas, 39 with nonseminomatous germ cell tumors (NSGCTs), and four with mixed germ cell tumors (GCTs). The 5-year overall survival was 45%, with a median survival time of 32.37 months. Except for the lost follow-up of seven patients, a univariate analysis of overall survival on the remaining patients showed significant differences in pathological type (mixed GCTs were regarded as NSGCTs) (p=0.036), tumor size (>11cm) (p=0.006), and other sites metastases (OSM) (p=0.001), respectively. Multivariate Cox regression analysis revealed that OSM and surgical resection were independently associated with overall survival in all kinds of PMMGCTs. Conclusion: OSM was an independent risk factor for patients with PMMGCTs. Surgery was proved to contribute to long-term survival. More in-depth clinical evidence is urgently needed to guide the treatment of PMMGCTs.

20.
Acta Pharmacol Sin ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845369

RESUMO

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

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