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1.
J Nanobiotechnology ; 19(1): 323, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654435

RESUMO

Knocking down the oncogene ROC1 with siRNA inhibits the proliferation of cancer cells by suppressing the Neddylation pathway. However, methods for delivering siRNA in vivo to induce this high anticancer activity with low potential side effects are urgently needed. Herein, a folic acid (FA)-modified polydopamine (PDA) nanomedicine used in photothermal therapy was designed for siRNA delivery. The designed nanovector can undergo photothermal conversion with good biocompatibility. Importantly, this genetic nanomedicine was selectively delivered to liver cancer cells by FA through receptor-mediated endocytosis. Subsequently, the siRNA cargo was released from the PDA nanomedicine into the tumor microenvironment by controlled release triggered by pH. More importantly, the genetic nanomedicine not only inhibited liver cancer cell proliferation but also promoted liver cell apoptosis by slowing ROC1 activity, suppressing the Neddylation pathway, enabling the accumulation of apototic factor ATF4 and DNA damage factor P-H2AX. Combined with photothermal therapy, this genetic nanomedicine showed superior inhibition of the growth of liver cancer in vitro and in vivo. Taken together, the results indicate that this biodegradable nanomedicine exhibits good target recognition, an effective pH response, application potential for genetic therapy, photothermal imaging and treatment of liver cancer. Therefore, this work contributes to the design of a multifunctional nanoplatform that combines genetic therapy and photothermal therapy for the treatment of liver cancer.

2.
Front Pharmacol ; 12: 668887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630073

RESUMO

Jujuboside B (JB) is one of the main biologically active ingredients extracted from Zizyphi Spinosi Semen (ZSS), a widely used traditional Chinese medicine for treating insomnia and anxiety. Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. The purpose of this study was to examine whether JB could prevent breast cancer and its underlying mechanism. First, we reported that JB induced apoptosis and autophagy in MDA-MB-231 and MCF-7 human breast cancer cell lines. Further mechanistic studies have revealed that JB-induced apoptosis was mediated by NOXA in both two cell lines. Moreover, the AMPK signaling pathway plays an important role in JB-induced autophagy in MCF-7. To confirm the anti-breast cancer effect of JB, the interaction of JB-induced apoptosis and autophagy was investigated by both pharmacological and genetic approaches. Results indicated that autophagy played a pro-survival role in attenuating apoptosis. Further in vivo study showed that JB significantly suppressed the growth of MDA-MB-231 and MCF-7 xenografts. In conclusion, our findings indicate that JB exerts its anti-breast cancer effect in association with the induction of apoptosis and autophagy.

3.
Front Oncol ; 11: 666549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195076

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. The Chinese herbal monomer fangchinoline (FCL) has been reported to have anti-tumor activity in several human cancer cell types. However, the therapeutic efficacy and underlying mechanism on ESCC remain to be elucidated. In the present study, for the first time, we demonstrated that FCL significantly suppressed the growth of ESCC both in vitro and in vivo. Mechanistic studies revealed that FCL-induced G1 phase cell-cycle arrest in ESCC which is dependent on p21 and p27. Moreover, we found that FCL coordinatively triggered Noxa-dependent intrinsic apoptosis and DR5-dependent extrinsic apoptosis by transactivating ATF4, which is a novel mechanism. Our findings elucidated the tumor-suppressive efficacy and mechanisms of FCL and demonstrated FCL is a potential anti-ESCC agent.

4.
Environ Pollut ; 287: 117613, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34147780

RESUMO

Species of the genus Microcystis are among the most notorious cyanobacteria in eutrophic lakes worldwide, with ability present adverse effects on many aquatic organisms. In the surface sediments, Microcystis can be ingested by benthic macroinvertebrates such as Chironomus. However, the potential negative effects of Microcystis on Chironomus life history traits remain unclear. In the present study, we investigated the effect of different Microcystis diets on specific behaviors (burrowing activity, locomotion ability) and life history traits of Chironomus pallidivittatus (Diptera, Chironomidae). We also studied the interactive effects of microcystin-producing M. aeruginosa and temperature (15, 20, and 25 °C) stress on chironomid larvae. The results showed that the inhibitory effect on the cumulative emergence and burrowing activity of larvae was more severe when they were fed M. aeruginosa among the three Microcystis diets groups. Locomotion ability (i.e., locomotor distance and velocity) and adult dry weight decreased significantly in the group fed M. aeruginosa. Locomotion was significantly inhibited and mortality increased when the larvae were fed a mixture of M. aeruginosa and M. wesenbergii, which may have been the result of additive or synergistic effect of the toxins. Under the stress of lower temperature, C. pallidivittatus larvae exhibited weaker locomotion and growth ability, and the emerging adults were mostly male. At both the lower and higher temperature conditions, M. aeruginosa cause cumulative emergence decreased, and sex ratio imbalance, which inhibited the reproduction of larvae from the population perspective. The fourth-instar larvae showed better adaption to Microcystis than did the other instars. This study thus highlights the adverse effects of microcystin-producing M. aeruginosa on Chironomus. It also provides a novel perspective on how environmental factors may influence the behavior and life history traits of chironomid larvae, and how they may respond to cyanobacterial blooms and global warming.


Assuntos
Chironomidae , Traços de História de Vida , Microcystis , Animais , Feminino , Masculino , Microcistinas/toxicidade
6.
Front Pharmacol ; 12: 680589, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995110

RESUMO

Lung adenocarcinoma is the most common pathological type of lung cancer with poor patient outcomes; therefore, developing novel therapeutic agents is critically needed. Andrographolide (AD), a major active component derived from the traditional Chinese medicine (TCM) Andrographis paniculate, is a potential antitumor drug, but the role of AD in lung adenocarcinoma remains poorly understood. In the present study, we demonstrated that AD inhibited the proliferation of broad-spectrum lung cancer cell lines in a dose-dependent manner. Meanwhile, we found that a high dose of AD induced Noxa-dependent apoptosis in human lung adenocarcinoma cells (A549 and H1299). Further studies revealed that Noxa was transcriptionally activated by activating transcription factor 4 (ATF4) in AD-induced apoptosis. Knockdown of ATF4 by small interfering RNA (siRNA) significantly diminished the transactivation of Noxa as well as the apoptotic population induced by AD. These results of the present study indicated that AD induced apoptosis of human lung adenocarcinoma cells by activating the ATF4/Noxa axis and supporting the development of AD as a promising candidate for the new era of chemotherapy.

7.
Front Oncol ; 11: 671180, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33898327

RESUMO

The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.

8.
Dermatol Clin ; 39(2): 269-280, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33745639

RESUMO

Nail unit melanoma is an uncommon form of melanoma with worse prognosis compared with nonacral cutaneous melanoma. Nail unit melanoma is often diagnosed at a late stage. Clinical and dermoscopic features may suggest a diagnosis of nail unit melanoma, but confirmation requires histologic analysis. Like the clinical diagnosis, histopathologic diagnosis of nail unit melanoma is also difficult. The surgical management of nail unit melanoma has evolved from aggressive amputations to digit-sparing approaches. This article reviews the clinical presentation, diagnosis, and surgical treatment of nail unit melanoma to promote early diagnosis and rational surgery.


Assuntos
Melanoma , Doenças da Unha , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Doenças da Unha/diagnóstico por imagem , Doenças da Unha/cirurgia , Unhas/cirurgia , Prognóstico , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia
9.
Sci Total Environ ; 754: 142395, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254876

RESUMO

The Orange County Sanitation District (OCSD) is a public agency that provides treatment of wastewater for residents in Orange County, California. The final effluent characteristics at OCSD have been altered in the last 18 years due to the ~20-fold increase of sodium hypochlorite usage for disinfecting waste streams from 2002 to 2010, implementation of the Ground Water Replenishment System (GWRS) in 2008, and conversion to full secondary treatment, together with a major reduction of sodium hypochlorite usage in 2011. This study analyzed infauna data gathered from 1994 to 2016 at the zone of initial dilution (ZID) and reference stations located on the San Pedro Shelf to assess the effects of these treatment process changes on biota in the receiving water. Impacts to the infauna community within the ZID were observed during the period of high chlorine usage, including the increased proportion of the pollution tolerant polychaete Capitella capitata complex from 6.2% in 2003 to nearly 60% in 2010, the lowest Infaunal Trophic Index score in 2009, and the highest Benthic Response Index score in 2006. The degradation of the infauna community in the ZID was correlated with chlorination and was coincidental with the initiation of the GWRS. The infauna community at the ZID recovered rapidly after the implementation of full secondary treatment as indicated by the significant reduction of the relative abundance of C. capitata complex from 59.8% in 2010 to less than 0.1% after 2012, and by the markedly improved community health index scores. This study demonstrated the composition and biointegrity of the infauna community at the ZID varied in response to changes in the wastewater treatment process. Caution should be exercised at wastewater treatment plants when relatively higher dosages of sodium hypochlorite are used over a multi-year period, as this may negatively impact aquatic biota in the receiving water.


Assuntos
Água Subterrânea , Águas Residuárias , Animais , Biota , California , Cloro
10.
Environ Sci Technol ; 54(18): 11127-11136, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32794702

RESUMO

Formation of halogenated disinfection byproducts (DBPs) from pharmaceutically active compounds has been observed in water supply systems following wastewater chlorination. Although research has been limited thus far, several studies have shown that halogenated DBPs may elicit increased toxicity compared to their parent compounds. For example, the lipid regulator gemfibrozil has been shown to form chlorogemfibrozil (Cl-gemfibrozil) and bromogemfibrozil (Br-gemfibrozil) following chlorination, which are more potent antiandrogens in male Japanese medaka (Oryzias latipes) compared to their parent compounds. In the present study, we aimed to characterize the bioaccumulative ability of halogenated gemfibrozil DBPs in marine polychaetes via chronic sediment exposures and, consequently, to assess the chronic and acute toxicity of halogenated gemfibrozil DBPs through sediment (in vivo) and aqueous (in vivo and in silico) toxicity evaluations. Following 28 day sediment exposures, Cl-gemfibrozil and Br-gemfibrozil bioaccumulated within Neanthes arenaceodentata, with both compounds reducing survival and growth. The biota-sediment accumulation factors determined for Cl-gemfibrozil and Br-gemfibrozil were 2.59 and 6.86, respectively. Furthermore, aqueous 96 h toxicity tests with N. arenaceodentata indicated that gemfibrozil DBPs elicited increased toxicity compared to the parent compound. While gemfibrozil had an acute LC50 value of 469.85 ± 0.096 mg/L, Cl-gemfibrozil and Br-gemfibrozil had LC50 values of 12.34 ± 0.085 and 9.54 ± 0.086 mg/L, respectively. Although acute toxicity is relatively low, our results indicate that halogenated gemfibrozil DBPs are bioaccumulative and may elicit effects in apex food web organisms prone to accumulation following lifelong exposures.


Assuntos
Desinfetantes , Preparações Farmacêuticas , Poluentes Químicos da Água , Purificação da Água , Animais , Desinfecção , Genfibrozila/toxicidade , Halogenação , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
12.
Environ Sci Pollut Res Int ; 27(12): 13066-13080, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32016869

RESUMO

The Yungui Plateau lakes, which are characterized by a highly endemic biodiversity, have been suffering severely from anthropogenic intervention in the recent decades. Studies on the response of these biodiversity to human-mediated effects are still limited. Here, we selected the typical Lake Dianchi to investigate the correlation between macroinvertebrate spatiotemporal dynamics and human-induced eutrophication across a 2-year span (2009-2010). A total of 26 taxa were recorded, and the assemblage pattern of the macroinvertebrate community was mainly controlled by the spatiotemporal (region, season, and year) density fluctuations of some pollution-tolerant species (Limnodrilus hoffmeisteri, Tubifex tubifex, Branchiura sowerbyi, and Chironomus plumosus). Taxon richness, total density, biomass, and the abundance of Oligochaeta and Chironomidae decreased from the north to the south of the lake but were much higher in 2009 than in 2010. Moreover, the high densities of total assemblages and oligochaete occurred during spring and/or autumn, whereas that of chironomids was only high during summer. The contributions of important factors varied in different seasons, but the community variations were mainly shaped by eutrophication-related factors (e.g., Chla, N, and P). Variance partitioning analyses showed that aquatic factors were able to explain more community variations than sediment (6.9-36.6 vs. 5.3-14.7%) across seasons, but their interactive effects were negligible. The results of this study will be beneficial for restoring and managing hypereutrophic lakes in the Yungui Plateau and imply the necessity of long-term monitoring in bioassessment projects involving intensively disturbed lakes.


Assuntos
Eutrofização , Lagos , Animais , Biodiversidade , China , Humanos , Estações do Ano
13.
Eur J Med Chem ; 185: 111848, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732254

RESUMO

Protein neddylation is a posttranslational modification of conjugating the neuronal precursor cell-expressed developmentally down-regulated protein 8 (Nedd8) to substrates. Our previous work revealed that neddylation pathway is overactivated in various human lung cancers and correlates with the disease progression, whereas pharmacologically targeting this pathway has emerged as an attractive therapeutic strategy. As a follow-up research, 1331 approved drugs were investigated the inhibitory activities of cullin1 neddylation for screening the hit compounds via an improved enzyme-based assay. An antihypertensive agent, candesartan cilexetic (CDC), was identified as a novel neddylation inhibitor that ATP-competitively suppressing Nedd8-activating enzyme (NAE, E1) in mechanism, which inhibited the cullins neddylation superior than two representative non-covalent NAE inhibitors, M22 and mitoxantrone. Following with the findings such as apoptotic induction and tumor growth suppression in human lung cancer A549 in vitro and in vivo, CDC represents a potential anticancer lead compound with promising neddylation inhibitory activity.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Compostos de Bifenilo/farmacologia , Descoberta de Drogas , Tetrazóis/farmacologia , Células A549 , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Benzimidazóis/administração & dosagem , Benzimidazóis/química , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Injeções Intraperitoneais , Injeções Subcutâneas , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Relação Estrutura-Atividade , Tetrazóis/administração & dosagem , Tetrazóis/química
15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(5): 879-884, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31631639

RESUMO

Radiotherapy is one of the main treatments for tumor with increasingly high request for technique precision and the equipment stability. Machine learning may bring radiotherapy simplicity, individualization and precision, and may improve the automatic level of planning and quality assurance. Based on the process of radiotherapy, this paper reviews the applications and researches on machine learning, with an emphasis on deep learning, and proposes the prospects in the following aspects: segmentation of normal tissue and tumor, planning, treatment delivery, quality assurance and prognosis prediction.


Assuntos
Aprendizado de Máquina , Neoplasias/radioterapia , Aprendizado Profundo , Humanos
16.
Genomics Proteomics Bioinformatics ; 17(1): 76-90, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31026580

RESUMO

Agricultural activities, including stock-farming, planting industry, and fish aquaculture, can affect the physicochemical and biological characters of freshwater lakes. However, the effects of pollution producing by agricultural activities on microbial ecosystem of lakes remain unclear. Hence, in this work, we selected Honghu Lake as a typical lake that is influenced by agriculture activities. We collected water and sediment samples from 18 sites, which span a wide range of areas from impacted and less-impacted areas. We performed a geospatial analysis on the composition of microbial communities associated with physicochemical properties and antibiotic pollution of samples. The co-occurrence networks of water and sediment were also built and analyzed. Our results showed that the microbial communities of impacted and less-impacted samples of water were largely driven by the concentrations of TN, TP, NO3--N, and NO2--N, while those of sediment were affected by the concentrations of Sed-OM and Sed-TN. Antibiotics have also played important roles in shaping these microbial communities: the concentrations of oxytetracycline and tetracycline clearly reflected the variance in taxonomic diversity and predicted functional diversity between impacted and less-impacted sites in water and sediment samples, respectively. Furthermore, for samples from both water and sediment, large differences of network topology structures between impacted and less-impacted were also observed. Our results provide compelling evidence that the microbial community can be used as a sentinel of eutrophication and antibiotics pollution risk associated with agricultural activity; and that proper monitoring of this environment is vital to maintain a sustainable environment in Honghu Lake.


Assuntos
Agricultura , Antibacterianos/análise , Lagos/microbiologia , Microbiota , Poluentes Químicos da Água/análise , Animais , China , Eutrofização , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiologia , Lagos/química , Fatores de Risco
17.
Zootaxa ; 4496(1): 382-394, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30313708

RESUMO

The Changbai Mountain in northeast China harbours a species-rich enchytraeid fauna, and ca. 50 species of 11 genera have been reported so far from its well-preserved ecosystems. Herein, we add two new species of Mesenchytraeus into this enchytraeid list. Both members belong to the lineage of Mesenchytraeus with enlarged ventral chaetae. Mesenchytraeus spermatoglomeratus sp. nov. is characterized by the presence of enlarged chaetae in V-VI and XI (2 per bundle), five pairs of preclitellar nephridia (VI/VII-X/XI), sperm sacs containing curly ball-shaped sperm bundles, spermathecae without diverticula, atrium with 4-6 developed prostate glands and long vasa deferentia backward to XV-XXII. Mesenchytraeus liberothecus sp. nov. is diagnosed by the presence of enlarged chaetae in V-VI (2 per bundle), five pairs of preclitellar nephridia (VI/VII-X/XI), asymmetrical paired sperm sacs containing flame-shaped sperm bundles, spermathecae with two small diverticula but free from oesophagus, atrium with 4-5 large prostate glands and short vasa deterentia confined to XI and XII. The major differences between the new species and their congeners are discussed. We also add them into the key of this enlarged chaetae lineage.


Assuntos
Ecossistema , Oligoquetos , Animais , China , Masculino
18.
Zootaxa ; 4496(1): 395-410, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30313709

RESUMO

The biodiversity in the Tibetan region is still poorly known, particularly for its soil organisms. Here, we describe eleven enchytraeid species based on several taxonomical surveys in 2015-2016, from some soil localities in south region of the Tibet, China. All are firstly recorded in this region; seven species (Fridericia ratzeli sensu stricto, F. peregrinabunda, F. cusanica, F. bretscheri, Buchholzia sp., Enchytraeus buchholzi and Henlea sp.) are new records for China.


Assuntos
Oligoquetos , Animais , Biodiversidade , China , Solo , Tibet
20.
J Am Acad Dermatol ; 78(6): 1060-1067, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29518455

RESUMO

BACKGROUND: Changes in patient perceptions of quality of life (QOL) after Mohs micrographic surgery (MMS) may benefit from different counseling or treatment. OBJECTIVE: To measure QOL before and after MMS and to identify risk factors associated with impaired QOL. METHODS: Prospective observational study of 727 patients with skin cancer who self-reported QOL via the Skin Cancer Index immediately before and at 1 to 2 weeks and 3 months after MMS. RESULTS: QOL fluctuated after MMS. At 1 to 2 weeks after surgery, overall QOL remained unchanged compared with before MMS. Patients reported reduced anxiety about skin cancer but had increased distress about social interactions and physical appearance. At 3 months after surgery, patients reported an overall improvement in QOL compared with before MMS (P = .0007). Age younger than 65 years (P = .0001), female sex (P = .0001), and tobacco use (P = .03) were associated with lower QOL scores at all assessment points. LIMITATIONS: Single-site observational study. Significant loss to follow-up at both time points after MMS. CONCLUSION: Patients with skin cancer had persistent concerns about social interactions and physical appearance 1 to 2 weeks after MMS, but all aspects of their QOL improved by 3 months after surgery. Patients who underwent MMS that were younger than 65 years, were female, or smoked were at increased risk for longitudinally impaired QOL.


Assuntos
Ansiedade/psicologia , Imagem Corporal/psicologia , Cirurgia de Mohs/psicologia , Qualidade de Vida , Neoplasias Cutâneas/cirurgia , Idoso , Estética , Feminino , Humanos , Relações Interpessoais , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Cirurgia de Mohs/métodos , Medidas de Resultados Relatados pelo Paciente , Assistência Perioperatória , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/psicologia , Estatísticas não Paramétricas , Fatores de Tempo
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