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1.
Micromachines (Basel) ; 12(3)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800834

RESUMO

Non-contact manipulation technology has a wide range of applications in the manipulation and fabrication of micro/nanomaterials. However, the manipulation devices are often complex, operated only by professionals, and limited by a single manipulation function. Here, we propose a simple versatile optoelectronic tweezer (OET) system that can be easily controlled for manipulating microparticles with different sizes. In this work, we designed and established an optoelectronic tweezer manipulation system. The OET system could be used to manipulate particles with a wide range of sizes from 2 µm to 150 µm. The system could also manipulate micro-objects of different dimensions like 1D spherical polystyrene microspheres, 2D rod-shaped euglena gracilis, and 3D spiral microspirulina. Optical microscopic patterns for trapping, storing, parallel transporting, and patterning microparticles were designed for versatile manipulation. The sorting, rotation, and assembly of single particles in a given region were experimentally demonstrated. In addition, temperatures measured under different objective lenses indicate that the system does not generate excessive heat to damage bioparticles. The non-contact versatile manipulation reduces operating process and contamination. In future work, the simple optoelectronic tweezers system can be used to control non-contaminated cell interaction and micro-nano manipulation.

2.
Nutrients ; 13(3)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802755

RESUMO

Obesity and hyperglycemia are two serious chronic diseases that are increasing in incidence worldwide. This research aimed to develop a fermented cloudy apple juice with good hyperglycemia intervention activities. Here, cloudy apple juice (CAJ), cloudy apple juice rich in polyphenols (CAJP) and fermented cloudy apple juice rich in polyphenols (FCAJP) were prepared sequentially, and then the effects of the three apple juices on weight, lipid level, gut microbiota composition and intestinal tract health were evaluated for obese mice induced by a high-fat diet. The research findings revealed that the FCAJP showed potential to inhibit the weight gain of mice, reduce fat accumulation, and regulate the blood lipid levels of obese mice by decreasing the ratio of the Firmicutes/Bacteroidotas, improving the Sobs, Ace, and Chao indexes of the gut microbiota and protecting intestinal tract health. In addition, the FCAJP augmented the abundance of Akkermansia and Bacteroides, which were positively related to SCFAs in cecal contents. This study inferred that FCAJP could be developed as a healthy food for preventing obesity and hyperglycemia.

3.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806437

RESUMO

Tiger nut (Cyperus esculentus), a perennial C4 plant of the Cyperaceae family, is an unconventional crop that is distinguished by its oil-rich tubers, which also possesses the advantages of strong resistance, wide adaptability, short life periods, and large biomass. To facilitate studies on gene expression in this species, we identified and validated a series of reference genes (RGs) based on transcriptome data, which can be employed as internal controls for qRT-PCR analysis in tiger nut. Fourteen putative candidate RGs were identified and evaluated across nine different tissues of two cultivars, and the RGs were analyzed using three different algorithms (geNorm, NormFinder, and BestKeeper). The stability rankings of the candidate RGs were merged into consensus lists with RankAggreg. For the below-ground storage organ of tiger nut, the optimal RGs were TUB4 and UCE2 in different developmental stages of tubers. UCE2 and UBL5 were the most stably expressed RGs among all tissues, while Rubisco and PGK exhibited the lowest expression stability. UCE2, UBL5 and Rubisco were compared to normalize the expression levels of the caleosin (CLO) and diacylglycerol acyltransferase 2-2 (DGAT2-2) genes across the same tissues. Our results showed that the RGs identified in this study, which exhibit more uniform expression patterns, may be utilized for the normalization of qRT-PCR results, promoting further research on gene expression in various tissues of tiger nut.

4.
Eur J Cancer ; 148: 297-306, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33770575

RESUMO

BACKGROUND: Genetic aberrations in the cyclin-dependent kinase (CDK)4 pathway occur in 82% of patients with acral melanoma (AM), which is the predominant subtype of melanoma in China. We aimed to evaluate the anti-tumour activity of palbociclib, a selective CDK4/6 inhibitor, in patients with advanced AM with CDK4 pathway gene aberrations. METHODS: In this phase II trial, patients with advanced AM with CDK4 or/and CCND1 gain or/and CDKN2A loss were treated with oral palbociclib (125 mg) on days 1-21 of a 28-day cycle. The primary end-point was overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Whole-exome sequencing and multiplex immunohistochemistry of the available formalin-fixed, paraffin-embedded samples of nine patients were analysed to explore the predictive biomarkers of palbociclib response. RESULTS: Fifteen patients were enrolled. Three (20.0%) patients achieved tumour shrinkage at 8 weeks, including one with confirmed partial response. At data cut-off date, treatment was ongoing for one patient. The median PFS was 2.2 mo (range: 1.5-13.3 mo; 95% confidence interval [CI]: 1.9-2.5), and the median OS was 9.5 mo (range: 2.6-14.1 mo, 95% CI: 5.7-13.4). Eight patients died due to disease progression. The most common TRAEs were leukopenia (87%; Grade III/IV, 27%), neutropenia (80%; grade III/IV, 27%), and fatigue (53%; grade III/IV, 7%). Significant JAK2 deletions and SH2B3 amplifications were observed in patients who did not achieve any clinical benefit (CB) with palbociclib treatment. MCM7 amplification or protein expression level was found to be associated with CB. CONCLUSIONS: Palbociclib monotherapy demonstrated preliminary efficacy and an acceptable safety profile in advanced AM patients with CDK4 pathway aberrations. Patients with amplification or high protein levels of MCM7 were more prone to benefit from palbociclib. The JAK-STAT pathway might play a role in the mechanism of action of palbociclib in AM. TRIAL REGISTRATION NUMBER: NCT03454919. THE DATE OF REGISTRATION: March 6, 2018.

5.
Oxid Med Cell Longev ; 2021: 6636510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763172

RESUMO

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor with high morbidity and mortality. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, is overexpressed in most cancers including GBM. It is well known that hTERT can compensate telomere shortening to immortalize cells. However, in addition to the canonical function, hTERT has the roles beyond canonical telomere maintenance. To further understand the effects of hTERT on glioblastoma progression, we investigated the role of hTERT in regulating autophagy-a conserved pathway, by which cells deliver cellular organic material and impaired organelles to the lysosomes for degradation and recycle these cargos to produce energy under a stressful condition. Our results showed that downregulation of hTERT impaired autophagy levels by suppressing BECN1/beclin-1 and induced an increase of reactive oxygen species (ROS), which resulted in cell death ultimately. On the contrary, overexpression of BECN1 or treating cells with the antioxidant N-acetylcysteine (NAC) could restore the survival of hTERT knockdown cells. Our study will provide an additional basis of telomerase-targeting therapy for future clinical anticancer treatment.

6.
BMC Geriatr ; 21(1): 204, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761888

RESUMO

BACKGROUND: It is common for older people to become grandparents in later life. However, the impacts of grandparenting on their health and well-being remain ambiguous, especially in Chinese society, where the family is in the core of culture. The current study explored the relationship between grandparenthood and Chinese older people's health and psychological well-being in Hong Kong. METHODS: Cross-sectional data were collected from a sample of 1208 Hong Kong Chinese older people aged 55 and above through a telephone survey conducted in 2019. Participants were grouped into three categories: current grandparents (n = 507), grandparents-to-be (n = 275), and grandparents-not-to-be (n = 426). Multivariate linear regressions were performed to examine the relationship between grandparenting status and health and well-being outcomes, including self-rated physical health, mental health, resilience, and happiness. The potential moderating roles of older adults' demographic characteristics, including age, sex, education, marital status, financial status, were also examined. RESULTS: Bivariate analyses suggested statistically significant differences between health and well-being across the three groups of participants. Regression models showed that, compared with grandparents-not-to-be, being a current grandparent was associated with a significantly higher happiness level. Being a future grandparent was associated with significantly higher levels of happiness, resilience, and self-rated physical health. Moderating analyses showed that age, marital status, and educational level could moderate the relationship between grandparent status and resilience and self-rated mental health. CONCLUSIONS: The current study offers preliminary insights into the significant relationship between grandparenthood and older adults' health and well-being. It calls for future studies to further explore the mechanisms between grandparenthood and the healthy ageing of different subgroups of older adults.

7.
Clin Chim Acta ; 518: 101-109, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766554

RESUMO

Tumor heterogeneity is a key characteristic of malignant tumors and a significant obstacle in cancer treatment and research. Although bulk tissue sequencing has wide coverage and high accuracy, it can only represent the dominant cell signal information of each sample, while masking the unique gene expression of rare cells; therefore it cannot represent genes that are unstable within a subgroup, but unchanged in a majority of cells. With the progress of genomic technology, the emergence of single-cell sequencing (SCS) has effectively solved the above problem. Genetic, transcriptomic and epigenetic sequencing at the single-cell level provides an important basis for us to correctly classify the cell subsets of heterogeneous tumor populations and to reveal the process of complex changes in tumor cells at the molecular level. Single-cell sequencing technology has been applied to the field of cancer, revealing exciting discoveries in the potential mechanisms of tumor driver gene mutation, clonal evolution, invasion and metastasis. It also provides favorable conditions for developing new tumor biomarkers and providing more accurate and individualized targeted tumor therapy. Herein, we review the steps and methods of single-cell sequencing and highlight the application of SCS in tumor diagnosis and clinical treatment.

8.
BMC Microbiol ; 21(1): 80, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750295

RESUMO

BACKGROUND: A wide variety of bacterial adaptative responses to environmental conditions are mediated by signal transduction pathways. Two-component signal transduction systems are one of the predominant means used by bacteria to sense the signals of the host plant and adjust their interaction behaviour. A total of seven open reading frames have been identified as putative two-component response regulators in the gram-negative nitrogen-fixing bacteria Azorhizobium caulinodans ORS571. However, the biological functions of these response regulators in the symbiotic interactions between A. caulinodans ORS571 and the host plant Sesbania rostrata have not been elucidated to date. RESULTS: In this study, we identified and investigated a two-component response regulator, AcfR, with a phosphorylatable N-terminal REC (receiver) domain and a C-terminal HTH (helix-turn-helix) LuxR DNA-binding domain in A. caulinodans ORS571. Phylogenetic analysis showed that AcfR possessed close evolutionary relationships with NarL/FixJ family regulators. In addition, six histidine kinases containing HATPase_c and HisKA domains were predicted to interact with AcfR. Furthermore, the biological function of AcfR in free-living and symbiotic conditions was elucidated by comparing the wild-type strain and the ΔacfR mutant strain. In the free-living state, the cell motility behaviour and exopolysaccharide production of the ΔacfR mutant were significantly reduced compared to those of the wild-type strain. In the symbiotic state, the ΔacfR mutant showed a competitive nodule defect on the stems and roots of the host plant, suggesting that AcfR can provide A. caulinodans with an effective competitive ability for symbiotic nodulation. CONCLUSIONS: Our results showed that AcfR, as a response regulator, regulates numerous phenotypes of A. caulinodans under the free-living conditions and in symbiosis with the host plant. The results of this study help to elucidate the involvement of a REC + HTH_LuxR two-component response regulator in the Rhizobium-host plant interaction.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33721542

RESUMO

Sample pre-treatment plays an important role in sample analysis, which directly affects the accuracy and reliability of the results. In this work we studied the influence of three common sample pre-treatment methods (direct injection, microwave digestion and wet digestion) on the determination of lead (Pb) content of Chinese health-care wines by graphite furnace atomic absorption spectrometry (GFAAS). Six different brands of Chinese health wines were selected for the research. After each Chinese health-care wine was digested by three digestion methods, GFAAS was used to detect the Pb content of the samples. For the selected six different health-care wines, the results showed that the Pb content obtained by GFAAS with different pre-treatment methods were different. Microwave digestion had the best recovery, and was proposed to be applied to the pre-treatment of many kinds of health-care wines, while the direct injection method might be suitable only for health-care wine with lesser amounts of ingredients such as sugar. In the practical work, due to the complexity of the base composition of Chinese health-care wines, currently there is no relevant standard analysis method for the pre-treatment of Chinese health wines. According to the accuracies of the three chosen common pre-treatment methods, it was proposed that microwave digestion might be more suitable as a standard digestion method for the determination of Pb in Chinese health-care wines. This work could provide theoretical support for the further establishment of a standard analytical method for the determination of lead and other (heavy) metal elements in Chinese health wines by GFAAS and other methods.

10.
Parasit Vectors ; 14(1): 130, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648561

RESUMO

BACKGROUND: Parasites of the genus Trichinella are the pathogenic agents of trichinellosis, which is a widespread and severe foodborne parasitic disease. Trichinella spiralis resides primarily in mammalian skeletal muscle cells. After invading the cells of the host organism, T. spiralis must elude or invalidate the host's innate and adaptive immune responses to survive. It is necessary to characterize the pathogenesis of trichinellosis to help to prevent the occurrence and further progression of this disease. The aims of this study were to elucidate the mechanisms of nurse cell formation, pathogenesis and immune evasion of T. spiralis, to provide valuable information for further research investigating the basic cell biology of Trichinella-infected muscle cells and the interaction between T. spiralis and its host. METHODS: We performed transcriptome profiling by RNA sequencing to identify global changes at 1, 3, 7, 10 and 15 days post-infection (dpi) in gene expression in the diaphragm after the parasite entered and persisted within the murine myocytes; the mice were infected by intravenous injection of newborn larvae. Gene expression analysis was based on the alignment results. Differentially expressed genes (DEGs) were identified based on their expression levels in various samples, and functional annotation and enrichment analysis were performed. RESULTS: The most extensive and dynamic gene expression responses in host diaphragms were observed during early infection (1 dpi). The number of DEGs and genes annotated in the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases decreased significantly in the infected mice compared to the uninfected mice at 3 and 7 dpi, suddenly increased sharply at 10 dpi, and then decreased to a lower level at 15 dpi, similar to that observed at 3 and 7 dpi. The massive initial reaction of the murine muscle cells to Trichinella infection steadied in the later stages of infection, with little additional changes detected for the remaining duration of the studied process. Although there were hundreds of DEGs at each time point, only 11 genes were consistently up- or downregulated at all 5 time points. CONCLUSIONS: The gene expression patterns identified in this study can be employed to characterize the coordinated response of T. spiralis-infected myocytes in a time-resolved manner. This comprehensive dataset presents a distinct and sensitive picture of the interaction between host and parasite during intracellular infection, which can help to elucidate how pathogens evade host defenses and coordinate the biological functions of host cells to survive in the mammalian environment.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33712428

RESUMO

Acetic acid and furfural are the two prevalent inhibitors coexisting with glucose and xylose in lignocellulosic hydrolysate. The transcriptional regulations of Saccharomyces cerevisiae in response to acetic acid (Aa), furfural (Fur), and the mixture of acetic acid and furfural (Aa_Fur) were revealed during mixed glucose and xylose fermentation. Carbohydrate metabolism pathways were significantly enriched in response to Aa, while pathways of xenobiotics biodegradation and metabolism were significantly enriched in response to Fur. In addition to these pathways, other pathways were activated in response to Aa_Fur, i.e., cofactors and vitamins metabolism, and lipid metabolism. Overexpression of Haa1p or Tye7p improved xylose consumption rate by nearly 50%, while the ethanol yield enhanced by nearly 8% under acetic acid and furfural stress conditions. Co-overexpression of Haa1p and Tye7p resulted in 59% increase in xylose consumption rate and 12% increase in ethanol yield, revealing the beneficial effects of Haa1p and Tye7p on improving the tolerance of yeast to mixed acetic acid and furfural.IMPORTANCEInhibitor tolerance is essential for S. cerevisiae when fermenting lignocellulosic hydrolysate with various inhibitors, including weak acids, furans, and phenols. The details regarding how xylose-fermenting S. cerevisiae strains respond to multiple inhibitors during fermenting mixed glucose and xylose are still unknown. This study revealed the transcriptional regulation mechanism of an industrial xylose-fermenting S. cerevisiae strain in response to acetic acid and furfural. The transcription factor Haa1p was found to be involved in both acetic acid and furfural tolerance. In addition to Haa1p, four other transcription factors, Hap4p, Yox1p, Tye7p, and Mga1p, were identified able to improve the resistance of yeast to these two inhibitors. This study underscores the feasibility of uncovering effective transcription factors for constructing robust strains for lignocellulosic bioethanol production.

12.
Iran J Parasitol ; 16(1): 122-135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33786054

RESUMO

Background: Trichinellosis is a serious food-borne parasitic zoonosis, thus finding high quality antigens is the key to serodiagnosis of trichinosis. This article reports the characterization and sensitivity of four recombinant proteins expressed by four genes (Wn10, Zh68, T668, and Wm5) from different developmental stages of Trichinella spiralis for the diagnosis of trichinellosis in mice. Methods: This study was conducted in Jilin University and National Institute of Parasitic Diseases of Chinese Center for Disease Control and Prevention in 2017-2018. The structures and functions of the proteins encoded by four genes were predicted by bioinformatics analysis. The four genes were cloned and expressed, and the recombinant proteins were purified. Anti-Trichinella IgM and IgG antibodies in the sera of mice infected with T. spiralis from 1-45 d post-infection (dpi) were evaluated by ELISA. Results: The optimal antigen epitopes of four proteins (P1, P2, P3, and P4) encoded by the four genes from T- and B-cells were predicted, and four purified recombinant proteins (r-P1, r-P2, r-P3, and r-P4) were successfully produced. For IgM, the antibody levels detected by the four recombinant antigens were approximately equal to the cut-off value. Anti-Trichinella IgG antibodies were first detected by r-P1 at 8 dpi, followed by r-P2, r-P3, and r-P4 at 10 dpi, 14 dpi, and 16 dpi, respectively, and the antibody levels remained high until 45 dpi. Conclusion: The recombinant antigens r-P1, r-P2, r-P3, and r-P4 could be antigens that react with antibodies, they showed high sensitivity in the detection of anti-Trichinella IgG antibodies in mice. Among these proteins, r-P1 may be a candidate antigen for the detection of anti-Trichinella IgG antibodies in the early infection phase and exhibited the best sensitivity among the antigens.

13.
Anal Chem ; 93(13): 5529-5536, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33752323

RESUMO

Cervical cancer is the fourth leading cause of death in women, especially in developing countries. Specific and economic methodologies for HPV typing are crucial in cancer diagnosis and further disease control. However, routine assays based on real-time polymerase chain reaction (qPCR) or DNA-chip hybridization are either incapable of offering detailed subtype information or involve tedious open-tube operations with the risk of cross-contamination from PCR amplicons. Herein, we proposed a multiplex visualized closed-tube PCR (Multi-Vision) for HPV typing. Using gold nanoparticle probes (AuNPs) as a color change indicator combined with a Hamming distance 2 coding scheme, 13 high-risk HPVs and two subtypes associated with high-incidence benign lesions were successfully typed by performing six closed-tube PCRs. The assay demonstrates high specificity with no cross-reaction among different subtypes under several artificial sample concentrations (from 100 to 103 copies per reaction) and enables highly sensitive detection of as low as 0.5 copies/µL. Further, 105 clinical samples were successfully analyzed using our method with a high concordance rate of 99.05% (104/105) compared to a HPV typing kit. The inconsistent sample was confirmed by sequencing to be consistent with the typing results determined by our method, indicating that Multi-Vision could be a useful tool for HPV detection, especially in resource-limited regions.

14.
Ann Palliat Med ; 10(1): 169-183, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545754

RESUMO

BACKGROUND: Hyperandrogenism (HA), inflammation, and oxidative damage play key roles in the pathophysiology of polycystic ovary syndrome (PCOS). Whether vitamin D adjuvant therapy improves hormonal, inflammation, and oxidative damage in PCOS patients has aroused widespread interest, but the results are controversial. To evaluate the effect of vitamin D supplementation on hormonal, oxidative stress, and inflammatory parameters in patients with PCOS. METHODS: A literature search was conducted in Medline, the Cochrane Library, EMBASE, and Web of Science for studies related to PCOS and vitamin D supplementation. All reports of randomized controlled trials (RCTs) published before December 2019 were identified. The fixed-effects model or random-effects model was used to calculate pooled estimates of standardized differences in means (SMD) with 95% confidence intervals (CI). RESULTS: A total of 956 identified studies were retrieved, and eighteen RCTs involving 1,060 participants were ultimately included in the current meta-analysis. The pooled results demonstrated that vitamin D supplementation in patients with PCOS resulted in a significant improvement in serum total testosterone (TT), high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and malondialdehyde (MDA). No significant effect on free testosterone (FT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), free androgen index (FAI), nitric oxide (NO), and total glutathione (GSH) levels was found. Subgroup analysis showed that vitamin D supplementation reduced hs-CRP and MDA irrespective of the treatment course, type of vitamin D intervention, supplementation frequency, and dosage. Twelve weeks of vitamin D supplementation improved TT and TAC while low-dose vitamin D supplementation (≤1,000 IU/day) improved TT and DHEA-S. Vitamin D co-supplementation reduced TT, FT, and DHEA-S, while a daily supplementation regime improved TT, DHEA-S, and TAC in patients with PCOS. CONCLUSIONS: The current meta-analysis demonstrates that vitamin D supplementation in patients with PCOS resulted in an improvement in the levels of TT, hs-CRP, TAC, and MDA, but did not affect FT, DHEA-S, SHBG, FAI, NO, and GSH levels. Vitamin D co-supplementation, low-dose vitamin D supplementation (≤1,000 IU/day), and daily supplementation frequency appeared to be more conducive to improving hormones, inflammation, and oxidative stress in PCOS patients.

15.
Mol Cell Proteomics ; : 100053, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561546

RESUMO

Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor therapeutic outcomes. However, the alterations in proteins and post-translational modifications (PTMs) leading to the pathogenesis of ESCC remains unclear. Here, we provide the comprehensive characterization of the proteome, phosphorylome, lysine acetylome and succinylome for ESCC and matched control cells using quantitative proteomic approach. We identify abnormal protein and post-translational modification (PTM) pathways, including significantly downregulated lysine succinylation sites in cancer cells. Focusing on hyposuccinylation, we reveal that this altered PTM was enriched on enzymes of metabolic pathways inextricably linked with cancer metabolism. Importantly, ESCC malignant behaviors such as cell migration are inhibited once the level of succinylation was restored in vitro or in vivo. This effect was further verified by mutations to disrupt succinylation sites in candidate proteins. Meanwhile, we found that succinylation has a negative regulatory effect on histone methylation to promote cancer migration. Finally, hyposuccinylation is confirmed in primary ESCC specimens. Our findings together demonstrate that lysine succinylation may alter ESCC metabolism and migration, providing new insights into the functional significance of PTM in cancer biology.

16.
Photodiagnosis Photodyn Ther ; : 102223, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609758

RESUMO

The photodamage induced by PDT drugs usually occurs at the site where the photosensitizers accumulate in the tumor cells, thus the modulation of intrinsic apoptosis by mitochondria-targeting PDT drugs might be a promising way to enhance the therapeutic efficacy of PDT drugs against tumor cells. Novel triphenylphosphonium-functionalized nanocomposites employed as carriers of a photoactive platinum diimine complex have been fabricated and characterized. Upon irradiation, the IC50 value of photosensitizer-loaded triphenylphosphonium-functionalized nanocomposites was found to be 17.4 or 14.4 times lower than that of the photosensitizer studied alone against HCT116 cells or A549 cells, respectively. The results suggested that the triphenylphosphonium- functionalized nanocomposites as drug delivery vehicles could significantly enhance the photodynamic therapy efficacy of the photosensitizer.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33611636

RESUMO

PURPOSE: We aimed to establish the clinicopathological characteristics and prognostic factors of patients with melanoma brain metastases (MBM) in the East Asian population. METHODS: Overall survival (OS) and intracranial progression-free survival (PFS) were evaluated by Kaplan-Meier analysis. Cox regression analyses were used to determine prognostic factors associated with intracranial PFS and OS. RESULTS: Between July 2007 and December 2019, 431 patients diagnosed with MBM were enrolled. Mucosal subtype (p = 0.013), LDH level (p = 0.014), the number of MBM ≥ 4 (p = 0.02), local treatment (p < 0.0001) and the use of PD-1 inhibitors (p < 0.0001) were independent prognostic factors for intracranial PFS. Mucosal subtype (p = 0.022), LDH level (p = 0.005), no extracranial metastasis (p = 0.01), concurrent liver metastasis (p = 0.004), local treatment (p = 0.001) and the use of PD-1 inhibitors (p < 0.0001) were independent prognostic factors for OS. Mucosal subtype brain metastases had a poor response to PD-1 inhibitors (p = 0.007), with a shorter intracranial PFS than other subtypes. In BRAF mutation patients with MBM, the first-line BRAF/MEK inhibitor therapy group had an advantage in OS compared to the first-line anti-PD-1 therapy group (p = 0.043). CONCLUSION: Our findings depict clinical characteristics and prognostic factors of MBM in the East Asian population, suggesting the mucosal subtype as an adverse prognostic and predictive factor for patients with MBM. For BRAF mutation patients with MBM, first-line BRAF/MEK inhibitor therapy may bring a potential survival benefit compared to first-line anti-PD-1 therapy.

18.
J Mol Model ; 27(3): 89, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33611758

RESUMO

Thiazole ring is an important active molecular skeleton of drugs. Thiazole in natural products and drugs are usually harmlessly eliminated. However, hepatotoxic reactions may occur due to the biological activation of thiazole to produce reactive thioamide. A typical example is hepatotoxic sudoxicam and safety meloxicam. The only structural difference between them is a methyl group on C5 position of thiazole in meloxicam. The molecular basis for the difference remains unknown and the bioactivation mechanism of the thiazole ring is still obscure. Quantum chemical calculations were performed to elucidate the activation mechanism of the thiazole ring under P450 catalysis, and the influence of the substituents on the activation pathways of thiazole ring was also studied. The calculated results show that the activation of thiazole is closely related to the substituents on the thiazole and spin state of Cpd I. The thiazole and substituted thiazole directly open the ring when catalyzed by doublet spin state Cpd I that catalyzed by the quartet spin state Cpd I can open the ring directly or indirectly, which is related to the substituents. Thiazoles modified with electron-donating substituents mainly undergo direct ring opening, while thiazoles modified with electron-withdrawing groups or weak electron-donating groups mainly undergo indirect ring-opening process accompanied by intermediate formation. The research results laid the foundation for the design of thiazole ring drugs, and also laid a theoretical foundation for the study of reducing the toxicity of thiazole ring drugs.

19.
Vis Comput Ind Biomed Art ; 4(1): 4, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620595

RESUMO

In this study, a virtual-point concept was introduced into fiber-laser photoacoustic tomography to improve the elevational image resolution. The flexible fiber laser was bent into an arc shape to conform to the ultrasound wavefront, which formed an ultrasound focus at the center of the arc. The synthetic aperture focusing technique was utilized to reconstruct the images; as a result, the elevational resolution particularly within the out-of-focus region was considerably improved compared to the resolution of an image retrieved by multiplexing the PA time-resolved signals with sound velocity. The all-optical fiber-laser photoacoustic tomography system with a high spatial resolution has potential for various applications, including biomedical research and preclinical/clinical diagnosis.

20.
PLoS Negl Trop Dis ; 15(2): e0009040, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33600403

RESUMO

Trichinella spiralis (T. spiralis) is a widely distributed pathogenic microorganism that causes trichinellosis, a disease that has the potential of causing severe harm to their host. Numerous studies have demonstrated that autophagy can be triggered by microbial infection, such as bacteria, viruses, protozoa, and parasitic helminths. However, it's still unknown whether autophagy can facilitate host resistance to T. spiralis infection. The present study examined the role of autophagy in striated muscle cell transformation following infection with T. spiralis in BALB/c mice. Transmission electron microscopy (TEM) was used to detect the production of the host diaphragm autophagosome after T. spiralis infection, and changes in the protein and transcriptional levels of autophagic marker proteins were also detected. The significance of autophagy in T. spiralis infection, namely inhibition of T. spiralis growth, was preliminarily evaluated by conducting in vivo experiments using autophagy inhibitors. Besides, we studied the effect of excretory-secretory products (ES) of T. spiralis on autophagy of C2C12 myoblasts. The changes in protein and gene expression levels in autophagy-related pathways in vitro and in vivo were measured as further evidence. The results showed that T. spiralis infection induced autophagy in the host muscle cells. Meanwhile, ES inhibited autophagy of myoblasts in vitro, but this did not affect the cell viability. The upregulation and downregulation of autophagy-related factors in skeletal muscle cells may indicate an adaptive mechanism providing a comfortable niche for the parasite.

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