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1.
J Steroid Biochem Mol Biol ; 236: 106425, 2024 02.
Article in English | MEDLINE | ID: mdl-37984747

ABSTRACT

Sphingosine-1-phosphate (S1P) is biologically active lipid, leading to neuroinflammation and macrophage invasion in central nervous system, plays an important role in the development of multiple sclerosis (MS) model in experimental allergic encephalomyelitis (EAE) rats. Vitamin D is observed to be a key factor in regulating cell S1P levels. We detected vitamin D can alleviate the symptoms of EAE rats, but the exact mechanism is unclear. In PC12 cells, vitamin D can reverse S1P-induced cell death, but the signaling pathway unclear. This study was aimed to investigate S1P regulation mechanism or signaling pathway mediated by vitamin D in EAE and PC12 model. In our experiments, S1P and Sphingosine kinase type 1 (SphK1) mRNA and protein expression in EAE rats group, control group, vitamin D feeding group were detected by HPLC, ELISA, RT-PCR and western blot. PC12 cell death was detected by Propidium (PI) staining. VDR plasmid overexpression and RNA interference, immunofluorescence, real-time cell analysis, protein immunoblotting was used to detect SphK1 transcriptional regulation, cell-substrate attachment quality, the signaling pathway of cell apoptosis and inflammation related gene expression (Bax/Bcl-2, Casepase-3, Il-6, TGF-ß, TNF-α). Our study showed vitamin D can reverse the elevation of S1P level in EAE rats, reduce the severity and shorten the course of EAE. 1,25-(OH) 2D3 coupled with vitamin D receptor (VDR) inhibited SphK1 transcription. 1,25-(OH)2D3 significantly reduced PC12 cell death rate induced by S1P, in addition improved the cell substrate attachment quality. 1,25-(OH) 2D3 can block S1P-induced p-ERK activation and PI3K /Akt signaling pathway reduced Il-6, TGF-ß, TNF-α cytokine release and Bax/Bcl-2, Casepase-3 apoptosis protein expression. On the other hand, immunofluorescence staining showed 1,25-(OH) 2D3 can increase the expression of neuronal perinuclear protein MAP2 in PC12 cells probably protect nerve cells further. In summary, the ameliorative effect of vitamin D was derived from its ability to reduce S1P levels, provides an idea for vitamin D as a combination therapy for disease.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Phosphotransferases (Alcohol Group Acceptor) , Rats , Animals , Vitamin D/pharmacology , Tumor Necrosis Factor-alpha/genetics , Interleukin-6 , bcl-2-Associated X Protein , Vitamins , Lysophospholipids/metabolism , Sphingosine/metabolism , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Transforming Growth Factor beta
2.
BMC Med Educ ; 23(1): 912, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38037047

ABSTRACT

BACKGROUND: Traditional problem-based learning (PBL) relying on tutored learning in small groups is very resource-intensive. Little is known about the benefits of PBL in a large classroom setting. This paper introduced a PBL case into the traditional didactic biochemistry course and investigated the acceptability of total online or partial online PBL in a large classroom setting introduced during the coronavirus pandemic. METHODS: The students were allocated into either total online Group 1, partial online Group 2, or partial online and with poorer academic performance Group 3. A questionnaire comprising of 8 closed-ended questions and 2 open-ended questions and final exam performances were used to evaluate the acceptability of total online or partial online PBL in a large classroom setting. The 8 closed-ended questions were analysed by the Kruskal-Wallis test or chi-square tests. The word cloud analysis of the 2 open-ended questions were conducted by Wenjuanxing. Students' performances in the final examination were analysed by One-way Anova. RESULTS: Both total online and partial online PBL were rated highly by the students. Overall, there were no significant differences in the effectiveness evaluation of PBL between Group 2 and Group 3. There were no significant differences in final exam performances between Group 1 and Group 2. However, Group 1 rated the effectiveness of PBL much higher than Group 2 and 3. Word cloud analysis of the 2 open-ended questions showed students' positive perspectives of PBL. In biochemistry teaching, from the perspective of the students, the expected optimal number of useful PBL cases might be 2. CONCLUSIONS: Both total online and partial online PBL in a large classroom setting were widely accepted as a beneficial supplement to traditional biochemistry classes.


Subject(s)
Problem-Based Learning , Students , Humans , Educational Measurement , Biochemistry/education , Surveys and Questionnaires
3.
Nanotechnology ; 35(9)2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37995375

ABSTRACT

Polyethylene glycol (PEG) is widely used as a phase change material (PCM) in thermal energy storage systems due to its high latent heat and chemical stability. However, practical application has been hindered by its low thermal conductivity and leakage issues. Therefore, developing shape-stable high thermal conductivity PCM is of great importance. In this study, new shape-stable composite PCM with high thermal conductivity and leak-prevention capabilities were designed. The porous carbon skeleton of diamond foam (DF) and dual-3D carbon nanotube-diamond foam (CDF) were prepared using the microwave plasma chemical vapor deposition method. The composite materials (DF/PEG and CDF/PEG) were produced by vacuum impregnation with PEG and skeletons. The results showed that CDF/PEG had the highest thermal conductivity, measuring 2.30 W·m-1·K-1, which is 707% higher than that of pure PEG. The employing of 3D networks of CNTs, which can improve the phonon mean free path in DF/PEG (1.79 W·m-1·K-1) while reducing phonon dispersion.The phonon vibration of dual-3D CDF plays an important role in heat transfer. PEG was physically absorbed and well-distributed in CDF, alleviating leakage of liquid PEG. The weight loss of CDF/PEG was only 25% at 70 °C for 120 s. Using CDF is an attractive and efficient strategy to increase the heat transfer of PEG and improve heat storage efficiency, alleviate the problem of poor shape-stability.

4.
ACS Appl Mater Interfaces ; 15(28): 33288-33298, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37400422

ABSTRACT

Avoiding the low specificity of phototheranostic reagents at the tumor site is a major challenge in cancer phototherapy. Meanwhile, angiogenesis in the tumor is not only the premise of tumor occurrence but also the basis of tumor growth, invasion, and metastasis, making it an ideal strategy for tumor therapy. Herein, biomimetic cancer cell membrane-coated nanodrugs (mBPP NPs) have been prepared by integrating (i) homotypic cancer cell membranes for evading immune cell phagocytosis to increase drug accumulation, (ii) protocatechuic acid for tumor vascular targeting along with chemotherapy effect, and (iii) near-infrared phototherapeutic agent diketopyrrolopyrrole derivative for photodynamic/photothermal synergetic therapy. The mBPP NPs exhibit high biocompatibility, superb phototoxicity, excellent antiangiogenic ability, and double-trigging cancer cell apoptosis in vitro. More significantly, mBPP NPs could specifically bind to tumor cells and vasculature after intravenous injection, inducing fluorescence and photothermal imaging-guided tumor ablation without recurrence and side effects in vivo. The biomimetic mBPP NPs could cause drug accumulation at the tumor site, inhibit tumor neovascularization, and improve phototherapy efficiency, providing a novel avenue for cancer treatment.


Subject(s)
Nanoparticles , Nanostructures , Neoplasms , Photochemotherapy , Humans , Biomimetics , Nanoparticles/therapeutic use , Phototherapy , Neoplasms/pathology , Cell Line, Tumor
5.
J Mater Chem B ; 11(26): 6131-6140, 2023 07 05.
Article in English | MEDLINE | ID: mdl-37345728

ABSTRACT

Combining the BRD4 and CDK9 inhibitors can trigger the significant down-regulation of the MYC oncogene as well as anti-apoptotic genes and induce tumor cell apoptosis by synergistically impairing RNA synthesis in cancer cells. However, the lack of tumor-targeting capacity and the different pharmacokinetic curves of these two inhibitors may impair the antitumor activity of simultaneous CDK9 and BRD4 inhibition. Herein, CDK9 inhibitor (CI) and BRD4 inhibitor (BI) were codelivered by macrophage membrane-encapsulated black phosphorus nanosheets (M@BP) for the treatment of gastric cancer (GC) via the high expression of BRD4 and CDK9. BP with prominent biocompatibility exhibited a high drug loading efficiency for both CI and BI and could efficiently decrease the expression of the MYC oncogene. More importantly, BP could also serve as a phototherapy agent collaborating with CDK9 and BRD4 inhibition for GC therapy upon near-infrared (NIR) irradiation. Furthermore, the introduction of a macrophage membrane endowed BP with tumor-targeting ability, which could simultaneously deliver CI and BI to tumor tissues. In a murine orthotopic GC model, M@BP could efficiently target and accumulate in the tumor tissues, exhibiting an excellent photothermal effect. The tumor growth monitoring demonstrated that the combination of CI and BI codelivered by M@BP significantly inhibited the tumor progress than the single inhibitors, and the inhibition effect could be further enhanced upon NIR irradiation. Taken together, M@BP with tumor-targeting capacity and high drug loading efficiency for CI and BI could efficiently block the activation of CDK9 and BRD4, exhibiting excellent antitumor activity under NIR irradiation without systemic toxicity in an orthotopic GC model.


Subject(s)
Stomach Neoplasms , Transcription Factors , Mice , Animals , Stomach Neoplasms/drug therapy , Nuclear Proteins/metabolism , Phosphorus , Biomimetics
6.
J Sci Food Agric ; 103(11): 5401-5411, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37029991

ABSTRACT

BACKGROUND: The widespread use of glyphosate has many adverse effects on Apis cerana cerana. Due to the incomplete understanding of the molecular mechanisms of glyphosate toxicity, there are no available methods for mitigating the threat of glyphosate to Apis cerana cerana. Small heat shock proteins (sHSPs) play an important role in resisting oxidative stress, but their mechanism of action in Apis cerana cerana remains unclear. RESULTS: In this experiment, we cloned and identified AccsHSP21.7. Studies have shown that AccsHSP21.7 contains binding motifs for various transcription factors related to oxidative stress. Abiotic stresses induced the expression of AccsHSP21.7. Bacteriostatic testing of a recombinant AccsHSP21.7 protein proved that Escherichia coli overexpressing AccsHSP21.7 showed increased resistance to oxidative stress. Knocking down the AccsHSP21.7 gene caused significant damage to midgut cells, which seriously disrupted the antioxidant system in Apis cerana cerana and greatly increased mortality under glyphosate stress. CONCLUSION: This study investigated the relationship between antioxidant regulation and the AccsHSP21.7 gene at the molecular level, and the results have guiding significance for the improvement of stress resistance in Apis cerana cerana. © 2023 Society of Chemical Industry.


Subject(s)
Antioxidants , Oxidative Stress , Bees/genetics , Animals , Antioxidants/metabolism , Stress, Physiological , Recombinant Proteins/genetics , Transcription Factors/metabolism , Insect Proteins/chemistry
7.
Front Bioeng Biotechnol ; 11: 1117555, 2023.
Article in English | MEDLINE | ID: mdl-36890917

ABSTRACT

Three-dimensional printing models (3DPs) have been widely used in medical anatomy training. However, the 3DPs evaluation results differ depending on such factors as the training objects, experimental design, organ parts, and test content. Thus, this systematic evaluation was carried out to better understand the role of 3DPs in different populations and different experimental designs. Controlled (CON) studies of 3DPs were retrieved from PubMed and Web of Science databases, where the participants were medical students or residents. The teaching content is the anatomical knowledge of human organs. One evaluation indicator is the mastery of anatomical knowledge after training, and the other is the satisfaction of participants with 3DPs. On the whole, the performance of the 3DPs group was higher than that of the CON group; however, there was no statistical difference in the resident subgroup, and there was no statistical difference for 3DPs vs. 3D visual imaging (3DI). In terms of satisfaction rate, the summary data showed that the difference between the 3DPs group (83.6%) vs. the CON group (69.6%) (binary variable) was not statistically significant, with p > 0.05. 3DPs has a positive effect on anatomy teaching, although there are no statistical differences in the performance tests of individual subgroups; participants generally had good evaluations and satisfaction with 3DPs. 3DPs still faces challenges in production cost, raw material source, authenticity, durability, etc. The future of 3D-printing-model-assisted anatomy teaching is worthy of expectation.

8.
Opt Express ; 31(5): 7764-7773, 2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36859901

ABSTRACT

Polarization holography is an effective tool for realizing light field manipulation and can be utilized to generate vector beams. Based on the diffraction characteristics of a linear polarization hologram in coaxial recording, an approach for generating arbitrary vector beams is proposed. Unlike the previous methods for generating vector beams, in this work, it is independent of faithful reconstruction effect and the arbitrary linear polarization waves can be used as reading waves. The desired generalized vector beam polarization patterns can be adjusted by changing the polarized direction angle of the reading wave. Therefore, it is more flexible than the previously reported methods in generating vector beams. The experimental results are consistent with the theoretical prediction.

9.
J Mater Chem B ; 11(8): 1609-1627, 2023 02 22.
Article in English | MEDLINE | ID: mdl-36744587

ABSTRACT

Aptamers, a class of oligonucleotides that can bind with molecular targets with high affinity and specificity, have been widely applied in research fields including biosensing, imaging, diagnosing, and therapy of diseases. However, compared with the rapid development in the research fields, the clinical application of aptamers is progressing at a much slower speed, especially in the therapy of cancer. Obstructions including nuclease degradation, renal clearance, a complex selection process, and potential side effects have inhibited the clinical transformation of aptamer-conjugated drugs. To overcome these problems, taking certain measures to improve the biocompatibility and stability of aptamer-conjugated drugs in vivo is necessary. In this review, the obstructions mentioned above are thoroughly discussed and the methods to overcome these problems are introduced in detail. Furthermore, landmark research works and the most recent studies on aptamer-conjugated drugs for cancer therapy are also listed as examples, and the future directions of research for aptamer clinical transformation are discussed.


Subject(s)
Aptamers, Nucleotide , Neoplasms , Humans , Neoplasms/drug therapy
10.
BMC Med Educ ; 23(1): 93, 2023 Feb 06.
Article in English | MEDLINE | ID: mdl-36747223

ABSTRACT

BACKGROUND: The nature of student learning in problem-based learning (PBL) largely depends on the quality of the case scenarios presented to them. The effect of case scenarios with higher challenge degree, especially common disease with atypical symptoms (CDAS)- and rare disease (RD)-based case scenarios, on undergraduate medical students remains unclear. This study compared the impact of all scenarios pertaining to common disease with typical symptoms (CDTS) case scenarios, CDTS interspersed with CDAS case scenarios, and CDTS interspersed with RD case scenarios on perceptions of undergraduate students studying organ/system integration curriculum via PBL. METHODS: After finishing four CDTS case scenarios, 294 third-year medical students were randomly allocated into three groups: CDTS, CDAS and RD, studying via CDTS, CDAS and RD case scenarios, respectively. A questionnaire with 15 items was conducted to evaluate the students' perceptions. The students' responses were scored using a 4-point rating scale. The data were analysed using the Kruskal-Wallis test. RESULTS: Among the three PBL conditions, the ones with a higher degree of challenge were rated higher by the students, which included the quality of the case scenarios and the overall performances of the students. The CDAS and RD cases were more effective in developing students' self-directed learning skills, stimulating them to acquire more knowledge required for future work. The satisfaction percentage of RD case scenario sessions was higher. CONCLUSIONS: Of all the three kinds of case scenarios, both CDTS interspersed with CDAS and RD case scenarios had more positive effects on the self-evaluated performance of students. Increasing the challenge and variety of case scenarios by the inclusion of CDAS and RD especially RD might be an effective stimulus in improving students' performance in PBL sessions.


Subject(s)
Education, Medical, Undergraduate , Students, Medical , Humans , Problem-Based Learning , Rare Diseases , Curriculum , Learning
11.
Small ; 19(19): e2207535, 2023 05.
Article in English | MEDLINE | ID: mdl-36807550

ABSTRACT

Activatable prodrugs have drawn considerable attention for cancer cell ablation owing to their high specificity in drug delivery systems. However, phototheranostic prodrugs with dual organelle-targeting and synergistic effects are still rare due to low intelligence of their structures. Besides, the cell membrane, exocytosis, and diffusional hindrance by the extracellular matrix reduce drug uptake. Moreover, the up-regulation of heat shock protein and short singlet-oxygen lifetime in cancer cells hamper photo-ablation efficacy, especially in the mono-therapeutic model. To overcome those obstacles, we prepare an esterase-activated DM nano-prodrug, which is conjugated by diiodine-substituted fluorogenic malachite green derivative (MG-2I) and phototherapeutic agent DPP-OH via hydrolyzable ester linkage, having pH-responsiveness and genetically targetable activity for dual organelles-targeting to optimize photo-ablation efficacy. The DM nanoparticles (NPs) present improved pH-responsive photothermal/photodynamic property by the protonation of diethylaminophenyl units in acidic environment. More importantly, the MG-2I and DPP-OH moieties can be released from DM nano-prodrug through overexpressed esterase; then specifically target lysosomes and mitochondria in CT-26 Mito-FAP cells. Hence, near-infrared DM NPs can trigger parallel damage in dual-organelles with strong fluorescence and effective phototoxicity, thus inducing serious mitochondrial dysfunction and apoptotic death, showing excellent photo-ablation effect based on esterase-activated, pH-responsive, and genetically targetable activities.


Subject(s)
Nanoparticles , Neoplasms , Prodrugs , Prodrugs/chemistry , Drug Delivery Systems , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Cell Line, Tumor
12.
Opt Express ; 30(26): 47264-47279, 2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36558658

ABSTRACT

Polarization is a natural property of a lightwave and makes a significant contribution to various scientific and technological applications, due to the different states of polarization (SoP) of a lightwave that may manifest distinct behaviors. Hence, it is important to determine the SoP of the lightwave. Generally, the SoP of a lightwave can be recognized by the Stokes parameters. In this paper, we proposed a novel method to simultaneously characterize the Stokes parameters of a lightwave, by employing the tensor polarization holography theory. This is done through merely a piece of polarization-sensitive material. Compared with the traditional method, this method requires only one measurement to obtain all the Stokes parameters, without using additional polarizing elements. The experimental result shows excellent agreement with the theoretical one, which confirmed the reliability and accuracy of the proposed method. We believe that this work may broaden the application field of polarization holography.

13.
BMC Endocr Disord ; 22(1): 306, 2022 Dec 07.
Article in English | MEDLINE | ID: mdl-36476135

ABSTRACT

BACKGROUND: Adropin is a potent metabolic regulator of insulin sensitivity and glycolipid metabolism. The present study investigated the effects of sitagliptin on adropin and metabolic parameters in participants with newly diagnosed type 2 diabetes (T2D). METHODS: Thirty-five participants newly-diagnosed with T2D were prescribed sitagliptin 100 mg once daily for 17 weeks. Twenty-eight age-, sex-, and BMI-matched healthy subjects were included as the control group. Adropin and clinical parameters were assessed at baseline and after treatment. RESULTS: At baseline, serum adropin levels were lower in T2D participants than in the healthy individuals (3.12 ± 0.73 vs. 5.90 ± 1.22 ng/ml, P <  0.01). Serum adropin levels were significantly higher in T2D patients after sitagliptin treatment (4.97 ± 1.01 vs. 3.12 ± 0.73 ng/ml, P <  0.01). The changes in serum adropin levels after sitagliptin treatment were associated with the improvements of fasting blood glucose (FBG) (ß = - 0.71, P <  0.01), glycosylated hemoglobin (HbA1c) (ß = - 0.44, P <  0.01) and homeostatic model assessment of ß-cell function (HOMA-ß) (ß = 9.02, P <  0.01). CONCLUSIONS: Sitagliptin treatment could significantly increase serum adropin levels in participants with newly diagnosed T2D. The increase in serum adropin levels could be associated with the amelioration of glucose metabolism, which might be involved in beneficial glucose-lowering mechanisms of sitagliptin. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04495881 . Retrospectively registered on 03/08/2020.


Subject(s)
Diabetes Mellitus, Type 2 , Sitagliptin Phosphate , Humans , Sitagliptin Phosphate/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Health Status
14.
Molecules ; 27(19)2022 Sep 23.
Article in English | MEDLINE | ID: mdl-36234816

ABSTRACT

Phenanthraquinone-doped polymethyl methacrylate (PQ/PMMA) photopolymers are considered to be the most promising holographic storage media due to their unique properties, such as high stability, a simple preparation process, low price, and volumetric shrinkage. This paper reviews the development process of PQ/PMMA photopolymers from inception to the present, summarizes the process, and looks at the development potential of PQ/PMMA in practical applications.


Subject(s)
Holography , Polymethyl Methacrylate
15.
Opt Express ; 30(10): 16159-16173, 2022 May 09.
Article in English | MEDLINE | ID: mdl-36221466

ABSTRACT

Vector vortex beams are a kind of special beam that simultaneously carry spin and orbital angular momentum. The generation of vector vortex beams usually requires a complex and expensive optical system, which becomes a bottleneck hindering its further application. Thus, a compact, low-cost and efficient special beam generation system is demanded. In this paper, a method that can produce vector vortex beams distributed anywhere in the equator of hybrid-order Poincaré Spheres based on polarization holography is proposed. Via changing some parameters of the device, this method can also produce the scalar vortex beams distributed at any position of the basic Poincaré Sphere and the vector beams distributed at the equator of the higher-order Poincaré Spheres. The work shows that polarization holography has the potential ability to regulate the spin and orbital angular momentum simultaneously, opening a new window for future research and applications of angular momentum space orientation.

16.
Biosensors (Basel) ; 12(9)2022 Aug 25.
Article in English | MEDLINE | ID: mdl-36140069

ABSTRACT

The traditional infectious disease detection process is cumbersome, and there is only a single application scenario. In recent years, with the development of the medical industry and the impact of the epidemic situation, the number of infectious disease detection instruments based on nursing point detection has been increasing. Due to this trend, many detection instruments and massive detection data urgently need to be managed. In addition, the experiment failed due to the abnormal fluorescence curve generated by a human operator or sample impurities. Finally, the geographic information system has also played an active role in spreading and preventing infectious diseases; this paper designs a "detection-service-mobile" three-terminal system to realize the control of diagnostic instruments and the comprehensive management of data. Machine learning is used to classify the enlarged curve and calculate the cycle threshold of the positive curve; combined with a geographic information system, the detection results are marked on the mobile terminal map to realize the visual display of the positive results of nucleic acid amplification detection and the early warning of infectious diseases. In the research, applying this system to portable field pathogen detection is feasible and practical.


Subject(s)
Communicable Diseases , Nucleic Acids , Communicable Diseases/diagnosis , Humans , Nucleic Acid Amplification Techniques/methods , Point-of-Care Systems , Software
17.
J Biomed Nanotechnol ; 18(3): 828-836, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35715923

ABSTRACT

The given research revealed that the size of Fe3O4 magnetic nanoparticles (MNPs) could be controlled by varying the pre-mixing conditions in the solvothermal method. Scanning electron microscopy (SEM) showed that the size of the MNPs gradually increased with increasing the initial temperature at which reaction components were mixed while the reaction component's mixing time was kept constant. The smallest sized MNPs were achieved among the five treatments (25, 50, 75, 100, and 125 °C) when reaction components were mixed at 25 °C, while the larger sized MNPs were synthesized among the five treatments when reaction components were mixed at 125 °C. Then, Stöber method was followed for coating silica layer onto the MNPs. However, ammonium hydroxide was replaced with potassium hydroxide as a catalyst, which significantly increased the speed of silica coating onto MNPs. The Fourier transform infrared (FTIR) spectrometer revealed that the MNPs were successfully covered with silica in five minutes. FTIR spectra exhibited a peak about 1088.8 cm-1, which belonged to the asymmetry stretching vibration of Si-O-Si. Transmission electronic microscopy (TEM) analysis was conducted to confirm the presence of silica layer onto MNPs. Thus, potassium hydroxide was successfully employed as a catalyst for quick silica layer coating onto MNPs. Furthermore, these silica coated MNPs were used to extract high quality nucleic acids from blood sample.


Subject(s)
Magnetite Nanoparticles , Nucleic Acids , Magnetics , Silicon Dioxide , Spectroscopy, Fourier Transform Infrared
18.
Anal Chem ; 94(16): 6242-6250, 2022 04 26.
Article in English | MEDLINE | ID: mdl-35403420

ABSTRACT

Most LC-MS based bile acid analyses target common bile acids. The identification of unknown bile acids remains challenging in untargeted experiments. Here, a software named BAFinder was developed to improve the identification of unknown bile acids from accurate mass LC-MS/MS data in both the positive and negative ESI modes. A wide variety of bile acid structures were covered in BAFinder, including oxidized bile acids and sugar conjugates that were often ignored. The annotation of unknown bile acids was based on a thorough investigation of MS/MS fragmentation patterns of 84 bile acid reference standards in both modes. Specifically, BAFinder took the peak alignment result and MS/MS spectra, grouped candidate features in positive and negative modes, searched their representative MS/MS spectra against a MS/MS library, and used characteristic product ions and neutral losses to annotate bile acids not covered in the library. Finally, the number of hydroxyl groups and double bonds, conjugation, and isomer information of bile acids were reported with four different levels of annotation confidence. The use of BAFinder was demonstrated through successful application to the analysis of human plasma and urine samples, in which a total of 112 and 244 bile acids were annotated and 75 and 111 of them were confirmed with standards or synthesized compounds, respectively. The software is freely available at https://bafinder.github.io/.


Subject(s)
Bile Acids and Salts , Tandem Mass Spectrometry , Chromatography, Liquid , Humans , Isomerism , Software
19.
J Cell Mol Med ; 26(5): 1606-1620, 2022 03.
Article in English | MEDLINE | ID: mdl-35106915

ABSTRACT

Acetylshikonin (ASK) is a natural naphthoquinone derivative of traditional Chinese medicine Lithospermum erythrorhyzon. It has been reported that ASK has bactericidal, anti-inflammatory and antitumour effects. However, whether ASK induces apoptosis and autophagy in acute myeloid leukaemia (AML) cells and the underlying mechanism are still unclear. Here, we explored the roles of apoptosis and autophagy in ASK-induced cell death and the potential molecular mechanisms in human AML HL-60 cells. The results demonstrated that ASK remarkably inhibited the cell proliferation, viability and induced apoptosis in HL-60 cells through the mitochondrial pathway, and ASK promoted cell cycle arrest in the S-phase. In addition, the increased formation of autophagosomes, the turnover from light chain 3B (LC3B) I to LC3B II and decrease of P62 suggested the induction of autophagy by ASK. Furthermore, ASK significantly decreased PI3K, phospho-Akt and p-p70S6K expression, while enhanced phospho-AMP-activated protein kinase (AMPK) and phospho-liver kinase B1(LKB1) expression. The suppression of ASK-induced the conversion from LC3B I to LC3B II caused by the application of inhibitors of AMPK (compound C) demonstrated that ASK-induced autophagy depends on the LKB1/AMPK pathway. These data suggested that the autophagy induced by ASK were dependent on the activation of LKB1/AMPK signalling and suppression of PI3K/Akt/mTOR pathways. The cleavage of the apoptosis-related markers caspase-3 and caspase-9 and the activity of caspase-3 induced by ASK were markedly reduced by inhibitor of AMPK (compound C), an autophagy inhibitor 3-methyladenine (3-MA) and another autophagy inhibitor chloroquine (CQ). Taken together, our data reveal that ASK-induced HL-60 cell apoptosis is dependent on the activation of autophagy via the LKB1/AMPK and PI3K/Akt-regulated mTOR signalling pathways.


Subject(s)
AMP-Activated Protein Kinases , Proto-Oncogene Proteins c-akt , AMP-Activated Protein Kinases/metabolism , Anthraquinones , Apoptosis , Autophagy , Caspase 3 , Cell Proliferation , HL-60 Cells , Humans , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism
20.
Anticancer Drugs ; 33(1): e444-e452, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34520434

ABSTRACT

Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side effects, here we used ORI in combination with cisplitin (CIS) against different esophageal squamous cell carcinoma (ESCC) cell lines in vitro, to investigate the synergistic anticancer effects of the two drugs against ESCC. Calcusyn Graphing Software was used to assess the synergistic effect. Apoptosis, wound healing and cell invasion assay were conducted to further confirm the synergistic effects of ORI and CIS. Intracellular glutathione (GSH) and reactive oxygen species assay, immunofluorescence staining and western blot were used to verify the mechanism of synergistic cytotoxicity. ORI and CIS pose selective synergistic effects on ESCC cells with p53 mutations. Moreover, we found that the synergistic effects of these drugs are mediated by GSH/ROS systems, such that intracellular GSH production was inhibited, whereas the ROS generation was induced following ORI and CIS application. In addition, we noted that DNA damage was induced as in response to ORI and CIS treatment. Overall, these results suggest that ORI can synergistically enhance the effect of CIS, and GSH deficiency and p53 mutation, might be biomarkers for the combinational usage of ORI and CIS.


Subject(s)
Cisplatin/pharmacology , Diterpenes, Kaurane/pharmacology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cisplatin/administration & dosage , Diterpenes, Kaurane/administration & dosage , Dose-Response Relationship, Drug , Drug Synergism , Glutathione/drug effects , Humans , Inhibitory Concentration 50 , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Tumor Suppressor Protein p53/drug effects
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