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1.
J Am Chem Soc ; 146(1): 801-810, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38129385

ABSTRACT

Taxol is a potent drug used in various cancer treatments. Its complex structure has prompted extensive research into its biosynthesis. However, certain critical steps, such as the formation of the oxetane ring, which is essential for its activity, have remained unclear. Previous proposals suggested that oxetane formation follows the acetylation of taxadien-5α-ol. Here, we proposed that the oxetane ring is formed by cytochrome P450-mediated oxidation events that occur prior to C5 acetylation. To test this hypothesis, we analyzed the genomic and transcriptomic information for Taxus species to identify cytochrome P450 candidates and employed two independent systems, yeast (Saccharomyces cerevisiae) and plant (Nicotiana benthamiana), for their characterization. We revealed that a single enzyme, CYP725A4, catalyzes two successive epoxidation events, leading to the formation of the oxetane ring. We further showed that both taxa-4(5)-11(12)-diene (endotaxadiene) and taxa-4(20)-11(12)-diene (exotaxadiene) are precursors to the key intermediate, taxologenic oxetane, indicating the potential existence of multiple routes in the Taxol pathway. Thus, we unveiled a long-elusive step in Taxol biosynthesis.


Subject(s)
Cytochrome P-450 Enzyme System , Taxus , Cytochrome P-450 Enzyme System/metabolism , Paclitaxel/metabolism , Ethers, Cyclic , Catalysis , Taxus/genetics , Taxus/metabolism
2.
Nat Commun ; 14(1): 8374, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38102110

ABSTRACT

Image processing plays a vital role in artificial visual systems, which have diverse applications in areas such as biomedical imaging and machine vision. In particular, optical analog image processing is of great interest because of its parallel processing capability and low power consumption. Here, we present ultra-compact metasurfaces performing all-optical geometric image transformations, which are essential for image processing to correct image distortions, create special image effects, and morph one image into another. We show that our metasurfaces can realize binary image transformations by modifying the spatial relationship between pixels and converting binary images from Cartesian to log-polar coordinates with unparalleled advantages for scale- and rotation-invariant image preprocessing. Furthermore, we extend our approach to grayscale image transformations and convert an image with Gaussian intensity profile into another image with flat-top intensity profile. Our technique will potentially unlock new opportunities for various applications such as target tracking and laser manufacturing.

3.
Nano Lett ; 23(22): 10157-10163, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37909774

ABSTRACT

A levitated nonspherical nanoparticle in a vacuum is ideal for studying quantum rotations and is an ultrasensitive torque detector for probing fundamental particle-surface interactions. Here, we optically levitate a silica nanodumbbell in a vacuum at 430 nm away from a sapphire surface and drive it to rotate at GHz frequencies. The relative linear speed between the tip of the nanodumbbell and the surface reaches 1.4 km s-1 at a submicrometer separation. The rotating nanodumbbell near the surface demonstrates a torque sensitivity of (5.0 ± 1.1) × 10-26 N m Hz-1/2 at room temperature. Moreover, we probed the near-field laser intensity distribution beyond the optical diffraction limit with a nanodumbbell levitated near a nanograting. Our numerical simulations show that the system can measure the Casimir torque and will improve the detection limit of non-Newtonian gravity by several orders of magnitude.

4.
AMB Express ; 13(1): 122, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37917339

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a severe threat to global public health due to its high mortality. Currently, polymyxins are mainly used for the treatment of Gram-negative bacterial-related infection, while exhibiting limited antibacterial activities against Staphylococcus aureus (S. aureus). However, the combination of antibiotics with antibiotic adjuvants is a feasible strategy for the hard-treated infection and toxicity reducing. We will investigate the antibacterial activity of simeprevir (SIM), which treated for genotype 1 and 4 chronic hepatitis C, combined with polymyxins against MRSA through high-throughput screening technology. In our study, the synergistic antibacterial effect of SIM and polymyxins against S. aureus in vitro was found by checkerboard assay and time-growth curve. The cytotoxicity of SIM combined with polymyxin B sulfate [PB(S)] or polymyxin E (PE) in vitro was evaluated using CCK-8, human RBC hemolysis and scratch assays. In addition, we investigated the eradication of biofilm formation of S. aureus by biofilm inhibition assay and the killing of persister cells. Moreover, we evaluated the therapeutic effect and in vivo toxicity of the combination against MRSA in murine subcutaneous abscess model. Furthermore, it was preliminarily found that SIM significantly enhanced the destruction of MRSA membrane by SYTOX Green and DISC3(5) probes. In summary, these results reveal that the therapy of SIM combined with polymyxins (especially PE) is promising for the treatment of MRSA infection.

5.
J Int Med Res ; 51(11): 3000605231210657, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37994021

ABSTRACT

Empyema is a common complication of pneumonia, caused by the accumulation of purulent exudate due to pathogenic bacteria invading the pleural cavity. Parvimonas micra and Streptococcus constellatus are pathogens that rarely cause pneumonia with empyema. Herein, a case of severe empyema caused by these two pathogens, confirmed by metagenomic next-generation sequencing (mNGS) of pleural effusion cultures, is reported. A male Chinese patient in his late sixties presented with wheezing, cough, sputum expectoration, and fever. Blood and sputum cultures were negative for pathogens, but the pleural effusion culture was positive for S. constellatus, and was also found to contain P. micra, confirmed by mNGS. The patient's symptoms improved after treatment with cefoperazone/sulbactam and moxifloxacin. Pneumonia caused by P. micra and S. constellatus is rare; however, coinfection with these pathogens may cause severe pneumonia, with or without empyema.


Subject(s)
Coinfection , Empyema, Pleural , Pleural Effusion , Pneumonia , Streptococcus constellatus , Humans , Male , Streptococcus constellatus/genetics , Empyema, Pleural/complications , Empyema, Pleural/diagnosis , Empyema, Pleural/microbiology , Pneumonia/complications , Pneumonia/diagnosis
6.
Nat Chem Biol ; 19(12): 1532-1539, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37828399

ABSTRACT

Terpenoids are the most diverse group of specialized metabolites with numerous applications. Their biosynthesis is based on the five-carbon isoprene building block and, as a result, almost all terpenoids isolated to date are based on backbones that contain multiples of five carbon atoms. Intrigued by the discovery of an unusual bacterial terpenoid with a 16-carbon skeleton, here we investigate whether the biosynthesis of 16-carbon terpenoids is more widespread than this single example. We mine bacterial genomic information and identify potential C16 biosynthetic clusters in more than 700 sequenced genomes. We study selected clusters using a yeast synthetic biology platform and reveal that the encoded synthases produce at least 47 different noncanonical terpenoids. By thorough chemical analysis, we explain the structures of 13 C16 metabolites, most of which possess intricate highly strained bi- and tricyclic backbones. Our results unveil the existence of an extensive class of terpenoids in bacteria.


Subject(s)
Bacteria , Terpenes , Terpenes/metabolism , Bacteria/genetics , Bacteria/metabolism , Saccharomyces cerevisiae/genetics , Synthetic Biology/methods
7.
Chemosphere ; 345: 140354, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37832879

ABSTRACT

Cyanide extraction dominates the gold smelting industry, which leads to the generation of large amounts of cyanide-containing wastewater. In this study, Aneurinibacillus tyrosinisolvens strain named JK-1 was used for cyanide wastewater biodegradation. First, we tested the performance of JK-1 in degrading cyanide under different conditions. Then, we screened metabolic compounds and pathways associated with cyanide degradation by JK-1. Finally, we explored the potential JK-1-mediated cyanide degradation pathway. Our results showed that the optimal pH and temperature for cyanide biodegradation were 7.0 and 30 °C, respectively; under these conditions, a degradation rate of >98% was achieved within 48 h. Untargeted metabolomics results showed that increased cyanide concentration decreased the abundance of metabolic compounds by 71.1% but upregulated 32 metabolic pathways. The Kyoto Encyclopedia of Genes and Genomes enrichment results revealed significant changes in amino acid metabolism pathways during cyanide degradation by JK-1, including cyanoamino acid metabolism, ß-alanine metabolism, and glutamate metabolism. Differential metabolic compounds included acetyl-CoA, l-asparagine, l-glutamic acid, l-phenylalanine, and l-glutamine. These results confirmed that cyanide degradation by JK-1 occurs through amino acid assimilation. This study provides new insights into the mechanism of cyanide biodegradation, which can be applied in the treatment of cyanide wastewater or tailings.


Subject(s)
Cyanides , Wastewater , Cyanides/analysis , Biodegradation, Environmental , Bioreactors , Amino Acids
8.
Tissue Cell ; 85: 102223, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37776785

ABSTRACT

Periodontitis represents a severe inflammatory illness in tooth supporting tissue. It has been supported that cAMP response element binding protein 1 (CREB1), a common transcription factor, extensively participates in osteogenic differentiation. Here, the current study was to look into the impacts of CREB1 on the process of periodontitis and its possible action mechanism. After human periodontal ligament stem cells (PDLSCs) were challenged with zoledronic acid (ZA), CREB1 expression was examined with RT-qPCR and western blotting. CCK-8 assay appraised cell activity. Following CREB1 elevation or/and vascular endothelial growth factor (VEGF) silencing in ZA-treated PDLSCs, CCK-8 and TUNEL assays separately estimated cell viability and apoptosis. Western blotting tested the expression of apoptosis- and osteogenic differentiation-associated proteins. ALP staining measured PDLSCs osteogenic ability and ARS staining estimated mineralized nodule formation. JASPAR predicted the potential binding of CREB1 with VEGF promoter, which was then testified by ChIP and luciferase reporter assays. RT-qPCR and western blotting tested VEGF expression. CREB1 expression was declined in ZA-exposed PDLSCs and CREB1 elevation exacerbated the viability and osteogenic differentiation while obstructed the apoptosis of PDLSCs. Additionally, CREB1 bond to VEGF promoter and transcriptionally activated VEGF expression. Further, VEGF absence partially stimulated the apoptosis while suppressed the osteogenic differentiation of CREB1-overexpressing PDLSCs treated by ZA. To be concluded, CREB1 might activate VEGF transcription to obstruct the apoptosis while contribute to the osteogenic differentiation of ZA-treated PDLSCs.


Subject(s)
Osteogenesis , Periodontitis , Humans , Apoptosis/genetics , Cell Differentiation/physiology , Cell Proliferation , Cells, Cultured , Cyclic AMP Response Element-Binding Protein/metabolism , Osteogenesis/physiology , Periodontal Ligament , Periodontitis/metabolism , Signal Transduction/physiology , Sincalide/metabolism , Stem Cells , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Zoledronic Acid/pharmacology , Zoledronic Acid/metabolism
9.
J Nat Prod ; 86(9): 2206-2215, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37650785

ABSTRACT

Thirty-five diverse polyphenols, belonging to seven structure classes, were isolated from Garcinia gracilis, a medicinal and edible plant sampled from Laos. The structures of nine new compounds, gargarcilones A-I (1-3, 5-7, 10, 12, and 17), were established using spectroscopic, X-ray diffraction, and experimental and calculated ECD methods. Additionally, we revised the stereochemical assignment of cochinchinoxanthone and cochinchinoxanthone C. The compounds were evaluated for antiproliferative activity against five human tumor cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480). Compounds 1-4, 7, and 8 exhibited cytotoxic activity with IC50 values of 0.5-8.9 µM. Compound 3 significantly induced apoptosis in SMMC-7721 cells.


Subject(s)
Antineoplastic Agents , Garcinia , Humans , Apoptosis , Cell Line, Tumor , Polyphenols/pharmacology
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(6): 868-876, 2023 Jun 28.
Article in English, Chinese | MEDLINE | ID: mdl-37587072

ABSTRACT

OBJECTIVES: Staphylococcus epidermidis (S. epidermidis) is a Gram-positive opportunistic pathogen that often causes hospital infections. With the abuse of antibiotics, the resistance of S. epidermidis gradually increases, and drug repurposing has become a research hotspot in the treating of refractory drug-resistant bacterial infections. This study aims to study the antimicrobial and antibiofilm effects of simeprevir, an antiviral hepatitis drug, on S. epidermidis in vitro. METHODS: The micro-dilution assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of simeprevir against S. epidermidis. Crystal violet staining assay was used to detect the biofilm inhibitory effect of simeprevir. The antimicrobial activity of simeprevir against S. epidermidis and its biofilm were explored by SYTO9/PI fluorescent staining. The combined effect between simeprevir and gentamycin was assessed by checkerboard assay and was confirmed by time-inhibition assay. RESULTS: Simeprevir showed significant antimicrobial effects against S. epidermidis type strains and clinical isolates with the MIC and MBC at 2-16 µg/mL and 4-32 µg/mL, respectively. The antimicrobial effects of simeprevir were confirmed by SYTO9/PI staining. Simeprevir at MIC could significantly inhibit and break the biofilm on cover slides. Similarly, simeprevir also significantly inhibit the biofilm formation on the surface of urine catheters either in TSB [from (0.700±0.020) to (0.050±0.004)] (t=54.03, P<0.001), or horse serum [from (1.00±0.02) to (0.13±0.01)] (t=82.78, P<0.001). Synergistic antimicrobial effect was found between simeprevir and gentamycin against S. epidermidis with the fractional inhibitory concentration index of 0.5. CONCLUSIONS: Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.


Subject(s)
Cross Infection , Simeprevir , Humans , Antiviral Agents , Anti-Bacterial Agents/pharmacology , Gentamicins
11.
Nat Chem ; 15(9): 1236-1246, 2023 09.
Article in English | MEDLINE | ID: mdl-37365337

ABSTRACT

Obesity is a major health risk still lacking effective pharmacological treatment. A potent anti-obesity agent, celastrol, has been identified in the roots of Tripterygium wilfordii. However, an efficient synthetic method is required to better explore its biological utility. Here we elucidate the 11 missing steps for the celastrol biosynthetic route to enable its de novo biosynthesis in yeast. First, we reveal the cytochrome P450 enzymes that catalyse the four oxidation steps that produce the key intermediate celastrogenic acid. Subsequently, we show that non-enzymatic decarboxylation-triggered activation of celastrogenic acid leads to a cascade of tandem catechol oxidation-driven double-bond extension events that generate the characteristic quinone methide moiety of celastrol. Using this acquired knowledge, we have developed a method for producing celastrol starting from table sugar. This work highlights the effectiveness of combining plant biochemistry with metabolic engineering and chemistry for the scalable synthesis of complex specialized metabolites.


Subject(s)
Anti-Obesity Agents , Triterpenes , Triterpenes/chemistry , Triterpenes/metabolism , Triterpenes/pharmacology , Anti-Obesity Agents/pharmacology , Pentacyclic Triterpenes , Cytochrome P-450 Enzyme System
12.
Surg Innov ; 30(1): 36-44, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35507460

ABSTRACT

Background. Robotic systems can overcome some limitations of laparoscopic total mesorectal excision (L-TME), thus improving the quality of the surgery. So far, many studies have reported the technical feasibility and short-term oncological results of robotic total mesorectal excision (R-TME) in treating rectal cancer (RC); however, only a few evaluated the survival and long-term oncological outcomes. The following study compared the medium-term oncological data, 3-year overall survival (OS), and disease-free survival (DFS) of L-TME and R-TME in patients with rectal cancer. Methods. In this retrospective study, records of patients (patients with stage I-III rectal cancer) who underwent surgery (127 cases of L-TME and 148 cases of R-TME) at the Gansu Provincial Hospital between June 2016 and March 2018 were included in the analysis. Kaplan-Meier analysis evaluated the 3-year OS and DFS for all patients treated with curative intent. Results. The conversion rate was significantly higher, and the postoperative hospital stay was significantly longer in the L-TME group than in the R-TME group (all P<.05). Major complications were significantly lower in the robotic group (P<.05). The 3-year DFS rate (for all stages) was 74.8% for L-TME and 85.8% for R-TME (P = .021). For disease stage III, the 3-year DFS and OS were significantly higher in the R-TME group (P<.05). Conclusion. R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage III rectal cancers. Nevertheless, further randomized controlled trials and a longer follow-up period are needed to confirm these findings.


Subject(s)
Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Robotics , Humans , Robotic Surgical Procedures/methods , Retrospective Studies , Laparoscopy/methods , Rectal Neoplasms/surgery , Treatment Outcome
13.
Nano Lett ; 23(1): 51-57, 2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36525639

ABSTRACT

Metalenses promise potential for a paradigm shift of conventional optical devices. However, the aperture sizes of metalenses are usually bound within hundreds of micrometers by the commonly used fabrication methods, limiting their usage on practical optical devices like telescopes. Here, for the first time, we demonstrate a high-efficiency, single-lens, refractive metalens telescope. We developed a mass production-friendly workflow for fabricating wafer-scale (80 mm aperture) metalenses using deep-ultraviolet (DUV) photolithography. Our metalens works in the near-infrared region with nearly diffraction-limited focal spot sizes and a high peak focusing efficiency of 80.84% at 1450 nm experimentally. Based on the metalens, we built a single-lens telescope and acquired images of the lunar surface, revealing its geographical structures. We believe our demonstration of the metalens telescope proves the exciting potential lying in the metasurfaces and could bring new possibilities for areas involving large optical systems, including geosciences, planetary observation, and astrophysical science.

14.
Front Endocrinol (Lausanne) ; 13: 970575, 2022.
Article in English | MEDLINE | ID: mdl-36204099

ABSTRACT

Background: Low klotho is associated with aging-related traits. However, no study has assessed the association between klotho and oral health in a large sample of population. This study aimed to explore the association between serum α-klotho and oral health in US Adults. Methods: Data were from the National Health and Nutrition Examination Survey. Oral health parameters included periodontitis, self-rated oral health, and tooth loss. Logistic regression and restricted cubic spline models were adopted to evaluate the associations. Results: A total of 6187 participants were included in the study. The median of the α-klotho level was 815.2 pg/mL. Serum α-Klotho was significantly lower in participants with poor oral health (all P <0.01). Compared with the highest tertile, the lowest tertile of α-klotho was associated with moderate/severe periodontitis, poor-rated oral health, and tooth loss, with OR (95% CI) being 1.21 (1.01, 1.48), 1.26 (1.01, 1.56) and 1.38 (1.05, 1.84), respectively. An increment of per 1 standard deviation in the α-klotho concentration was associated with lower odds of moderate/severe periodontitis (OR: 0.93; 95% CI: 0.87, 0.99). Linear dose-response relationships were found between α-klotho and the odds of moderate/severe periodontitis (P for non-linearity=0.88) and poor-rated oral health (P for non-linearity=0.66). An L-shaped dose-response relationship was found between levels of α-klotho and the odds of tooth loss (P for non-linearity=0.04). Conclusions: Serum α-klotho was associated with oral health. Further studies are necessary to clarify the potential mechanisms and demonstrate the predictive ability of klotho in oral diseases.


Subject(s)
Periodontitis , Tooth Loss , Adult , Humans , Logistic Models , Nutrition Surveys , Oral Health , Periodontitis/epidemiology , Tooth Loss/epidemiology
15.
Nat Commun ; 13(1): 5188, 2022 09 03.
Article in English | MEDLINE | ID: mdl-36057727

ABSTRACT

Humankind relies on specialized metabolites for medicines, flavors, fragrances, and numerous other valuable biomaterials. However, the chemical space occupied by specialized metabolites, and, thus, their application potential, is limited because their biosynthesis is based on only a handful of building blocks. Engineering organisms to synthesize alternative building blocks will bypass this limitation and enable the sustainable production of molecules with non-canonical chemical structures, expanding the possible applications. Herein, we focus on isoprenoids and combine synthetic biology with protein engineering to construct yeast cells that synthesize 10 non-canonical isoprenoid building blocks with 16 carbon atoms. We identify suitable terpene synthases to convert these building blocks into C16 scaffolds and a cytochrome P450 to decorate the terpene scaffolds and produce different oxygenated compounds. Thus, we reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones, synthesizing 28 different non-canonical terpenes, some of which have interesting odorant properties.


Subject(s)
Carbon , Terpenes , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Protein Engineering , Synthetic Biology , Terpenes/metabolism
16.
Bioengineered ; 13(5): 12055-12066, 2022 05.
Article in English | MEDLINE | ID: mdl-35546327

ABSTRACT

Periodontitis is a chronic infectious disease that affects the oral health of adults. Long non-coding RNA OIP5 antisense RNA 1 (OIP5-AS1) has been reported to downregulated in the periodontal tissue of patients with periodontitis. Therefore, the study sought to look at the possible functions of OIP5-AS1 in periodontitis and the associated underlying mechanisms. In the present study, the expression level of OIP5-AS1 and microRNA-92a-3p were analyzed using reverse transcription-quantitative PCR. The levels of osteogenic proteins were determined using western blotting and inflammatory cytokines and oxidative stress were also examined. The proliferation of human periodontal ligament stem cells (hPDLSCs) was evaluated using MTT assays. Assay of osteogenic differentiation was undertaken by means of Alkaline phosphatase staining. The possible association between OIP5-AS1 and miR-92a-3p was determined applying dual-luciferase reporter assays and verified by RNA immunoprecipitation assay. We found that OIP5-AS1 was expressed at low levels in lipopolysaccharide (LPS)-stimulated hPDLSCs. OIP5-AS1 overexpression promoted proliferation and osteogenic differentiation ability and reduced LPS-induced inflammation in hPDLSCs. Furthermore, OIP5-AS1 directly targeted and reduced miR-92a-3p expression. The overexpression of miR-92a-3p partly abolished the effects of OIP5-AS1 on LPS-induced cell proliferation and osteogenic differentiation as well as inflammation in hPDLSCs. Collectively, the results indicated that OIP5-AS1 overexpression inhibited the LPS-induced inflammatory response and promoted the osteogenic differentiation of hPDLSCs by sponging miR-92a-3p. Thus, OIP5-AS1 is probably an essential objective for research during periodontitis treatment.


Subject(s)
MicroRNAs , Periodontitis , RNA, Long Noncoding , Humans , Inflammation/genetics , Lipopolysaccharides/toxicity , MicroRNAs/genetics , MicroRNAs/metabolism , Osteogenesis/genetics , Periodontal Ligament , Periodontitis/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
17.
Anticancer Agents Med Chem ; 22(15): 2799-2806, 2022 08 04.
Article in English | MEDLINE | ID: mdl-35331101

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a rampant cancer type in head and neck cancers with a poor prognosis and a high recurrence rate. Eugenol shows an anticancer effect in a variety of cancers, but it has been rarely studied in oral squamous cell carcinoma (OSCC). OBJECTIVE: The purpose of this study was to explore the role of Eugenol in OSCC and the underlying mechanism. METHODS: After different concentrations of Eugenol (0, 200, 400, and 800 µM) treatment, the viability, proliferation, migration, and invasion of OSCC cell line SCC9 were measured by CCK-8, colony formation, wound-healing, and transwell assays, respectively. TUNEL staining was employed to detect apoptosis. Western blotting was used to evaluate gene expression at the protein level. Molecular docking was used to identify the target of Eugenol. RESULTS: Eugenol decreased the proliferation and reduced the abilities of invasion and migration along with the expression of matrix metalloproteinases (MMP) 2 and MMP9 in SCC9 cells. On the contrary, the ratio of apoptotic cells was increased by Eugenol. In addition, Eugenol down-regulated B cell lymphoma-2 (Bcl-2) expression, but up-regulated BCL-2 associated X (Bax), cleaved caspase 3, and cleaved poly-ADP ribose polymerase (PARP) expression. Meanwhile, Eugenol exerted its effect on SCC9 cells in a concentration-dependent manner. Eugenol could bind to macrophage migration inhibitory factor (MIF), the expression of which was down-regulated after Eugenol treatment. Besides, overexpression of MIF reversed all the effects of Eugenol on OSCC cells. CONCLUSION: In summary, Eugenol suppressed the malignant processes of OSCC cells by targeting MIF, which could guide the clinical application of Eugenol in OSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Macrophage Migration-Inhibitory Factors , Mouth Neoplasms , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Eugenol/pharmacology , Eugenol/therapeutic use , Humans , Intramolecular Oxidoreductases/pharmacology , Intramolecular Oxidoreductases/therapeutic use , Macrophage Migration-Inhibitory Factors/pharmacology , Macrophage Migration-Inhibitory Factors/therapeutic use , Molecular Docking Simulation , Mouth Neoplasms/drug therapy , Mouth Neoplasms/metabolism , Proto-Oncogene Proteins c-bcl-2 , Squamous Cell Carcinoma of Head and Neck
18.
ACS Photonics ; 9(2): 398-404, 2022 Feb 16.
Article in English | MEDLINE | ID: mdl-35224133

ABSTRACT

We show that a metasurface-coated two-dimensional (2D) slab waveguide enables the generation of arbitrary complex light fields by combining the extreme versatility and freedom on the wavefront control of optical metasurfaces with the compactness of photonic integrated circuits. We demonstrated off-chip 2D focusing and holographic projection with our metasurface-dressed photonic integrated devices. This technology holds the potential for many other optical applications requiring 2D light field manipulation with full on-chip integration, such as solid-state LiDAR and near-eye AR/VR displays.

19.
Exp Ther Med ; 23(2): 130, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34970353

ABSTRACT

The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Murine MC3T3-E1 osteoblasts were stimulated with zoledronic acid (ZA) for 7 days. VEGF mRNA and protein expression levels were determined via reverse transcription-quantitative PCR and western blot analysis, respectively. Cell viability was evaluated using Cell Counting Kit-8 assay. In addition, the cell apoptotic rate and the expression levels of apoptosis-related proteins were measured using a TUNEL staining kit and western blot analysis, respectively. To evaluate mineralization, cells were stained with alizarin red, while the secretion levels of alkaline phosphatase (ALP) were measured using the corresponding assay kit. Finally, the expression levels of differentiation-related proteins and proteins of the Nod-like receptor family pyrin domain-containing 3 (NLRP3)/caspase 1/gasdermin D (GSDMD) pyroptosis pathway were measured by western blot analysis. VEGF expression level was notably decreased in ZA-stimulated MC3T3-E1 cells. However, the viability of these cells was enhanced following VEGF addition. Furthermore, VEGF attenuated apoptosis, promoted mineralization and increased ALP activity in ZA-stimulated MC3T3-E1 cells. The ZA-mediated decrease in the protein expression of the osteogenic genes osteopontin, osteocalcin and runt-related transcription factor 2 was restored after MC3T3-E1 cell treatment with 10 ng/ml VEGF. The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway.

20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 40(5): 576-581, 2022 Oct 01.
Article in English, Chinese | MEDLINE | ID: mdl-38596979

ABSTRACT

OBJECTIVES: This study aims to investigate the diagnostic application of an artificial intelligence (AI) computer-aided diagnostic system based on a convolutional neural network algorithm in detecting chronic apical periodontitis in cone beam computed tomography (CBCT) images. METHODS: CBCT raw data of 55 single root chronic apical pe-riodontitis taken in 2nd Dental Center of Peking University School and Hospital from 49 patients from January 2017 to December 2021 were collected, and the chronic apical periodontitis areas were identified by experienced clinicians ma-nually and segmented layer by layer in Materialise Mimics Medical Software. Deep learning of lesion characterization was conducted via AI 3D U-Net, and the network segmentation results were compared manually with the test sets in terms of intersection over union (IOU), Dice coefficient, and pixel accuracy (PA). RESULTS: In our deep learning algorithm, the IOU for all actual true lesions in test set samples was 92.18%, and the Dice coefficient and the PA index were 95.93% and 99.27%, respectively. Lesion segmentation and volume measurements performed by humans and AI systems showed excellent agreement. CONCLUSIONS: AI systems based on deep learning methods can be applied for detecting chronic apical periodontitis on CBCT images in clinical applications.

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