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1.
Opt Lett ; 49(19): 5523-5526, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352997

ABSTRACT

An aperiodic snake-like optical chain has been proposed and generated by using an optical pen technique, whose numbers and positions of focal points are controllable. Moreover, by introducing a fan phase together with a twisted phase into the optical pen technique, a self-rotation optical chain can be obtained; meanwhile, it transforms the bright optical chain into a twisted optical chain with a rotating hollow region in a three-dimensional (3D) space. The properties of the rotatable focal points and the variable diameters of cross-sectional intensities during the propagation of the optical chain are demonstrated in the experimental results. Consequently, this research framework can be applied in the techniques such as deep multiplexing and rotation angle multiplexing while also enabling the realization of multiple capture sites and more intricate manipulations.

2.
Int J Biol Macromol ; 279(Pt 4): 135512, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39260633

ABSTRACT

Tobacco stalks, as one of the annual economic crops rich in biomacromolecules such as cellulose and hemicellulose, are more difficult to decompose into cellulose fibers due to their high degree of lignification compared to other ordinary straw feedstocks, resulting in their underutilization. In this study, we developed a mild three-stage alkali­oxygen (AO) process to efficiently deconstruct the tobacco stalk cell walls. The process, involving alkaline dosages of 15 %, 10 %, and 3 % at each stage, effectively dissociated the cell walls and yielded cellulose fibers with high brightness (42.0 % ISO). The organics in the spent liquor, including lignin, hemicellulose, and small-molecular extracts, were isolated through acid/ethanol precipitation and organic solvent extraction. Lignin characterization by 2D HSQC NMR indicated that the majority of native ß-aryl ether linkages were preserved after AO treatment, making it suitable for producing chemicals or biofuels via depolymerization. Additionally, the small-molecular extracts contained numerous depolymerized products from lignin and carbohydrates, as well as bioactive compounds derived from the tobacco stalk. Overall, this mild, efficient, and eco-friendly process offers a promising approach for the valorization of tobacco stalks and similar biomass resources.


Subject(s)
Alkalies , Lignin , Nicotiana , Oxygen , Lignin/chemistry , Nicotiana/chemistry , Alkalies/chemistry , Oxygen/chemistry , Cell Wall/chemistry , Cellulose/chemistry , Biomass
3.
Quintessence Int ; 0(0): 0, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39190015

ABSTRACT

BACKGROUND: The pathogenesis of periodontitis may be related to host-mediated inflammatory and immune responses caused by accumulation of oral microbial plaque. Nutrients have anti-inflammatory and pro-inflammatory capabilities. Dietary intake of antioxidants and micronutrients is associated with the inflammatory burden of the diet. The Composite Dietary Antioxidant Index (CDAI) is a composite index for assessing the antioxidant properties of a diet and the relationship with periodontitis is unclear. The aim of this study was to investigate the relationship between periodontitis and CDAI. METHODS: The study was a cross-sectional design and included 7471 participants from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 database. Participants were divided into experimental and control groups according to the relevant criteria, where the control group consisted of participants with no/mild periodontitis (including 3646 participants) and the experimental group consisted of participants with moderate/severe periodontitis (including 3825 participants). First, baseline characteristics 22 of the two groups of participants were compared. Weighted logistic regression analyses was used to explore the relationship between periodontitis and CDAI. And the linear relationship between the two was assessed using restricted cubic spline. Finally, subgroup analyses was used to assess model stability. RESULTS: Differences between the two groups of participants were statistically significant in age, gender, race, education, ratio of household income to poverty(PIR), body mass index(BMI), smoking status, drinking status, and prevalence of diabetes. CDAI, as a continuous variable, was not found to be significantly associated with periodontitis. The CDAI was converted to categorical variables according to quartile. In model1, participants in the second and third quartile groups had a lower risk of developing periodontitis compared with participants in the lowest quartile group(OR(95%CI):0.81(0.681,0.963),P=0.021;OR(95%CI):0.811(0.691,0. 951),P=0.014;respectively). In model2, participants in the second, third, and fourth quartile groups had a lower risk of developing periodontitis compared to the lowest quartile group(OR(95%CI):0.803(0.66,0.978),P=0.0349;OR(95%CI):0.753( 0.632, 0.897),P=0.0028;OR(95%CI):0.753(0.617,0.92),P=0.0083;respectively). There was a non-linear relationship between CDAI and periodontitis (p non-linearity = 0.0055), with the inflection point occurring at a CDAI equal to 0.6342. CONCLUSION: There is a nonlinear relationship 44 between CDAI and periodontitis in US adults. However, further prospective studies are still needed to validate our results.

4.
Int J Biol Macromol ; 267(Pt 2): 131592, 2024 May.
Article in English | MEDLINE | ID: mdl-38621571

ABSTRACT

Nanocellulose is a kind of renewable natural polymer material with high specific surface area, high crystallinity, and strong mechanical properties. RC nanofibers (RCNFs) have attracted an increasing attention in various applications due to their high aspect ratio and good flexibility. Herein, a novel and facile strategy for RCNFs preparation with high-speed shear induced in urea solution through "bottom-up" approach was proposed in this work. Results indicated that the average diameter and yield of RCNF was approach to 136.67 nm and 53.3 %, respectively. Meanwhile, due to the regular orientation RC chains and arrangement micro-morphology, RCNFs exhibited high crystallinity, strong mechanical properties, stable thermal degradation performance, and excellent UV resistance. In this study, a novel regeneration process with high-speed shear induced was developed to produce RCNFs with excellent properties. This study paved a strategy for future low-energy production of nanofibers and high value-added conversion applications of agricultural waste.


Subject(s)
Cellulose , Nanofibers , Urea , Zea mays , Nanofibers/chemistry , Cellulose/chemistry , Zea mays/chemistry , Urea/chemistry , Solutions
5.
J Biol Chem ; 300(5): 107233, 2024 May.
Article in English | MEDLINE | ID: mdl-38552738

ABSTRACT

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.


Subject(s)
Inflammasomes , Mitochondrial Proteins , NLR Family, Pyrin Domain-Containing 3 Protein , Phosphate Transport Proteins , Animals , Humans , Mice , HEK293 Cells , Inflammasomes/metabolism , Mitochondria/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Phosphate Transport Proteins/metabolism , Phosphate Transport Proteins/genetics , Ubiquitination , Cell Line , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Gene Knockdown Techniques
6.
Mol Cell Biochem ; 479(3): 629-642, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37140813

ABSTRACT

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Chemotherapy is the mainstay of treatment for patients with CRC in II-IV stages. Resistance to chemotherapy occurs commonly, which results in treatment failure. Therefore, the identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and developing new therapeutic strategies. Herein, we assessed the roles of KIAA1549 in promoting tumor development and chemoresistance in colorectal cancer. As a result, we found that KIAA1549 expression is up-regulation in CRC. Public databases revealed a progressive up-regulation of KIAA1549 expression from adenomas to carcinomas. Functional characterization uncovered that KIAA1549 promotes tumor malignant phenotypes and boosts the chemoresistance of CRC cells in an ERCC2-dependent manner. Inhibition of KIAA1549 and ERCC2 effectively enhanced the sensitivity to chemotherapeutic drugs oxaliplatin and 5-fluorouracil. Our findings suggest that endogenous KIAA1549 might function as a tumor development-promoting role and trigger chemoresistance in colorectal cancer partly by upregulating DNA repair protein ERCC2. Hence, KIAA1549 could be an effective therapeutic target for CRC and inhibition of KIAA1549 combined with chemotherapy might be a potential therapeutic strategy in the future.


Subject(s)
Colorectal Neoplasms , Humans , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic , Xeroderma Pigmentosum Group D Protein/genetics , Xeroderma Pigmentosum Group D Protein/metabolism
7.
J Opt Soc Am A Opt Image Sci Vis ; 40(8): 1537-1544, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37707109

ABSTRACT

A lens-less method for generating vortex arrays with tunable parameters is proposed based on quasi-Talbot effects. By illuminating a two-dimensional periodic sinusoidal grating with a vortex beam carrying a fourth-order cross-phase, the continuous vortex array structure can be generated in the Fresnel diffraction region. Due to the shaping effect of the fourth-order cross-phase on the vortex beam, by changing the constant parameter of the fourth-order cross-phase, it is possible to shape the generation of optical vortex arrays at different positions. This will somewhat broaden the flexibility of the lens-free optical vortex array in terms of generation position. In addition, the generation of polygonal optical vortex arrays is achieved by higher-order cross-phases of different orders. This technique has potential applications in various fields such as optical tweezers, multi-particle screening, microscopic manipulation, etc.

9.
J Ethnopharmacol ; 308: 116174, 2023 May 23.
Article in English | MEDLINE | ID: mdl-36669597

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Selaginella moellendorffii (SM) has been applied as an ethnic drug to treat conditions such as osteoporosis, idiopathic thrombocytopenic purpura, and chronic inflammation. It is known to be rich in flavonoids, including apigenin glycosides and unique elements of bioflavonoids. AIM OF THE STUDY: To investigate estrogen-like constituents of SM and the possible mechanism. MATERIALS AND METHODS: We identified the main components in liquid chromatography and liquid chromatography-mass spectrometry. The estrogenic effects were examined using a recombinant yeast screening assay, an E-screen cell proliferation assay, and an in vivo uterotrophic assay. RESULTS: Flavonoid glycosides extract, some flavonoid glycosides, and apigenin showed estrogen agonistic activity in the yeast screening assay. They also induced cell proliferation in estrogen receptor-positive (ER+) cells but not in estrogen receptor-negative (ER-) cells. Consistently, the protein expression of ERα, phosphorylation protein kinase B (p-AKT), phosphatidylinositol 3 kinase (PI3K), phosphorylation mammalian target of rapamycin (p-mTOR), phosphorylation 38,000-Da protein (p-P38), and phosphorylation extracellular-regulated kinase 1/2 (p-ERK1/2) elevated following treatment with flavonoid glycoside extract (P < 0.01 or P < 0.05). These effects could be blocked by ER antagonist or ERα antagonist but not be blocked by ERß antagonist. In vivo assay, flavonoid glycoside extract could significantly increase body weight, serum estradiol level, uterine wet weight, alter uterine morphology, and promote ERα protein expression (P < 0.01 or P < 0.05). CONCLUSIONS: ERα induction via mitogen-activated protein kinases (MAPK) and PI3K/Akt/mTOR pathways might be the possible mechanism underlying the phytoestrogen effect of SM, and the flavonoid glycosides might be the critical estrogenic constituents.


Subject(s)
Receptors, Estrogen , Selaginellaceae , Receptors, Estrogen/metabolism , Phytoestrogens/pharmacology , Estrogen Receptor alpha/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Flavonoids/pharmacology , Glycosides/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Apigenin/pharmacology , Saccharomyces cerevisiae , Signal Transduction , Estrogens/pharmacology , TOR Serine-Threonine Kinases/metabolism
10.
Int J Biol Macromol ; 228: 548-558, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36423811

ABSTRACT

High-speed shear system is usually used for the dispersion improvement of slurry, nanomaterials preparation, and even two-dimensional materials production. However, there is barely study that focused on the regenerated cellulose (RC) which was coagulated with shear induced. In this work, a new type of all-cellulose air filter was fabricated through high-speed shear in aqueous regeneration system using parenchyma cellulose from corn stalk. The obtained RC were aggregated by ribbon-like fine cellulose and nanocellulose sheets. The study exhibited the micro-structure of RC displayed excellent unidirectional alignment and a relatively high crystallinity. All-cellulose air filter which was produced via RC presented excellent filtration efficiency (PM2.5 97.3 %, PM10.0 97.7 %) with slightly pressure drop (19 Pa). Therefore, this work provides a facile method to obtain a novel RC with nanocellulose particles used for air filtration, which gives an effective strategy application in the conversion of all-cellulose materials from agricultural waste.


Subject(s)
Air Filters , Nanostructures , Cellulose/chemistry , Nanostructures/chemistry , Water/chemistry , Zea mays/chemistry
11.
Cell Death Discov ; 8(1): 431, 2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36307402

ABSTRACT

Nuclear protein 1 (NUPR1) is a transcriptional coregulator that has been implicated in the development of various cancer types. In addition, de novo fatty acid synthesis plays a pivotal role in hepatocellular carcinoma (HCC) development. However, little is currently known on the role of NUPR1 in hepatocellular carcinoma. In this study, bioinformatics analysis was conducted to analyze the expression level, prognosis value and enriched pathways of NUPR1 in Liver Hepatocellular Carcinoma (LIHC). We found that NUPR1 was significantly upregulated in human hepatocellular carcinoma cells compared with normal hepatocytes from LIHC patients in TCGA cohorts and our patients. Kaplan-Meier analysis and COX proportional hazard progression model showed that high expression of NUPR1 was correlated with a poor prognosis of LIHC patients. CCK-8, EdU and colony formation assays were performed to explore the effect of NUPR1 on the proliferation of HCC cells, then wound healing and transwell migration assays were performed to evaluate the effects of NUPR1 on cell migration. Furthermore, subcutaneous xenograft models were established to study tumor growth. Results showed that NUPR1 overexpression correlated with a highly proliferative and aggressive phenotype. In addition, NUPR1 knockdown significantly inhibited hepatocellular carcinoma cell proliferation and migration in vitro and hindered tumorigenesis in vivo. Mechanistically, endogenous NUPR1 could interact with sterol regulatory element binding protein 1 (SREBP1) and upregulated lipogenic gene expression of fatty acid synthase (FASN), resulting in the accumulation of lipid content. Moreover, pharmacological or genetic blockade of the NUPR1-SREBP1/FASN pathway enhanced anticancer activity in vitro and in vivo. Overall, we identified a novel function of NUPR1 in regulating hepatocellular carcinoma progression via modulation of SREBP1-mediated de novo lipogenesis. Targeting NUPR1-SREBP1/FASN pathway may be a therapeutic alternative for hepatocellular carcinoma.

12.
Molecules ; 27(17)2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36080189

ABSTRACT

The renin-angiotensin system (RAS) is the primary pathway for regulating blood pressure in the body, and angiotensin-converting enzymes (ACEs) play a crucial role in it. Hirudo nipponia is an invertebrate that contains a variety of active peptides; however, there are no studies on the ACE inhibitory activity of hirudo. In the present study, our aim was to identify the active peptides in hirudo based on active peptide database analysis, unexpectedly filling the gap in hirudo ACE inhibitory activity research. Prep-HPLC was used to separate the part below 3 kD from hirudo. The peptide composition of the isolates was obtained based on Orbitrap LC-MS. The activity of each group of peptides was predicted by the database and the activity was determined by bioassay. Peptides with validation activity were screened through the database. In total, 337 peptides and 18 peptides matching the NCBI leech protein database were identified. All four fractions showed ACE inhibitory activity, and the IC50 was 0.8266, 0.2708, 0.4432, and 0.1764 mg/mL, respectively. Six screened peptides showed good affinity for ACE. This work reveals for the first time that low-molecular-weight peptides from H. nipponia have ACE inhibitory activity, which can provide a new explanation for leech treatment of hypertension.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Leeches , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Chromatography, High Pressure Liquid , Peptides/chemistry , Peptidyl-Dipeptidase A/chemistry
13.
Br J Cancer ; 127(4): 637-648, 2022 09.
Article in English | MEDLINE | ID: mdl-35597868

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC. METHODS: Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance. RESULTS: Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2. CONCLUSIONS: Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.


Subject(s)
Colorectal Neoplasms , NF-kappa B , Animals , Apoptosis , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/radiotherapy , Gene Expression Regulation, Neoplastic , Humans , NF-kappa B/genetics , NF-kappa B/metabolism , Radiation Tolerance/genetics , Signal Transduction , Thioredoxins/genetics , Thioredoxins/metabolism , Thioredoxins/therapeutic use
14.
Int J Biol Macromol ; 203: 1-9, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35063490

ABSTRACT

Wound healing is a challenged and complicated process due to the bacterial infections and frequent replacement in healing process. Hydrogels with properties of visibility and biocompatibility provided convenient and effective treatment during the wound healing process. Bamboo parenchyma cells have a great potential utilized on cellulosic materials fabrication for their high specific surface area and accessibility of chemical reagents. Herein, we present a simple and facile manufacture of transparent wound dressing from bamboo parenchymal cellulose via dissolution in DMAc/LiCl system. Rifampicin (RIF) was loaded on the hydrogel through immersion method. The result exhibited that the maximum drug loading efficiency of cellulose hydrogels was 82.13%. Hydrogel loaded RIF (HLR) showed that the inhibition zones against Gram-negative and Gram-positive bacteria were 19.11 mm and 36.93 mm, respectively. It was observed that the wound was healed more than 60% at 11th day in murine wound models. Meanwhile, RIF provided an exceptionally antibacterial property to hydrogels and promoted proliferation of epidermis cells in wound. As a result of observations, HLR demonstrating potential application in visual wound dressing materials for their excellent transparency, antibacterial effect, wound healing, and biocompatibility.


Subject(s)
Anti-Infective Agents , Hydrogels , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Cellulose/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Mice , Rifampin/pharmacology , Wound Healing
15.
Hepatology ; 75(6): 1386-1401, 2022 06.
Article in English | MEDLINE | ID: mdl-34580888

ABSTRACT

BACKGROUND AND AIMS: Poor response to ionizing radiation (IR) due to resistance remains a clinical challenge. Altered metabolism represents a defining characteristic of nearly all types of cancers. However, how radioresistance is linked to metabolic reprogramming remains elusive in hepatocellular carcinoma (HCC). APPROACH AND RESULTS: Baseline radiation responsiveness of different HCC cells were identified and cells with acquired radio-resistance were generated. By performing proteomics, metabolomics, metabolic flux, and other functional studies, we depicted a metabolic phenotype that mediates radiation resistance in HCC, whereby increased glucose flux leads to glucose addiction in radioresistant HCC cells and a corresponding increase in glycerophospholipids biosynthesis to enhance the levels of cardiolipin. Accumulation of cardiolipin dampens the effectiveness of IR by inhibiting cytochrome c release to initiate apoptosis. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1) signaling-mediated translational control of hypoxia inducible factor-1α (HIF-1α) and sterol regulatory element-binding protein-1 (SREBP1) remodels such metabolic cascade. Targeting mTORC1 or glucose to cardiolipin synthesis, in combination with IR, strongly diminishes tumor burden. Finally, activation of glucose metabolism predicts poor response to radiotherapy in cancer patients. CONCLUSIONS: We demonstrate a link between radiation resistance and metabolic integration and suggest that metabolically dismantling the radioresistant features of tumors may provide potential combination approaches for radiotherapy in HCC.


Subject(s)
Carcinoma, Hepatocellular , Cardiolipins , Glucose , Liver Neoplasms , Radiation Tolerance , Carcinoma, Hepatocellular/metabolism , Cardiolipins/metabolism , Cell Line, Tumor , Glucose/metabolism , Humans , Hypoxia-Inducible Factor 1, alpha Subunit , Liver Neoplasms/genetics , Mechanistic Target of Rapamycin Complex 1 , Sterol Regulatory Element Binding Protein 1
16.
Front Oncol ; 11: 774201, 2021.
Article in English | MEDLINE | ID: mdl-34900724

ABSTRACT

BACKGROUND: Evodiamine (EVO), an alkaloid extracted from the traditional Chinese medicine Euodia rutaecarpa, plays an important role in the treatment of cancer. This study was performed to clarify the effects of evodiamine in mice tumor model studies. METHODS: Electronic databases and search engines involved China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, and ClinicalTrials.gov databases, which were searched for literature related to the antitumor effects of evodiamine in animal tumor models (all until 1 October 2021). The evodiamine effects on the tumor volume and tumor weight were compared between the treatment and control groups using the standardized mean difference (SMD). RESULTS: Evodiamine significantly inhibited tumor growth in mice, as was assessed with tumor volume [13 studies, n=267; 138 for EVO and 129 for control; standard mean difference (SMD)= -5.99; 95% (CI): -8.89 to -3.10; I2 = 97.69%, p ≤ 0.00], tumor weight [6 studies, n=89; 49 for EVO and 40 for control; standard mean difference (SMD)= -3.51; 95% (CI): -5.13 to -3.90; I2 = 83.02%, p ≤ 0.00]. CONCLUSION: EVO significantly suppresses tumor growth in mice models, which would be beneficial for clinical transformation. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether EVO can be used in the adjuvant treatment of clinical tumor patients.

18.
Nat Commun ; 12(1): 4664, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34341353

ABSTRACT

Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1ß and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.


Subject(s)
COVID-19/metabolism , Coronavirus Nucleocapsid Proteins/metabolism , Inflammasomes/metabolism , Inflammation/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , SARS-CoV-2/metabolism , Animals , COVID-19/virology , Cells, Cultured , Cytokines/metabolism , HEK293 Cells , Humans , Inflammasomes/genetics , Lung Injury/genetics , Lung Injury/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Phosphoproteins/metabolism , Protein Binding , SARS-CoV-2/physiology , THP-1 Cells
19.
PLoS Pathog ; 17(7): e1008603, 2021 07.
Article in English | MEDLINE | ID: mdl-34310658

ABSTRACT

Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients and highly associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure, and disseminated intravascular coagulation as the disease progresses of DHF/DSS patients, which can lead to the death of patients. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patients' sera, peripheral blood mononuclear cells (PBMCs), and macrophages. This study further reveals that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor κB (NF-κB) signaling pathway. Additionally, NS1 facilitates the MMP-9 enzymatic activity, which alters the adhesion and tight junction and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with ß-catenin and Zona occludens protein-1/2 (ZO-1 and ZO-2) and to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients.


Subject(s)
Dengue/pathology , Endothelial Cells/metabolism , Matrix Metalloproteinase 9/metabolism , Viral Nonstructural Proteins/metabolism , Animals , Capillary Permeability/physiology , Cell Adhesion/physiology , Dengue/metabolism , Dengue/virology , Dengue Virus/metabolism , Humans , Mice , Tight Junctions/metabolism
20.
Respir Physiol Neurobiol ; 294: 103741, 2021 12.
Article in English | MEDLINE | ID: mdl-34273552

ABSTRACT

We screened key miRNAs in an intermittent hypoxia rat model and explored the biological roles of downstream target genes and related regulatory pathways. We analyzed the expression profile of miRNAs in the lung tissues of rats in the 5 % (IH1), 7.5 % (IH2), 10 % (IH3), 12.5 % (IH4) oxygen concentration and negative control (NC) groups and identified common miRNAs. Multiple differentially expressed miRNAs were detected, and intersection of their expression profiles yielded 10 common miRNAs with 929 target genes mainly distributed in the nucleus. Molecular functions pertained mainly to the activation of transcription factors, while biological processes focused on cell interaction and signal transduction. Among signaling pathways, the top 5 included the LKB1 signaling, nectin adhesion, and S1P pathways. 8 of 10 common miRNAs had excellent diagnostic value for detecting intermittent hypoxia. The miRNAs binds to the target gene might play a key role in the pathophysiological process of OSA through the LKB1/AMPK and S1P/Akt/eNOS signaling pathways.


Subject(s)
Hypoxia/metabolism , Lung/metabolism , MicroRNAs/metabolism , Signal Transduction/physiology , Sleep Apnea, Obstructive/metabolism , Animals , Disease Models, Animal , Rats
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