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"Hao-Yu, Dai"
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Holothurian Glycosaminoglycan (hGAG) Promoted Bim-Induced Apoptosis in Human Lung Adenocarcinoma A549 Cell Line Through Inhibition of Akt-Mediated FOXO3a Translocation
Holothurian glycosaminoglycan (hGAG) is an extract from the body wall of sea cucumber and previous studies have proved many unique bioactivities of it, such as anti-tumor, anti-coagulation and immune regulation. Previous studies of our research group have shown hGAG promoted cell apoptosis in human lung adenocarcinoma A549 cells by upregulating Bax and caspase-3 and downregulating Bcl-2, indicating mitochondrial apoptosis pathway participated in the process. In the mitochondrial apoptosis pathway, Bim induces cell apoptosis by either direct activation of pro-apoptotic Bax/Bak or neutralization of anti-apoptotic Bcl-2 proteins. The transcription of Bim was regulated by FOXO3a. Akt, one of the most important cellular signaling molecules, regulates apoptosis through its phosphorylation. Phosphorylation of Akt results in translocation of FOXO3a from nuclear to cytoplasm. This study aimed to explore the mechanism by which hGAG induced apoptosis in A549 cells, focusing on its regulation of the Akt/FOXO3a/Bim signaling pathway.
A549 cells were divided into three groups: control group, hGAG group and hGAG+SC79 (an Akt activator) group. Cell proliferation was detected by CCK-8 assay. Cell apoptosis was detected by flow cytometry. mRNA and protein expression levels were detected by Real-time Fluorescence Quantitative PCR and Western blotting assay, respectively. Protein localization was detected by immunofluorescence.
The results showed that hGAG induced apoptosis in A549 cells by downregulating p-Akt level, promoting FOXO3a expression, preventing FOXO3a nuclear export, and upregulating Bim expression, while SC79 reversed these effects, further demonstrating that hGAG regulated FOXO3a and Bim through inhibition of phosphorylation of Akt.
In conclusion, our data demonstrated that hGAG promoted apoptosis in A549 cells via the Akt/FOXO3a/Bim-mediated intrinsic apoptosis pathway.
Journal Article
Two Molecular Weights Holothurian Glycosaminoglycan and Hematoporphyrin Derivative-Photodynamic Therapy Inhibit Proliferation and Promote Apoptosis of Human Lung Adenocarcinoma Cells
Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups: control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG + HPD-PDT group, and 5W molecular weight hGAG + HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.
Journal Article
Extranodal NK/T-Cell Lymphoma Misdiagnosed as Pulmonary Infection
Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is highly invasive. Its etiology and pathogenesis may be related to Epstein-Barr virus infection. In this article, we report a case of a man with ENKTL affecting the right vocal cord and right lung. Initially, the lesion was misdiagnosed as a pulmonary infection. However, subsequent histopathological examinations confirmed the diagnosis through analysis of a surgically resected specimen. Following 14 cycles of immune therapy and chemotherapy, the lesion in the right lung significantly shrank. This case underscored the importance of obtaining surgically resected specimens for pathology when ENKTL is suspected, which can improve diagnostic accuracy and mitigate misdiagnosis.
Journal Article
LYMPHOMA /Extranodal NK/T-Cell Lymphoma Misdiagnosed as Pulmonary Infection
Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is highly invasive. Its etiology and pathogenesis may be related to Epstein-Barr virus infection. In this article, we report a case of a man with ENKTL affecting the right vocal cord and right lung. Initially, the lesion was misdiagnosed as a pulmonary infection. However, subsequent histopathological examinations confirmed the diagnosis through analysis of a surgically resected specimen. Following 14 cycles of immune therapy and chemotherapy, the lesion in the right lung significantly shrank. This case underscored the importance of obtaining surgically resected specimens for pathology when ENKTL is suspected, which can improve diagnostic accuracy and mitigate misdiagnosis.
Journal Article
LYMPHOMA /Extranodal NK/T-Cell Lymphoma Misdiagnosed as Pulmonary Infection
Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is highly invasive. Its etiology and pathogenesis may be related to Epstein-Barr virus infection. In this article, we report a case of a man with ENKTL affecting the right vocal cord and right lung. Initially, the lesion was misdiagnosed as a pulmonary infection. However, subsequent histopathological examinations confirmed the diagnosis through analysis of a surgically resected specimen. Following 14 cycles of immune therapy and chemotherapy, the lesion in the right lung significantly shrank. This case underscored the importance of obtaining surgically resected specimens for pathology when ENKTL is suspected, which can improve diagnostic accuracy and mitigate misdiagnosis.
Journal Article
Fumigant dazomet induces tobacco plant growth via changing the rhizosphere microbial community
After continuous cropping for many years, crops are often subject to growth inhibition, which seriously affects their yields.In agricultural production, soil fumigation can effectively alleviate the biological stress on plants. However, the relationship between the microbial groups that respond to soil fumigation changes and plants, as well as whether their existence makes a beneficial contribution to plants, remains unclear. We explored the mechanism of soil fumigation promoting plant growth by affecting microorganisms. The results showed that dazomet treatment significantly alleviated the growth retardation of tobacco, and this difference was most obvious in the flourishing period of tobacco, when the plant height and leaf area increased by 3.33 times and 3.24 times respectively. In addition, the growth advantage of the above-ground tissue was significantly correlated with the root advantage (
P
< 0.05). At the same time, we found that dazomet treatment significantly increased a large number of microbial groups positively related to roots, such as
g_Pedobacter
,
g_Microbacterium
and
g_Brevundimonas
. The results of structural equation modeling indicated that the microbial community, which was positively correlated with the amount of dazomet applied and also positively correlated with roots (
P
< 0.05), was an important factor contributing to the growth advantage of tobacco. Overall, the findings of this study are of great significance for enhancing our understanding of soil remediation by fumigation and may have far reaching implications for the practical application of dazomet fumigation.
Journal Article
Heat shock protein 90 acts as a molecular chaperone in late-phase activation of extracellular signal-regulated kinase 1/2 stimulated by oxidative stress in vascular smooth muscle cells
Aim： To investigate whether cytosolic heat shock protein 90 （HSP90） acts as a molecular chaperone on the activated extracellular signal-regulated kinase 1/2 （ERK1/2） and cell proliferation stimulated by reactive oxygen species （ROS） in rat vascular smooth muscle cells （VSMC）. Methods： VSMC were exposed to 1 pmol/L LY83583 （6-anilinoquinoline-5,8-quinolinedione, producer of ROS） for 120 min in the presence or absence of 5 μmol/L geldanamycin, a specific inhibitor of HSP90. Then the total, soluble, and insoluble proteins of the cells were collected. HSP90, ERK1/2, and phosphor-ERK 1/2 in the cell lysate were measured by Western blotting. The interaction of HSP90 and phosphor-ERK1/2 was analyzed by immunoprecipi- tation assay, and the nuclear phosphor-ERK1/2 was measured by Western blot- ting and immunofluorescence. Cell proliferation was tested by cell counting and 3-（4,5-dimethylthiazol-2-yl）-3,5-di-phenyltetrazoliumbromide （MTT）. Results： The cytosolic HSP90 of VSMC was upregulated by LY83583 in a time-dependent man- ner with the peak at 120 min, which is consistent with the late peak of phosphor- ERK1/2. Immunoprecipitation and Western blotting analyses showed that LY83583 increased the interaction of HSP90 with phosphor-ERK1/2, the phosphor-ERK1/2 level, and the soluble phosphor-ERK1/2 level by 1.8-, 2.5-, and 2.9-fold, respectively. In contrast, the insoluble phosphor-ERK1/2 of VSMC was decreased. Interestingly, LY83583 treatment promoted the nuclear phosphor-ERK1/2 by 7.6-fold as con- firmed by Western blotting and immunofluorescence assays. Furthermore, cell counting and the MTT assay showed that LY83583 stimulated VSMC prolifera- tion with the increased expression of HSP90 and levels of soluble and nuclear phosphor-ERK1/2. Pretreatment of geldanamycin antagonized the effect of LY83583. Conclusion： HSP90 could mediate the oxidative stress-stimulated, late- phase activation of ERK1/2 and VSMC proliferation by promoting the ERK1/2 phosphorylation, the association of itself with phosphor-ERK1/2, and the solubil- ity and nuclear translocation of phosphor-ERK 1/2.
Journal Article
O-FIB: far-field-induced near-field breakdown for direct nanowriting in an atmospheric environment
Nanoscale surface texturing, drilling, cutting, and spatial sculpturing, which are essential for applications, including thin-film solar cells, photonic chips, antireflection, wettability, and friction drag reduction, require not only high accuracy in material processing, but also the capability of manufacturing in an atmospheric environment. Widely used focused ion beam (FIB) technology offers nanoscale precision, but is limited by the vacuum-working conditions; therefore, it is not applicable to industrial-scale samples such as ship hulls or biomaterials, e.g., cells and tissues. Here, we report an optical far-field-induced near-field breakdown (O-FIB) approach as an optical version of the conventional FIB technique, which allows direct nanowriting in air. The writing is initiated from nanoholes created by femtosecond-laser-induced multiphoton absorption, and its cutting “knife edge” is sharpened by the far-field-regulated enhancement of the optical near field. A spatial resolution of less than 20 nm (λ/40, with λ being the light wavelength) is readily achieved. O-FIB is empowered by the utilization of simple polarization control of the incident light to steer the nanogroove writing along the designed pattern. The universality of near-field enhancement and localization makes O-FIB applicable to various materials, and enables a large-area printing mode that is superior to conventional FIB processing.Nanotechnology: Better writing with lightAn optical version of Focused Ion Beam technology (FIB) allows nanoscale “writing” such as surface texturing, drilling and sculpting of materials to be performed in air, avoiding the need for a vacuum which limits the application of conventional FIB. The “Optical Far-field-Induced near-field Breakdown” (O-FIB) approach has been developed by Hong-Bo Sun of Tsinghua University and colleagues at Jilin University in China and Swinburne University of Technology in Austrilia. It works by creating nanoholes with a femtosecond laser, which is controlled by sophisticated optical effects. The process can cover larger areas than conventional FIB, and with a spatial resolution below 20 nanometres. The ability to be performed in an open atmosphere offers new possibilities for nanoscale writing. These range from working on industrial scale materials such as ship hulls, down to living tissues and cells.
Journal Article
Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis
ObjectiveTo compare the efficacy and safety between and within glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in overweight or obese adults with or without diabetes mellitus.MethodsPubMed, ISI Web of Science, Embase and Cochrane Central Register of Controlled Trials database were comprehensively searched to identify randomised controlled trials (RCTs) of effects of GLP-1RAs and SGLT-2is in overweight or obese participants from inception to 16 January 2022. The efficacy outcomes were the changes of body weight, glucose level and blood pressure. The safety outcomes were serious adverse events and discontinuation due to adverse events. The mean differences, ORs, 95% credible intervals (95% CI), the surface under the cumulative ranking were evaluated for each outcome by network meta-analysis.ResultsSixty-one RCTs were included in our analysis. Both GLP-1RAs and SGLT-2is conferred greater extents in body weight reduction, achieving at least 5% wt loss, HbA1c and fasting plasma glucose decrease compared with placebo. GLP-1RAs was superior to SGLT-2is in HbA1c reduction (MD: −0.39%, 95% CI −0.70 to −0.08). GLP-1RAs had high risk of adverse events, while SGLT-2is were relatively safe. Based on intraclass comparison, semaglutide 2.4 mg was among the most effective interventions in losing body weight (MD: −11.51 kg, 95% CI −12.83 to −10.21), decreasing HbA1c (MD: −1.49%, 95% CI −2.07 to −0.92) and fasting plasma glucose (MD: −2.15 mmol/L, 95% CI −2.83 to −1.59), reducing systolic blood pressure (MD: −4.89 mm Hg, 95% CI −6.04 to −3.71) and diastolic blood pressure (MD: −1.59 mm Hg, 95% CI −2.37 to −0.86) with moderate certainty evidences, while it was associated with high risk of adverse events.ConclusionsSemaglutide 2.4 mg showed the greatest effects on losing body weight, controlling glycaemic level and reducing blood pressure while it was associated with high risk of adverse events.PROSPERO registration numberCRD42021258103.
Journal Article