Publications by authors named "Xiaolong Tang"

127 Publications

BEZ235 Increases the Sensitivity of Hepatocellular Carcinoma to Sorafenib by Inhibiting PI3K/AKT/mTOR and Inducing Autophagy.

Biomed Res Int 2021 16;2021:5556306. Epub 2021 Apr 16.

Medical School, Anhui University of Science & Technology, Huainan 232001, China.

Acquired resistance of hepatocellular carcinoma (HCC) to sorafenib (SFB) is the main reason for the failure of SFB treatment of the cancer. Abnormal activation of the PI3K/AKT/mTOR pathway is important in the acquired resistance of SFB. Therefore, we investigated whether BEZ235 (BEZ) could reverse acquired sorafenib resistance by targeting the PI3K/mTOR pathway. A sorafenib-resistant HCC cell line Huh7 was established. MTT assay, clone formation assay, flow cytometry, and immunofluorescence were used to analyze the effects of BEZ235 alone or combined with sorafenib on cell proliferation, cell cycle, apoptosis, and autophagy of Huh7 and Huh7 cells. The antitumor effect was evaluated in animal models of Huh7 xenografts . Western blot was used to detect protein levels of the PI3K/AKT/mTOR pathway and related effector molecules. results showed that the Huh7 had a stronger proliferation ability and antiapoptosis effect than did Huh7, and sorafenib had no inhibitory effect on Huh7. SFB + BEZ inhibited the activation of the PI3K/AKT/mTOR pathway caused by sorafenib. Moreover, SFB + BEZ inhibited the proliferation and cloning ability, blocked the cell cycle in the G0/G1 phase, and promoted apoptosis in the two cell lines. The autophagy level in Huh7 cells was higher than in Huh7 cells, and BEZ or SFB + BEZ further promoted autophagy in the two cell lines. , SFB + BEZ inhibited tumor growth by inducing apoptosis and autophagy. We concluded that BEZ235 enhanced the sensitivity of sorafenib through suppressing the PI3K/AKT/mTOR pathway and inducing autophagy. These observations may provide the experimental basis for sorafenib combined with BEZ235 in trial treatment of HCC.
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http://dx.doi.org/10.1155/2021/5556306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079203PMC
June 2021

LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway.

Mol Med Rep 2021 Jul 13;24(1). Epub 2021 May 13.

Medical School, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China.

Liver cancer remains one of the leading causes of cancer deaths worldwide. The therapeutic effect of oxaliplatin on liver cancer is often limited by acquired resistance of the cancer cells. Abnormal activation of the PI3K/AKT pathway plays an important role in the acquired resistance of oxaliplatin. The present study investigated the effects of the PI3K inhibitor LY‑294002 and AKT inhibitor MK2206 on the chemosensitivity of oxaliplatin‑resistant liver cancer cells and the molecular mechanism involved. An oxaliplatin‑resistant liver cancer cell line HepG2 was developed. MTT assay, clone formation experiments, flow cytometry and Annexin V‑FITC/PI staining were used to determine the proliferation, cycle and apoptosis of HepG2 cells when oxaliplatin was combined with LY‑294002 or MK2206 treatment. The effects of LY‑294002 and MK‑2206 on the abnormal activation of PI3K/AKT pathway and hypoxia inducible factor (HIF)‑1α protein level in HepG2 cells were detected using western blotting. The results indicated that the PI3K/AKT pathway is stably activated in HepG2 cells. Compared with the AKT inhibitor MK2206, the PI3K inhibitor LY‑294002 more effectively downregulated the phosphorylation levels of p85, p110α, p110β, p110γ and AKT in the PI3K/AKT pathway in HepG2 cells, and more effectively inhibited the proliferation of the cells. LY‑294002 enhanced the chemotherapy sensitivity of HepG2R cells to oxaliplatin by inducing G/G phase arrest and increasing the proportion of apoptotic cells. In addition, LY‑294002 reduced the level of HIF‑1α, which is highly expressed in HepG2 cells. It was concluded that LY‑294002 enhanced the chemosensitivity of liver cancer cells to oxaliplatin by inhibiting the PI3K/AKT signaling pathway, which may be related to the inhibition of HIF‑1α expression. These findings may have clinical significance for the treatment of oxaliplatin‑resistant liver cancer.
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http://dx.doi.org/10.3892/mmr.2021.12147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134878PMC
July 2021

Evolution mechanism of transition metal in NH-SCR reaction over Mn-based bimetallic oxide catalysts: Structure-activity relationships.

J Hazard Mater 2021 Jul 9;413:125361. Epub 2021 Feb 9.

Department of Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China; Beijing Key Laboratory of Resource-oriented Treatment of Industrial Pollutants, Beijing 100083, China. Electronic address:

The unexpected phenomenon in which different transition metals (Co, Ni and Cu) presented significant variation of participation levels as the auxiliaries in Mn-based bimetallic oxide catalysts were reported here. It is found that the Co element more easily to form Mn enriched surface bimetallic oxides with Mn than Ni and Cu, resulting in Co-MnO exhibited the best deNO activity and SO tolerance, followed by Ni-MnO and Cu-MnO. The role of different transition metal and structure-activity relationships were systematically investigated by advanced techniques including Synchrotron XAFS and in situ DRIFTs analysis. The excellent activity of Co-MnO was related to its unique Mn-enriched surface (Co)(Mn Co)O structure with Mn cations occupying the octahedral sites, which is superior to the Ni-MnO and Cu-MnO with Mn-lean surface. In addition, the reaction energy barrier of Co-MnO is weakened due to the lower electron cloud density around the Mn atom as compared to Ni-MnO and Cu-MnO. Moreover, Co-MnO benefiting from the rapid electron migration between Mn and Co, more active bidentate/bridged nitrates could react with adsorbed NH in faster reaction rates following the L-H mechanism.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125361DOI Listing
July 2021

Comparison of hematological traits and oxygenation properties of hemoglobins from highland and lowland Asiatic toad (Bufo gargarizans).

J Comp Physiol B 2021 Apr 19. Epub 2021 Apr 19.

Department of Animal and Biomedical Sciences, School of Life Science, Lanzhou University, Lanzhou, 730000, Gansu, China.

The Asiatic toad (Bufo gargarizans) belonging to the family of Bufonidae (Anura: Amphibia) is successfully residing on the Qinghai-Tibetan Plateau (QTP). To investigate whether the oxygen delivery undergoes adaptive adjustments to high-altitude environments in Asian toads inhabiting the QTP (Zoige County, 3446 m), choosing low-altitude populations (Chengdu City, 500 m) as control, we measured hematological traits, O affinities of whole blood, Hb-O affinities of purified Hbs, their sensitivities to temperature, and allosteric effectors (H, Cl and ATP). Our results showed that high-altitude Asiatic toads possessed significantly increased hemoglobin concentration, hematocrit, and red blood cell count, but significantly decreased erythrocyte volume compared with low-altitude toads. The whole blood and purified Hbs of high-altitude Asiatic toads both exhibited significantly higher O affinities compared with low-altitude toads. Substantially increased intrinsic Hb-O affinities of high-altitude Asiatic toads Hbs are likely to be the main reason for its elevated Hb-O affinities given the anionic cofactor sensitivities of high- and low-altitude toads were similar. The Hbs of high-altitude toads were also characterized by distinctly strong Bohr effects at the low temperature and low-temperature sensitivities. The adaptive adjustments of hematological traits could enhance the blood-O carrying capacity of high-altitude Asiatic toads. The increased Hb-O affinities could safeguard the pulmonary O uploading under hypoxia. The strong Bohr effects at the low temperature could help the release of O in metabolic tissues and cold limbs, while low-temperature sensitivity could minimize the effect of temperature fluctuation on the Hb-O affinity.
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http://dx.doi.org/10.1007/s00360-021-01368-8DOI Listing
April 2021

Tail display is regulated by anaerobic metabolism in an Asian agamid lizard.

Integr Zool 2021 Mar 17. Epub 2021 Mar 17.

Chengdu Institute of Biology, Chinese academy of sciences, Chengdu, China.

Understanding the mechanism underlying signal variation is an important goal in the study of animal communication. Several potential causes have been proposed for signal variation, including environmental noise (e.g. wind, sound), energy limitation, and predation risk, among others, but the physiological control of many signals are often unclear. Here, we examined the correlation between tail display signal variation and energy metabolic activity using an Asian agamid lizard Phrynocephalus vlangalii. Individual tail display signals were observed in the field, and blood lactate concentration as well as 2 energy metabolic enzymes was assayed. Our results showed that average tail coil speed was positively associated with blood lactate concentration, while tail coil duration was negatively associated with LDH activity. We also found that average tail lash speed was positively associated with blood lactate concentration, suggesting that the tail display behavior of P. vlangalii was regulated by anaerobic metabolism. Furthermore, the correlation between tail display behavior and energy metabolism was not sex-dependent. Taken together, our research provides insight into the physiological mechanisms underlying tail display variation in lizards, and suggests that tail display variation likely transmits important information on individual body condition and resource holding potential.
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http://dx.doi.org/10.1111/1749-4877.12536DOI Listing
March 2021

A four-protein metabolon assembled by a small peptide protein creates the pentacyclic carbonate ring of aldgamycins.

Acta Pharm Sin B 2021 Feb 30;11(2):588-597. Epub 2020 Jul 30.

Institute of Traditional Chinese Medicine and Natural Product/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive -hydroxylcarbamoyl moiety to the decarboxylated aldgamycins followed by a non-enzymatic condensation to give the pentacyclic carbonate ring. Our results have documented an unprecedent mechanism for carbonate formation.
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http://dx.doi.org/10.1016/j.apsb.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893128PMC
February 2021

Transition in air pollution, disease burden and health cost in China: A comparative study of long-term and short-term exposure.

Environ Pollut 2021 May 16;277:116770. Epub 2021 Feb 16.

Department of Environmental Engineering, School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, PR China; Beijing Key Laboratory of Resource-oriented Treatment of Industrial Pollutants, University of Science and Technology Beijing, Beijing, 100083, PR China. Electronic address:

Ambient air pollution is one of the leading environmental risk factors to human health, largely offsetting economic growth. This study evaluated health burden and cost associated with the short-term and long-term exposure of major air pollutants (fine particulate matter [PM] and ozone [O]) during 2013-2018. We developed a database of gridded daily and annual PM and O exposure in China at 15 km × 15 km resolution. Then, we estimated the age- and cause-specific premature deaths and quantified related health damage with an age-adjusted value of statistical life (VSL) measure. The health cost estimated in this study captured direct cost, indirect cost and intangible cost of the premature death attributable to ambient PM and O. We found that the national premature deaths attributable to long-term and short-term exposure to PM decreased by 15% and 59%, whereas the national premature deaths attributable to long-term and short-term exposure to O increased by 36% and 94%. Despite a 15% reduction of attributable deaths, the health cost attributable to long-term exposure to PM did not change significantly as a result of GDP growth and population aging. On the other hand, the long-term O related health cost in 2018 doubled that in 2013. Our study suggests that while premature deaths fell as a result of China's clean air actions, the health costs of air pollution remained high. The growing trends of O highlighted the needs for strategies to reduce both PM and O emissions, for the sake of public health and social well-being in China.
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http://dx.doi.org/10.1016/j.envpol.2021.116770DOI Listing
May 2021

LY3214996 relieves acquired resistance to sorafenib in hepatocellular carcinoma cells.

Int J Med Sci 2021 29;18(6):1456-1464. Epub 2021 Jan 29.

Medical school, Anhui University of Science and Technology, Huainan 232001, China.

Sorafenib, an oral multi-kinase inhibitor of rapidly accelerated fibrosarcoma; vascular endothelial growth factor receptor-2/3, platelet-derived growth factor receptor, c-Kit, and Flt-3 signaling, is approved for treatment of advanced hepatocellular carcinoma (HCC). However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. In this work, we investigated whether adding LY3214996, a selective ERK1/2 inhibitor, to sorafenib would increase the anti-tumor effectiveness of sorafenib to HCC cells. The Huh7 cell line was used as a cell model for treatment with sorafenib, LY3214996, and their combination. Phosphorylation of the key kinases in the Ras/Raf/MAPK and PI3K/Akt pathways, protein expression of the cell cycle, and apoptosis migration were assessed with western blot. MTT and colony-formation assays were used to evaluate cell proliferation. Wound-healing assay was used to assess cell migration. Cell cycle and apoptosis analyses were conducted with flow cytometry. LY3214996 decreased phosphorylation of the Ras/Raf/MAPK and PI3K/Akt pathways, including p-c-Raf, p-P90RSK, p-S6K and p-eIF4EBP1 activated by sorafenib, despite increased p-ERK1/2 levels. LY3214996 increased the anti-proliferation, anti-migration, cell-cycle progression, and pro-apoptotic effects of sorafenib on Huh7 cells. Reactivation of ERK1/2 appears to be a molecular mechanism of acquired resistance of HCC to sorafenib. LY3214996 combined with sorafenib enhanced the anti-tumor effects of sorafenib in HCC. These findings form a theoretical basis for trial of LY3214996 combined with sorafenib as second-line treatment of sorafenib-resistant in advanced HCC.
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http://dx.doi.org/10.7150/ijms.51256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893555PMC
January 2021

Simultaneous removal of gaseous CO and elemental mercury over Cu-Co modified activated coke at low temperature.

J Environ Sci (China) 2021 Mar 21;101:36-48. Epub 2020 Aug 21.

School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China.

Cu-Co multiple-oxides modified on HNO-pretreated activated coke (AC) were optimized for the simultaneous removal of gaseous CO and elemental mercury (Hg) at low temperature (< 200 °C). It was found that 2%CuOx-10%CoOx/AC catalyst calcined at 400°C resulted in the coexistence of complex oxides including CuO, CuO, CoO, CoO and CoO phases, which might be good for the simultaneous catalytic oxidation of CO by Co-species and removal of Hg by Cu-species, benefiting from the synergistic catalysis during the electro-interaction between Co and Cu cations (CoO ⇌ CoO and CuO ⇌ CuO). The catalysis removal of CO oxidation was obviously depended on the reaction temperature obtaining 94.7% at 200 °C, while no obvious promoting effect on the Hg removal (68.3%-78.7%). These materials were very substitute for the removal of CO and Hg° from the flue gas with the conditions of 8-20 vol.% O and flue-gas temperature below 200 °C. The removal of Hg° followed the combination processes of adsorption and catalytic oxidation reaction via Langmuir-Hinshelwood mechanism, while the catalysis of CO abided by the Mars-van Krevelen mechanism with lattice oxygen species.
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http://dx.doi.org/10.1016/j.jes.2020.05.029DOI Listing
March 2021

LncRNA HAND2-AS1 suppressed the growth of triple negative breast cancer via reducing secretion of MSCs derived exosomal miR-106a-5p.

Aging (Albany NY) 2020 12 3;13(1):424-436. Epub 2020 Dec 3.

Department of General Surgery, Shanghai Eighth People Hospital, Xuhui, Shanghai, China.

Background: Triple-negative breast cancer (TNBC) is a special type of breast cancer, its tumor cell metastasis rate is much higher than other types, and at the same time has a high rate of postoperative recurrence, which significantly threatens the health of women. Thus, it is urgent to explore a new treatment for TNBC.

Results: MiR-106a-5p was up-regulated in TNBC tissues and cells, and was positively correlated with the tumor grade, which indicated poor prognosis in TNBC patients. Mesenchymal stem cells (MSCs) can transport miR-106a-5p into TNBC cells via exosomes. Functional analysis showed exo-miR-106a-5p secreted by MSCs promoted tumor progression in TNBC cells. Furthermore, lncRNA HAND2-AS1 inhibited miR-106a-5p levels, and HAND2-AS1 was decreased in TNBC tissues and cells. Besides, overexpression of HAND2-AS1 reduced the secretion of exo-miR-106a-5p secretion from MSCs, thus suppressed TNBC development.

Conclusion: Our study revealed that HAND2-AS1 inhibited the growth of TNBC, which were mediated by the inhibitory effects of MSC-derived exosomal miR-106a-5p.
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http://dx.doi.org/10.18632/aging.202148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835037PMC
December 2020

TRIM27 Functions as a Novel Oncogene in Non-Triple-Negative Breast Cancer by Blocking Cellular Senescence through p21 Ubiquitination.

Mol Ther Nucleic Acids 2020 Dec 15;22:910-923. Epub 2020 Oct 15.

Department of General Surgery, Shanghai Eighth People Hospital, Shanghai 200235, China.

In the current study, we aimed to explore the correlation between TRIM27 and breast cancer prognosis, as well as the functions of TRIM27 in breast cancer and their underlying mechanisms. Bioinformatics analyses were used to examine the correlation between TRIM27 and breast cancer prognosis. Moreover, TRIM27 knockdown and overexpression in breast cancer cells were performed to investigate its functions in breast cancer. Tamoxifen (TAM) was applied to evaluate the influence of TRIM27 on chemoresistance of breast cancer cells, while co-immunoprecipitation (coIP) was performed to identify the E3 ubiquitin ligase capability of TRIM27. High expression of TRIM27 was found in non-triple-negative breast cancer (non-TNBC) tumor tissues and was positively correlated with the mortality of non-TNBC patients. Moreover, TRIM27 could suppress non-TNBC cell apoptosis and senescence, promote cell viability and tumor growth, counteract the anti-cancer effects of TAM, and mediate ubiquitination of p21. In addition, EP300 could enhance the expression of TRIM27 and its transcription promoter H3K27ac. TRIM27, through ubiquitination of p21, might serve as a prognostic biomarker for non-TNBC prognosis. TRIM27 functions as a novel oncogene in non-TNBC cellular processes, especially suppressing cell senescence and interfering with non-TNBC chemoresistance.
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http://dx.doi.org/10.1016/j.omtn.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666371PMC
December 2020

hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway.

Nanoscale Res Lett 2020 Nov 26;15(1):220. Epub 2020 Nov 26.

Wuhu Research Institute, Anhui University of Science and Technology, Huainan, 232001, China.

Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles modified with antibody hGC33 to glypican-3 (GPC3 +), a membrane protein overexpressed in hepatocellular carcinoma. We found that hGC33-modified NPs (hGC33-SFB-NP) targeted GPC3 hepatocellular carcinoma (HCC) cells by specifically binding to GPC3 on the surface of HCC cells, inhibited Wnt-induced signal transduction, and inhibited HCC cells in G0/1 by down-regulating cyclin D1 expression, thus attenuating HCC cell migration by inhibiting epithelial-mesenchymal transition. hGC33-SFB-NP inhibited the migration, cycle progression, and proliferation of HCC cells by inhibiting the Ras/Raf/MAPK pathway and the Wnt pathway in tandem with GPC3 molecules, respectively. hGC33-SFB-NP inhibited the growth of liver cancer in vivo and improved the survival rate of tumor-bearing mice. We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway.
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http://dx.doi.org/10.1186/s11671-020-03451-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691417PMC
November 2020

Shionone alleviates NLRP3 inflammasome mediated pyroptosis in interstitial cystitis injury.

Int Immunopharmacol 2021 Jan 19;90:107132. Epub 2020 Nov 19.

Li Shicai School Inheritance Studio, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu 215101, China. Electronic address:

Shionone is a triterpenoid component derived from the herbal medicine Aster tataricus, and it has been reported to possess marked anti-inflammatory properties. The activation of NLRP3 inflammasome plays an important role in cystitis, and the effect of Shionone on NLRP3 inflammasome-dependent pyroptosis remains unclear. In this study, we established an interstitial cystitis (IC) rat model and SV-HUC-1 cell model with CYP or LPS + ATP treatment to mimic inflammation response and induce NLRP3 inflammasome activation. Shionone treatment significantly attenuated the bladder wet weight, score of edema and hemorrhage, enhanced the viability of SV-HUC-1 cell, decreased the rate of pyroptosis. Moreover, Shionone reduced the expression of NF-κB, NLRP3, ASC, Pro-caspase-1, Caspase-1, GSDMD, GSDMD-N at the mRNA and protein levels both in rat and SV-HUC-1 cell model, demonstrating NLRP3 inflammasome pathway was blocked and pyroptosis degree was reduced. These results indicated that Shionone could alleviate interstitial cystitis in Rat model and enhancing the viability of SV-HUC-1 cells via NF-κB/NLRP3/GSDMD-N pathway, which illustrated that Shionone could be used as a drug candidate for the treatment of interstitial cystitis.
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http://dx.doi.org/10.1016/j.intimp.2020.107132DOI Listing
January 2021

Recent advances in selective catalytic oxidation of nitric oxide (NO-SCO) in emissions with excess oxygen: a review on catalysts and mechanisms.

Environ Sci Pollut Res Int 2021 Jan 26;28(3):2549-2571. Epub 2020 Oct 26.

School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, China.

Nitric oxides (NO, which mainly include more than 90% NO) are one of the major air pollutants leading to a series of environmental problems, such as acid rain, haze, photochemical smog, etc. The selective catalytic oxidation of NO to NO (NO-SCO) is regarded as a key process for the development of selective catalytic reduction of NO by ammonia (via fast selective catalytic reduction reaction) and also the simultaneous removal of multipollutant (pre-oxidation and post-absorption). Until now, scholars have developed various types of NO-SCO catalysts, dividing the main groups into noble metals (Pt, Pd, Ru, etc.), metal oxides (Mn-, Co-, Cr-, Ce-based, etc.), perovskite-type oxides (LaMnO, LaCoO, LaCeCoO, etc.), carbon materials (activated carbon, carbon fiber, carbon nanotube, graphene, etc.), and zeolites (ion-exchanged ZSM-5, CHA, SAPO, MCM-41, etc.) in this review. This paper summarizes the recent progress of the above typical catalysts and mostly analyzes the catalytic performance for NO oxidation in terms of the HO and/or SO resistances and also the influencing factors, and their reaction mechanisms are described in detail. Finally, this review points out the key problems and possible solutions of the current researches and presents the application prospects and future development directions of NO-SCO technology using the above typical catalysts.
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http://dx.doi.org/10.1007/s11356-020-11253-6DOI Listing
January 2021

Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis.

Cancer Cell Int 2020 12;20:494. Epub 2020 Oct 12.

Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107, West of Wenhua Street, Lixia District, Jinan, 250012 China.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC.

Methods: qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo.

Results: Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB.

Conclusions: In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.
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http://dx.doi.org/10.1186/s12935-020-01593-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549246PMC
October 2020

Protective effect of Aster tataricus extract on NLRP3-mediated pyroptosis of bladder urothelial cells.

J Cell Mol Med 2020 11 8;24(22):13336-13345. Epub 2020 Oct 8.

Li Shicai School Inheritance Studio, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China.

Aster tataricus L.f. is a traditional Eastern Asian herbal medicine used for the relief of uroschesis-related illnesses and has been demonstrated clinically to exert satisfied effects. However, the mechanism of its therapeutic action remains unclear. The present study aimed to evaluate the protective mechanism of Aster tataricus extract (ATE) on CYP or LPS + ATP-induced interstitial cystitis (IC), we successfully constructed the induced IC Sprague-Dawley (SD) rat model and IC human urothelium cell (SV-HUC-1) model. The main compounds of ATE were determined by LC-MS. After intervention, the changes on the bladder wall morphology and inflammation were observed in each group. SV-HUC1 cell viability was measured by MTT and double stained with Hoechst 33342 and propidium iodide (PI). The expression levels of NLRP3, Pro-caspase-1, Caspsae-1 p20, GSDMD, GSDMD-N and Cleave-IL-1β in vivo and in vitro in different groups were detected by Western blotting. ATE significantly alleviated oedema and haemorrhage and reduced the inflammation index and histopathological score in SD rat bladder. The results of cell revealed that ATE could improve cell viability and decrease pyroptosis ratio. The expression of NLRP3 and other pyroptosis-related protein was remarkably decreased by ATE both in vivo and in vitro. ATE may be used as an inhibitor of NLRP3 in treating IC. The discovery of NLRP3/Caspase-1/GSDMD-N as a new protective pathway provides a new direction for protecting cell against IC.
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http://dx.doi.org/10.1111/jcmm.15952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701514PMC
November 2020

Freeze tolerance and the underlying metabolite responses in the Xizang plateau frog, Nanorana parkeri.

J Comp Physiol B 2021 Jan 6;191(1):173-184. Epub 2020 Oct 6.

School of Life Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China.

The frog Nanorana parkeri (Dicroglossidae) is endemic to the Tibetan Plateau, and overwinters shallow pond within damp caves for up to 6 months. Herein, we investigate the freeze tolerance of this species and profile changes in liver and skeletal muscle metabolite levels using an untargeted LC-MS-based metabolomic approach to investigate molecular mechanisms that may contribute to freezing survival. We found that three of seven specimens of N. parkeri could survive after being frozen for 12 h at - 2.0 °C with 39.91% ± 5.4% (n = 7) of total body water converted to ice. Freezing exposure induced partial dehydration of the muscle, which contributed to decreasing the amount of freezable water within the muscle and could be protective for the myocytes themselves. A comparative metabolomic analysis showed that freezing elicited significant responses, and a total of 33 and 36 differentially expressed metabolites were identified in the liver and muscle, respectively. These metabolites mainly participate in alanine, aspartic acid and glutamic acid metabolism, arginine and proline metabolism, and D-glutamine and D-glutamate metabolism. After freezing exposure, the contents of ornithine, melezitose, and maltotriose rose significantly; these may act as cryoprotectants. Additionally, the content of 8-hydroxy-2-deoxyguanine, 7-Ketocholesterol and hypoxanthine showed a marked increase, suggesting that freezing induced oxidative stress in the frogs. In summary, N. parkeri can tolerate a brief and partial freezing of their body, which was accompanied by substantial changes in metabolomic profiles after freezing exposure.
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http://dx.doi.org/10.1007/s00360-020-01314-0DOI Listing
January 2021

Histological Differentiated/Undifferentiated Mixed Type Should Not Be Considered as a Non-Curative Factor of Endoscopic Resection for Patients With Early Gastric Cancer.

Front Oncol 2020 3;10:1743. Epub 2020 Sep 3.

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.

Background: Histological differentiated/undifferentiated mixed-type adenocarcinomas are frequently found in patients with early gastric cancer (EGC). Yet it is unclear whether these mixed-type adenocarcinomas can be treated by endoscopic resection (ER) in EGC patients.

Aims: To evaluate the lymph node metastasis (LNM) rate and long-term outcomes in mixed-type EGC patients and assess the feasibility of ER in these patients.

Methods: Clinicopathological features, risk factors of LNM, and overall survival (OS) and progression-free survival (PFS) rates of EGC patients were analyzed according to different histological types.

Results: Patients with mixed-type EGC had higher LNM rates than patients with non-mixed-type EGC (11.4 vs. 6.2%, = 0.044). In the multivariate analysis, larger tumor diameter, presence of an ulcer, submucosal invasion, histological undifferentiated type, histological mixed type, and lymphovascular invasion resulted as independent risk factors for LNM in EGC patients (all < 0.05). The LNM rate in mixed-type patients who met the Japanese ER criteria was 3.3%, including fulfilling the absolute criteria 0%. The 5-year OS and PFS rates in mixed-type patients were 94.59 and 91.47%, respectively. There was no statistical significance in the OS ( = 0.870) and PFS ( = 0.705) between mixed-type and non-mixed-type EGC patients fulfilling the Japanese ER criteria.

Conclusion: Histological differentiated/undifferentiated mixed type in EGC patients meeting the Japanese absolute criteria for ER are associated with low risk of LNM and favorable prognosis, and thus, it should not be considered as a non-curative factor for ER.
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http://dx.doi.org/10.3389/fonc.2020.01743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494733PMC
September 2020

Anti-GPC3 Antibody-Conjugated BEZ235 Loaded Polymeric Nanoparticles (Ab-BEZ235-NP) Enhances Radiosensitivity in Hepatocellular Carcinoma Cells by Inhibition of DNA Double-Strand Break Repair.

J Biomed Nanotechnol 2020 Apr;16(4):446-455

Aim: To assess AB-BEZ235-NP potential as a radio-sensitizer in hepatocellular carcinoma models.

Method: By comparing hepatocellular carcinoma cell with simple radiation or combined AB-BEZ235-NP therapy, the HCC apoptosis and self-repair level have significant differences in mortality rates and cell migration abilities.

Results: Cell proliferation and DNA damage increased by pretreatment with AB-BEZ235-NP after irradiation; further studies on the repair pathway indicated that AB-BEZ235-NP inhibited the important pathway of DSB repair. Our results further show that AB-BEZ235-NP significantly inhibits the phosphorylation of the canonical protein, -H2AX, in the NHEJ DSB repair pathway and Serine Protein Kinase (SPK) ATM, and TP53-Binding Protein one. More importantly, AB-BEZ235-NP increased the mount of mean -H2AX Foci in irradiated cells, indicating that AB-BEZ235-NP can selectively inhibit DSB repair in HCC cells. Therefore, these results clearly eludicate that treatment with AB-BEZ235-NP is a potential promising therapy which can increase the radiosensitivity to HCC.
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http://dx.doi.org/10.1166/jbn.2020.2834DOI Listing
April 2020

Preservation of the left colic artery and superior rectal artery in laparoscopic surgery can reduce anastomotic leakage in sigmoid colon cancer.

J Minim Access Surg 2021 Apr-Jun;17(2):208-212

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.

Background: The aim was to study the clinical significance in the preservation of the left colic artery (LCA) and superior rectal artery (SRA) for the laparoscopic resection of sigmoid colon cancer (SCC).

Patients And Methods: A total of 316 patients with SCC were divided into two groups. Group A received D3 resection with preservation of LCA and SRA, whereas Group B ligatured artery at the root of the inferior mesenteric artery. The operation time, number of resected lymph nodes, blood loss and anastomotic leakage rate were compared.

Results: In Group A, the average operation time was 283.02 ± 51.48 min, the average blood loss was 111.81 ± 77.08 ml and the average lymph node dissection was 14.8 ± 7.7. There was no statistical significance in blood loss and number of resected lymph nodes between Group A and B (P > 0.05). Longer operating time were observed in Group A as compared to Group B (P < 0.05). The anastomotic leakage rate had statistical significance between these two groups (P < 0.05).

Conclusions: Preservation of LCA and SRA was safe and feasible for the laparoscopic surgery of SCC, which could reduce anastomotic leakage rate.
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http://dx.doi.org/10.4103/jmas.JMAS_15_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083730PMC
September 2020

Discovery of Prognostic Signature Genes for Overall Survival Prediction in Gastric Cancer.

Comput Math Methods Med 2020 25;2020:5479279. Epub 2020 Aug 25.

The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.

Background: Gastric cancer (GC) is one of the most common malignant tumors in the digestive system with high mortality globally. However, the biomarkers that accurately predict the prognosis are still lacking. Therefore, it is important to screen for novel prognostic markers and therapeutic targets.

Methods: We conducted differential expression analysis and survival analysis to screen out the prognostic genes. A stepwise method was employed to select a subset of genes in the multivariable Cox model. Overrepresentation enrichment analysis (ORA) was used to search for the pathways associated with poor prognosis.

Results: In this study, we designed a seven-gene-signature-based Cox model to stratify the GC samples into high-risk and low-risk groups. The survival analysis revealed that the high-risk and low-risk groups exhibited significantly different prognostic outcomes in both the training and validation datasets. Specifically, , , , , , , and were selected by the multivariable Cox model. Functionally, PI3K-Akt signaling pathway and platelet-derived growth factor receptor (PDGFR) were found to be hyperactive in the high-risk group. The multivariable Cox regression analysis revealed that the risk stratification based on the seven-gene-signature-based Cox model was independent of other prognostic factors such as TNM stages, age, and gender.

Conclusion: In conclusion, we aimed at developing a model to predict the prognosis of gastric cancer. The predictive model could not only effectively predict the risk of GC but also be beneficial to the development of therapeutic strategies.
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http://dx.doi.org/10.1155/2020/5479279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468614PMC
August 2020

Primary gastric squamous cell carcinoma presenting as a large submucosal mass: A case report and literature review.

Medicine (Baltimore) 2020 Sep;99(36):e22125

Qilu Medical College of Shandong University.

Rationale: Primary gastric squamous cell carcinoma (SCC) is rarely encountered clinically. SCC, which presents as a submucosal tumor, is even rarer. Without the support of pathological evidence, it is difficult to make a correct preoperative diagnosis. Due to limited clinical data, the pathogenesis and treatment of gastric SCC remain unclear.

Patient Concerns: A 69-year-old man was admitted to our hospital with unexplained weight loss. Endoscopy revealed a submucosal mass without any ulcer on its surface located on the body of the stomach. The results of 2 gastroscopic mucosal biopsies were chronic inflammation.

Diagnoses: The clinical diagnosis by computed tomography (CT) and gastroscopy was gastrointestinal stromal tumor (GIST) preoperatively. The postoperative pathological examination demonstrated this tumor as moderately differentiated SCC.

Interventions: Total gastrectomy, distal pancreatectomy, and splenectomy were performed.

Outcomes: The patient was discharged 7 days after the surgery without any complications. The follow-up CT scan showed no evidence of metastatic disease 6 months after surgery.

Lessons: Large primary gastric SCC could present as a submucosal mass. Gastroscopic mucosal biopsy may not be able to get tumor tissue due to inflammatory reaction.
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http://dx.doi.org/10.1097/MD.0000000000022125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478421PMC
September 2020

Circular noncoding RNA circMBOAT2 is a novel tumor marker and regulates proliferation/migration by sponging miR-519d-3p in colorectal cancer.

Cell Death Dis 2020 08 14;11(8):625. Epub 2020 Aug 14.

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China.

Colorectal cancer (CRC) is a common malignant tumor with a poor prognosis. However, its pathogenesis has not been fully elucidated, accounting for poor overall survival. Circular RNA (circRNA) is a class of noncoding RNAs discovered many years ago. Only recently have they been re-evaluated for their important roles in the regulation of gene expression. Studies have confirmed that circRNAs have important biological functions in a variety of malignant tumors. This study aimed to characterize one circRNA derived from the MBOAT2 gene and termed it circMBOAT2, which has been reported to promote prostate cancer progression. CircMBOAT2 is highly expressed in both CRC tissues and serum samples, and has a correlation with tumor stage. The receiver-operating characteristic curves suggested that circMBOAT2 acted as a novel diagnostic tumor marker in CRC. Univariate and multivariate analyses showed that the levels of circMBOAT2 in tissues were independent prognostic markers of CRC. Further functional studies revealed that circMBOAT2 served as a microRNA (miRNA) sponge of miR-519d-3p and promoted the proliferation, migration, and invasion of CRC cells. Also, circMBOAT2 regulated cell proliferation and migration by competitively binding to miR-519d-3p and targeting troponin-associated protein (TROAP) in CRC cells. These results suggested that circMBOAT2 might be a novel potential biomarker of CRC.
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http://dx.doi.org/10.1038/s41419-020-02869-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429508PMC
August 2020

SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice.

EMBO J 2020 09 21;39(18):e104365. Epub 2020 Jul 21.

Shenzhen Key Laboratory for Systemic Aging and Intervention (SAI), National Engineering Research Center for Biotechnology (Shenzhen), International Cancer Center, Shenzhen University, Shenzhen, China.

Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life-cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen-to-anagen transition, and HFSC-specific Sirt7 knockout mice (Sirt7 ;K15-Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ-dependent proteasomal degradation to terminate Nfatc1-mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7 mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.
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http://dx.doi.org/10.15252/embj.2019104365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507325PMC
September 2020

SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis.

Nat Metab 2019 11 15;1(11):1141-1156. Epub 2019 Nov 15.

Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China.

The central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes peripheral oscillators to coordinate physiological and behavioural activities throughout the body. How circadian phase coherence between the SCN and the periphery is controlled is not well understood. Here, we identify hepatic SIRT7 as an early responsive element to light that ensures circadian phase coherence in the mouse liver. The SCN-driven body temperature (BT) oscillation induces rhythmic expression of HSP70, which promotes SIRT7 ubiquitination and proteasomal degradation. Acute temperature challenge dampens the BT oscillation and causes an advanced liver circadian phase. Further, hepatic SIRT7 deacetylates CRY1, promotes its FBXL3-mediated degradation and regulates the hepatic clock and glucose homeostasis. Loss of Sirt7 in mice leads to an advanced liver circadian phase and rapid entrainment of the hepatic clock upon daytime-restricted feeding. These data identify a BT-HSP70-SIRT7-CRY1 axis that couples the mouse hepatic clock to the central pacemaker and ensures circadian phase coherence and glucose homeostasis.
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http://dx.doi.org/10.1038/s42255-019-0136-6DOI Listing
November 2019

Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice.

Elife 2020 06 15;9. Epub 2020 Jun 15.

Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Shenzhen University Health Science Center, Shenzhen, China.

The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.
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http://dx.doi.org/10.7554/eLife.55828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324161PMC
June 2020

Translation regulatory long non-coding RNA 1 represents a potential prognostic biomarker for colorectal cancer.

Oncol Lett 2020 Jun 10;19(6):4077-4087. Epub 2020 Apr 10.

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

Long non-coding RNAs (lncRNAs) have attracted a lot of attention for their role in the development, progression and prognosis of colorectal cancer (CRC). However, little is known on the clinical significance of the translation regulatory lncRNA 1 (TRERNA1) in CRC. The present study aimed to explore the clinical value of TRERNA1 in patients with CRC. A total of 89 cancer-associated lncRNA genes were analyzed using the RT lncRNA PCR array Human Cancer PathwayFinder. Following the PCR array, reverse transcription-quantitative (RT-q)PCR was conducted to identify the differential expression of TRERNA1 between 130 CRC and corresponding non-tumorous adjacent tissues. Additionally, the association between TRERNA1 expression and clinical characteristics was analyzed. Furthermore, TRERNA1 expression was knocked down via small interfering RNAs. The results of the PCR array and RT-qPCR revealed that TRERNA1 expression was significantly upregulated in CRC tissues compared with in adjacent normal tissues. TRERNA1 upregulation was positively associated with distant metastasis, perineural invasion, TNM stage, node metastasis stage and tumor diameter. Multivariate analysis revealed that patients with higher TRERNA1 expression had a shorter overall survival (OS) time and a less favorable prognosis compared with those in the low TRERNA1 expression group. Knockdown of TRERNA1 inhibited invasion and metastasis of CRC cells via regulating Snail expression. In conclusion, TRERNA1 expression was upregulated in CRC tissues. High expression levels of TRERNA1 may be associated with poor OS times, a less favorable prognosis and lymph node metastasis in patients with CRC. TRERNA1 may therefore serve as a useful and novel biomarker for CRC lymph node metastasis and prognosis.
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http://dx.doi.org/10.3892/ol.2020.11532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204641PMC
June 2020

PML2-mediated thread-like nuclear bodies mark late senescence in Hutchinson-Gilford progeria syndrome.

Aging Cell 2020 06 29;19(6):e13147. Epub 2020 Apr 29.

Shenzhen Key Laboratory for Systemic Aging and Intervention (SAI), National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen, China.

Progerin accumulation disrupts nuclear lamina integrity and causes nuclear structure abnormalities, leading to premature aging, that is, Hutchinson-Gilford progeria syndrome (HGPS). The roles of nuclear subcompartments, such as PML nuclear bodies (PML NBs), in HGPS pathogenesis, are unclear. Here, we show that classical dot-like PML NBs are reorganized into thread-like structures in HGPS patient fibroblasts and their presence is associated with late stage of senescence. By co-immunoprecipitation analysis, we show that farnesylated Progerin interacts with human PML2, which accounts for the formation of thread-like PML NBs. Specifically, human PML2 but not PML1 overexpression in HGPS cells promotes PML thread development and accelerates senescence. Further immunofluorescence microscopy, immuno-TRAP, and deep sequencing data suggest that these irregular PML NBs might promote senescence by perturbing NB-associated DNA repair and gene expression in HGPS cells. These data identify irregular structures of PML NBs in senescent HGPS cells and support that the thread-like PML NBs might be a novel, morphological, and functional biomarker of late senescence.
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http://dx.doi.org/10.1111/acel.13147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294779PMC
June 2020

Gefitinib sensitization of cisplatin-resistant wild-type EGFR non-small cell lung cancer cells.

J Cancer Res Clin Oncol 2020 Jul 27;146(7):1737-1749. Epub 2020 Apr 27.

Medical School, Anhui University of Science and Technology, 168 Taifeng Street, Tianjiaan District, Huainan, 232001, China.

Purpose: The usual first-line strategy of wild-type EGFR (wtEGFR) non-small cell lung cancer (NSCLC) remains cisplatin-based chemotherapy. However, cisplatin often loses effectiveness because most tumors acquire drug resistance over time. As EGFR is the most important pro-survival/proliferation signal receptor in NSCLC cells, we aimed at investigating whether cisplatin resistance is related to EGFR activation and further evaluating the combined effects of cisplatin/gefitinib (EGFR-tyrosine kinase inhibitor, EGFR-TKI) on cisplatin-resistant wtEGFR NSCLC cells.

Materials And Methods: EGFR activation was analysed in parental and cisplatin-resistant wtEGFR NSCLC cell lines (H358 and H358, A549 and A549). Cellular proliferation and apoptosis of H358/A549 cells treated with cisplatin or gefitinib, alone or in combination were investigated, and the related effector protein was detected by western blot analysis. Anti-tumor effect of two drugs combined was evaluated in animal models of H358 xenografts in vivo.

Results: EGFR was significantly phosphorylated in cisplatin-resistant wtEGFR NSCLC cells H358 and A549 than their parental cells. In H358 and A549 cells, anti-proliferative ability of gefitinib was further improved, and gefitinib combined with cisplatin enhanced inhibition of cellular survive/proliferation, and promotion of apoptosis in vitro. The combined effects were also associated with the inhibition of EGFR downstream effector proteins. Similarly, in vivo, gefitinib and cisplatin in combination significantly inhibited tumor growth of H358 xenografts.

Conclusion: Abnormal activation of EGFR may induce wtEGFR NSCLC cell resistance to cisplatin. The combined effects of cisplatin/gefitinib suggest that gefitinib, as a combination therapy for patients with cisplatin-resistant wtEGFR NSCLC should be considered.
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http://dx.doi.org/10.1007/s00432-020-03228-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185832PMC
July 2020

Metabolic characteristics of overwintering by the high-altitude dwelling Xizang plateau frog, Nanorana parkeri.

J Comp Physiol B 2020 07 9;190(4):433-444. Epub 2020 Apr 9.

Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China.

The Xizang plateau frog, Nanorana parkeri, has the highest altitudinal distribution of all frogs in the world and survives the cold of winter without feeding by entering into a hibernating state. However, little attention has been paid to its physiological and biochemical characteristics that support overwintering underwater in small ponds. Here, we measured metabolic rate and heart rate, and collected liver and muscle samples from N. parkeri in summer and winter for analysis of mitochondrial respiration rate, and activities and relative mRNA transcript expression of metabolic enzymes. Compared with summer-collected frogs, both resting metabolic rate and heart rate were significantly reduced in winter-collected frogs. Both state 3 and state 4 respiration of liver mitochondria were also significantly reduced in winter but muscle mitochondria showed a decline only in state 3 respiration in winter. The activities and corresponding mRNA expression of cytochrome c oxidase showed a marked decline in winter, whereas the activities and corresponding mRNA expression of lactate dehydrogenase increased in winter-collected frogs, compared to summer. The thermal sensitivity (Q values) for state 3 respiration rate by liver mitochondria, and activities of lactate dehydrogenase, and cytochrome c oxidase all increased in winter-collected frogs, compared with summer frogs, suggesting that overwintering frogs were more sensitive to changes in external temperature. Enzyme changes mainly result from lower overall quantities of these enzymes as well as post-translational modifications. We conclude that overwintering N. parkeri exhibit a seasonal, temperature-independent suppression of metabolism that is mediated at multiple levels: physiological, mitochondrial, gene expression and enzyme activity levels.
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http://dx.doi.org/10.1007/s00360-020-01275-4DOI Listing
July 2020