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| 1 | Regulation of glucose and lipid metabolism in health and disease显示文摘Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases. | Ligong Chen Xiao-Wei Chen Xun Huang Bao-Liang Song Yan Wang Yiguo Wang | 2019 | Science China(Life Sciences)2019，62，11： | 40 |
| 2 | Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma显示文摘Sorafenib is the first-line medication for advanced hepatocellular carcinoma(HCC),but it can only extend limited survival.It is imperative to find a combination strategy to increase sorafenib efficacy.Artesunate is such a preferred candidate,because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms.In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms.We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7,SNU-449,and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice.The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic.Compared with the treatment with artesunate or sorafenib alone,combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis,which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate,but not by inhibitors of other types of cell death(z-VAD,necrostatin-1 and belnacasan).In Huh7 cells,we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy,two essential aspects of ferroptosis.Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion.Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation,ferritin degradation,lipid peroxidation,and consequent ferroptosis.Taken together,artesunate could be repurposed to sensitize sorafenib in HCC treatment.The combined treatment can be easily translated into clinical applications. | Zhong-jie Li Hui-qi Dai Xiao-wei Huang Ji Feng Jing-huan Deng Zi-xuan Wang Xiao-mei Yang Yu-jia Liu Yong Wu Pan-hong Chen Huan Shi Ji-gang Wang Jing Zhou Guo-dong Lu | 2021 | Acta Pharmacologica Sinica2021，42，2： | 31 |
| 3 | Therapeutic regulation of autophagy in hepatic metabolism显示文摘Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ thatgoverns body energy metabolism. Autophagy’s role in hepatic energy regulation has just begun to emerge and autophagy seems to have a much broader impact than what has been appreciated in the field. Though classically known for selective or bulk degradation of cellular components or energy-dense macromolecules, emerging evidence indicates autophagy selectively regulates various signaling proteins to directly impact the expression levels of metabolic enzymes or their upstream regulators. Hence, we review three specific mechanisms by which autophagy can regulate metabolism: A) nutrient regeneration, B) quality control of organelles, and C) signaling protein regulation. The plasticity of the autophagic function is unraveling a new therapeutic approach. Thus, we will also discuss the potential translation of promising preclinical data on autophagy modulation into therapeutic strategies that can be used in the clinic to treat common metabolic disorders. | Katherine Byrnes Sophia Blessinger Niani Tiaye Bailey Russell Scaife Gang Liu Bilon Khambu | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 11 |
| 4 | Tubeimoside-1 induces TFEB-dependent lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting mTOR显示文摘Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity.Using flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 level.TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1.Furthermore,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell immunity.Mechanistically,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent pathway.TBM-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome biogenesis.Moreover,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)cells.Our findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy. | Xiaojia Liu Mingxiao Yin Jingwen Dong Genxiang Mao Wenjian Min Zean Kuang Peng Yang Lu Liu Na Zhang Hongbin Deng | 2021 | Acta Pharmaceutica Sinica B2021，11，10： | 5 |
| 5 | Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells显示文摘Vascular calcification(VC)is a common characteristic of aging,diabetes,chronic renal failure,and atherosclerosis.The basic component of VC is hydroxyapatite(HAp).Nano-sized HAp(nHAp)has been identified to play an essential role in the development of pathological calcification of vasculature.However,whether nHAp can induce calcification in vivo and the mechanism of nHAp in the progression of VC remains unclear.We discovered that nHAp existed both in vascular smooth muscle cells(VSMCs)and their extracellular matrix(ECM)in the calcified arteries from patients.Synthetic nHAp had similar morphological and chemical properties as natural nHAp recovered from calcified artery.nHAp stimulated osteogenic differentiation and accelerated mineralization of VSMCs in vitro.Synthetic nHAp could also directly induce VC in vivo.Mechanistically,nHAp was internalized into lysosome,which impaired lysosome vacuolar H+-ATPase for its acidification,therefore blocked autophagic flux in VSMCs.Lysosomal re-acidification by cyclic-3′,5′-adenosine monophosphate(cAMP)significantly enhanced autophagic degradation and attenuated nHAp-induced calcification.The accumulated autophagosomes and autolysosomes were converted into calcium-containing exosomes which were secreted into ECM and accelerated vascular calcium deposit.Inhibition of exosome release in VSMCs decreased calcium deposition.Altogether,our results demonstrated a repressive effect of nHAp on lysosomal acidification,which inhibited autophagic degradation and promoted a conversion of the accumulated autophagic vacuoles into exosomes that were loaded with undissolved nHAp,Ca^(2+),Pi and ALP.These exosomes bud off the plasma membrane,deposit within ECM,and form calcium nodules.Vascular calcification was thus accelerated by nHAP through blockage of autophagic flux in VSMCs. | Qi Liu Yi Luo Yun Zhao Pingping Xiang Jinyun Zhu Wangwei Jing Wenjing Jin Mingyao Chen Ruikang Tang Hong Yu | 2022 | Bioactive Materials2022，7，2： | 5 |
| 6 | The late stage of autophagy: cellular events and molecular regulation显示文摘Autophagy is an intracellular degradation system that delivers cytoplasmic contents to the lysosome for degradation.It is a“self-eating”process and plays a“house-cleaner”role in cells.The complex process consists of several sequential steps-induction,autophagosome formation,fusion of lysosome and autophagosome,degradation,efflux transportation of degradation products,and autophagic lysosome reformation.In this review,the cellular and molecular regulations of late stage of autophagy,including cellular events after fusion step,are summarized. | Jingjing Tong Xianghua Yan Li Yu | 2010 | Protein & Cell2010，1，10： | 4 |
| 7 | α-Synuclein aggregation and transmission in Parkinson’s disease: a link to mitochondria and lysosome显示文摘The presence of intraneuronal Lewy bodies(LBs) and Lewy neurites(LNs) in the substantia nigra(SN) composed of aggregatedα-synuclein(α-syn) has been recognized as a hallmark of pathological changes in Parkinson’s disease(PD). Numerous studies have shown that aggregated α-syn is necessary for neurotoxicity. Meanwhile, the mitochondrial and lysosomal dysfunctions are associated with α-syn pathogenicity. The hypothesis that α-syn transmission in the human brain contributes to the instigation and progression of PD has provided insights into PD pathology. This review will provide a brief overview of increasing researches that shed light on the relationship of α-syn aggregation with mitochondrial and lysosomal dysfunctions, and highlight recent understanding of α-syn transmission in PD pathology. | Rui Wang Hongyang Sun Haigang Ren Guanghui Wang | 2020 | Science China(Life Sciences)2020，63，12： | 4 |
| 8 | VL30 retrotransposition signals activation of a caspaseindependent and p53-dependent death pathway associated with mitochondrial and lysosomal damage显示文摘长终端重复(LTR ) 的影响房间命运上的 retrotransposition 是未知的。这里,我们在转变 SV40 的老鼠 SVTT1 房间在房间死亡上调查了 VL30 retrotransposition 的效果。VL30 retrotransposon 的 Transfection 减少了由 17 褶层的 SVTT1 的 clonogenicity,作为与父母 NIH3T3 房间相比。频率和房间死亡率在 retrotransposition 积极的 SVTT1 被发现的 retrotransposition 的相关层次克隆房间,展出 DNA 破碎,原子冷凝作用, multinucleation 和细胞质的 vacuolization。受动器 caspases 的激活的分析揭示了 caspase 独立的房间死亡机制。然而,房间死亡与感应的 p53 和 Bcl-2 和 Hsp70 蛋白质表示的美洲狮伪和 Bax 和 downregulation 的伴随物 upregulation 被联系。而且,我们发现了大 T 抗原(副)/p53 和 p53 translocation 的 colocalization 的部分损失到线粒体,导致外部膜 permeabilization (MOMP ) 由 lysosomal 膜 permeabilization (LMP ) 伴随了的 mitochondrial。有趣地,有抗氧化剂 N-acetylcysteine 的处理废除了细胞死亡,建议导出 mitochondrial 的反应的氧种类的参与,并且导致了 retrotransposition 频率的增加。重要地,当 VL30 动员被导致,房间死亡的正式就职是 retrotransposon 特定的 VL30;相反, non-LTR L1 的动员(LINE-1,长散布的原子 element-1 ) , B2 和 LTR MusD retrotransposons 减少了。第一次,我们的结果提供 VL30 retrotransposition 调停的充分证据经由 mitochondrial 和 lysosomal 损坏的房间死亡,揭开是的 retrotransposition 的角色在触发房间死亡激活 mitochondrial-lysosomal 串音的一个原子信号。 | Dimitrios Noutsopoulos Georgios Markopoulos Georgios Vartholomatos Evangelos Kolettas Nicolaos Kolaitis Theodore Tzavaras | 2010 | Cell Research2010，20，5： | 3 |
| 9 | Oblongifolin C suppresses lysosomal function independently of TFEB nuclear translocation显示文摘Lysosomes are the terminal organelles of the autophagic-endocytic pathway and play a key role in the degradation of autophagic contents. We previously reported that a natural compound oblongifolin C (OC) increased the number of autophagosomes and impaired the degradation of P62, most likely via suppression of lysosomal function and blockage of autophagosome-lysosome fusion. However, the precise mechanisms of how OC inhibits the lysosome-autophagy pathway remain unclear. In the present study, we investigated the effect of OC on transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, lysosomal function and autophagy. We showed that treatment with OC (15 μM) markedly enhanced the nuclear translocation of TFEB in HeLa cells, concomitantly reduced the interaction of TFEB with 14-3-3 proteins. We further demonstrated that OC caused signi?cant inhibition of mTORC1 along with TFEB nuclear translocation, and OC-mediated TFEB nuclear translocation was dependent on mTORC1 suppression. Intriguingly, this increased nuclear TFEB was accompanied by reduced TFEB luciferase activity, increased lysosomal pH and impaired cathepsin enzyme activities. In HeLa cells, treatment with OC (7.5 μM) resulted in about 30% of cell death, whereas treatment with hydroxycitrate, a caloric restriction mimetic (20 μM) did not affect the cell viability. However, cotreatment with OC and hydroxycitrate caused signi?cantly great cytotoxicity (>50%). Taken together, these results demonstrate that inhibition of lysosome function is mediated by OC, despite evident TFEB nuclear translocation. | Man Wu Yuan-zhi Lao Hong-sheng Tan Guang Lu Yi Ren Zhao-qing Zheng Juan Yi Wen-wei Fu Han-ming Shen Hong-xi Xu | 2019 | Acta Pharmacologica Sinica2019，40，7： | 3 |
| 10 | CID 1067700, a late endosome GTPase Rab7 receptor antagonist, attenuates brain atrophy, improves neurologic deficits and inhibits reactive astrogliosis in rat ischemic stroke显示文摘Increasing evidence suggests that Ras-related in brain 7 (Rab7), an endosome-localized small GTPase contributes to cerebral ischemic brain injury. In the present study, we investigated the role of Rab7 in ischemic stroke-induced formation of astrogliosis and glial scar. Rats were subjected to transient middle cerebral artery occlusion (tMCAO);the rats were injected with the Rab7 receptor antagonist CID1067700 (CID). Primary astrocytes were subjected to an oxygen and glucose deprivation and reoxygenation (OGD/Re) procedure;CID was added to the cell culture media. We found that Rab7 was significantly elevated over time in both the in vivo and in vitro astrocytic injury models, and administration of CID significantly down-regulated the glial scar markers such as glial fibillary acidic protein (GFAP), neurocan and phosphacan. Moreover, administration of CID significantly attenuated the brain atrophy and improved neurologic deficits in tMCAO rats, and protected astrocytes against OGD/Re-induced injury. Further, CID downregulated the protein levels of Lampl and active cathepsin B in astrocytes after OGD/Re or tMCAO injury;CID inhibited the co-localization of cathepsin B and Rab7, Lampl and Rab7;CID decreased OGD/Re-induced increase in lysosomal membrane permeability and blocked OGD/Re-induced release of cathepsin B from the lysosome into the cytoplasm in astrocytes. Taken together, these results suggest that Rab7 is involved in ischemic stroke-induced formation of astrogliosis and glial scar. CID administration attenuates brain atrophy and improves neurologic deficits and inhibits astrogliosis and glial scar formation after ischemic stroke via reducing the activation and release of cathepsin B from the lysosome into the cytoplasm. | Yuan Qin Yang He Yong-ming Zhu Min Li Yong Ni Jin Liu Hui-ling Zhang | 2019 | Acta Pharmacologica Sinica2019，40，6： | 3 |
| 11 | Adaptive immunity at the crossroads of autophagy and metabolism显示文摘The function of lymphocytes is dependent on their plasticity,particularly their adaptation to energy availability and environmental stress,and their protein synthesis machinery.Lymphocytes are constantly under metabolic stress,and macroautophagy/autophagy is the primary metabolic pathway that helps cells overcome stressors.The intrinsic role of autophagy in regulating the metabolism of adaptive immune cells has recently gained increasing attention.In this review,we summarize and discuss the versatile roles of autophagy in regulating cellular metabolism and the implications of autophagy for immune cell function and fate,especially for T and B lymphocytes. | Shree Padma Metur Daniel J.Klionsky | 2021 | Cellular & Molecular Immunology2021，18，5： | 3 |
| 12 | Nanoscale monitoring of mitochondria and lysosome interactions for drug screening and discover显示文摘Technology advances in genomics,proteomics,and metabolomics largely expanded the pool of potential therapeutic targets.Compared with the in vitro setting,cell-based screening assays have been playing a key role in the processes of drug discovery and development.Besides the commonly used strategies based on colorimetric and cell viability,we reason that methods that capture the dynamic cellular events will facilitate optimal hit identification with high sensitivity and specificity.Herein,we propose a live-cell screening strategy using structured illumination microscopy (SIM) combined with an automated cell colocalization analysis software,CellprofilerTM,to screen and discover drugs for mitochondria and lysosomes interaction at a nanoscale resolution in living cells.This strategy quantitatively benchmarks the mitochondria-lysosome interactions such as mitochondria and lysosomes contact (MLC) and mitophagy.The automatic quantitative analysis also resolves fine changes of the mitochondria-lysosome interaction in response to genetic and pharmacological interventions.Super-resolution live-cell imaging on the basis of quantitative analysis opens up new avenues for drug screening and development by targeting dynamic organelle interactions at the nanoscale resolution,which could facilitate optimal hit identification and potentially shorten the cycle of drug discovery. | Qixin Chen Xintian Shao Zhiqi Tian Yang Chen Payel Mondal Fei Liu Fengshan Wang Peixue Ling Weijiang He Kai Zhang Zijian Guo Jiajie Diao | 2019 | Nano Research2019，12，5： | 2 |
| 13 | C.elegans-based screen identifies lysosome-damaging alkaloids that induce STAT3-dependent lysosomal cell death显示文摘Lysosomes are degradation and signaling centers within the cell,and their dysfunction impairs a wide variety of cellular processes.To understand the cellular effect of lysosome damage,we screened natural smallmolecule compounds that induce iysosomal abnormality using Caenorhabditis elegans (C.elegans)as a model system.A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D)were identified that caused lysosome enlargement in C.elegans macrophage-like cells.Intriguingly,these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway.In mammalian cells, ervachinines A-D induced lysosomal enlargement and damage,leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death.Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling,but not RIP1 or RIP3 signaling.These findings suggest that lysosomedamaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders. | Yang Li Yu Zhang Qiwen Gan Meng Xu Xiao Ding Guihua Tang Jingjing Liang Kai Liu Xuezhao Liu Xin Wang Lingli Guo Zhiyang Gao Xiaojiang Hao Chonglin Yang | 2018 | Protein & Cell2018，9，12： | 2 |
| 14 | Lysosome and proteasome dysfunction in alcohol-induced liver injury显示文摘The review describes research findings on the influence of alcohol consumption on two crucial catabolic systems in hepatocytes:the lysosome and the ubiquitin-proteasome system(UPS).The lysosome is a membrane-bound organelle that degrades all aging and/or damaged organelles and hydrolyzes all forms of macromolecules.The UPS is mostly proteolytic.It carries out the majority of its functions in the soluble portion of the cytoplasm(cytosol)and degrades nearly all intracellular proteins,particularly those with short half-lives,so that their levels are tightly controlled.Our review will briefly discuss the epidemiology of alcohol abuse and the spectrum of alcohol-induced liver disease(AILD).We will explain why ethanol(EtOH)metabolism,but not EtOH alone,is hepatotoxic.Then,we will summarize how heavy drinking alters hepatic catabolic systems,resulting in liver enlargement that develops from hepatocyte swelling due,in part,to aberrant accumulation of undegraded lipid droplets(steatosis)and undegraded proteins(proteopathy).Our detailed description of each catabolic system will highlight its discoverer(s)and emphasize each system’s characteristics.Most important,we will review the evidence that chronic EtOH consumption disrupts hepatic lysosome biogenesis and inhibits the UPS by impeding hepatic proteasome activity.It will become evident that each of these EtOH-induced defects has far-reaching functional consequences.Finally,we will describe current and potential therapeutic interventions for alleviating EtOH-induced liver injury.The most effective intervention is the cessation of EtOH consumption.However,there are other potential approaches using natural or synthetic compounds that activate autophagy or the proteasome to enhance the degradation of accumulated lipid droplets or proteins,respectively,which could alleviate AILD.These approaches,now in their early stages of investigation,will also be discussed in this review. | Terrence M.Donohue.Jr Natalia A.Osna Kusum K.Kharbanda Paul G.Thomes | 2019 | Liver Research2019，3，3： | 2 |
| 15 | Ratiometric sensing lysosomal pH in inflammatory macrophages by a BODIPY-rhodamine dyad with restrained FRET显示文摘Inflammation,as the pathophysiological response of body to harmful stimuli,leads to changes in cellular microenvironment.To research pH changes in lysosomes of macrophages during inflammation,we designed a FRET(F(o|')rster resonance energy transfer)based probe,BDP-RhB.The probe showed good lysosome targeting ability,wide response range of pH from 8.0 to 4.0 with significant ratio(I582/I518)change from 0.6 to 3.4,and good reversibility and sustainability.By applying BDP-RhB,we found a decrease of lysosomal pH of macrophages during inflammation. | Yu Yan Xiaodong Zhang Xinfu Zhang Ning Li Huizi Man Lingcheng Chen Yi Xiao | 2020 | Chinese Chemical Letters2020，31，5： | 2 |
| 16 | Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy——lysosomal pathway显示文摘Nonalcoholic fatty liver disease(NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment.Hyperactivation of mTOR complex1(mTORCl) and subsequent impairment of the transcription factor EB(TFEB)-mediated autophagy-lysosomal pathway(ALP) are implicated in the development of NAFLD.Accordingly,agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD.The objective of this study was to investigate the effects of nuciferine,a major active component from lotus leaf,on NAFLD and its underlying mechanism of action.Here we show that nuciferine activated ALP and alleviated steatosis,insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner.Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases,thereby suppressing lysosomal localization and activity of mTORC1,which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance.Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORCl-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD. | Xiliang Du Chiara Di Malta Zhiyuan Fang Taiyu Shen Xiaodi Niu Meng Chen Bo Jin Hao Yu Lin Lei Wenwen Gao Yuxiang Song Zhe Wang Chuang Xu Zhijun Cao Guowen Liu Xinwei Li | 2022 | Acta Pharmaceutica Sinica B2022，12，6： | 2 |
| 17 | Concanavalin A-induced changes in lysosomal morphology of macrophages under confocal microscope显示文摘Changes in lysosomal morphology of cultured mouse peritoneal macrophages after stimu1ation by Concanavalin A (Con A) were observed with a laser scanning confocal microscope (LSCM). A series of images were obtained including phase-contrast images, optical sectioning images, 3-dimensional reconstruction images. The changes of lysosomal fluorescence intensity and pH were measured. It was found that macrophage lysosomes were Cllstributed mainly at the periphery of the cells in resting conditions, the lysosomal area containing fluorescence probe became markedly enlarged after stimulation by Con A for 30 min, and the fluorescence intensity in the medium increased about 15 min after suggesting that Con A could induce outflow of the fluorescence probe within the macrophage lysosomes. The lysosomal pH rose from 4. 6 to 5. 7 in 7 min after Con A was added, and maintained at that level hereafter. | 雷国华 朴英杰 鲍永耀 吴建春 黄辉 | 1997 | Journal of Medical Colleges of PLA(China)1997，12，2： | 1 |
| 18 | THE DISTRIBUTION, DEPOSITION AND EFFECT OF SAMARIUM IN HEPATOCYTES OF MICE——AN ELECTRON MICROSCOPIC AND X-RAY MICROANALYTICAL STUDY显示文摘The rare earth elements at large dose are poisonous to organisms. The mechanism of the poisoning may be complex. But the rare earth elements poisoning as well as some other metal poisonings (e. g. lead, gold and mercury) exhibit a common feature——to deposit in bodies. The rare earth elements, from lanthanum to samarium (Sm)which were injected in- | 邹仲之 栗振宝 王晓辉 朱秀雄 尹昕 倪嘉缵 | 1991 | Chinese Science Bulletin1991，36，15： | 1 |
| 19 | Enhanced lysosomal function is critical for paclitaxel resistance in cancer cells: reversed by artesunate显示文摘The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells.Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells.Artesunate,a derivative of artemisinin,displays broad antitumor activity and direct cytotoxicity on various tumor cells.Our previous study shows that artesunate increases autophagosome accumulation,while significantly decreases autolysosome number in cancer cells,suggesting that artesunate might impair the lysosomal function.In this study,we investigated the effects of artesunate on lysosomal function and its relationship with chemotherapeutic drug resistance in cancer cells.We found that the lysosomal function was significantly enhanced in two drug-resistant(A549/TAX and A549/DDP)cells.Furthermore,we showed that the enhanced lysosomal function by overexpression of transcription factor EB(TFEB)significantly increased MCF-7 cells resistance to doxorubicin(DOX),whereas the decreased lysosomal function by TFEB-knockdown or lysosome inhibitor chloroquine increased MCF-7 cells sensitivity to DOX.Treatment of A549/TAX cells with artesunate(2.5–50μM)dose-dependently inhibited lysosomal function and the clearance of dysfunctional mitochondria,and induced cell apoptosis.Moreover,we demonstrated that artesunate exerted more potent inhibition on the resistant(A549/TAX and MCF-7/ADR)cells with higher activity of lysosomal function.Our results suggest that artesunate or other inhibitors of lysosomal function would be potential in the treatment of cancer cells with drug resistance caused by the enhanced lysosomal function. | Zhe Li Yu-ting Zhu Min Xiang Jun-lan Qiu Shou-qing Luo Fang Lin | 2021 | Acta Pharmacologica Sinica2021，42，4： | 1 |
| 20 | Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs显示文摘Background:Recently,defects in mammalian oocytes maturation induced by environmental pollution results in the decreasing animal reproduction.Animal exposed to glyphosate is largely unavoidable because glyphosate is one of the most widely used herbicide worldwide due to its high-efficiency and broad-spectrum effects,which causes glyphosate an environmental contaminant found in soil,water and food.During the last few years,the growing and wider use of glyphosate has raised great concerns about its effects of reproductive toxicity.In this study,using porcine models,we investigated effects of glyphosate on organelle functions during oocyte meiosis.Results:The results showed glyphosate exposure disrupted porcine oocyte maturation.Expression levels of cumulus expansion-related genes were interfered,further indicating the meiotic defects.The damaging effects were mediated by destruction of mitochondrial distribution and functions,which induced ROS accumulation and oxidative stress,also indicated by the decreased mRNA expression of related antioxidant enzyme genes.We also found an interference of endoplasmic reticulum(ER)distribution,disturbance of Ca^(2+)homeostasis,as well as fluctuation of ER stress,showing with the reduced ER stress-related mRNA or protein expression,which could indicate the dysfunction of ER for protein processing and signal transduction in glyphosate-exposed oocytes.Moreover,glyphosate exposure induced the disruption of lysosome function for autophagy,showing with the decrease of LAMP2 expression and autophagy-related genes mRNA expression.Additionally,our data showed the distribution of Golgi apparatus and the functions of ribosome were disturbed after glyphosate exposure,which might affect protein synthesis and transport.Conclusions:Collectively,our study showed that exposed to glyphosate could affect animal reproduction by compromising the quality of oocytes through its wide toxic effects on organelle functions. | Chunhua Xing Shun Chen Yue Wang Zhennan Pan Yuanjing Zou Shaochen Sun Zili Ren Yu Zhang | 2022 | Journal of Animal Science and Biotechnology2022，13，6： | 1 |
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