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Contribution of Baroreflex Afferent Pathway to NPY-Mediated Regulation of Blood Pressure in Rats

Neuroscience Bulletin 2020年第4期36卷 396-406页

作者： yang liu Shu-yang Zhao yan Feng Jie Sun Xiao-Long Lu Qiu-Xin yan Ying li Zhuo liu Lu-Qi Wang Xun Sun Shijun li Guo-Fen Qiao bai-yan li Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular Medicine ResearchMinistry of EducationCollege of PharmacyHarbin Medical UniversityHarbin 150081China Department of Clinical Laboratory The First Affiliated Hospital of Dalian Medical UniversityDalian 116011China Department of Pharmacology College of PharmacyDalian Medical UniversityDalian 116044China Riley Heart Center Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Neuropeptide Y (NPY), a metabolism-related cardiovascular factor, plays a crucial role in blood pressure(BP) regulation via peripheral and central pathways. The expression of NPY receptors (Y1R/Y2R) specific to baroreflex afferents impacts on the sexually dimorphic neural control of circulation. This study was designed to investigate the expression profiles of NPY receptors in the nodose ganglion (NG) and nucleus tractus solitary (NTS) under hypertensive conditions. To this end, rats with hypertension induced by NG-nitro-L-arginine methylester (L-NAME) or high fructose drinking (HFD), and spontaneously hypertensive rats (SHRs) were used to explore the effects/mechanisms of NPY on BP using functional, molecular, and electrophysiological approaches. The data showed that BP was elevated along with baroreceptor sensitivity dysfunction in model rats;Y1R was up-or down-regulated in the NG or NTS of male and female HFD/L-NAME groups,while Y2R was only down-regulated in the HFD groups as well as in the NG of the male L-NAME group. In SHRs,Y1R and Y2R were both down-regulated in the NTS, and not in the NG. In addition to NPY-mediated energy homeostasis, leptin-melanocortin activation may be essential for metabolic disturbance-related hypertension. We found that leptin and a-melanocyte stimulating hormone (aMSH) receptors were aberrantly down-regulated in HFD rats. In addition, a-MSH concentrations were reduced and NPY concentrations were elevated in the serum and NTS at 60 and 90 min after acute leptin infusion. Electrophysiological recordings showed that the decay time-constant and area under the curve of excitatory post-synaptic currents were decreased by Y1R activation in A-types, whereas, both were increased by Y2R activation in Ah-or C-types. These results demonstrate that sex-and afferent-specific NPY receptor expression in the baroreflex afferent pathway is likely to be a novel target for the clinical management of metabolism-related and essential hypertension.

关键词： Neuropeptide Y Hypertension Nucleus of the solitary tract Excitatory post-synaptic current Baroreflex

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Exploring Shaking for Cancer Treatment

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Engineering 2024年第9期40卷 12-14页

作者： Hiroki Yokota bai-yan li Department of Biomedical Engineering Indiana University Purdue University IndianapolisIndianapolisIN 46202USA Indiana University Simon Comprehensive Cancer Center&Indiana Center for Musculoskeletal Health School of MedicineIndiana UniversityIndianapolisIN 46202USA State Key Laboratory of Frigid Zone Cardiovascular Diseases Department of PharmacologyCollege of PharmacyHarbin Medical UniversityHarbin 150081China

***-sided role of vibration and shaking Removing vibration and shaking is a pivotal engineering task,which is showcased,for instance,in spacecraft attitude control systems that ensure a precise three-dimensional *** or shaking,such as precession caused by external torque,nutation stemming from off-axis angular momentum,and wobbling due to geometric misalignment,necessitate active and passive damping *** principle extends beyond spacecraft to centrifugation techniques,pivotal not only in washing machines but also in a spectrum of biomedical apparatuses used for isolating cells and organelles and separating DNA and proteins.

关键词： shaking sided separating

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Anti-Hypertensive Action of Fenofibrate via UCP2 Upregulation Mediated by PPAR Activation in Baroreflex Afferent Pathway

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Neuroscience Bulletin 2019年第1期35卷 15-24页

作者： Jian Guan Miao Zhao Chao He Xue li Ying li Jie Sun Wei Wang Ya-li Cui Qing Zhang bai-yan li Guo-Fen Qiao Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular Medicine ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha(PPAR-a), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-a and PPAR-c was assessed in the nodose ganglion(NG) and the nucleus of the solitary tract(NTS). Hypertension induced by drinking high fructose(HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-a and PPAR-c were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-a, the mitochondrial uncoupling protein 2(UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD *** results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.

关键词： Fenofibrate Peroxisome proliferator-activated receptor Mitochondrial uncoupling protein Baroreflex afferent function Blood pressure regulation

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A Systematic Study on Scaling Law of Spiral Waves

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Communications in Nonlinear Science and Numerical Simulation 1999年第3期4卷 3-5页

作者： Shufeng bai,yan li and Qi QUyanG(These auhors attribute equally to this article)(Department of Physics,Peking University,Beijing 100871,China) Department of Physics Peking University Beijing 100871 China

Pactedsformationfarfromthermodynamicsequilibriumareubiquitousintheworld,typicalofwhichisthespiralpattern,***-diffusionsystems,***,whOSetiporbitsaci... 详细信息

Pactedsformationfarfromthermodynamicsequilibriumareubiquitousintheworld,typicalofwhichisthespiralpattern,***-diffusionsystems,***,whOSetiporbitsaci...

关键词： spirals non-linear waves scaling law

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Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone

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Bone Research 2021年第4期9卷 494-506页

作者： Shengzhi liu Di Wu Xun Sun Yao Fan Rongrong Zha Aydin Jalali yan Feng Kexin li Tomohiko Sano Nicole Vike Fangjia li Joseph Rispoli Akihiro Sudo Jing liu Alexander Robling Harikrishna Nakshatri bai-yan li Hiroki Yokota Department of Biomedical Engineering Indiana University Purdue University IndianapolisIndianapolisINUSA Department of Pharmacology School of PharmacyHarbin Medical UniversityHarbinChina Department of Pharmacy The Second Affiliated Hospital of Dalian Medical UniversityDalianChina Department of Orthopedic Surgery Mie UniversityTsuMieJapan Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteINUSA Department of Physics Indiana University Purdue University IndianapolisIndianapolisINUSA Department of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisINUSA Indiana Center for Musculoskeletal Health Indiana University School of MedicineIndianapolisINUSA Department of Surgery Indiana University School of MedicineIndianapolisINUSA Simon Cancer Center Indiana University School of MedicineIndianapolisINUSA

Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer ***,we focused on Wnt signaling and evaluated tumor-osteocyte *** animal experiments,mammary tumor cells were inoculated into the mammary fat pad and *** role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse *** results revealed that administration of osteocytes or their conditioned medium(CM)inhibited tumor progression and *** overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity,accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as *** antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating ***,silencing Lrp5 in tumors inhibited tumor progression,while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor *** exhibited elevated Lrp5 expression in response to tumor cells,implying that osteocytes protect bone through canonical Wnt ***,our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in *** envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.

关键词： cytes elevated inhibited

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Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes

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Genes & Diseases 2023年第4期10卷 1641-1656页

作者： Kexin li Xun Sun Hudie li Hailan Ma Meng Zhou Kazumasa Minami Keisuke Tamari Kazuhiko Ogawa Pankita HPandya MReza Saadatzadeh Melissa AKacena Karen EPollok bai-yan li Hiroki Yokota Department of Pharmacology School of PharmacyHarbin Medical UniversityHarbinHeilongjiang 150081China Department of Biomedical Engineering Indiana University Purdue University IndianapolisIndianapolisIN 46202USA Department of Radiation Oncology Osaka University Graduate School of MedicineSuitaOsaka 565-0871Japan Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA Department of Pediatrics Indiana University School of MedicineIndianapolisIN 46202USA Department of Orthopaedic Surgery Indiana University School of MedicineIndianapolisIN 46202USA Indiana Center for Musculoskeletal Health Indiana University School of MedicineIndianapolisIN 46202USA

Cancer cells tend to develop resistance to chemotherapy and enhance aggressive-ness.A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic *** on this strategy,induced tumor-suppressing cells(iTSCs)have been generated from tumor cells and mesenchymal stem ***,we examined the possi-bility of generating iTSCs from lymphocytes by activating PKA signaling for suppressing the pro-gression of osteosarcoma(OS).While lymphocyte-derived CM did not present anti-tumor capabilities,the activation of PKA converted them into *** PKA conversely gener-ated tumor-promotive *** a mouse model,PKA-activated CM suppressed tumorinduced bone *** analysis revealed that moesin(MSN)and calreticulin(Calr),which are highly expressed intracellular proteins in many cancers,were enriched in PKA-activated CM,and they acted as extracellular tumor suppressors through CD44,CD47,and *** study presented a unique option for cancer treatment by generating iTSCs that secret tumor-suppressive proteins such as MSN and *** envision that identifying these tu-mor suppressors and predicting their binding partners such as CD44,which is an FDA-approved oncogenic target to be inhibited,may contribute to developing targeted protein therapy.

关键词： Calreticulin Lymphocytes Moesin Osteosarcoma PKA Proteome

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Effects of salinity and betaine addition on anaerobic granular sludge properties and microbial community succession patterns in organic saline wastewater

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Journal of Environmental Sciences 2025年第1期147卷 310-321页

作者： Zhifei Zhang Jinquan Wan Gang Ye yan Wang Yuwei bai Zhicheng yan College of Environment and Energy South China University of TechnologyGuangzhou 510006China Shijiazhuang High Tech Industrial Development Zone Water Supply and Drainage Company Shijiazhuang 050000China

In this study,the effects of different salinity gradients and addition of compatible solutes on anaerobic treated effluent water qualities,sludge characteristics and microbial communities were *** increase in salinity resulted in a decrease in particle size of the granular sludge,which was concentrated in the range of 0.5-1.0 *** content of EPS(extracellular polymeric substances)in the granular sludge gradually increased with increasing salinity and the addition of betaine(a typical compatible solute).Meanwhile,the microbial community structure was significantly affected by salinity,with high salinity reducing the diversity of *** higher salinity,Patescibacteria and Proteobacteria gradually became the dominant phylum,with relative abundance increasing to 13.53%and 12.16%at 20 g/L *** and its subordinate Desulfovibrio,which secrete EPS in large quantities,dominated significantly after betaine *** relative abundance reached 13.65%and 7.86%at phylum level and genus *** effect of these changes on the treated effluent was shown as the average chemical oxygen demand(COD)removal rate decreased from 82.10%to 79.71%,78.01%,68.51%and 64.55%when the salinity gradually increased from 2 g/L to 6,10,16 and 20 g/*** the salinity of 20 g/L,average COD removal increased to 71.65%by the addition of 2 mmol/L *** gradient elevated salinity and the exogenous addition of betaine played an important role in achieving stability of the anaerobic system in a highly saline environment,which provided a feasible strategy for anaerobic treatment of organic saline wastewater.

关键词： Organic saline wastewater Anaerobic granular sludge Compatible solute Extracellular polymeric substance Microbial community

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Therapeutic Insights into Low-intensity Vibration for Generating Induced Tumor-Suppressive Cells and Modulating the Bone Microenvironment

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Engineering 2024年第12期43卷 201-215页

作者： Xue Xiong Qingji Huo Changpeng Cui Uma KAryal BonHeon Ku Chin-Suk Hong HeeChang lim Jing liu Andy Chen William R.Thompson bai-yan li Xue-lian li Hiroki Yokota Department of Pharmacology College of PharmacyHarbin Medical UniversityHarbin 150081China Department of Biomedical Engineering Purdue University in IndianapolisIndianapolisIN 46202USA Department of Physics and Astronomy Purdue UniversityWest LafayetteIN 47907USA Department of Comparative Pathobiology Purdue UniversityWest LafayetteIN 47907USA School of Mechanical Engineering Pusan National UniversityBusan 46241Republic of Korea Department of Mechanical Engineering Ulsan CollegeUlsan 44022Republic of Korea Indiana University Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA Department of Medical Genetics Indiana University School of MedicineIndianapolisIN 46202USA Indiana Center for Musculoskeletal Health Indiana University School of MedicineIndianapolisIN 46202USA Department of Physical Therapy Indiana UniversityIndianapolisIN 46202USA Department of Breast Surgery Harbin Medical University Cancer HospitalHarbin Medical UniversityHarbin 150086China Department of Anatomy Cell Biology and PhysiologyIndiana University School of MedicineIndianapolisIN 46202USA

Bone frequently serves as a metastatic site for breast and prostate cancers. Given the potential of low-intensity vibration(liV) to increase bone health and reduce cancer risk, this study investigated the impact of liV on cancer cells, as well as noncancer cells such as lymphocytes and peripheral blood mononuclear cells(PBMCs). The results revealed that liV exposure not only suppressed cancer cell migration but also triggered the generation of induced tumor-suppressing(iTS) cells. Conditioned medium(CM) derived from liV-treated PBMCs shrank freshly isolated breast and prostate cancer tissues, and when CM was combined with a chemotherapeutic agent, additional antitumor effects were ***, iTS cell-derived CM hindered the maturation of the receptor activator of nuclear factor-kappa B ligand(RANKL)-stimulated bone-resorbing osteoclasts while promoting the differentiation of bone-forming osteoblasts. Intriguingly, the anticancer effects induced by liV were replicated by simply shaking a cell-containing tube with a regular tube shaker. Using mass spectrometry-based proteomics, this study revealed enrichment of tumor-suppressing proteins, including enolase 1, moesin(MSN), and aldolase A(ALDOA), which are commonly found in oncogene-activated iTS cells, in liV-induced CM. Sad1 and UNC-84 domain containing 1(SUN1), a core component of the linker of the nucleoskeleton and cytoskeleton(liNC) complex, exhibited heightened expression, notably enhancing the response of lymphocytes to liV. An ex vivo bone cancer model further demonstrated the potent anticancer effects of lymphocyte-derived CM. In conclusion, this study underscores the pivotal role of liV in preventing bone loss in the tumor microenvironment.

关键词： Low-intensity vibrations Induced tumor-suppressing cells Lymphocytes Breast cancer Bone metastasis

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Skeletal loading regulates breast cancer-associated osteolysis in a loading intensity-dependent fashion

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Bone Research 2020年第2期8卷 238-248页

作者： Yao Fan Aydin Jalali Andy Chen Xinyu Zhao Shengzhi liu Meghana Teli Yunxia Guo Fangjia li Junrui li Amanda Siegel lianxiang yang Jing liu Sungsoo Na Mangilal Agarwal Alexander G.Robling Harikrishna Nakshatri bai-yan li Hiroki Yokota Department of Pharmacology School of PharmacyHarbin Medical UniversityHarbin 150081China Department of Biomedical Engineering Indiana University Purdue University IndianapolisIndianapolisIN 46202USA Peking Union Medical College Hospital Chinese Academy of Medical SciencesBeijing 100730China Department of Physics Indiana University Purdue University IndianapolisIndianapolisIN 46202USA Department of Mechanical Engineering Oakland UniversityRochesterMI 48309USA Integrative Nanosystems Development Institute Indiana University Purdue University IndianapolisIndianapolisIN 46202USA Department of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisIN 46202USA Indiana Center for Musculoskeletal Health Indiana University School of MedicineIndianapolisIN 46202USA Department of Surgery Simon Cancer Research CenterIndiana University School of MedicineIndianapolisIN 46202USA

Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium(CM) and fluid flow-treated conditioned medium(FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition(MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition(EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer(FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumorinduced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFβ levels and the composition of tumor-associated volatile organic compounds in the ***, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumorosteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment.

关键词： breast cancer loading

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Realgar transforming solution is involved of JNK, P38 MAPK pathway in down-regulating Ras/MAPK pathway in Caenorhabditis elegans

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中国药理学与毒理学杂志 2019年第9期33卷 690-691页

作者： liU Dong-ling ZHI De-juan WAN Feng-qi WANG Meng-qi ZHOU Ting bai yan-li li Hong-yu Institute of Microbiology School of Life SciencesLanzhou UniversityLanzhou 730000China Gansu University of Chinese Medicine Lanzhou 730000China

OBJECTIVE To investigate the effect and the mechanisms of realgar transforming solution(RTS)on down-regulating over activated *** we used the optimizing technical processes to obtain the RTS,and eval⁃uate the mechanisms of RTS on down-regulating overactivated ras in Caenorhabditis *** We found that the mRNA level of let60 and lin45 significantly decreased following exposure to RTS,but mRNA levels of mpk1 were not statistically significant in let60/ras(gf)*** together with sorafenib(RAF inhibitors)significantly enhanced the activity of RTS on down-regulating overactivated ras more than RTS only,but 50μmol·L^-1 PD98059,a specific ERK inhibitor did ***45 gene RNAi decreased the ability of RTS on down-regulating overactivated ras significantly,but mpk1 gene RNAi did not,indicating that the activity of RTS on down-regulating overactivated ras mainly through targeting to lin45/*** addition,RTS significantly increased mRNA level of pmk1/p38 and jnk1/jnk in let-60/ras(gf)mutant,50μmol·L^-1 SB203580(p38 inhibitor)and SP600125(JNK inhibitor)significantly attenuated the effects of RTS on down-regulating overactivated ras in some degree,and pmk1,jnk1 gene RNAi displayed the similar results,suggesting that P38 and JNK/MAPK pathways in some degree were involved in the effects of RTS on down-regulating overactivated ras in ***⁃*** Realgar transforming solution down-regulate the Ras/MAPK pathway through JNK and P38 MAPK pathways.

关键词： realgar transforming solution C.elegans P38 JNK/MAPK pathway

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