112 results on '"Ke-Yong Wang"'
Search Results
2. Fluid evolution and ore genesis of Cu–Pb–Zn veins in the Panjiaduan deposit, Great Xing’an Range, NE China: evidence from fluid inclusion and H–O–He–Ar isotopes
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Qing-Fei Sun, Ke-Yong Wang, Feng-Yue Sun, Miao Zhang, Chen-Guang Zhao, and Li-Xue Sun
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Geology - Abstract
The southern Great Xing’an Range (SGXR), located in the eastern segment of the Central Asian Orogenic Belt (CAOB), is one of the most economically important Cu–Mo–Fe–Sn–Pb–Zn–Ag metallogenic provinces in China. The newly discovered Panjiaduan Cu–Pb–Zn deposit (9.3 Mt; at 1.36% Cu, 2.90% Pb, 3.80% Zn and 38.12 g/t Ag), located in the SE segment of the SGXR, is primarily hosted in fracture zones in volcanic rocks and granodiorite of the Manitu Formation. Four paragenetic stages of metallic mineralization are identified: (I) quartz-pyrite-arsenopyrite; (II) quartz-polymetallic sulphide; (III) quartz-galena-sphalerite-argentite; and (IV) quartz-calcite-minor sulphide. The hydrothermal quartz contains three types of primary fluid inclusion (FIs): vapour-rich two-phase liquid-vapour (LV-type), liquid-rich two-phase liquid-vapour (VL-type) and three-phase liquid-vapour-solid FIs (SL-type). Stages I and II contain all types with homogenization temperatures (Th) of 324–386 °C and 276–334 °C as well as salinities of 0.7–38.0 wt% and 0.9–34.7 wt%, respectively, whereas stage III is composed of VL- and LV-type FIs with Th of 210–269 °C and salinities of 0.5–7.2 wt%. Only VL-type FIs occur in stage IV, with Th of 139–185 °C and salinities of 1.6–4.2 wt%. The δ18OH2O and δD values vary from −15.7 to 2.6‰ and −132.7 to −110.2‰, respectively, indicating predominant meteoric water with an initial magmatic source. The He–Ar isotopic compositions of the pyrite inclusions from the Panjiaduan Cu–Pb–Zn veins suggest that fluids were derived from the crust.
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- 2022
3. Delayed cortical bone healing due to impaired nuclear Nrf2 translocation in COPD mice
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Takayuki Nabeshima, Manabu Tsukamoto, Ke-Yong Wang, Yosuke Mano, Daisuke Arakawa, Kenji Kosugi, Takafumi Tajima, Yoshiaki Yamanaka, Hitoshi Suzuki, Makoto Kawasaki, Soshi Uchida, Eiichiro Nakamura, Kagaku Azuma, and Akinori Sakai
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Histology ,Physiology ,Endocrinology, Diabetes and Metabolism - Published
- 2023
4. Chewing Behavior Attenuates Lung-Metastasis-Promoting Effects of Chronic Stress in Breast-Cancer Lung-Metastasis Model Mice
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Jia-He Zhang, Ke-Yong Wang, Kin-Ya Kubo, and Kagaku Azuma
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Cancer Research ,Oncology ,psychological stress ,chewing ,breast cancer ,metastasis ,Glucocorticoid ,β2-adrenergic receptor - Abstract
We assessed the effects of chewing behavior on the lung-metastasis-promoting impact of chronic psychological-stress in mice. Human breast-cancer cells (MDA-MB-231) were injected into the tail vein of female nude mice. Mice were randomly divided into stress, stress-with-chewing, and control groups. We created chronic stress by placing mice in small transparent tubes for 45 min, 3 times a day for 7 weeks. Mice in the stress-with-chewing group were allowed to chew wooden sticks during the experimental period. The histopathological examination showed that chronic psychological-stress increased lung metastasis, and chewing behavior attenuated the stress-related lung metastasis of breast-cancer cells. Chewing behavior decreased the elevated level of the serum corticosterone, normalized the increased expression of glucocorticoid, and attenuated the elevated expression of adrenergic receptors in lung tissues. We also found that chewing behavior normalized the elevated expression of inducible nitric oxide synthase, 4-hydroxynonenal, and superoxide dismutase 2 in lung tissues, induced by chronic stress. The present study demonstrated that chewing behavior could attenuate the promoting effects of chronic psychological-stress on the lung metastasis of breast-cancer cells, by regulating stress hormones and their receptors, and the downstream signaling-molecules, involving angiogenesis and oxidative stress.
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- 2022
5. Pulmonary disorder induced by cross-linked polyacrylic acid
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Yasuyuki Higashi, Yasuo Morimoto, Chinatsu Nishida, Taisuke Tomonaga, Hiroto Izumi, Ke‐Yong Wang, Hidenori Higashi, Ryohei Ono, Kazuki Sumiya, Kazuo Sakurai, Kei Yamasaki, and Kazuhiro Yatera
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Male ,Lung Diseases ,Public Health, Environmental and Occupational Health ,Acrylic Resins ,Animals ,Bronchoalveolar Lavage Fluid ,Rats, Inbred F344 ,Rats - Abstract
Organic polymers are materials widely used in our daily lives, such as daily necessities, foods, and medicines. There have been reports recently that cross-linked polyacrylic acid (CL-PAA) can possibly cause serious lung disease. We investigated whether intratracheal instillation of CL-PAA causes pulmonary disorder in rats.Male F344 rats were administered low (0.2 mg/rat) and high (1.0 mg/rat) doses of CL-PAA intratracheally and were dissected 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses in the lungs. Only the high-dose specimens were subjected to ultrasonic dispersion treatment of the administered material.There was a dose-dependent increase in the total cell count, neutrophil count, neutrophil percentage, lactate dehydrogenase (LDH), surfactant protein D (SP-D), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 values in bronchoalveolar lavage fluid (BALF) from 3 days to at least 3 months after intratracheal administration of CL-PAA. Heme oxygenase-1 (HO-1) in lung tissue was also persistently elevated from 3 days to 6 months after exposure. Alkaline phosphatase (ALP) in BALF was elevated at 3 days and 1 month after exposure only in the high-dose group. Histopathological findings in lung tissue showed inflammatory and fibrotic changes from 3 days after administration, and we observed obvious inflammatory changes for up to 3 months and fibrotic changes for up to 6 months.Intratracheal administration of CL-PAA induced persistent neutrophilic inflammation and fibrosis in the rats' lungs, suggesting that CL-PAA may have inflammogenic and fibrogenic effects.
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- 2022
6. Pulmonary toxicity of tungsten trioxide nanoparticles in an inhalation study and an intratracheal instillation study
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Takashi Marui, Taisuke Tomonaga, Hiroto Izumi, Yukiko Yoshiura, Chinatsu Nishida, Hidenori Higashi, Ke‐Yong Wang, Miyako Shijo, Masaru Kubo, Manabu Shimada, and Yasuo Morimoto
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Male ,Public Health, Environmental and Occupational Health ,Animals ,Nanoparticles ,Water ,Bronchoalveolar Lavage Fluid ,Lung ,Rats, Inbred F344 ,Rats - Abstract
We conducted inhalation and intratracheal instillation studies in order to examine the effects of tungsten trioxide (WOIn the inhalation study, male 10-week-old Fischer 334 rats were classified into 3 groups. The control, low-dose, and high-dose groups inhaled clean air, 2, and 10 mg/mThe inhalation and instillation of WOOur results suggest that WO
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- 2022
7. Oxidative stress causes muscle structural alterations via p38 MAPK signaling in COPD mouse model
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Yosuke Mano, Manabu Tsukamoto, Ke-Yong Wang, Takayuki Nabeshima, Kenji Kosugi, Takafumi Tajima, Yoshiaki Yamanaka, Hitoshi Suzuki, Makoto Kawasaki, Eiichiro Nakamura, Qian Zhou, Kagaku Azuma, Tamiji Nakashima, Yuki Tamura, Karina Kozaki, Koichi Nakazato, Yun-shan Li, Kazuaki Kawai, Kazuhiro Yatera, and Akinori Sakai
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Male ,Sarcopenia ,Pancreatic Elastase ,Swine ,Endocrinology, Diabetes and Metabolism ,General Medicine ,p38 Mitogen-Activated Protein Kinases ,Mice, Inbred C57BL ,Mice ,Oxidative Stress ,Pulmonary Disease, Chronic Obstructive ,Disease Models, Animal ,Endocrinology ,Quality of Life ,Animals ,Orthopedics and Sports Medicine ,Muscle, Skeletal ,Lung - Abstract
Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models.Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor.The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway.This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.
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- 2022
8. Corrigendum to 'Geochronology, fluid inclusion, and C–H–O–S–Pb isotopic study of the Huitongshan skarn Cu deposit in Gansu, northwest China' Ore Geol. Rev. [155 (2023) 1–18, 105357]
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Ling-ling Gao, Shunda Li, Chuan Chen, Ke-yong Wang, and Fang Xia
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Geochemistry and Petrology ,Economic Geology ,Geology - Published
- 2023
9. Geochronology, fluid inclusion, and C H O S Pb isotopic study of the Huitongshan skarn Cu deposit in Gansu, northwest China
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Ling-ling Gao, Shunda Li, Chuan Chen, Ke-yong Wang, and Fang Xia
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Geochemistry and Petrology ,Economic Geology ,Geology - Published
- 2023
10. Petrogenesis and tectonic setting of the Middle Mesozoic volcanic rocks in the Ganhe area, northern Great Xing’an Range, northeastern China: constraints from geochronology and geochemistry
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Qi Yu, Ke-Yong Wang, and Xiang-Kun Meng
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
11. Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice
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Jia-He Zhang, Takashi Tasaki, Manabu Tsukamoto, Ke-Yong Wang, Kin-ya Kubo, and Kagaku Azuma
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nervous system ,Medicine (miscellaneous) ,hippocampus ,Wnt10a ,neurogenesis ,neuroinflammation ,spatial memory ,synapse ,General Biochemistry, Genetics and Molecular Biology - Abstract
The hippocampus plays an important role in maintaining normal cognitive function and is closely associated with the neuropathogenesis of dementia. Wnt signaling is relevant to neuronal development and maturation, synaptic formation, and plasticity. The role of Wnt10a in hippocampus-associated cognition, however, is largely unclear. Here, we examined the morphological and functional alterations in the hippocampus of Wnt10a-knockout (Wnt10a-/-) mice. Neurobehavioral tests revealed that Wnt10a-/- mice exhibited spatial memory impairment and anxiety-like behavior. Immunostaining and Western blot findings showed that the protein expressions of β-catenin, brain-derived neurotrophic factor, and doublecortin were significantly decreased and that the number of activated microglia increased, accompanied by amyloid-β accumulation, synaptic dysfunction, and microglia-associated neuroinflammation in the hippocampi of Wnt10a-/- mice. Our findings revealed that the deletion of Wnt10a decreased neurogenesis, impaired synaptic function, and induced hippocampal neuroinflammation, eventually leading to hippocampal neurodegeneration and memory deficit, possibly through the β-catenin signaling pathway, providing a novel insight into preventive approaches for hippocampus-dependent cognitive impairment.
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- 2022
12. Development of a novel knee contracture mouse model by immobilization using external fixation
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Soshi Uchida, Yasuaki Okada, Manabu Tsukamoto, Kenji Kosugi, Takafumi Tajima, Akinori Sakai, Eiichiro Nakamura, Hitoshi Suzuki, Kotaro Tokuda, Haruki Nishimura, Makoto Kawasaki, Yoshiaki Yamanaka, and Ke-Yong Wang
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musculoskeletal diseases ,Contracture ,External Fixators ,Knee Joint ,medicine.medical_treatment ,0206 medical engineering ,02 engineering and technology ,Biochemistry ,Immobilization ,Mice ,03 medical and health sciences ,External fixation ,Rheumatology ,Fracture Fixation ,Joint capsule ,medicine ,Animals ,Orthopedics and Sports Medicine ,Joint Contracture ,Molecular Biology ,030304 developmental biology ,Orthodontics ,0303 health sciences ,business.industry ,Cell Biology ,musculoskeletal system ,Fibrosis ,020601 biomedical engineering ,Knee joint contracture ,Disease Models, Animal ,medicine.anatomical_structure ,medicine.symptom ,business ,human activities ,Joint Capsule - Abstract
Several studies have used animal models to examine knee joint contracture; however, few reports detail the construction process of a knee joint contracture model in a mouse. The use of mouse models is beneficial, as genetically modified mice can be used to investigate the pathogenesis of joint contracture. Compared to others, mouse models are associated with a lower cost to evaluate therapeutic effects. Here, we describe a novel knee contracture mouse model by immobilization using external fixation.The knee joints of mice were immobilized by external fixation using a splint and tape. The passive extension range of motion (ROM), histological and immunohistochemical changes, and expression levels of fibrosis-related genes at 2 and 4 weeks were compared between the immobilized (Im group) and non-immobilized (Non-Im group) groups.The extension ROM at 4 weeks was significantly lower in the Im group than in the Non-Im group (p 0.01). At 2 and 4 weeks, the thickness and area of the joint capsule were significantly greater in the Im group than in the Non-Im group (p 0.01 in all cases). At 2 weeks, the mRNA expression levels of the fibrosis-related genes, except for theThis mouse model may serve as a useful tool to investigate the etiology of joint contracture and establish new treatment methods.
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- 2021
13. Fluid evolution and ore genesis of the A'gui Cu deposit in southern Great Xing'an Range, Northeast China: Evidence from fluid inclusion and C–H–O–S–Pb isotopes
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Xue Wang, Ke-yong Wang, Li-juan Fu, Qing-ying Zhao, Qing-fei Sun, and Chao Zhang
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Geophysics ,Geochemistry and Petrology - Published
- 2023
14. Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation
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Kazuhiro Yatera, Manabu Tsukamoto, Toshiharu Mori, Hokuto Fukuda, Eiichiro Nakamura, Yasuaki Okada, Satoshi Kuboi, Yoshiaki Yamanaka, Ke-Yong Wang, Akinori Sakai, Ken Sabanai, and Takeshi Hanagiri
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0301 basic medicine ,medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Osteoporosis ,030209 endocrinology & metabolism ,Lumbar vertebrae ,Disease ,Bone remodeling ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Alkaline phosphatase ,medicine ,Male osteoporosis ,Tartrate-resistant acid phosphatase 5b ,Risk factor ,Procollagen type 1 N-Terminal propeptide ,COPD ,business.industry ,Chronic obstructive pulmonary disease ,medicine.disease ,respiratory tract diseases ,medicine.anatomical_structure ,Orthopedic surgery ,Original Article ,030101 anatomy & morphology ,lcsh:RC925-935 ,business ,Body mass index - Abstract
Objectives Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers. Methods We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1 and serum levels of bone metabolism biomarkers. Results All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors. Conclusions The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.
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- 2020
15. Deficiency of Wnt10a causes female infertility via the β-catenin/Cyp19a1 pathway in mice
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Jia-He Zhang, Takashi Tasaki, Manabu Tsukamoto, Ke-Yong Wang, and Kagaku Azuma
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Mice, Knockout ,Wnt Proteins ,Mice ,Aromatase ,Ovary ,Animals ,Humans ,Female ,Nerve Tissue Proteins ,General Medicine ,Infertility, Female ,Wnt Signaling Pathway ,beta Catenin - Abstract
Wnt signaling is relevant for a wide range of biological processes, including reproductive function. The function of Wnt10a in female fertility, however, remains obscure. In the present study, we explored the structure and function of the female reproductive organs in Wnt10a knockout (KO) mice. The expression of β-catenin signaling was significantly lower in the ovaries of the Wnt10a KO mice compared with wild-type (WT) mice. In addition, the estrous cycles were disrupted, ovarian follicles were diminished, and endometria were thinner, accompanied by lower serum estrogen levels, and higher testosterone and progesterone levels in Wnt10a KO mice. The expression of the ovarian cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) was significantly lower in Wnt10a KO mice. We detected no significant changes in the levels of the gonadotropins between WT and KO mice. Together, our findings indicate that deficiency of Wnt10a causes female infertility through β-catenin and Cyp19a1signaling pathways in mice.
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- 2022
16. Multistage Genesis of the Haerdaban Pb-Zn Deposit, West Tianshan: Constraints From Fluid Inclusions and H-O-S-Pb Isotopes
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Ling-ling Gao, Shunda Li, Xuebing Zhang, Ke-Yong Wang, Fang Xia, and Chuan Chen
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Mineralization (geology) ,Proterozoic ,Science ,Metamorphic rock ,multistage mineraliztion ,Geochemistry ,chemistry.chemical_compound ,fluid inclusions ,Haerdaban ,δ34S ,chemistry ,General Earth and Planetary Sciences ,Sedimentary rock ,Fluid inclusions ,Seawater ,Sulfate ,SEDEX ,isotopes - Abstract
The Haerdaban Pb-Zn deposit is located on the western edge of the Chinese Western Tianshan Orogen. This deposit consists of stratiform and veined mineralization hosted in Proterozoic carbonaceous and dolomitic limestone. Three metallogenic stages were recognized: an early sedimentary exhalative stage (stage 1), an intermediate metamorphic remobilization stage (stage 2), and a late magmatic-hydrothermal stage (stage 3). Fluid inclusions (FIs) present in stage 1 are liquid-rich aqueous, with homogenization temperatures of 206–246 C and salinities of 5.9–11.6 wt% NaCl eq. FIs present in stage 2 are also liquid-rich aqueous, with homogenization temperatures of 326–349 C and salinities of 3.4–6.6 wt% NaCl eq. FIs present in stage 3 include halite-bearing, vapor-rich aqueous, and liquid-rich aqueous FIs. Homogenization temperatures for these FIs span a range of 249–316 C. Halite-bearing, vapor-rich aqueous, and liquid-rich aqueous FIs yield salinities of 33.8–38.9, 2.6–3.5, and 4.2–8.1 wt% NaCl eq., respectively. Oxygen and hydrogen isotopic data (δ18OH2O = 2.6–13.6‰, δDH2O = −94.7 to −40.7‰) indicate that the ore-forming fluids of stages 1–3 were derived from modified seawater, metamorphic water, and magmatic-meteoric mixed water, respectively. Sulfur isotopic data (δ34S = 2.1–16.3‰) reveal that ore constituents were derived from mixing of marine sulfate and magmatic materials. Lead isotopic data (206Pb/204Pb = 17.002–17.552, 207Pb/204Pb = 15.502–15.523, 208Pb/204Pb = 37.025–37.503) reveal that ore constituents were derived from a mixed crust-mantle source. We propose that the Haerdaban deposit was a Proterozoic sedimentary exhalative deposit overprinted by later metamorphic remobilization and magmatic-hydrothermal mineralization.
- Published
- 2021
17. Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats
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Taisuke Tomonaga, Chinatsu Nishida, Hiroto Izumi, Naoki Kawai, Ke-Yong Wang, Hidenori Higashi, Jun-Ichi Takeshita, Ryohei Ono, Kazuki Sumiya, Shota Fujii, Yuki Hata, Kazuo Sakurai, Toshiki Morimoto, Yasuyuki Higashi, Kei Yamasaki, Kazuhiro Yatera, and Yasuo Morimoto
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Organic Chemistry ,General Medicine ,Rats, Inbred F344 ,Catalysis ,Rats ,Computer Science Applications ,Inorganic Chemistry ,polyacrylic acid (PAA) ,organic chemicals ,crosslinking ,pulmonary toxicity ,Animals ,Rats, Wistar ,Physical and Theoretical Chemistry ,Lung ,Bronchoalveolar Lavage Fluid ,Molecular Biology ,Spectroscopy - Abstract
We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.
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- 2022
18. Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation
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Chinatsu Nishida, Hiroto Izumi, Taisuke Tomonaga, Ke-Yong Wang, Hidenori Higashi, Jun-Ichi Takeshita, Ryohei Ono, Kazuki Sumiya, Shota Fujii, Yuki Hata, Kazuo Sakurai, Yasuyuki Higashi, Kei Yamasaki, Kazuhiro Yatera, and Yasuo Morimoto
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Chemotactic Factors ,Organic Chemistry ,Acrylic Resins ,General Medicine ,Rats, Inbred F344 ,polyacrylic acid (PAA) ,organic compounds ,molecular weight ,pulmonary toxicity ,Catalysis ,Rats ,Computer Science Applications ,Molecular Weight ,Inorganic Chemistry ,Intubation, Intratracheal ,Animals ,Cytokines ,Physical and Theoretical Chemistry ,Bronchoalveolar Lavage Fluid ,Lung ,Molecular Biology ,Heme Oxygenase-1 ,Spectroscopy - Abstract
Background: We conducted intratracheal instillations of different molecular weights of polyacrylic acid (PAA) into rats in order to examine what kinds of physicochemical characteristics of acrylic acid-based polymer affect responses in the lung. Methods: F344 rats were intratracheally exposed to a high molecular weight (HMW) of 598 thousand g/mol or a low molecular weight (LMW) of 30.9 thousand g/mol PAA at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months post exposure. Results: HMW PAA caused persistent increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 3 months and 6 months following instillation. On the other hand, LMW PAA caused only transient increases in neutrophil influx, CINC in BALF, and HO-1 in the lung tissue from 3 days to up to 1 week or 1 month following instillation. Histopathological findings of the lungs demonstrated that the extensive inflammation and fibrotic changes caused by the HMW PAA was greater than that in exposure to the LMW PAA during the observation period. Conclusion: HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.
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- 2022
19. Depletion of WNT10A Prevents Tumor Growth by Suppressing Microvessels and Collagen Expression
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Manabu Tsukamoto, Ke Yong Wang, Hiroto Izumi, Motona Kumagai, Takashi Tasaki, Sohsuke Yamada, Hidetaka Uramoto, Yasuyuki Sasaguri, Kimitoshi Kohno, Xin Guo, Nozomu Kurose, and Tamiji Nakashima
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Male ,Skin Neoplasms ,Necrosis ,Melanoma, Experimental ,Nerve Tissue Proteins ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Wnt10a-deficient mice (Wnt10a-/-) ,Tumor growth ,collagen expression ,Microvessel ,Mice, Knockout ,Chemistry ,Melanoma ,Wnt signaling pathway ,General Medicine ,Skin ulcer ,medicine.disease ,WNT10A ,Mice, Inbred C57BL ,Wnt Proteins ,tumor growth ,microvessel ,Microvessels ,Cancer research ,Female ,030211 gastroenterology & hepatology ,Collagen ,Stromal Cells ,medicine.symptom ,Wound healing ,Gene Deletion ,Research Paper - Abstract
Background: We recently reported that WNT10A plays a pivotal role in wound healing by regulating collagen expression/synthesis, as the depletion of WNT10A dramatically delays skin ulcer formation. WNT signaling also has a close correlation with the cancer microenvironment and proliferation, since tumors are actually considered to be 'unhealing' or 'overhealing' wounds. To ascertain the in vivo regulatory functions of WNT10A in tumor growth, we examined the net effects of WNT10A depletion using Wnt10a-deficient mice (Wnt10a -/-). Methods and Results: We subjected C57BL/6J wild-type (WT) or Wnt10a -/- mice to murine melanoma B16-F10 cell transplantation. Wnt10a -/- mice showed a significantly smaller volume of transplanted melanoma as well as fewer microvessels and less collagen expression and more necrosis than WT mice. Conclusions: Taken together, our observations suggest that critical in vivo roles of Wnt10a-depleted anti-stromagenesis prevent tumor growth, in contrast with true wound healing/scarring.
- Published
- 2019
20. Age and genesis of the Lamahanshan Ag-Pb-Zn deposit, southern Great Xing'an Range, northeastern China: Constraints from sphalerite Rb-Sr dating, fluid inclusions and H-O-S-Pb isotopes
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Qing-fei Sun, Ke-yong Wang, Jian-zhen Geng, Wen-chao Liu, and Chun-kit Lai
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Geochemistry and Petrology ,Economic Geology - Published
- 2022
21. Relationship between CCL22 Expression by Vascular Smooth Muscle Cells and Macrophage Histamine Receptors in Atherosclerosis
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Toshiyuki Nakayama, Uki Nanbu, Ke-Yong Wang, Satoshi Kimura, Yasuyuki Sasaguri, and Hirotsugu Noguchi
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Male ,0301 basic medicine ,Chemokine ,Vascular smooth muscle ,Macrophage ,Inflammation ,Muscle, Smooth, Vascular ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Histamine receptor ,Apolipoproteins E ,Internal Medicine ,medicine ,Animals ,Humans ,Receptors, Histamine H2 ,Receptors, Histamine H1 ,Cells, Cultured ,Chemokine CCL22 ,Mice, Knockout ,biology ,Macrophages ,Monocyte ,Biochemistry (medical) ,Atherosclerosis ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cancer research ,biology.protein ,Original Article ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Biomarkers ,CCL22 ,Histamine - Abstract
Aim: CCL22, mainly synthesized by monocyte-derived alternative (M2) macrophages, belongs to the CC family of chemokines and is involved in monocyte migration and recruitment. We have previously investigated CCL22 and histamine in atherosclerosis. Here, we investigated the hypothesis that CCL22 is involved in atherosclerosis, which is influenced by the differentiation of macrophage phenotypes via histamine. Methods: CCL22 expression was investigated in human carotid arteries and coronary arteries with bare metal stents. Ligated carotid arteries of wild-type (C57BL/6J) and apolipoprotein E-deficient mice were also used as atherosclerotic models. The localization and expression of CCL22 and classical (M1)-like and M2-like macrophages in various human and mouse atherosclerotic lesions were investigated by immunohistochemical examination and quantitative real-time polymerase chain reaction. Histamine is expressed in atherosclerosis, and it induces inflammation and immunity. Human- and mice-derived monocytes and macrophages were used to examine the role of histamine in macrophage differentiation and CCL22-expression. Macrophages derived from histamine receptor 1 (H1R)- and 2 (H2R)-knockout (KO) mice were also examined. Results: Atherosclerotic lesions showed a distribution of heterogeneous macrophage phenotypes with M1-like and M2-like macrophage dominant sites. CCL22 was distributed in sparse areas of vascular smooth muscle cells (VSMCs) and associated with M2-like macrophages. Moreover, H2R stimulation was associated with CCL22 expression via M2-like macrophage dominant differentiation. Conclusion: The expression of M1- or M2-like macrophages in atherosclerosis were observed to be dependent on the distribution of VSMCs owing to differences in causal stimuli and the switching of histamine receptors via Th1 or Th2 cytokines. These results suggest that CCL22 may control atherosclerosis.
- Published
- 2018
22. Inflammogenic Effect of Polyacrylic Acid in Rat Lung Following Intratracheal Instillation
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Yasuo Morimoto, Chinatsu Nishida, Toru Ishidao, Taisuke Tomonaga, Jun-ichi Takeshita, Kei Yamasaki, Ke-Yong Wang, Kazuhiro Yatera, Hiroto Izumi, Ryohei Ono, Kazuki Sumiya, Shota Fujii, Shinichi Mochizuki, and Kazuo Sakurai
- Subjects
chemistry.chemical_compound ,Lung ,medicine.anatomical_structure ,Chemistry ,Intratracheal instillation ,Polyacrylic acid ,medicine ,Pharmacology - Abstract
BackgroundOrganic chemicals are known to cause allergic diseases such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats.MethodsMale F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO2 nanoparticles were used as comparators.ResultsPersistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5) (which had the highest expression of all chemokines by cDNA microarray using the lung tissue) were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO2 nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure. Conclusion Our results suggest that CL-PAA may potentially cause strong neutrophil inflammation in the rat and human lung.
- Published
- 2021
23. Quantitative immunohistochemistry using an antibody-fused bioluminescent protein
- Author
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Hidefumi Akiyama, Chun Wu, Toshiteru Enomoto, Yoshihiro Ohmiya, Ke-Yong Wang, Shohei Shimajiri, and Hidehiro Kubota
- Subjects
0303 health sciences ,biology ,040301 veterinary sciences ,Chemistry ,Protein Array Analysis ,04 agricultural and veterinary sciences ,Molecular biology ,Immunohistochemistry ,General Biochemistry, Genetics and Molecular Biology ,Antibodies ,0403 veterinary science ,03 medical and health sciences ,Luminescent Proteins ,Antigen ,Tumor progression ,biology.protein ,Protein microarray ,Bioluminescence imaging ,Bioluminescence ,Humans ,Luciferase ,Antibody ,030304 developmental biology ,Biotechnology - Abstract
We established a quantitative detection method for immunohistochemistry based on a reference standard light-emitting diode, protein microarray and antibody-fused bioluminescent protein. In this procedure, we calibrated the bioluminescence imaging system and prepared the calibration curve between antigen and antibody-fused bioluminescent protein using a protein microarray. Then we converted the detecting light signal to antigen count via absolute photon number in the bioluminescent images; there was a resulting threefold difference in the target antigen number between normal and cancerous tissues. Our technique can easily compare immunohistological images and evaluate tumor progression in quantitative pathological diagnosis.
- Published
- 2020
24. Effects of Maternal Chewing on Prenatal Stress-Induced Cognitive Impairments in the Offspring via Multiple Molecular Pathways
- Author
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Ke-Yong Wang, Qian Zhou, Mitsuo Iinuma, Kagaku Azuma, Kin-ya Kubo, and Ayumi Suzuki
- Subjects
0301 basic medicine ,hippocampus ,Placenta ,Morris water navigation task ,Hippocampal formation ,lcsh:Chemistry ,Histones ,Mice ,0302 clinical medicine ,Glucocorticoid receptor ,Neurotrophic factors ,Pregnancy ,glucocorticoid receptor ,chewing ,lcsh:QH301-705.5 ,Spectroscopy ,digestive, oral, and skin physiology ,Brain ,Acetylation ,General Medicine ,Computer Science Applications ,Prenatal Exposure Delayed Effects ,Female ,Glucocorticoid ,medicine.drug ,Signal Transduction ,medicine.medical_specialty ,Offspring ,Neurogenesis ,Spatial Learning ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Receptors, Glucocorticoid ,stomatognathic system ,Internal medicine ,medicine ,Animals ,Cognitive Dysfunction ,Physical and Theoretical Chemistry ,Histone H3 acetylation ,Molecular Biology ,Glucocorticoids ,Brain-Derived Neurotrophic Factor ,Organic Chemistry ,DNA Methylation ,stomatognathic diseases ,030104 developmental biology ,Endocrinology ,BDNF ,Prenatal stress ,lcsh:Biology (General) ,lcsh:QD1-999 ,prenatal stress ,Mastication ,cognitive impairments ,030217 neurology & neurosurgery ,Stress, Psychological - Abstract
We aimed to investigate the effects of maternal chewing on prenatal stress-induced cognitive impairments in the offspring and to explore the molecular pathways of maternal chewing in a mice model. Maternal chewing ameliorated spatial learning impairments in the offspring in a Morris water maze test. Immunohistochemistry and Western blot findings revealed that maternal chewing alleviated hippocampal neurogenesis impairment and increased the expression of hippocampal brain-derived neurotrophic factor in the offspring. In addition, maternal chewing increased the expression of glucocorticoid receptor (GR) and 11&beta, hydroxysteroid dehydrogenase isozyme 2 (11&beta, HSD2) and decreased the expression of 11&beta, HSD1 in the placenta, thereby attenuating the increase of glucocorticoid in the offspring. Furthermore, maternal chewing increased the expression of 11&beta, HSD2, FK506-binding protein 51 (FKBP51) and FKBP52 and decreased the expression of 11&beta, HSD1, thereby increasing hippocampal nuclear GR level. In addition, maternal chewing attenuated the increase in expression of DNMT1 and DNMT3a and the decrease in expression of histone H3 methylation at lysine 4, 9, 27 and histone H3 acetylation at lysine 9 induced by prenatal stress in the offspring. Our findings suggest that maternal chewing could ameliorate prenatal stress-induced cognitive impairments in the offspring at least in part by protecting placenta barrier function, alleviating hippocampal nuclear GR transport impairment and increasing the hippocampal brain-derived neurotrophic factor (BDNF) level.
- Published
- 2020
25. Spontaneous Development of Pulmonary Emphysema in Mice Lacking All Three Nitric Oxide Synthases
- Author
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Ke-Yong Wang, Hiroaki Shimokawa, Kaori Kato, M. Tsutsui, Keisuke Naito, Kazuhiro Yatera, Shingo Noguchi, and Takaaki Ogoshi
- Subjects
chemistry.chemical_compound ,Pathology ,medicine.medical_specialty ,chemistry ,business.industry ,Pulmonary emphysema ,medicine ,business ,Nitric oxide - Published
- 2020
26. The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis
- Author
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Takashi Kido, Hirotsugu Noguchi, Sohsuke Yamada, Keishi Oda, Tetsuya Hanaka, Ke-Yong Wang, Hiroshi Mukae, Hiroshi Ishimoto, Hiroto Izumi, Xin Guo, Aya Nawata, Shingo Noguchi, Kazuhiro Yatera, and Tsutomu Takaki
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Exacerbation ,Idiopathic pulmonary fibrosis ,Bleomycin ,Peroxiredoxin 4 ,Gastroenterology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrosis ,Lactate dehydrogenase ,Internal medicine ,Pulmonary fibrosis ,medicine ,Animals ,Humans ,Aged ,Retrospective Studies ,030304 developmental biology ,lcsh:RC705-779 ,0303 health sciences ,Lung ,business.industry ,Surfactant protein D ,lcsh:Diseases of the respiratory system ,Peroxiredoxins ,Middle Aged ,respiratory system ,medicine.disease ,humanities ,respiratory tract diseases ,Disease Models, Animal ,Acute exacerbation ,medicine.anatomical_structure ,030228 respiratory system ,chemistry ,Disease Progression ,Female ,business ,Biomarkers ,Research Article - Abstract
Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. Methods Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. Results Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. Conclusions PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.
- Published
- 2019
27. Podocyte and endothelial cell injury lead to nephrotic syndrome in proliferative lupus nephritis
- Author
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Toshiyuki Nakayama, Shohei Shimajiri, Satoshi Hisano, Ke-Yong Wang, Yoshiya Tanaka, and Aya Nawata
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Nephrotic Syndrome ,Histology ,Adolescent ,Sialoglycoproteins ,Kidney Glomerulus ,Lupus nephritis ,Pathology and Forensic Medicine ,Podocyte ,Nephrin ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Membranous nephropathy ,medicine ,Humans ,Child ,WT1 Proteins ,Aged ,biology ,Podocytes ,Glomerular basement membrane ,Microfilament Proteins ,Endothelial Cells ,General Medicine ,Middle Aged ,medicine.disease ,Lupus Nephritis ,Proteinuria ,030104 developmental biology ,medicine.anatomical_structure ,Podocalyxin ,chemistry ,030220 oncology & carcinogenesis ,Disease Progression ,biology.protein ,Female ,Synaptopodin ,Nephrotic syndrome - Abstract
Aims Nephrotic syndrome (NS) is a major manifestation of lupus nephritis (LN). The dysregulation of podocytes, the glomerular basement membrane (GBM) and endothelial cells (ECs) results in proteinuria in glomerular diseases. The aim of our study was to clarify whether the dysregulation of these barriers is associated with NS in proliferative LN and membranous LN. Methods and results Fifty-six patients with NS, including minimal change NS in 15, primary membranous nephropathy (PMN) in 13, class III/IV LN in 15, and class V LN in 13, were enrolled in this study. Subjects with idiopathic haematuria were assigned as controls. Glomerular expression of Wilms tumour protein 1 (WT1), nephrin, synaptopodin and podocalyxin was evaluated by immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction. EC injury was evaluated by CD31 immunostaining and electron microscopy (EM). Reduced expression of WT1, nephrin and synaptopodin was found in PMN, class III/IV LN and class V LN as compared with controls by IHC and mRNA analysis. Reduced expression of these molecules was not different between class III/IV LN and class V LN. Reduced numbers of CD31-positive ECs were found in class III/IV LN as compared with class V LN. EC injury showing subendothelial widening on EM was apparent in class III/IV LN as compared with class V LN. Foot process effacement was found only along the GBM showing EC injury in class III/IV LN. Conclusions Our study suggests that coexistence of podocyte and EC injury may lead to NS in proliferative LN. Podocyte damage alone leads to NS in membranous LN.
- Published
- 2018
28. Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin
- Author
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Takashi Saito, Kagaku Azuma, Xiao Liu, Ke-Yong Wang, Qian Zhou, Xiumei Gao, Xiaoying Wang, Jia-He Zhang, and Takaomi C Saido
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Alzheimer’s disease ,AppNL-G-F ,dioscin ,amyloid-β ,synaptic dysfunction ,microglia ,neuroinflammation ,QH301-705.5 ,Hippocampus ,Mice, Transgenic ,Disease ,Neuropathology ,Diosgenin ,Models, Biological ,Article ,Amyloid beta-Protein Precursor ,Alzheimer Disease ,medicine ,Animals ,Dementia ,Biology (General) ,Young adult ,beta Catenin ,Neuroinflammation ,Sex Characteristics ,Microglia ,business.industry ,Body Weight ,NF-kappa B ,Brain ,General Medicine ,medicine.disease ,Cortex (botany) ,Mice, Inbred C57BL ,Disease Models, Animal ,A ppNL-G-F ,medicine.anatomical_structure ,Synapses ,Cytokines ,Female ,business ,Signal Transduction - Abstract
Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.
- Published
- 2021
29. Chronology and Geochemistry of the Berezitovoe Polymetallic Gold Deposit in Eastern Siberia, Russia and its Geological Significance
- Author
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Guobin Zhang, Shijiong Han, Songqing Ye, Ke-Yong Wang, A. S. Vakh, Yanchen Yang, and V. G. Khomich
- Subjects
020209 energy ,0202 electrical engineering, electronic engineering, information engineering ,Geochemistry ,Geology ,Fluid inclusions ,Gold deposit ,02 engineering and technology ,010502 geochemistry & geophysics ,01 natural sciences ,0105 earth and related environmental sciences ,Chronology - Published
- 2017
30. Fluid evolution in the Beidabate porphyry Cu-Mo deposit, Xinjiang, northwest China: Evidence from fluid inclusions and H-O-C-S isotopes
- Author
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Gulfira Omar, Chuan Chen, Shunda Li, Ke-Yong Wang, Fang Xia, Ling-ling Gao, and Xuebing Zhang
- Subjects
Chalcopyrite ,Geochemistry ,Geology ,Hydrothermal circulation ,Geochemistry and Petrology ,Boiling ,visual_art ,Molybdenite ,Genetic model ,Meteoric water ,visual_art.visual_art_medium ,Economic Geology ,Fluid inclusions ,Inclusion (mineral) - Abstract
The Beidabate deposit is a porphyry Cu-Mo deposit located in the West Tianshan Orogenic Belt , Xinjiang Uygur Autonomous Region. The fluid evolution path and Cu-Mo mineralization mechanism remain obscured by multiple hydrothermal pulses. Systematic fluid inclusion and H-O-C-S isotope analyses were performed on five identifiable mineralization stages. Variations in fluid composition, temperature, and pressure record the fluid evolution path: (1) During the formation of barren quartz veins (stage I), fluid inclusions were trapped under single- to two-phase transitional conditions, as evidenced by the presence of intermediate-density inclusions as well as coexisting daughter mineral-bearing inclusions and vapor-rich inclusions (boiling FIAs). Fluid phase separation occurred at temperatures of 387–412 °C and pressures of 180–300 bar. (2) Fluid inclusions in K-feldspar-quartz veins (stage II) and molybdenite-quartz veins (stage III) were trapped under two-phase conditions. Boiling FIAs were also recognized, with homogenization temperatures of 306–368 °C and entrapment pressures of 80–200 bar. Fluid boiling is the main precipitation mechanism of molybdenite . (3) Fluid inclusions in pyrite-chalcopyrite-quartz veins (stage IV) and fluorite-chalcopyrite veins (stage V) are predominantly liquid-rich and CO 2 -bearing inclusions, which represent extraneous fluids. These inclusions homogenized at temperatures of 192° to 285 °C, and minimum entrapment pressures of 40–50 bar. Fluid mixing is the main precipitation mechanism of chalcopyrite . H-O-C-S isotope data (δ 18O = 3.2 to 15.2‰, δD = −103.6 to −75.1‰, δ13C = −24.2 to −9.7‰ and δ34 S = 4.6 to 7.0‰) indicate that the ore-forming fluids have a predominantly magmatic signature with subsequent dilution by late meteoric water and intense water–rock interaction. We established a genetic model of the Beidabate porphyry Cu-Mo deposit with the aim of providing insight into prospecting at a regional scale.
- Published
- 2021
31. Chewing Behavior Attenuates the Tumor Progression-Enhancing Effects of Psychological Stress in a Breast Cancer Model Mouse
- Author
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Ke-Yong Wang, Kin-ya Kubo, Xiao Liu, Qian Zhou, Jia-He Zhang, Masahisa Katano, Kagaku Azuma, and Mitsuo Iinuma
- Subjects
β2-adrenergic receptor ,medicine.medical_specialty ,β2‐adrenergic receptor ,medicine.disease_cause ,Article ,lcsh:RC321-571 ,Superoxide dismutase ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,stomatognathic system ,Internal medicine ,medicine ,oxidative stress ,Receptor ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,psychological stress ,030304 developmental biology ,0303 health sciences ,biology ,Cell growth ,business.industry ,chewing behavior ,General Neuroscience ,digestive, oral, and skin physiology ,Nitric oxide synthase ,stomatognathic diseases ,Endocrinology ,Tumor progression ,030220 oncology & carcinogenesis ,biology.protein ,glucocorticoid ,business ,Oxidative stress ,Glucocorticoid ,medicine.drug ,Hormone - Abstract
We examined whether chewing behavior affects the tumor progression-enhancing impact of psychological stress. Human breast cancer cell line (MDA-MB-231) cells were inoculated into the mammary fat pads of athymic nude mice. The mice were assigned randomly to control, stress, and stress+chewing groups. Psychological stress was created by keeping mice in a transparent restraint cylinder for 45 min, three times a day, for 35 days after cell inoculation. Animals in the stress+chewing group were provided with a wooden stick for chewing on during the psychological stress period. Chewing behavior remarkably inhibited the tumor growth accelerated by the psychological stress. Immunohistochemical and Western blot findings revealed that chewing behavior during psychological stress markedly suppressed tumor angiogenesis and cell proliferation. In addition, chewing behavior decreased serum glucocorticoid levels and expressions of glucocorticoid and β2-adrenergic receptors in tumors. Chewing behavior decreased expressions of inducible nitric oxide synthase and 4-hydroxynonenal, and increased expression of superoxide dismutase 2 in tumors. Our findings suggest that chewing behavior could ameliorate the enhancing effects of psychological stress on the progression of breast cancer, at least partially, through modulating stress hormones and their receptors, and the subsequent signaling pathways involving reactive oxygen and nitrogen species.
- Published
- 2021
32. Protective role of nitric oxide synthases in pulmonary emphysema in mice
- Author
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Kaori Kato, Masato Tsutsui, Keisuke Naito, Ke-Yong Wang, Takaaki Ogoshi, Shingo Noguchi, Kazuhiro Yatera, and Hiroaki Shimokawa
- Subjects
Pathology ,medicine.medical_specialty ,Lung ,medicine.diagnostic_test ,business.industry ,Pulmonary emphysema ,medicine.medical_treatment ,Nitric oxide ,Pathogenesis ,chemistry.chemical_compound ,Bronchoalveolar lavage ,medicine.anatomical_structure ,chemistry ,Medicine ,In patient ,business ,Pancreatic elastase ,Saline - Abstract
Background: It has been reported that alveolar nitric oxide (NO) levels and lung expression levels of several types of NO synthase (NOS) isoforms are increased in patients with pulmonary emphysema. However, the roles of NO and NOSs in the development of pulmonary emphysema remain to be fully elucidated. In this study, we addressed this point in our mice lacking all three NOSs. Methods: Experiments were performed in wild-type (WT), single nNOS-/-, iNOS-/-, eNOS-/-, and triple n/i/eNOS-/- mice. They were treated with intratracheal instillation of either 0.05 unit porcine pancreatic elastase (PPE) or saline (control). Twenty-one days later, pulmonary emphysematous changes were evaluated. Results: At 21 days after intratracheal PPE administration, plasma NOx levels were by far lowest in the triple NOSs-/- mice as compared with the WT mice. Intratracheal PPE administration caused pulmonary emphysematous changes in all the mice studied. Notably, the extents of pulmonary emphysematous changes, as assessed by mean distance of alveolar space and by micro computed tomography value, were most aggravated in the triple n/i/eNOS-/- mice as compared with the WT mice. Those changes were associated with highest number of total cells, macrophages, and lymphocytes in bronchoalveolar lavage fluid. Long-term treatment with sodium nitrate significantly prevented PPE-induced pulmonary emphysematous changes in the triple NOSs-/- mice. Conclusion: These results provide the first evidence that genetic disruption of all NOSs results in markedly exacerbated pulmonary emphysematous changes in mice, indicating an important protective role of NO/NOSs in the pathogenesis of pulmonary emphysema.
- Published
- 2019
33. Long-term observation of pulmonary toxicity of toner with external additives following a single intratracheal instillation in rats
- Author
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Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Chinatsu Nishida, Takashi Marui, Ke-Yong Wang, Yasuo Morimoto, and Taisuke Tomonaga
- Subjects
Pathology ,medicine.medical_specialty ,Pulmonary toxicity ,DNA damage ,Intratracheal instillation ,Carcinogenesis ,Inflammation ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,toner ,Fibrosis ,medicine ,Animals ,rat ,030212 general & internal medicine ,Rats, Wistar ,Lung ,Inhalation Exposure ,business.industry ,Public Health, Environmental and Occupational Health ,intratracheal instillation ,Pneumonia ,Original Articles ,external additives ,medicine.disease ,030210 environmental & occupational health ,Rats ,Trachea ,tumorigenesis ,medicine.anatomical_structure ,Female ,Ink ,Original Article ,medicine.symptom ,business ,Bronchoalveolar Lavage Fluid ,Immunostaining - Abstract
Objectives Along with technological innovations for improving the efficiency of printing, nanoparticles have been added to the surface of toners, and there is concern about the harmful effects of those components. We investigated, through a long‐term observation following intratracheal instillation using rats, whether exposure to a toner with external additives can cause tumorigenesis. Methods Female Wistar rats were intratracheally instilled with dispersed toner at low (1 mg/rat) and high (2 mg/rat) doses, and the rats were sacrificed at 24 months after exposure, after which we examined pulmonary inflammation, histopathological changes, and DNA damage in the lung. Rats that had deceased before 24 months were dissected at that time as well, to compare tumor development. Results Although alveolar macrophages with pigment deposition in the alveoli were observed in the 1 and 2 mg exposure groups, no significant lung inflammation/fibrosis or tumor was observed. Since immunostaining with 8‐OHdG or γ‐H2AX did not show a remarkable positive reaction, it is thought that toner did not cause severe DNA damage to lung tissue. Conclusion These results suggest that toner with external additives may have low toxicity in the lung.
- Published
- 2019
34. Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials
- Author
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Chinatsu Nishida, Shingo Noguchi, Hiroto Izumi, Takashi Marui, Takami Okada, Masaru Kubo, Ke-Yong Wang, Manabu Shimada, Takako Oyabu, Toshihiko Myojo, Yasuo Morimoto, Byeong-Woo Lee, Taisuke Tomonaga, Yukiko Yoshiura, and Kazuhiro Yatera
- Subjects
Male ,0301 basic medicine ,Neutrophils ,Pulmonary toxicity ,Health, Toxicology and Mutagenesis ,lcsh:Industrial hygiene. Industrial welfare ,010501 environmental sciences ,Pharmacology ,Toxicology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,lcsh:RA1190-1270 ,Lactate dehydrogenase ,Macrophages, Alveolar ,medicine ,Animals ,Lung ,Peroxidase ,lcsh:Toxicology. Poisons ,0105 earth and related environmental sciences ,Inhalation exposure ,Inhalation Exposure ,Myeloperoxidase ,Inhalation ,medicine.diagnostic_test ,biology ,Research ,Biomarker ,General Medicine ,Nanomaterial ,Rats, Inbred F344 ,Heme oxygenase ,030104 developmental biology ,Bronchoalveolar lavage ,chemistry ,Toxicity ,biology.protein ,Rat ,Nanoparticles ,Chemokines ,Bronchoalveolar Lavage Fluid ,Intratracheal instillation ,Biomarkers ,lcsh:HD7260-7780.8 - Abstract
Background In order to examine whether myeloperoxidase (MPO) can be a useful marker for evaluating the pulmonary toxicity of nanomaterials, we analyzed MPO protein in bronchoalveolar lavage fluid (BALF) samples obtained from previous examinations of a rat model. In those examinations we performed intratracheal instillation exposures (dose: 0.2–1.0 mg) and inhalation exposures (exposure concentration: 0.32–10.4 mg/m3) using 9 and 4 nanomaterials with different toxicities, respectively. Based on those previous studies, we set Nickel oxide nanoparticles (NiO), cerium dioxide nanoparticles (CeO2), multi wall carbon nanotubes with short or long length (MWCNT (S) and MWCNT (L)), and single wall carbon nanotube (SWCNT) as chemicals with high toxicity; and titanium dioxide nanoparticles (TiO2 (P90) and TiO2 (Rutile)), zinc oxide nanoparticles (ZnO), and toner with external additives including nanoparticles as chemicals with low toxicity. We measured the concentration of MPO in BALF samples from rats from 3 days to 6 months following a single intratracheal instillation, and from 3 days to 3 months after the end of inhalation exposure. Results Intratracheal instillation of high toxicity NiO, CeO2, MWCNT (S), MWCNT (L), and SWCNT persistently increased the concentration of MPO, and inhalation of NiO and CeO2 increased the MPO in BALF. By contrast, intratracheal instillation of low toxicity TiO2 (P90), TiO2 (Rutile), ZnO, and toner increased the concentration of MPO in BALF only transiently, and inhalation of TiO2 (Rutile) and ZnO induced almost no increase of the MPO. The concentration of MPO correlated with the number of total cells and neutrophils, the concentration of chemokines for neutrophils (cytokine-induced neutrophil chemoattractant (CINC)-1 and heme oxygenase (HO)-1), and the activity of released lactate dehydrogenase (LDH) in BALF. The results from the receiver operating characteristics (ROC) for the toxicity of chemicals by the concentration of MPO proteins in the intratracheal instillation and inhalation exposures showed that the largest areas under the curves (AUC) s in both examinations occurred at 1 month after exposure. Conclusion These data suggest that MPO can be a useful biomarker for the ranking of the pulmonary toxicity of nanomaterials, especially at 1 month after exposure, in both intratracheal instillation and inhalation exposure. Electronic supplementary material The online version of this article (10.1186/s12989-018-0277-x) contains supplementary material, which is available to authorized users.
- Published
- 2018
35. Novel function of histamine signaling via histamine receptors in cholesterol and bile acid metabolism: Histamine H2 receptor protects against nonalcoholic fatty liver disease
- Author
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Ke-Yong Wang, Yasuyuki Sasaguri, Sohsuke Yamada, Xin Guo, and Akihide Tanimoto
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,Biology ,Pathology and Forensic Medicine ,Bile Acids and Salts ,Mice ,03 medical and health sciences ,Histamine receptor ,chemistry.chemical_compound ,Histamine H2 receptor ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Receptors, Histamine H2 ,Liver X receptor ,Bile acid ,Cholesterol ,Reverse cholesterol transport ,Cholic acid ,General Medicine ,medicine.disease ,030104 developmental biology ,Endocrinology ,Liver ,chemistry ,Histamine ,Signal Transduction - Abstract
We have reported that the function of histamine and its receptors (HRs) has a close relationship with the development of nonalcoholic fatty liver disease (NAFLD). However, much less is known regarding its pathogenic and molecular mechanism(s), including the early stage of hepatic and intestinal function for lipid and bile acid (BA) metabolism. We used H1R and H2R knockout mice (H1/2R-KO) to clarify those pivotal roles in cholesterol/BA metabolism, in which H1/2R-KO mice were separately fed a short-term 1% cholesterol or cholic acid (CA) diet. [(3) H]Cholesterol absorption study revealed that significantly enhanced accumulation occurred in the jejunum, blood and liver, but not in the feces, of H2R-KO mice, compared to wild-type and H1R-KO mice. Furthermore, four weeks after the high-cholesterol diet, the H2R-KO jejunum but not liver exhibited increased expressions of cholesterol transporters, consistent with higher plasma lipoprotein levels. Five days after CA diet, the H2R-KO mice showed significantly higher expressions of ileal BA-reabsorption and hepatic BA-efflux factors, corresponding to higher serum but lower fecal BA levels. The following long-term CA diets resulted in severe injury to the H2R-KO liver. Histamine/H2R signaling might have a protective role in the initial phase during NAFLD progression, correlated with cholesterol and BA metabolism in the liver/intestine.
- Published
- 2016
36. Polypeptide N-acetylgalactosaminyltransferase-6 expression independently predicts poor overall survival in patients with lung adenocarcinoma after curative resection
- Author
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Ying Wu, Kimitoshi Kohno, Zhi Li, Ke-Yong Wang, Yasuyuki Sasaguri, Sohsuke Yamada, Hidetaka Uramoto, and Yunpeng Liu
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Multivariate analysis ,glycosylation ,overall survival ,Polypeptide N-acetylgalactosaminyltransferase ,Adenocarcinoma of Lung ,Adenocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Clinical significance ,Stage (cooking) ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Aged, 80 and over ,Lung ,business.industry ,Cancer ,Middle Aged ,lung adenocarcinoma ,medicine.disease ,Immunohistochemistry ,Surgery ,carbohydrates (lipids) ,030104 developmental biology ,medicine.anatomical_structure ,GalNAc-T6 ,Cardiothoracic surgery ,030220 oncology & carcinogenesis ,N-Acetylgalactosaminyltransferases ,Female ,prognosis ,business ,Research Paper - Abstract
// Zhi Li 1, 2 , Sohsuke Yamada 2, 9, 10 , Ying Wu 1 , Ke-Yong Wang 3 , Yun-Peng Liu 1 , Hidetaka Uramoto 4, 7 , Kimitoshi Kohno 5, 8 , Yasuyuki Sasaguri 2, 6 1 Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, China 2 Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan 3 Bio-information Research Center, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan 4 Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan 5 The President Laboratory, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan 6 Laboratory of Pathology, Fukuoka Wajiro Hospital, Fukuoka, Japan 7 Division of Thoracic Surgery, Saitama Cancer Center, Saitama, Japan 8 Asahi-Matsumoto Hospital, Kitakyushu, Japan 9 Institute of Pathology, Medical University of Graz, Graz, Austria 10 Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Correspondence to: Yun-Peng Liu, email: cmuliuyunpeng@hotmail.com Sohsuke Yamada, email: sousuke@med.uoeh-u.ac.jp Keywords: GalNAc-T6, glycosylation, lung adenocarcinoma, prognosis, overall survival Received: March 02, 2016 Accepted: May 04, 2016 Published: June 03, 2016 ABSTRACT Background: Polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) are important glycosyltransferases in cancer, but the clinical role of its individual isoforms is unclear. We investigated the clinical significance and survival relevance of one isoform, GalNAc-T6 in lung adenocarcinoma after curative resection. Results: GalNAc-T6 was identified in 27.8% (55/198) of patients, and statistically indicated advanced TNM stage ( P = 0.069). Multivariate analysis showed GalNAc-T6 to be an independent predictor for reduced overall survival of patients ( P = 0.027), and the result was confirmed with bootstraping techniques, and on line "Kaplan-Meier Plotter" and "SurvExpress" database analysis, respectively. Moreover, ROC curve demonstrated that GalNAc-T6 expression significantly improved the accuracy of survival prediction. Methods: With 198 paraffin-embedded tumor samples from lung adenocarcinoma patients, GalNAc-T6 expression was immunohistochemically assessed for the association with clinicopathological parameters. The prognostic significance was evaluated by Cox proportional hazards regression analysis with 1000 bootstraping. "Kaplan-Meier Plotter", "SurvExpress" database analysis, and receiver-operating characteristic (ROC) curve were performed to provide further validation. Conclusions: GalNAc-T6 expression correlated significantly with advanced TNM stage, and independently predicted worse OS for lung adenocarcinoma.
- Published
- 2016
37. Calcifying giant cell cardiomyopathy: a possible new entity
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Ke-Yong Wang, Tetsuya So, Sohsuke Yamada, Akihide Tanimoto, Naoki Yamashita, Ryuji Nakano, and Shohei Shimajiri
- Subjects
Pathology ,medicine.medical_specialty ,Myocarditis ,Cardiomyopathy ,General Medicine ,030204 cardiovascular system & hematology ,Biology ,medicine.disease ,Sudden death ,Pathology and Forensic Medicine ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Giant cell ,Fibrosis ,medicine ,Cardiology and Cardiovascular Medicine ,Pathological ,Calcification - Abstract
We demonstrated an extremely unusual case of an 83-year-old male's sudden death secondary to characteristic myocardial necrosis and fibrosis with calcification and multinucleated giant cells infiltration, possibly due to sepsis and Stage IV pulmonary pleomorphic carcinoma-induced cachexia after postmortem study. We propose that this calcifying giant cell cardiomyopathy (CGC) would be a new entity especially from the pathological viewpoints and should be considered in the classification of noninfectious myocarditis. Further prospective studies are needed to validate the presence and significance of CGC and the association with any triggers of somewhat microvascular dysfunction and/or toxic agents, after collecting and investigating a larger number of CGC cases examined.
- Published
- 2017
- Full Text
- View/download PDF
38. Findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle
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Kagaku Azuma, Kimitoshi Kohno, Eiichiro Nakamura, Sohsuke Yamada, Qian Zhou, Hiroto Izumi, Takashi Tasaki, Akinori Sakai, Ke-Yong Wang, Yoichi Murata, Yasuaki Okada, Manabu Tsukamoto, Yoshiaki Yamanaka, and Yasuyuki Sasaguri
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,030209 endocrinology & metabolism ,Bone Marrow Cells ,Nerve Tissue Proteins ,Myostatin ,Biology ,Models, Biological ,Bone and Bones ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,Bone Marrow ,Osteogenesis ,Internal medicine ,Adipocyte ,medicine ,Animals ,Mice, Knockout ,Adipogenesis ,Muscles ,Wnt signaling pathway ,Organ Size ,Phenotype ,Wnt Proteins ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Adipose Tissue ,biology.protein ,Bone marrow ,Gene Deletion ,Protein Binding - Abstract
Wnt10a is a member of the WNT family. Although deficiency of this gene causes symptoms related to teeth, hair, nails, and skin, we recently demonstrated a new phenotype of Wnt10a knockout (KO) mice involving bone and fat. The in vivo effect of the Wnt10a gene on bone and fat is unclear, and the relationship between bone/fat and muscle in Wnt10a signaling is also interesting. We aimed to evaluate the tissue changes in Wnt10a KO mice compared to wild-type mice and show the findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle. Trabecular bone loss in the lower limbs of Wnt10a mice and decreased bone mineralization were observed. The adipose tissue in bone marrow was also decreased, and adipocyte differentiation was reduced. The body fat mass in Wnt10a KO mice was decreased, and white adipocytes in subcutaneous fat were converted to beige adipocytes. The muscle weight of the lower limbs was not decreased despite trabecular bone loss, but Gdf8/myostatin expression was reduced in the subcutaneous fat and gastrocnemius muscles of Wnt10a KO mice. Thus, in vivo deletion of Wnt10a inhibited osteogenic activity, promoted beige adipogenesis of white adipocytes and maintained muscle mass. These results suggest that regulation of Gdf8 by Wnt10a may help maintain the muscle mass of Wnt10a KO mice. This study was the first to histologically evaluate the bone, fat and muscle phenotypes of Wnt10a KO mice. The results of this study, which were obtained by investigating the three tissues together, could influence the understanding of in vivo interactions involving the Wnt10a gene.
- Published
- 2018
39. Systemic bone loss, impaired osteogenic activity and type I muscle fiber atrophy in mice with elastase-induced pulmonary emphysema: Establishment of a COPD-related osteoporosis mouse model
- Author
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Akinori Sakai, Yasuaki Okada, Keisuke Naito, Toshiharu Mori, Ke-Yong Wang, Hokuto Fukuda, Ken Sabanai, Kazuhiro Yatera, Eiichiro Nakamura, Manabu Tsukamoto, and Yoshiaki Yamanaka
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Pulmonary emphysema ,Osteoporosis ,Muscle Fibers, Skeletal ,030209 endocrinology & metabolism ,Lumbar vertebrae ,Bone and Bones ,Bone remodeling ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Atrophy ,Bone Density ,Osteogenesis ,Internal medicine ,medicine ,Animals ,Bone Resorption ,Pathological ,Lung ,COPD ,Pancreatic Elastase ,business.industry ,Elastase ,Body Weight ,Organ Size ,X-Ray Microtomography ,medicine.disease ,respiratory tract diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Pulmonary Emphysema ,Cancellous Bone ,business ,Biomarkers - Abstract
Although it is suggested that chronic obstructive pulmonary disease (COPD) and bone are related, almost all of the pathological mechanisms of COPD-related osteoporosis remain unknown. There is a mouse model showing a deterioration of bone quality after cigarette smoke exposure; however, in smoking exposure models, various factors exist that affect bone metabolism, such as smoking and body weight loss (muscle and fat mass loss). We considered it appropriate to use an elastase-induced emphysema model to exclude factors influencing bone metabolism and to investigate the influence of pulmonary emphysema on bone metabolism. The purpose of this study was to establish a COPD/emphysema-related osteoporosis mouse model by using the elastase-induced emphysema model. The lumbar vertebrae and femurs/tibiae exhibited trabecular bone loss and impaired osteogenic activity in 24-week-old male elastase-induced emphysema model mice. In addition, the model mice showed atrophy of type I muscle fibers without atrophy of type II muscle fibers. We believe that the mice described in this experimental protocol will be accepted as a COPD/emphysema-related osteoporosis mouse model and contribute to further investigations.
- Published
- 2018
40. Protective Role of Myelocytic Nitric Oxide Synthases against Hypoxic Pulmonary Hypertension in Mice
- Author
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Hiroaki Masuzaki, Keishi Oda, Takashi Kido, Ke-Yong Wang, Yumiko Toyohira, Takaaki Ogoshi, Nobuyuki Yanagihara, Hiroshi Ishimoto, Hiroto Izumi, Sohsuke Yamada, Keisuke Naito, Hiroshi Mukae, Kazuhiro Yatera, Masato Tsutsui, Mayuko Sakanashi, and Hiroaki Shimokawa
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Male ,Hypertension, Pulmonary ,Bone Marrow Cells ,Pharmacology ,Critical Care and Intensive Care Medicine ,Protective Agents ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Right ventricular hypertrophy ,No synthase ,Medicine ,Animals ,Humans ,Granulocyte Precursor Cells ,Hypoxia ,business.industry ,Editorials ,medicine.disease ,Pulmonary hypertension ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,chemistry ,Models, Animal ,Bone marrow ,Nitric Oxide Synthase ,business - Abstract
Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive.To determine the role of NOSs in BM cells in PH.Experiments were performed on 36 patients with idiopathic pulmonary fibrosis and on wild-type (WT), nNOS (neuronal NOS)In the patients, there was a significant correlation between higher pulmonary artery systolic pressure and lower nitrite plus nitrate levels in the BAL fluid. In the mice, hypoxia-induced PH deteriorated significantly in the n/i/eNOSsThese results demonstrate that myelocytic n/i/eNOSs play an important protective role in the pathogenesis of PH.
- Published
- 2018
41. Novel function of histamine signaling in hyperlipidemia-induced atherosclerosis: Histamine H1 receptors protect and H2 receptors accelerate atherosclerosis
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Akihide Tanimoto, Yasuyuki Sasaguri, Ke-Yong Wang, and Sohsuke Yamada
- Subjects
Apolipoprotein E ,medicine.medical_specialty ,General Medicine ,Histamine H1 receptor ,Biology ,Pathology and Forensic Medicine ,Histamine receptor ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Histamine H2 receptor ,Internal medicine ,medicine ,lipids (amino acids, peptides, and proteins) ,Histamine H4 receptor ,Scavenger receptor ,Liver X receptor ,Histamine - Abstract
Histamine is not only essential for acute inflammatory reactions, but it also participates in a chronic inflammatory disorder. We generated apolipoprotein E (apoE) and histamine receptors (HHRs), including the major H1 and H2 receptors (HH1R, HH2R) double knockout mice (DKO) to clarify the role of HHRs in hyperlipidemia-induced atherosclerosis, in which apoE-KO and DKO mice were fed a high cholesterol diet. We found that pronounced hyperlipidemia-induced atherosclerotic progression occurred in HH1R/apoE-DKO mice, but in HH2R/apoE-DKO mice less atherosclerosis, despite pro-atherogenic serum cholesterol levels compared with apoE-KO mice. Furthermore, the increased expressions of scavenger receptors (SRs), such as SR-A, CD36 and lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), nuclear factor-kappa B (NFκB), monocyte chemoattractant protein (MCP-1), matrix metalloproteinases (MMPs) or liver X receptor (LXR)-related inflammatory signaling factors, were consistent with the pro-atherogenic phenotype of HH2R/apoE-DKO mice. We hypothesize that histamine/HH1R and HH2R signaling has conflicting innate functions, inflammatory/atherogenic and anti-inflammatory/anti-atherogenic actions, and that there are innate links between histamine signaling and hyperlipidemia-induced atherosclerosis, independently of serum cholesterol metabolism. Specific histamine signaling blockers, in particular, HH2R blockers, are a possible novel therapeutic target for hyperlipidemia-induced atherosclerosis.
- Published
- 2015
42. CCL22/Macrophage-derived Chemokine Expression in Apolipoprotein E-deficient Mice and Effects of Histamine in the Setting of Atherosclerosis
- Author
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Ke-Yong Wang, Yasuyuki Sasaguri, Hirotsugu Noguchi, Satoshi Kimura, Sohsuke Yamada, Masaru Harada, Takeshi Watanabe, Atsunori Nabeshima, and Xin Guo
- Subjects
Male ,Apolipoprotein E ,Chemokine ,Enzyme-Linked Immunosorbent Assay ,Real-Time Polymerase Chain Reaction ,Monocytes ,Mice ,chemistry.chemical_compound ,Histamine receptor ,Apolipoproteins E ,Histamine H2 receptor ,Internal Medicine ,Animals ,Humans ,Receptors, Histamine H2 ,RNA, Messenger ,Histamine H4 receptor ,Cells, Cultured ,Chemokine CCL22 ,Mice, Knockout ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Macrophages ,Biochemistry (medical) ,Atherosclerosis ,Molecular biology ,Histidine decarboxylase ,Mice, Inbred C57BL ,Disease Models, Animal ,chemistry ,Immunology ,Knockout mouse ,biology.protein ,Microscopy, Polarization ,Cardiology and Cardiovascular Medicine ,Histamine - Abstract
Aim Macrophage-derived chemokine (CCL22) is a member of the CC-family of chemokines synthesized by monocyte-derived macrophages. Previous studies have reported a relationship between CCL22 and atherosclerosis and the role of histamine in this pathway. Histamine ncreases the CCL22 expression in human monocytes via the H2 receptor. In this study, we investigated the effects of CCL22 and the role of histamine in mouse monocytes with respect to atherosclerosis. Methods and results The expression of CCL22 was investigated in apolipoprotein E (apoE)-deficient mice. The mice had high serum concentrations of CCL22 and their atherosclerotic lesions contained abundant levels of CCL22. In addition, when the mouse monocyte cell line (J774A.1 cells) differentiated into macrophage-like cells, the cells showed a similar expression of CCL22 and reduced expression of H2 receptors. Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) in a single enzymatic step. HDC knockout mice were compared with apoE/HDC double knockout mice. The findings indicated that the expression of CCL22 in atherosclerosis models is under the influence of histamine. In addition, in vitro studies using J774A.1 cells and an in vivo study using histamine receptor knockout mice showed that histamine stimulates the CCL22 expression via the histamine H2 receptor. Conclusions The current results support our previous CCL22 studies in the setting of human atherosclerosis and suggest that this molecule is involved in the atherogenic processes in a mouse model of atherosclerosis.
- Published
- 2015
43. Calcifying giant cell cardiomyopathy: a possible new entity: Images in Cardiovascular Pathology
- Author
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Ke-Yong, Wang, Sohsuke, Yamada, Shohei, Shimajiri, Ryuji, Nakano, Naoki, Yamashita, Tetsuya, So, and Akihide, Tanimoto
- Subjects
Aged, 80 and over ,Male ,Necrosis ,Fatal Outcome ,Biopsy ,Myocardium ,Calcinosis ,Humans ,Autopsy ,Cardiomyopathies ,Fibrosis ,Giant Cells ,Immunohistochemistry - Abstract
We demonstrated an extremely unusual case of an 83-year-old male's sudden death secondary to characteristic myocardial necrosis and fibrosis with calcification and multinucleated giant cells infiltration, possibly due to sepsis and Stage IV pulmonary pleomorphic carcinoma-induced cachexia after postmortem study. We propose that this calcifying giant cell cardiomyopathy (CGC) would be a new entity especially from the pathological viewpoints and should be considered in the classification of noninfectious myocarditis. Further prospective studies are needed to validate the presence and significance of CGC and the association with any triggers of somewhat microvascular dysfunction and/or toxic agents, after collecting and investigating a larger number of CGC cases examined.
- Published
- 2017
44. Hypersensitivity to Aurora Kinase Inhibitors in Cells Resistant against Platinum- Containing Anticancer Agents
- Author
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Masaki Akiyama, Ke-Yong Wang, Koji Yamaguchi, Yoshikazu Harada, Ryoichi Oya, Noriaki Kitamura, Akihiro Kuma, Hiroto Izumi, Takahiro Yamaguchi, Kimitoshi Kohno, and Yoshiko Iwai
- Subjects
Cancer Research ,Organoplatinum Compounds ,medicine.medical_treatment ,Aurora inhibitor ,Aurora B kinase ,Antineoplastic Agents ,Biology ,Pharmacology ,Targeted therapy ,chemistry.chemical_compound ,Aurora kinase ,Aurora Kinases ,Cell Line, Tumor ,medicine ,Humans ,Protein Kinase Inhibitors ,Cisplatin ,Kinase ,Organophosphates ,Oxaliplatin ,ZM447439 ,chemistry ,Drug Resistance, Neoplasm ,Benzamides ,Quinazolines ,Molecular Medicine ,medicine.drug - Abstract
The aurora kinases are serine/threonine kinases that are essential for mitosis and contribute to tumorigenesis. Therefore, aurora kinases hold promise for molecularly targeted therapy. In the present study, we demonstrated that aurora B kinase (AURKB) is overexpressed in both cisplatin- and oxaliplatin-resistant cells. Downregulation of AURKB sensitized cells to both cisplatin and oxaliplatin, but not to paclitaxel, 5-FU or hydrogen peroxide. Interestingly, we found that both cisplatin- and oxaliplatin-resistant cells were hypersensitive to the AURKB specific inhibitors, AZD1152 HQPA and ZM447439, suggesting that both cisplatin- and oxaliplatinresistant cells develop an addiction to AURKB. These data provide evidence that aurora kinase inhibitors can overcome both cisplatin and oxaliplatin resistance. Therefore, AURKB inhibitors could offer potential benefits if used after first-line platinum-based chemotherapy.
- Published
- 2014
45. Protective Role of Myelocytic Nitric Oxide Synthases in Hypoxic Pulmonary Hypertension in Mice
- Author
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Takashi Kido, Hiroshi Mukae, Nobuyuki Yanagihara, Sohsuke Yamada, Masato Tsutsui, Yumiko Toyohira, Takaaki Ogoshi, Kazuhiro Yatera, Hiroaki Shimokawa, and Ke-Yong Wang
- Subjects
chemistry.chemical_compound ,chemistry ,business.industry ,Applied Mathematics ,General Mathematics ,Medicine ,Pharmacology ,business ,medicine.disease ,Pulmonary hypertension ,Nitric oxide - Published
- 2018
46. Peroxiredoxin 4 Protects Against Nonalcoholic Steatohepatitis and Type 2 Diabetes in a Nongenetic Mouse Model
- Author
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Yasuyuki Sasaguri, Teruo Watanabe, Sohsuke Yamada, Hirotsugu Noguchi, Kimitoshi Kohno, Atsunori Nabeshima, Shohei Kitada, Shohei Shimajiri, Junichi Fujii, Akihide Tanimoto, Ke-Yong Wang, Takashi Tasaki, Xin Guo, and Satoshi Kimura
- Subjects
Male ,medicine.medical_specialty ,Physiology ,T-Lymphocytes ,medicine.medical_treatment ,Clinical Biochemistry ,Apoptosis ,Mice, Transgenic ,Type 2 diabetes ,Biology ,Thiobarbituric Acid Reactive Substances ,Biochemistry ,Diabetes Mellitus, Experimental ,Mice ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Animals ,Humans ,Molecular Biology ,Cells, Cultured ,General Environmental Science ,Aldehydes ,Guanosine ,Adiponectin ,Insulin ,Fatty liver ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Peroxiredoxins ,Cell Biology ,medicine.disease ,Fatty Liver ,Disease Models, Animal ,Oxidative Stress ,Original Research Communications ,Endocrinology ,Diabetes Mellitus, Type 2 ,Liver ,Hepatocytes ,General Earth and Planetary Sciences ,Inflammation Mediators ,Receptors, Adiponectin ,Metabolic syndrome ,Steatosis - Abstract
Aims: Consumption of a high-fructose diet (HFrD) can induce the development of a metabolic syndrome, manifesting as nonalcoholic steatohepatitis (NASH) and/or type 2 diabetes mellitus (T2DM), via a process in which oxidative stress plays a critical role. Peroxiredoxin 4 (PRDX4) is a unique and only known secretory member of the PRDX antioxidant family. However, its putative roles in the development of NASH and/or T2DM have not been investigated. Results: To elucidate the functions of PRDX4 in a metabolic syndrome, we established a nongenetic mouse model of T2DM by feeding mice a HFrD after injecting a relatively low dose of streptozotocin. Compared with wild-type (WT), human PRDX4 transgenic (Tg) mice exhibited significant improvements in insulin resistance, characterized by a lower glucose and insulin concentration and faster responses in glucose tolerance tests. The liver of Tg also showed less severe vesicular steatosis, inflammation, and fibrosis, along with lower lipid concentrations, lower levels of oxidative stress markers, more decreased expression of hepatic aminotransferase, and more reduced stellate cell activation than those in the WT liver, reminiscent of human early NASH. Hepatocyte apoptosis was also significantly repressed in Tg mice. By contrast, serum adiponectin levels and hepatic adiponectin receptor expression were significantly lower in WT mice, consistent with greater insulin resistance in the peripheral liver tissue compared with Tg mice. Innovation and Conclusion: Our data for the first time show that PRDX4 may protect against NASH, T2DM, and the metabolic syndrome by ameliorating oxidative stress-induced injury. Antioxid. Redox Signal. 19, 1983–1998.
- Published
- 2013
47. Re–Os Pyrite Geochronological Evidence of Three Mineralization Styles within the Jinchang Gold Deposit, Yanji–Dongning Metallogenic Belt, Northeast China
- Author
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Ke-Yong Wang, Zhi-Gao Wang, Shun-da Li, Da-Wei Peng, Wen-yan Cai, Jie Li, and Li Xiao
- Subjects
Isochron ,Mineralization (geology) ,lcsh:Mineralogy ,lcsh:QE351-399.2 ,010504 meteorology & atmospheric sciences ,geochronology ,Geochemistry ,Geology ,Crust ,Yanji–Dongning Metallogenic Belt ,engineering.material ,010502 geochemistry & geophysics ,Geotechnical Engineering and Engineering Geology ,01 natural sciences ,Mantle (geology) ,Diorite ,Re–Os isotopes ,Breccia ,Geochronology ,engineering ,Pyrite ,Jinchang gold deposit ,0105 earth and related environmental sciences - Abstract
The Jinchang gold deposit is located in the eastern Yanji&ndash, Dongning Metallogenic Belt in Northeast China. The orebodies of the deposit are hosted within granite, diorite, and granodiorite, and are associated with gold-mineralized breccia pipes, disseminated gold in ores, and fault-controlled gold-bearing veins. Three paragenetic stages were identified: (1) early quartz&ndash, pyrite&ndash, arsenopyrite (stage 1), (2) quartz&ndash, chalcopyrite (stage 2), and (3) late quartz&ndash, galena&ndash, sphalerite (stage 3). Gold is hosted predominantly within pyrite. Pyrite separated from quartz&ndash, arsenopyrite cement within the breccia-hosted ores (Py1) yield a Re&ndash, Os isochron age of 102.9 ±, 2.7 Ma (MSWD = 0.17). Pyrite crystals from the quartz&ndash, chalcopyrite veinlets (Py2) yield a Re&ndash, Os isochron age of 102.0 ±, 3.4 Ma (MSWD = 0.2). Pyrite separated from quartz&ndash, sphalerite veins (Py3) yield a Re&ndash, Os isochron age of 100.9 ±, 3.1 Ma (MSWD = 0.019). Re&ndash, Os isotopic analyses of the three types of auriferous pyrite suggest that gold mineralization in the Jinchang Deposit occurred at 105.6&ndash, 97.8 Ma (includes uncertainty). The initial 187Os/188Os values of the pyrites range between 0.04 and 0.60, suggesting that Os in the pyrite crystals was derived from both crust and mantle sources.
- Published
- 2018
48. Histamine receptors expressed in circulating progenitor cells have reciprocal actions in ligation-induced arteriosclerosis
- Author
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Yasuyuki Sasaguri, Xin Guo, Ke-Yong Wang, Akihide Tanimoto, Atsunori Nabeshima, Sohsuke Yamada, and Takeshi Watanabe
- Subjects
medicine.medical_specialty ,General Medicine ,Arteriosclerosis ,Biology ,medicine.disease ,Histidine decarboxylase ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,Histamine receptor ,Endocrinology ,chemistry ,Internal medicine ,medicine ,biology.protein ,Progenitor cell ,Receptor ,Liver X receptor ,Histamine ,Platelet-derived growth factor receptor - Abstract
Histamine is synthesized as a low-molecular-weight amine from L-histidine by histidine decarboxylase (HDC). Recently, we demonstrated that carotid artery-ligated HDC gene-deficient mice (HDC(-/-)) showed less neointimal formation than wild-type (WT) mice, indicating that histamine participates in the process of arteriosclerosis. However, little is known about the roles of histamine-specific receptors (HHRs) in arteriosclerosis. To define the roles of HHRs in arteriosclerosis, we investigated intimal remodeling in ligated carotid arteries of HHR-deficient mice (H1R(-/-) or H2R(-/-)). Quantitative analysis showed that H1R(-/-) mice had significantly less arteriosclerogenesis, whereas H2R(-/-) mice had more, as compared with WT mice. Bone marrow transplantation from H1R(-/-) or H2R(-/-) to WT mice confirmed the above observation. Furthermore, the increased expression of monocyte chemoattractant protein (MCP-1), platelet-derived growth factor (PDGF), adhesion molecules and liver X receptor (LXR)-related inflammatory signaling factors, including Toll-like receptor (TLR3), interleukin-1 receptor (IL-1R) and tumor necrosis factor receptor (TNF-R), was consistent with the arteriosclerotic phenotype of H2R(-/-) mice. Peripheral progenitor cells in H2R(-/-) mice accelerate ligation-induced arteriosclerosis through their regulation of MCP-1, PDGF, adhesion molecules and LXR-related inflammatory signaling factors. In contrast, peripheral progenitor cells act to suppress arteriosclerosis in H1R(-/-) mice, indicating that HHRs reciprocally regulate inflammation in the ligation-induced arteriosclerosis.
- Published
- 2013
49. Sol-Gel Derived TiO2 Coating on Hydrothermally Roughened NiTi Alloy
- Author
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Chen Zhang, Zafer Alajmi, Bing Hui Dong, Ke Yong Wang, and Tao Fu
- Subjects
Contact angle ,Anatase ,Materials science ,Nickel titanium ,Metallurgy ,General Engineering ,Nanoparticle ,Composite material ,Hydrothermal circulation ,Titanate ,Corrosion ,Sol-gel - Abstract
Nearly equiatomic NiTi alloy is hydrothermally treated in a urea solution at 150°C to form nanostructures at the surface, with the aim to improve the structural quality of sol-gel deposited TiO2 film. Nanosheets film of ammonium titanate is formed on NiTi alloy after 8 h hydrothermal treatment, and the sol-gel TiO2 film on it is smooth and crack-free. Anatase TiO2 films consisting of nanoparticles and granular deposits are formed on the NiTi samples hydrothermally treated for 16 h and 24 h. The subsequently deposited TiO2 films have short cracks, because the nanostructured films can not completely balance volume shrinkage of the gel film during the drying and heat treatment processes. Water contact angles of the duplex treated NiTi samples increase during ageing in air, but are all reduced to below 10 after 2 h UV irradiation treatment. Potentiodynamic polarization tests in 0.9% NaCl solution indicate that the duplex treated NiTi samples have much better corrosion resistance than the polished one.
- Published
- 2013
50. Apoptosis Signal–Regulating Kinase 1 Deficiency Attenuates Vascular Injury–Induced Neointimal Hyperplasia by Suppressing Apoptosis in Smooth Muscle Cells
- Author
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Hirotsugu Noguchi, Ke-Yong Wang, Shohei Kitada, Yasuyuki Sasaguri, Takashi Tasaki, Shohei Shimajiri, Xin Guo, Kimitoshi Kohno, Sohsuke Yamada, Satoshi Kimura, Hidenori Ichijo, Atsunori Nabeshima, and Akihide Tanimoto
- Subjects
Male ,Myocytes, Smooth Muscle ,Becaplermin ,Apoptosis ,Biology ,MAP Kinase Kinase Kinase 5 ,p38 Mitogen-Activated Protein Kinases ,Pathology and Forensic Medicine ,Mice ,Stress, Physiological ,Neointima ,medicine ,Myocyte ,Animals ,ASK1 ,Phosphorylation ,Protein kinase A ,Ligation ,Aorta ,Cells, Cultured ,Cell Proliferation ,Neointimal hyperplasia ,Inflammation ,Hyperplasia ,Cell adhesion molecule ,Kinase ,Tumor Necrosis Factor-alpha ,Proto-Oncogene Proteins c-sis ,medicine.disease ,Immunohistochemistry ,Mice, Inbred C57BL ,Carotid Arteries ,Gene Expression Regulation ,cardiovascular system ,Cancer research ,Tumor necrosis factor alpha ,Cell Adhesion Molecules ,Signal Transduction - Abstract
Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays a crucial role in stress-induced apoptosis. Recently, we have reported that suppressed macrophage apoptosis in ASK1 and apolipoprotein E double-knockout mice accelerates atheromatous plaques in the hyperlipidemia-induced atherosclerotic model. However, the pathogenic role of smooth muscle cell (SMC) apoptosis in atherosclerosis still remains unclear. We investigated neointimal remodeling in ligated carotid arteries of ASK1-deficient mice (ASK1(-/-)) for 3 weeks. ASK1(-/-) mice had significantly more suppressed intimal formation, inversely manifesting as potential anti-atherogenic aspects of ASK1 deficiency, characterized by fewer SMCs and less collagen synthesis; and fewer apoptotic SMCs, infiltrating T lymphocytes, and microvessels, associated with decreased apoptosis of luminal endothelial cells, compared with those of wild-type mice. Injured arteries of ASK1(-/-) mice also showed significantly down-regulated expression of pro-apoptotic markers, adhesion molecules, and pro-inflammatory signaling factors. Moreover, tumor necrosis factor-α-induced apoptosis was markedly suppressed in cultured aortic SMCs from ASK1(-/-) mice. These findings suggest that ASK1 accelerates mechanical injury-induced vascular remodeling with activated SMC migration via increased neovascularization and/or enhanced SMC and endothelial cell apoptosis. ASK1 expression, especially in the SMCs, might be crucial, and reciprocally responsible for various pro-atherogenic functions, and SMC apoptosis seems to be detrimental in this model.
- Published
- 2013
- Full Text
- View/download PDF
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