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1.
Nature ; 618(7967): 921-927, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37380691

RESUMO

Spin-triplet topological superconductors should exhibit many unprecedented electronic properties, including fractionalized electronic states relevant to quantum information processing. Although UTe2 may embody such bulk topological superconductivity1-11, its superconductive order parameter Δ(k) remains unknown12. Many diverse forms for Δ(k) are physically possible12 in such heavy fermion materials13. Moreover, intertwined14,15 density waves of spin (SDW), charge (CDW) and pair (PDW) may interpose, with the latter exhibiting spatially modulating14,15 superconductive order parameter Δ(r), electron-pair density16-19 and pairing energy gap17,20-23. Hence, the newly discovered CDW state24 in UTe2 motivates the prospect that a PDW state may exist in this material24,25. To search for it, we visualize the pairing energy gap with µeV-scale energy resolution using superconductive scanning tunnelling microscopy (STM) tips26-31. We detect three PDWs, each with peak-to-peak gap modulations of around 10 µeV and at incommensurate wavevectors Pi=1,2,3 that are indistinguishable from the wavevectors Qi=1,2,3 of the prevenient24 CDW. Concurrent visualization of the UTe2 superconductive PDWs and the non-superconductive CDWs shows that every Pi:Qi pair exhibits a relative spatial phase δϕ ≈ π. From these observations, and given UTe2 as a spin-triplet superconductor12, this PDW state should be a spin-triplet PDW24,25. Although such states do exist32 in superfluid 3He, for superconductors, they are unprecedented.

2.
Nat Mater ; 23(4): 492-498, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38438620

RESUMO

The primordial ingredient of cuprate superconductivity is the CuO2 unit cell. Theories usually concentrate on the intra-atom Coulombic interactions dominating the 3d9 and 3d10 configurations of each copper ion. However, if Coulombic interactions also occur between electrons of the 2p6 orbitals of each planar oxygen atom, spontaneous orbital ordering may split their energy levels. This long-predicted intra-unit-cell symmetry breaking should generate an orbitally ordered phase, for which the charge transfer energy ε separating the 2p6 and 3d10 orbitals is distinct for the two oxygen atoms. Here we introduce sublattice-resolved ε(r) imaging to CuO2 studies and discover intra-unit-cell rotational symmetry breaking of ε(r). Spatially, this state is arranged in disordered Ising domains of orthogonally oriented orbital order bounded by dopant ions, and within whose domain walls low-energy electronic quadrupolar two-level systems occur. Overall, these data reveal a Q = 0 orbitally ordered state that splits the oxygen energy levels by ~50 meV, in underdoped CuO2.

3.
Metab Brain Dis ; 37(7): 2277-2290, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35751788

RESUMO

Long non-coding RNAs (lncRNAs) have been confirmed to be involved in epilepsy development. It has been reported that lncRNA ZFAS1 plays a vital regulatory role in epilepsy progression. Therefore, the role and molecular mechanism of ZFAS1 in epilepsy progression deserve further investigation. Mice status epilepticus (SE) model was constructed, and hippocampal neurons were isolated from mice hippocampus tissues. The expression of ZFAS1, miR-15a-5p and oxidative stress responsive 1 (OXSR1) were determined by quantitative real-time PCR. ELISA assay was used to detect the concentrations of inflammation factors. Cell viability and apoptosis were examined by MTT assay, EdU staining and flow cytometry. Western blot analysis was conducted to measure protein levels, and the productions of SOD and MDA were measured to assess cell oxidative stress. Dual-luciferase reporter assay and RIP assay were employed to validate the relationship between miR-15a-5p and ZFAS1 or OXSR1. LncRNA ZFAS1 was highly expressed in SE mice and SE-stimulated hippocampal neurons. Silenced ZFAS1 promoted viability, while inhibited inflammation, apoptosis and oxidative stress in SE-induced hippocampal neurons. MiR-15a-5p could be targeted by ZFAS1, and its inhibitor also reversed the suppressive effect of ZFAS1 knockdown on SE-induced hippocampal neurons injury. In addition, OXSR1 was a target of miR-15a-5p, and its silencing also could relieve SE-induced hippocampal neurons injury. OXSR1 overexpression reversed the inhibition effect of miR-15a-5p on SE-induced hippocampal neurons injury. Moreover, ZFAS1 positively regulated OXSR1 expression by sponging miR-15a-5p, thereby activating the NF-κB pathway. LncRNA ZFAS1 might contribute to the progression of epilepsy by regulating the miR-15a-5p/OXSR1/NF-κB pathway.


Assuntos
Epilepsia , MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , RNA Longo não Codificante/metabolismo , NF-kappa B/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Apoptose/genética , Neurônios/metabolismo , Hipocampo/metabolismo , Epilepsia/genética , Inflamação , Superóxido Dismutase/metabolismo
4.
Zhonghua Nan Ke Xue ; 19(11): 972-6, 2013 Nov.
Artigo em Zh | MEDLINE | ID: mdl-24341088

RESUMO

OBJECTIVE: To explore the pathogenesis of male sexual dysfunction by studying cell apoptosis and carbonate monoxide (CO) contents in the penile tissue of rats at different ages. METHODS: We equally divided 24 male Wistar rats into an adult group (8 months old), an elderly group (16 months old) and an aged group (24 months old), and detected cell apoptosis by HE staining and TUNEL and CO levels in the penile tissues of different groups by modified dual-wavelength spectrophotometry. RESULTS: Cell apoptosis increased with aging: 4.38 +/- 1.06 in the adult, 9.38 +/- 1.69 in the elderly and 18.50 +/- 1.60 in the aged group, while the CO content decreased with aging: 12.19 +/- 0.87 in the adult, 7.93 +/- 0.63 in the elderly and 5.68 +/- 0.62 in the aged group, both with statistically significant differences among the 3 groups (P < 0.05). The change of cell apoptosis showed a good negative correlation with that of the CO content (r = -0.889, P < 0.01). CONCLUSION: Cell apoptosis and CO content change in the penile tissue of aging rats, and CO may participate in the development of ED by regulating cell apoptosis.


Assuntos
Envelhecimento , Apoptose , Monóxido de Carbono/metabolismo , Pênis/citologia , Pênis/metabolismo , Animais , Masculino , Ratos , Ratos Wistar
5.
Zhonghua Nan Ke Xue ; 19(5): 398-402, 2013 May.
Artigo em Zh | MEDLINE | ID: mdl-23757959

RESUMO

OBJECTIVE: To study the changes in the activities of carbon monoxide (CO) and heme oxygenase 2 (HO-2) in ED rats with hyperhomocysteinemia (HHcy). METHODS: This study included 40 male Wistar rats weighing 280 - 310 g, 10 as normal controls (group A). HHcy models were made in the other 30 by giving 3% methionine for 4 weeks, and then divided into groups B, C and D. The rats in group B continued to be fed with 3% methionine, those in group C were treated with betaine hydrochloride, and those in group D were given zinc porphyrin IX at 45 micromol per kg per d. Penile erections of the rats were recorded, and 4 weeks later, all were killed for determination of the levels of homocysteine (Hcy) in the blood plasma and the activities of CO and HO-2 in the corpus cavernosum of the penis. RESULTS: The level of plasma Hcy, penile erection frequency and the content of CO in the corpus cavernosum were (12.55 +/- 0.82) micromol/L, (1.88 +/- 0.05) times and (10.55 +/- 1.73) micromol/L in group A, the Hcy level significantly higher while the penile erection frequency and CO content remarkably lower than in group B ([25.01 +/- 0.94] micromol/L, [0.70 +/- 0.05] times and [9.51 +/- 1.52] micromol/L, P < 0.05 or P < 0.01), with a negative correlation between the level of Hcy and that of CO and HO-2 (P < 0.01). Compared with group B, the three parameters were all significantly increased in C ([14.37 +/- 0.47] micromol/L, [1.18 +/- 0.08] times and [10.36 +/- 1.56] micromol/L, all P < 0.05 or P < 0.01). CONCLUSION: Decreased expressions of CO and HO-2 in the corpus cavernosum of the penis may result in ED in HHcy rats. Betaine can reduce the Hcy level in the blood plasma and CO content in the corpus cavernosum, which might be one of the mechanisms of its action on ED with HHcy.


Assuntos
Disfunção Erétil/sangue , Heme Oxigenase (Desciclizante)/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/metabolismo , Pênis/metabolismo , Animais , Monóxido de Carbono/sangue , Disfunção Erétil/metabolismo , Hiper-Homocisteinemia/sangue , Masculino , Ratos , Ratos Wistar
6.
Zhonghua Nan Ke Xue ; 18(2): 126-9, 2012 Feb.
Artigo em Zh | MEDLINE | ID: mdl-22568208

RESUMO

OBJECTIVE: To study the correlation of homocysteine (Hcy) in plasma with nitric oxide synthetase (NOS) and endogenous carbon monoxide (CO) in the penile corpus cavernosum of type 2 diabetic rats. METHODS: This study included 40 male Wistar rats, 10 as controls (Group A) and the other 30 as diabetes mellitus (DM) models. Four weeks after the model establishment, the model rats were divided into a DM group (Group B, n = 10), an insulin treated group (Group C, n = 10), and a folic acid and vitamin B12 treated group (Group D, n = 10). All the rats were injected with apomorphine and observed for penile erection at 8 and 12 weeks, and the levels of total plasma Hcy (tHcy), NOS and CO in the penile corpus cavernosum were measured at 12 weeks. RESULTS: Compared with Group A, the level of tHcy was significantly increased, while NOS and CO activities in the penile cavernous tis-sue and erectile function remarkably decreased in Group B (P < 0.01). The incidence rate of high Hcy was 55% in the DM rats. In comparison, the level of tHcy was obviously decreased, and the NOS activity and erectile function markedly increased in Groups C and D (P < 0.01). The Hcy level showed a significant negative correlation with NOS activity (rA = -0.89, rB = -0.76, rc = -0.91, rD = -0.91) and CO content (TA = -0.82, r, = -0.77, rc = -0.93, rD = -0.81). CONCLUSION: High plasma Hcy can decrease NOS and CO activities in the penile corpus cavernosum, and consequently induce erectile dysfunction in DM rats, while insulin, folic acid and vitamin B12 can improve their penile erectile function by increasing NOS and CO activities.


Assuntos
Monóxido de Carbono/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Homocisteína/sangue , Óxido Nítrico Sintase/metabolismo , Pênis/metabolismo , Animais , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Ácido Fólico/farmacologia , Insulina/farmacologia , Masculino , Pênis/efeitos dos fármacos , Ratos , Ratos Wistar , Vitamina B 12/farmacologia
7.
Dis Markers ; 2022: 5709259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783012

RESUMO

Background: Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients. Methods: Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting. Results: Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins. Conclusion: The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.


Assuntos
Metformina , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Ftalazinas , Piperazinas , Proteínas Proto-Oncogênicas c-myc , Transdução de Sinais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia
8.
Biomed Res Int ; 2022: 5940372, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093409

RESUMO

Ganoderic acid A (GAA) exhibited neuron protection in in vitro epilepsy study, but no study has been done in vivo. Rats were administered (i.p.) pentylenetetrazole daily for 28 days to induce seizure. Rats with grade II or above of epileptic score were divided into three groups and given placebo, sodium valproate, or GAA treatment, respectively, for 7 days. The electrical signals of brain were monitored with electroencephalography (EGG); epileptic behavior was assessed using the Racine scale; morphological changes and apoptosis rate of cortical neurons were assessed with H&E staining and TUNEL staining, respectively. Protein expression of calcium-sensing receptor, p-ERK, p-JNK, and p-p38 in hippocampal tissue and Bcl-2, cleaved caspase-3, and Bax in cortical tissues was observed by Western blot and immunohistochemistry assay, respectively. After GAA treatment, apparent seizure-like EEG with significant arrhythmic disorder and spike waves was reduced or disappeared, and wave amplitude of EEG was reduced significantly. GAA showed similar effect with sodium valproate treatments on epilepsy. There were an apparent improvement of the epileptic behavior and a significant increase in the epileptic latency and shortening of the epileptic duration in the treatment group compared to control. GAA treatment ameliorated the nuclear pyknosis of neurons which appeared seriously in the epilepsy group. GAA treatment significantly reduced the cortical neuron apoptosis of epilepsy and the expression of calcium-sensing receptor, p-P38, p-JNK, cleaved caspase-3, and Bax but increased the expression of both p-ERK and Bcl-2. In conclusion, GAA treatment showed strong antiepileptic effect by decreasing apoptosis in cortical neuron and the expression of calcium-sensing receptor and stimulating the MAPK pathway.


Assuntos
Epilepsia , Pentilenotetrazol , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Caspase 3/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Ácidos Heptanoicos , Lanosterol/análogos & derivados , Pentilenotetrazol/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Receptores de Detecção de Cálcio , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Ácido Valproico/efeitos adversos , Proteína X Associada a bcl-2/metabolismo
9.
Biomed Res Int ; 2022: 4314415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299891

RESUMO

Ganoderma lucidum polysaccharides (GLP) have renal protection effect but there was no study on the diabetic nephropathy. This study was designed to investigate its effect and mechanism using a diabetic rat model induced by streptozotocin (50 mg/kg, i.p.). The diabetic rats were treated with GLP (300 mg/kg/day) for 10 weeks. The blood glucose, glycated hemoglobin, body weight, and the levels of blood creatinine, urea nitrogen, and urine protein were assessed. And renal pathologies were assessed by the tissue sections stained with hematoxylin-eosin, Masson's trichome, and periodic acid-Schiff. The expression of phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR), the autophagy proteins beclin-1, LC3-II, LC3-I, and P62; the apoptosis-related proteins caspase-3 and caspase-9; and the inflammation markers IL-6, IL-1ß, and TNF-ɑ were assessed. Results showed that GLP alleviated the impairment of renal function by reducing urinary protein excretion and the blood creatinine level and ameliorated diabetic nephropathy. The expression of p-PI3K, p-Akt, and p-mTOR in the diabetic kidney were significantly reduced in the GLP treatment group compared to the without treatment group. GLP treatment activated the autophagy indicators of beclin-1 and the ratio of LC3-II/LC3-I but reduced p62 and also inhibited the expression of caspase-3, caspase-9 and IL-6, IL-1ß, and TNF-ɑ. In conclusion, the effect of GLP amelioration diabetic nephropathy may be via the PI3k/Akt/mTOR signaling pathway by inhibition of the apoptosis and inflammation and activation of the autophagy process.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Polissacarídeos/farmacologia , Reishi , Animais , Biomarcadores/metabolismo , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental , Masculino , Ratos , Transdução de Sinais , Estreptozocina
10.
Biol Pharm Bull ; 34(2): 197-202, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21415527

RESUMO

Radix Lithosperm eyrthrorhizon is a common prescription compound in traditional Chinese medicine. Shikonin is a major component of Radix Lithospermi and has various biological activities. We have investigated the inhibitory effect of shikonin on the growth of adenovirus type 3 (AdV3) in vitro. The antiviral function of shikonin against AdV3 and its virus inhibition ratio were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method (MTT). The expression of hexon protein in AdV3 was determined by immunofluorescence assay using laser scanning confocal microscopy (LSCM) and Western blot analysis. In addition, the rate of apoptosis in cells infected by AdV3 was determined by flow cytometry. Shikonin (0.0156-1 µM) inhibited growth of AdV3 in a concentration-dependent manner with a virus inhibition rate of 23.8-69.1%. Expression of hexon protein in AdV3 was higher in the virus control group than in the shikonin-treated groups as determined by immunofluorescence assay and Western blotting (p<0.05). The rate of shikonin-treated HeLa cell apoptosis had a statistically significant decrease with increasing concentration of drug (p<0.05). Our data demonstrate that shikonin possesses anti-AdV3 capabilities and that the potential antiviral mechanism might involve inhibiting the degree of apoptosis and hexon protein expression of AdV.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Adenoviridae/efeitos dos fármacos , Antivirais/farmacologia , Proteínas do Capsídeo/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Lithospermum/química , Naftoquinonas/farmacologia , Adenoviridae/crescimento & desenvolvimento , Antivirais/uso terapêutico , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/uso terapêutico , Células HeLa , Humanos , Naftoquinonas/uso terapêutico , Fitoterapia , Raízes de Plantas
11.
Nat Commun ; 12(1): 6087, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34667154

RESUMO

An unidentified quantum fluid designated the pseudogap (PG) phase is produced by electron-density depletion in the CuO2 antiferromagnetic insulator. Current theories suggest that the PG phase may be a pair density wave (PDW) state characterized by a spatially modulating density of electron pairs. Such a state should exhibit a periodically modulating energy gap [Formula: see text] in real-space, and a characteristic quasiparticle scattering interference (QPI) signature [Formula: see text] in wavevector space. By studying strongly underdoped Bi2Sr2CaDyCu2O8 at hole-density ~0.08 in the superconductive phase, we detect the 8a0-periodic [Formula: see text] modulations signifying a PDW coexisting with superconductivity. Then, by visualizing the temperature dependence of this electronic structure from the superconducting into the pseudogap phase, we find the evolution of the scattering interference signature [Formula: see text] that is predicted specifically for the temperature dependence of an 8a0-periodic PDW. These observations are consistent with theory for the transition from a PDW state coexisting with d-wave superconductivity to a pure PDW state in the Bi2Sr2CaDyCu2O8 pseudogap phase.

12.
Cardiovasc Toxicol ; 21(4): 286-300, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33165770

RESUMO

Hypertension, as one of the major risk factors for cardiovascular disease, significantly affects human health. Prostaglandin E2 (PGE2) and the E3-class prostanoid (EP3) receptor have previously been demonstrated to modulate blood pressure and hemodynamics in various animal models of hypertension. The PGE2-evoked pressor and biochemical responses can be blocked with the EP3 receptor antagonist, L-798106 (N-[(5-bromo-2methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl) phenyl]-2-propenamide). In the hypothalamic paraventricular nucleus (PVN), sympathetic excitation can be introduced by PGE2, which can activate EP3 receptors located in the PVN. In such a case, the central knockdown of EP3 receptor can be considered as a potential therapeutic modality for hypertension management. The present study examined the efficacy of the PVN infusion of L-798106, by performing experiments on spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The rats were administered with chronic bilateral PVN infusion of L-798106 (10 µg/day) or the vehicle for 28 days. The results indicated that the SHRs had a higher mean arterial pressure (MAP), an increased Fra-like (Fra-LI) activity in the PVN, as well as a higher expression of gp91phox, mitogen-activated protein kinase (MAPK), and proinflammatory cytokines in the PVN compared with the WKYs. Additionally, the expression of Cu/Zn-SOD in the PVN of the SHRs was reduced compared with the WKYs. The bilateral PVN infusion of L-798106 significantly reduced MAP, as well as plasma norepinephrine (NE) levels in the SHRs. It also inhibited Fra-LI activity and reduced the expression of gp91phox, proinflammatory cytokines, and MAPK, whereas it increased the expression of Cu/Zn-SOD in the PVN of SHRs. In addition, L-798106 restored the balance of the neurotransmitters in the PVN. On the whole, the findings of the present study demonstrate that the PVN blockade of EP3 receptor can ameliorate hypertension and cardiac hypertrophy partially by attenuating ROS and proinflammatory cytokines, and modulating neurotransmitters in the PVN.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/prevenção & controle , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Antagonistas de Prostaglandina/farmacologia , Receptores de Prostaglandina E Subtipo EP3/antagonistas & inibidores , Sulfonamidas/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Modelos Animais de Doenças , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismo , Receptores de Prostaglandina E Subtipo EP3/metabolismo , Transdução de Sinais
13.
Diabetes Metab Syndr Obes ; 13: 4809-4822, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335409

RESUMO

BACKGROUND: Ganoderma lucidum spores (GLS) exhibit disease prevention properties, but no study has been carried out on the anti-diabetic cardiomyopathy property of GLS. The aim of this study was to evaluate the hyperglycemia-mediated cardiomyopathy protection and mechanisms of GLS in streptozotocin (STZ)induced diabetic rats. METHODS: Male SD rats were randomly divided into three groups. Two groups were given STZ (50 mg/kg, i.p.) treatment and when their fasting plasma glucose was above 16.7 mmol/L, among them, one group was given placebo, as diabetic group, and another group was given GLS (300 mg/kg) treatment. The group without STZ treatment was given placebo as a control group. The experiment lasted 70 days. The histology of myocardium and biomarkers of antioxidants, myocardial injury, pro-inflammatory cytokines, pro-apoptotic proteins and phosphorylation of key proteins in PI3K/AKT pathway were assessed. RESULTS: Biochemical analysis showed that GLS treatment significantly reduced the blood glucose (-20.3%) and triglyceride (-20.4%) levels compared to diabetic group without treatment. GLS treatment decreased the content of MDA (-25.6%) and activity of lactate dehydrogenase (-18.9%) but increased the activity of GSH-Px (65.4%). Western blot analysis showed that GLS treatment reduced the expression of both alpha-smooth muscle actin and brain natriuretic peptide. Histological analysis on the cardiac tissue micrographs showed that GLS treatment reduced collagen fibrosis and glycogen reactivity in myocardium. Both Western blot and immunohistochemistry analyses showed that GLS treatment decreased the expression levels of pro-inflammatory factors (cytokines IL-1ß, and TNF-α) as well as apoptosis regulatory proteins (Bax, caspase-3 and -9), but increased Bcl-2. Moreover, GLS treatment significantly increased the phosphorylation of key proteins involved in PI3K/AKT pathway, eg, p-AKT p-PI3K and mTOR. CONCLUSION: The results indicated that GLS treatment alleviates diabetic cardiomyopathy by reducing hyperglycemia, oxidative stress, inflammation, apoptosis and further attenuating the fibrosis and myocardial dysfunction induced by STZ through stimulation of the PI3K/Akt/mTOR signaling pathway.

14.
J Hazard Mater ; 398: 122819, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32506046

RESUMO

Papermaking raw materials are usually digested by NaOH and Na2S solution. The fate of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during the kraft pulping process is still poorly known. In this study, a comprehensive investigation was conducted on the variation in PCDD/Fs in the kraft pulping section of 3 modern non-wood pulp mills adopting elemental chlorine-free (ECF) bleaching technology. Similar dioxin homologue profiles, dominated by Cl1-3DF and Cl2DD homologues, were observed in the raw materials, black liquors and brown pulps; and the partitioning behaviors of dioxin congeners between black liquor and brown pulp were found to be partly dependent on their octanol-water partitioning coefficients. Dioxin mass flow analysis indicated that the raw materials contributed more than 95 % to the dioxins entering the pulping section. Approximately 7 - 30 % of the input dioxins were exported by black liquor, and the brown pulp carried 44 - 51 % of the input dioxins into the subsequent bleaching section. The kraft pulping process caused a 40 - 48 % reduction in input dioxins. Alkaline hydrolysis and coupling reaction between dioxins and the aromatic fragments of lignin were proposed as two most possible mechanisms for dioxin elimination. In general, modern pulp mills have actually become industrial plants that eliminate environmental dioxins.

15.
Biomed Res Int ; 2020: 7136075, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32775437

RESUMO

Even with substantial advances in cardiovascular therapy, the morbidity and mortality rates of diabetic cardiomyopathy (DCM) continually increase. Hence, a feasible therapeutic approach is urgently needed. Objectives. This work is aimed at systemically reviewing literature and addressing cell targets in DCM through the possible cardioprotection of G. lucidum through its antioxidant effects by using the Open Targets Platform (OTP) website. Methods. The OTP website version of 19.11 was accessed in December 2019 to identify the studies in DCM involving G. lucidum. Results. Among the 157 cell targets associated with DCM, the mammalian target of rapamycin (mTOR) was shared by all evidence, drug, and text mining data with 0.08 score association. mTOR also had the highest score association 0.1 with autophagy in DCM. Among the 1731 studies of indexed PubMed articles on G. lucidum published between 1985 and 2019, 33 addressed the antioxidant effects of G. lucidum and its molecular signal pathways involving oxidative stress and therefore were included in the current work. Conclusion. mTOR is one of the targets by DCM and can be inhibited by the antioxidative properties of G. lucidum directly via scavenging radicals and indirectly via modulating mTOR signal pathways such as Wnt signaling pathway, Erk1/2 signaling, and NF-κB pathways.


Assuntos
Antioxidantes , Cardiotônicos , Cardiomiopatias Diabéticas , Extratos Vegetais , Reishi/química , Antioxidantes/química , Antioxidantes/uso terapêutico , Cardiotônicos/química , Cardiotônicos/uso terapêutico , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
16.
Zhonghua Nan Ke Xue ; 15(2): 122-5, 2009 Feb.
Artigo em Zh | MEDLINE | ID: mdl-19323370

RESUMO

OBJECTIVE: To explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats. METHODS: Twenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry. RESULTS: The contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01). CONCLUSION: Aging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.


Assuntos
Envelhecimento/fisiologia , Monóxido de Carbono/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Pênis/metabolismo , Animais , Masculino , Ratos , Ratos Wistar
17.
Epilepsy Res ; 156: 106183, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31404716

RESUMO

To investigate the neuroprotective effect of ferulic acid (FA) in a pentylenetetrazol (PTZ)-induced seizures model in rat, the motor response, spatial learning ability and memory capability of the rats were assessed. Both the antioxidation and anti-apoptosis pathways were also investigated. In this study, male Wistar rats were randomly divided into 3 groups (n = 12 in each group). For 28 days, the rats were administered saline alone (i.p. normal saline, NS group), PTZ (40 mg/kg, i.p., PTZ group) once daily to induce seizures, or FA (i.p. 60 mg/kg) 20 min before being given PTZ (40 mg/kg, i.p., FA + PTZ group) to assess the neuroprotective effect of FA. The motor response of the rats was analysed with the Racine scale. The spatial learning and memory capacity of the rats were assessed by the Morris water maze test. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and both in situ staining with the DNA-binding bisbenzimide Hoechst 33258 and TUNEL assays were used to assess apoptosis. Western blotting was used to further analyse the expression of Apaf-1, caspase-9, caspase-3, Bcl-2, Bid, Bax, cleaved caspase-3 and cytochrome c. The results showed that compared to the those of the PTZ group, FA pre-treatment significantly (p < 0.01) reduced the Racine scores starting at day 4, prolonged the latency of the onset of seizure at day 28, reduced the escape latency period starting at day 2, increased the frequency of crossing the platform location, increased the SOD activity, reduced the MDA content and apoptosis percentage, and upregulated the Bcl-2 levels whilst downregulating the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3 and Bid expression levels. This study demonstrated that pre-treatment with FA exerts strong neuroprotective effects by reducing the motor response and by improving spatial learning ability and memory capacity. The neuroprotective effect may be a result of a reduction in neuron cell death that occurs via the antioxidative and anti-apoptotic pathways.


Assuntos
Antioxidantes/farmacologia , Convulsivantes/farmacologia , Neurônios/efeitos dos fármacos , Pentilenotetrazol/farmacologia , Convulsões/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Ácidos Cumáricos , Malondialdeído/metabolismo , Malondialdeído/farmacologia , Memória/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/metabolismo
18.
Nanoscale ; 11(5): 2412-2422, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30667032

RESUMO

Two-dimensional materials with a honeycomb lattice, such as graphene and hexagonal boron nitride, often contain local defects in which the hexagonal elements are replaced by four-, five-, seven-, and eight-membered rings. An example is the Stone-Wales (S-W) defect, where a bond rotation causes four hexagons to be transformed into a cluster of two pentagons and two heptagons. A further series of similar defects incorporating divacancies results in larger structures of non-hexagonal elements. In this paper, we use scanning tunneling microscopy (STM) and density functional theory (DFT) modeling to investigate the structure and energetics of S-W and divacancy defects in a honeycomb (2 × 2) Ti2O3 monolayer grown on an Au(111) substrate. The epitaxial rumpled Ti2O3 monolayer is pseudomorphic and in a state of elastic compression. As a consequence, divacancy defects, which induce tension in freestanding films, relieve the compression in the epitaxial Ti2O3 monolayer and therefore have significantly lower energies when compared with their freestanding counterparts. We find that at the divacancy defect sites there is a local reduction of the charge transfer between the film and the substrate, the rumpling is reduced, and the film has an increased separation from the substrate. Our results demonstrate the capacity of the substrate to significantly influence the energetics, and hence favor vacancy-type defects, in compressively strained 2D materials. This approach could be applied more broadly, for example to tensile monolayers, where vacancy-type defects would be rare and interstitial-type defects might be favored.

19.
Zhonghua Nan Ke Xue ; 14(9): 792-5, 2008 Sep.
Artigo em Zh | MEDLINE | ID: mdl-18998461

RESUMO

OBJECTIVE: To investigate the changes of xanthine oxidase (XOD), myeloperoxidase (MPO) and mitochondrial succinate dehydrogenase (SDH) in the testis and the protective effect of ganoderma lucidum spores on the testicular tissue of rats with non-insu- lin-dependent diabetes mellitus (NIDDM). METHODS: Fifty male Wistar rats were divided randomly into a model, a ganoderma and a normal control group, the first two groups injected with 2% STZ (25 mg/kg) through the peritoneum, and the last one with half-and-half sodium citrate/citrate buffer solution. Two weeks after normal diet, glucose tolerance tests were performed and the rats with abnormal glucose tolerance in the model and ganoderma groups received high-fat and high-carbohydrate food, the latter given ganoderma lycium spores (250 mg/kg x d) in addition, both for 10 weeks and all rats fed alone. Glucose tolerance tests were repeated 1 day before the end of the experiment and the testes of the rats were harvested for the determination of XOD, MPO and SDH. RESULTS: SDH was significantly lower (P < 0.05) while XOD and MPO significantly higher in the model group than in the ganoderma and control groups (P < 0.05). The model rats exhibited abnormal convoluted seminiferous tubules, indistinct parietal layers, decreased or abolished gonepoiesis, luminal peripheral fibrous tissue (interstitial substance) accrementition, basal lamina thickening, and vessel wall fibrous tissue accrementition and sclerosis. CONCLUSION: Ganoderma lucidum spores can protect the testis of diabetic rats by reducing free radical-induced damage to the testicular tissue and enhancing the activity of SDH.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Reishi , Testículo/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Esporos Fúngicos , Succinato Desidrogenase/metabolismo , Xantina Oxidase/metabolismo
20.
Adv Struct Chem Imaging ; 4(1): 7, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29930895

RESUMO

The usual way to present images from a scanning tunneling microscope (STM) is to take multiple images of the same area, to then manually select the one that appears to be of the highest quality, and then to discard the other almost identical images. This is in contrast to most other disciplines where the signal to noise ratio (SNR) of a data set is improved by taking repeated measurements and averaging them. Data averaging can be routinely performed for 1D spectra, where their alignment is straightforward. However, for serial-acquired 2D STM images the nature and variety of image distortions can severely complicate accurate registration. Here, we demonstrate how a significant improvement in the resolving power of the STM can be achieved through automated distortion correction and multi-frame averaging (MFA) and we demonstrate the broad utility of this approach with three examples. First, we show a sixfold enhancement of the SNR of the Si(111)-(7 × 7) reconstruction. Next, we demonstrate that images with sub-picometre height precision can be routinely obtained and show this for a monolayer of Ti2O3 on Au(111). Last, we demonstrate the automated classification of the two chiral variants of the surface unit cells of the (4 × 4) reconstructed SrTiO3(111) surface. Our new approach to STM imaging will allow a wealth of structural and electronic information from surfaces to be extracted that was previously buried in noise.

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