Ampelopsin, a flavonoid with a wide variety of biological activities, has been proposed to be a potent antitumor agent. However, the mechanism by which Ampelopsin shows anti-breast cancer activity ...remains unclear. Therefore, this study will explore the mechanism of Ampelopsin’s anti-breast cancer activity by culturing MDA-MB-231 and MCF-7 breast cancer cells. Cell Counting Kit-8 (CCK-8) method and plate cloning method were used to detect the proliferation inhibition of breast cancer cells. Fluorescence microscopy was used to detect mitochondrial membrane potential (MMP). 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA) method was used to determine the content of intracellular reactive oxygen species (ROS). Hoechst 33258 staining was used to detect the apoptotic morphological changes. Transmission electron microscope was used to observe the mitochondrial structure. Western blot was used to detect the protein expression of Bax and Bcl-2. The results showed that Ampelopsin could significantly inhibit the proliferation of breast cancer cells, and promote cells apoptosis. In addition, the occurrence of apoptosis in breast cancer cells was associated with mitochondrial dysfunction, including the loss of mitochondrial membrane potential, the production of large amounts of reactive oxygen species, and the up-regulation of Bax/Bcl-2 expression. In conclusion, Ampelopsin-induced mitochondria damage leads to loss of mitochondria membrane potential, overproduction of ROS and activation of Bax, increasing mitochondria membrane permeability and ultimately inducing breast cell apoptosis. These findings provided a new perspective on the role of Ampelopsin in breast cancer prevention and treatment.
Abstract We present a study of seven spectroscopically confirmed (Ly α -emitting) galaxies at redshift z ≃ 6 using the JWST/NIRCam imaging data. These galaxies, with a wide range of Ly α ...luminosities, were recently observed in a series of NIRCam broad and medium bands. We constrain the rest-frame UV/optical continua and measure the H α line emission of the galaxies using the combination of JWST/NIRCam and archival HST/WFC3 infrared photometry. We further estimate the escape fractions of their Ly α photons ( f esc Ly α ) and the production efficiency of ionizing photons ( ξ ion ). Among the sample, six out of seven galaxies have Ly α escape fractions of ≲10%, which might be the status for most of the star-forming galaxies at z ≃ 6. One UV-faint Ly α galaxy with an extremely blue UV slope has a large value of f esc Ly α reaching ≃50%. These galaxies have a broad range of ξ ion over log 10 ξ ion,0 (Hz erg −1 ) ∼ 25.0–26.5. We find that UV-fainter galaxies with bluer UV-continuum slopes likely have higher escape fractions of Ly α photons. We also find that galaxies with higher Ly α line emission tend to produce ionizing photons more efficiently. The most Ly α -luminous galaxy in the sample has a very high ξ ion,0 of log 10 ξ ion,0 (Hz erg −1 ) > 26. Our results support the scenario that Ly α galaxies may have served as an important contributor to cosmic reionization. Blue and bright Ly α galaxies are excellent targets for JWST follow-up spectroscopic observations.
Androgen receptor (AR) has been reported to play vital roles in exercise-induced increase of muscle mass in rats, but needs to be further verified and the mechanism behind remains unclear. As AR ...target genes, insulin growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) promote muscle hypertrophy through activating PI3K/Akt- mammalian target of rapamycin (mTOR) pathway, a classic pathway of muscle hypertrophy. So the main purpose of this study was using AR antagonist flutamide to demonstrate AR's effect on training-induced muscle hypertrophy and its possible mechanism: IGF-1/IGF-1R- PI3K/Akt- mTOR pathway?
Forty-eight Sprague Dawley male rats aged 7 weeks were randomly divided into six groups: control (C), flutamide (F), resistance training (R), resistance training plus flutamide (R + F), endurance training (E), and endurance training plus flutamide (E + F) groups. Flutamide was used to block AR in rats. Rats in R and R + F groups fulfilled 3 weeks of ladder climbing with progressively increased load, while E and E + F rats completed 3-week moderate intensity aerobic exercise on a treadmill. The relative muscle mass (muscle mass/body weight) of rats was detected. Serum levels of testosterone and IGF-1 of rats were determined by ELISA, and mRNA levels of IGF-1R and mTOR in muscles by real-time PCR. Protein levels of AR, IGF-1, IGF-1R, mTOR, PI3K, Akt, p-PI3K and p-Akt in muscles were detected by Western blot.
(1) The training-induced rise in the relative muscle mass and the expression levels of AR were only found in the gastrocnemius of R rats and in the soleus of E rats (selective muscle hypertrophy), which were blocked by flutamide. (2) Serum testosterone in the R and E rat were increased, and flutamide exerted no effect. (3) The levels of IGF-1, IGF-1R and mTOR as well as the activities of PI3K and Akt were enhanced selectively (in the gastrocnemius of R rats and in the soleus of E rats), which were reduced by flutamide.
AR exerted an essential role in both resistance training and endurance training-induced muscle hypertrophy, which was mediated at least partly through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Myoblast proliferation is crucial to skeletal muscle hypertrophy and regeneration. Our previous study indicated that mechanical stretch altered the proliferation of C2C12 myoblasts, associated with ...insulin growth factor 1 (IGF-1)-mediated phosphoinositide 3-kinase (PI3K)/Akt (also known as protein kinase B) and mitogen-activated protein kinase (MAPK) pathways through IGF-1 receptor (IGF-1R). The purpose of this study was to explore the same stretches on the proliferation of L6 myoblasts and its association with IGF-1-regulated PI3K/Akt and MAPK activations. L6 myoblasts were divided into three groups: control, 15% stretch, and 20% stretch. Stretches were achieved using FlexCell Strain Unit. Cell proliferation and IGF-1 concentration were detected by CCK8 and ELISA, respectively. IGF-1R expression, and expressions and activities of PI3K, Akt, and MAPKs (including extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38) were determined by Western blot. We found that 15% stretch promoted, while 20% stretch inhibited L6 myoblast proliferation. A 15% stretch increased IGF-1R level, although had no effect on IGF-1 secretion of L6 myoblasts, and PI3K/Akt and ERK1/2 (not p38) inhibitors attenuated 15% stretch-induced pro-proliferation. Exogenous IGF-1 reversed 20% stretch-induced anti-proliferation, accompanied with increases in IGF-1R level as well as PI3K/Akt and MAPK (ERK1/2 and p38) activations. In conclusion, stretch regulated L6 myoblasts proliferation, which may be mediated by the changes in PI3K/Akt and MAPK activations regulated by IGF-1R, despite no detectable IGF-1 from stretched L6 myoblasts.
Heat stroke is characterized by hyperthermia, systemic inflammation, and multiple organ failure including arterial hypotension. This definition can be fulfilled by a rat model of heat stroke used in ...the present study. Anesthetized animals were exposed to heat exposure (43 °C for 70 min) and then returned to room temperature (26 °C) for recovery. One hour before heat exposure, an intraperitoneal dose of quercetin (30 mg/kg) or vehicle (normal saline 1 ml/kg) was administered to the experimental groups of rats. Additional injection was administered immediately after the onset of heat stroke. Immediately after the onset of heat stroke. Vehicle-treated rats displayed (i) hyperthermia; (ii) suppressed left ventricular function; (iii) decreased contents of cardiac total antioxiant capacity (e.g., superoxide dismutase, glutathione peroxidase, catalase); (iv) increased contents of cardiac oxidative capacity malondialdehyde and thiobarbituric acid reactive substances; (v) increased cardiac levels of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6; and (vi) decreased cardiac levels of an anti-inflammatory cytokine interleukin 10. Histopathologic and survival observation provided supportive evidence for biochemical analyses. These heat stroke reactions all can be significantly attenuated by quercetin therapy. Our data suggest that quercetin therapy might improve outcomes of heat stroke in rats by attenuating excessive hyperthermia as well as myocardial injury. The protective effects of quercetin could be attributed to anti-lipid peroxidative, anti-oxidant, and anti-inflammatory properties.
•Heat stroke male rats displayed hyperthermia, hypotension, and myocardial inflammation and oxidative stress.•Hypothermia is related to myocardial inflammation and oxidative injury in heat stroke.•Quercetin protects against heat stroke-induced hyperthermia, hypotension, and myocardial injury.•Quercetin may exert its protection via anti-oxidant and anti-inflammatory action.
Androgen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous ...study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR's role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified. Firstly, the discrepancy in proliferation and the above indicators between L6 (without AR) and C2C12 (with AR) myoblasts were compared under 15% or 20% stretch. Then the influences of transfection AR or exogenous IGF-1 treatment on proliferation and these indicators were detected in stretched L6 myoblasts. (1) Under un-stretched state, the proliferation of L6 was slower than C2C12 cells. Furthermore, AR knockdown in C2C12 myoblasts repressed, while AR overexpression in L6 myoblasts promoted the proliferation. (2) 15% stretch-induced increases in the proliferation and activities of p38 and ERK1/2 were lower in L6 than C2C12 cells; AR overexpression enhanced the proliferation of 15% stretched L6 cells accompanied with the increases of p38 and ERK1/2 activities. (3) 20% stretch-induced anti-proliferation and inhibition of p38 activity were severer in L6 than C2C12 myoblasts; AR overexpression reversed the anti-proliferation of 20% stretch and enhanced p38 activity in L6 myoblasts. (4) In stretched L6 myoblasts, AR overexpression increased IGF-1R level despite no detectable IGF-1; and recombinant IGF-1 increased the proliferation, the level of IGF-1R, and the activities of p38 and ERK1/2 in 15% stretched L6 myoblasts. The study demonstrated AR's crucial roles in stretches-regulated proliferation of myoblasts, and increased AR fulfilled 15% stretch's pro-proliferation via activating IGF-1R- p38 and ERK1/2 pathways while decreased AR achieved 20% stretch's anti-proliferation via inhibiting IGF-1R- p38 pathway, which is useful to understand in depth the role and mechanisms of AR in appropriate exercise increasing while excessive exercise decreasing muscle mass.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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•The preparation procedure for hierarchical Bi2O2CO3 microspheres is convenient.•An ion exchange method is used to synthesize Bi2O2CO3/Bi2S3 heterojunctions.•The prepared ...Bi2O2CO3/Bi2S3 is very efficient under visible light irradiation.•The photosensitization and quantum size confinement of Bi2S3 play a key role.
Bismuth subcarbonate (Bi2O2CO3) microspheres were synthesized by a simple hydrothermal method using bismuth citrate and sodium hydrogen carbonate as precursors. Furthermore, through a facile ion exchange method between the Bi2O2CO3 microspheres and thioacetamide (TAA), bismuth subcarbonate/bismuth sulfide (Bi2O2CO3/Bi2S3) heterojunctions were fabricated. The structures and morphologies of the Bi2O2CO3 and Bi2O2CO3/Bi2S3 products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The photocatalytic activities of the products were evaluated by decomposing rhodamine B (RhB) under visible light irradiation. In contrast with Bi2O2CO3, the Bi2O2CO3/Bi2S3 heterojunctions showed enhanced visible light photocatalytic properties. In addition, the effect of ion exchange reaction time on the photodegradation quality was studied, and the mechanism of the enhanced photocatalytic properties was proposed.
Abstract
Layered double hydroxides are promising candidates for the electrocatalytic oxygen evolution reaction. Unfortunately, their catalytic kinetics and long-term stabilities are far from ...satisfactory compared to those of rare metals. Here, we investigate the durability of nickel-iron layered double hydroxides and show that ablation of the lamellar structure due to metal dissolution is the cause of the decreased stability. Inspired by the amino acid residues in photosystem II, we report a strategy using trimesic acid anchors to prepare the subsize nickel-iron layered double hydroxides with kinetics, activity and stability superior to those of commercial catalysts. Fundamental investigations through operando spectroscopy and theoretical calculations reveal that the superaerophobic surface facilitates prompt release of the generated O
2
bubbles, and protects the structure of the catalyst. Coupling between the metals and coordinated carboxylates via C‒O‒Fe bonding prevents dissolution of the metal species, which stabilizes the electronic structure by static coordination. In addition, the uncoordinated carboxylates formed by dynamic evolution during oxygen evolution reaction serve as proton ferries to accelerate the oxygen evolution reaction kinetics. This work offers a promising way to achieve breakthroughs in oxygen evolution reaction stability and dynamic performance by introducing functional ligands with static and dynamic compatibilities.
Abstract
We present a study of the mass–metallicity relation (MZR) of 51 dwarf galaxies (
M
⋆
≈ 10
6.5
–10
9.5
M
⊙
) at
z
= 2–3 from the A2744 and SMACS J0723-3732 galaxy cluster fields. These dwarf ...galaxies are identified and confirmed by deep JWST/NIRISS imaging and slitless grism spectroscopic observations. By taking advantage of the superior performance of JWST and the gravitational lensing effect, we extend the previous MZR relation at
z
= 2–3 to a much lower-mass regime down by ≈2.5 orders of magnitude as compared with previous studies. We find that the MZR has a shallower slope at the low-mass end (
M
⋆
< 10
9
M
⊙
), with a slope turnover point of ≈10
9
M
⊙
. This implies that the dominating feedback processes in dwarf galaxies may be different from that in massive galaxies. From
z
= 3, to
z
= 2, the metallicity of the dwarf galaxies is enhanced by ≈0.09 dex for a given stellar mass, consistent with the mild evolution found in galaxies with higher mass. Furthermore, we confirm the existence of a fundamental metallicity relation (FMR) between the gas-phase metallicity, stellar mass, and star formation rate in dwarf galaxies at
z
= 2–3. Our derived FMR, which has no significant redshift evolution, can be used as a benchmark to understand the origin of the anticorrelation between the star formation rate and metallicity of dwarf galaxies in the high-
z
Universe.
To explore the metabolic effect of chemerin, adipose‐specific chemerin knockout (adipo‐chemerin−/−) male mice were established and fed with 5‐week normal diet (ND) or high‐fat diet (HFD), and then ...the glycolipid metabolism index was measured and epididymal adipose tissue metabolomics detected using untargeted LC–tandem mass spectrometry (LC–MS/MS). Under HFD, adipo‐chemerin−/− mice showed improved glycolipid metabolism (decreased total cholesterol, low‐density lipoprotein‐cholesterol, insulin and Homeostasis Model Assessment of Insulin Resistance) compared with flox (control) mice. Furthermore, orthogonal partial least squares‐discriminant analysis score plots identified separation of metabolites between adipo‐chemerin−/− mice and flox mice fed ND and HFD. Under HFD, 28 metabolites were significantly enhanced in adipo‐chemerin−/− mice, and pathway enrichment analysis suggested strong relationship of the differential metabolites with arginine and proline metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis, which were directly or indirectly related to lipid metabolism, inflammation and oxidative stress. Under ND, taurine was increased in adipo‐chemerin−/− mice, resulting in taurine and hypotaurine metabolism and primary bile acid biosynthesis. In conclusion, the improved effect of chemerin knockdown on the glycolipid metabolism of HFD‐feeding male mice might be associated with the increases in differential metabolites and metabolic pathways involved in lipid metabolism, inflammation and oxidative stress, which provided insights into the mechanism of chemerin from a metabolomics aspect.
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