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1.
Food Chem ; 336: 127700, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768906

RESUMO

The processing stability and antioxidant capacity of blueberry anthocyanins (ANs) in the presence of whey protein isolate (WPI) were examined. WPI was found to enhance both the stability and antioxidant activity of ANs during processing and simulated in vitro digestion, especially at a concentration of 0.15 mg·mL-1. Fluorescence and ultraviolet-visible absorption spectroscopy showed that ANs were primarily stabilized by hydrophobic forces between WPI and malvidin-3-O-galactoside (M3G), the major anthocyanin monomer. Circular dichroism and Fourier-transform infrared spectroscopy confirmed that the structure of WPI changed and the microenvironments of certain amino acid residues were modulated by non-covalent binding to M3G; furthermore, fewer α-helices and more ß-sheets were formed. Molecular docking studies revealed that WPI, especially immunoglobulin (IgG), contributed the most to ANs stability via hydrogen bonds and hydrophobic forces according to molecular docking scores (-141.30 kcal/mol). These results provided an important fundamental basis for improving the stabilities of ANs in milk systems.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32561375

RESUMO

The central neurotensin system has been implicated in reward, memory processes, also in the regulation of anxiety. However, the neural substrates where neurotensin acts to regulate anxiety have not been fully identified. The prelimbic region of medial prefrontal cortex (PrL) holds a key position in the modulation of anxiety-related behaviors and expresses neurotensin 1 receptor (NTS1). This study investigated the effects of activation or blockade of NTS1 in the PrL on anxiety-like behaviors of rats. Our results demonstrated that infusion of a selective NTS1 agonist or neurotensin into the PrL produced anxiogenic-like effects. Administration of a NTS1 antagonist into the PrL did not affect anxiety-like behaviors of normal rats, but attenuated anxiogenic effects induced by restraint stress. Moreover, we employed molecular approaches to downregulate the expression of NTS1 in the PrL, and found that downregulation of NTS1 in the PrL induced anxiolytic effects in restraint stress rats, also confirming the pharmacological results. Together, these findings suggest that NTS1 in the PrL is actively involved in the regulation of anxiety.

3.
Food Chem ; 334: 127526, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32702589

RESUMO

Blueberry anthocyanins are well-known for their diverse biological functions. However, the instability during digestion results in their weak bioavailability. The current study aimed to investigate the alteration in the stability, antioxidant capacity and bioaccessibility of blueberry anthocyanins with the addition of α-casein and ß-casein in a simulated digestion system using pH differential method, HPLC-MS analysis, peroxyl scavenging capacity (PSC) assay, cellular antioxidant activity (CAA) and penetration test. The results showed that both α-casein and ß-casein could increase the stability of blueberry anthocyanins during intestinal digestion and protect their antioxidant capacity. Moreover, the addition of α-casein or ß-casein would enhance the bioaccessibility of blueberry anthocyanins. In conclusion, our study highlights that the interaction between α-casein or ß-casein with blueberry anthocyanins can protect the compounds against influences associated with the simulated digestion.

4.
Neural Regen Res ; 16(1): 150-157, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788470

RESUMO

Acrylamide has been shown to be neurotoxic. Brain-derived neurotrophic factor (BDNF) can alleviate acrylamide-induced synaptic injury; however, the underlying mechanism remains unclear. In this study, dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma (NB-1) cells were exposed with 0-100 µg/mL acrylamide for 24-72 hours. Acrylamide decreased cell viability and destroyed synapses. Exposure of co-cultured NB-1 cells and Schwann cells to 0-100 µg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF, suggesting that Schwann cells can activate self-protection of neurons. Under co-culture conditions, activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect. Exogenous BDNF can increase expression of TrkB, Erk1/2, and synapsin I, while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes. Taken together, Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway, indicating that BDNF plays an important role in this process. Therefore, exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control, a division of the Chinese Center for Disease Control and Prevention (approval No. EAWE-2017-008) on May 29, 2017.

5.
Food Chem ; 337: 127763, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32791431

RESUMO

In this work, water-resistant poly (vinyl alcohol) (PVA)/poly (acrylic acid) (PAA) electrospun fibers encapsulating tangeretin (Tan) were fabricated by emulsion-electrospinning. To optimize the electrospinning condition, the size and morphology of electrospun fibers were characterized by dynamic light scattering (DLS), optical light microscope, fluorescence microscopy, and scanning electron microscopy (SEM), respectively. The optimized initial concentration of PVA/PAA was 10% (w/w) with a mass ratio of 3:7. The time and temperature of optimized thermal crosslinking treatment were 2 h and 145 °C, respectively. The results of XRD and SEM showed that the Tan was successfully incorporated into smooth PVA/PAA electrospun fibers and those fibers possessed nano-diameter size and high porosity. The encapsulation of Tan had no significant impact on the antioxidant activity of PVA/PAA/Tan crosslinking electrospun fibers. The in vitro release test showed the PVA/PAA/Tan crosslinking electrospun fibers achieved durable release profiles and lower burst release rates than that from the pure Tan emulsion. Based on these results, it is concluded that PVA/PAA/Tan crosslinking electrospun fibers prepared by emulsion-electrospinning serve as a promising technique in the fields of water-insoluble drug delivery and slow-release.

6.
Bioresour Technol ; 319: 124209, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33045547

RESUMO

Choline chloride based deep eutectic solvents have showed great potential in lignocellulosic biomass pretreatment. In this study, for DES pretreatment with different hydrogen bond donners of different raw materials under different reaction conditions, multivariate analysis methods including principal component analysis and partial least squares analysis were used for reveal the pretreatment mechanism by evaluating the inner relationships among 42 key process factors. Furthermore, based on molecular simulation, the detailed relationships between key variables were further analyzed. Meanwhile, four-dimensional color graphs were used to intuitively reveal the synergistic influence of multivariate conditions variables on pretreatment effect to obtain better economic benefits and energy consumption indicators for DES pretreatment. The results showed that HBD hydrophilic ability, HBD polarity, HBD acidity, HBD ability to form hydrogen bonds, molar ratio of HBD to choline chloride and pretreatment severity had great influence on the Choline chloride based deep eutectic solvents pretreatment effect.

7.
Soft Matter ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057553

RESUMO

In this work, coarse-grained molecular dynamics simulation is adopted to investigate the effect of hybrid fillers [nanospheres (NSs) and nanorods (NRs)] on the conductive probability of polymer nanocomposites (PNCs) in the quiescent state and under the shear field. The percolation threshold gradually rises as the volume fraction ratio (α) of NSs to all the fillers increases in the quiescent state. Compared to the NSs, the greater number of beads in the NRs help them connect to other NRs to form the conductive network. Meanwhile, compared to NSs, more NRs participate in building the conductive network. A transition from the synergistic effect to the antagonistic effect occurs as the NS-NR tunneling distance is reduced. Furthermore, the shear field induces a more direct aggregation structure of NSs, which act as linkers between fillers to protect the conductive network. This result is confirmed by the fact that more NSs occupy the conductive network under the shear field. As a result, the percolation threshold declines with increasing shear rate. Finally, compared to in the quiescent state, the percolation threshold increases at α = 0.0 and remains nearly unchanged for α = 0.25 under the shear field, while it gradually decreases for α ≥ 0.5. In total, the results further our understanding of how to realize the synergistic effect between NSs and NRs when forming a conductive network of PNCs.

8.
FASEB J ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33064329

RESUMO

The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23-25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2-3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle-specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT-deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle.

9.
J Mol Med (Berl) ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047154

RESUMO

Epidemiological studies have shown an increased prevalence of cancer in some patients with neurodevelopmental disorder (NDD); however, the genetic mechanisms regarding how cancer-related genes (CRGs) contribute to NDD remain unclear. We performed bioinformatic analyses on 219 CRGs from OMIM and de novo mutations (DNMs) from 16,498 patients with different NDDs and 3391 controls. Our results showed that autism spectrum disorder, undiagnosed neurodevelopmental disorder, congenital heart disease and intellectual disability, but not epileptic encephalopathy and schizophrenia, harboured significantly more putative functional DNMs in CRGs, compared with controls, providing genetic evidence supporting previous epidemiological surveys. We further detected 26 CRGs with recurrent putative functional DNMs that showed high expression in the human brain during the prenatal stage and in non-brain organs in adults. The proteins coded by the 26 CRGs and known NDD candidate genes formed a functional network that is involved in brain development and tumorigenesis. Overall, we proposed 39 cancer-targeting drugs that could be investigated for treating patients with NDD, which would be potentially cost-effective. In conclusion, DNMs contribute to specific NDDs and there may be a shared genetic basis between NDDs and cancer, highlighting the importance of considering cancer-targeting drugs with potential curative effects in patients with NDDs. KEY MESSAGES: • The contribution of DNMs in NDD is consistent with epidemiological surveys. • We highlighted 26 CRGs, including nine genes with more than five functional DNMs. • Specific expression patterns underlie the genetic mechanism of CRGs in NDD. • Specific functional networks underlie the genetic mechanism of CRGs in NDD. • The shared genetic aetiology suggests potential mutual treatment strategies.

10.
Chem Commun (Camb) ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001080

RESUMO

A novel expanded metal-organic framework (UTSA-111a) with functional pyrimidine sites exhibits simultaneously high gravimetric and volumetric methane storage working capacities of 309 cm3 (STP) g-1 and 183 cm3 (STP) cm-3 at 298 K and 5.8-65 bar.

11.
Nanomaterials (Basel) ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008115

RESUMO

To control the disease caused by Sclerotinia sclerotiorum, a total of 15 isolates of the Trichoderma species was screened for the biosynthesis of silver nanoparticles (AgNPs). Among them, the highest yield occurred in the synthesis of AgNPs using a cell-free aqueous filtrate of T.virens HZA14 producing gliotoxin. The synthetic AgNPs were charactered by SEM, EDS, TEM, XRD, and FTIR. Electron microscopy studies revealed that the size of AgNPs ranged from 5-50 nm and had spherical and oval shapes with smooth surfaces. Prepared AgNPs interacted with protein, carbohydrate and heterocyclic compound molecules, and especially, interaction patterns of AgNPs with the gliotoxin molecule were proposed. The antifungal activity assays demonstrated that percentage inhibition of the prepared AgNPs was 100, 93.8 and 100% against hyphal growth, sclerotial formation, and myceliogenic germination of sclerotia at a concentration of 200 µg/mL, respectively. The direct interaction between nanoparticles and fungal cells, including AgNPs' contact, accumulation, lamellar fragment production and micropore or fissure formation on fungal cell walls, was revealed by SEM and EDS. These will extend our understanding of the mechanisms of AgNPs' action for preventing diversified fungal disease.

12.
Food Chem ; 341(Pt 1): 128149, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33039745

RESUMO

This research established an optimized method for the extraction and enrichment of flavonoids from R. corchorifolius fruit. Under the optimized extraction conditions, 12 flavonoids (1-12) were isolated, of which six (2-4, 9-10, 12) were obtained from R. corchorifolius for the first time. Compound 4 showed significant α-glucosidase (4.96 µM) and α-amylase (8.04 µM) inhibitory effects. Molecular modeling revealed that compound 4 exhibits strong binding with the active sites of α-glucosidase and α-amylase. Lineweaver-Burk plot analysis and surface plasmon resonance revealed the possible dynamic binding mechanism of the flavonoids with α-glucosidase and α-amylase. The enriched flavonoids and compound 4 showed significant hypoglycemic effects in mice administered a high dose of glucose. In this study, a variety of flavonoids with hypoglycemic activity were found for the first time, revealing the rich chemical composition of R. corchorifolius fruit and highlighting the potential value of R. corchorifolius fruit flavonoids as dietary supplements.

13.
Toxicol Lett ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33098907

RESUMO

Mushroom toxicity is the main branch of foodborne poisoning, and liver damage caused by amatoxin poisoning accounts for more than 90% of deaths due to mushroom poisoning. Alpha-amatoxin (α-AMA) has been considered the primary toxin from amatoxin-containing mushrooms, which is responsible for hepatotoxicity and death. However, the mechanism underlying liver failure due to α-AMA remains unclear. This study constructed animal and cell models. In the animal experiments, we investigated liver injury in BALB/c mice at different time points after α-AMA treatment, and explored the process of inflammatory infiltration using immunohistochemistry and western blotting. Then, a metabonomics method based on gas chromatography mass spectrometry (GC-MS) was established to study the effect of α-AMA on liver metabonomics. The results showed a significant difference in liver metabolism between the exposed and control mice groups that coincided with pathological and biochemical indicators. Moreover, 20 metabolites and 4 metabolic pathways related to its mechanism of action were identified, which suggested that energy disorders related to mitochondrial dysfunction may be one of the causes of death. The significant changes of trehalose and the fluctuation of LC3-II and sqstm1 p62 protein levels indicated that autophagy was also involved in the damage process, suggesting that autophagy may participate in the clearance process of damaged mitochondria after poisoning. Then, we constructed an α-AMA-induced human normal liver cells (L-02 cells) injury model. The above hypothesis was further verified by detecting cell necrosis, mitochondrial reactive oxygen species (mtROS), mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (Δψ m), and cellular ATP level. Collectively, our results serve as direct evidence of elevated in vivo hepatic mitochondrial metabolism in α-AMA-exposed mice and suggest that mitochondrial dysfunction plays an important role in the early stage of α-AMA induced liver failure.

14.
Acta Biomater ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33099024

RESUMO

The analysis of T cell responses to mechanical properties of antigen presenting cells (APC) is experimentally challenging at T cell-APC interfaces. Soft hydrogels with adjustable mechanical properties and biofunctionalization are useful reductionist models to address this problem. Here, we report a methodology to fabricate micropatterned soft hydrogels with defined stiffness to form spatially confined T cell/hydrogel contact interfaces at micrometer scale. Using automatized microcontact printing we prepared arrays of anti-CD3 microdots on poly(acrylamide) hydrogels with Young's Modulus in the range of 2 to 50 kPa. We optimized the printing process to obtain anti-CD3 microdots with constant area (50 mm2, corresponding to 8 µm diameter) and comparable anti-CD3 density on hydrogels of different stiffness. The anti-CD3 arrays were recognized by T cells and restricted cell attachment to the printed areas. To test functionality of the hydrogel-T cell contact, we analyzed several key events downstream of T cell receptor (TCR) activation. Anti-CD3 arrays on hydrogels activated calcium influx, induced rearrangement of the actin cytoskeleton, and lead to Zeta-chain-associated protein kinase 70 (ZAP70) phosphorylation. Interestingly, upon increase in the stiffness, ZAP70 phosphorylation was enhanced, whereas the rearrangements of F-actin (F-actin clearance) and phosphorylated ZAP70 (ZAP70/pY centralization) were unaffected. Our results show that micropatterned hydrogels allow tuning of stiffness and receptor presentation to analyze TCR mediated T cell activation as function of mechanical, biochemical, and geometrical parameters.

15.
J Am Chem Soc ; 142(42): 17897-17902, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33044819

RESUMO

Recent advances in spherical mesoporous metal oxides (SMMOs) have demonstrated their enormous potential in a large variety of research fields. However, a direct creation of these materials with precise control on their key shape features, particularly pore architectures, remains a major challenge as compared to the widely explored counterpart of silica. Here, using Al2O3 as an example, we identified that deposition kinetics in solution played an essential role in the construction of different SMMOs. Specifically, a controlled Al3+ precipitation is critical to maintaining the electrostatic interaction between the inorganic precursors and the molecular templates, thereby achieving a designable assembly of these two components toward uniform mesoporous Al2O3-based nanospheres. We demonstrated that such a synthesis strategy is not only able to precisely control the channel orientations from concentric to radial and dendritic, a synthesis capability impeded so far for SMMOs, but is readily applicable to other metal oxides. Our study showed that the growth-kinetics control is a simple but powerful synthesis protocol and opened up a multifunctional platform to achieve systematic design of SMMOs for their future applications.

16.
BMC Health Serv Res ; 20(1): 956, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066769

RESUMO

BACKGROUND: This study aimed to translate the English version of the supportive care needs scale of head and neck cancer patients (SCNS-HNC) questionnaire into Mandarin and to test the reliability and validity of the SCNS-SF34 and SCNS-HNC module in head and neck cancer patients. METHODS: The Mandarin version of the Supportive Care Needs Survey Short-Form (SCNS-SF34) and SCNS-HNC scales were used to assess 206 patients with head and neck cancer in Chengdu, China. Among them, 51 patients were re-tested 2 or 3 days after the first survey. The internal consistency of the scale was evaluated by Cronbach's alpha coefficient, the retest reliability of the scale was evaluated by retest correlation coefficient r, the structural validity of the scale was evaluated by exploratory factor analysis, and the ceiling and floor effects of the scale were evaluated. RESULTS: The Mandarin version of the SCNS-HNC had Cronbach's alpha coefficients greater than 0.700 (0.737 ≤ 0.962) for all of the domains. Except for the psychological demand dimension (r = 0.674) of the SCNS-SF34 scale, the retest reliability of the other domains was greater than 0.8. Three common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 64.39%. CONCLUSIONS: The Mandarin version of the SCNS-SF34 and SCNS-HNC demonstrated satisfactory reliability and validity and is able to measure the supportive care needs of Chinese patients with head and neck cancer. TRIAL REGISTRATION: ChiCTR, ChiCTR1900026635 . Registered 16 October 2019- Retrospectively registered.

17.
Medicine (Baltimore) ; 99(42): e22786, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080750

RESUMO

RATIONALE: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. It appears as patches, plaques, and tumors depending on the stage of the disease, which presents a chronic progressive course. Compared to CD4/CD8 MF, CD4/CD8 dual-positive MF is an uncommon immune phenotype. PATIENT CONCERNS: A 36-year-old male patient presented with dryness and scales on his whole body. DIAGNOSIS: The patient was diagnosed with MF based on results of pathological examination, immunohistochemical staining, and T-cell receptor gene rearrangement test. INTERVENTIONS: The patient was advised to take an herbal medicine orally twice daily and apply a topical moisturizer after showering. OUTCOMES: After treatment and follow-up, the patient's symptoms of dryness and scales improved and his condition stabilized. CONCLUSIONS: While reviewing the literature, we found no previous reports on the treatment of dual-positive MF with Chinese medicine. In this report, we presented the first case of dual-positive MF successfully treated with Chinese medicine. The results suggest that oral ingestion of herbal medicine may be a feasible method for alleviating clinical symptoms of early stage MF. Therefore, the therapy should be explored for clinical use in the future.

18.
Molecules ; 25(20)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086640

RESUMO

Bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most devastating diseases, resulting in significant yield losses in rice. The extensive use of chemical antibacterial agents has led to an increase the environmental toxicity. Nanotechnology products are being developed as a promising alternative to control plant disease with low environmental impact. In the present study, we investigated the antibacterial activity of biosynthesized chitosan nanoparticles (CSNPs) and zinc oxide nanoparticles (ZnONPs) against rice pathogen Xoo. The formation of CSNPs and ZnONPs in the reaction mixture was confirmed by using UV-vis spectroscopy at 300-550 nm. Moreover, CSNPs and ZnONPs with strong antibacterial activity against Xoo were further characterized by scanning and transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. Compared with the corresponding chitosan and ZnO alone, CSNPs and ZnONPs showed greater inhibition in the growth of Xoo, which may be mainly attributed to the reduction in biofilm formation and swimming, cell membrane damage, reactive oxygen species production, and apoptosis of bacterial cells. Overall, this study revealed that the two biosynthesized nanoparticles, particularly CSNPs, are a promising alternative to control rice bacterial disease.

19.
PLoS One ; 15(10): e0241072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095796

RESUMO

Third-variable effect refers to the effect transmitted by third-variables that intervene in the relationship between an exposure and a response variable. Third-variable effect analysis has been broadly studied in many fields. However, it remains a challenge for researchers to differentiate indirect effect of individual factor from multiple third-variables, especially when the involving variables are of hierarchical structure. Yu et al. (2014) defined third-variable effects that were consistent for all different types of response (categorical or continuous), exposure, or third-variables. With these definitions, multiple third-variables can be considered simultaneously, and the indirect effects carried by individual third-variables can be separated from the total effect. In this paper, we extend the definitions of third-variable effects to multilevel data structures, where multilevel additive models are adapted to model the variable relationships. And then third-variable effects can be estimated at different levels. Moreover, transformations on variables are allowed to present nonlinear relationships among variables. We compile an R package mlma, to carry out the proposed multilevel third-variable analysis. Simulations show that the proposed method can effectively differentiate and estimate third-variable effects from different levels. Further, we implement the method to explore the racial disparity in body mass index accounting for both environmental and individual level risk factors.

20.
J Ethnopharmacol ; : 113496, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33091494

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases. AIM OF THE STUDY: To explore the protective effects of KHS against carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials. MATERIALS AND METHODS: The acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400 mg/kg/d, mice in positive control group were treated with bifendate (30 mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot. RESULTS: The MTD of KHS was determined to be 26 g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl4-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400 mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues. CONCLUSIONS: This research firstly clarified that KHS has a significant protective effect against CCl4-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis.

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