High-compatibility properties of Aronia melanocarpa extracts cross-linked chitosan/polyvinyl alcohol composite film for intelligent food packaging.

Although the active and intelligent properties of rich in anthocyanin extracts added to films have been extensively studied, there remains a sparsity of research pertaining to the miscibility of blended films. This work focused on the miscibility of the chitosan/polyvinyl alcohol (CP) film caused by the addition of Aronia melanocarpa extracts (AME), which are rich anthocyanins and phenolic acids, and its effect on physicochemical and functional properties. AME facilitated the amidation reaction and ionic interaction of chitosan in CP films, leading to loss of the crystallinity degree of chitosan. Furthermore, the crystal disruption promoted the formation of hydrogen bonds with polyvinyl alcohol (PVA) with the promoted miscibility. CP film incorporated with 8 % AME possessed the highest tensile strength (26.79 MPa), and elongation at break (66.38 %) as well as excellent ultraviolet-visible (UV-vis) light barrier property, water vapor barrier properties, due to its high miscibility degree. Moreover, this film also showed excellent antioxidant, antibacterial activity, and pH response function, which could be used to monitor the storage of highly perishable shrimp. Hence, the AME provided extra functionality and improved miscibility between chitosan and PVA, which showed great potential for the preparation of high-performance bioactive-fortified and intelligent food packaging films.

Comprehensive analysis of cuproptosis-related long non-coding RNAs in prognosis, immune microenvironment infiltration and chemotherapy response of hepatocellular carcinoma.

The objective of this study is to explore the relationship between cuproptosis-related long noncoding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). RNA-seq data, including lncRNAs and related clinical information of HCC patients, were downloaded from The Cancer Genome Atlas database. A signature composed 3 cuproptosis-related lncRNAs was constructed by LASSO analysis, and HCC patients were classified into high- and low-risk groups. Patients in the high-risk group had a poorer prognosis compared with the low-risk group. Univariate Cox and multivariate Cox regression analyses confirmed that the signature model was an independent risk factor compared to other clinical biomarkers. Furthermore, gene set enrichment analysis indicated that metabolism-related pathways were enriched in low-risk group, including drug metabolism, and fatty acid metabolism. Further research demonstrated that there were markedly differences in drug response between the high- and low-risk group. Immune related analysis showed that the most type of immune cells and immunological function in the high-risk group were different with the risk-group. Finally, TP53 mutation rate and the tumor mutational burden in the high-risk group were higher compared with the low-risk group. In conclusion, we constructed a prognostic signature based on the expression of cuproptosis-related lncRNAs to predict HCC patients' prognosis, drug response and immune microenvironment, and further research will be conducted to uncover the mechanisms.

[Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases].

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038). CONCLUSION: The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

Piezoelectricity and Thermophysical Properties of Ba0.90Ca0.10Ti0.96Zr0.04O3 Ceramics Modified with Amphoteric Nd3+ and Y3+ Dopants.

Lead-free barium calcium titanate zirconate (BCTZ) ceramics doped with a single rare-earth element generally exhibit excellent piezoelectric properties. However, their electrical properties deteriorate at an excessive dopant content, limiting their application. In this study, amphoteric neodymium (Nd3+) and yttrium (Y3+)-codoped BCTZ-NYx ceramics were synthesized via a solid-state reaction at 1240 °C. The influences of the Y3+ content (x) on the structural features, electrical properties, mechanical properties, and thermophysical properties were investigated. At a small x (<0.18 mol%), Y3+ could enhance the fracture strength and electrical properties by eliminating oxygen vacancies, defect dipoles, and/or structural defects. However, the outstanding performance deteriorated with excessive x. Additionally, the mechanism of the defect chemistry at different x was deduced. At an yttrium content of 0.18 mol%, the ceramic exhibited high piezoelectricity and ferroelectricity with low domain-switching activation energy (Ea = 0.401 eV), indicating that it could replace commercial lead-based piezoelectric ceramics.

Dynamic Response Characteristics of Railway Subgrade Using a Newly-Developed Prestressed Reinforcement Structure: Case Study of a Model Test.

Poor subgrade conditions usually induce various subgrade diseases in railways, leading to some adverse influences. An innovative technology that involves installing a prestressed reinforcement structure (PRS) that consists of steel bars and lateral pressure plates (LPP) for subgrade was introduced to improve its stress field and provide compulsive lateral deformation constraints for slope. In this study, an investigation into the dynamic acceleration responses of railway subgrade strengthened according to different PRS schemes was presented using a 1:5 scale model test, aiming to explore the effects of the axle load, the reinforcement pressure, and the loading cycles on the acceleration characteristics of the subgrade. The experimental results showed that (1) after pretension of the steel bar, prestress loss occurred due to the soil creep behavior and group anchor effect, so a moderate amount of over-tension in practices would be necessary; (2) a distinctive periodical behavior of subgrade subjected to the cyclic loads was observed, the horizontal accelerations were generally less than the vertical accelerations at the same measurement heights, and the vibration energy attenuated gradually from the shoulder to the toe along the slope; (3) in the short-term tests, the peak accelerations at all measurement points had a linear correlation with the axle load, and oppositely, it showed an approximately linear decrease with the increasing reinforcement pressure; And (4) in the long-term tests, to simulate the heavy haul wagon with a 35 t axle load, the variation in the effective acceleration with loading cycles under reinforcement pressure 100 kPa initially exhibited a decrease and subsequently tended to be stable, which is apparently less than that without reinforcement pressure. Consequently, it was demonstrated that the PRS itself and increasing reinforcement pressure can effectively mitigate the subgrade vibration, and provide an appropriate alternative to improve the dynamic performance of railway subgrade under the moving train loads.

Experimental Investigation of the Mechanical Properties of the Sand-Concrete Pile Interface Considering Roughness and Relative Density.

The aim of this study was to investigate the effect of roughness and relative density on the mechanical properties of sand-concrete pile interface. A series of direct shear tests were carried out on the interface using a large-scale direct shear apparatus with various relative densities of sand (73%, 47%, and 23%) and concrete blocks with four roughness values (I = 0, 10, 20, and 30 mm). Various mechanical properties (such as shear stress, volume change, peak shear strength, secant friction angle, and normalized friction coefficient) from the interface tests were compared with trends obtained from the pure sand direct shear test. For the smooth interface, the shear stress-horizontal displacement curves of the dense sand specimen exhibited a slight softening response, which became more apparent as the roughness increased. The curves of the loose sand specimen demonstrated a hardening response. The volumetric response was influenced by the combination of normal stress, relative density, and roughness. The peak shear strength demonstrated a nonlinear increasing trend as the normal stress increased. With an increase in the normal stress, the secant friction angle and peak friction coefficient decreased as exponential and power functions, respectively. Additionally, a critical roughness value Icr resulted from the tests, which halted the upward trend of the peak friction coefficient and normalized the secant friction angle when I exceeded Icr.

Alkaloids from Aconitum carmichaelii Alleviates DSS-Induced Ulcerative Colitis in Mice via MAPK/NF-κB/STAT3 Signaling Inhibition.

Fuzi (Aconitum carmichaelii Debx) has been traditionally used for the treatment of ulcerative colitis (UC) in China for thousands of years. The total alkaloids of A. carmichaelii (AAC) have been considered as the main medicinal components of fuzi, whereas its underlying anti-UC mechanisms remain elusive. In the present study, the dextran sulfate sodium (DSS)-induced UC mice model, which was consistent with the symptoms and pathological features of human UC, was established to comprehensively evaluate the anti-UC effects of AAC. The results indicated that AAC effectively improved the weight loss, disease activity index (DAI), spleen hyperplasia, and colon shortening, and thus alleviated the symptoms of UC mice. Meanwhile, AAC not only inhibited the MPO enzyme and the abnormal secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IFN-γ, and IL-17A) and suppressed the overexpression of inflammatory mediators (TNF-α, IL-1ß, and IL-6) of mRNA but also reduced the phosphorylation of p38 MAPK, ERK, and JNK, and the protein expressions of NF-κB, IκB-α, STAT3, and JAK2 in the colon tissue. Furthermore, the LC-MS/MS quantitative determination suggested that the three low toxic monoester alkaloids were higher in both contents and proportion than that of the three high toxic diester alkaloids. Additionally, molecular docking was hired to investigate the interactions between alkaloid-receptor complexes, and it suggested the three monoester alkaloids exhibited higher binding affinities with the key target proteins of MAPK, NF-κB, and STAT3. Our finding showcased the noteworthy anti-UC effects of AAC based on the MAPK/NF-κB/STAT3 signaling pathway, which would provide practical and edge-cutting background information for the development and utilization of A. carmichaelii as a potential natural anti-UC remedy.

Chitosan/zein bilayer films with one-way water barrier characteristic: Physical, structural and thermal properties.

Chitosan (C) and zein (Z) were used to develop bilayer films with a characteristic one-way water barrier using a layer-by-layer (LBL) casting method. The effects of mass ratios (C:Z1:1, C:Z1:2, C:Z1:3, C:Z3:1, C:Z2:1) on the microstructure and physicochemical properties of bilayer films were investigated. Bilayer films had uniform microstructures, and C:Z = 1:3 showed a firmer structure as the Z aggregates were distributed in the continuous phase of C. The intermolecular interactions between the C and Z layers were observed using FTIR and XRD analysis. TGA demonstrated that adding Z layer enhanced the thermal stability of C films. LBL coating gave the C/Z bilayer film an increased elongation and tensile strength, as well as a decreased water vapor and oxygen permeability, especially for C:Z = 1:3 which had better properties. The results suggested that C and Z bilayer films may be a promising material for food packaging with the desired water resistance.

Characterization of the diastaphenazine/izumiphenazine C biosynthetic gene cluster from plant endophyte Streptomyces diastaticus W2.

Two phenazine compounds, diastaphenazine and izumiphenazine C, with complex structures and promising antitumour activity have been isolated from the plant endophytic actinomycete Streptomyces diastaticus W2. Their putative biosynthetic gene cluster (dap) was identified by heterologous expression and gene knockout. There are twenty genes in the dap cluster. dap14-19 related to shikimic pathway were potentially involved in the precursor chorismic acid biosynthesis, and dapBCDEFG were confirmed to be responsible for the biosynthesis of the dibenzopyrazine ring, the nuclear structure of phenazines. Two transcriptional regulatory genes dapR and dap4 played the positive regulatory roles on the phenazine biosynthetic pathway. Most notably, the dimerization of the dibenzopyrazine ring in diastaphenazine and the loading of the complex side chain in izumiphenazine C could be catalysed by the cyclase homologous gene dap5, suggesting an unusual modification strategy tailoring complex phenazine biosynthesis. Moreover, metabolite analysis of the gene deletion mutant strain S. albus::23C5Δdap2 and substrate assay of the methyltransferase Dap2 clearly revealed the biosynthetic route of the complex side chain in izumiphenazine C.

Multifunctional bioactive coatings based on water-soluble chitosan with pomegranate peel extract for fish flesh preservation.

This study aimed to reveal the effects of vacuum-impregnated carboxymethyl chitosan (CMCS) coating with pomegranate peel extract (PPE) on quality retention of fish flesh during refrigeration. Herein, CMCS-PPE coating was effective in attenuating quality loss of grass carp fillets. Compared to Control, the levels of drip loss, total volatile base nitrogen, and K value in coated samples were sharply decreased (p < 0.05) by 24.5%, 35.3% and 25.2% on day 9, respectively. Meanwhile, the coating also helped inhibit oxidation, bioamine accumulation, and texture softening in fillets. Moreover, the microbial enumeration was reduced by >1.4 lg cfu/g as compared to Control on day 6 afterward, and high throughput sequencing analysis further showed the active coating contributed to the notable growth suppression of spoilage bacteria like Shewanella. Additionally, the positive effect of the coating scheme was also verified in longsnout catfish and snakehead, further confirming its good applicability for fish flesh preservation.

MicroRNA miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture by inhibiting the glutamate AMPA receptor subunit 1 gene (GRIA1).

The promoting role that miR-18a-3p plays in osteoporosis (OP) has been previously described. However, the detailed mechanisms remain unclear. Bone tissues were collected from healthy patients, OP patients, and patients with osteoporotic spinal fractures. An osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) was constructed to detect the expression of miR-18a-3p and glutamate AMPA receptor subunit 1 (GRIA1). Alkaline phosphatase (ALP) activity and a qRT-PCR analysis were used to detect ALP content, alizarin red S staining was used to detect calcium deposition, and qRT-PCR was used to evaluate runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) expression levels. A dual-luciferase reporter and RNA pull-down assay was used to verify the targeted correlation between miR-18a-3p and GRIA1. We observed an increase in miR-18a-3p expression and a decrease in GRIA1 expression in OP and osteoporotic vertebral fracture patients. Upregulation of miR-18a-3p restrained the activity and expression of ALP in hBMSCs, inhibited the expression of RUNX2, OCN, and OPN, and inhibited calcium deposition. Knockdown of miR-18a-3p or upregulation of GRIA1 promoted osteogenic differentiation. Our findings indicate that miR-18a-3p promotes OP progression by regulating GRIA1 expression, suggesting that targeting miR-18a-3p/GRIA1 may be a therapeutic strategy for OP.

A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation.

Autophagy is a conserved biological process that maintains cell homeostasis by targeting macromolecules for lysosome-mediated degradation. The levels of autophagy are relatively lower under normal conditions than under stress conditions (e.g., starvation), as autophagy is usually stimulated after multiple stresses. However, many autophagy-related regulators are still expressed under normal conditions. Although these regulators have been studied deeply in autophagy regulation, the nonautophagic roles of these regulators under normal conditions remain incompletely understood. Here, we found that autophagy-related 5 (ATG5), which is a key regulator of autophagy, regulates c-Myc protein degradation under normal conditions through the ubiquitin-proteasome pathway. We also found that ATG5 binds c-Myc and recruits the E3 ubiquitin-protein ligase FBW7 to promote c-Myc degradation. Moreover, ATG5-mediated degradation of c-Myc limits cell growth under normal conditions and is essential for embryonic stem cell differentiation. Therefore, this study reveals a nonautophagic role of ATG5 in regulating of c-Myc protein degradation.

Evaluation of Critical Dynamic Stress and Accumulative Plastic Strain of an Unbound Granular Material Based on Cyclic Triaxial Tests.

Critical dynamic stress (σcri) and accumulative plastic strain (εp) are primary indicators regarding the dynamic stability of unbound granular materials (UGMs). This study aims to seek an effective method to evaluate the dynamic stability of UGMs used in railway subgrades. First, the dynamic characteristics of an UGM used in railway subgrade bed construction were investigated by performing a series of large-scale cyclic triaxial tests, with the results showing that εp versus cycle number (N) curves can be categorized into stable, failure, and critical patterns. Grey relational analyses were then established, where the analyzed results demonstrated that the εp-N curve pattern and final accumulative plastic strain (εs) of the stable curves are strongly correlated with the moisture content (w), confining pressure (σ3), and dynamic deviator stress (σd). The analyzed grey relational grades distributed in a narrow range of 0.72 to 0.81, indicating that w, σ3, and σd have similar degrees of importance on determining the εp-N curve patterns and the values of εs of the UGM. Finally, a data processing method using a back-propagation (BP) neural network is introduced to analyze the test data, and an empirical approach is developed to evaluate the σcri (considering the effects of σ3 and w) and εs (considering the effects of σ3, w, and σd) of the UGM. The analyzed results illustrated that the developed method can effectively reflect the linear/non-linear relationships of σcri and εs with respect to σ3 and/or σd. The σcri approximately increases linearly with increasing σ3, and a simple empirical formula is proposed for the σcri. In addition, εs and its variation rate increase non-linearly with increasing σd but decrease non-linearly as σ3 increases.

In vitro ubiquitination and degradation of bacteria-purified human histone H2B by the nucleoli fractions.

Histones are the main components of chromatin, and the protein levels of histones significantly affect chromatin assembly. Here, we describe detailed protocols for histone H2B purification from bacteria and for the separation of nucleolar fractions and cytoplasmic and nucleoplasmic fractions. Finally, the in vitro ubiquitination and degradation of H2B by distinct cellular fractions are described. For complete details on the use and execution of this protocol, please refer to Liu et al. (2021).

Low-spatial-frequency information facilitates threat detection in a response-specific manner.

The role of different spatial frequency bands in threat detection has been explored extensively. However, most studies use manual responses and the results are mixed. Here, we aimed to investigate the contribution of spatial frequency information to threat detection by using three response types, including manual responses, eye movements, and reaching movements, together with a priming paradigm. The results showed that both saccade and reaching responses were significantly faster to threatening stimuli than to nonthreatening stimuli when primed by low-spatial-frequency gratings rather than by high-spatial-frequency gratings. However, the manual response times to threatening stimuli were comparable to nonthreatening stimuli, irrespective of the spatial frequency content of the primes. The findings provide clear evidence that low-spatial-frequency information can facilitate threat detection in a response-specific manner, possibly through the subcortical magnocellular pathway dedicated to processing threat-related signals, which is automatically prioritized in the oculomotor system and biases behavior.

By inhibiting ADCY5, miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture.

To investigate the influence of miR-18a-3p and ADCY5 on OP and osteogenic differentiation of human Mesenchymal stem cell (hBMSCs) and its possible mechanism. Samples were collected from osteoporotic patients with or without vertebral compression fracture, and without OP volunteers. MiR-18a-3p and ADCY5 mRNA expression levels in the tissue samples and hBMSCs during osteogenic differentiation were detected。MiR-18a-3p mimic and OE-ADCY5 were introduced into hBMSCs to research the effects of miR-18a-3p and ADCY5 on osteogenesis differentiation of hBMSCs. Dual luciferase reporter system and RNA pull-down were applied to determine whether ADCY5 was a target gene of miR-18a-3p. Compared with the control group, ADCY5 expression level was down-regulated in patients with OP-no-Frx and OP-Frx, but that of miR-18a-3p was up-regulated. In addition, ADCY5 increased during osteogenesis differentiation of hBMSCs, whereas miR-18a-3p did not. OE-ADCY5 significantly facilitated calcium deposition, ALP activity, osteoblast protein expression (OSX, ALP and EUNX2), miR-18a-3p mimic inhibited osteogenic differentiation, and partially reversed the effect of OE-ADCY5 on osteogenic differentiation. In general, miR-18a-3p targets ADCY5 to promote OP and may be involved in spinal fracturs.

Effects of positive end-expiratory pressure/recruitment manoeuvres compared with zero end-expiratory pressure on atelectasis in children: A randomised clinical trial.

BACKGROUND: Atelectasis is a common postoperative complication. Peri-operative lung protection can reduce atelectasis; however, it is not clear whether this persists into the postoperative period. OBJECTIVE: To evaluate to what extent lung-protective ventilation reduces peri-operative atelectasis in children undergoing nonabdominal surgery. DESIGN: Randomised, controlled, double-blind study. SETTING: Single tertiary hospital, 25 July 2019 to 18 January 2020. PATIENTS: A total of 60 patients aged 1 to 6 years, American Society of Anesthesiologists physical status 1 or 2, planned for nonabdominal surgery under general anaesthesia (≤2 h) with mechanical ventilation. INTERVENTIONS: The patients were assigned randomly into either the lung-protective or zero end-expiratory pressure with no recruitment manoeuvres (control) group. Lung protection entailed 5 cmH2O positive end-expiratory pressure and recruitment manoeuvres every 30 min. Both groups received volume-controlled ventilation with a tidal volume of 6 ml kg-1 body weight. Lung ultrasound was conducted before anaesthesia induction, immediately after induction, surgery and tracheal extubation, and 15 min, 3 h, 12 h and 24 h after extubation. MAIN OUTCOME MEASURES: The difference in lung ultrasound score between groups at each interval. A higher score indicates worse lung aeration. RESULTS: Patients in the lung-protective group exhibited lower median [IQR] ultrasound scores compared with the control group immediately after surgery, 4 [4 to 5] vs. 8 [4 to 6], (95% confidence interval for the difference between group values -4 to -4, Z = -6.324) and after extubation 3 [3 to 4] vs. 4 [4 to 4], 95% CI -1 to 0, Z = -3.161. This did not persist from 15 min after extubation onwards. Lung aeration returned to normal in both groups 3 h after extubation. CONCLUSIONS: The reduced atelectasis provided by lung-protective ventilation does not persist from 15 min after extubation onwards. Further studies are needed to determine if it yields better results in other types of surgery. TRIAL REGISTRATION: Chictr.org.cn (ChiCTR2000033469).

Qingxue jiedu formulation ameliorated DNFB-induced atopic dermatitis by inhibiting STAT3/MAPK/NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingxue jiedu Formulation (QF) is composed of two classic prescriptions which have been clinically used for more than 5 centuries and appropriately modified through basic theory of traditional Chinese medicine for treating various skin inflammation such as atopic dermatitis (AD), acute dermatitis and rash. Although QF possesses a prominent clinical therapeutic effect, seldom pharmacological studies on its anti-AD activity are conducted. AIM OF THE STUDY: We used AD mice model to investigate the anti-AD activities of QF, as well as its underlying molecular mechanisms which involved signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. MATERIALS AND METHODS: 2,4-dinitrofluorobenzene (DNFB)-induced AD mice were used to collect serum and skin tissues for consequential determination. The levels of various inflammatory factors [interleukin (IL)-12, Interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-4, IL-6 and immunoglobulin E (IgE)] were determined by enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (RT-PCR) was contributed to detect the effects of relevant inflammatory factors on mRNA. The roles of STAT3, NF-κB and MAPK signaling pathways in AD response were analyzed by Western blotting (WB), and the thickening of mice dorsal skin and inflammatory cell infiltration were observed by hematoxylin and eosin (H&E) staining. RESULTS: QF significantly reduced the skin thickening, inflammatory cell infiltration and other symptoms in AD mice. The levels of IL-12, TNF-α, IL-4, IL-6 and IgE were decreased, while IFN-γ was increased by QF in the ELISA analysis. QF lessened the levels of lL-6 and elevated IFN-γ on the mRNA level. In addition, WB analysis showed QF thoroughly inhibited the activation of NF-κB, STAT3 and phosphorylation of JAK1, JAK2, JAK3, while partially suppressed MAPK signaling pathways. CONCLUSIONS: QF inhibited the activations of STAT3, MAPK and NF-κB signaling pathways and possessed a significant therapeutic effect on AD. Therefore, QF deserves our continuous attention and research as a prominent medicine for AD.

Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi and ganjiang are widely used as traditional Chinese medicines (TCM) in China, Korea, Japan, and many other southeast Asian countries for treating ulcerative colitis (UC), emesis and heart failure for more than 1800 years. However, the underlying mechanism of fuzi, ganjiang and fuzi-ganjiang herb pair is still unclear. In our study, we explored the therapeutic effects of fuzi, ganjiang and fuzi-ganjiang herb pair against dextran sulfate sodium (DSS)-induced UC in mice model, along with the relevant mechanism. MATERIALS AND METHODS: The contents of each marker compound in fuzi decoction (FD), ganjiang decoction (GD) and fuzi-ganjiang decoction (FGD) were determined using LC-MS/MS. During the experiment, bodyweight changes in each group were monitored every 5 days. On the day of sacrifice, colonic length, disease activity index (DAI) and spleen weight were also evaluated and histopathological examination was performed through hematoxylin & eosin (H&E) staining. The levels of myeloperoxidase (MPO) and inflammatory cytokines in colon tissues were determined by enzyme-linked immunosorbent assay (ELISA), and then the relative mRNA productions of inflammatory mediators, such as MPO, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time polymerase chain reaction (PCR). Involvement of MAPK, STAT3 and NF-κB signaling pathways in the pathogenesis of UC was determined in each group using Western Blot (WB) analysis. RESULTS: Compared with fuzi and ganjiang single decoction, the content of the alkaloids derived from fuzi (especially the diester alkaloid with strong toxicity, hypaconitine) in fuzi-ganjiang herb pair decoction was reduced. Additionally, the 6-gingerol, which was not found in ganjiang single decoction, was retained in fuzi-ganjiang herb pair decoction. FD, GD, and FGD significantly restored the bodyweight reduction, colon shortening, DAI elevation, splenomegaly and histological score in DSS-induced UC mice. Furthermore, except for the failure of low dosage of ganjiang decoction (GD-L) on IL-17A, all FD, GD and FGD significantly inhibited the production of MPO and inflammatory cytokines, such as IFN-γ, TNF-α, IL-1ß, IL-6, IL-10 and IL-17A, and suppressed the relative expression of inflammatory mediators, such as MPO, iNOS and COX-2 mRNA in colon tissues of DSS-induced mice. According to WB analysis, fuzi, ganjiang and fuzi-ganjiang combination inhibited the activation of MAPK, NF-κB and STAT3 signaling pathways. CONCLUSIONS: Our study demonstrated that fuzi, ganjiang and fuzi-ganjiang combination possess prominent anti-inflammatory activities against DSS-induced UC mice; the involved mechanism may be related to inhibition the activation of MAPK, NF-κB, and STAT3 signaling pathways.

Attenuation of doxorubicin-induced cardiotoxicity by cryptotanshinone detected through association analysis of transcriptomic profiling and KEGG pathway.

OBJECTIVE: The cardiotoxicity of doxorubicin (DOX) reduces the quality of life and prognosis of cancer patients, and therefore its clinical application has been largely restricted. This study aimed to assess the effects of cryptotanshione (CPT) on DOX-induced rat cardiac insufficiency. RESULTS: CPT treatment significantly suppressed apoptosis in vitro. The oral administration of CPT significantly improved cardiac function in the rat model, reduced collagen production and suppressed apoptosis and the production of reactive oxygen species in the heart tissue. Transcriptomic profiling and its relevant bioinformatics analysis showed that CPT suppressed doxorubicin-induced cardiotoxicity by inhibiting p53 signaling pathway. CONCLUSION: Transcriptomic profiling and bioinformatics analysis can be used to evaluate the cardio-protective effect of CPT through inactivating p53 signaling pathway in the doxorubicin-mediated myocardial damage model. METHODS: F-actin staining and flow cytometry were used to assess the effects of CPT on cardiomyocytes. In vivo, echocardiography and hemodynamic evaluation were used to assess the effects of CPT on the cardiac dysfunction in rats. Furthermore, transcriptomic profiling and bioinformatics analysis, as well as western blot analysis, were used to determine that CPT induced changes in the signaling pathways in the model.