Advances in antitumor activity and mechanism of natural steroidal saponins: A review of advances, challenges, and future prospects.

BACKGROUND: Cancer, the second leading cause of death worldwide following cardiovascular diseases, presents a formidable challenge in clinical settings due to the extensive toxic side effects associated with primary chemotherapy drugs employed for cancer treatment. Furthermore, the emergence of drug resistance against specific chemotherapeutic agents has further complicated the situation. Consequently, there exists an urgent imperative to investigate novel anticancer drugs. Steroidal saponins, a class of natural compounds, have demonstrated notable antitumor efficacy. Nonetheless, their translation into clinical applications has remained unrealized thus far. In light of this, we conducted a comprehensive systematic review elucidating the antitumor activity, underlying mechanisms, and inherent limitations of steroidal saponins. Additionally, we propose a series of strategic approaches and recommendations to augment the antitumor potential of steroidal saponin compounds, thereby offering prospective insights for their eventual clinical implementation. PURPOSE: This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations. METHODS: The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others. RESULTS: A comprehensive summary of over 40 steroidal saponin compounds with proven antitumor activity, including their applicable tumor types and structural characteristics, has been compiled. These steroidal saponins can be primarily classified into five categories: spirostanol, isospirostanol, furostanol, steroidal alkaloids, and cholestanol. The isospirostanol and cholestanol saponins are found to have more potent antitumor activity. The primary antitumor mechanisms of these saponins include tumor cell apoptosis, autophagy induction, inhibition of tumor migration, overcoming drug resistance, and cell cycle arrest. However, steroidal saponins have limitations, such as higher cytotoxicity and lower bioavailability. Furthermore, strategies to address these drawbacks have been proposed. CONCLUSION: In summary, isospirostanol and cholestanol steroidal saponins demonstrate notable antitumor activity and different structural categories of steroidal saponins exhibit variations in their antitumor signaling pathways. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy.

Green Synthesis of Narrow-Size Silver Nanoparticles Using Ginkgo biloba Leaves: Condition Optimization, Characterization, and Antibacterial and Cytotoxic Activities.

Natural products derived from medicinal plants offer convenience and therapeutic potential and have inspired the development of antimicrobial agents. Thus, it is worth exploring the combination of nanotechnology and natural products. In this study, silver nanoparticles (AgNPs) were synthesized from the leaf extract of Ginkgo biloba (Gb), having abundant flavonoid compounds. The reaction conditions and the colloidal stability were assessed using ultraviolet-visible spectroscopy. X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy (FTIR) were used to characterize the AgNPs. AgNPs exhibited a spherical morphology, uniform dispersion, and diameter ranging from ~8 to 9 nm. The FTIR data indicated that phytoconstituents, such as polyphenols, flavonoids, and terpenoids, could potentially serve as reducing and capping agents. The antibacterial activity of the synthesized AgNPs was assessed using broth dilution and agar well diffusion assays. The results demonstrate antibacterial effects against both Gram-positive and Gram-negative strains at low AgNP concentrations. The cytotoxicity of AgNPs was examined in vitro using the CCK-8 method, which showed that low concentrations of AgNPs are noncytotoxic to normal cells and promote cell growth. In conclusion, an environmentally friendly approach for synthesizing AgNPs from Gb leaves yielded antibacterial AgNPs with minimal toxicity, holding promise for future applications in the field of biomedicine.

A High CMRR Differential Difference Amplifier Employing Combined Input Pairs for Neural Signal Recordings.

This article introduces a Combined .symmetrical and complementary Input Pairs (CIP) of a Differential Difference Amplifier (DDA), to boost the total Common-Mode Rejection Ratio (CMRR) for multi-channel neural signal recording. The proposed CIP-DDA employs three input pairs (transconductors). The dc-coupled input neural signal connection, via the gate terminal of the first transconductor, yields a high input impedance. The high-pass corner frequency and dc quiescent operation point are stabilized by the second transconductor. The calibration path of differential-mode gain and Common-Mode Feedback (CMFB) is provided by the proposed third transconductor. The parallel connection has no need for extra voltage headroom of input and output. The proposed CIP-DDA is targeted at integrated circuit realization and designed in a 0.18-µm CMOS technology. The proposed CIP-DDAs with system CMFB achieve an average CMRR of 103 dB, and each channel consumes circa 3.6 µW power consumption.

Discovery of novel dual Bruton's tyrosine kinase (BTK) and Janus kinase 3 (JAK3) inhibitors as a promising strategy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronically systemic autoimmune disorder, which is related with various cellular signal pathways. Both BTK (Bruton's Tyrosine Kinase) and JAK3 (Janus Kinase 3) play important roles in the pathogenesis of rheumatoid arthritis. Herein, we reported the discovery of dual BTK/JAK3 inhibitors through bioisosterism and computer-aided drug design based on the structure of BTK inhibitor ibrutinib. We reported the discovery of dual BTK/JAK3 inhibitors which are based on the structure of BTK inhibitor ibrutinib via the method of bioisosterism and computer-aided drug design) Most of the target compounds exhibited moderate to strong inhibitory activities against BTK and JAK3. Among them, compound XL-12 stood out as the most promising candidate targeting BTK and JAK3 with potent inhibitory activities (IC50 = 2.0 nM and IC50 = 14.0 nM respectively). In the in vivo studies, compound XL-12 (40 mg/kg) exhibited more potent antiarthritic activity than ibrutinib (10 mg/kg) in adjuvant arthritis (AA) rat model. Furthermore, compound XL-12 (LD50 > 1600 mg/kg) exerted improved safety compared with ibrutinib (LD50 = 750 mg/kg). These results indicated that compound XL-12, the dual BTK/JAK3 inhibitor, might be a potent drug candidate for the treatment of RA.

Dietary artemisinin boosts intestinal immunity and healthy in fat greenling (Hexagrammos otakii).

Introduction: Artemisinin (ART) is very common as a diet additive due to its immunoregulatory activities. Nonetheless, the immunoregulatory mechanism of ART in marine fish remains unknown. This study comprehensively examined the effects and explored the potential mechanism of ART ameliorating intestinal immune disease (IID) in fat greenlings (Hexagrammos otakii). Methods and results: The targets of ART were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Here, eight putative targets of ART were collected and identified with the Uniprot database, and 1419 IID-associated target proteins were filtered through the Drugbank, Genecards, OMIM, and PHARMGKB Databases. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways point out that ART may have immunoprotective effects by regulating cellular responses to stress, hypoxia, inflammation, and vascular endothelial growth factor stimulus through the hypoxia-inducible factor 1 (HIF-1) signaling pathway. The findings of molecular docking indicated that ART contains one active ingredient and three cross-targets, which showed a kind combination with hypoxia-inducible factor 1-alpha (HIF1-a), transcription factor p65 (RELA), and vascular endothelial growth factor A (VEGF-A), respectively. Furthermore, an ART feeding model was established to assess the ART's immunoprotect effect on the intestine of H.otakii in vivo. The D48 group showed smaller intestinal structural changes after being challenged by Edwardsiella tarda. The supplementation of ART to the diet improved total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced the malondialdehyde (MDA) in intestine of H. otakii. The expression of transcription factor p65, HIF1-α, VEGF-A, cyclin D1, matrix metalloprotease 9 (MMP9), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) was decreased after dietary ART in the intestinal of H. otakii. Discussion: The present results demonstrated that dietary ART improved antioxidants and immunity, optimized the intestinal structure, and increased resistance to E. tarda through the SOD2/nuclear-factor-kappa- B (NFkB)/HIF1-a/VEGF-A pathway in the intestinal tract of H.otakii. This study integrated pharmacological analysis and experimental validation and revealed the mechanism of ART on IID, which provides insight into the improvement of IID in H. otakii.

A novel glycoprotein from earthworm extract PvE-3: Insights of their characteristics for promoting diabetic wound healing and attenuating methylglyoxal-induced cell damage.

Diabetic chronic wound is a worldwide medical burden related to overdosed methylglyoxal (MGO) synthesis, which is the major precursor of glycation of proteins and DNA and is related to the dysfunction of dermal cells thus leading to chronic refractory wounds. Previous studies proved that earthworm extract accelerates diabetic wound healing and possesses cell proliferation and antioxidative effects. However, the effects of earthworm extract on MGO-damaged fibroblasts, the inner mechanisms of MGO-induced cell damage and the functional components in earthworm extract are still poorly understood. Firstly, we evaluated the bioactivities of the earthworm extract PvE-3 on the diabetic wound model and the diabetic related cell damage model. Then the mechanisms were investigated through transcriptomics, flow cytometry and fluorescence probe. The results revealed that PvE-3 promoted diabetic wound healing and protected fibroblast function in cell-damaged conditions. Meanwhile, the high-throughput screening implied the inner mechanisms of diabetic wound healing and PvE-3 cytoprotection effect were involved in the muscle cell function, the cell cycle regulation and the mitochondrial transmembrane potential depolarization. The functional glycoprotein isolated from PvE-3 possessed EGF-like domain which had a strong binding affinity with EGFR. The findings provided references to explore the potential treatments of diabetic wound healing.

Effects of Solidago canadensis L. on mineralization-immobilization turnover enhance its nitrogen competitiveness and invasiveness.

The effects of exotic plants on soil nitrogen (N) transformations may influence species invasion success. However, the complex interplay between invasive plant N uptake and N transformation in soils remains unclear. In the present study, a series of 15N-labeled pot experiments were carried out with Solidago canadensis L. (S. canadensis), an invasive plant, and the Ntrace tool was used to clarify the preferred inorganic N form and its effects on soil N transformation. According to the results, nitrate-N (NO3--N) uptake rates by S. canadensis were 2.38 and 2.28 mg N kg-1 d-1 in acidic and alkaline soil, respectively, which were significantly higher than the ammonium-N (NH4+-N) uptake rates (1.76 and 1.56 mg N kg-1 d-1, respectively), indicating that S. canadensis was a NO3--N-preferring plant, irrespective of pH condition. Gross N mineralization rate was 0.41 mg N kg-1 d-1 in alkaline soil in the presence of S. canadensis L., which was significantly lower than that in the control (no plant, CK, 2.44 mg N kg-1 d-1). Gross autotrophic nitrification rate also decreased from 5.95 mg N kg-1 d-1 in the CK to 0.04 mg N kg-1 d-1 in the presence of S. canadensis in alkaline soil. However, microbial N immobilization rate increased significantly from 1.09 to 2.16 mg N kg-1 d-1, and from 0.02 to 2.73 mg N kg-1 d-1 after S. canadensis planting, in acidic and alkaline soil, respectively. Heterotrophic nitrification rate was stimulated in the presence of S. canadensis to provide NO3--N to support the N requirements of plants and microbes. The results suggested that S. canadensis can influence the mineralization-immobilization turnover (MIT) to optimize its N requirements while limiting N supply for other plants in the system. The results of the present study enhance our understanding of the competitiveness and mechanisms of invasion of alien plants.

Effects of L-theanine on intestinal morphology, barrier function, and MAPK signaling pathways in diquat-challenged piglets.

This study aimed to explore the protective effects of L-theanine supplementation on the diquat-challenged weaned piglets. A total of 160 weaned piglets were randomly divided into 4 groups using a 2 × 2 two-factor design, there were 4 replicates per group and 10 pigs per replicate. Piglets were fed diets (with 1000 mg/kg L-theanine addition or not), then challenged with diquat or saline on day 7. 21 days after challenge, two pigs from each replicate were selected for sample collection. Results showed that supplement with 1000 mg/kg L-theanine down-regulated the diarrhea rate, serum D-lactate level, tumor necrosis factor-α, and phosphorylation of extracellular regulated protein kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signaling in pigs without diquat challenge (p < 0.05). While for diquat-challenged piglets, L-theanine addition increased average daily gain, jejunum villus height, and interferon-γ level (p < 0.05). Meanwhile, L-theanine addition decreased the diarrhea rates and mortality, serum D-lactate level, and phosphorylation of ERK and JNK in diquat-challenged pigs (p < 0.05). These results demonstrate that L-theanine pretreatment could alleviate diquat-induced oxidative stress and improve intestinal barrier function in diquat-challenged weaned piglets, which can be attributed to suppression of MAPK phosphorylation signaling pathways.

Ultrasound-assisted enzymatic extraction of Scutellaria baicalensis root polysaccharide and its hypoglycemic and immunomodulatory activities.

Scutellaria baicalensis is a medicinal plant possessing abundant bioactive polysaccharides. This study aimed to optimize the ultrasound-assisted enzymatic extraction of S. baicalensis root polysaccharide (SRP) and investigate its hypoglycemic and immunomodulatory activities. The optimal extraction conditions found in this study were as follows: cellulase concentration 165.6 U/mL, temperature 57.3 °C, liquid-solid ratio 44.8 mL/g, time 50 min, and ultrasonic power 225 W; with the yield reached up to 12.27 %. The ion exchange and gel filtration chromatographies were used to obtain a purified SRP. The carbohydrate content of SRP was 85.09 %, with a relatively high content of uronic acids (11.27 %). The SRP had a molecular weight of 89.7 kDa and was composed of eight monosaccharides. The inhibitory activity of SRP against α-amylase and α-glucosidase was determined. It was revealed that SRP could effectively inhibit these two enzymes with IC50 values of 1.23 and 0.63 mg/mL, respectively. Finally, the immunomodulatory effect of SRP on the dendritic cell activation was investigated, and the expressions of MHC II, CD80, CD86, and CD40 increased by 1.56, 1.96, 1.75, and 1.70 times, respectively, by the SRP treatment. This work will provide a foundation for SRP's efficient extraction and utilization for diabetes and immune therapy.

In vitro production of atractylon and ß-eudesmol from Atractylodes chinensis by adventitious root culture.

Atractylodes chinensis is a medicinal plant widely used for the treatment of gastric disorders, and its main bioactive compounds are atractylon and ß-eudesmol. This study was purposed to establish the adventitious root culture system of A. chinensis for in vitro production of atractylon and ß-eudesmol. The main parameters in the adventitious root induction and suspension cultures were optimized to maximize the culture efficiency. Adventitious roots were induced most efficiently from leaf explants on Murashige and Skoog (MS) solid medium containing 1.5 mg/L naphthaleneacetic acid (NAA) and 30 g/L sucrose with the highest root induction rate of approximately 92% and 12.9 roots per explant. During the adventitious root suspension culture, the root biomass and the accumulated content of the target compounds simultaneously increased to reach the maximum values after 8 weeks of culture. The maximum yield of the target compounds (total concentration 3.38 mg/g DW, total yield 2.66 mg) was achieved in the roots cultured in ½ MS liquid medium supplemented with 2.0 mg/L IBA, 3.2 mg/L NAA, and 40 g/L sucrose with the inoculum density of 8 g/L. Through the central composite design experiment, it was found that the combined use of different types of auxins in the suspension culture could further improve root growth and metabolite accumulation than the application of only one type of auxin. This work provides a new possibility to have a promising candidate for the industrial production of A. chinensis pharmaceuticals without relying on wild resources or field cultivation. KEY POINTS: • The induction culture was optimized for efficient root induction. • Suspension culture was optimized for the atractylon and ß-eudesmol production. • Combined use of different auxins improves root growth and metabolite accumulation.

How does UV-B stress affect secondary metabolites of Scutellaria baicalensis in vitro shoots grown at different 6-benzyl aminopurine concentrations?

Ultraviolet-B (UV-B) radiation is one of the abiotic stresses that can significantly affect the secondary metabolite accumulation in in vitro tissue cultures of medicinal plants. The present study investigated the effects of UV-B radiation on the secondary metabolites and antioxidant activities of Scutellaria baicalensis in vitro shoots grown at different concentrations of 6-benzyl aminopurine (6-BA), which is the cytokinin most widely used in plant tissue culture. The UV-B radiation caused significant increases in lipid peroxidation, total phenolic, and flavonoid contents, and antioxidant activities in the in vitro shoots grown at lower 6-BA concentrations (0 and 1 mg L-1 ), while it did not cause any significant changes in those grown at higher 6-BA concentrations (2 and 3 mg L-1 ). However, the UV-B radiation significantly altered the contents of main individual flavonoids at both lower and higher 6-BA concentrations. Upon UV-B radiation, aglycones (including baicalein, wogonin, and scutellarein) increased, while glucuronides such as baicalin and wogonoside decreased; this was more evident at higher 6-BA concentrations. This study demonstrated that the effects of UV-B radiation on the secondary metabolites of S. baicalensis in vitro shoots highly depended on the 6-BA concentration in the culture medium.

Achieving visible and near-infrared dual-emitting mechanoluminescence in Mn2+ single-doped magnesium aluminate spinel.

Visible (VIS) and near-infrared (NIR) mechanoluminescence (ML) materials have been developed rapidly for use in energy conversion, biological applications and mechanical sensing. The realization of visible and NIR ML in single host materials meets the dual requirements of visualization and anti-interference for high-precision mechanical sensing. In this work, Mn2+ single-doped magnesium aluminate spinel MgAl2O4 with excellent ML performance was studied in detail. Bright, visible green and NIR ML were achieved under mechanical stimulation, and the ratio between visible and NIR ML intensity can be regulated by manipulating the doping concentration of Mn2+. The generation of ML without additional pre-irradiation proved that the self-powered ML phenomenon was independent of trap. The functional relationship between mechanical parameters and ML intensity indicated that the doped spinel can be used for visualization, anti-interference and non-contact mechanical sensing. In addition, the NIR ML of MgAl2O4:Mn2+, centered at 835 nm, is located in the first NIR window (NIR-I, 650-950 nm), which effectively penetrates living tissue such as skin, fat, and lean meat, respectively, showing that it has potential applications in in vivo optical imaging.

Comparative transcriptomic analysis unveils the deep phylogeny and secondary metabolite evolution of 116 Camellia plants.

Camellia plants include more than 200 species of great diversity and immense economic, ornamental, and cultural values. We sequenced the transcriptomes of 116 Camellia plants from almost all sections of the genus Camellia. We constructed a pan-transcriptome of Camellia plants with 89 394 gene families and then resolved the phylogeny of genus Camellia based on 405 high-quality low-copy core genes. Most of the inferred relationships are well supported by multiple nuclear gene trees and morphological traits. We provide strong evidence that Camellia plants shared a recent whole genome duplication event, followed by large expansions of transcription factor families associated with stress resistance and secondary metabolism. Secondary metabolites, particularly those associated with tea quality such as catechins and caffeine, were preferentially heavily accumulated in the Camellia plants from section Thea. We thoroughly examined the expression patterns of hundreds of genes associated with tea quality, and found that some of them exhibited significantly high expression and correlations with secondary metabolite accumulations in Thea species. We also released a web-accessible database for efficient retrieval of Camellia transcriptomes. The reported transcriptome sequences and obtained novel findings will facilitate the efficient conservation and utilization of Camellia germplasm towards a breeding program for cultivated tea, camellia, and oil-tea plants.

Association between NF-κB Signal Pathway-Related Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density.

Background: Osteoporosis is a systemic bone disease characterized by reduction of bone content. Bisphosphonates are first-line treatments for osteoporosis, but they have variable effectiveness. Genetic factors may explain these differences. The NF-κB signaling pathway plays a key role in the regulation of bone metabolism. We aimed to determine whether genetic variations in the NF-κB signaling pathway affect the effectiveness of alendronate in postmenopausal Chinese women with low bone mass. Methods: We recruited 455 postmenopausal Han Chinese women with primary osteoporosis or osteopenia aged 48-90 yrs who had experienced no spontaneous menses for at least 1 yr. All participants had dual X-ray absorptiometry (DEXA) bone mineral density (BMD) measurement at baseline and 1 yr after treatment. Treatment involved 1 yr administration of 70 mg oral alendronate weekly and 600 mg calcium and 125 IU of vitamin D daily. Thirteen tagSNPs in NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068), RELA (rs7119750, rs11820062), and NLRC5 (rs289747, rs1566439, rs1684575, rs289726, rs289723, and rs41383) were chosen from the NCBI Locus Link and HapMap and genotyped individually. Genetic variation in these genes and the corresponding therapeutic response to alendronate treatment were analyzed. Results: Among the 13 tagSNPs, rs289747 was significantly correlated with the BMD change rate at the femoral neck (P=0.048). This significance no longer existed after Bonferroni correction. We then performed principal component analysis (PCA) and found NLRC5 (rs289747 and rs1566439) were strongly correlated with alendronate efficacy in femoral phenotypes and were major components of BMD change values, particularly total hip and intertrochanteric phenotypes. Furthermore, the PLINK linear regression GLM model revealed that haplotype TT of RELA (rs7119750 and rs11820062) and ICCTA of NF-κB1 (rs28362491, rs3774937, rs230521, rs230510, and rs4648068) were associated with BMD of the total hip among each haplotype after 1 yr of treatment. Conclusion: The NF-κB1, RELA, and NLRC5 genetic variations affect the therapeutic response of alendronate treatment for postmenopausal osteoporosis.

EEG characteristic investigation of the sixth-finger motor imagery and optimal channel selection for classification.

Objective.Supernumerary robotic limbs are body augmentation robotic devices by adding extra limbs or fingers to the human body different from the traditional wearable robotic devices such as prosthesis and exoskeleton. We proposed a novel motor imagery (MI)-based brain-computer interface (BCI) paradigm based on the sixth-finger which imagines controlling the extra finger movements. The goal of this work is to investigate the electromyographic (EEG) characteristics and the application potential of MI-based BCI systems based on the new imagination paradigm (the sixth finger MI).Approach.Fourteen subjects participated in the experiment involving the sixth finger MI tasks and rest state. Event-related spectral perturbation was adopted to analyze EEG spatial features and key-channel time-frequency features. Common spatial patterns were used for feature extraction and classification was implemented by support vector machine. A genetic algorithm (GA) was used to select combinations of EEG channels that maximized classification accuracy and verified EEG patterns based on the sixth finger MI. And we conducted a longitudinal 4 weeks EEG control experiment based on the new paradigm.Main results.Event-related desynchronization (ERD) was found in the supplementary motor area and primary motor area with a faint contralateral dominance. Unlike traditional MI based on the human hand, ERD was also found in frontal lobe. GA results showed that the distribution of the optimal eight-channel is similar to EEG topographical distributions, nearing parietal and frontal lobe. And the classification accuracy based on the optimal eight-channel (the highest accuracy of 80% and mean accuracy of 70%) was significantly better than that based on the random eight-channel (p< 0.01).Significance.This work provided a new paradigm for MI-based MI system and verified its feasibility, widened the control bandwidth of the BCI system.

Role of hyperbaric oxygen in glioma: a narrative review.

Gliomas are common brain mass with a high mortality rate. Patients with gliomas have a severely bad outcome, with an average survive duration less 15 months because of high recurrent rate and being resistant to radio-therapy and chemistry drugs therapy. Hyperbaric oxygen is extensively taken as an adjuvant treatment for various disease conditions. To know the characteristics of hyperbaric oxygen as a remedy for gliomas, we find that, in general, hyperbaric oxygen shows an obviously positive effect on the treatment of gliomas, and it can also relieve the complications caused by postoperative radiotherapy and chemotherapy of gliomas. Whereas, several researches have shown that hyperbaric oxygen promotes glioma progression.

Isovitexin Inhibits Ginkgolic Acids-Induced Inflammation Through Downregulating SHP2 Activation.

It has been reported that Celtis sinensis Pers. is employed as a folk medicine for the treatment of inflammatory diseases. But the mechanism supporting its use as anti-inflammatory remains unclear. To investigate the anti-inflammatory of Celtis sinensis Pers. ICR mice were provided Celtis sinensis Pers. leaf extract (CLE) at 100, 200 mg/kg after ginkgolic acids (GA) sensitization. Our data showed that CLE and the main flavonoid isovitexin in CLE could ameliorate GA-induced contact dermatitis in mice. Ear swelling, inflammatory cell infiltration and splenomegaly were inhibited significantly by isovitexin, while the weight loss of mice in the isovitexin-treated group was much better than that in the dexamethasone-treated group (positive control drug). It has been reported in previous research that GA-induced inflammation is closely related to the T cell response. Therefore, T cells were the focus of the anti-inflammatory effect of isovitexin in this paper. The in vivo results showed that isovitexin (10, 20 mg/kg) inhibited the expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-2 and IL-17A) in lymph nodes, inhibited the secretion of cytokines into the serum from mice with contact dermatitis and promoted the expression of apoptosis-related proteins. In vitro, isovitexin also induced apoptosis and inhibited proinflammatory cytokine expression in Con A-activated T cells. Further study showed that the MAPK and STAT signaling pathways and the phosphorylation of SHP2 were inhibited by isovitexin. Both molecular docking and biological experiments indicated that SHP2 may be an anti-inflammatory target of isovitexin in T cells. Taken together, isovitexin can serve as a potential natural agent for the treatment or prevention of GA-induced inflammatory problems.

Loss of MIC60 Aggravates Neuronal Death by Inducing Mitochondrial Dysfunction in a Rat Model of Intracerebral Hemorrhage.

Mitochondrial damage has been reported to be a critical factor for secondary brain injury (SBI) induced by intracerebral hemorrhage (ICH). MIC60 is a key element of the mitochondrial contact site and cristae junction organizing system (MICOS), which takes a principal part in maintaining mitochondrial structure and function. The role of MIC60 and its underlying mechanisms in ICH-induced SBI are not clear, which will be investigated in this present study. To establish and emulate ICH model in vivo and in vitro, autologous blood was injected into the right basal ganglia of Sprague-Dawley (SD) rats; and primary-cultured cortical neurons were treated by oxygen hemoglobin (OxyHb). First, after ICH induction, mitochondria were damaged and exhibited mitochondrial crista-structure remodeling, and MIC60 protein levels were reduced. Furthermore, MIC60 overexpression reduced ICH-induced neuronal death both in vivo and in vitro. In addition, MIC60 upregulation reduced ICH-induced cerebral edema, neurobehavioral impairment, and cognitive dysfunction; by contrast, MIC60 knockdown had the opposite effect. Additionally, in primary-cultured neurons, MIC60 overexpression could reverse ICH-induced neuronal cell death and apoptosis, mitochondrial membrane potential collapse, and decrease of mitophagy, indicating that MIC60 overexpression can maintain the integrity of mitochondrial structures. Moreover, loss of MIC60 is after ICH-induced reduction in PINK1 levels and mislocalization of Parkin in primary-cultured neurons. Taken together, our findings suggest that MIC60 plays an important role in ICH-induced SBI and may represent a promising target for ICH therapy.

Dietary iron and vitamins in association with mortality.

BACKGROUND & AIMS: Although disorders of iron metabolism are among the most common diseases and dietary intakes of vitamin A, B2, B6, C, E, and folic acid are known to affect the absorption or oxidation of iron, limited data are available on the association of dietary iron and these vitamins with mortality in the same population. Specifically, the holistic dietary vitamins intake and its combined effect with iron on mortality are unclear. The purpose of this study was to evaluate the association of dietary iron, holistic dietary vitamins, and their interactive effect with total and cause-specific mortality. METHODS: We evaluated the effects of dietary total/heme/non-heme iron, vitamins, and their interaction on all-cause/cardiovascular disease (CVD)/cancer mortality among 14,826 US adults in the National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative study. We developed a vitamin score to represent the holistic dietary intakes of vitamin A, B2, B6, C, E, and folic acid. RESULTS: A total of 2154 deaths occurred during a median follow-up of 9.3 years. Results from multivariate Cox proportional hazards models showed that higher vitamin score was associated lower risk of all-cause mortality (P-trend = 0.027). Negative interactions between dietary heme iron and vitamin score were observed on all-cause/CVD mortality. Dietary higher vitamins combined with lower heme iron was associated with lower risk of all-cause and CVD mortality (HR (95% confidence intervals (CIs)): 0.80 (0.64-0.98) and 0.55 (0.31-0.98), respectively). Higher dietary vitamins combined with higher total/non-heme iron was associated with lower risk of CVD mortality (HR (95%CIs): 0.69 (0.48-0.99) and 0.70 (0.48-0.99), respectively). These results remained significant even excluding participants with iron supplementation. CONCLUSION: Our findings suggested that interactive effect of holistic dietary vitamins and iron play a protective role in decreasing all-cause and CVD mortality. Future studies, including cohort studies and clinical trials, are necessary to confirm these findings.

Research progress on the protective effects of licorice-derived 18ß-glycyrrhetinic acid against liver injury.

The first description of the medical use of licorice appeared in "Shennong Bencao Jing", one of the well-known Chinese herbal medicine classic books dated back to 220-280 AD. As one of the most commonly prescribed Chinese herbal medicine, licorice is known as "Guo Lao", meaning "a national treasure" in China. Modern pharmacological investigations have confirmed that licorice possesses a number of biological activities, such as antioxidation, anti-inflammatory, antiviral, immune regulation, and liver protection. 18ß-glycyrrhetinic acid is one of the most extensively studied active integrants of licorice. Here, we provide an overview of the protective effects of 18ß-glycyrrhetinic acid against various acute and chronic liver diseases observed in experimental models, and summarize its pharmacological effects and potential toxic/side effects at higher doses. We also make additional comments on the important areas that may warrant further research to support appropriate clinical applications of 18ß-glycyrrhetinic acid and avoid potential risks.