DHEA down-regulates mitochondrial dynamics and promotes apoptosis of lung adenocarcinoma cells through FASTKD2.

Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.

Cnidii Fructus: A traditional Chinese medicine herb and source of antiosteoporotic drugs.

BACKGROUND: Osteoporosis (OP) is a prevalent chronic metabolic bone disease for which limited countermeasures are available. Cnidii Fructus (CF), primarily derived from Cnidium monnieri (L.) Cusson., has been tested in clinical trials of traditional Chinese medicine for the management of OP. Accumulating preclinical studies indicate that CF may be used against OP. MATERIALS AND METHODS: Comprehensive documentation and analysis were conducted to retrieve CF studies related to its main phytochemical components as well as its pharmacokinetics, safety and pharmacological properties. We also retrieved information on the mode of action of CF and, in particular, preclinical and clinical studies related to bone remodeling. This search was performed from the inception of databases up to the end of 2022 and included PubMed, China National Knowledge Infrastructure, the National Science and Technology Library, the China Science and Technology Journal Database, Weipu, Wanfang, the Web of Science and the China National Patent Database. RESULTS: CF contains a wide range of natural active compounds, including osthole, bergapten, imperatorin and xanthotoxin, which may underlie its beneficial effects on improving bone metabolism and quality. CF action appears to be mediated via multiple processes, including the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK), Wnt/ß-catenin and bone morphogenetic protein (BMP)/Smad signaling pathways. CONCLUSION: CF and its ingredients may provide novel compounds for developing anti-OP drugs.

Integrating serum pharmacochemistry and network pharmacology to explore the molecular mechanisms of Acanthopanax senticosus (Rupr. & Maxim.) Harms on attenuating doxorubicin-induced myocardial injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. or Siberian ginseng, has a rich history of use as an adaptogen, a substance believed to increase the body's resistance to stress, fatigue, and infectious diseases. As a traditional Chinese medicine, AS is popular for its cardioprotective effects which can protect the cardiovascular system from hazardous conditions. Doxorubicin (DOX), on the other hand, is a first-line chemotherapeutic agent against a variety of cancers, including breast cancer, lung cancer, gastric cancer, and leukemia, etc. Despite its effectiveness, the clinical use of DOX is limited by its side effects, the most serious of which is cardiotoxicity. Considering AS could be applied as an adjuvant to anticancer agents, the combination of AS and DOX might exert synergistic effects on certain malignancies with mitigated cardiotoxicity. Given this, it is necessary and meaningful to confirm whether AS would neutralize the DOX-induced cardiotoxicity and its underlying molecular mechanisms. AIM OF THE STUDY: This paper aims to validate the cardioprotective effects of AS against DOX-induced myocardial injury (MI) while deciphering the molecular mechanisms underlying such effects. MATERIALS AND METHODS: Firstly, the cardioprotective effects of AS against DOX-induced MI were confirmed both in vitro and in vivo. Secondly, serum pharmacochemistry and network pharmacology were orchestrated to explore the in vivo active compounds of AS and predict their ways of functioning in the treatment of DOX-induced MI. Finally, the predicted mechanisms were validated by Western blot analysis during in vivo experiments. RESULTS: The results demonstrated that AS possessed excellent antioxidative ability, and could alleviate the apoptosis of H9C2 cells and the damage to mitochondria induced by DOX. In vivo experiments indicated that AS could restore the conduction abnormalities and ameliorate histopathological changes according to the electrocardiogram and cardiac morphology. Meanwhile, it markedly downregulated the inflammatory factors (TNF-α, IL-6, and IL-1ß), decreased plasma ALT, AST, LDH, CK, CK-MB, and MDA levels, as well as increased SOD and GSH levels compared to the model group, which collectively substantiate the effectiveness of AS. Afterward, 14 compounds were identified from different batches of AS-dosed serum and selected for mechanism prediction through HPLC-HRMS analysis and network pharmacology. Consequently, the MAPKs and caspase cascade were confirmed as primary targets among which the interplay between the JNK/Caspase 3 feedback loop and the phosphorylation of ERK1/2 were highlighted. CONCLUSIONS: In conclusion, the integrated approach employed in this paper illuminated the molecular mechanism of AS against DOX-induced MI, whilst providing a valuable strategy to elucidate the therapeutic effects of complicated TCM systems more reliably and efficiently.

Miniaturized centrifugation accelerated pipette-tip matrix solid-phase dispersion based on poly(deep eutectic solvents) surface imprinted graphene oxide composite adsorbent for rapid extraction of anti-adipogenesis markers from Solidago decurrens Lour.

Overweight and obesity are the causes of many diseases and have become global "epidemics". Research on natural active components with anti-adipogenesis effects in plants has aroused the interest of researchers. One of the most critical problems is establishing sample preparation and analytical techniques for quickly and selectively extracting and determining the active anti-adipogenesis components in complex plant matrices for developing new anti-adipogenic drugs. In this study, a new poly(deep eutectic solvents) surface imprinted graphene oxide composite (PDESs-MIP/GO) with high selectivity for phenolic acids was prepared using deep eutectic solvents as monomers and crosslinkers. A miniaturized centrifugation-accelerated pipette-tip matrix solid-phase dispersion method (CPT-MSPD) with PDESs-MIP/GO as adsorbent, coupled with high-performance liquid chromatography, was further developed for the rapid determination of anti-adipogenesis markers in Solidago decurrens Lour. (SDL). The established method was successfully used to determination anti-adipogenesis markers in SDL from different regions, with the advantages of accuracy (recoveries: 94.4 - 115.9 %, RSDs ≤ 9.8 %), speed (CPT-MSPD time: 11 min), selectivity (imprinting factor: ∼2.0), and economy (2 mg of adsorbent and 1 mL of solvents), which is in line with the current advanced principle of "3S+2A" in analytical chemistry.

Simiao San alleviates hyperuricemia and kidney inflammation by inhibiting NLRP3 inflammasome and JAK2/STAT3 signaling in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Simiao San (SmS), a famous traditional Chinese formula, is clinically used to treat patients with hyperuricemia (HUA). However, its mechanism of action on lowering uric acid (UA) and inhibiting inflammation still deserves further investigation. AIM OF THE STUDY: To examine the effect and its possible underlying mechanism of SmS on UA metabolism and kidney injury in HUA mouse. MATERIALS AND METHODS: The HUA mouse model was constructed with the combined administration of both potassium oxalate and hypoxanthine. The effects of SmS on UA, xanthine oxidase (XOD), creatinine (CRE), blood urea nitrogen (BUN), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by ELISA or biochemical assays. Hematoxylin and eosin (H&E) was used to observe pathological alterations in the kidneys of HUA mice. The expression levels of organic anion transporter 1 (OAT1), recombinant urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), nucleotide binding domain and leucine rich repeat pyrin domain containing 3 (NLRP3), Cleaved-Caspase 1, apoptosis-associated speck like protein (ASC), nuclear factor kappa-B (NF-κB), IL-6, janus kinase 2 (JAK2), phosphor (P)-JAK2, signal transducers and activators of transcription 3 (STAT3), P-STAT3, suppressor of cytokine signaling 3 (SOCS3) were examined by Western blot and/or immunohistochemical (IHC) staining. The major ingredients in SmS were identified by a HPLC-MS assay. RESULTS: HUA mouse exhibited an elevation in serum levels of UA, BUN, CRE, XOD, and the ratio of urinary albumin to creatinine (UACR), and a decline in urine levels of UA and CRE. In addition, HUA induces pro-inflammatory microenvironment in mouse, including an increase in serum levels of IL-1ß, IL-6, and TNF-α, and renal expressions of URAT1, GULT9, NLRP3, ASC, Cleaved-Caspase1, P-JAK2/JAK2, P-STAT3/STAT3, and SOCS3, and a decrease in serum IL-10 level and renal OAT1 expression as well as a disorganization of kidney pathological microstructure. In contrast, SmS intervention reversed these alterations in HUA mouse. CONCLUSION: SmS could alleviate hyperuricemia and renal inflammation in HUA mouse. The action mechanisms behind these alterations may be associated with a limitation of the NLRP3 inflammasome and JAK2/STAT3 signaling pathways.

Traditional Chinese Medicine Rhodiola Sachalinensis Borissova from Baekdu Mountain (RsBBM) for Rheumatoid Arthritis: Therapeutic Effect and Underlying Molecular Mechanisms.

The lack of effective rheumatoid arthritis (RA) therapies is a persistent challenge worldwide, prompting researchers to urgently evaluate traditional Chinese medicines (TCMs) as potential clinical RA treatments. The present investigation was conducted to evaluate the therapeutic effects and potential molecular mechanisms of the active components isolated from TCM Rhodiola sachalinensis Borissova from Baekdu Mountain (RsBBM) using an experimental adjuvant arthritis model induced by injection of rats with Freund's complete adjuvant. After induction of the adjuvant arthritis rat model, the extract-treated and untreated groups of arthritic rats were evaluated for RsBBM therapeutic effects based on comparisons of ankle circumferences and ELISA-determined blood serum inflammatory factor levels (TNF-α, IL-1ß, and PGE2). In addition, the joint health of rats was evaluated via microscopic examination of hematoxylin-eosin-stained synovial tissues. Furthermore, to explore whether NF-κB and RANK/RANKL/OPG signaling pathways participated in observed therapeutic effects from a molecular mechanistic viewpoint, mRNA and protein levels related to the expression of nuclear factor kappa-B (NF-κB), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-Β ligand (RANKL) were analyzed via quantitative RT-PCR and Western blot analysis, respectively. Treatment of arthritic rats with the extract of RsBBM was shown to reduce ankle swelling, reduce blood serum levels of inflammatory factors, and alleviate arthritis-associated synovial inflammation and joint damage. Moreover, an RsBBM 50% ethanol extract treatment inhibited bone destruction by up-regulating OPG-related mRNA and protein expression and down-regulating RANKL-related mRNA and protein expression, while also reducing inflammation by the down-regulating of the NF-κB pathway activity. The results clearly demonstrated that the extract of RsBBM alleviated adjuvant arthritis-associated joint damage by altering activities of inflammation-associated NF-κB and the RANK/RANKL/OPG signaling pathways. Due to its beneficial effects for alleviating adjuvant arthritis, this RsBBM 50% ethanol extract should be further evaluated as a promising new therapeutic TCM treatment for RA.

Integrated strategy of network pharmacology, molecular docking, HPLC-DAD and mice model for exploring active ingredients and pharmacological mechanisms of Penthorum chinense Pursh against alcoholic liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense Pursh (PCP, Saxifragaceae) is an edible plant and frequently-used Chinese herbal medicine, and is commonly used as Miao medicine in China. It showed well effect on alcoholic liver injury (ALI), but studies on its active ingredients and mechanisms against ALI remain at the starting stage. AIM OF THE STUDY: This work aims to explore the active ingredients and pharmacological mechanisms of PCP against ALI. MATERIALS AND METHODS: First, network pharmacology was applied to decipher the potential active ingredients and pharmacological mechanisms of PCP against ALI by ingredient identification, ADMET evaluation, target identification, network construction and analysis, protein-protein interaction (PPI) analysis, and gene enrichment analysis. Second, molecular docking was used to explore the interaction between key active ingredient and hub protein of PCP against ALI. Then, the ingredient analysis of PCP aqueous extract and semiquantitative analysis of key active ingredient were carried out on HPLC-DAD. Subsequently, mice with ALI were used to investigate the therapeutic effect or verify the predicted mechanisms of PCP or key active ingredient against ALI by analyzing body weight, liver index, ALT and AST activities in serum and liver tissues, oxidation related indices (SOD activity, GSH level and MDA level) in liver tissues, histopathology of liver tissues (oil red O, hematoxylin-eosin and DAB-TUNEL staining), and changes of related proteins (PI3K, Akt, p-Akt, Bax and Bcl-2) in liver tissues with the aid of Western blot. RESULTS: Network pharmacology showed that the active ingredients and related genes of PCP against ALI comprised 10 ingredients and 52 genes. Based on the result of ingredient analysis of PCP aqueous extract, quercitrin was identified as the key active ingredient of PCP against ALI. PPI analysis indicated that AKT1 was the hub gene of PCP against ALI, and molecular docking suggested that there were good interaction between quercetin and Akt1 protein. Gene enrichment analysis showed that the pivotal molecular mechanism of PCP against ALI might be to inhibit hepatocyte apoptosis via activation of PI3K-Akt signaling pathway. PCP and quercitrin showed anti-ALI effect by offsetting weight loss and increase of liver index, and reversing the imbalance of oxidative stress and histopathological changes of liver tissues (abnormal fatty acid metabolism, hepatic cord swelling and inflammatory cell infiltration) in mice with ALI. PCP caused the decrease of DAB-TUNEL-positive cells, upregulated the anti-apoptotic proteins (PI3K, Akt and p-Akt) levels and the ratio of p-Akt/Akt, and downregulated pro-apoptotic protein (Bax) level and the ratio of Bax/Bcl-2 in liver tissues of mice with ALI, indicating that the mechanism of PCP against ALI involved in inhibiting hepatocyte apoptosis via activation of PI3K-Akt signaling pathway. CONCLUSION: PCP and quercitrin showed well anti-ALI effect. The key active ingredient of PCP against ALI was identified as quercitrin. The underlying pharmacological mechanisms of PCP against ALI may be related to PI3K-Akt signaling pathway-mediated inhibition of hepatocyte apoptosis. This work provided new evidence to support the application of PCP in treatment of ALI, and a research basis for the research and development of functional foods or drugs against ALI from PCP.

Mutation of glucose-methanol-choline oxidoreductase leads to thermosensitive genic male sterility in rice and Arabidopsis.

Thermosensitive genic male sterility (TGMS) lines serve as the major genetic resource for two-line hybrid breeding in rice. However, their unstable sterility under occasional low temperatures in summer highly limits their application. In this study, we identified a novel rice TGMS line, ostms18, of cultivar ZH11 (Oryza sativa ssp. japonica). ostms18 sterility is more stable in summer than the TGMS line carrying the widely used locus tms5 in the ZH11 genetic background, suggesting its potential application for rice breeding. The ostms18 TGMS trait is caused by the point mutation from Gly to Ser in a glucose-methanol-choline (GMC) oxidoreductase; knockout of the oxidoreductase was previously reported to cause complete male sterility. Cellular analysis revealed the pollen wall of ostms18 to be defective, leading to aborted pollen under high temperature. Further analysis showed that the tapetal transcription factor OsMS188 directly regulates OsTMS18 for pollen wall formation. Under low temperature, the flawed pollen wall in ostms18 is sufficient to protect its microspore, allowing for development of functional pollen and restoring fertility. We identified the orthologous gene in Arabidopsis. Although mutants for the gene were fertile under normal conditions (24°C), fertility was significantly reduced under high temperature (28°C), exhibiting a TGMS trait. A cellular mechanism integrated with genetic mutations and different plant species for fertility restoration of TGMS lines is proposed.

Amygdalin Induced Mitochondria-Mediated Apoptosis of Lung Cancer Cells via Regulating NF[Formula: see text]B-1/NF[Formula: see text]B Signaling Cascade in Vitro and in Vivo.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Amygdalin, a natural compound commonly distributed in plants of the Rosaceae species, owns anticancer activity, less side effects, wide source, and relatively low price. Although the apoptosis is a central process activated by amygdalin in cancer cells, the underlying molecular mechanisms through which amygdalin induces the apoptosis of lung cancer cells remain poorly understood. In this research work, amygdalin could suppress the proliferation of lung cancer A549 and PC9 cells by CCK8 assay. Amygdalin significantly promoted the apoptosis of lung cancer A549 and PC9 cells stained with Annexin V-FITC/PI by flow cytometry assay. Furthermore, amygdalin dose-dependently decreased the mitochondrial membrane potential (MMP) with JC-1 dye by flow cytometry. To investigate the underlying molecular mechanisms through which amygdalin induced mitochondria-mediated apoptosis of cancer cells, the differentially-expressed genes with a fold change >2.0 and p < 0.05 were acquired from the cDNA microarray analysis. The results of qRT-PCR further confirmed that the differentially-expressed level of the NF[Formula: see text]B-1 gene was most obviously enhanced in lung cancer cells treated with amygdalin. The results of immunofluorescence staining, Western blotting and siRNA knockdown indicated that amygdalin induced mitochondria-mediated apoptosis of lung cancer cells via enhancing the expression of NF[Formula: see text]B-1 and inactivating NF[Formula: see text]B signaling cascade and further changing the expressions of proteins (Bax, Bcl-2, cytochrome C, caspase 9, caspase 3 and PARP) related to apoptosis, which were further checked by in vivo study of the lung cancer cell xenograft mice model accompanying with immunohistochemical staining and TUNEL staining. Our results indicated that amygdalin might be a potential activator of NF[Formula: see text]B-1, which sheds more light on the molecular mechanism of anticancer effects of amygdalin. These results highlighted amygdalin as a potential therapeutic anticancer agent, which warrants its development as a therapy for lung cancer.

Cell-Selective Encapsulation within Metal-Organic Framework Shells via Precursor-Functionalized Aptamer Identification for Whole-Cell Cancer Vaccine.

Single-cell encapsulation is an emerging technology to endow cells with various functions, of which developing new applications in vivo is in high demand. Currently, metal-organic frameworks (MOFs) that are used as nanometric shells to coat living cells, however, have not realized cell-selective encapsulation. Here, a biocompatible and selective cell encapsulation strategy based on precursor-functionalized nucleolin aptamer and in situ MOF mineralization on the aptamer-identified cancer cell surface are developed. After MOF coating, the encapsulated cancer cells undergo immunogenic cell death, which is found associated with the changed cell stiffness (indicated by Young's modulus). The immunogenic dead cancer cells are used as whole-cell cancer vaccines (WCCVs), forming the integral WCCV-in-shell structure with enhanced immunogenicity ascribing from the surface-exposed calreticulin to promote dendritic cell recruitment, antigen presentation, and T-cell activation. The major activation pathways in the immune response are identified including tumor necrosis factor signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway, suggesting the potential adjuvant effect of the MOF shells. After vaccination, WCCV-in-shell shows much better tumor immunoprophylaxis than either the imperfectly coated cancer cells or the traditional WCCV. This strategy is promising for the universal and facile development of novel whole-cell vaccines.

A Systematic Review on Polysaccharides from Dendrobium Genus: Recent Advances in the Preparation, Structural Characterization, Bioactive Molecular Mechanisms, and Applications.

Dendrobium polysaccharides (DPSs) have aroused people's increasing attention in recent years as a result of their outstanding edible and medicinal values and non-toxic property. This review systematically summarized recent progress in the different preparation techniques, structural characteristics, modification, various pharmacological activities and molecular mechanisms, structure-activity relationships, and current industrial applications in the medicinal, food, and cosmetics fields of DPSs. Additionally, some recommendations for future investigations were provided. A variety of methods were applied for the extraction and purification of DPSs. They possessed primary structures (e.g., glucomannan, rhamnogalacturonan I type pectin, heteroxylan, and galactoglucan) and conformational structures (e.g., random coil, rod, globular, and a slight triple-helical). And different molecular weights, monosaccharide compositions, linkage types, and modifications could largely affect DPSs' bioactivities (e.g., immunomodulatory, anti-diabetic, hepatoprotective, gastrointestinal protective, antitumor, anti-inflammatory, and anti-oxidant activities). It was worth mentioning that DPSs were significant pharmaceutical remedies and therapeutic supplements especially due to their strong immunity enhancement abilities. We hope that this review will lay a solid foundation for further development and applications of Dendrobium polysaccharides.

Interrelation among one-carbon metabolic (OCM) pathway-related indicators and its impact on the occurence of pregnancy-induced hypertension disease in pregnant women supplemented with folate and vitamin B12: Real-world data analysis.

Background and objective: A considerable number of pregnant women who were supplemented with folate and vitamin B12 were selected as major participants in studying the one-carbon metabolic (OCM) pathway. Our study aimed to explore the effects of OCM-related indicators on pregnancy-induced hypertension (PIH) and preeclampsia (PE) in pregnant women with folate and vitamin B12 supplementation. Subjects and methods: A total of 1,178 pregnant women who took multivitamin tablets containing 800 µg folate and 4 µg vitamin B12 daily from 3 months before pregnancy to 3 months after pregnancy were enrolled in this study. These pregnant women were classified into three groups: the normotensive group (n = 1,006), the PIH group (n = 131), and the PE group (n = 41). The information on age, weight, body mass index (BMI), number of embryos, gravidity, parity, and OCM-related indicators (serum level of homocysteine, folate, and vitamin B12; MTHFR C677T genotype) was collected. Results: The accuracy of the prediction model based on the screened independent risk factors (hyperhomocysteine, OR = 1.170, 95% CI = 1.061-1.291; high folate status, OR = 1.018, 95% CI = 0.999-1.038; and high BMI, OR = 1.216, 95% CI = 1.140-1.297) for PIH in subjects with MTHFR CC genotype (AUC = 0.802) was obviously higher than that in subjects with MTHFR CT, TT genotype (AUC = 0.684,0.685, respectively) by receiver operating characteristic curve analysis. The homocysteine level of the PIH group was significantly higher than that of the normotensive group only in subjects with the MTHFR CC genotype (p = 0.005). A negative correlation between homocysteine and folate appeared in subjects with MTHFR CT + TT genotype (p = 0.005). A model including multiple embryos, nulliparas, and lower folate could predict the process from PIH to PE (AUC = 0.781, p < 0.0001). Conclusion: The prediction model composed of homocysteine, folate, and BMI for PIH was suitable for subjects with MTHFR CC genotype in pregnant women with supplementation of folate and vitamin B12. Lower folate levels could be an independent risk factor in developing the process from PIH to PE.

Novel active starch films incorporating tea polyphenols-loaded porous starch as food packaging materials.

A novel active food packaging film was developed by casting a corn starch/tea polyphenol (TP)-loaded porous starch (PS, obtained by enzymatic hydrolysis) film forming solution, with the latter helping to regulate the slow release of TP. Results showed that PS had a favorable TP adsorption capacity, and the casted films had a homogeneous distribution of the formulation components. Likewise, the active films had good mechanical properties, UV barrier properties, thermal stability, and excellent antioxidant properties. The slow release of TP from the films was sustained, which is a desired characteristic for extending the protection afforded by the active film to the food under consideration.

A review of Acanthopanax senticosus (Rupr and Maxim.) harms: From ethnopharmacological use to modern application.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (AS), previously classified as Eleutherococcus senticosus, is one of the most commonly used herbs in the Chinese materia medica. However, there is currently no comprehensive review summarising advances in AS research. AS has been used as a functional food and in various preparations since ancient times, to invigorate the liver and kidneys, replenish vitality, strengthen the bones, stimulate appetite, and improve memory. It is widely used in countries such as China, Korea, Japan, and Russia, for specific pharmacologic effects, although it contains various chemical components that ensure its broad-spectrum effect. Its chemical constituents mainly include glycosides and flavonoids. Over the past several decades, researchers worldwide have conducted systematic investigations on this herb. AS has positive pharmacological effects on the cardiovascular, central nervous, and immune systems. Representative pathways stimulated by AS are related to neuroactive ligand-receptor interactions, cancer, and phosphatidylinositol 3 kinase/protein kinase B signalling. Importantly, AS is safe and exerts no significant adverse effects at normal doses. AIM OF THE STUDY: To provide comprehensive insights into the ethnobotany, medicinal uses, chemical composition, pharmacological activity, and toxicology of AS to aid its future development and utilisation. MATERIALS AND METHODS: Information about AS was collected from various sources, including classic books about Chinese herbal medicine and scientific databases including scientific journals, books, and pharmacopoeia. We discuss the ethnopharmacology of AS from 1965 to 2020 and summarise the knowledge of AS phytochemicals, pharmacological activity, quality control, and toxicology. CONCLUSIONS: From the current literature, we conclude that AS is a promising dietary Chinese herb with various potential applications owing to its multiple therapeutic effects.

Degradation Kinetics of Anthocyanins from Purple Eggplant in a Fortified Food Model System during Microwave and Frying Treatments.

A model food system was designed with dietary fiber and crude anthocyanins from purple eggplant peel to explore the degradation mechanism of anthocyanins during microwave and frying treatments. Our results found that delphinidin-3-O-rutinoside was either hydrolyzed into delphinidin or condensed with p-coumaric acid to form p-coumaroyl-delphinidin-3-O-glucoside. Delphinidin was cleaved into gallic acid and phloroglucinaldehyde, which might be further oxidized into pyrogallol and phloroglucinol, respectively. The total anthocyanin degradation followed the first-order kinetics in fried and microwaved solid matrix samples as well as microwaved liquid matrix samples. However, the total anthocyanin degradation followed the second-order kinetics in the heated liquid matrix samples at the frying temperature. The brown/polymeric color index, which negatively correlated with the anthocyanin content, increased faster in the liquid matrix samples than in the solid matrix samples. Compared with frying treatment, a higher rate of anthocyanin degradation in solution was observed under microwave treatment. However, anthocyanins were subject to much more damage under frying treatment than microwave treatment in a solid food system.

Autophagy inhibition enhances the inhibitory effects of ursolic acid on lung cancer cells.

The aim of the present study was to identify natural compounds that bear significant anti­tumor activity. Thus, the effects of 63 small molecules that were isolated from traditional Chinese medicinal herbs on A549 human non­small cell lung cancer (NSCLC) and MCF­7 breast cancer cells were examined. It was found that ursolic acid (UA), a natural pentacyclic triterpenoid, exerted significant inhibitory effect on these cells. Further experiments revealed that UA inhibited the proliferation of various lung cancer cells, including the NSCLC cells, H460, H1975, A549, H1299 and H520, the human small cell lung cancer (SCLC) cells, H82 and H446, and murine Lewis lung carcinoma (LLC) cells. UA induced the apoptosis and autophagy of NSCLC cells. The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway, but not the activation of the extracellular signal­regulated kinase 1/2 (ERK1/2) signaling pathway contributed to the UA­induced autophagy of NSCLC cells. Moreover, the inhibition of autophagy by chloroquine (CQ) or siRNA for autophagy­related gene 5 (ATG5) enhanced the UA­induced inhibition of cell proliferation and promotion of apoptosis, indicating that UA­induced autophagy is a pro­survival mechanism in NSCLC cells. On the whole, these findings suggest that combination treatment with autophagy inhibitors may be a novel strategy with which enhance the antitumor activity of UA in lung cancer.

Adsorption and desorption characteristics of ginsenosides from Panax ginseng C. A. Meyer on middle-pressure chromatogram isolated gels.

Four types of middle-pressure chromatogram isolated gels are evaluated for adsorption or desorption characteristics of ginsenosides from Panax ginseng. Among them, SP207SS and SP2MGS were selected for dynamic investigations based on their static adsorption or desorption capacity of total ginsenoside. Their adsorption kinetics was better explained by pseudosecond-order model and isotherms were preferably fitted to Langmuir model. Dynamic breakthrough experiments indicated an optimum sample loading speed of 4 bed volume/h for either SP207SS or SP2MGS. Desorption speed was determined to be 2 bed volume/h according to desorption amount of total ginsenoside in their effluents. Eight ginsenosides were identified and quantified by high performance liquid chromatography-triple quadropole-mass spectrometry in total ginsenoside extract and different fractions during stepwise dynamic elution. For SP207SS, 27.62% of loaded ginsenosides was detected in 40% ethanol fraction, while 59.12% of them were found in 60% ethanol fraction. As on SP2MGS, the number went to 53.71 and 44.43%, respectively. Recovery rate of ginsenosides were calculated to 78.65% for SP207SS and 89.53% for SP2MGS, respectively. Intriguingly, content of Rg1 and Re in 40% ethanol fraction from SP207SS became 20.1 and 18.6 times higher than that in total ginsenoside extract by one-step elution, which could be leveraged for the facile enrichment of these two ginsenosides from natural sources.

Functional Regulation of Ginsenosides on Myeloid Immunosuppressive Cells in the Tumor Microenvironment.

Ginsenosides, the key components isolated from ginseng, have been extensively studied in antitumor treatment. Numerous studies have shown that ginsenosides have direct function in tumor cells through the induction of cancer cell apoptosis and the inhibition of cancer cell growth and enhance the antitumor immunity through the activation of cytotoxic T lymphocytes and natural killer cells. However, little is known about the function of ginsenosides on myeloid immunosuppressive cells including dendritic cells in tumor, tumor-associated macrophages, and myeloid-derived suppressor cells in the tumor microenvironments. Those myeloid immunosuppressive cells play important roles in promoting tumor angiogenesis, invasion, and metastasis. In the review, we summarize the regulatory functions of ginsenosides on myeloid immunosuppressive cells in tumor microenvironment, providing the novel therapeutic methods for clinical cancer treatment.

Acyl-CoA synthetases from Physcomitrella, rice and Arabidopsis: different substrate preferences but common regulation by MS188 in sporopollenin synthesis.

MAIN CONCLUSION: ACOS5, OsACOS12 and PpACOS6 are all capable of fatty acyl-CoA synthetase activity but exhibit different substrate preferences. The transcriptional regulation of ACOS for sporopollenin synthesis appears to have been conserved in Physcomitrella, rice and Arabidopsis during evolution. Sporopollenin is the major constituent of spore and pollen exines. In Arabidopsis, acyl-CoA synthetase 5 (ACOS5) is an essential enzyme for sporopollenin synthesis, and its orthologues are PpACOS6 from the moss Physcomitrella and OsACOS12 from monocot rice. However, knowledge regarding the evolutionary conservation and divergence of the ACOS gene in sporopollenin synthesis remains limited. In this study, we analysed the function and regulation of PpACOS6 and OsACOS12. A complementation test showed that OsACOS12 driven by the ACOS5 promoter could partially restore the male fertility of the acos5 mutant in Arabidopsis, while PpACOS6 did not rescue the acos5 phenotype. ACOS5, PpACOS6 and OsACOS12 all complemented the acyl-CoA synthetase-deficient yeast strain (YB525) phenotype, although they exhibited different substrate preferences. To understand the conservation of sporopollenin synthesis regulation, we constructed two constructs with ACOS5 driven by the OsACOS12 or PpACOS6 promoter. Both constructs could restore the fertility of acos5 plants. The MYB transcription factor MS188 from Arabidopsis directly regulates ACOS5. We found that MS188 could also bind the promoters of OsACOS12 and PpACOS6 and activate the genes driven by the promoters, suggesting that the transcriptional regulation of these genes was similar to that of ACOS5. These results show that the ACOS gene promoter region from Physcomitrella, rice and Arabidopsis has been functionally conserved during evolution, while the chain lengths of fatty acid-derived monomers of sporopollenin vary in different plant species.

Artificial Intelligence Transforms the Future of Health Care.

Life sciences researchers using artificial intelligence (AI) are under pressure to innovate faster than ever. Large, multilevel, and integrated data sets offer the promise of unlocking novel insights and accelerating breakthroughs. Although more data are available than ever, only a fraction is being curated, integrated, understood, and analyzed. AI focuses on how computers learn from data and mimic human thought processes. AI increases learning capacity and provides decision support system at scales that are transforming the future of health care. This article is a review of applications for machine learning in health care with a focus on clinical, translational, and public health applications with an overview of the important role of privacy, data sharing, and genetic information.