Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity.

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

Efficacy evaluation, active ingredients, and multitarget exploration of herbal medicine.

Evidence shows that herbal medicine (HM) could be beneficial for the treatment of various diseases. However, complexities present in HM due to the unclear bioactive compounds, mechanisms of action, undetermined targets for therapy, and nonspecific features for metabolism, are currently an obstacle for the progression of novel drug discovery. Metabolomics could be a potential tool to overcome these issues and for the understanding of HM from a small-molecule metabolism level. The chinmedomics-based metabolomics method assesses the overall metabolism of organisms with a holistic view and shows great potential for understanding metabolic pathways, evaluating curative effects, clarifying mechanisms, discovering active ingredients, and precision medicine. This review focuses on the efficacy evaluation, active ingredient discovery, and target exploration of HM based on metabolomics and chinmedomics.

[Overview of research and development of polypeptide drugs and traditional Chinese medicine-peptides].

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.

Multi-Omics Approaches in Colorectal Cancer Screening and Diagnosis, Recent Updates and Future Perspectives.

Colorectal cancer (CRC) is common Cancer as well as the third leading cause of mortality around the world; its exact molecular mechanism remains elusive. Although CRC risk is significantly correlated with genetic factors, the pathophysiology of CRC is also influenced by external and internal exposures and their interactions with genetic factors. The field of CRC research has recently benefited from significant advances through Omics technologies for screening biomarkers, including genes, transcripts, proteins, metabolites, microbiome, and lipidome unbiasedly. A promising application of omics technologies could enable new biomarkers to be found for the screening and diagnosis of CRC. Single-omics technologies cannot fully understand the molecular mechanisms of CRC. Therefore, this review article aims to summarize the multi-omics studies of Colorectal cancer, including genomics, transcriptomics, proteomics, microbiomics, metabolomics, and lipidomics that may shed new light on the discovery of novel biomarkers. It can contribute to identifying and validating new CRC biomarkers and better understanding colorectal carcinogenesis. Discovering biomarkers through multi-omics technologies could be difficult but valuable for disease genotyping and phenotyping. That can provide a better knowledge of CRC prognosis, diagnosis, and treatments.

Discovery of Q-markers of Wenxin Formula based on a Chinmedomics strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Wenxin Formula (WXF) is a well-known prescription with a significant curative effect in the treatment of cardiac disease. However, the lack of quality control standards caused by unclear quality control components limits the development of new drugs. AIM OF THE STUDY: The aims of this research were to discover the effective materials and screen the quality markers of WXF through a chinmedomics strategy to aid in efficacy evaluation. MATERIAL AND METHODS: The therapeutic effect of WXF against myocardial ischaemia (MI) was evaluated by serum metabolic profiling combined with routine electrocardiography; analyses of the serum biochemical indices CK, CK-MB and α-HBDH; and histopathological tests involving TTC staining and HE staining. The raw data of serum samples were obtained by UPLC-HDMS, and multivariate statistical analysis was performed with Progenesis QI software. PCMS software was used to sift the quality markers of WXF. RESULTS: A total of 25 metabolites were characterized as biomarkers for myocardial ischaemia, and Wenxin Formula reversed the levels of 23 of them that were involved in arachidonic acid metabolism, glycerophospholipid metabolism, lysine degradation, and tyrosine metabolism. Eight constituents absorbed into blood were considered to form the effective material basis of Wenxin Formula for treating myocardial ischaemia, and the Q-markers selected through PCMS were ginsenoside Rb1, cinnamic acid, paeoniflorin and berberine. CONCLUSIONS: WXF significantly ameliorated the clinical symptoms, pathological changes and metabolic abnormalities of myocardial ischaemia. This study shows that chinmedomics is a powerful strategy to filter Q-markers from effective constituents to rationally evaluate the efficacy and safety of TCMs.

The Signaling Pathways and Targets of Natural Compounds from Traditional Chinese Medicine in Treating Ischemic Stroke.

Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA is currently used in less than 5% of stroke patients. Natural compounds have been widely used in the treatment of IS in China and have a wide range of therapeutic effects on IS by regulating multiple targets and signaling pathways. The keywords "ischemia stroke, traditional Chinese Medicine, Chinese herbal medicine, natural compounds" were used to search the relevant literature in PubMed and other databases over the past five years. The results showed that JAK/STAT, NF-κB, MAPK, Notch, Nrf2, and PI3K/Akt are the key pathways, and SIRT1, MMP9, TLR4, HIF-α are the key targets for the natural compounds from traditional Chinese medicine in treating IS. This study aims to update and summarize the signaling pathways and targets of natural compounds in the treatment of IS, and provide a base of information for the future development of effective treatments for IS.

Chinmedomics Strategy for Elucidating the Pharmacological Effects and Discovering Bioactive Compounds From Keluoxin Against Diabetic Retinopathy.

Keluoxin (KLX) is an active agent in the treatment of diabetic retinopathy (DR). However, its mechanism, targets, and effective constituents against DR are still unclear, which seriously restricts its clinical application. Chinmedomics has the promise of explaining the pharmacological effects of herbal medicines and investigating the effective mechanisms. The research results from electroretinography and electron microscope showed that KLX could reduce retinal dysfunction and pathological changes by the DR mouse model. Based on effectiveness, we discovered 64 blood biomarkers of DR by nontargeted metabolomics analysis, 51 of which returned to average levels after KLX treatment including leukotriene D4 and A4, l-tryptophan, 6-hydroxymelatonin, l-phenylalanine, l-tyrosine, and gamma-linolenic acid (GLA). The metabolic pathways involved were phenylalanine metabolism, steroid hormone biosynthesis, sphingolipid metabolism, etc. Adenosine monophosphate-activated protein kinase (AMPK), extracellular signal-regulated protein kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K), and protein 70 S6 kinase (p70 S6K) might be potential targets of KLX against DR. This was related to the mammalian target of rapamycin (mTOR) signaling and AMPK signaling pathways. We applied the chinmedomics strategy, integrating serum pharm-chemistry of traditional Chinese medicine (TCM) with metabolomics, to discover astragaloside IV (AS-IV), emodin, rhein, chrysophanol, and other compounds, which were the core effective constituents of KLX when against DR. Our study was the first to apply the chinmedomics strategy to discover the effective constituents of KLX in the treatment of DR, which fills the gap of unclear effective constituents of KLX. In the next step, the research of effective constituents can be used to optimize prescription preparation, improve the quality standard, and develop an innovative drug.

Targets and Effective Constituents of ZhiziBaipi Decoction for Treating Damp-Heat Jaundice Syndrome Based on Chinmedomics Coupled with UPLC-MS/MS.

Background: Damp-heat jaundice syndrome (DHJS) is a diagnostic model of traditional Chinese medicine (TCM) that refers to jaundice caused by damp-heat pathogen invasion. DHJS is the most common clinical manifestation of TCM, with yellow skin, yellow eyes and anorexia. ZhiziBaipi Decoction (ZBD) is a classic TCM formula that is effective at treating DHJS and various liver diseases. However, the effective components of ZBD in the context of DHJS and the underlying mechanism are unclear. Purpose: This study of ZBD using the DHJS rat model aimed to elucidate the pathobiology of DHJS and the metabolic targets of therapeutic ZBD, construct the network relationship between the components of ZBD and endogenous biomarkers, and clarify the underlying mechanism of ZBD in preventing and treating DHJS. Methods: Using chinmedomics as the core strategy, an animal model was generated, and the therapeutic effect of ZBD was evaluated based on behavioral, histopathological and biochemical indicators. Metabonomics tools were used to identify biomarkers of DHJS, TCM-based serum pharmacochemistry was used to analyze the effective constituents of ZBD, and chinmedomics technology was used to identify ZBD components highly related to DHJS biomarkers. Results: A total of 42 biomarkers were preliminarily identified, and ZBD significantly affected the levels of 29 of these biomarkers. A total of 59 compounds in ZBD were characterized in vivo. According to chinmedomics analysis, the highly correlated components found in blood were isoformononetin, 3-O-feruloylquinic acid, glycyrrhizic acid, oxyberberine, obaculactone and five metabolites. Conclusions: Chinmedomics combined with UPLC-MS/MS was used to study the targets and effective constituents of ZBD for the treatment of DHJS.

Prediction of the mechanism of Dachengqi Decoction treating colorectal cancer based on the analysis method of " into serum components -action target-key pathway".

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) is a common digestive tract malignant tumor that its morbidity and mortality seriously affect human health. At present, Dachengqi Decoction (DCQ), a traditional Chinese medicine formula, has been clinically used as an adjuvant therapy for CRC. However, pharmacodynamic substance basis and therapeutic mechanism are still unclear. AIM OF THE STUDY: The main constituents absorbed in the blood and possible active targets after DCQ administration were explored based on the analysis method of "into serum components, action target and key pathway", which may provide reference for the study of the pharmacodynamic material basis and action mechanism of Dachengqi Decoction in the treatment of CRC. MATERIAL AND METHODS: Based on the serum pharmacochemistry of traditional Chinese medicine (TCM), the prescription prototype ingredients of DCQ in mice serum samples were identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology (UPLC-Q-TOF-MSE). Taking the prototype ingredients absorbed into serum as the research object, the possible targets and key pathways of DCQ in vivo were demonstrated by network pharmacology. Finally, using molecular docking verified the binding activity of prototype components and potential action targets. RESULTS: A total of 46 prototype components of DCQ were identified in mice serum, most of which were derived from flavonoids and anthraquinones in Citrus aurantium L. and Rheum palmatum L. Network pharmacology prediction results indicated that the drug prototype components entering the serum may mainly regulate targets including mitogen-activated protein kinase (MAPK), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. and main pathways such as (phosphatidylinositol 3-kinase/protein kinase B) PI3K-AKT signaling pathway, advanced glycation end products-receptor for AGE (AGE-RAGE) signaling pathway and IL-17 signaling pathway, etc. Molecular docking showed that the prototype active components had strong binding activity to VEGF, Harvey rat sarcoma viral oncogene homolog (HRAS) and MAPK1. CONCLUSIONS: This study elucidated that most of the direct acting substances of DCQ in vivo were flavonoids and anthraquinones, which may play a role in regulating cell reproduction and apoptosis and inhibiting inflammation, providing a reference for the research of pharmacodynamic material basis and mechanism of DCQ in the treatment of CRC.

A Hypothesis From Metabolomics Analysis of Diabetic Retinopathy: Arginine-Creatine Metabolic Pathway May Be a New Treatment Strategy for Diabetic Retinopathy.

Diabetic retinopathy is one of the serious complications of diabetes, which the leading causes of blindness worldwide, and its irreversibility renders the existing treatment methods unsatisfactory. Early detection and timely intervention can effectively reduce the damage caused by diabetic retinopathy. Metabolomics is a branch of systems biology and a powerful tool for studying pathophysiological processes, which can help identify the characteristic metabolic changes marking the progression of diabetic retinopathy, discover potential biomarkers to inform clinical diagnosis and treatment. This review provides an update on the known metabolomics biomarkers of diabetic retinopathy. Through comprehensive analysis of biomarkers, we found that the arginine biosynthesis is closely related to diabetic retinopathy. Meanwhile, creatine, a metabolite with arginine as a precursor, has attracted our attention due to its important correlation with diabetic retinopathy. We discuss the possibility of the arginine-creatine metabolic pathway as a therapeutic strategy for diabetic retinopathy.

Therapeutic Effect and Mechanism of Si-Miao-Yong-An-Tang on Thromboangiitis Obliterans Based on the Urine Metabolomics Approach.

Si-Miao-Yong-An-Tang (SMYAT) is a classic prescription for the treatment of thromboangiitis obliterans (TAO). However, the effect and mechanism are still unclear. This experiment aims to evaluate the therapeutic effect and mechanism of SMYAT on sodium laurate solution induced thromboangiitis obliterans model rats using urine metabolomics. The therapeutic effect of SMYAT was evaluated by histopathology, hemorheology and other indexes. The urine metabolomic method, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for clustering group and discriminant analysis to screen urine differential metabolic biomarkers, and explore new insight into pathophysiological mechanisms of SMYAT in the treatment of TAO. SMYAT has significant antithrombotic and anti-inflammatory effects, according to the results of urine metabolomic analysis, and regulate the metabolic profile of TAO rats, and its return profile is close to the state of control group. Through metabolomics technology, a total of 35 urine biomarkers of TAO model were characterized. Among them, SMYAT treatment can regulate 22 core biomarkers, such as normetanephrine and 4-pyridoxic acid. It is found that the therapeutic effect of SMYAT is closely related to the tyrosine metabolism, vitamin B6 metabolism and cysteine and methionine metabolism. It preliminarily explored the therapeutic mechanism of SMYAT, and provided a scientific basis for the application of SMYAT.

Estimates of (co)variance components and phenotypic and genetic parameters of growth traits and wool traits in Alpine Merino sheep.

The (co)variance components and corresponding phenotypic and genetic parameters for growth traits and wool traits of economic importance were estimated in the Alpine Merino sheep population maintained at Gansu Provincial Sheep Breeding Technology Extension Station in northwestern China. Data from a maximum of 49,474 animals sired by 526 rams and born from 22,531 ewes over 20 years from 2000 to 2019 were used in this study. Birth type, age of dam, birth year, sex and/or management group, and age at measurement were initially fitted as fixed effects in an animal model with various random effects. Genetic groups were defined for all animals by the sire breed and breed genotype interacted with dam-strain flocks and were fitted as one of the random effects. Analyses were conducted using a residual maximum likelihood procedure (ASReml). Seven different animal models were fitted for all traits, and the most appropriate model with relevant random effects was selected through log-likelihood ratio testing. After identifying the appropriate model through single-trait analysis, bivariate analyses were used to obtain the phenotypic and genetic correlations among the traits. The estimates of additive direct heritability for birth weight (BWT), weaning weight (WWT), preweaning growth rate (prwADG), postweaning growth rate (powADG), yearling body weight (YWT), average fibre diameter (AFD), greasy fleece weight (GFW), clean fleece weight (CFW), yield (YLD), yearling wool staple length (YSL), coefficient of variation of average fibre diameter (FDcv) and wool visual fineness counts (VFC) were 0.30, 0.18, 0.18, 0.20, 0.29, 0.20, 0.19, 0.20, 0.35, 0.19, 0.16 and 0.13, respectively, with standard errors ranging from 0.02 to 0.05. The corresponding ratios of genetic group variance to additive genetic variance were significant and, respectively, 0.35, 0.80, 0.62, 0.26, 0.13, 1.06, 0.38, 0.64, 0.09, 0.12, 0.06 and 0.58. These results suggest for these traits that there is potential to exploit both the additive genetic variation and between genetic group variation although for most traits the between group variation was smaller than the variation within groups. Favourable genetic correlations were found among the growth traits, and between growth traits and fleece production traits, and among wool traits GFW, CFW, YSL and YLD. This study provides the required estimates of genetic parameters of both growth and wool traits of the new breed for the design of more effective breeding programmes.

Alterations in the Gut Microbiota and Their Metabolites in Colorectal Cancer: Recent Progress and Future Prospects.

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The etiology and pathogenesis of CRC remain unclear. A growing body of evidence suggests dysbiosis of gut bacteria can contribute to the occurrence and development of CRC by generating harmful metabolites and changing host physiological processes. Metabolomics, a systems biology method, will systematically study the changes in metabolites in the physiological processes of the body, eventually playing a significant role in the detection of metabolic biomarkers and improving disease diagnosis and treatment. Metabolomics, in particular, has been highly beneficial in tracking microbially derived metabolites, which has substantially advanced our comprehension of host-microbiota metabolic interactions in CRC. This paper has briefly compiled recent research progress of the alterations of intestinal flora and its metabolites associated with CRC and the application of association analysis of metabolomics and gut microbiome in the diagnosis, prevention, and treatment of CRC; furthermore, we discuss the prospects for the problems and development direction of this association analysis in the study of CRC. Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.

[Effects of mid-palatal suture opening and midfacial bony structure changes induced by maxillary skeletal expansion in adults].

PURPOSE: To analyze the opening of mid-palatal suture, transverse changes in dental and dentoalveolar measurements and shift of midfacial bony structures induced by maxillary skeletal expansion (MSE) with cone-beam CT (CBCT), and to evaluate the effect of maxillary skeletal expansion and its influence on adjacent bony structures in adults. METHODS: The study sample consisted of 12 adult patients with maxillary transverse deficiency (4 males, 8 females) at a mean age of (21.17±4.13) years old. All patients were treated with MSE. After treatment, the posterior crossbite was corrected, and the width of the maxillary arch was achieved the optimal width. Pre- and post-treatment CBCT exams were taken before and after MSE treatment. Multiplanar coronal and axial slices obtained from CBCT images were used to measure the changes in transverse widths, angular changes and tooth inclination with Dolphin Imaging 11.9. SPSS 26.0 software package was used for statistical analysis. RESULTS: After MSE treatment, the anterior nasal spine width increased by (2.38±1.01) mm, posterior nasal spine width increased by (2.25±1.08) mm (P<0.01). The inter-crown and inter-apex distance at the first molar increased by (5.56±1.38) mm and (4.14±1.29) mm, respectively (P<0.01). No significant difference was seen in terms of tooth inclination of the first molar(P>0.05). Pterygoid process angle, pterygoid process width, anterior inter-maxillary distance, upper and lower inter-zygomatic distance were significantly larger after treatment (P<0.01), while the inter-temporal distance and bilateral zygomaticomaxillary angle remained unchanged(P>0.05). CONCLUSIONS: MSE has a favorable effect in adult patients with parallel skeletal expansion of the mid-palatal suture achieved after expansion. The teeth present with certain buccal inclination but show no significant movement relative to the alveolar bone. The midfacial bony structures also shift in three-dimensional under the effect of the expansion force.

Immunoregulatory mechanism studies of ginseng leaves on lung cancer based on network pharmacology and molecular docking.

Panax ginseng is one of the oldest and most generally prescribed herbs in Eastern traditional medicine to treat diseases. Several studies had documented that ginseng leaves have anti-oxidative, anti-inflammatory, and anticancer properties similar to those of ginseng root. The aim of this research was to forecast of the molecular mechanism of ginseng leaves on lung cancer by molecular docking and network pharmacology so as to decipher ginseng leaves' entire mechanism. The compounds associated with ginseng leaves were searched by TCMSP. TCMSP and Swiss Target Prediction databases were used to sort out the potential targets of the main chemical components. Targets were collected from OMIM, PharmGKB, TTD, DrugBank and GeneCards which related to immunity and lung cancer. Ginseng leaves exert its lung cancer suppressive function by regulating the several signaling proteins, such as JUN, STAT3, AKT1, TNF, MAPK1, TP53. GO and KEGG analyses indicated that the immunoreaction against lung cancer by ginseng leaves might be related to response to lipopolysaccharide, response to oxidative stress, PI3K-Akt, MAPK and TNF pathway. Molecular docking analysis demonstrated that hydrogen bonding was interaction's core forms. The results of CCK8 test and qRT-PCR showed that ginseng leaves inhibit cell proliferation and regulates AKT1 and P53 expression in A549. The present study clarifies the mechanism of Ginseng leaves against lung cancer and provides evidence to support its clinical use.

Deciphering the Q-markers of nourishing kidney-yin of Cortex Phellodendri amurense from ZhibaiDihuang pill based on Chinmedomics strategy.

BACKGROUND: Cortex Phellodendri amurensis (CPA) has high medicinal value in the treatment of kidney-yin deficiency diseases. However, due to the lack of research on the therapeutic material basis of CPA, the current quality control standard for CPA is defective, and the effect of the nourishing kidney-yin of CPA was limited. PURPOSE: Based on the principle of correspondence between the syndrome and prescriptions, we studied the CPA in ZhibaiDihuang pill (ZBDH) to identify quality markers (Q-markers) of CPA in ZBDH for treating kidney-yin deficiency and seek the potential Q-markers of CPA under nourishing kidney-yin effect combined with the analysis of single CPA. METHODS: Taking Chinmedomics as the core strategy, metabonomics analysis and effective component identification were performed by UPLC-MS. RESULTS: A total of 121 chemical components of ZBDH were identified, among which the contents of berberine, palmatine, jatrorrhizine and magnoflorine changed the most obviously with the addition of CPA. Forty-five components were identified in the blood in the markedly effective state, including berberine, palmatine, jatrorrhizine and magnoflorine. The therapeutic material basis of ZBDH in the treatment of kidney-yin deficiency was found, and 6 components were found to derive from CPA, including magnoflorine and jatrorrhizine. In addition, seventeen components were identified in the blood in the single CPA treatment, including berberine, palmatine, jatrorrhizine and magnoflorine. CONCLUSIONS: Magnoflorine and jatrorrhizine were the Q-markers of CPA for treating kidney-yin deficiency in the formula of ZBDH and they were also potential Q-markers of the nourishing kidney-yin of CPA.

Permeability characteristics and structural evolution of compacted loess under different dry densities and wetting-drying cycles.

Permeability characteristics of compacted loess is always an important topic in soil mechanics and geotechnical engineering. This study explored the permeability characteristics of compacted loess under different dry densities and wetting-drying cycles, and found that as the dry density increases, the compacted loess surface became denser, the saturation permeability coefficient and saturation infiltration rate decreased. However, the wetting-drying cycle presented the opposite result. Meanwhile, the evolution of the microstructure was investigated by Scanning Electron Microscope (SEM) and Nuclear Magnetic Resonance (NMR) to explain the change of its permeability characteristics. The size of compacted loess aggregates was quantitatively analyzed by Image-Pro Plus (IPP) software. It showed that the size of compacted loess aggregates for different dry densities were concentrated from 10-100 µm, occupying 65.0%, 58.19%, and 51.64% of the total aggregates area respectively. And the interesting finding was that the area occupied by 10-50 µm aggregates remained basically unchanged with the number of wetting-drying cycles increasing. Therefore, the size of 10-50 µm aggregates represented the transition zone of compacted loess. NMR analyses revealed that with increasing dry density, the volume of macropores in the compacted loess rapidly decreased, the volume of mesopores and small pores increased. Meanwhile, the change in micropores was relatively small. The pore volume of the compacted loess after three wetting-drying cycles increased by 8.56%, 8.61%, and 6.15%, respectively. The proportion of macropores in the total pore volume shows the most drastic change. Variations in aggregate size and connection relationships made it easier to form overhead structures between aggregates, and the increased of macropore volume will form more water channels. Therefore, the change in permeability characteristics of compacted loess is determined by aggregate size, loess surface morphology, and the total pore volume occupied by macropores.

Efficacy of berberine in treatment of rheumatoid arthritis: From multiple targets to therapeutic potential.

Rheumatoid arthritis is a systemic autoimmune disorder involved in persistent synovial inflammation. Berberine is a nature-derived alkaloid compound with multiple pharmacological activities in different pathologies, including RA. Recent experimental studies have clarified several determinant cellular and molecular targets of BBR in RA, and provided novel evidence supporting the promising therapeutic potential of BBR to combat RA. In this review, we recapitulate the therapeutic potential of BBR and its mechanism of action in ameliorating RA, and discuss the modulation of gut microbiota by BBR during RA. Collectively, BBR might be a promising lead drug with multi-functional activities for the therapeutic strategy of RA.

Identification of key lipid metabolites during metabolic dysregulation in the diabetic retinopathy disease mouse model and efficacy of Keluoxin capsule using an UHPLC-MS-based non-targeted lipidomics approach.

Diabetic retinopathy (DR) is an important complication of diabetes, and is currently the main cause of blindness among young adults in the world. Previous studies have shown that Keluoxin (KLX) capsules have a significant effect on DR in C57BL/KsJ/db-/- mice (db/db mice), however the unclear mechanism limits its further clinical application and actual value. Further research is urgently needed for the treatment of DR disease. Discovery of key lipid biomarkers and metabolic pathways can reveal and explore the molecular mechanisms related to DR development and discover the effect of Keluoxin (KLX) capsule against DR in db/db mice. Lipidomics has been used for characterizing the pathological conditions via identification of key lipid metabolites and the metabolic pathway. In this study, the high-throughput lipidomics using UHPLC-Q-TOF/MS combined with multivariate statistical analysis, querying multiple network databases and employing ingenuity pathway analysis (IPA) method for molecular target prediction. A total of 30 lipid biomarkers were identified and 7 metabolic pathways including arachidonic acid metabolism and steroid hormone biosynthesis were found. The preventive effect of KLX intervention can regulate 22 biomarkers such as LysoPA(16:0/0:0), prostaglandin D2, cortisol and γ-linolenic acid, etc. IPA platform has predicted that PI3K/MAPK pathway are closely related to DR development. It also showed that high-throughput lipidomics combined with multivariate statistical analysis could deep excavate of the biological significance of the big data, and can provide molecular targets information about the disease treatment.

Chinmedomics, a new strategy for evaluating the therapeutic efficacy of herbal medicines.

Herbal medicines have accumulated valuable clinical experience in thousands of years of applications in traditional Chinese medicine (TCM) or ethnomedicine. The unique multi-target efficacy on complex diseases made herbal medicines gained a global popularity in recent years. However, the characteristic of multi-component acting on multi-target poses a dilemma for the evaluation of therapeutic efficacy of herbal medicines. Advances in metabolomics enable efficient identification of the various changes in biological systems exposed to different treatments or conditions. The use of serum pharmacochemistry of TCM has significant implications for tackling the major issue in herbal medicines development-pharmacodynamic material basis. Chinmedomics integrates metabolomics and serum pharmacochemistry of TCM to investigate the pharmacodynamic material basis and effective mechanisms of herbal medicines on the basis of TCM syndromes and holds the promise of explaining therapeutic efficacy of herbal medicines in scientific language. In this review, the historical development of chinmedomics from concept formation to successful applications was discussed. We also took the systematic research of Yin Chen Hao Tang (YCHT) as an example to show the research strategy of chinmedomics.