Tricaprylin, a medium-chain triglyceride, aggravates high-fat diet-induced fat deposition but improves intestinal health.

Medium-chain triglycerides (MCTs) are absorbed and metabolized more rapidly than long-chain triglycerides (LCTs) and therefore are considered to have obesity-prevention potential in foods. The effect of adding tricaprylin, an MCT, to food on fat deposition and intestinal health is uncharted. In this study, mice were randomly divided into four groups and fed a normal diet (ND), ND with tricaprylin, a high-fat diet (HFD), or HFD with tricaprylin. Supplementation of 2% tricaprylin in HFD significantly increased the body weight, fat mass, liver weight, adipocyte size in adipose tissue and liver, and upregulated genes related to fat deposition. Metabolomic analysis of serum and adipose tissue revealed that tricaprylin significantly increased the contents of metabolites related to lipid metabolism, triglyceride storage, and fat deposition related signaling pathways. In vitro experiments and molecular docking analysis suggest that octanoic acid, a primary decomposition product of tricaprylin, may promote adipogenic differentiation of preadipocytes by acting as a PPARγ ligand to activate the expression of lipogenesis-related genes. Although supplementation with 2% tricaprylin in HFD cannot reduce fat deposition, it has a beneficial effect on intestinal health. Tricaprylin improved intestinal morphology, digestive enzyme activity, short-chain fatty acid concentration, and intestinal barrier function-related protein expression, while reducing inflammatory factor levels and the abundance of harmful intestinal microorganisms.

Multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector assay of ginsenosides for quality evaluation of ginseng from diverse Chinese patent medicines.

For quality control of Chinese patent medicines (CPMs) containing the same herbal medicine or different herbal medicines that have similar chemical composition, current ″one standard for one species″ research mode leads to poor universality of the analytical approaches unfavorable to discriminate easily confused species. Herein, we were aimed to elaborate a multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector (MHC-2DLC/CAD) approach to quantitatively assess ginseng from multiple CPMs. Targeting baseline resolution of 16 ginsenosides (noto-R1/Rg1/Re/Rf/Ra2/Rb1/Rc/Ro/Rb2/Rb3/Rd/Rh1/Rg2/Rg3/Rg3(R)/24(R)-p-F11), experiments were conducted to optimize key parameters and validate its performance. A Poroshell 120 EC-C18 column and an XBridge Shield RP18 column were separately utilized in the first-dimensional (1D) and the second-dimensional (2D) chromatography. Eight consecutive cuttings could achieve good separation of 16 ginsenosides within 85 min. The developed MHC-2DLC/CAD method showed good linearity (R2 > 0.999), repeatability (RSD < 6.73%), stability (RSD < 5.63%), inter- and intra-day precision (RSD < 5.57%), recovery (93.76-111.14%), and the limit of detection (LOD) and limit of quantification (LOQ) varied between 0.45-2.37 ng and 0.96-4.71 ng, respectively. We applied it to the content determination of 16 ginsenosides simultaneously from 28 different ginseng-containing CPMs, which unveiled the ginsenoside content difference among the tested CPMs, and gave useful information to discriminate ginseng in the preparation samples, as well. The MHC-2DLC/CAD approach exhibited advantages of high specificity, good separation ability, and relative high analysis efficiency, which also justified the feasibility of our proposed ″Monomethod Characterization of Structure Analogs″ strategy in quality evaluation of diverse CPMs that contained different ginseng.

Characterization of peripheral blood inflammatory indicators and OCT imaging biological markers in diabetic retinopathy with or without nephropathy.

Objective: To observe the distribution characteristics of peripheral blood inflammatory indexes and retinal macular area optical coherence tomography (OCT) imaging biomarkers in patients with diabetic retinopathy (DR) with or without diabetic nephropathy (DN), in order to seek clinical biomarkers that can predict the development of DR and DN. Methods: A total of 169 inpatients with DR who visited the ophthalmology department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from October 2020 to June 2022 and had complete clinical data were collected, and the patients with DR were divided into two major groups, DR and DR/DN, according to whether they had DN, and then further divided into four subgroups, Non-proliferative DR(NPDR), proliferative DR(PDR), NPDR/DN and PDR/DN, according to the stage of DR. The distribution characteristics of peripheral blood inflammatory indexes [Neutrophil to lymphocyte ratio(NLR) and Platelet to neutrophil ratio(PLR)], renal function indexes [Cystatin-C(CYS-C), Creatinine(Crea), Uric acid(UA)and Urinary albumin to creatinine ratio(UACR)] and OCT imaging indexes [Hyperreflective foci(HRF), Disorgnization of retinal inner layers(DRIL), Outer retinal tubulations(ORTs), Central retinal thickness(CRT), Retinal nerve fiber layer(RNFL) and Ganglion cell layer(GCL)] were analyzed between the above subgroups. Results: There was no difference between DR and DR/DN groups in terms of gender, family history of diabetes, duration of diabetes and Body mass index(BMI) (P>0.05), the mean age of the DR/DN group was significantly lower than that of the DR group (P<0.05), and the proportion of the DR/DN group with a history of hypertension was significantly higher than that of the DR group (P<0.05); there was no significant difference in hemoglobin A1C(HbA1c) between DR and DR/DN groups (P>0.05). (P>0.05), Hemoglobin(HGB) was significantly higher in the DR group than in the DR/DN group (P <0.05), NLR, PLR, Crea, UA and CYS-C were significantly higher in the DR/DN group than in the DR group (P<0.05); there was no significant difference in the comparison of HRF, DRIL, ORTs positive rate and CRT between the DR and DR/DN groups (P>0.05). RNFL and GCL thickness were significantly lower in the DR/DN group than in the DR group (P<0.05); history of hypertension (OR=2.759), NLR (OR=1.316), PLR (OR=1.009), Crea (OR=1.018), UA (OR=1.004), CYS-C (OR=3.742) were the independent (OR=0.951), age (OR=0.951), HGB (OR=0.976), RNFL (OR=0.909) and GCL (OR=0.945) were independent protective factors for DR/DN; RNFL (OR=0.899) and GCL (OR=0.935) were independent protective factors for NPDR/DN, RNFL (OR=0.852) and GCL (OR=0.928) were independent protective factors for PDR/DN. ROC curve analysis showed that the area under the curve (AUC) for CYS-C, PLR, Crea, UA and the combination of the four indicators to predict DR/DN were 0.717, 0.625, 0.647, 0.616 and 0.717, respectively. Conclusions: (1) Low age combined with hypertension HGB, NLR, PLR, CYS-C, Crea and UA may be serum biological markers for predicting DN in DR; meanwhile, PLR, CYS-C, Crea, UA and the combination of the four indicators can be used for risk assessment and adjunctive diagnosis of DN in DR combined with hypertension. (2) The RNFL and GCL thickness in the temporal aspect of the central macular sulcus may be imaging biological markers for predicting DN in DR; meanwhile, GCL thickness may have important value for risk prediction and diagnosis of DN in combination with DR.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS: YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Reveal the Patterns of Prescriptions for Recurrent Respiratory Tract Infections' Treatment Based on Multiple Illustrious Senior Traditional Chinese Medicine Practitioners.

Background: Recurrent respiratory tract infections (RRTIs) are one of the most common diseases in children and adolescents. The causes of RRTIs are various. In addition to the factors related to infection, basic diseases such as respiratory system, immune system, and digestive system are also involved. The cost of patients' frequent medical treatment and hospitalization has been deemed to be a heavy burden to the society and family. In China, traditional Chinese medicine (TCM) is commonly used to treat RRTIs. TCM treatment has been appraised to be effective, for reducing the number of hospital stays. Illustrious senior TCM practitioners of pediatrics are recognized as a group of outstanding physicians with significantly better patient outcomes. However, different illustrious senior TCM practitioners can lead to differences in treatment strategies due to factors such as region, prescription theory, and individual differences of patients. This makes it difficult for the experience of illustrious senior TCM practitioners to be popularized. However, there have been no prescription mining studies for the treatment of RRTIs based on different and multiple illustrious senior TCM practitioners. We explored the core prescriptions and drug mechanisms through data mining based on the prescriptions of illustrious senior TCM practitioners treating RRTIs from different clinical settings. This is important to promote the effective treatment of RRTIs with TCM. The objective of this study is to reveal the strategies (core prescriptions) from the prescriptions of multiple illustrious senior TCM practitioners for the treatment of RRTIs. We hope that this core prescription can help all TCM pediatricians to improve RRTIs children's outcome. Meanwhile, it could provide a new way for researchers to study the treatment of RRTIs. Methods: In this study, we prospectively collected 400 children's prescriptions with RRTIs receiving TCM treatment from four illustrious senior TCM practitioners in different hospitals. We described and analyzed the characteristics of TCM prescriptions. The prescription regularity was analyzed by hierarchical clustering and association rules. Network pharmacology methods has been used to reveal the pathway mechanism of core prescriptions which have been mined and visualized with the help of SymMap, Genecards, KEGG, Metascape databases, and R. The execution of all methods was completed in May 2022. Results: According to RRTIs multiple clinical syndromes, five new prescriptions were obtained based on illustrious senior TCM practitioners. Among them, the prescription composed of Scutellariae radix (Huangqin), Armeniacae semen amarum (Kuxingren), Peucedani radix (Qianhu), and Pheretima (Dilong) is the core strategy for the treatment of RRTIs. Cold herbs and heat herbs in the core prescription are approximately equal. Scutellariae radix (Huangqin) was dominant, and other herbs exert synergistic effects. The core prescription covered 76 pathways and 226 herb-disease genes. It promotes the differentiation of Th1, Th2, and Th17 cells and the secretion of inflammatory factors through toll-like receptor signaling pathway in the immune system, T cell receptor signaling pathway, and PPAR signaling pathway in the endocrine system, thereby exerting immune regulation and anti-inflammation. Conclusion: In this study, we revealed the prescription regularity of TCM in the treatment of RRTIs and analyzed the mechanism of core prescriptions, which provided new ideas for the treatment of RRTIs.

Comparing Arsenic-Containing Qinghuang Powder and Low-Intensity Chemotherapy in Elderly Patients with Acute Myeloid Leukemia.

OBJECTIVE: To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients. METHODS: Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups. RESULTS: The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01). CONCLUSIONS: QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers.

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants.

Alcohol extracts from Anemone flaccida Fr. Schmidt treat rheumatoid arthritis via inhibition of synovial hyperplasia and angiogenesis.

Anemone flaccida Fr. Schmidt, a Traditional Chinese Medicine, has been used in the treatment of rheumatoid arthritis (RA) for numerous years. However, the specific mechanisms remain to be elucidated. Thus, the present study aimed to investigate the main chemical constituents and potential mechanisms of Anemone flaccida Fr. Schmidt. The ethanol extract obtained from Anemone flaccida Fr. Schmidt (EAF) was analyzed using mass spectrometry to determine the main components and the therapeutic effects of EAF on RA were verified using a collagen­induced arthritis (CIA) rat model. Results of the present study demonstrated that synovial hyperplasia and pannus of the model rats were significantly improved following EAF treatment. Moreover, the protein expression levels of VEGF and CD31­labeled neovascularization were significantly reduced in the synovium of CIA rats following treatment with EAF, compared with those of the untreated model group. Subsequently, in vitro experiments were carried out to verify the impact of EAF on synovial proliferation and angiogenesis. Results of the western blot analysis revealed that EAF inhibited the PI3K signaling pathway in endothelial cells, which is associated with anti­angiogenesis. In conclusion, results of the present study demonstrated the therapeutic effects of Anemone flaccida Fr. Schmidt on RA and preliminarily revealed the mechanisms of this drug in the treatment of RA.

Middle Holocene Siberian genomes reveal highly connected gene pools throughout North Asia.

The peopling history of North Asia remains largely unexplored due to the limited number of ancient genomes analyzed from this region. Here, we report genome-wide data of ten individuals dated to as early as 7,500 years before present from three regions in North Asia, namely Altai-Sayan, Russian Far East, and the Kamchatka Peninsula. Our analysis reveals a previously undescribed Middle Holocene Siberian gene pool in Neolithic Altai-Sayan hunter-gatherers as a genetic mixture between paleo-Siberian and ancient North Eurasian (ANE) ancestries. This distinctive gene pool represents an optimal source for the inferred ANE-related population that contributed to Bronze Age groups from North and Inner Asia, such as Lake Baikal hunter-gatherers, Okunevo-associated pastoralists, and possibly Tarim Basin populations. We find the presence of ancient Northeast Asian (ANA) ancestry-initially described in Neolithic groups from the Russian Far East-in another Neolithic Altai-Sayan individual associated with different cultural features, revealing the spread of ANA ancestry ∼1,500 km further to the west than previously observed. In the Russian Far East, we identify 7,000-year-old individuals that carry Jomon-associated ancestry indicating genetic links with hunter-gatherers in the Japanese archipelago. We also report multiple phases of Native American-related gene flow into northeastern Asia over the past 5,000 years, reaching the Kamchatka Peninsula and central Siberia. Our findings highlight largely interconnected population dynamics throughout North Asia from the Early Holocene onward.

Identification of chemical components and network pharmacology of Huanglian Decoction based on UPLC-Q-TOF-MS/MS technology / 中国中药杂志

The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.

A Retrospective Study on the Characteristics of Traditional Chinese Medical Syndromes in 3088 Cases of Atherosclerotic Cerebral Infarction / 中医杂志

ObjectiveTo investigate the characteristics of traditional Chinese medicine syndrome and the evolution of pathogenesis in different stages of atherosclerotic thrombotic cerebral infarction （ATCI）. MethodsClinical data of 3088 ATCI patients from 8 hospitals in 6 provinces and cities were collected from the hospital information system during January 1， 2015 to December 31， 2019. After staging and counting clinical symptoms， common factors were extracted using the principal component analysis method in factor analysis. Cluster analysis was then carried out on the basis of the factor analysis. The results of the combination of the evidence element identification， cluster analysis and expert discussion were used to discuss the evidence of the different disease stages of atherosclerotic cerebral infarction. ResultsOf the 3088 ATCI patients included， 2290 cases were in the acute phase and 798 in the non-acute phase. Excluding the main symptoms of ischaemic stroke， such as numbness and weakness of limbs， unfavourable movement， unfavourable speech and dizziness， we identified 84 indicators with a frequency ≥5% of the four diagnostic information variables. Of these， 36 indicators were observed in the acute phase and 35 in the non-acute phase. Factor analysis extracted 14 common factors from each phase. We selected factors with a loading coefficient ＞0.3 for evidence determination. These 14 groups of common factors were used as variables for clustering. After clustering， the acute， non-acute phase were each divided into 5 categories. Based on a combination of clinical practice and expert opinion， the symptoms identified in the acute period were syndrome of deficiency of both qi and yin， syndrome of blockade of wind-phlegm-static blood （36.07%）， syndrome of qi deficiency and blood stasis （20.74%）， syndrome of upward disturbance of wind-fire （15.15%）， syndrome of stirring wind due to yin deficiency （9.43%）， and syndrome of spleen deficiency and liver hyperactivity （3.80%）. In the non-acute phase， the symptoms were qi and yin deficiency with syndrome of qi stagnation and blood stasis （45.49%）， syndrome of deficiency of both qi and yin （20.05%）， syndrome of qi stagnation and blood stasis （16.42%）， spleen-kidney deficiency syndrome （8.52%）， and syndrome of hyperactivity of liver yang （4.89%）. ConclusionThe acute phase of AICI is mainly characterized by blood stasis， fire， internal wind， hyperactivity of yang， qi deficiency and yin deficiency， while the non-acute phase is characterized by yin deficiency， qi deficiency， blood stasis and qi stagnation. The main pathomechanism of ATCI involves deficiency of qi and yin， as well as obstruction of the channels by phlegm and blood stasis， and the fundamental pathomechanism is deficiency of qi and yin.

Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury.

BACKGROUND: Every year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influences cardiac function and prognosis in cardiac surgery patients. Jiawei Danshen Decoction (JWDSD) is a traditional Chinese herbal prescription that has been used clinically for many years in China to treat MIRI. The underlying molecular mechanisms, however, remain unknown. To investigate the proteomic changes in myocardial tissue of rats given JWDSD for MIRI therapy-based proteomics. METHODS: MIRI rat model was created by ligating/releasing the left anterior descending coronary artery. For seven days, the drugs were administered twice daily. The model was created following the last drug administration. JWDSD's efficacy in improving MIRI was evaluated using biochemical markers and cardiac histology. Tandem mass tag-based quantitative proteomics (TMT) technology was also used to detect proteins in the extracted heart tissue. To analyze differentially expressed proteins (DEPs), bioinformatics analysis, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways, were employed. Furthermore, western blotting confirmed the potential targets regulated by JWDSD. RESULTS: The histopathologic characteristics and biochemical data showed JWDSD's protective effects on MIRI rats. A total of 4549 proteins were identified with FDR (false discovery rate) ≤1%. Twenty overlapping were identified (162 DEPs and 45 DEPs in Model/Control or JWDSD/Model group, respectively). Of these DEPs, 16 were regulated by JWDSD. GO analysis provided a summary of the deregulated protein expression in the categories of biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment analysis revealed that the signaling pathways of neutrophil extracellular trap formation, RNA polymerase, serotonergic synapse, and linoleic acid metabolism are all closely related to JWDSD effects in MIRI rats. Furthermore, T-cell lymphoma invasion and metastasis 1 (TIAM1) was validated using western blotting, and the results were consistent with proteomics data. CONCLUSIONS: Our study suggests that JWDSD may exert therapeutic effects through multi-pathways regulation in MIRI treatment. This work may provide proteomics clues for continuing research on JWDSD in treating MIRI.

On the Core Prescriptions and Their Mechanisms of Traditional Chinese Medicine in Hepatitis B, Liver Cirrhosis, and Liver Cancer Treatment.

Background: As a frequent cause of death in cancer patients, liver cancer usually occurs in hepatitis B and cirrhosis. In China, Chinese people have been using traditional Chinese medicine (TCM) in treating various chronic liver diseases, which could effectively improve the symptoms and slow down the progression of liver diseases. However, due to the complexity rules of TCM prescription, their action mechanisms are still not clearly understood, which may affect the popularization of effective prescriptions. This study aims to identify the core TCM herbs in the treatment of hepatitis B, liver cirrhosis, and liver cancer so as to clarify the mechanism of action of the core herb networks. Methods: There were 1,673 prescriptions for chronic liver diseases collected in this study, of which 854 were hepatic B prescriptions, 530 were for liver cirrhosis, and 289 were for liver cancer. The basic characteristics of herbal medicine were firstly explained via descriptive analysis, then the core prescriptions of herbal medicine were analyzed through association rule, and finally, the mechanism of core prescriptions was explored with the help of systematic network pharmacology and by applying such databases as TCMIP, HERB, OMIM, GeneCards, KEGG, and software like RStudio and Cytoscape. Results: The rule of the core prescriptions in these cases was characterized by the application of herbs with both cold and warm properties, in which bitter herbs with cold property took priority. Tonifying deficiency, clearing heat, and activating blood circulations to remove stasis were common treatment principles for the three liver diseases. Turmeric Root Tuber (YuJin), White Peony Root (BaiShao), Bupleurum (ChaiHu), Salvia miltiorrhiza (DanShen), and Astragali Radix (HuangQi) were prescribed the most in hepatitis B treatment to invigorate the spleen and soothe the liver. Astragali Radix (HuangQi), Tuckahoe (FuLing), Atractylodis Macrocephalae Rhizoma (BaiZhu), Fructus Polygoni Orientalis (ShuiHongHuaZi), and Curcumae Rhizome (EZhu) were most frequently applied in liver cirrhosis treatment to replenish qi and activate blood. Oldenlandia (BaiHuaSheSheCao), Bearded Scutellaria (BanZhiLian), Curcumae Rhizome (EZhu), and Cardamom (DouKou) were most frequently prescribed to eliminate cancer toxin, invigorate the spleen, and activate blood. These core herbs mainly act through signal transduction and immune system pathways, in which the PI3K-Akt pathway plays a key role. The core prescription for liver cirrhosis regulated more endocrine system pathways than the hepatitis B prescription, and liver cancer prescription regulated more nervous system-related pathways. Conclusion: Three core prescriptions for hepatitis B, liver cirrhosis, and liver cancer treatment were identified, which acted mainly through signal transduction and immune system pathways to regulate immunity and cell growth and participate in inflammation inhibition, in which liver cancer prescription regulated more pathways, especially more nervous system-related pathways than the other two.

Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice.

CONTEXT: Fibraurea recisa Pierre. (Menispermaceae) (FR) is a traditional Chinese medicine known as "Huangteng." The total alkaloids of FR (AFR) are the main active ingredients. However, the pharmacological effects of AFR in the treatment of depression have not been reported. OBJECTIVES: This study investigates the antidepressant effects of AFR by network pharmacology and verification experiments. MATERIALS AND METHODS: Compound-Target-Pathway (C-P-T) network of FR and depression was constructed through network pharmacology. In vitro, HT-22 cells were treated with corticosterone (CORT) solution (0.35 mg/mL), then AFR (0.05 mg/mL) solution and inhibitor AZD6244 (14 µM/mL) or BAY11-7082 (10 µM/mL) were added, respectively. The cell viability was detected by CCK-8. In vivo, C57BL/6 mice were divided into 5 groups, namely the normal group, the CUMS group, the AFR (400 mg/kg) group, and the 2 groups that were simultaneously administered the inhibitory group AZD6244 (8 mg/kg) and BAY11-7082 (5 mg/kg). Western blotting was used to assess the expression level of the proteins. RESULTS: AFR could protect HT-22 cells from CORT-induced damage and increase the cell viability from 49.12 ± 3.4% to 87.26 ± 1.5%. Moreover, AFR significantly increased the levels of BDNF (1.3, 1.4-fold), p-ERK (1.4, 1.2-fold) and p-CERB (1.6, 1.3-fold), and decreased the levels of NLRP3 (11.3%, 31.6%), ASC (19.2%, 34.2%) and caspase-1 (18.0%, 27.6%) in HT-22 cells and the hippocampus, respectively. DISCUSSION AND CONCLUSIONS: AFR can improve depressive-like behaviours and can develop drugs for depression treatment. Further studies are needed to validate its potential in clinical medicine.

[Seed morphology and germination characteristics of Tripterygium wilfordii].

The seeds of Tripterygium wilfordii are characterized by dormancy and a long germination cycle under natural sowing conditions. In this study, we developed a method for rapid germination of T. wilfordii seeds by analyzing the size, morphology, thousand-grain weight, viability, moisture content, physicochemical properties, and seed germination rates under different germination conditions. The seeds of T. wilfordii were fine columnar with a thick and hard outer seed coat. They had the length of 6.69 mm, the width of 2.14 mm, the thickness of 1.68 mm, the thousand-grain weight of 8.99 g, the moisture content of 8.86%, the soluble sugar content of 21.3 mg·g~(-1), the starch content of 28.9 mg·g~(-1), the soluble protein content of 44.2 mg·g~(-1), and the seed viability of only 54.0%. The seeds were respectively treated with distilled water, ultrasonication, low-temperature storage, 50 ℃ water, 100 mg·L~(-1) 6-BA, 0.6% KMnO_4, 1% KNO_3, 50 mg·L~(-1) NAA, and 100 mg·L~(-1) GA_3 solution. The results showed that soaking the seeds in 100 mg·L~(-1) GA_3 solution significantly promoted the germination. Further, the seeds were soaked in 50, 100, 250, 500, and 1 000 mg·L~(-1) GA_3 solutions, which demonstrated that high concentration(500 mg·L~(-1), 1 000 mg·L~(-1)) of GA_3 solutions increased the germination rate and speed and shortened the germination cycle from more than 3 months to less than 15 days. The findings of this study are of great significance to the breeding of T. wilfordii and lay a foundation for the large-scale propagation of T. wilfordii seeds and the excavation of T. wilfordii germplasm resources.

Mangiferin, a natural glucoxilxanthone, inhibits mitochondrial dynamin-related protein 1 and relieves aberrant mitophagic proteins in mice model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease featured to mitochondrial dysfunction in neuronal cells. Dynamin-related protein 1 (Drp1) is an important regulator of mitochondrial fission and subsequent mitophagy. Mangiferin (MGF) is a glucosyl xanthone mainly derived from Mangifera indica L., possessing multifaceted properties, e.g., antioxidant, anti-inflammatory, and enhancement of cognitive ability. Besides, it can cross the blood-brain barrier, thereby exerting a neuroprotective effect. However, so far, MGF's effect in balancing mitochondrial homeostasis via regulation of Drp1 level and mitophagic pathway in PD remains rarely reported. PURPOSE: We aimed to investigate the neuroprotective effect of MGF against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and examine the possible mechanisms. METHODS: We utilized C57BL/6 mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Behavioral parameters, containing the open field test, balance beam, pole test, and rotarod test, assessed the locomotor activity; immunohistochemistry assessed the number of TH-positive neurons; transmission electron microscopy detected ultrastructural mitochondrial morphology in the dopaminergic neuron; complex I enzymatic activity microplate assay kit measured the mitochondrial complex I activity; ATP determination kit measured ATP levels in mitochondria isolated from cells or striatal tissues; western blot measured the levels of Drp1 and mitophagic proteins. RESULTS: We observed that MGF could mitigate motor deficiency and improve the expression of tyrosine hydroxylase in the substantia nigra of MPTP-induced PD mice. Furthermore, MGF not only ameliorated mitochondrial ultrastructure, but also improved mitochondrial ATP content. Within mitochondria, MGF could reduce Drp1 expression and reverse the expressions of mitophagic proteins, including PINK1, Parkin, NIX, BNIP3, FUNDC1, and p62. CONCLUSION: Present study indicates that MGF benefits mitochondrial networks by recovering mitochondrial ultrastructure and ATP contents, reducing mitochondrial Drp1, and modulating mitophagic proteins in the MPTP-induced PD mice model, which revealed a novel acting mechanism of MGF in PD's treatment.

Intestinal Flora: A Potential Mechanism by Which Yinlai Decoction Treats Lipopolysaccharide-Induced Pneumonia.

Background: We intended to explore the mechanism of Yinlai decoction in the treatment of lipopolysaccharide (LPS)-induced pneumonia from the perspective of intestinal flora. Methods: Thirty Sprague-Dawley rats were randomly assigned to the blank control group (N), the pneumonia group (P), and the Yinlai decoction group (PT). The rat pneumonia model was established using LPS inhalation (0.5 mg/mL, 5 mL, 30 min/day, 3 days). Yinlai decoction was administered intragastrically (2 mL/100 g, 3 days). Lung tissue pathology, organ indexes, serum inflammatory factors, tumor necrosis factor-alpha (TNF-α), and intestinal flora changes were measured. Results: Lung tissue inflammation was prevented by Yinlai decoction. IL-6 levels showed a higher tendency to be higher, and IL-12 and TNF-α were significantly higher in the PT group than in the P group. The structure of the intestinal flora in the P differed from that in the N. The relative abundance of 10 out of 12 microflora was significantly higher in the P group than in the N and PT groups. In the PT group, the structure and the distribution of microbial groups were like those of the N group. Conclusions: Yinlai decoction inhibited LPS-induced lung and systemic inflammation in rats and may help the intestinal flora restore equilibrium by inhibiting the colonization of pathogenic bacteria and adjusting the ratio between probiotics and pathogenic bacteria. Intestinal flora may serve as a mediator of Yinlai decoction's effect on LPS-induced pneumonia.

Chondroitin sulfate deposited on foxtail millet prolamin/caseinate nanoparticles to improve physicochemical properties and enhance cancer therapeutic effects.

In this study, curcumin (Cur)-loaded chondroitin sulfate (CS)-sodium caseinate (NaCas)-stabilized foxtail millet prolamin (FP) composite nanoparticles (NPs) were fabricated via a one-pot process. FP is capable of self-assembly via liquid antisolvent precipitation under neutral and alkaline conditions (pH 7.0-11.0). Under this condition, the microstructures of hydrophobic FP cores, amphiphilic NaCas and hydrophilic CS shells were fabricated readily by a one-pot method. With an optimal FP/NaCas/CS weight ratio of 3 : 2 : 4, FP-NaCas-CS NPs shared globular microstructures at about 145 nm, and hydrophobic interactions, electrostatic forces, and hydrogen bonds were the main driving forces for the formation and maintenance of stable FP-NaCas-CS NPs. CS coating enhanced the pH stability but reduced the ionic strength stability. The formed NPs were stable over a wide pH range from 2.0 to 8.0 and elevated salt concentrations from 0 to 3 mol L-1 NaCl. FP-NaCas-CS NPs exhibited a higher Cur encapsulation efficiency of 93.4% and re-dispersion capability after lyophilization. Moreover, CS coating promoted selective accumulation in CD44-overexpressing HepG2 cells, resulting in higher inhibition of tumor growth compared to free Cur and FP-NaCas NP-encapsulated Cur. As for comparison, encapsulated Cur exhibited reduced cytotoxicity on normal liver cells L-O2. This preclinical study suggests that FP-NaCas-CS NPs could be very beneficial in terms of encapsulating hydrophobic drugs, improving the effectiveness of cancer therapies and reducing side effects on normal tissues.

Multi-level fingerprinting and cardiomyocyte protection evaluation for comparing polysaccharides from six Panax herbal medicines.

The role of polysaccharides in quality control of ginseng is underestimated. Large-scale comparison on the polysaccharides of Panax ginseng (PG), P. quinquefolius (PQ), P. notoginseng (PN), Red ginseng (RG), P. japonicus (ZJS), and P. japonicus var. major (ZZS), was performed by both chemical and biological approaches. Holistic fingerprinting at polysaccharide and the hydrolyzed oligosaccharide and monosaccharide levels utilized various chromatography methods, while OGD and OGD/R models on H9c2 cells were introduced to evaluate the protective effects on cell viability and mitochondrial function. Polysaccharides from six ginseng species exhibited remarkable content difference (RG > PG/ZZS/ZJS/PQ > PN), but weak differentiations in molecular weight distribution and oligosaccharide profiles, while Glc and GalA were richer for monosaccharide compositions of PG and RG polysaccharides, respectively. RG polysaccharides (25/50/100 µg/mL) showed significant cardiomyocyte protection by regulating mitochondrial functions. These new evidences may provide support for the supplementary role of polysaccharides in quality control of ginseng.