TMT-based quantitative proteomics analysis of neuroprotective effects of Forsythoside A on the MPTP-induced Parkinson's disease mouse model.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characteristized by the presence of dyskinesia and the progressive loss of dopaminergic neurons. Although certain drugs can mitigate the symptoms of PD, they are unable to delay the disease progression, and their prolonged use may result in complications. Therefore, there exists an urgent necessity to identify potential agents that can effectively delay PD progression with fewer side effects. Recent research has unveiled that several traditional Chinese medicines (TCM) exhibit neuroprotective properties in various models pertinent to PD. Forsythoside A (FSA), the primary bioactive compound derived from TCM Lianqiao, has undergone extensive research in animal models of Alzheimer's disease and cerebral ischemia. However, the investigation into the impact of FSA on PD is limited in existing research. In this study, we aimed to evaluate the neuroprotective effects of FSA on MPTP-induced PD mouse model. FSA demonstrated significant improvements in the behavioral and neuropathological changes triggered by MPTP in mice. Furthermore, it exerted a suppressive effect on the activations of astrocyte and microglia. Meanwhile, Tandem mass tag (TMT)-based quantitative proteomics of striatal tissue and bioinformatics analysis were performed to elucidate the underlying mechanisms of FSA on PD mouse model. Proteomics demonstrated a total of 68 differentially expressed proteins (DEPs) were identified between HFSA and MPTP groups including 26 upregulated and 42 downregulated. Systematic bioinformatics analysis of the 68 DEPs illustrated that they were predominantly related to estrogen signaling pathway and calcium signaling pathway. The related DEPs (PLCß4, Grm2, HPAC and Cox4i1) expression levels were verified by Western blot. FSA effectively restored the altered expression of the four DEPs induced by MPTP. Summarily, FSA exerted remarkable neuroprotective effects in MPTP-induced mice. Further, our research may provide proteomics insights that contribute to the further exploration of FSA as a potential treatment for PD.

Exploring the mechanisms underlying the therapeutic effect of the Radix Bupleuri-Rhizoma Cyperi herb pair on hepatocellular carcinoma using multilevel data integration and molecular docking.

Traditional Chinese medicine (TCM) is a promising and effective treatment for cancer with minimal side effects through a multi-active ingredient multitarget network. Radix Bupleuri and Rhizoma Cyperi are listed as herbs dispersing stagnated liver Qi in China. They have been used clinically to treat liver diseases for many years and recent pharmacological studies have shown that they inhibit the proliferation of hepatocellular carcinoma (HCC). However, the pharmacological mechanisms, potential targets, and clinical value of the Radix Bupleuri-Rhizoma Cyperi herb pair (CXP) for suppressing HCC growth have not been fully elucidated. We identified 44 CXP targets involved in the treatment of HCC using the GEO dataset and HERB database. An analysis of the Traditional Chinese Medicine System Pharmacology Database (TCMSP) showed that CXP exerts synergistic effects through 4 active ingredients, including quercetin, stigmasterol, isorhamnetin, and kaempferol. GO and KEGG analyses revealed that CXP mainly regulates HCC progression through metabolic pathways, the p53 signaling pathway, and the cell cycle. Additionally, we applied The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) database to perform the expression patterns, clinical features, and prognosis of 6 genes (CCNB1, CDK1, CDK4, MYC, CDKN2A, and CHEK1) in cell cycle pathways to reveal that CXP suppresses HCC clinical therapeutic value. Moreover, based on molecular docking, we further verified that CXP exerts its anti-HCC activity through the interaction of multiple active components with cell cycle-related genes. We systematically revealed the potential pharmacological mechanisms and targets of CXP in HCC using multilevel data integration and molecular docking strategies.

Elucidating the pharmacological mechanism by which Si-Wu-Tang induces cellular senescence in breast cancer via multilevel data integration.

Traditional Chinese medicine (TCM) is a promising strategy for effectively treating cancer by inducing cellular senescence with minimal side effects. Si-Wu-Tang (SWT) is a TCM composed of four herbs that is commonly used in China for the treatment of gynecological diseases; SWT can prevent breast cancer (BC), but the molecular mechanism by which SWT induces cellular senescence and its clinical application value remain unknown. We identified 335 differentially expressed genes (DEGs) in SWT-treated MCF-7 cells through Gene Expression Omnibus (GEO) dataset analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the enrichment of biological processes and key signaling pathways including cellular senescence, the cell cycle, the MAPK signaling pathway, and the p53 signaling pathway. Additionally, SWT induced BC cell senescence by upregulating the expression of 33 aging/senescence-induced genes (ASIGs). According to LASSO regression analysis, NDRG1, ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 levels were associated with BC prognosis and were used to develop risk scores. ERRFI1, SOCS1, IRS2, IGFBP4, and BIRC3 were identified as protective factors (P < 0.05, HR < 1), while NDRG1 was identified as a risk factor (P < 0.05, HR > 1). Notably, patients with low risk scores had increased senescence-associated secretory phenotypes (SASPs) and immune cell infiltration. Overall, we systematically integrated biological databases and biocomputational methods to reveal the mechanisms by which SWT induces senescence in breast cancer and its clinical value.

[Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease].

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

[Systematic review and Meta-analysis on efficacy and safety of Gongxuening Capsules in treatment of abnormal vaginal bleeding after medical abortion].

To systematically evaluate the efficacy and safety of Gongxuening Capsules in the treatment of abnormal vaginal bleeding after medical abortion. CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to comprehensively collect the clinical randomized controlled trials(RCTs) of Gongxuening Capsules for treatment of abnormal vaginal bleeding after medical abortion from the establishment of the databases to October 10, 2020. Literature screening, data extraction and quality evaluation were conducted independently by two system reviewers according to the inclusion and exclusion criteria. Cochrane Handbook bias risk assessment tool was used for the literature methodology quality evaluation, RevMan 5.3 software was used for Meta-analysis, and the evidence quality of outcomes was evaluated by the evidence quality grading system(GRADE). A total of 16 RCTs were inclu-ded. The results of Meta-analysis showed that as compared with the western medicine treatment alone, the addition of Gongxuening Capsules to the western medicine treatment can reduce the amount of vaginal bleeding(RR=1.23, 95%CI[1.19, 1.27], P<0.000 01), shorten vaginal bleeding time(RR_(≤15 d number of people)=1.39, 95%CI[1.31, 1.48], P<0.000 01; MD_(number ofdays)=-1.20, 95%CI[-1.66,-0.74],P<0.000 01). However, there was no obvious advantage in abortion effect(RR=1.02, 95%CI[0.99, 1.06], P=0.14) and menstrual recovery(MD=-0.35, 95%CI[-0.96, 0.25], P=0.25). The results of GRADE showed that the grading level was low for vaginal bleeding volume and vaginal bleeding time, and extremely low for abortion effect and mens-trual recovery. In terms of safety, 16 studies reported adverse events. Only one study showed no adverse events and the rest showed transient nausea, vomiting, stomach burning, upper abdominal discomfort and other gastrointestinal symptoms. The results show that the addition of Gongxuening Capsules to the application of western medicine in treatment of drug abortion can reduce the amount of vaginal bleeding and shorten vaginal bleeding time, but the abortion effect and menstrual recovery have no obvious advantages. The use of Gongxuening Capsules helps to achieve less adverse reactions and higher safety. Due to the small sample size of the included studies and many methodological quality problems, no conclusions with clinical guidance value can be obtained. Large sample-zise, high-qua-lity randomized controlled trials are still needed for further verification.

Specific Recognition of Uranyl Ion Employing a Functionalized Nanochannel Platform for Dealing with Radioactive Contamination.

Radioactive contamination is a highly concerning global environmental issue along with the development of the nuclear industry. On account of sophisticated operations and high cost of instrument detection methods, numerous efforts have been focused on rapid and simple detection of pollution elements and uranium is the most common one. It is an enormous challenge to push the limit of determination as low as possible while carrying out ultrasensitive detection. Here, we report an intelligent platform based on functionalized solid nanochannels to monitor ultratrace uranyl ions. The platform has a detection limit of 1 fM, which is far below the value that traditional instrumental methods can reach. What is more, the system also exhibits uranyl removal property. The mesenchymal stem cells cultivated in media containing uranyl can achieve excellent viability in the presence of the membranes. This work provides a new choice for handling global radioactive contamination of water.

Protective effect of gui zhi (Ramulus Cinnamomi) on abnormal levels of four amino acid neurotransmitters by chronically ma huang (Herb Ephedra) intoxicated prefrontal cortex in rats treated with a ma huang-gui zhi herb pair.

ETHNOPHARMACOLOGICAL RELEVANCE: The Herb Ephedra (Ma Huang in Chinese)-Ramulus Cinnamomi (Gui Zhi in Chinese) herb pair is a classic traditional Chinese herb pair used to treat asthma, nose and lung congestion, and fever with anhidrosis. In previous study, we found that chronic administration of ma huang induced obvious neurodegeneration in rat brains, with the prefrontal cortex showing the greatest effect. Gui zhi decreased hyperactivity produced by repeated ma huang administration, and attenuated oxidative stress in rat prefrontal cortex induced by ma huang. AIM OF THE STUDY: The study was aimed to investigate the protective effect of gui zhi on ma huang-induced abnormal levels of four amino acid neurotransmitters in rat prefrontal cortex. MATERIALS AND METHODS: All ma huang and ma huang-gui zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (6 rats/group) were administered ma huang or ma huang-gui zhi herb pair extracts for 1, 3, 5 or 7 days (ephedrine = 48 mg/kg). The contents of ephedrine, glutamate (Glu), aspartic acid (Asp), glycine (Gly), and gamma-aminobutyric acid (GABA) in the prefrontal cortex were determined using ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) at 0.5, 1.0, 5.0 h after administration. RESULTS: Ma huang significantly enhanced the levels of GABA, Gly, Glu and Asp in the prefrontal cortex, while gui zhi partially abolished the effects. CONCLUSIONS: Ma huang-induced neurotoxicity may be associated with its effects on amino acid neurotransmitters. Gui zhi is a promising neuroprotective agent against for ma huang-induced neurotoxicity. The information presented in this study will help supplement the available data for future ma huang-gui zhi herb pair compatibility studies.

The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.

Folate deficiency in early development leads to disturbance in multiple processes, including neurogenesis during which fibroblast growth factor (FGF) pathway is one of the crucial pathways. Whether folic acid (FA) directly affects FGF pathways to influence neurodevelopment and the possible mechanism remains unclear. In this study, we presented evidence that in human FA-insufficient encephalocele, the FGF pathway was interfered. Furthermore, in Brachyury knockout mice devoid of such T-box transcription factors regulating embryonic neuromesodermal bipotency and a key component of FGF pathway, change in expression of Brachyury downstream targets, activator Fgf8 and suppressor dual specificity phosphatase 6 was detected, along with the reduction in expression of other key FGF pathway genes. By using a FA-deficient cell model, we further demonstrated that decrease in Brachyury expression was through alteration in hypermethylation at the Brachyury promoter region under FA deficiency conditions, and suppression of Brachyury promoted the inactivation of the FGF pathway. Correspondingly, FA supplementation partially reverses the effects seen in FA-deficient embryoid bodies. Lastly, in mice with maternal folate-deficient diets, aberrant FGF pathway activity was found in fetal brain dysplasia. Taken together, our findings highlight the effect of FA on FGF pathways during neurogenesis, and the mechanism may be due to the low expression of Brachyury gene via hypermethylation under FA-insufficient conditions.-Chang, S., Lu, X., Wang, S., Wang, Z., Huo, J., Huang, J., Shangguan, S., Li, S., Zou, J., Bao, Y., Guo, J., Wang, F., Niu, B., Zhang, T., Qiu, Z., Wu, J., Wang, L. The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.

Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription.

The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development.

An extract from the earthworm Eisenia fetida non-specifically inhibits the activity of influenza and adenoviruses.

OBJECTIVE: To test the in vitro antiviral activity of a crude tissue extract (CTE) from the earthworm Eisenia fetida, determine any effective components in the CTE, and elucidate possible mechanisms of action. METHODS: A CTE was made by homogenizing earthworms, followed by treatment with ammonium sulfate, then thermal denaturation. Inhibition of virus-induced cytopathic effect (CPE) was used to assess antiviral activity. Chromatographic analysis was used to identify effective components in the CTE. RESULTS: The CTE inhibited viral CPE at non-cytotoxic concentrations. Chromatography indicated that antiviral components corresponded to three active peaks indicative of proteases, nucleases and lysozymes. For adenoviruses, reduction in viral activity occurred for 100 microg/mL CTE. The reduction in adenoviral activity for four fractions was 100%, 91.8%, 86.9%, and 94.7%. For influenza viruses, reduction in viral activity of 100%, 86.6%, 69.1% and 88.3% was observed for 37 microg/mL CTE. In addition, three active fractions mixture had stronger antiviral activity (98.7% and 96.7%) than three fractions alone. Gel electrophoresis results indicated that nucleases from E. fetida could degrade the genome of influenza viruses and adenoviruses. CONCLUSION: The earthworm CTE displayed non-specific antiviral properties, possibly mediated by a combination of proteases, nucleases and lysozymes. Nucleases likely participate in the antiviral process, and degrade the genome of the virus thereby preventing further replication.

[Observation on clinical therapeutic effect of point sticking therapy on hyperplasia of mammary glands].

OBJECTIVE: To compare therapeutic effects of point sticking therapy and Chinese herbs on hyperplasia of mammary glands. Methods Sixty-three female patients with hyperplasia of mammary glands were randomly divided into an observation group (n=33) and a control group (n=30). The observation group were treated with point sticking therapy, i.e., Sanleng (Rhizoma Spargani), Ezhu (Rhizoma Zedoariae), Zhi Nanxing (Pedate Pinallia Jackinthepulpit Rhizome) and Bingpian (Borneolum) were made a plaster to apply Qihai (CV 6), Guanyuan (CV 4) and Ashi points on breast. The control group were treated with oral administration of Rupixiao. RESULTS: After treatment of 3 courses, the total effective rate was 97.0% in the observation group, and 83.3% in the control group, the former significantly being better than the latter (P < 0.05). The score of mastalgia improvement was (13.82 +/- 5.90) points in the observation group and (7.00 +/- 3.89) points in the control group with a very significant difference between the two groups (P < 0.01). CONCLUSION: ooint sticking therapy has a definite therapeutic effect n hyperplasia of mammary glands.