Integrated Network Pharmacology and Metabolomics Analysis to Reveal the Potential Mechanism of Siwu Paste on Aplastic Anemia Induced by Chemotherapy Drugs.

Purpose: This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways. Materials: Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH). Results: A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway. Conclusion: The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.

Huxie Huaji Ointment Induced Apoptosis of Liver Cancer Cells In Vivo and In Vitro by Activating the Mitochondrial Pathway.

Huxie Huaji (HXHJ) Ointment is a famous traditional Chinese medicinal prescription and is commonly used for the clinical treatment of hepatocellular carcinoma by boosting immunity and detoxification. However, the scientific evidence for the effect of HXHJ Ointment on hepatocellular carcinoma and the underlying molecular mechanism are lacking. The present study aimed to identify the effects of HXHJ Ointment on hepatocellular carcinoma in vitro and in vivo as well as investigating the mechanistic basis for the anticancer effect of HXHJ ointment. First, liquid chromatography-mass spectrometry was used to verify the composition of HXHJ Ointment and quality control. Second, in vitro, Cell Counting Kit (CCK8) cell viability assay and Hoechst 33342 staining assay were performed to explain the cell apoptosis. The protein levels of tumor suppressor protein (p53), B-cell lymphoma 2 gene (Bcl-2), cytochrome C (Cyt-C), and aspartate proteolytic enzyme-3 (caspase-3) were examined by immunofluorescence. Finally, in vivo, hematoxylin and eosin (H&E) staining was used to observe the pathological changes in hepatocellular carcinoma samples. Western blots and immunohistochemistry were used to detect the anticancer properties of HXHJ ointment. The results in vitro showed that 20% HXHJ Ointment serum could significantly inhibit HepG2 cell proliferation, increased tumor suppressor gene p53, downregulated antiapoptotic protein Bcl-2, promoted the release of mitochondrial Cyt-C, activated caspase-3, and induced HepG2 cell apoptosis. Furthermore, in vivo experiments showed that HXHJ Ointment could effectively inhibit tumor growth in nude mice xenotransplanted with HepG2 cells, changed the morphology of tumor cells, and regulated the expression of apoptosis-related protein pathway p53/Bcl-2/Cyt-C/caspase-3. HXHJ Ointment can significantly inhibit the development of hepatocellular carcinoma, and its mechanism may be related to the regulation of p53/Bcl-2/Cyt-C/caspase-3 signaling pathway to induce cell mitochondrial apoptosis.

Research Trends, Hot Spots, and Prospects for Traditional Chinese Medicine in the Field of Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) injury is one of the most common phenomena in ischemic disease or processes that causes progressive disability or even death. It has a major impact on global public health. Traditional Chinese medicine (TCM) has a long history of application in ischemic diseases and has significant clinical effect. Numerous studies have shown that the formulas or single herbs in TCM have specific roles in regulating oxidative stress, anti-inflammatory, inhibiting cell apoptosis, etc., in I/R injury. We used bibliometrics to quantitatively analyze the global output of publications on TCM in the field of I/R injury published in the period 2001-2021 to identify research hotspots and prospects. We included 446 related documents published in the Web of Science during 2001-2021. Visualization analysis revealed that the number of publications related to TCM in the field of I/R injury has increased year by year, reaching a peak in 2020. China is the country with the largest number of publications. Keywords and literature analyses demonstrated that neuroregeneration is likely one of the research hotspots and future directions of research in the field. Taken together, our findings suggest that although the inherent limitations of bibliometrics may affect the accuracy of the literature-based prediction of research hotspots, the results obtained from the included publications can provide a reference for the study of TCM in the field of I/R injury.

Mesenchymal stem cell-derived exosomes for gastrointestinal cancer.

Gastrointestinal (GI) malignancies, a series of malignant conditions originating from the digestive system, include gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. GI cancers have been regarded as the leading cancer-related cause of death in recent years. Therefore, it is essential to develop effective treatment strategies for GI malignancies. Mesenchymal stem cells (MSCs), a type of distinct non-hematopoietic stem cells and an important component of the tumor microenvironment, play important roles in regulating GI cancer development and progression through multiple mechanisms, such as secreting cytokines and direct interactions. Currently, studies are focusing on the anti-cancer effect of MSCs on GI malignancies. However, the effects and functional mechanisms of MSC-derived exosomes on GI cancer are less studied. MSC-derived exosomes can regulate GI tumor growth, drug response, metastasis, and invasion through transplanting proteins and miRNA to tumor cells to activate the specific signal pathway. Besides, the MSC-derived exosomes are also seen as an important drug delivery system and have shown potential in anti-cancer treatment. This study aims to summarize the effect and biological functions of MSC-derived exosomes on the development of GI cancers and discuss their possible clinical applications for the treatment of GI malignancies.

Indole-based alkaloids from Ophiocordyceps xuefengensis.

Seven undescribed indole-based alkaloids, xuefengins A-D and xuefenglasins A-C, were isolated from natural Ophiocordyceps xuefengensis, along with six known alkaloids. Their structures were elucidated by comprehensive spectroscopy, with absolute configurations confirmed by comparison with calculated electronic circular dichroism spectra. Eleven of the isolates were tested for cytotoxicity against the U937, NB4, MCF-7, Hep G2, and A549 cancer cell lines. Two compounds exhibited moderate activities, with IC50 values of 2.83-25.68 µM and 1.54-12.16 µM. Further pharmacological studies showed that these two compounds inhibit cell proliferation by inducing apoptosis, and decreasing p38 and caspase-3 levels in A549 cells.

Efficacy of N-Acetylcysteine in Preventing Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis Study.

PURPOSE: To evaluate whether perioperative N-acetylcysteine (NAC) administration reduces the risk of cardiac surgery associated acute kidney injury (CSA-AKI). MATERIALS AND METHODS: A systematic literature review (Medline, PubMed, Cochrane, Biomedical central, Google Scholar) identified 10 studies (1391 patients; 695 NAC and 696 placebo) that compared the efficacy and adverse effects of perioperative NAC administration for CSA-AKI prevention in adults undergoing elective cardiac surgery. Meta-analysis was performed using Comprehensive Meta-Analysis statistical software. RESULTS: Patients in the NAC-treated and placebo groups had similar rate of CSA-AKI occurrence, change in creatinine levels, as well as the in-hospital mortality rate (RR = 0.841, 95% CI = 0.691 to 1.023, p = 0.083; pooled difference in means = -0.328, 95% CI = -0.712 to 0.056, p = 0.094; RR = 0.741, 95% CI = 0.388 to 1.418, p = 0.366, respectively). CONCLUSIONS: Our study does not support perioperative NAC administration as a mean to reduce the risk of CSA-AKI.

Synthesis and investigation of physico-chemical properties of dicationic ionic liquids.

A series of dicationic ionic liquids (ILs) including [C4(MIM)2][PF6]2, [C5(MIM)2][PF6]2, [C6(MIM)2][PF6]2 and [C4(PYR)2][PF6]2 were synthesized. Their thermal stability and melting points were analysed. It was found that dicationic ILs presented important implications in the design of homogeneous and heterogeneous system with water. A homogeneous system of dicationic ILs with water could be formed at a relatively high temperature and then a heterogeneous system was formed when the solution was cooled to a low temperature. The ILs recovered by altering the temperature were obtained in high percentage yields of [C4(MIM)2][PF6]2 (97.6%), [C5(MIM)2][PF6]2 (97.3%), [C6(MIM)2][PF6]2 (98.0%) and [C4(PYR)2][PF6]2 (94.2%). On the other hand, [C4(MIM)2][PF6]2 and [C5(MIM)2][PF6]2 exhibited good solubility in acetonitrile and acetone. A homogeneous system could be achieved with imidazolium-based ILs with a relatively low amount of water and acetonitrile at room temperature. All of the properties of dicationic ILs have a strong correlation with the nature of dications, the linkage chain and the symmetry of dications. Dicationic ILs may provide a new opportunity for some specific applications in order to enable the effective separation and isolation of products.

Screening of potential IL-tolerant cellulases and their efficient saccharification of IL-pretreated lignocelluloses.

Lignocellulosic biomass as one of the most abundant and renewable resources has great potential for biofuel production. The complete conversion of biomass to biofuel is achieved through the effective pretreatment process and the following enzyme saccharification. Ionic liquids (ILs) are considered as a green solvent for lignocellulose pretreatment. However, ILs exhibit an inhibitory effect on cellulase activity, leading to a subsequent decrease in the efficiency of saccharification. The screening of new potential IL-tolerant cellulases is important. In the current study, a fungal strain with a relatively high cellulase production was isolated and identified as Penicillium oxalicum HC6. The culture conditions were optimized using corn stover and peptone as the carbon source and nitrogen source at pH 4.0 and 30 °C with an inoculation size of 2% (v/v) for 8 days. It was found that P. oxalicum HC6 exhibited potential salt tolerance with the increase of the enzyme production at a salt concentration of 5.0% (w/v). In addition, high enzyme activities were obtained at pH 4.0-6.0 and 50-65 °C. The crude enzyme from P. oxalicum HC6 with good thermal stability was also stable in the presence of salt and ILs. Good yields of reducing sugar were obtained by the crude enzyme from P. oxalicum HC6 after the saccharification of corn stover that was pretreated by ILs. P. oxalicum HC6 with potentially salt-tolerant and IL-tolerant enzymes has great potential application in the enzymatic saccharification of lignocellulose.

[HPLC Fingerprint of QingGuangAn and Determination of the Main Components].

OBJECTIVE: To establish an HPLC fingerprint of ethanol extract of QingGuangAn, and to determine the contents of paeoniflorin and calycosin-7-glucosid. METHODS: HPLC analysis was performed on an Agilent 1260 Infinity LC system and carried out at 35 degrees C on a column of GRACE Alltima C18 (250 mm x 4.6 mm, 5 µm). A binary gradient elution system was composed of acetonitrile (phase A) and water solution (phase B). Detection was performed at the wavelength of 254 nm, the mobile flow rate was 0.8 mL/min. A matrix including 20 variations (characteristic peaks area) and 10 samples was constructed for similarity evaluation. RESULTS: The results showed that the collected samples had a good similarity. A specificity fingerprint was produced and 20 characteristic peaks were designated. The content of paeoniflorin and calycosin-7-glucosid was 0.368 and 0.049 mg/g, respectively. CONCLUSION: It is a reliable, available and quick method for quality control of QingGuangAn,which provides some reference for the comparison of different extracting methods of QingGuangAn and the differences of pharmacodynamic.

[Stability of C60 nanoparticles in aquatic systems].

The influences of storage time, pH, electrolytes and organic matters on the stability of two different suspensions of C60 nanoparticles were investigated. The results showed that the C60 nanoparticles prepared by solvent substitution (C60/son) were more stable than that prepared by prolonged stirring (C60/aq), and kept stable for a period of time. Higher pH enhanced the stability of C60 nanoparticles. The presence of electrolyte made a dramatic decrease in the surface zeta potential and an increase in the particle size. The aggregation process of C60 nanoparticles exhibited slow and rapid regions, which was found to be consistent with the classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloidal stability. The critical coagulation concentration (CCC) values of C60/son, obtained from the intersection of the interpolated lines through the slow and fast regions, were estimated as 321 mmol x L(-1) NaCl, 316 mmol x L(-1) KCl, 9.6 mmol x L(-1) MgCl2 and 6.7 mmol x L(-1) CaCl2. The CCC values of C60/aq were estimated as 295 mmol x L(-1) NaCl, 278 mmol x L(-1) KCl, 7.8 mmol x L(-1) MgCl2 and 5.9 mmol x L(-1) CaCl2, which were much higher than their concentrations in natural waters. The presence of humic acid enhanced the stability of C60 nanoparticles, which was attributable to steric repulsion. Therefore, C60 nanoparticles will keep relatively stable in typical aquatic environments.

[The clinical characteristics of etiologies, diagnoses and treatment of emergency gastrointestinal hemorrhage.].

OBJECTIVE: To investigate the causes, clinical features, treatment and prognosis of gastrointestinal bleeding (GIB) patients in emergency department. METHODS: To analyze prospectively the clinical data of 168 GIB patients admitted to the emergency department of Peking Union Medical College Hospital during 2006.1 - 2006.12. RESULTS: (1) General data: male:female = 1.75:1 (107:61), mean age 13 - 87 (56.5 +/- 17.8) years with a peak in 60 - 69 years. The percentage of old patients was significantly higher than that of young and middle age (52.4% vs 19.6% and 28.0%, P = 0.000). (2) The incidence of acute gastric mucosal lesion in patients taking non-steroidal antiinflammatory drugs (NSAIDs) (18.5%) was significantly higher than that in patients not taking (0.7%, P = 0.000). (3) 86.9% (146/168) of the patients had anemia. (4) More patients who took emergency gastroscopy could be diagnosed than those patients who did not (89.4% vs 58.5%, P = 0.000), while no significant difference could be seen between patients who took emergency enteroscopy and patients who had non-emergency gastroscopy (20.0% vs 57.9%, P = 0.315). (5) The hemostatic ratio in GIB patients due to peptic ulcer was obviously higher than that in GIB patients due to other causes (86.0% vs 40.7%, P = 0.000). The rate of emergency operation for GIB patients was 1.8%. CONCLUSIONS: Most of the GIB patients admitted to tertiary general hospitals are elderly males. NSAIDs administration is one of the most important causes of upper GIB. Upper GIB patients should have gastroscopy as soon as possible, while emergency coloscopy is of little significance in cases with lower gastrointestinal hemorrhage.