Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

The relationship between MHC-peptide interaction and resistance to virus in chickens.

INTRODUCTION: The MHC-peptide interaction has a subtle influence on host resistance to virus. This paper aims to study the relationship between MHC-peptide interaction and MHC-related virus-resistance. METHODS: By 3D homology modeling, the structure of chicken BF2 molecule BF2*0201 (PDB code: 4d0d) was studied and compared with the known structures of BF2 molecule BF2*0401 (PDB code: 4e0r) to elucidate the characteristics of BF2*0201-binding antigenic peptides. RESULTS: The results show that due to the amino acid difference between the two binding groove of 4e0r and 4d0d, the size of the binding groove of the two are 1130 ų and1380 ų respectively, indicating the amino acid species that 4e0r binding peptide has lower selectivity than 4d0d; and because of large side chain conformation of Arg (especially Arg111) of 4e0r replaced by small side chain Tyr111 of 4d0d, the volume of central part of the binding groove of 4d0d is obviously larger than that of 4e0r, indicating that the restrictive of binding antigenic peptides for 4d0d is narrower than that of 4e0r; and on account of the chargeability of the binding groove of the two are different, namely the binding groove chargeability of 4e0r (strong positive polarity) and 4d0d (weak negative polarity). CONCLUSION: There are generally more peptides presented by the BF2 of B2 haplotype than by that of B4 haplotype, leading to more resistance of B2 than that of B4 to virus.

Study on the contrast of the MHC-peptide interaction of B2/B21 haplotype and MHC-related virus resistance in chickens.

INTRODUCTION: Three-dimensional (3D) structures of MHC class I exert some influence by the MHC-peptide interaction over host resistance to the virus. The thesis aims at studying the connection between MHC-peptide interaction of B2/B21 haplotype and MHC-related resistance to the virus. METHODS: The structure of chicken MHC class I BF2*0201 from B2 haplotype was studied and contrasted with that of BF2*2101 from B21 haplotype by using DNAMAN and PyMol software. RESULTS: The amino acid difference resulted in the difference in size and changeability of the binding groove of the two, resulting in different choices on the binding polypeptide. 3bew's (the crystal structure of BF2*2101 bound to peptide RV10) small side chain His111 replaces the short side chain Tyr111 of 4cvx (the crystal structure of BF2*0201 bound to peptide YL9), and the very small amino acid of Ser69 and Ser97 make the middle of the 3bew's binding groove become apparently broad and bound restrictive of amino acid smaller. Moreover, due to the specific amino acids-Arg9, Asp24, and Asp73 of 4cvx and Arg9, Asp24, and His111 of 3bew, the effect of the polypeptide and the binding groove differ between the two, and 3bew tends to bind polypeptides with negatively charged amino acids, but the large space in the middle can also accommodate other amino acids. Contrasted with the binding groove characteristic of 4cvx, it can be said that the selectivity of 3bew is higher than that of 4cvx in the amino acid type of the binding polypeptide, so the B21 haplotype has more host resistance to the virus than that of the B2 haplotype in chicken. CONCLUSION: There are usually various kinds of peptides presented by the BF2*2101 molecules of B21 haplotypes, resulting in resistance to pathogenic microorganisms, such as Rous sarcoma virus and/or Marek's disease virus. These findings may have an important theoretical foundation for screening of virus antigen, vaccine design, and genetic resistance breeding.

Perfluorodecanoic acid induces meiotic defects and deterioration of mice oocytes in vitro.

Perfluorodecanoic acid (PFDA) is a member of the perfluoroalkyl substances, which are toxic to organic functions. Recently, it has been found in follicular fluid, seriously interfering with reproduction. Follicular fluid provides the oocyte with necessary resources during the process of oocytes maturation. However, the effects of PFDA on the oocyte need investigation. Our study evaluated the impacts of PFDA on the meiosis and development potential of mouse oocytes by exposing oocytes to PFDA in vitro at 350, 400, and 450 µM concentrations. The results showed that exposure to PFDA resulted in the first meiotic prophase arrest by obstructing the function of the maturation-promoting factor. It also induced the dysfunction of the spindle assembly checkpoint, expedited the progression of the first meiotic process, and increased the risk of aneuploidy. The oocytes treated with PFDA had a broken cytoskeleton which also contributed to meiotic maturation failure. Besides, PFDA exposure caused mitochondria defections, increased the reactive oxygen species level in oocytes, and consequently induced oocyte apoptosis. Moreover, PFDA produced epigenetic modifications in oocytes and increased the frequency of mature oocytes with declined development potential. In summary, our data indicated that PFDA disturbs the meiotic process and induces oocyte quality deterioration.

The Efficacy and Safety of Carbon Ion Radiotherapy for Meningiomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this systematic review and meta-analysis is to evaluate the efficacy and safety of carbon ion radiotherapy (CI-RT) in improving meningioma by comparing photon and protons radiotherapy. METHODS: A comprehensive search for relevant studies published until March 17, 2021, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database and EMBASE. Statistical analyses were performed with R 4.0.3. RESULTS: We identified 396 studies, of which 18 studies involving 985 participants were included. Except for one low quality study, the quality of the included studies was found to be either moderate or high quality. The analyses conducted according random effects model indicated that the 1-year overall survival rate (OS) of benign and non-benign meningiomas after the CI-RT treatment was 99% (95%CL=.91-1.00, I 2 = 0%). The overall average 5-year OS for meningiomas was 72% (95%CL=0.52-0.86, I 2 = 35%), not as effective as proton radiotherapy (PR-RT) 85% (95%CL=.72-.93, I 2 = 73, Q=4.17, df=2, p=.12). Additionally, 5-year OS of atypical meningiomas (81%) was found to be significantly higher than anaplastic meningiomas (52%). The 10-year OS after CI-RT of patients with mixed grade meningioma was 91% (95%CL=.75-.97, I 2 = 73%). The 15-year OS after CI-RT 87% (95%CL=.11-1.00) or PR-RT 87% (95%CL=.23-.99, I 2 = 79%) were the same (Q=0, df=1, p=.99). After undergoing CI-RT for 3 and 5 years, the LC for benign meningioma was 100% and 88%, respectively, while the 2-year LC of non-benign meningiomas (atypical/anaplastic) was 33%. Headache, sensory impairment, cognitive impairment, and hearing impairment were found to be the most common adverse reactions, with individual incidences of 19.4%, 23.7%, 9.1%, and 9.1%, respectively. CONCLUSION: CI-RT is a rapidly developing technique that has been proven to be an effective treatment against meningioma. The efficacy and safety of CI-RT for meningiomas were similar to those of PR-RT, better than photon radiotherapy (PH-RT). However, there is a need for more prospective trials in the future that can help provide more supportive evidence.

Effect of Oral Chinese Medicine Combined with Western Medicine on Cancer Pain: A Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To assess the effect of oral Chinese medicine (OCM) combined with Western medicine (WM) on cancer pain.@*METHODS@#PubMed, Embase, Cochrane Library, Clinical Trials Registry Platform, Chinese National Knowledge Infrastructure (CNKI), Wanfang and VIP databases were searched from their inception to September {dy2019}. Randomized controlled trials (RCTs) treating cancer pain by Chinese medicine (CM) combined with WM were included. The primary outcome were total pain relief rate and the quality of life (QOL), and the other outcomes were the average daily dosage of analgesics, the primary time of pain, the analgesic duration time, and adverse events. The methodological quality of RCTs was assessed in accordance with Cochrane 5.1.0 handbook of systematic reviews of interventions. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.@*RESULTS@#There were 1,087 patients in the 14 studies, with 544 in the experiment group and 543 in the control group. These studies were all conducted in China, and published between 2006 and {dy2019}. Compared with the WM, OCM combined with WM could significantly relieve the cancer pain [risk ratio (RR)=1.43, 95% confidence interval (CI): 1.32, 1.56), improve QOL (RR=8.57, 95% CI: 4.25, 12.89), decrease the primary time of pain (RR=-0.20, 95% CI: -0.24, -0.16], prolong the analgesic duration time (RR=3.47, 95% CI: 2.09, 4.85), reduce the dosage of analgesics (RR=-19.52, 95% CI: -36.32, -2.72), and reduce side events (RR=0.49, 95% CI: 0.37, 0.65). Evidence levels for total pain relief rate, primary time of pain and side events were low, evidence level for QOL, analgesic duration time and average daily dosage of analgesics were very low.@*CONCLUSIONS@#Compared with the WM, OCM combined with WM could significantly relieve the cancer pain, improve the QOL, decrease the primary time of pain, prolong the analgesic duration time, reduce the dosage of analgesics and side events. The evidence levels were low or very low.