Fanconi Anemia: Exploration of DNA Repair Pathways from Genetic Diseases to Cancer and Prospects for Treatment / 肿瘤防治研究

Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis

Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

Effects of probiotics on intestinal flora, intestinal function and T lymphocyte level in patients with cervical cancer after radiotherapy / 中国基层医药

Objective:To investigate the effects of probiotics on intestinal flora, intestinal function, and T lymphocyte level in patients with cervical cancer after radiotherapy.Methods:A total of 92 patients with cervical cancer who underwent pelvic radiotherapy in The Second Affiliated Hospital of Zhengzhou University from September 2020 to February 2022 were included in this study. They were randomly divided into control and experimental groups ( n = 46/group). The patients in the experimental group took probiotics during radiotherapy, while the patients in the control group did not take probiotics during radiotherapy. The amount of intestinal flora, D-lactic acid, diamine oxidase, and T lymphocyte subset levels pre- and post-radiotherapy were compared between the two groups. Urinary lactulose (L) and mannitol (M) concentrations were determined in each group. Urinary excretion ratios of L to M were calculated. Results:After 10, 15, and 20 times of radiotherapy and after all radiotherapies, the amount of Escherichia coli and Enterococcus in the experimental group was significantly lower than that in the control group ( F = 128.60, 224.99, all P < 0.05). The amount of Bifidobacteria and Lactobacilli in the experimental group was significantly higher than that in the control group ( F = 2 065.46, 948.23, both P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma D-lactic acid level in the experimental group was (9.34 ± 1.63) μg/L, (9.15 ± 1.36) μg/L, (8.68 ± 1.06) μg/L, and (8.05 ± 0.82) μg/L, respectively. After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma diamine oxidase level in the experimental group was (86.34 ± 20.25) μg/L, (84.28 ± 17.45) μg/L, (80.40 ± 13.35) μg/L, and (76.85 ± 10.87) μg/L, respectively, and urinary excretion ratio of L to M in the experimental group was (1.84 ± 0.16), (1.55 ± 0.12), (1.26 ± 0.09), (0.98 ± 0.06), respectively, all of which were significantly lower than those in the control group ( F = 121.60, 31.73, 417.84, all P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, CD4 + level in the experimental group was (39.80 ± 4.90)%, (40.92 ± 5.30)%, (42.52 ± 6.14)%, (43.83 ± 6.55)%, respectively, CD4 +/CD8 + was (1.52 ± 0.25), (1.63 ± 0.22), (1.71 ± 0.39), (1.83 ± 0.22), respectively, all of which were significantly higher than those in the control group ( F = 58.69, 31.07, all P < 0.05). Conclusion:Probiotics can improve the status of intestinal flora and intestinal barrier function in patients with cervical cancer after radiotherapy, and simultaneously improve the cellular immune function of patients.

Determination of antioxidant activity of Polygoni Multiflori Radix Praeparata by HPLC-DPPH / 中国药科大学学报

@#An on-line HPLC-DPPH system was developed to determine the antioxidant activity of 16 batches of Polygoni Multiflori Radix Praeparata. By analyzing the chromatographic and biological activity fingerprints of 16 batches of Polygoni Multiflori Radix Praeparata, the dose-effect relationship was established and the total antioxidant activity was quantified by activity addition.The results suggested that the online HPLC-DPPH method can evaluate the antioxidant activity of different bathches of Polygoni Multiflori Radix Praeparata, with different processing methods, aiming to provide datasupport and scientific basis forquality evaluation of Polygoni Multiflori Radix Praeparata.

Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats / 分析化学

A liquid chromatography-quadrupole-time-of-flight mass spectrometer(LC-Q/TOF-MS) based urinary metabolomic approach was employed to assess the toxicity-alleviation effect of Huangqi oral solution(HOs) on cisplatin-exposed rats and explore its possible mechanisms. Rat toxicity model was developed by multiple intraperitoneal injection of low-dose cisplatin, while HOs was orally administrated to rats simultaneously for 16 consecutive days to attenuate or reduce the cisplatin-induced toxicity. 24-hour urine samples on day 18 were collected and analyzed using LC-Q/TOF-MS to obtain the dataset of urinary metabolites. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to assess the quality of the dataset and screen the potential toxicity-alleviation biomarkers. The serum level of rat creatinine and urea nitrogen on day 20 was determined, and the results showed that successive administration of HOs significantly reduced the cisplatin-induced increase of creatinine and urea nitrogen. PCA cluster analysis clearly demonstrated that HOs could partly improve the CDDP-induced abnormality of metabolic profiling. 35 urinary metabolites were finally screened as the potential biomarkers associated with the toxicity-attenuation effect of HOs, according to the combination of the analysis results of OPLS-DA, t-test and fold change analysis. Further metabolic pathway analysis revealed that HOs could restore the metabolic disorders of amino acid, energy and nucleotide, thereby exerted its toxicity-alleviation effect.

Comparative analysis on difference between China and Russian traditional medical treatments / 国际中医中药杂志

This article analyzed the difference between Chinese and Russian traditional medical treatments from the part of herbs,acupuncture/acupressure therapy,manual therapy,psychotherapy,and sports.TCM had a separate comprehensive diagnosis and treatment system,Russia traditional medicine,attached to Western medicine,had not formed the independent diagnostic and treatment system.

The development of Chinese medicine trade between China and Russia in context of “One Belt and One Road” / 国际中医中药杂志

The strategy of One Belt and One Road established new era for China to open-door to the world. It is an important way to establish and strengthen the relationship among countries along the belt and the road. This paper has analyzed and shown the history, prespects and development of Chinese medicine trade between China and Russia in context of “One Belt and One Road”. And then counter measures were proposed, such as promoting diversification of Chinese medicine service, developing international standard in Chinese medicine, strengthening cultural exchanges of Chinese medicine, advertising Chinese medicine in Russia, and so on.

Pharmacokinetic effect of aspirin on caffeic acid in dengzhanxixin injection / 中国药理学通报

Aim To investigate the pharmacokinetic effect of aspirin on caffeic acid in dengzhanxixin injec-tion( DI) . Methods Concentration of caffeic acid in rat plasma was detected by LC-MS/MS after rats were given intravenous administration of DI or DI combined with aspirin by gavage. Pharmacokinetic parameters were calculated by DAS 1. 0 pharmacokinetic software. Results In vivo pharmacokinetic models of caffeic acid were two-compartment open models in both the caffeic acid group and the caffeic acid combined with aspirin group. After compatibility, caffeic acid showed a significant increase in T 12β, with a slight decrease in CL. Conclusions Aspirin can reduce metabolic process of caffeic acid in vivo.

Study on pharmacokinetics of danshensu sodium in danshen dripping solution in Beagles / 中国中药杂志

<p><b>OBJECTIVE</b>To detect pharmacokinetics of Danshensu Sodium in Danshen dripping solution in Beagles.</p><p><b>METHOD</b>Danshen dripping solution was dripped intravenously into healthy Beagles at a dose of 10 mL x kg(-1). Their plasma samples were extracted with acetic ether, the blood concentrations were determined by HPLC method.</p><p><b>RESULT</b>Danshensu Sodium showed a good linear relationship within the range of 0.225-18.000 mg x L(-1), with the lowest detectable limit of 0.113 mg x L(-1). Its pharmacokinetic parameters were as follows: tmax was 30 min, Cmax was (9.5742 +/- 2.3715) mg x L(-1), t1/2 was (19.23 +/- 2.97) min, CL was (0.0127 +/- 0.0030) L x min(-1) x kg(-1), AUC(0-tn) was (474.954 +/- 95.483) mg x min x L(-1) and AUC(0-infinity) was (482.494 +/- 95.353) mg x min x L(-1).</p><p><b>CONCLUSION</b>The accurate, stable and reliable blood concentration method shows a one-compartment mode of Danshensu Sodium in Beagles.</p>

Pharmacokinetic study of asiaticoside in rat plasma by UPLC-MS / 中国药理学通报

Aim To establish an UPLC-ESI-MS method for determination of asiaticoside and investigate its application to pharmacokinetic study in rats.Methods Eight rats were given 40 mg·kg~(-1) asiaticoside iv respectively.Drug plasma concentration was determined by UPLC-ESI-MS.Pharmacokinetic parameters were evaluated.Results Calibration curves were linear over 0.038～7.6 mg·L~(-1) and LLOQ was 38 μg·L~(-1),the recoveries of asiaticoside from plasma were larger than 95%,and RSD of inter-day and intra-day assay were below 10%.After iv administration of 40 mg·kg~(-1) asiaticoside,the pharmacokinetic parameters of AUC(0-t),T(1)/(2)β,CL,Vd were (81 443.67±57 156.81) μg·L~(-1)·min~(-1),(23.44±9.60) min,(0.19±0.07) L·min~(-1)·kg~(-1),(8.92±6.68) L·kg~(-1),respectively.Conclusion The method described in this report was sensitive and specific,and suitable for pharmacokinetic studies of asiaticoside in rats.

Effects of Huangkui Capsule on the P450 activities in rats / 中国临床药理学与治疗学

0.05), meanwhile,after being treated with higher-dose Huangkui Capsule,there were no significant differences for theophylline pharmacokinetics in rats,but AUC_(0-24 h) of chlorzoxazone after treatment was 1.75 times larger than that before treatment(P

Absorption mechanism of aesculin across Caco-2 monolayer mode / 中成药

AIM:To research the absorption mechanism of aesculin across Caco-2 monolayer model.METHODS:The Caco-2 cell monolayers drug transport model was assigned to study the double transport mechanism of aesculin to explore the absorption of aesculin according as time and drug concentration determined through HPLC and the P_ app was calcalated.RESULTS:In the Caco-2 monolayer model,the transport of aesculin form Apical to Basolateral was similar to the transport form basolateral to apical.CONCLUSION:The main mechanism of the aesculin intestinal absorption in the Caco-2 monolayer model is passive transference.

Studies on Pharmacokinetic Interaction Among CYP1A2,CYP2E1 and CYP3A4 Probes in Rats / 中药新药与临床药理

0.05).Conclusion When given concomitantly as a Cocktail,theophylline,chlorzoxazone and dapsone have no pharmacokinetic interaction,which could be used together to evaluate CYP1A2,CYP2E1 and CYP3A4 activity.