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C13H10N4O7, monoclinic, P21/n (no. 14), a = 10.7017(7) Å, b = 7.1240(5) Å, c = 19.0878(13) Å, β = 99.280(3)°, V = 1436.19(17) Å3, Z = 4, Rgt (F) = 0.0586, wRref (F 2) = 0.1746, T = 296.15 K.

C13H10N4O7, monoclinic, P21/n (no. 14), a = 10.7017(7) Å, b = 7.1240(5) Å, c = 19.0878(13) Å, β = 99.280(3)°, V = 1436.19(17) Å3, Z = 4, Rgt(F) = 0.0586, wRref(F2) = 0.1746, T = 296.15 K. [ABSTRACT FROM AUTHOR]

A type of sorafenib- (SOR-) loaded long-circulating nanoliposome was constructed, and the targeting performance and antitumor effects of the prepared liposome were evaluated in the present study. Polyethylene glycol- (PEG-) modified long-circulating nanoliposomes (LC-NPs) were designed and prepared using reverse evaporation, and the LC-NPs were used for delivering sorafenib (LC-PEG-SOR-NPs). Then, the anti-VEGFR antibody as a targeting moiety was chemically coupled with LC-PEG-SOR-NPs to form liver cancer-targeted nanoliposomes (anti-VEGFR-LC-PEG-SOR-NPs). The drug entrapment and loading efficiency were measured. And the cancer-targeting performance and therapeutic efficiency were evaluated both in vitro and in vivo. The anti-VEGFR-LC-PEG-SOR-NPs with an average of 119.8 ± 4.2 nm showed a uniform spherical structure. The drug entrapment and loading efficiency were 92.5% and 18.5%, respectively. The killing efficiency of anti-VEGFR-LC-PEG-SOR-NPs was up to 18% after incubating with liver cancer cells for 72 h. Furthermore, the anti-VEGFR-LC-PEG-SOR-NPs could actively target at the tumor region and could efficiently inhibit tumor growth with negligible side effects. This newly designed nanoliposomes had desirable dispersibility, high drug entrapment efficiency, tumor targeting and therapeutic efficiency, and good safety. As a biocompatible nanocomposite, it was promising to become a novel and useful tumor-targeting nanodrug for liver cancer therapy. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease that occurs in the intestinal tract. It is mainly divided into two subtypes, i.e., the Crohn's disease (CD) and ulcerative colitis (UC). At present, its pathogenesis has not been fully elucidated, but it has been generally believed that the environment, immune disorders, genetic susceptibility, and intestinal microbes are the main factors for the disease pathogenesis. With the development of the sequencing technology, microbial factors have received more and more attention. The gut microbiota is in a state of precise balance with the host, in which the host immune system is tolerant to immunogenic antigens produced by gut commensal microbes. In IBD patients, changes in the balance between pathogenic microorganisms and commensal microbes lead to changes in the composition and diversity of gut microbes, and the balance between microorganisms and the host would be disrupted. This new state is defined as dysbiosis. It has been confirmed, in both clinical and experimental settings, that dysbiosis plays an important role in the occurrence and development of IBD, but the causal relationship between dysbiosis and inflammation has not been elucidated. On the other hand, as a classic research method for pathogen identification, the Koch's postulates sets the standard for verifying the role of pathogens in disease. With the further acknowledgment of the disease pathogenesis, it is realized that the traditional Koch's postulates is not applicable to the etiology research (determination) of infectious diseases. Thus, many researchers have carried out more comprehensive and complex elaboration of Koch's postulates to help people better understand and explain disease pathogenesis through the improved Koch's postulates. Therefore, focusing on the new perspective of the improved Koch's postulates is of great significance for deeply understanding the relationship between dysbiosis and IBD. This article has reviewed the studies on dysbiosis in IBD, the use of microbial agents in the treatment of IBD, and their relationship to the modified Koch's postulates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Zhang, Cheng, You, Huang and Lu.)

Objective: We investigated the clinical significance of preoperative pan-immune-inflammation value (PIV) in patients with colorectal cancer (CRC)., Methods: In this retrospective study, 366 cases who underwent surgery for CRC were enrolled. Their clinical data were collected. PIV was calculated with the formula PIV = [neutrophil count (10 9 /L)× platelet count (10 9 /L) × monocyte count (10 9 /L) /lymphocyte count (10 9 /L). Patients were divided into high PIV (> median PIV) and low PIV (< median PIV) groups. The relationship between PIV and clinicopathological features of CRC was investigated. Receiver operating characteristic (ROC) curve was plotted to indicate the value of immune-inflammatory biomarkers (IIBs) in predicting the TNM stage of CRC, and the area under the curve (AUC) was calculated to evaluate the actual clinical value of IIBs. AUC > 0.5 and closer to 1 indicated the better predictive efficacy. The influencing factors of PIV in CRC were analyzed., Results: We found that PIV was positively correlated with tumor size ( r  = 0.300, p  < 0.05), carcinoembryonic antigen (CEA) ( r  = 0.214, p  < 0.05) and carbohydrate antigen 125 (CA-125) ( r  = 0.249, p  < 0.05), but negatively correlated with albumin (Alb) ( r  = -0.242, p  < 0.05). PIV was significantly different in patients with different tumor locations (left or right), surgical methods (laparotomy versus laparoscopic surgery) ( p  < 0.05), and patients with different pathological T stages, N-stage and TNM stages ( p  < 0.05). ROC curve analysis of IIBs showed the AUC of PIV was greater than other markers when combined with CEA or carbohydrate antigen 19-9 (CA19-9). Multivariate regression analysis identified T stage, CEA, Alb, and tumor size as the independent influential factors of PIV in CRC., Conclusion: PIV is associated with the tumor stage in patients with CRC, which may be useful in preoperative assessment of CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Zhao, Chen, Zhang, Cheng, Lu, Wang, Li, You, Yu, Guo, Li and Huang.)

With the medical model shifting from a single biomedical model to a biopsychological-social model, the impact of psychosocial factors on cancer patients has attracted attention. Studies have shown that chronic stress caused by long-term psychological stress, such as anxiety and depression, can promote the malignant progression of tumors by acting on β2-adrenergic receptor (β2-AR). β2-AR can promote tumor migration by activating epithelial-mesenchymal transition (EMT). However, the underlying mechanisms in the regulation of EMT by β2-AR are still unclear. In this study, we established a chronic stress model by treating MGC-803 and SGC-7901 human gastric cancer cells with isoproterenol (ISO), a β2-AR agonist. EMT in the two gastric cancer cell lines was enhanced after ISO treatment. Thereafter, we found that the interaction between β2-AR and PlexinA1 was involved in the process by which chronic stress affects EMT in both MGC-803 and SGC-7901 cells. Moreover, the activation of β2-AR by ISO increased the expression of PlexinA1, activated JAK-STAT3 signaling and further promoted EMT in human gastric cancer cells. Importantly, the knockdown of PlexinA1 by small hairpin RNAs inhibited JAK-STAT3 signaling and abolished the EMT induced by β2-AR. In conclusion, PlexinA1 was an important downstream target of β2-AR, through which β2-AR promoted EMT in human gastric cancer cells by activating JAK-STAT3 signaling., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aim: To study the relationship between quantitative structure and pharmacokinetics (QSPkR) of fluoroquinolone antibacterials., Methods: The pharmacokinetic (PK) parameters of oral fluoroquinolones were collected from the literature. These pharmacokinetic data were averaged, 19 compounds were used as the training set, and 3 served as the test set. Genetic function approximation (GFA) module of Cerius(2) software was used in QSPkR analysis., Results: A small volume and large polarizability and surface area of substituents at C-7 contribute to a large area under the curve (AUC) for fluoroquinolones. Large polarizability and small volume of substituents at N-1 contribute to a long half life elimination., Conclusion: QSPkR models can contribute to some fluoroquinolones antibacterials with excellent pharmacokinetic properties.