Advances on the treatment of Fusobacterium nucleatum-promoted colorectal cancers using nanomaterials / 生物工程学报

Fusobacterium nucleatum (Fn) is an oral anaerobic bacterium that has recently been found to colonize on the surface of colorectal cancer cells in humans, and its degree of enrichment is highly negatively correlated with the prognosis of tumor treatment. Numerous studies have shown that Fn is involved in the occurrence and development of colorectal cancer (CRC), and Fn interacts with multiple components in the tumor microenvironment to increase tumor resistance. In recent years, researchers have begun using nanomedicine to inhibit Fn's proliferation at the tumor site or directly target Fn to treat CRC. This review summarizes the mechanism of Fn in promoting CRC and the latest research progress on Fn-related CRC therapy using different nanomaterials. Finally, the applications perspective of nanomaterials in Fn-promoted CRC therapy was prospected.

Association between air pollutants and digestive system cancers: a systematic review / 公共卫生与预防医学

Objective To understand the relationship between air pollutants and digestive system cancers, and to provide a reference for future research and prevention and control of digestive system cancer. Methods All relevant literature published in English between 1970-2022 was searched through the databases of PubMed, web of science and Embase, and meta-analysis was used to explore the effects of specific air pollutants on digestive system cancers. Results PM2.5 was able to increase the risk of incidence or mortality of total digestive cancers by 11% (1.05 to 1.17). For specific cancers, PM2.5 was only associated with an increased risk of liver cancer in this study, with a combined RR (95% CI) of 1.31 (1.19 to 1.46), while there was no statistically significant association with other specific digestive cancers ( P>0.05）. NO2 increased the risk of incidence or mortality of total digestive cancers by 3% (1.00 to 1.07). Conclusion For specific digestive system cancers, PM2.5 has the most pronounced effect on liver cancer. More evidence is needed to support the relationship between NO2 and cancer. Currently, it has been observed that NO2 has a negative effect on overall digestive cancers. This study provides insights for the prevention and control of digestive system cancer in countries and regions with high PM2.5 and NO2 concentrations.

Selectively enhancing radiosensitivity of cancer cells

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity. For the first time, we used the

Research progress of RRx-001 as a sensitizer for radiotherapy / 天津医药

Radiotherapy is one of the most important methods to treat malignant tumors. Due to the presence of radiation resistance, the effect of radiotherapy is not entirely satisfactory. To alleviate radiation resistance and improve the radiotherapy effect, radiosensitizers have emerged. As a newly discovered radiosensitizer, RRx-001 has a good clinical application prospect. This paper reviewed the research progress of RRx-001 in source, safety, radiotherapy sensitizing activity and related mechanisms.

Synthesis of acid-sensitive doxorubicin prodrug nanoparticle and its application in brain glioma treatment / 天津医药

Objective To synthesize a new kind of acid-sensitive doxorubicin prodrug nanoparticles and to evaluate its anti-brain glioma effect and efficiency through blood-brain barrier (BBB). Methods The prodrug acid-sensitive poly-ethylene glycol (PEG)-doxorubicin (PEG-DOX) copolymer was synthesized by Schiff base reaction, and PEG-DOX pro-drug nanoparticles (PEG-DOX NPs) were prepared by self-assembling. The character of PEG-DOX copolymer was detected by dynamic light scattering (DLS) instrument and 1H NMR. The morphology of PEG-DOX NPs was observed by transmission electron microscopy (TEM). The character of drug release was detected by UV mothed. The cellular uptake efficiency of glio-ma cells to PEG-DOX NPs was observed by inverted fluorescence microscope. The anti-brain glioma effects of PEG-DOX NPs and Free DOX were studied by MTT mothed. PS80-PEG-DOX NPs were gained by the modification of PEG-DOX NPs with Tween 80. Nine BALB/c mice were separated into Free DOX, PEG-DOX NPs and PS80-PEG-DOX NPs groups by ran-dom drawing lots. The mean fluorescence intensity of brain and main organs were observed by in vivo imaging system. Re-sults The copolymer of PEG-DOX can self-assemble into nanoparticles with the diameter of 100 nm. PEG-DOX NPs can quickly release DOX in acid environment. Although PEG-DOX NPs had slow cancer cell uptake than Free DOX, it had lon-ger accumulation. MTT results showed that PEG-DOX NPs had concentration dependent anti-brain glioma effect. Indepen-dent samples t-test indicated that the efficiency through BBB was significantly higher in PS80-PEG-DOX NPs group than that of Free DOX group and PEG-DOX NPs group. Conclusion PEG-DOX NPs show well anti-brain glioma effect in vi-tro, and can across BBB with high efficiency after modification, which make it possible for a potential therapeutic prodrug for brain glioma.

Synthesis and biocompatibility of ethynylated open ring derivatives of polyasparamide / 中国生化药物杂志

Objective To synthesize a new ethynylated open ring derivatives of polyasparamide as functional drug carrier.Methods L-phenylalanine methyl ester hydrochloride was prepared using L-phenylalanine and then was used for ring opening reaction of polysuccinimide.To synthesize the target product of PSI-Phe-OMe-PA, the obtained polyasparamide-g-phenylalanine derivatives ( PSI-Phe-OMe) was further ring opened by propargylamine.The structure of PSI-Phe-OMe-PA was confirmed by 1 H NMR.The biocompatibility of PSI-Phe-OMe-PA was evaluated by MTT method, inverted microscope observation and cell cycles analysis ( propidium iodide staining ) .Results The ring-opening rate of polyasparamide by L-phenylalanine methyl ester and propargylamine was 40%and 100%, respectively.All results of biocompatibility studies indicated that PSI-Phe-OMe-PA may be a good candidate for functional drug carrier.Conclusion Based on the ring-opening capability of amino-group and the specificity of click reaction, L-phenylalanine methyl ester hydrochloride and propargylamine were used successively to react with polyasparamide.PSI-Phe-OMe-PA is a biocompatible functional drug carrier.

Synthesis of poly asparagine derivatives and its cytotoxicity study / 天津医药

Objective To synthesize poly asparagine derivatives and to evaluate its safety at the cellular level, which provide research platform for its potential application as drug carrier. Methods Polysuccinimide was synthesized by ther?mal polymerization of L-polyaspartic acid, and the target product of PSI-Phe-EA was obtained by the ring-opening reaction of polysuccinimide using L-phenylalanine methyl ester hydrochloride and ethanol amine. The structure of PSI-Phe-EA were characterized by 1H NMR. The rate of ring-opening of PSI was calculated by internal standard method of 1H NMR. The change of hydrophilicity was studied by the comparison of solubility. The cytotoxicity and morphology modification by PSI-Phe-EA at designate concentrations was investigated by MTT method and inverted microscopy respectively. The effects on cell cycles were analyzed by flow cytometry after propidium iodide (PI) staining. Results 1H NMR results confirmed the structure of PSI-Phe-EA and the ring-openning rate of PSI was 40%. The hydrophilicity of PSI-Phe-EA was greatly in?creased upon ring opening using ethanol amine. MTT test showed that the cell survival rates of NIH 3T3 and HepG2 cells were higher than 80%under the examined concentration (<100 mg/L). Inverted microscopy showed that 50 mg/L of PSI-Phe-EA treatment had no adverse effects on cell morphology. Cell cycle analysis indicated that PSI-Phe-EA treatment had no in?fluence on cell cycles of NIH 3T3 and HepG2 cell lines. Conclusion PSI-Phe-EA showed high hydrophilicity without sig?nificant effects on the cells survival, cells morphology and cell cycles. It is a kind of safe polymer material.

Application of multimodal imaging in stem cell research / 中华核医学与分子影像杂志

In recent years,stem cell research has been developing quickly in biological science.As the key of regenerative medicine,stem cell therapy becomes another innovative treatment following drug therapy and surgery.In vivo stem cell tracking,including optical imaging,radionuclide imaging and MRI,can trace the viability,distribution and function of engrafted cells.Multimodal imaging integrates two or more types of imaging techniques to obtain the combined advantages of each technology,and therefore is able to accurately and effectively trace stem cell in vivo,hopefully promoting its clinical transformation.This paper reviews the application of multimodal imaging in stem cell research.

The Effect of Amino Acid Configuration on the Biodistribution of Peptide Nanofiber / 天津医药

Objective To compare the biodistribution difference of peptide nanofibers, which were self-assembled by peptide composed of L-or D-amino acids, respectively, and provide the guidance for the in vivo applications of peptide nanofibers. Methods The Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide, F and Y were D-configura-tion) were synthesized with solid phase peptide synthesis (SPPS). The structure of the two peptides was identified by nuclear magnetic resonance spectroscopy (1H NMR) and high-resolution mass spectrometry (HR-MS). The two peptides could self-assemble into nanofibers during the cooling process after being boiled. The morphology of the nanofibers was observed with transmission electron microscope (TEM). The peptides were radiolabeled with iodine-125 and self-assembled into nanofi-bers, which were then administered into BALB/c mice via tail vein. The blood samples were collected and then mice were sacrificed at 1, 3, 6 and 12 hours. The main organs (heart, liver, spleen, lung, kidney, stomach, large intestine, small intes-tine, muscle and brain) were isolated and weighed. The radioactivity of organs was detected with a gamma counter. Results The two peptides could self-assemble into nanofibers with diameter of 10-20 nanometers. There were no significant differ-ences in the diameter and morphology between two naofibers. There was significant difference in the biodistribution between two nanofibers. The blood concentration of D-fiber was (8.17±0.32)%ID/g at one hour after injection and then cleared rapid-ly from the blood. The blood concentration of L-fiber was (5.96±0.30)%ID/g at one hour after injection and maintained at a stable level for six hours. The L-fiber was mainly distributed in stomach while the D-fiber was mainly accumulated in liver. Conclusion The configuration of amino acids (D/L) could affect the biodistribution of peptide nanofibers dramatically, which may provide the guidance for the medical applications of peptide nanofibers.

Isolation and Sequencing the Differential Gene Fragments Expressed in Human Stomach Cancer Tissue / 中国肿瘤生物治疗杂志

Objective: Identification of the genes specially expressed in tumor cell but not in normal cell is important for understanding the molecular mechanisms of carcinogencsis. This study will focus on identification of differentially expressed gene fragments in human stomach cancer. Methods: By using the new developing mRNA differential display (DD) technique, genes fragments differentially expressed in stomach cancer tissues from a patient and the adjacent normal tissues beyond the tumor mass were studied. Results: Two differentially displayed complementary DNA fragments from stomach cancer tissues, scgl and scg2 (stomach cancer-associated gene, scg), cofirmed by Northern Blot, were cloned and sequenced. The nucleotide length of scgl is 194 base pairs and that of scg2 is 343 base pairs. After searching against GenBank databases by BLASTN, neither scgl nor scg2 had significant homological gene sequences with the known genes. Conclusion: These results suggested scgl and scg2 might be complementary DNA fragments of novel genes expressed in stomach cancer tissues, but not in normal tissues and may play a role in the occurrence and development of stomach cancer. Further characterization of full-length of these two complementary DNA fragments will be continued.