Preliminary study to explore gene-PM2.5 interactive effects on respiratory system in traffic policemen

Objectives: Traffic-related particulate matter (PM) is one of the major sources of air pollution in metropolitan areas. This study is to observe the interactive effects of gene and fine particles (particles smaller than 2.5 μm – PM2.5) on the respiratory system and explore the mechanisms linking PM2.5 and pulmonary injury. Material and Methods: The participants include 110 traffic policemen and 101 common populations in Shanghai, China. Continuous 24 h individual-level PM2.5 is detected and the pulmonary function, high-sensitivity C-reactive protein (hs-CRP), Clara cell protein 16 (CC16) and the polymorphism in CXCL3, NME7 and C5 genes are determined. The multiple linear regression method is used to analyze the association between PM2.5 and health effects. Meanwhile, the interactive effects of gene and PM2.5 on lung function are analyzed. Results: The individual PM2.5 exposure for traffic policemen was higher than that in the common population whereas the forced expiratory volume in 1 s (FEV1), the ratio of FEV1 to forced vital capacity (FEV1/FVC) and lymphocytes are lower. In contrast, the hs-CRP level is higher. In the adjusted analysis, PM2.5 exposure was associated with the decrease in lymphocytes and the increase in hs-CRP. The allele frequencies for NME7 and C5 have significant differences between FEV1/FVC ≤ 70% and FEV1/FVC > 70% participants. The results didn’t find the interaction effects of gene and PM2.5 on FEV1/FVC in all the 3 genes. Conclusions: The results indicated that traffic exposure to high levels of PM2.5 was associated with systemic inflammatory response and respiratory injury. Traffic policemen represent a high risk group suffering from the respiratory injury

Prevention of post-surgical abdominal adhesions by a novel biodegradable thermosensitive PECE hydrogel.

<p>Abstract</p> <p>Background</p> <p>Post-operative peritoneal adhesions are common and serious complications for modern medicine. We aim to prevent post-surgical adhesions using biodegradable and thermosensitive poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel. In this work, we investigated the effect of PECE hydrogel on preventing post-surgical abdominal adhesions in mouse and rat models.</p> <p>Results</p> <p>The PECE hydrogel in sol state could be transformed into gel in less than 20 s at 37°C. In addition, the PECE hydrogel could be easily adhered to the damaged peritoneal surfaces, and be gradually degraded and absorbed by the body within 14 days along with the healing of peritoneal wounds. A notable efficacy of the PECE hydrogel in preventing peritoneal adhesions was demonstrated in the animal models. In contrast, all untreated animals developed adhesions requiring sharp dissection. Furthermore, no significant histopathological changes were observed in main organs of the hydrogel-treated animals.</p> <p>Conclusion</p> <p>Our results suggested that the thermosensitive PECE hydrogel was an effective, safe, and convenient agent on preventing post-surgical intro-abdominal adhesions.</p

A novel Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) grafted Polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study

<p>Abstract</p> <p>Background</p> <p>Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection <it>in vitro</it>. However, its <it>in vivo </it>application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.</p> <p>Results</p> <p>Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-<it>g</it>-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-<it>g</it>-PEI was characterized by ¹H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-<it>g</it>-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-<it>g</it>-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD.</p> <p>Conclusion</p> <p>The cytotoxicity and <it>in vitro </it>transfection study indicated that PCFC-<it>g</it>-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).</p

Mechanisms of action of the BCL-2 inhibitor venetoclax in multiple myeloma: a literature review

Abnormal cellular apoptosis plays a pivotal role in the pathogenesis of Multiple Myeloma (MM). Over the years, BCL-2, a crucial anti-apoptotic protein, has garnered significant attention in MM therapeutic research. Venetoclax (VTC), a small-molecule targeted agent, effectively inhibits BCL-2, promoting the programmed death of cancerous cells. While VTC has been employed to treat various hematological malignancies, its particular efficacy in MM has showcased its potential for broader clinical applications. In this review, we delve into the intricacies of how VTC modulates apoptosis in MM cells by targeting BCL-2 and the overarching influence of the BCL-2 protein family in MM apoptosis regulation. Our findings highlight the nuanced interplay between VTC, BCL-2, and MM, offering insights that may pave the way for optimizing therapeutic strategies. Through this comprehensive analysis, we aim to lay a solid groundwork for future explorations into VTC’s clinical applications and the profound effects of BCL-2 on cellular apoptosis

Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes

The divergence of archaea, bacteria and eukaryotes was a fundamental step in evolution. One marker of this event is a major difference in membrane lipid chemistry between these kingdoms. Whereas the membranes of bacteria and eukaryotes primarily consist of straight fatty acids ester-bonded to glycerol-3-phosphate, archaeal phospholipids consist of isoprenoid chains ether-bonded to glycerol-1-phosphate. Notably, the mechanisms underlying the biosynthesis of these lipids remain elusive. Here, we report the structure of the CDP-archaeol synthase (CarS) of Aeropyrum pernix (ApCarS) in the CTP- and Mg(2+)-bound state at a resolution of 2.4 Å. The enzyme comprises a transmembrane domain with five helices and cytoplasmic loops that together form a large charged cavity providing a binding site for CTP. Identification of the binding location of CTP and Mg(2+) enabled modeling of the specific lipophilic substrate-binding site, which was supported by site-directed mutagenesis, substrate-binding affinity analyses, and enzyme assays. We propose that archaeol binds within two hydrophobic membrane-embedded grooves formed by the flexible transmembrane helix 5 (TM5), together with TM1 and TM4. Collectively, structural comparisons and analyses, combined with functional studies, not only elucidated the mechanism governing the biosynthesis of phospholipids with ether-bonded isoprenoid chains by CTP transferase, but also provided insights into the evolution of this enzyme superfamily from archaea to bacteria and eukaryotes.Cell Research advance online publication 29 September 2017; doi:10.1038/cr.2017.122

Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review

Regulatory T cells (Treg), as members of CD4+ T cells, have garnered extensive attention in the research of tumor progression. Treg cells have the function of inhibiting the immune effector cells, preventing tissue damage, and suppressing inflammation. Under the stimulation of the tumor inflammatory microenvironment (IM), the reprogramming of Treg cells enhances their suppression of immune responses, ultimately promoting tumor immune escape or tumor progression. Reducing the number of Treg cells in the IM or lowering the activity of Treg cells while preventing their reprogramming, can help promote the body’s anti-tumor immune responses. This review introduces a reprogramming mechanism of Treg cells in the IM; and discusses the regulation of Treg cells on tumor progression. The control of Treg cells and the response to Treg inflammatory reprogramming in tumor immunotherapy are analyzed and countermeasures are proposed. This work will provide a foundation for downregulating the immunosuppressive role of Treg in the inflammatory environment in future tumor immunotherapy

5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice

<p>Abstract</p> <p>Background</p> <p>Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a preferable option for colorectal cancer. Here we reported that a new system, 5-FU-loaded hydrogel system, can improve the therapeutic effects of intraperitoneal chemotherapy.</p> <p>Methods</p> <p>A biodegradable PEG-PCL-PEG (PECE) triblock copolymer was successfully synthesized. The biodegradable and temperature sensitive hydrogel was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed for visible observation of the drug release. The effects and toxicity of the 5-FU-hydrogel system were evaluated in a murine CRPC model.</p> <p>Results</p> <p>The hydrogel system is an injectable flowing solution at ambient temperature and forms a non-flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently injected into abdominal cavity in mice with CT26 cancer cells peritoneal dissemination. The results showed that the hydrogel delivery system prolonged the release of methylene blue; the 5-FU-hydrogel significantly inhibited the peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal administration of the 5-FU-hydrogel was well tolerated and showed less hematologic toxicity.</p> <p>Conclusions</p> <p>Our data indicate that the 5-FU-hydrogel system can be considered as a new strategy for peritoneal carcinomatosis, and the hydrogel may provide a potential delivery system to load different chemotherapeutic drugs for peritoneal carcinomatosis of cancers.</p

Measurement report: Brown Carbon Aerosol in Polluted Urban Air of North China Plain: Day-night Differences in the Chromophores and Optical Properties

&lt;ul&gt; &lt;li&gt; &lt;p&gt;Drawing data set of Yuquan Gong et al&nbsp;article&lt;/p&gt; &lt;/li&gt; &lt;/ul&gt