Multimodal imaging and photothermal/chemodynamic therapy of cervical cancer using GSH-responsive MoS2@MnO2 theranostic nanoparticles.

The development of nanoparticles capable of inducing reactive oxygen species (ROS) formation has become an important strategy for cancer therapy. Simultaneously, the preparation of multifunctional nanoparticles that respond to the tumor microenvironment is crucial for the diagnosis and treatment of tumors. In this study, we designed a Molybdenum disulfide (MoS2) core coated with Manganese dioxide (MnO2), which possessed a good photothermal effect and could produce Fenton-like Mn2+ in response to highly expressed glutathione (GSH) in the tumor microenvironment, thereby generating a chemodynamic therapy (CDT). The nanoparticles were further modified with Methoxypoly(Ethylene Glycol) 2000 (mPEG-NH2) to improve their biocompatibility, resulting in the formation of MoS2@MnO2-PEG. These nanoparticles were shown to possess significant Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging capabilities, making them useful in tumor diagnosis. In vitro and in vivo experiments demonstrated the antitumor ability of MoS2@MnO2-PEG, with a significant killing effect on tumor cells under combined treatment. These nanoparticles hold great potential for CDT/photothermal therapy (PTT) combined antitumor therapy and could be further explored in biomedical research.

Microbiota-derived short-chain fatty acids and modulation of host-derived peptides formation: Focused on host defense peptides.

The byproducts of bacterial fermentation known as short-chain fatty acids (SCFAs) are chemically comprised of a carboxylic acid component and a short hydrocarbon chain. Recent investigations have demonstrated that SCFAs can affect intestinal immunity by inducing endogenous host defense peptides (HDPs) and their beneficial effects on barrier integrity, gut health, energy supply, and inflammation. HDPs, which include defensins, cathelicidins, and C-type lectins, perform a significant function in innate immunity in gastrointestinal mucosal membranes. SCFAs have been demonstrated to stimulate HDP synthesis by intestinal epithelial cells via interactions with G protein-coupled receptor 43 (GPR43), activation of the Jun N-terminal kinase (JNK) and Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, and the cell growth pathways. Furthermore, SCFA butyrate has been demonstrated to enhance the number of HDPs released from macrophages. SCFAs promote monocyte-to-macrophage development and stimulate HDP synthesis in macrophages by inhibiting histone deacetylase (HDAC). Understanding the etiology of many common disorders might be facilitated by studies into the function of microbial metabolites, such as SCFAs, in the molecular regulatory processes of immune responses (e.g., HDP production). This review will focus on the current knowledge of the role and mechanism of microbiota-derived SCFAs in influencing the synthesis of host-derived peptides, particularly HDPs.

Exploring the Interplay between Metabolism and Tumor Microenvironment Based on Four Major Metabolism Pathways in Colon Adenocarcinoma.

Tumor metabolism plays a critical role in tumor progression. However, the interaction between metabolism and tumor microenvironment (TME) has not been comprehensively revealed in colon adenocarcinoma (COAD). We used unsupervised consensus clustering to establish three molecular subtypes (clusters) based on the enrichment score of four major metabolism pathways in TCGA-COAD dataset. GSE17536 was used as a validation dataset. Single-cell RNA sequencing data (GSE161277) was employed to further verify the reliability of subtyping and characterize the correlation between metabolism and TME. Three clusters were identified and they performed distinct prognosis and molecular features. Clust3 had the worst overall survival and the highest enrichment score of glycolysis. 86 differentially expressed genes (DEGs) were identified, in which 11 DEGs were associated with favorable prognosis and 75 DEGs were associated with poor prognosis. Striking correlations were observed between hypoxia and glycolysis, clust3 and hypoxia, and clust3 and angiogenesis (P < 0.001).We constructed a molecular subtyping system which was effective and reliable for predicting COAD prognosis. The 86 identified key DEGs may be greatly involved in COAD progression, and they provide new perspectives and directions for further understanding the mechanism of metabolism in promoting aggressive phenotype by interacting with TME.

[Effects of benzo[a]pyrene subacute administrate on the cardiovascular of male Wistar rats].

OBJECTIVE: To explore subacute toxic effects of benzo[a]pyrene on the cardiovascular system of male Wistar rats. METHODS: Forty SPF grade male Wistar rats were randomly divided into blank control group, solvent control group, low, medium and high dose group(B[a]P concentrations were 1. 0, 2. 5 and 6. 25 mg/kg, respectively), eight in each group. The solvent group was given the same amount of olive oil and the blank group was not treated at all for 28 consecutive days. After the end of the exposure, the left ventricular structural function and hemodynamic changes were observed with Prospect 3. 0 small animal ultrasound imager and BL-410 biological function test system. Pathological changes of rat thoracic aorta and left ventricle were observed by HE staining. RESULTS: The total difference in ejection fraction(EF), fractional shortening(FS) and left ventricular end diastolic pressure(LVEDP) between the groups was statistically significant(H=11. 497, P=0. 022; H=11. 422, P=0. 022; H=10. 104, P=0. 039). The EF and FS of the middle dose group were lower than the solvent group(adjusted P<0. 05), the LVEDP of the high dose group was higher than that of the solvent group(adjusted P<0. 05). The HE staining of thoracic aorta in the medium and high dose groups showed the loss of endothelial cells, the shedding of some endothelial cells, the exposure of subintimal collagen, the large gap of the middle layer. In the medium and high dose group, left ventricular transverse striations were blurred, muscle fibers reduced or disappeared, the myocardial space widened, inflammatory cells or the myocardial interspace bleeding phenomenon was occasionally observed. CONCLUSION: Benzo[a]pyrene can cause cardiovascular and endothelial damage in male Wistar rats.

Modulation of Myb-induced NF-kB -STAT3 signaling and resulting cisplatin resistance in ovarian cancer by dietary factors.

c-Myb regulates tumorigenesis in multiple cancers. Here we show, for the first time, the mechanism of c-Myb-mediated proliferation, invasion, and drug resistance in ovarian cancer (OC), the most lethal gynecological cancer, and a comparative analyses of dietary agents, curcumin, epigallocatechin-3-gallate (EGCG), and sulforaphane in inhibiting c-Myb activity. We evaluated myb expression in patients with OC and found its increased expression in patients with cancer, compared with normal controls and in higher grade tumors, compared with low-grade tumors. Using ES2 and OVCAR3 cell line models, along with the silencing or overexpression of c-Myb, we establish a role of c-Myb in determining resistance to cisplatin. c-Myb overexpression activated NF-κB and STAT3 signaling leading to enhanced proliferation, invasion, and cisplatin resistance. Contrary to this, silencing of c-Myb inhibited proliferation, invasion, and sensitized OC cells to cisplatin. Further, among the dietary agents tested, EGCG almost completely inhibited the c-Myb-induced proliferation and invasion whereas sulforaphane also had significant inhibitory effect. Both compounds significantly sensitized OC cells to cisplatin, reversing the c-Myb effects. Higher c-Myb levels in patients with ovarian cancer lead to poor survival and our results indicate a possible effect of dietary factors EGCG and sulforaphane against c-Myb-mediated ovarian cancer progression and chemoresistance.

Regulation Mechanism of Long Noncoding RNAs in Colon Cancer Development and Progression.

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and its high rates of relapse and metastasis are associated with a poor prognosis. Despite extensive research, the underlying regulatory mechanisms of CRC remain unclear. Long noncoding RNAs (lncRNAs) are a major type of noncoding RNAs that have received increasing attention in the past few years, and studies have shown that they play a role in many biological processes in CRC. Here, we summarize recent studies on lncRNAs associated with CRC and the signaling pathways and mechanisms underlying this association. We show that dysregulated lncRNAs may be new prognostic and diagnostic biomarkers or therapeutic targets for clinical application. This review contributes not only to our understanding of CRC, but also suggests novel signaling pathways associated with lncRNAs that can be targeted to block or eradicate CRC.

[Diagnosis and treatment of intra-abdominal infection complicated with hypothyroidism].

Intra-abdominal infection complicated with hypothyroidism is very common. It mostly featured decreased T3, with or without decreased T4, and without elevated thyroid stimulating hormone(TSH). This particular type of hypothyroidism was called "low T3 syndrome" or "thyroid illness syndrome", and is called "non-thyroid illness syndrome" increasingly in recent years. Its pathogenesis has not been fully understood, and probably is associated with abnormality of hypothalamic-pituitary-thyroid axis, disorder of peripheral thyroid hormone metabolism, change in thyroid hormone binding protein, regulation of triiodothyronine receptors, effect of cytokines, and lack of trace element selenium. Intra-abdominal infection complicated with hypothyroidism should be differentiated from primary hypothyroidism, which may be one cause of mental depression, insufficient anabolism, and poor tissue healing. Therefore, the changes of T3 and T4 levels should be actively monitored in patients with severe or prolonged intra-abdominal infection. Whether treatment is needed for intra-abdominal infection complicated with hypothyroidism remains controversial. T3 replacement therapy may improve prognosis. When low T3 syndrome presents as a disease-mediated hypothyroidism, we recommend the use of levothyroxine(L-T4) or liothyronine (L-T3) treatment to improve the prognosis of critical patients. Enteral nutrition can improve hypothyroidism and has good efficacy for enterocutaneous fistula patients with intra-abdominal infection.

Identification and Phylogenetic Analysis of Pear Psyllids (Hemiptera: Psyllidae) in Chinese Pear Orchards.

Pear psyllids are among the most damaging pests in pear orchards, but little knowledge exists of psyllid species in cultivated pear orchards in China. In this study, DNA sequence analyses of the 16S rDNA and cytochrome oxidase I (COI) DNA regions were performed to identify pear psyllids from 28 regions of 20 provinces in China and to classify their genetic relationships to understand the origin of the species. The results showed that Cacopsylla chinensis Yang et Li (Hemiptera: Psyllidae) was found in most pear orchards in China, but Cacopsylla qianli (Hemiptera: Psyllidae) was found in only the cities of Guiyang (Guizhou province) and Xiangyang (Hubei province). The results for the 16S rDNA and COI regions were similar. Based on the nucleotide sequences and phylogenetic analyses of 16S rDNA and COI, C. chinensis could be divided into three groups: lineages I, II, and III. Based on 16S rDNA and COI, lineage II showed approximately 4% and 3% difference from lineage I, and lineage III showed approximately 12% and 9% difference from lineage I, respectively. C. chinensis lineage I was found in most provinces of China, while C. chinensis lineage II samples were mainly found in the Bohai rim region of China, and lineage III samples were found in Northeast China. The results of this study will provide information to pear producers regarding effective control measures to prevent further damage from pear psyllids.

[Clinical experience of combined laparoscopic-endoscopic Heller myotomy and modified Dor fundoplication for cardiochalasia].

OBJECTIVE: To investigate the efficacy of combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication for cardiochalasia patients. METHODS: Clinical data of 11 cardiochalasia patients who underwent combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication by the same medical team from January 2015 to December 2016 at The Second Hospital of Jilin University were retrospectively analyzed. The procedure was as follows: an incision was made in the anterior wall of esophagus and dissection of esophageal muscular layer was performed, then the bulged esophageal mucosa was covered by the fundus after 180 degrees fold to the right (fundoplication), finally the gastric fundus was joined to the right diaphragmatic foot by 3 to 5 knotted suture. The efficacy was judged by the Eckardt scoring standard: the postoperative Eckardt score ≤3 points indicated effectiveness, otherwise the treatment was invalid. RESULTS: Combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication was completed successfully in all the 11 patients without any subsequent laparotomy and death. The mean operative time was 85 (78 to 137) min, blood loss was 15 (5 to 35) ml, and no upper digestive tract perforation occurred. The mean postoperative hospital stay was 7.0(6 to 9) d. After the operation, the pressure of lower esophageal sphincter decreased significantly compared to that before operation [(5.31±6.23) mmHg vs. (35.72±17.13) mmHg, P<0.05], and the Eckardt score decreased significantly as well (0.53±0.56 vs. 6.17±1.17, P<0.05). During the follow-up of 2 to 23 months, there was no postoperative mortality. One case experienced mild gastroesophageal reflux 6 months after operation, and another patient had recurrent dysphagia 17 months after operation, who both were improved after receiving proton pump inhibitors or gastric dynamic drugs, and balloon dilation. CONCLUSION: Combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication is an effective and safe surgical procedure for cardiochalasia with minimal invasion and fast recovery.

Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer cells.

Beclin1 is an essential autophagy regulator and a haploinsufficient tumor-suppressor. Reduced Berclin1 expression has been associated with many types of human malignancies including gastric cancer. However, the mechanism of how Beclin1 represses tumorigenesis of gastric cancer remains elusive. In recent proteomics study, we found that Beclin1 is associated with Lysosome-associated transmembrane protein 4ß (LAPTM4B). LAPTM4B plays an important role in promoting the growth and proliferation of tumor cells, it is overexpressed in a variety of solid tumors and serves as a biomarker for tumor therapy. Further analysis showed that Beclin1 interacts with both the N- and C-termini of LAPTM4B and this interaction is independent of Vps34 complex. We demonstrated that Beclin1 competes with Epidermal growth factor receptor (EGFR) for LAPTM4B binding and Beclin1 can repress the LAPTM4B mediated EGFR activation and gastric cancer cell growth. Taken together, our study proposes a role of Beclin1 in repressing gastric cancer through disrupting the oncogenic promoting function of LAPTM4B.