"Spark" PtMnIr Nanozymes for Electrodynamic-Boosted Multienzymatic Tumor Immunotherapy.

Multienzyme-mimicking redox nanozymes capable of efficient reactive oxygen species (ROS) generation and cellular homeostasis disruption are highly pursued for cancer therapy. However, it still faces challenges from the complicate tumor microenvironment (TME) and high chance for tumor metastasis. Herein, well-dispersed PtMnIr nanozymes are designed with multiple enzymatic activities, including catalase (CAT), oxidase (OXD), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx), which continuously produce ROS and deplete glutathione (GSH) concurrently in an "inner catalytic loop" way. With the help of electrodynamic stimulus, highly active "spark" species (Ir3+ and Mn3+) are significantly increased, resulting in an effective cascade enzymatic and electrodynamic therapy. Moreover, the cyclic generation of ROS can also facilitate ferroptosis and apoptosis in tumor cells, boosting synergistic therapy. Importantly, lung metastasis inhibition is found, which confirms efficient immunotherapy by the combined effect of immunogenic cell death (ICD) and Mn2+-induced cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway, contributing great potential in the treatment of malignant tumors.

Preparation of carboxymethyl cellulose nanofibers and their application in warp size of textile.

How to develop the warp sizing process with energy saving and emission reduction have been a problem for the textile sizing industry. In this work, a series of carboxymethyl cellulose nanofibers (CCNFs) with different degree of substitution (DS) were prepared from bleached eucalyptus kraft pulp, and their applications in warp size of textile were investigated in detail. AFM and TEM analyses confirmed that the prepared CCNFs were of nanoscale fibers. Zeta potential analysis showed that CCNFs aqueous dispersion had good stability. Response surface methodology was applied to optimize the high-count cotton warp sizing formula containing a small amount of CCNFs. It could be found that the optimized sizing formula still had much better sizing performance than that of the original sizing formula even if the sizing percentage and temperature were reduced. The results exhibited that CCNFs with DS of 0.38 had a potential industry application prospect as sizing auxiliary in pure cotton warp sizing, and the new developed sizing formula had the advantages of excellent sizing performance, environmental friendliness, energy saving and emission reduction.

Phenotypic changes of interstitial cells of Cajal after intestinal obstruction in rat model.

The objective was to study the effect of mechanical intestinal obstruction in rats on the phenotype of interstitial cells of Cajal (ICC). Healthy Wistar rats were randomly divided into sham-operation group (C), one day obstruction group (M1), two days obstruction group (M2), and three days obstruction group (M3), with 10 rats in each group. The expression of SCF mRNA and c-Kit protein in intestinal tissue was investigated by RT-PCR and immunohistochemistry. Compared with the sham-operation group, the relative expression of SCF mRNA and the expression of c-Kit protein in intestinal tissue were significantly decreased in both obstruction groups. Levels decreased gradually with the prolongation of obstruction time, and significantly decreased on the 3rd day after obstruction (P<0.05). Immunohistochemical staining of the small intestine showed that the number of ICC in the sham-operation group was the highest, and they were gradually decreased with the extension of obstruction time in the M1 to M3 groups. There was a significant difference between groups (P<0.05). Intestinal obstruction caused a decrease in the concentrations of SCF mRNA and c-Kit protein in ICC. With the prolongation of intestinal obstruction, the number of ICCs gradually decreased.

Phenotypic changes of interstitial cells of Cajal after intestinal obstruction in rat model

The objective was to study the effect of mechanical intestinal obstruction in rats on the phenotype of interstitial cells of Cajal (ICC). Healthy Wistar rats were randomly divided into sham-operation group (C), one day obstruction group (M1), two days obstruction group (M2), and three days obstruction group (M3), with 10 rats in each group. The expression of SCF mRNA and c-Kit protein in intestinal tissue was investigated by RT-PCR and immunohistochemistry. Compared with the sham-operation group, the relative expression of SCF mRNA and the expression of c-Kit protein in intestinal tissue were significantly decreased in both obstruction groups. Levels decreased gradually with the prolongation of obstruction time, and significantly decreased on the 3rd day after obstruction (P<0.05). Immunohistochemical staining of the small intestine showed that the number of ICC in the sham-operation group was the highest, and they were gradually decreased with the extension of obstruction time in the M1 to M3 groups. There was a significant difference between groups (P<0.05). Intestinal obstruction caused a decrease in the concentrations of SCF mRNA and c-Kit protein in ICC. With the prolongation of intestinal obstruction, the number of ICCs gradually decreased.

Application of transanal ileus tube in acute obstructive left-sided colorectal cancer.

OBJECTIVE: The efficacy of transanal ileus tube in acute obstructive left-sided colorectal cancer was discussed. METHOD: A total of 101 cases of acute obstructive left-sided colorectal cancer were divided into two treatment groups. For the experimental group consisting of 52 cases, decompression was performed using transanal ileus tube along with drainage and flushing as preparations for one-stage resection and anastomosis. For the control group consisting of 49 cases, the traditional preoperative preparation including fasting and water deprivation, gastrointestinal (GI) decompression, enema and nutritional therapy was performed. RESULTS: After the ileus tube was indwelled for 3 days, the abdominal circumference, GI decompression amount, and maximum transverse diameter of colon proximal to obstruction changed significantly in the experimental group. The response rate within 24 h and the operation rate of one-stage resection and anastomosis were higher. The incidence and mortality rate after surgery were reduced, the hospitalization time was shorter, and less expenditures were incurred. CONCLUSION: Decompression using transanal ileus tube along with drainage and flushing as preparations for one-stage resection and anastomosis is a safe and effective method for treating acute obstructive left-sided colorectal cancer.

Tubeimoside-1 (TBMS1) inhibits lung cancer cell growth and induces cells apoptosis through activation of MAPK-JNK pathway.

Tubeimoside-1 (TBMS1) is a natural compound isolated from tubeimoside, which has anti-tumor properties in some cancer cells, but its mechanisms are unclear. In the present study, we determined if TBMS1 would inhibit cell growth of human lung cancer cell lines. We found that TBMS1 inhibited growth in A549 and PC9 human lung cancer cell. Flow cytometry revealed TBMS1 arrested the cells in the G2/M phase and induced cell apoptosis. Furthermore, results from Western blotting and real-time PCR indicated that decreased the cell proliferation and cell growth-associated protein levels, such as p21, p15 and cyclin B1, TBMS1 up-regulated proapoptotic bax and cleavage of procaspase-3, down-regulated antiapoptotic Mcl-1 and cIAP-1, but did not change expression of PARP and procaspase-8. And TBMS1 also found to increase the phosphorylation, of JNK and p38, suggesting TBMS1 could activate the MAPK-JNK signaling pathway. Luciferase reporter assay revealed that TBMS1 reduced the promoter activity of AP-1, NF-κB and TNFα. In addition, TBMS1 caused the production of reactive oxygen species (ROS). These results provide evidence that TBMS1 may have potential as a novel anti-cancer agent for the treatment of lung cancer. TBMS1 inhibited cell proliferation may through MAPK-JNK signaling pathway.

Phasic study of intestinal homeostasis disruption in experimental intestinal obstruction.

AIM: To investigate the phasic alteration of intestinal homeostasis in an experimental model of intestinal obstruction. METHODS: A rabbit model of intestinal obstruction was established by transforming parts of an infusion set into an in vivo pulled-type locking clamp and creating a uniform controllable loop obstruction in the mesenteric non-avascular zone 8 cm from the distal end of the ileum. The phasic alteration of intestinal homeostasis was studied after intestinal obstruction. The changes in goblet cells, intraepithelial lymphocytes, lamina propria lymphocytes, and intestinal epithelium were quantified from periodic acid-Schiff-stained sections. Ornithine decarboxylase (ODC) activity and serum citrulline levels were measured by high-performance liquid chromatography. Claudin 1 mRNA expression was examined by real-time polymerase chain reaction analysis. Intestinal microorganisms, wet/dry weight ratios, pH values, and endotoxin levels were determined at multiple points after intestinal obstruction. Furthermore, the number and ratio of CD3(+), CD4(+) and CD8(+) T cells were determined by flow cytometry, and secretory IgA levels were measured with an enzyme-linked immunosorbent assay. RESULTS: A suitable controllable rabbit model of intestinal obstruction was established. Intestinal obstruction induced goblet cell damage and reduced cell number. Further indicators of epithelial cell damage were observed as reduced serum citrulline levels and claudin 1 gene expression, and a transient increase in ODC activity. In addition, the wet/dry weight ratio and pH of the intestinal lumen were also dramatically altered. The ratio of Bacillus bifidus and enterobacteria was reversed following intestinal obstruction. The number and area of Peyer's patches first increased then sharply decreased after the intestinal obstruction, along with an alteration in the ratio of CD4/CD8(+) T cells, driven by an increase in CD3(+) and CD8(+) T cells and a decrease in CD4(+) T cells. The number of lamina propria lymphocytes also gradually decreased with prolonged obstruction. CONCLUSION: Intestinal obstruction can induce disruption of intestinal homeostasis.

Si-jun-zi decoction treatment promotes the restoration of intestinal function after obstruction by regulating intestinal homeostasis.

Intestinal obstruction is a common disease requiring abdominal surgery with significant morbidity and mortality. Currently, an effective medical treatment for obstruction, other than surgical resection or decompression, does not exist. Si-Jun-Zi Decoction is a famous Chinese medicine used to replenish qi and invigorate the functions of the spleen. Modern pharmacological studies show that this prescription can improve gastrointestinal function and strengthen immune function. In this study, we investigated the effects of a famous Chinese herbal formula, Si-Jun-Zi Decoction, on the restoration of intestinal function after the relief of obstruction in a rabbit model. We found that Si-Jun-Zi Decoction could reduce intestinal mucosal injury while promoting the recovery of the small intestine. Further, Si-Jun-Zi Decoction could regulate the intestinal immune system. Our results suggest that Si-Jun-Zi Decoction promotes the restoration of intestinal function after obstruction by regulating intestinal homeostasis. Our observations indicate that Si-Jun-Zi Decoction is potentially a therapeutic drug for intestinal obstruction.

Upregulation of human telomerase reverse transcriptase mRNA expression by in vitro transfection of hepatitis B virus X gene into human hepatocarcinoma and cholangiocarcinoma cells.

AIM: To study the changes of human telomerase reverse transcriptase (hTERT) mRNA expression in human hepatocarcinoma cell lines (HepG2) and cholangiocarcinoma cell lines (QBC939) after HBx gene transfection and to illustrate the significance of transcriptional regulation of hTERT gene by HBx gene in the carcinogenesis. METHODS: HepG2 and QBC939 cell lines were cultured and co-transfected with eukaryotic expression vector containing the HBx coding region and cloning vector containing enhanced green fluorescent protein (EGFP) coding sequence using lipid-mediated gene transduction technique. Thirty-six hours after transfection, EGFP expression in cells was used as the indicator of successful transfection. Flow cytometry was performed to determine the transfection efficiency. Cells were harvested and total RNA was extracted using TRIzol reagent. The expression of hTERT mRNA in HepG2 and QBC939 cell lines was assayed by reverse transcription-polymerase chain reaction. The expression of HBx protein in both cell lines was detected by immunocytochemical staining and Western blotting. RESULTS: Flow cytometry showed that the transfection efficiency was 46.4% in HepG2 cells and 29.6% in QBC939 cells for both HBx gene expression vector and blank vector. The expression of hTERT mRNA was meaningfully increased in HepG2 and QBC939 cell lines when transfected with HBx gene expression vector compared to those transfected with OPTI-MEM medium and blank vector. Immunocytochemical staining and Western blotting revealed HBx protein expression in HepG2 and QBC939 cells only when transfected with HBx gene. CONCLUSION: HBx gene transfection can upregulate the transcriptional expression of hTERT mRNA. The transactivation of hTERT gene by HBx gene is a newfound mechanism for pathogenesis of hepatocarcinomas and cholangiocarcinomas after HBV infection.

[Changes in pro-inflammatory cytokines and media and peptide hormones during multiple organ dysfunction syndrome following acute abdominal diseases].

OBJECTIVE: To inquire into effects of cytokines and other inflammatory media, and peptide hormones during multiple organ dysfunction syndrome (MODS) subsequent to acute abdominal diseases. METHODS: In 19 patients with MODS due to acute abdominal diseases, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), thromboxane B(2) (TXB(2)), 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), endotoxin, gene-related peptide(CGRP), endothelin-1 (ET-1) and substance P (SP) in plasma, and lipid peroxide (LPO) and nitric oxide (NO) in serum were determined dynamically. RESULTS: Both TNF-alpha and IL-6 at increased significantly in MODS patients; IL-6 on day 0 in patients without treatment of endoscopic retrograde bile duct drainage (ERBD) were higher than that in patients with correspondent treatment, IL-6 in severe acute cholangitis patients was higher than that in patients with acute necrotic pancreatitis, it approached 24,000 ng/L during toxic shock. TNF-alpha and IL-6 during early stage of MODS were higher than that during systemic inflammatory response syndrome (SIRS) respectively. Endotoxin and LPO levels in MODS patients increased significantly. The levels of NO in emergency patients with MODS was elevated, but lowered in patients with acute necrotic pancreatitis, hepatocarcinoma, advanced age's patients with long time fever due to hepatic abscess. TXB(2) and 6-keto-PGF(1alpha) during early stage rose significantly, both decreased after treatment. ET-1 and CGRP during early stage increased significantly, SP peaked on day 0. CONCLUSION: The level of IL-6 persistently higher than 300 ng/L suggests the diagnosis of MODS. The levels of IL-6 and TNF-alpha could be taken as an indication of the degree of SIRS. NO maybe either increased or decreased, ET-1, CGRP, TXB(2), 6-keto-PGF(1alpha), endotoxin, and LPO are found to be increased MODS.