The Effects of a Crosslinking Agent on the Microrheological Properties and Cellular Structure of Silicone Rubber Foam Prepared via a Green Process.

Chemical foaming technology is widely used in the preparation of silicone rubber foam and is attributable to its one-step molding capability and eco-friendly production processes. The microrheological properties of silicone rubber play a pivotal role during the foaming process. In this study, Rheolaser Lab (Formulaction, Toulouse, France) was used to conduct in situ examinations for the influence of a crosslinking agent on the microrheological properties of silicone rubber foam for the first time. This study monitors the entire reaction process of silicone rubber foam from liquid to solid, as well as the matching of crosslinking and foaming reactions. Various parameters, including solid-liquid balance, elasticity index, and macroscopic viscosity index, are measured to analyze the microrheological properties of silicone rubber foam. The results show that the silicone rubber foam exhibits good microrheological properties, thereby demonstrating excellent performance at a crosslinking agent content of 2%. Through adjusting the experimental conditions, a sustainable and efficient approach was proposed for better cellular structure control in the industrial preparation of silicone rubber foam.

OTX1 regulates tumorigenesis and metastasis in glioma.

The most prevalent kind of primary brain tumors, gliomas, have a dismal prognosis. Recent advances in the tumor-promoting ability of OTX1 have drawn increasing attention. The overexpression of OTX1 has been reported to be associated with tumor-promoting effects in several malignancies, but its expression in gliomas is unknown. The oncogene OTX1 is increased in gliomas and is linked to a poor prognosis, as we show here. The degree of OTX1 positive expression is doubtlessly concomitant with the grade of glioma. We observed that OTX1 was up-regulated in gliomas, influenced the epithelial-mesenchymal transition (EMT), encouraged glioma cell growth and proliferation, and was linked to a poor clinical outcome for patients. At present, the prognosis of glioma is still not optimistic, and further research is needed to find a new target for treatment. According to our research, OTX1 is anticipated to emerge as a novel biological target for determining glioma prognosis and treatment.

Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.

Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.

A Pixel Circuit for Compensating Electrical Characteristics Variation and OLED Degradation.

In recent years, the active-matrix organic light-emitting diode (AMOLED) displays have been greatly required. A voltage compensation pixel circuit based on an amorphous indium gallium zinc oxide thin-film transistor is presented for AMOLED displays. The circuit is composed of five transistors-two capacitors (5T2C) in combination with an OLED. In the circuit, the threshold voltages of both the transistor and the OLED are extracted simultaneously in the threshold voltage extraction stage, and the mobility-related discharge voltage is generated in the data input stage. The circuit not only can compensate the electrical characteristics variation, i.e., the threshold voltage variation and mobility variation, but also can compensate the OLED degradation. Furthermore, the circuit can prevent the OLED flicker, and can achieve the wide data voltage range. The circuit simulation results show that the OLED current error rates (CERs) are lower than 3.89% when the transistor's threshold voltage variation is ±0.5V, lower than 3.49% when the mobility variation is ±30%.

Synergistic Effects of 2-Butyne-1,4-Diol and Chloride Ions on the Microstructure and Residual Stress of Electrodeposited Nickel.

To assess the individual and synergistic effects of 2-butyne-1,4-diol (BD) and chloride ions on the microstructure and residual stress of electrodeposited nickel, various nickel layers were prepared from sulfamate baths comprising varying concentrations of BD and chloride ions by applying direct-current electrodeposition. And their surface morphologies, microstructure, and residual stress were tested using SEM, XRD, EBSD, TEM, and AFM. While the nickel layers composed of pyramid morphology were prepared from additive-free baths, the surface flattened gradually as the BD concentration of the baths was increased, and the acicular grains in the deposits were replaced with <100> oriented columnar grains or <111> oriented nanograins; additionally, the residual tensile stress of the deposits increased. The addition of chloride ions to the baths containing BD significantly increased the residual stress in the nickel layers, although it only slightly promoted surface flattening and columnar grain coarsening. The effects of BD and chloride ions on the growth mode and residual stress of nickel deposits were explained via analysis of surface morphologies and microstructure. And the results indicate that the reduction of chloride ion concentration is a feasible way to reduce the residual stress of the nickel deposits when BD is included in the baths.

N-Acetyl-l-cysteine ameliorates gestational diabetes mellitus by inhibiting oxidative stress.

Objective: Gestational diabetes mellitus (GDM) affects 7% of pregnant women worldwide. How to effectively treat GDM has always been a concern of people.Research methods: In this study, a diabetes model was established by drug-induced mice. Subsequently, the blood glucose levels and serum insulin changes of the mice after N-acetyl-l-cysteine (NAC) treatment were observed. At the same time, the effect of NAC on reproduction of GDM mice was recorded.Results of the study: Mice fed NAC showed significantly improved glucose tolerance and insulin sensitivity compared to Diabetic/Control. Total serum cholesterol, serum triglycerides, and serum low-density lipoprotein were significantly reduced, and atherosclerosis index was much lower than in control mice. In addition, Diabetic/Control mice had lower litter sizes and higher birth weights. NAC treatment significantly restored litter size and reduced birth weight in Diabetic/Control mice. It was found in WB assay that the NAC-fed group significantly increased nuclear Nrf2 and HO-1 expression levels.Conclusion: NAC can improve blood glucose tolerance in GDM mice; NAC effectively relieves the symptoms of hyperlipidemia caused by GDM; NAC enhances the expression of Nrf2/HO-1 in the liver, thereby restoring redox homeostasis. NAC can reduce gestational diabetes-related disease indicators by oral administration, and has a beneficial effect on the offspring of pregnant mice (reduces its diabetes disease indicators).

The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

Genome-wide characterization of the tomato GASA family identifies SlGASA1 as a repressor of fruit ripening.

Gibberellins (GAs) play crucial roles in a wide range of developmental processes and stress responses in plants. However, the roles of GA-responsive genes in tomato (Solanum lycopersicum) fruit development remain largely unknown. Here, we identify 17 GASA (Gibberellic Acid-Stimulated Arabidopsis) family genes in tomato. These genes encode proteins with a cleavable signal peptide at their N terminus and a conserved GASA domain at their C terminus. The expression levels of all tomato GASA family genes were responsive to exogenous GA treatment, but adding ethylene eliminated this effect. Comprehensive expression profiling of SlGASA family genes showed that SlGASA1 follows a ripening-associated expression pattern, with low expression levels during fruit ripening, suggesting it plays a negative role in regulating ripening. Overexpressing SlGASA1 using a ripening-specific promoter delayed the onset of fruit ripening, whereas SlGASA1-knockdown fruits displayed accelerated ripening. Consistent with their delayed ripening, SlGASA1-overexpressing fruits showed significantly reduced ethylene production and carotenoid contents compared to the wild type. Moreover, ripening-related genes were downregulated in SlGASA1-overexpressing fruits but upregulated in SlGASA1-knockdown fruits compared to the wild type. Yeast two-hybrid, co-immunoprecipitation, transactivation, and DNA pull-down assays indicated that SlGASA1 interacts with the key ripening regulator FRUITFULL1 and represses its activation of the ethylene biosynthesis genes ACS2 and ACO1. Our findings shed new light on the role and mode of action of a GA-responsive gene in tomato fruit ripening.

Cyclic helix B peptide ameliorated the sepsis-induced injury in human HPMEC cells through regulating NF-κB.

BACKGROUND: Sepsis is a life-threatening condition. The incidence of severe sepsis is increasing. Sepsis is often complicated with organ dysfunctions. Cyclic helix B peptide (CHBP) is a peptide derivant of erythropoietin with powerful tissue-protective efficacies. However, the role of CHBP in sepsis-induced injury remains unclear. MATERIAL AND METHODS: Lyso-phosphatidylserine (LPS) was used to induce sepsis in human pulmonary microvascular endothelial cells (HPMECs). Cell growth was detected using Cell Counting Kit-8. Cell permeability was measured using fluorescein isothiocyanate (FITC)-dextran. Cecal ligation and puncture (CLP) method was applied to induce sepsis and CHBP was provided to test its efficacy. Western blot assays were used to evaluate gene expression. RESULTS: Administration of CHBP ameliorated LPS-induced injury in HPMECs dose-dependently. Administration of CHBP decreased the permeability of LPS-treated HPMEC cells in a same way as well. Furthermore, we identified that recombinant CHBP protein (Re-CHBP) ameliorated CLP-induced injury in vivo. Finally, we found that administration of NF-κB activator, TNF-α, abolished the function of Re-CHBP in LPS-treated HPMEC cells. CONCLUSION: CHBP ameliorated sepsis-induced injury dose dependently both in vitro and in vivo through decreasing the permeability of HPMEC cells via suppressing NF-κB signaling and inflammation. Present findings highlight the importance of CHBP/NF-κB signaling in septic injury and provide new insights into therapeutic strategies for sepsis-induced injury.

Co-delivery of sorafenib and metformin from amphiphilic polypeptide-based micelles for colon cancer treatment.

Colorectal cancer (CRC) is a common clinical disease with a poor prognosis and a high recurrence rate. Chemotherapy is important to inhibit the post-surgical recurrence of CRC patients. But many limitations restrict the further application of chemotherapy. In this study, sorafenib (Sor) and metformin (Met) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) [mPEG-b-P(Glu-co-Phe)] micelles were developed. The characterizations, drug release, in vivo biodistribution, and pharmacokinetics of the micelles were analyzed. The treatment efficacy of the dual-drug loaded micelles was evaluated in a subcutaneous colon cancer mice model. Sor is a common molecular target agent that can inhibit the mitogen-activated protein kinase (MAPK) pathway to treat solid tumors. Met can also regulate the MAPK pathway and inhibit the expression of the phosphorylated extracellular signal-regulated kinase (p-ERK). Moreover, both Sor and Met play important roles in cell cycle arrest. The integration of these two drugs aims to achieve synergistic effects against colon cancer. The micelles can be targeted to cancer cells and possess longer blood circulation time. The two agents can be released rapidly in the tumor sites. The in vivo study showed that the micelles can prevent tumor progression by inhibiting the expressions of p-ERK and cyclin D1. This study indicated that the Sor/Met-loaded micelles are suitable for CRC treatment.

Fast-track surgery nursing intervention in CRC patients with laparotomy and laparoscopic surgery.

In this study, the application effect of fast-track surgery (FTS) nursing intervention in laparotomy and laparoscopic surgery for colorectal cancer (CRC) is investigated, and the optimal perioperative management strategy for CRC surgery is explored. One hundred thirty CRC patients are included in this study, in which 67 patients undergo laparotomy (Group A) and 63 patients undergo laparoscopic surgery (Group B). These patients were also randomly divided into traditional nursing subgroup (Group A1 [n = 33] and Group B1 [n = 31]) and FTS nursing subgroup (Group A2 [n = 34] and Group B2 [n = 32]). The general data of patients, pre-operative preparation, intra-operative data, postoperative recovery data, and postoperative complications are recorded. Both FTS and laparoscopic surgery can advance the anal exhaust time, and shorten postoperative fasting and water deprivation time, and the hospitalization time without increasing the incidence of complications. FTS has advantages in reducing the indwelling time of gastric tube and throat pain. Simultaneous implementation of FTS and laparoscopic surgery has the best effect on the postoperative recovery of CRC patients.

Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome.

Background and Aims: The effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms. Methods: Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and serum biochemical parameters, hepatic index and histopathological analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Immunohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs). Results: Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment. D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin (IL)-1ß, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration. Conclusions: Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

Undifferentiated high-grade pleomorphic sarcoma of the colon: a rare case report and literature review.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma (MFH), hardly originates from the colorectum. CASE PRESENTATION: We reported a 65-year-old female presented with UPS in the descending colon. Computed tomography (CT) revealed an irregularly thickened descending colon. On colonoscopy examination, an ulcerative tumour was identified. The patient received radical resection of the left colon and partial enterectomy. The resected tumor was ulcerative, 10 cm × 8 cm × 5 cm in size, and infiltrated the serosa layer. Postsurgical pathology showed that the tumor was high-graded UPS in the colon with large amounts of necrotic tissues. CONCLUSIONS: UPS in the large intestine is a rare malignant tumor with a poor prognosis and unknown pathogenesis. The main treatment for UPS is early complete resection. Postsurgery adjuvant radiotherapy or chemotherapy can be attempted.

Gut and Vaginal Microbiomes in PCOS: Implications for Women's Health.

PCOS is defined as a kind of endocrine and metabolic disorder which affects females at reproductive ages, is becoming much more common, nowadays. Microbiomes are known as microorganisms that inhabit the body to play a vital role in human health. In recent years, several basic and clinical studies have tried to investigate the correlation between the reproductive health/disorder and microbiomes (gut microbiomes and vaginal microbiomes). However, the mechanism is still unclear. In this review, we reviewed the relationship between PCOS and microbiomes, including gut/vaginal microbiomes compositions in PCOS, mechanism of microbiomes and PCOS, and then collectively focused on the recent findings on the influence of microbiomes on the novel insight regarding the therapeutic strategies for PCOS in the future clinical practice.

Association between blood glucose levels and Glasgow Outcome Score in patients with traumatic brain injury: secondary analysis of a randomized trial.

BACKGROUND: Blood glucose levels that are too high or too low after traumatic brain injury (TBI) negatively affect patient prognosis. This study aimed to demonstrate the relationship between blood glucose levels and the Glasgow Outcome Score (GOS) in TBI patients. METHODS: This study was based on a randomized, dual-center, open-label clinical trial. A total of 208 patients who participated in the randomized controlled trial were followed up for 5 years. Information on the disease, laboratory examination, insulin therapy, and surgery for patients with TBI was collected as candidate variables according to clinical importance. Additionally, data on 5-year and 6-month GOS were collected as primary and secondary outcomes, respectively. For multivariate analysis, a generalized additive model (GAM) was used to investigate relationships between blood glucose levels and GOS. The results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). We further applied a two- piecewise linear regression model to examine the threshold effect of blood glucose level and GOS. RESULTS: A total of 182 patients were included in the final analysis. Multivariate GAM analysis revealed that a bell-shaped relationship existed between average blood glucose level and 5-year GOS score or 6-month GOS score. The inflection points of the average blood glucose level were 8.81 (95% CI: 7.43-9.48) mmol/L considering 5-year GOS as the outcome and were 8.88 (95% CI 7.43-9.74) mmol/L considering 6-month GOS score as the outcome. The same analysis revealed that there was also a bell relationship between average blood glucose levels and the favorable outcome group (GOS score ≥ 4) at 5 years or 6 months. CONCLUSION: In a population of patients with traumatic brain injury, blood glucose levels were associated with the GOS. There was also a threshold effect between blood glucose levels and the GOS. A blood glucose level that is either too high or too low conveys a poor prognosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02161055 . Registered on 11 June 2014.

Gastric adenocarcinoma with germ cell tumor components: a rare case report.

Germ cell tumors (GCTs) often occur in male testes and female ovaries. Extragonadal GCTs account for approximately 2% to 5% of all GCTs and mainly occur in the mediastinum, retroperitoneum, and pineal gland. In this study, we reported a rare case of gastric adenocarcinoma with GCT components. The patient's serum α-fetoprotein (AFP) level was higher than normal. Abdominal computed tomography (CT) showed a 10-cm × 10-cm tumor between the spleen and the bottom of the stomach. Gastric endoscopy indicated an ulcerative lesion extending from the bottom of the stomach to the antrum. Tissue biopsy identified the tumor as an adenocarcinoma. The patient underwent abdominal tumor resection, subtotal gastrectomy, D2 lymphadenectomy, and splenectomy. Postoperative histopathology showed that the tumor was a moderately to poorly differentiated adenocarcinoma. Immunohistochemistry analysis revealed positive staining for AFP, glypican-3, and placental alkaline phosphatase. Gastric adenocarcinoma with GCT components is particularly uncommon and rarely reported. Elevated serum AFP and/or ß-human chorionic gonadotropin levels, abdominal CT, histopathology, and immunohistochemistry may help diagnose GCTs. Radical surgery resection is the primary treatment method for GCTs. Adjuvant chemotherapy and radiotherapy are effective for advanced GCTs.

Fatal methanol poisoning with different clinical and autopsy findings: Case report and literature review.

Methanol poisoning is responsible for high morbidity and mortality, and the elevated concentration of methanol in the body is the major criteria for forensic diagnosis of methanol poisoning. However, in cases with lower methanol concentrations, diagnosis is mainly dependent on highly variable postmortem manifestations.Herein, we report a fatal methanol poisoning cases that two subjects ingested the same amount of methanol simultaneously, yet the subject one presented only non-specific gastrointestinal and mild central nervous system symptoms, while the other subject exhibited typical toxic manifestations with the exception of visual compromise. In autopsy, subject number 1 did not show typical pathological changes caused by methanol poisoning, except for the elevated levels of methanol in body fluids. On the contrary, bilateral basal ganglia hemorrhage and necrosis caused by methanol-induced brain lesion was observed in case number 2. Due to the complex and multifactorial process of methanol intoxication, many factors, including comprehensive autopsy, quantitative detection of methanol and formic acid, and genotype analysis, participate in its metabolism and toxicity, and can impact the clinical symptoms, prognosis and postmortem manifestations. Therefore, a combination of multiple diagnosis methods may more accurately contribute to the forensic diagnosis of methanol poisoning and should be tailored on an individual basis. This case report also reviews forensic diagnosis literature on methanol poisoning to provide a reference for forensic pathologists.

Cysteine-rich intestinal protein 1 enhances the progression of hepatocellular carcinoma via Ras signaling.

The present study aimed to explore the expression and clinical significance of cysteine-rich intestinal protein 1 (CRIP1) mRNA in the serum of patients with hepatocellular carcinoma (HCC). Reverse transcription polymerase chain reaction (RT-PCR) was performed to explore the level of CRIP1 mRNA in the tissues and serum of patients with HCC. Our data showed that the mRNA level of CRIP1 was significantly elevated in the serum and tissues of HCC patients. Moreover, serum CRIP1 mRNA was significantly elevated in HCC patients with larger tumor sizes and higher tumor node metastasis (TNM) stages. Receiver operating characteristic analysis showed that compared with a single marker, the combined detection of alpha-fetoprotein, carcinoembryonic antigen, and CRIP1 had the highest accuracy, sensitivity, and specificity. Further study showed that the overexpression of CRIP1 enhanced the proliferation and migration of HepG2 cells, but the inhibition of CRIP1 decreased the proliferation and migration of HepG2 cells. Microarray assays and KyotoEncyclopedia of Genes and Genomes (KEGG) pathway analysis showed that overexpression of CRIP1 induced the activation of Ras signaling. Co-immunoprecipitation (Co-IP) assays indicated that CRIP1 could interact with Ras. To further evaluate whether CRIP1 interacts with Ras, a specific siRNA targeting Ras was selected. We found that Ras knockdown reduced the activation of Ras/AKT signaling even in HepG2 cells transfected with CRIP1. Moreover, elevated expression of CRIP1 increased the proliferation of HepG2 cells, but such effects could be abolished by silencing Ras. In summary, elevated CRIP1 levels enhanced the progression of CRIP1 via Ras signaling.

Doxorubicin-Loaded Tumor-Targeting Peptide-Decorated Polypeptide Nanoparticles for Treating Primary Orthotopic Colon Cancer.

Colorectal cancer is the third most common malignant disease worldwide, and chemotherapy has been the standard treatment for colorectal cancer. However, the therapeutic effects of chemotherapy are unsatisfactory for advanced and recurrent colorectal cancers. Thus, increasing the treatment efficacy of chemotherapy in colorectal cancer is a must. In this study, doxorubicin (DOX)-loaded tumor-targeting peptide-decorated mPEG-P(Phe-co-Cys) nanoparticles were developed to treat orthotopic colon cancer in mice. The peptide VATANST (STP) can specifically bind with vimentin highly expressed on the surface of colon cancer cells, thus achieving the tumor-targeting effects. The nanoparticles are core-shell structured, which can protect the loaded DOX while passing through the blood flow and increase the circulation time. The disulfide bonds within the nanoparticles are sensitive to the glutathione-rich microenvironment of tumor tissues. Rupture of disulfide bonds of the nanoparticles leads to the continuous release of DOX, thus resulting in the apoptosis of the tumor cells. The in vivo experiments in mice with orthotopic colon cancer demonstrated that the synthesized DOX-loaded tumor-targeting peptide-decorated polypeptide nanoparticles showed properties of drug delivery systems and exhibited good antitumor properties. The synthesized nanoparticles show appropriate properties as one of the drug delivery systems and exhibit good antitumor properties after encapsulating DOX.