Preparation and in vivo imaging of NIR-emissive carbonized polymer dots derived from biomass olive leaves with a quantum yield of 71.4.

The conversion of biomass materials into high value-added chemicals is receiving more and more attention. Herein, biomass olive leaves are converted into carbonized polymer dots (CPDs) through a simple hydrothermal reaction. The CPDs show near infrared light emission properties, and the absolute quantum yield reaches a record breaking value of 71.4% under the excitation wavelength of 413 nm. Detailed characterization determines that CPDs only contain three elements: carbon, hydrogen and oxygen, which is very different from most carbon dots which contain nitrogen atoms. Subsequently, NIR fluorescence imaging both in vitro and in vivo is performed to test their feasibility as fluorescence probes. The metabolic pathways of CPDs in the living body are inferred by studying the bio-distribution of CPDs in major organs. Their outstanding advantage is expected to further broaden the application field of this material.

p16INK4A flow cytometry of exfoliated cervical cells: Its role in quantitative pathology and clinical diagnosis of squamous intraepithelial lesions.

BACKGROUND: P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co-test for detecting high-grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high-throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. METHODS: P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A -knockout) standards. Since 2018, 24 100-women (HPV-positive/-negative, Pap-normal/-abnormal) have been enrolled nationwide for two-tier validation work. In cross-sectional studies, age- and viral genotype-dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut-offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2-year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV-positive Pap-normal, Pap-abnormal biopsy-negative and biopsy-confirmed LSIL. RESULTS: P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A -positive ratio was 13.9 ± 1.8% among HPV-negative NILM women and peaked at the ages of 40-49 years; after HPV infection, the ratio increased to 15.1 ± 1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV-negative: 17.7 ± 5.0-21.4 ± 7.2%; HPV-positive: 18.0 ± 5.2-20.0 ± 9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV-combined double-cut-off-ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co-test. The p16INK4A -abnormal situation was an independent HSIL+ risk factor for 2-year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3-7.2). CONCLUSIONS: FCM-based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk-stratification-based interventions.

A nanocomposite competent to overcome cascade drug resistance in ovarian cancer via mitochondria dysfunction and NO gas synergistic therapy.

Ovarian cancer (OC) is one of the most common and recurring malignancies in gynecology. Patients with relapsed OC always develop "cascade drug resistance" (CDR) under repeated chemotherapy, leading to subsequent failure of chemotherapy. To overcome this challenge, amphiphiles (P1) carrying a nitric oxide (NO) donor (Isosorbide 5-mononitrate, ISMN) and high-density disulfide are synthesized for encapsulating mitochondria-targeted tetravalent platinum prodrug (TPt) to construct a nanocomposite (INP@TPt). Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum, depleting glutathione, and preventing apoptosis escape through generating highly toxic peroxynitrite anion (ONOO-). To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor, an OC patient-derived tumor xenograft (PDXOC) model in BALB/c nude mice was established. INP@TPt showed the best therapeutic effects in the PDXOC model. The corresponding tumor tissues contained high ONOO- levels, which were attributed to the simultaneous release of O2•- and NO in tumor tissues. Taken together, INP@TPt-based systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR, providing practical applications for ovarian therapy.

Bioinformatics Analysis of miRNAs Targeting TRAF5 in DLBCL Involving in NF-κB Signaling Pathway and Affecting the Apoptosis and Signal Transduction.

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma with high heterogeneity. There is an unmet need to investigate valid indicators for the diagnosis and therapy of DLBCL. Methods: GEO database was utilized to screen for differentially expressed genes (DEGs) and differential miRNAs in DLBCL tissues. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyse DEGs. Then multiple databases were searched for related miRNAs within DLBCL, TNF receptor-associated factor 5 (TRAF5) and NF-kappa B (NF-κB) signaling pathways. The KOBAS database was used to assist in the screening of miRNAs of interest and construct the regulatory network of miRNA-mRNA. Finally, the expression level and diagnostic performance of miRNAs were analyzed with GEO datasets, and DEGs were identified from the GEPIA database. Results: DEGs were significantly concentrated in the NF-κB signaling pathway and cytokine-cytokine receptor interaction, and involved in the process of immune response and protein binding. MiR-15a-5p, miR-147a, miR-192-5p, miR-197-3p, miR-532-5p, and miR-650 were revealed to be targeting TRAF5 and participating in NF-κB signaling pathway and might impact the apoptosis and signal transduction of DLBCL. In the GEPIA database, TRAF5 was significantly overexpressed in DLBCL. The expression of miR-197-3p was upregulated within GEO datasets, while the rest of the miRNAs were downregulated in DLBCL. Conclusions: Subsets of miRNAs may participate in the NF-κB signaling pathway by co-targeting TRAF5 and could be prospective biomarkers exploring the pathogenesis of DLBCL.

Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1.

Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated ß-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.

Effects of polysaccharides from selenium-enriched Pyracantha fortuneana on mice liver injury.

We have previously reported that polysaccharides extracted from Pyracantha fortuneana (Maxim.) Li (P. fortuneana) lowered the oxidative stress and inhibited the inflammatory responses in mice. Our present study aims to determine the effects of Selenium enriched P. fortuneana polysaccharides (Se-PFPs) against carbon tetrachloride (CCl4)-induced liver injury in a mouse model. Our results displayed that CCl4 remarkably elevated the levels of alanine transferase (ALT), aspartate transaminase (AST), lactic dehydrogenase (LDH), cholesterol, triglycerides in serum. However, similar to BP treatment, supplementation of mice with Se-PFPs resulted in reversal of ALT, AST, LDH, cholesterol, triglycerides in serum. Contrary to CCl4, supplementation of mice with Se-PFPs elevated the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and levels of glutathione (GSH) in liver. Furthermore, Se-PFPs treatment increased the expression of GPx and catalase (CAT) at mRNA and protein levels in liver which were decreased in CCl4 group. Contrary to CCl4, Se-PFPs supplement decreased the levels of thiobarbituric acid reactive substances (TBAR) and H2O2, which served as lipid peroxidation biomarker. Our study indicates that Se-PFPs administration is effective in attenuating CCl4-induced liver injury. The mechanism underlying this effect may be attributed to the reduction of oxidative stress and inflammation in the liver by Se-PFPs through up-regulation of the antioxidant system. Our study suggests that Se-PFPs might be a potential dietary agent in the prevention of hepatic damage.

[Expression of survivin protein in prostatic carcinoma tissues and its correlation with apoptosis of cancer cells].

OBJECTIVE: To investigate the expression of survivin protein in the tissues of prostatic carcinoma and its correlation with apoptosis of cancer cells. METHODS: Expression of survivin protein and apoptosis index(AI) were detected by immunohistochemical and terminal deoxynucleotidyl transterase-mediated dUTP biotin nich end labeling(TUNEL) technique in the tissues of 42 cases of prostatic carcinima (PCa) and 10 cases of normal prostate (NP). RESULTS: Survivin prosteins were expressed in 34 of the 42 (80.59%) cases of PCa. The positive rate of survivin was strongly associated with pathological grades, clinical stages and lymphmetastasis in PCa(P < 0.05). In contrast, NP did not express survivin. Survivin protein expression was negatively correlated with AI in PCa(r = -0.679, P < 0.001). CONCLUSIONS: Apoptosis inhibition by survivin may participate in the onset and progression of PCa, and the detection of survivin protein and AI in PCa may help to evaluate the degree of cell differentiation, decide therapeutic strategies and estimate prognosis.

[Clinicopathologic features and diagnosis of metastatic carcinoma to the spleen].

OBJECTIVE: To study the clinicopathologic features and diagnosis of metastatic carcinoma to the spleen (MCS). METHODS: Four patients (1 man and 3 women, mean age 43.5 years) with MCS were analyzed clinicopathologically. RESULTS: The four MCS patients accounted for 1.3% of 308 patients having spleen biopsy from 1959 to 1999. Their chief presentations were pain and mass in the left upper quadrant of the abdomen. The mass was located in the upper pole of the spleen (1 patient), the lower pole of the spleen (2), or the lower pole and hilum of the spleen (1). Macroscopically, all of the lesions were nodular. Histologic type of these MCSs included acinar cell carcinoma of the pancreas (2 patients), transverse colon adenocarcinoma (1), and hepatic cell carcinoma (1). Clinically, 1 patient was diagnosed as having MCS and 3 were misdiagnosed. According to Chinese literature, the clinicopathologic features of MCS were as follows: (1) 66.7% of the patients with MCS were aged 30 approximately 60 years, with a mean of 51.2 years. (2) 76.3% of the patients presented with pain in the left upper quadrant of the abdomen and 63.2% with splenomegaly and splenic masses. (3) Macroscopically, nodular lesions accounted for 68.4%. (4) Microscopically, 84.2% of the lesions were adenocarcinomas and 70.3% originated from carcinomas of the colon, liver, ovary and pancreas. (5) B-mode ultrasonography and/or CT showed occupying lesions or masses in the spleen in 76.7%, and MCS in 11.8%. (6) Clinically, 73.7% of the patients were misdiagnosed. CONCLUSIONS: MCS is uncommon but its clinical misdiagnosis rate is high. Image examination is of value in clinical diagnosis. Cooperation of clinicians and pathologists may enhance the diagnostic level of MCS.