Co-exposure to pentachlorophenol (PCP) and cadmium (Cd) triggers apoptosis-like cell death in Eschericia coli.

Pentachlorophenol (PCP) - cadmium (Cd) complex pollution has been identified as a form of persistent soil pollution in south China, exerting detrimental impacts on the indigenous soil bacterial communities. Hence, it is worthwhile to investigate whether and how bacterial populations alter in response to these pollutants. In this study, Escherichia coli was used as a model bacterium. Results showed that PCP exposure caused bacterial cell membrane permeability changes, intracellular ROS elevation, and DNA fragmentation, and triggered apoptosis-like cell death at low exposure concentration and necrosis at high exposure concentration. Cd exposure caused severe oxidative damage and cell necrosis in the tested bacterial strain. The co-exposure to PCP and Cd elevated the ROS level, stimulated the bacterial caspase activity, and induced DNA fragmentation, thereby leading to an apoptosis-like cell death. In conclusion, PCP-Cd complex pollution can cause bacterial population to decrease through apoptosis-like cell death pathway. However, it is worth noting that the subpopulation survives under the complex pollution stress.

Sequentially degradable hydrogel-microsphere loaded with doxorubicin and pioglitazone synergistically inhibits cancer stemness of osteosarcoma.

Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs) are thought to be the major cause of failure in cancer therapy due to their considerable resistance to most chemotherapeutic agents, resulting in tumor recurrence and eventually metastasis. Here, we report a treatment strategy for osteosarcoma using hydrogel-microspheres (Gel-Mps) complex mainly composed of collagenase (Col) and PLGA microspheres (Mps) carrying Pioglitazone (Pio) and Doxorubicin (Dox). Col was encapsulated in the thermosensitive gel to preferentially degrade tumor extracellular matrix (ECM), ensuring subsequent drug penetration, while Mps with Pio and Dox were co-delivered to synergistically inhibit tumor growth and metastasis. Our results showed that the Gel-Mps dyad functions as a highly biodegradable, extremely efficient, and low-toxic reservoir for sustained drug release, displaying potent inhibition of tumor proliferation and subsequent lung metastasis. Selective PPARγ agonist Pio reversed drug resistance to Dox by significantly down-regulating the expression of stemness markers and P-glycoprotein (P-gp) in osteosarcoma cells. The Gel@Col-Mps@Dox/Pio exhibited advanced therapeutic efficacy in vivo, demonstrating its great potential to serve a novel osteosarcoma therapy, which not only inhibits the growth of, but also attenuates the stemness of osteosarcoma. The dual effects reinforce the sensitivity and efficacy of chemotherapy.

Astragaloside IV drug-loaded exosomes (AS-IV EXOs) derived from endothelial progenitor cells improve the viability and tube formation in high-glucose impaired human endothelial cells by promoting miR-214 expression.

INTRODUCTION: The high glucose changes caused by diabetes mellitus (DM) can damage the vascular system. Astragaloside IV (AS-IV) can improve diabetes and promote angiogenesis. Exosomes (EXOs) help to carry specific drugs into cells efficiently. However, whether AS-IV loaded EXOs (AS-IV EXOs) can improve damaged endothelial cells through miR-214 remains to be determined. MATERIAL AND METHODS: We prepared and identified AS-IV EXOs derived from endothelial progenitor cells (EPCs) and high glucose stimulated endothelial cell models to investigate whether AS-IV EXOs can improve damaged endothelial cells through miR-214. We used a transmission electron microscope (TEM) and DAPI staining to identify the morphology and characteristic expression of EPCs and EXOs, and then prepared AS-IV EXOs. Cell function tests were performed to detect the cloning, proliferation, and migration capabilities of cells. Western blot (WB) and real-time quantitative polymerase chain reaction (qRT-PCR) were used to assess the expression level of Tie-2, Ang-1, and PI3K/Akt-related protein. RESULTS: The DAPI staining results showed that inducing human umbilical vein endothelial cells (HUVECs) could effectively absorb AS-IV EXOs. The results of plate clone formation assay, CCK-8, cell adhesion, and transwell assay of HUVECs stimulated by high glucose showed that AS-IV EXOs had a damage relief effect. By the detection of WB and qRT-PCR, it was found that AS-IV EXOs promoted the expression of miR-214 and proteins related to blood vessel growth. After transfection of miR-214 to pre-treat HUVECs under high glucose stimulation, AS-IV EXOs promoted the tube formation of HUVECs by regulating the level of miR-214. CONCLUSIONS: By promoting the expression of miR-214, AS-IV EXOs significantly improved the activity and tubularization of HUVECs under high glucose stimulation.

Improvement in the condition of patients with primary liver cancer with transcatheter arterial chemoembolization before and after microwave ablation interventional therapy.

BACKGROUND: We compared the clinical efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) and TACE alone for the treatment of patients with primary liver cancer (PLC). MATERIALS AND METHODS: A total of 160 patients with PLC were enrolled and randomized into a study group (n=80) and a control group (n=80). Patients in the study group were treated with TACE combined with MWA, whereas those in the control group were treated with TACE alone. Treatment efficacy, changes in hepatic function indices after the treatment, incidence of adverse reactions, quality of life after treatment, and 3-year survival rates of the two groups were compared. Cox proportional hazards model was used for analyzing the patients' prognostic factors. RESULTS: The total effective rate in the study group was higher than that in the control group (P<0.05). Patients in the study group had lower alanine aminotransferase and total bilirubin levels (P<0.05) and higher albumin levels (P<0.05) than those in the control group. The 1-, 2-, and 3-year overall survival rates in the study group were higher than those in the control group (P<0.05). Cox proportional hazards model showed that tumor size, extrahepatic metastasis, portal vein tumor thrombosis, severity of liver cirrhosis, and therapeutic methods were independent risk factors for patients with PLC. CONCLUSIONS: TACE combined with MWA is more effective than TACE alone in treating PLC, reducing the damage to the patients' cardiac function and prolonging survival.

Ginseng Consumption Possible Effect on Liver Cancer: A Meta-Analysis.

INTRODUCTION: Ginseng is associated to the reduction of the risk of liver-cancer and some time is used as adjuvant therapy to treat liver-cancer, but its outcome remains uncertain. Hence, the present study aimed to determine the association between Ginseng consumption and liver-cancer. METHODS: By a systematic-literature search up to Decamber-2019, 9-studies included 13,766 subjects, 9235 Ginseng consumer. Odds ratio (OR) with 95% confidence intervals (CIs) was determined comparing Ginseng consumption and liver-cancer relationship using the dichotomous method with a fixed-effect or random-effect models. RESULTS: Subjects consuming Ginseng had a significantly lower risk of developing liver-cancer than those not consuming Ginseng (OR, 0.46; 95% CI, 0.40-0.52, p < 0.001). Also, there was a significant relationship between Ginseng consumption as adjuvant-therapy and disease control rate (OR, 4.47; 95% CI, 2.41-8.28, p < 0.001), Karnofsky Performance Scale (OR, 4.31; 95% CI, 1.80-10.36, p = 0.001), response to chemotherapy rate (OR, 1.79; 95% CI, 1.05-3.02, p = 0.03) and decline of leukocyte count (OR, 0.17; 95% CI, 0.07-0.42, p < 0.001). However, there was no significant effect, but relatively favoring Ginseng consumption, between Ginseng consumption as adjuvant-therapy and one year survival rate (OR, 1.48; 95% CI, 0.78-2.81, p = 0.23), two year survival rate (OR, 1.69; 95% CI, 0.87-3.25, p = 0.12) gastrointestinal dysfunction (OR, 0.55; 95% CI, 0.17-1.79, p = 0.32), and the hepatic dysfunction (OR, 1.15; 95% CI, 0.59-2.22, p = 0.68). CONCLUSIONS: Ginseng may have an independent relationship with reducing liver-cancer incidence when administrated to healthy subjects as a supplement and with reducing cancer-chemotherapy related outcomes risk when administrated with chemotherapy as adjuvant therapy.

Aberrant brain-expressed X-linked 4 (BEX4) expression is a novel prognostic biomarker in gastric cancer.

BACKGROUND: This study aimed to investigate the expression level of X-linked 4 (BEX4) in patients with gastric cancer (GC) and to investigate the prognostic significance of BEX4. METHODS: The mRNA expression of BEX4 was analyzed using the Cancer Genome Atlas (TCGA) datasets. The relationship between the expression of BEX4 and GC patient survival was assessed using a Kaplan-Meier plot and Log Rank test. Multivariate cox regression analysis was used to evaluate prognostic factor. The diagnostic value of BEX4 expression in GC tissue was determined through receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was used to explore BEX-4 related signaling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further validation. RESULTS: BEX4 was expressed at lower level in GC tissues than normal gastric tissues. The lower expression of BEX4 was also validated at protein level in HPA database. The area under the ROC curve for BEX4 expression in normal gastric tissue and GC was 0.791, which presented modest diagnostic value. Kaplan-Meier survival analysis revealed that patients in low BEX4 expression group had a worse prognosis than those with high BEX4 expression (P = .009). Multivariate analysis showed that BEX4 is an independent risk factor for overall survival both in TCGA and GSE62254 (P = .0142, .013, respectively). GSEA identified that the expression of BEX4 was related to DNA replication, RNA polymerase, cell cycle, and P53 signaling pathway. CONCLUSION: BEX4 is expressed at low levels in GC. BEX4 expression independently predicted poor OS for GC. It is a promising independent molecular predictor for the diagnosis and prognosis of GC.

The antimicrobial peptides and their potential clinical applications.

Nowadays, the bacterial drug resistance leads to serious healthy problem worldwide due to the long-term use and the abuse of traditional antibiotics result in drug resistance of bacteria. Finding a new antibiotic is becoming more and more difficult. Antimicrobial peptides (AMPs) are the host defense peptides with most of them being the cationic (positively charged) and amphiphilic (hydrophilic and hydrophobic) α-helical peptide molecules. The membrane permeability is mostly recognized as the well-accepted mechanism to describe the action of cationic AMPs. These cationic AMPs can bind and interact with the negatively charged bacterial cell membranes, leading to the change of the electrochemical potential on bacterial cell membranes, inducing cell membrane damage and the permeation of larger molecules such as proteins, destroying cell morphology and membranes and eventually resulting in cell death. These AMPs have been demonstrated to have their own advantages over the traditional antibiotics with a broad-spectrum of antimicrobial activities including anti-bacteria, anti-fungi, anti-viruses, and anti-cancers, and even overcome bacterial drug-resistance. The natural AMPs exist in a variety of organisms and are not stable with a short half-life, more or less toxic side effects, and particularly may have severe hemolytic activity. To open the clinical applications, it is necessary and important to develop the synthetic and long-lasting AMP analogs that overcome the disadvantages of their natural peptides and the potential problems for the drug candidates.

Sensitive detection of oxidative DNA damage in cyanobacterial cells using supercoiling-sensitive quantitative PCR.

Supercoiling-sensitive quantitative PCR (ss-qPCR) is a sensitive technique to detect DNA damage in cultured animal cells and cultured/clinical human cells in vitro. In this study, we investigated whether the ss-qPCR method can be applied as a sensitive means to detect oxidative DNA damage in unicellular organisms. We used the model cyanobacterium Synechococcus elongatus PCC 7942 as a test organism and H2O2 as an exogenetic oxidative toxicant. Results showed that a significant increase in the plasmid DNA damage of S. elongatus PCC 7942 was induced by H2O2 in a dose- and time-dependent manner. The sensitivity of ss-qPCR in detecting DNA damage of the cyanobacterium was higher than the cell inhibition method (up to 255 times) as calculated from the slopes of fitted curves in the tested sub-toxic concentration range of 1-5 mM H2O2. Ss-qPCR also detected repairable low-intensity DNA damage in the cyanobacterium when DNA repair inhibitors were used. The detection limit of modified ss-qPCR was one tenth of that of previous methods. We also observed that ss-qPCR can be used to detect genomic DNA conformation change of cyanobacterium exposed to H2O2. Thus, this method will provide a powerful technical support for investigating the mechanisms of cyanobacterial DNA damage by environmental factors, especially intracellular reactive oxygen species enhancement-related factors.