Optimizing removal of antiretroviral drugs from tertiary wastewater using chlorination and AI-based prediction with response surface methodology.

Chemical and pharmaceutical chemicals found in water sources create substantial risks to human health and the environment. The presence of pharmaceutical contaminants in water can cause antibiotic resistance development, toxicity to aquatic organisms, and endocrine disruption. Hence, the elimination of chemicals and other contaminants from wastewater prior to its release is a burgeoning concern in the domains of engineering and science. The use of treatment technologies in wastewater treatment plants can remove pharmaceutical contaminants through the oxidation process. However, many traditional wastewater treatment plants lack the advanced monitoring tools required to detect low concentrations of pharmaceuticals. Without the ability to detect these compounds, it's challenging to treat them effectively. The goal of this study was to use Response Surface Methodology (RSM) and Artificial Neural Networks (ANN) algorithms to model and improve how Nevirapine and Efavirenz break down in different chlorination conditions. The RSM analysis revealed statistically significant models (F-values: Nevirapine, pH-t: 108.15, T-t: 76.55, ICC-t: 110.84), indicating a strong correlation between operational parameters (pH, temperature, and initial chlorine concentration) and degradation behavior. The ANN model accurately predicted the degradation of both Nevirapine and Efavirenz under various chlorination conditions, as confirmed by analyzing actual-predicted graphs, residual plots, and Mean Squared Error (MSE) values. The ANN model using ICC-t achieved the highest MOD value of 31.31 % for Nevirapine. The ANN model based on ICC-t yielded a maximum MOD value of 16.06 % for Efavirenz. These findings provide valuable insights into optimizing chlorination processes for better removal of these pharmaceutical contaminants from water.

Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms?

Neoplasms are one of the most concerned public health problems worldwide. Digestive system neoplasms, with a high morbidity and mortality, is one of the most common malignant tumors in human being. It is found that exosomes act as an intercellular communication media to carry the metabolic and genetic information of parental cells to target cells. Likely, exosomes participate in lipid metabolism and regulates multiple processes in digestive system neoplasms, including the information transmission among cancer cells, the formation of neoplastic microenvironment, and the neoplastic biological behaviors like metastasis, invasion, and the chemotherapy resistance. In this review, we firstly introduce the main mechanisms whereas exosomes act as intercellular lipometabolic communication mediator in digestive system neoplasms. Thereafter we introduce the relationship between exosomes lipid metabolism and various type of digestive system neoplasms, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Eventually, we summarized and prospected the development and implication of exosomes in digestive system neoplasms. The further research of exosomes as intercellular lipid metabolism mediator will contribute to accurate and efficient diagnosis and treatment of digestive system neoplasms.

Reduced expression of microRNA-432-5p by DNA methyltransferase 3B leads to development of colorectal cancer through upregulation of CCND2.

BACKGROUND: The tumor suppressive function of microRNA-432-5p (miR-432-5p) has been reported in several human malignances. This study aimed to probe the expression profile and role of miR-432-5p in colorectal cancer (CRC) and the molecular mechanism. METHODS: Differentially expressed miRNAs between CRC and healthy samples were screened using a miRNA expression dataset GSE136020. The related molecules were identified by integrated bioinformatic analyses. A murine model of primary CRC was established and xenograft tumors were induced in mice. Altered expression of DNMT3B, miR-432-5p and cyclin D2 (CCND2) were introduced in CRC cells to determine their roles in the development of CRC. RESULTS: miR-432-5p was downregulated in CRC according to the GSE136020 dataset. CCND2 mRNA was confirmed as a target of miR-432-5p. miR-432-5p was downregulated, whereas CCND2 was abundantly expressed in CRC tissues and cells. DNA methyltransferase 3B (DNMT3B) induced DNA methylation at the CpG island of miR-432-5p to inhibit its expression. miR-432-5p mimic significantly suppressed tumorigenesis of primary CRC in mice. Downregulation of DNMT3B weakened viability, invasiveness, blocked the cell cycle progression of CRC cells in vitro, and inhibited xenograft tumor growth and metastasis in nude mice. However, additional downregulation of miR-432-5p or upregulation of CCND2 restored the malignant behaviors of CRC cells. CONCLUSION: This study showed that DNMT3B induced DNA methylation and downregulation of miR-432-5p to promote development of CRC by upregulating CCND2.

NEDD4 triggers FOXA1 ubiquitination and promotes colon cancer progression under microRNA-340-5p suppression and ATF1 upregulation.

NEDD4 is an E3 ubiquitin ligase that recognizes substrates through protein-protein interactions and is involved in cancer development. This study aimed to elucidate the function of NEDD4 in colon cancer (CC) progression and its mechanism of action. NEDD4 was abundantly expressed in CC tissues and cells, and the overexpression of NEDD4 promoted the growth and metastasis of xenograft tumours as well as the tumorigenesis rate of primary CC in mouse models. In in vitro experiments, the silencing (or upregulation) of NEDD4 inhibited (or increased) the viability, invasion, and epithelial-to-mesenchymal transition of CC cells. The binding relationships between NEDD4 and FOXA1, FOXA1 and microRNA (miRNA)-340-5p, and miR-340-5p and ATF1 were validated by Co-immunoprecipitation, chromatin immunoprecipitation and luciferase assays, and NEDD4 was demonstrated to trigger FOXA1 ubiquitination and degradation. FOXA1 transcriptionally activated miR-340-5p, which subsequently bound to ATF1 mRNA. The upregulation of FOXA1 or miR-340-5p or the downregulation of ATF1 blocked certain functions of NEDD4 in CC cells. Altogether, NEDD4 was demonstrated to trigger FOXA1 ubiquitination and promote CC progression under the involvement of microRNA-340-5p suppression and ATF1 upregulation.

Lysine demethylase 5B suppresses CC chemokine ligand 14 to promote progression of colorectal cancer through the Wnt/ß-catenin pathway.

AIMS: Epigenetic and genetic alterations are crucial events in the onset and progression of human cancers including colorectal cancer (CRC). This work aims to probe the relevance of lysine demethylase 5B (KDM5B) to the progression of CRC and the possible molecules involved. MATERIALS AND METHODS: KDM5B expression in CRC tissues and cells was determined. The association between KDM5B and the prognosis of patients was analyzed. Gain- and loss-of function studies of KDM5B were performed in HT-29 and KDM5B cells to explore the impact of KDM5B on cell behaviors. Expression of CC chemokine ligand 14 (CCL14) in CRC tissues and cells and its correlation with KDM5B were analyzed. Altered expression of CCL14 was introduced in CRC cells, and a Wnt/ß-catenin-specific antagonist KYA1797K was induced in cells as well. KEY FINDINGS: KDM5B was abundantly expressed while CCL14 was poorly expressed in CRC tissues and cells. High KDM5B expression was relevant to poor prognosis of patients. Downregulation of KDM5B suppressed proliferation and aggressiveness of HT-29 cells, and reduced the growth of xenograft tumors in mice, while upregulation of KDM5B in SW480 cells led to reverse results. KDM5B reduced CCL14 expression through demethylation modification of H3K4me3. Upregulation of CCL14 suppressed colony formation and invasiveness of CRC cells. KDM5B downregulated CCL14 to activate the Wnt/ß-catenin. Inhibition of ß-catenin by KYA1797K blocked the oncogenic roles of KDM5B in cells and in xenograft tumors. SIGNIFICANCE: This study suggested that KDM5B suppresses CCL14 through demethylation modification of H3K4me3, leading to activation of the Wnt/ß-catenin and the CRC progression.

Matrix metalloproteinase-8 rs11225395 polymorphism correlates with colorectal cancer risk and survival in a Chinese Han population: a case-control study.

Matrix metalloproteinase-8 (MMP-8) is a gene associated with inflammation and prognosis in colorectal cancer (CRC). Here, we studied the link between the rs11225395 polymorphism of MMP-8 gene and CRC risk. We recruited 551 CRC cases and 623 controls from among a subpopulation of Han Chinese patients. Data found that this variant was connected to an increased risk of CRC (TT versus CC: OR, 1.76; 95%CI, 1.09-2.84; P = 0.021; T versus C: OR, 1.29; 95%CI, 1.07-1.56; P = 0.007). Stratified analyses indicated a positive association among smokers (TT versus CC: OR, 2.31; 95%CI, 1.12-4.79; P = 0.024), males, and patients ≥ 60 years old. Crossover analysis showed that the potential interaction between smoking or drinking and the MMP-8 rs11225395 polymorphism was related to elevated risk for CRC. The rs11225395 polymorphism was also connected with lymph node metastasis and TNM stage. Moreover, the CRC cases carrying a TT genotype of MMP-8 rs11225395 presented had poorer overall survival than the CC genotype carriers. These findings show that MMP-8 rs11225395 correlates with an elevated risk of CRC and poor patient prognosis in a subpopulation of the Han Chinese subpopulation. Thus, the MMP-8 rs11225395 polymorphism could potentially function as a biomarker predictive of CRC susceptibility.

MicroRNA­766 inhibits the malignant biological behaviours of pancreatic ductal adenocarcinoma by directly targeting ETS1.

Increasing evidence indicates that numerous microRNAs (miRNAs) are altered in pancreatic ductal adenocarcinoma (PDAC), and their alterations significantly influence the malignant behaviour of PDAC. Therefore, identifying miRNAs associated with PDAC and their biological roles in the disease may provide promising therapeutic opportunities. Alteration of the expression of miRNA­766 (miR­766) has been previously reported in several types of human malignancy. However, to the best of our knowledge, whether miR­766 exhibits different expression patterns in PDAC and its underlying functions in the progression of PDAC remain to be elucidated. In the present study, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to detect miR­766 expression levels in PDAC tissues and cell lines. The effects of miR­766 upregulation on PDAC cell proliferation and invasion were evaluated using MTT and invasion assays, respectively. The mechanisms underlying the role of miR­766 in PDAC cells were explored using bioinformatics analysis, luciferase reporter assay, RT­qPCR and western blot analysis. It was found that miR­766 was significantly downregulated in PDAC tissues and cell lines. The detailed roles of miR­766 in the progression of PDAC were characterised using Panc­1 and Aspc­1 cell lines. The results revealed that the upregulation of miR­766 restricted the proliferation and invasion of PDAC cells. Through a series of experiments, it was found that E26 transformation specific­1 (ETS1) was a direct target of miR­766 in PDAC cells. Furthermore, ETS1 knockdown simulated the inhibitory effects of the overexpression of miR­766 on PDAC cells, whereas the effects of miR­766 restoration on the PDAC cells were reversed by overexpressing ETS1. In conclusion, the findings of the present study demonstrate that miR­766 offers potential as a therapeutic target for patients with PDAC.

Short- and long-term outcomes of laparoscopic complete mesocolic excision for transverse colon cancer.

PURPOSE: To compare the short- and long-term outcomes of open and laparoscopic complete mesocolic excision (CME) for transverse colon cancer (TCC) using propensity score matching (PSM). METHODS: The clinical and follow-up data of 97 TCC patients who were subjected to CME in our institution from January 2012 to October 2017 were retrospectively analyzed. The patients were divided into the laparoscopic and open group according to the surgical approaches. The patients were 1:1 matched using the PSM method. The matching variables included age, sex, body mass index (BMI), clinical stage, and American Society of Anesthesiologists (ASA) score. Forty-three patients were included in each study group. Short- and long-term outcomes were compared between the two groups. RESULTS: Compared with the open group, the laparoscopic group showed benefits including less intraoperative blood loss, faster postoperative recovery, and shorter hospital stay. There was no significant difference in the incidence of 30- day postoperative complications, the incidence of major complications, and the pathological results between the two groups. The intraoperative and postoperative 30-day mortality rates in both groups were 0%. There was no significant difference in the tumor recurrence rate, 5-year overall survival (OS), and 5-year disease-free survival (DFS) between the two groups. CONCLUSION: Short-term outcomes were better with laparoscopic CME than with open surgery although the long-term outcomes were similar in both groups.

Short- and long-term outcomes of laparoscopic hepatectomy for colorectal liver metastases in elderly patients.

PURPOSE: This study aimed to evaluate the short- and long-term outcomes of laparoscopic hepatectomy (LH) for colorectal liver metastases (CRLM) in elderly patients. PATIENTS AND METHODS: Between January 2009 and January 2016, LH was performed for 241 consecutive patients who were ≥60 years old and had CRLM. Based on their age at the LH, the patients were divided into an elderly group (≥70 years old, 78 patients) and a middle-aged group (60-69 years old, 163 patients). The short- and long-term outcomes were compared between the two groups. RESULTS: Compared to the middle-aged group, the elderly group had higher values for Charlson comorbidity index, proportion of preoperative chemotherapy, and American Society of Anesthesiologists score. No other significant differences were observed in the preoperative characteristics. The elderly group had a higher conversion rate, compared to the middle-aged group, although no significant differences were observed in the surgical procedures, surgical times, intraoperative blood losses, numbers and severities of postoperative 90-day complications, postoperative 90-day mortality rates, pathology results, and other short-term outcomes. Long-term follow-up revealed similar rates of recurrence, disease-free survival, and overall survival in the two groups. Multivariable analysis revealed that age did not independently predict overall survival or disease-free survival. CONCLUSION: Similar short- and long-term outcomes were observed after LH for CRLM in elderly and middle-aged patients. Thus, advanced age is not a contraindication for LH treatment in this setting.

Levels of peripheral Th17 cells and serum Th17-related cytokines in patients with colorectal cancer: a meta-analysis.

Studies suggest that inflammation is involved in the colorectal cancer (CRC) pathology and symptoms. This study sought to quantitatively summarize the clinical cytokine data. Multiple reports have described the proportion of Th17 cells in peripheral blood and serum levels of Th17-related cytokines in patients with colorectal cancer (CRC). To clarify the status of Th17 cells and Th17-related cytokines in CRC patients, we did a meta-analysis of the results published previously to quantitatively assess the levels of peripheral Th17 cells and serum Th17-related cytokines in patients with CRC. We searched PubMed, Embase, web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI) systematically for studies reporting the proportion of Th17 cells and the serum levels of Th17-related cytokines (IL-17, IL-17A, IL-6, IL-22, IL-23) in CRC patients. Studies measuring the proportion of Th17 cells and the serum levels of Th17-related cytokines (IL-17, IL-17A, IL-6, IL-22, IL-23) in CRC and healthy control subjects were included. Mean (standard deviation) proportion of Th17 cells and cytokine concentrations for CRC and control subjects were extracted. We assessed pooled data by using a random-effects model. We identified 1276 studies, of which 24 studies were included in the final meta-analytical processes. The quality was reliable according to the Newcastle-Ottawa Quality Assessment Scale (Case Control Studies). Compared with control subjects, CRC patients had a higher proportion of Th17 cells [2.37%, (0.53, 2.21)]; an elevated levels of serum IL-17A 1.11 pg./ml, 95%CI (0.16-2.07); an elevated levels of serum IL-6 3.42 pg/ml, 95%CI (3.14-3.70); an elevated levels of serum IL-22 1.32 pg/ml, 95%CI (0.94-1.70); an elevated levels of serum IL-23 0.16pg/ml, 95%CI(1.94-5.39). After sensitivity analysis, an elevated level of serum IL-17 was showed. The data showed that the proportion of Th17 cells in PB and levels of serum IL-17, IL-17A, IL-6, IL-22, IL-23 increased among CRC patients compared to control subjects. This result demonstrated that Th17 cells and Th17-related cytokines may be involved in the pathogenic mechanisms of CRC.

Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

Kinetics and Immunodominance of Virus-Specific T Cell Responses During Hantaan Virus Infection.

Immunodominant T cell responses are important for protection against virus challenge. However, studies screening for the immunodominant T cell responses and following their kinetics in acute Hantaan virus (HTNV) infection are very limited. Herein, the HTNV nucleocapsid protein-specific T cell responses were longitudinally screened in 15 patients with acute HTNV infection, eight of whom had a particularly severe hemorrhagic fever with renal syndrome (HFRS). An extremely impaired IFN-γ-producing T cell response was observed in patients with severe HFRS at the early stage of infection, especially to the immunodominant epitopes detected in the mild to moderate group, namely peptides N127-141, N139-153, N241-255, and N355-369. The initially insufficient T cell response to the immunodominant epitopes may play a role in influencing the severity of HTNV infection. These findings provide information that may aid the design of future vaccines against hantaviruses.

CLC-3 channels in cancer (review).

Ion channels are involved in regulating cell proliferation and apoptosis (programed cell death). Since increased cellular proliferation and inhibition of apoptosis are characteristic features of tumorigenesis, targeting ion channels is a promising strategy for treating cancer. CLC-3 is a member of the voltage-gated chloride channel superfamily and is expressed in many cancer cells. In the plasma membrane, CLC-3 functions as a chloride channel and is associated with cell proliferation and apoptosis. CLC-3 is also located in intracellular compartments, contributing to their acidity, which increases sequestration of drugs and leads to chemotherapy drug resistance. In this review, we summarize the recent findings concerning the involvement of CLC-3 in cancer and explore its potential in cancer therapy.

Histone deacetylase HDAC4 promotes gastric cancer SGC-7901 cells progression via p21 repression.

Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5'-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.

Generation of rat monoclonal antibodies against human RANTES.

RANTES (or regulated upon activation, normal T cell expressed and secreted) belongs to the rapidly growing chemokine family. It is mainly produced by T cells, epithelial cells, monocytes, fibroblasts, and mesanglial cells. Increased RANTES expression has been associated with a wide range of inflammatory disorders and pathologies. Mouse RANTES is the homolog molecule of human RANTES. The two have considerable homology in both sequence and structure. Using hRANTES as immunogen and the technique of rat B lymphocyte hybridoma, we raised two hybridoma cell lines secreting monoclonal antibodies (MAbs) to hRANTES, designated no. 1 and no. 2. Both MAbs can bind the hRANTES in FCM, Western blot analysis, and immunocytochemistry. No. 1 also worked well in immunohistochemistry of rat transplanted intestine, which may recognize the same epitope on human RANTES and rat RANTES. Thus, successful production of rat anti-human RANTES MAbs may provide a useful tool in further exploration of the biological function and pathological significance of RANTES and may provide a new method to judge early rejection after small bowel transplantation.

[Preparation and characterization of monoclonal antibodies against human RANTES molecule].

AIM: To prepare monoclonal antibodies against human RANTES molecule and identify the expression of RANTES in rat small intestine after small bowel transplantation. METHODS: Murine mAbs were prepared by B lymphocyte hybridoma technique. The expression of RANTES in rat small intestine after small bowel transplantation was detected by immunohistochemistry. RESULTS: Four hybridoma cell lines secreting monoclonal antibodies to human RANTES, FMU-RANTES 1, FMU-RANTES 2, FMU-RANTES 3 and FMU-RANTES 4, were established. The titers of a scetic mAbs reached to 1 x 10(-6) and the Ig subclass of FMU-RANTES 1, FMU-RANTES 3 and FMU-RANTES 4 was IgG1(kappa) and that of FMU-RANTES 2 was IgG2b(kappa). Among these mAbs, FMU-RANTES 1, FMU-RANTES 2 and FMU-RANTES 3 could bind human RANTES protein in Western bolt. FMU-RANTES 1, FMU-RANTES 2 and FMU-RANTES 4 could be used in immunohistochemistry staining. Rat RANTES molecule could be detected in the cyto plasm of epithelial cells in rat small intestine after small bowel transplantation. CONCLUSION: Four mAbs against RANTES molecule were prepared, which can provide a useful tool in research on the structure and function of RANTES molecule. High expression of RANTES may be involved in the rejection of allogeneic graft.