Cancer-associated genes serve a crucial role in carcinogenesis. The present study aimed to investigate the mRNA expression levels of microspherule protein 1 (MCRS1) and MCRS2 in colorectal cancer (CRC) and their association with clinical variables. The mRNA expression levels of MCRS1 and MCRS2 were assessed by semi-quantitative reverse transcription polymerase chain reaction in the tumor and corresponding non-tumor tissues of 54 newly-diagnosed CRC patients, as well as in the normal colonic mucosa tissue of 19 age/gender-matched healthy controls. Immunofluorescence was also employed to identify the expression of MCRS1 in CRC tissues, while the concentration of serum carcinoembryonic antigen (CEA) was determined by an enzyme-linked immunoassay. The results identified a negative correlation between MCRS1 and MCRS2 expression levels (r=-0.3018, P=0.0266). MCRS1 mRNA expression was significantly increased and MCRS2 mRNA expression was decreased in CRC tissues compared with the levels in the corresponding normal tissues (both P<0.001). An increase in MCRS1 expression and a decrease in MCRS2 expression was detected in advanced stage when compared with early stage CRC patients. Immunofluorescence analysis revealed increased expression of MCRS1 in CRC patients. Furthermore, the expression levels of MCRS1 displayed positive correlation, whilst those of MCRS2 displayed negative correlation, with the serum CEA level in patients with CRC. The results suggest that increased MCRS1 and decreased MCRS2 expression appeared to be involved in the pathogenesis of CRC. The present study provides evidence suggesting that MCRS1 and MCRS2 may identify CRC patients at a risk of disease relapse, and thus, may be potential tools for monitoring disease activity and act as novel diagnostic markers in the treatment of CRC.

Worldwide, human pancreatic cancer is a rare malignancy with a poor prognosis. Long non-coding RNAs (lncRNAs) are known to have a crucial role in cancer occurrence and progression; however, the role of pseudogene-expressed lncRNAs, a major type of lncRNA, have not been thoroughly analyzed in cancer. Therefore, the present study focused on zinc finger protein 91 pseudogene (ZFP91-P). ZFP91-P expression was initially detected in two pancreatic cancer cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the highest expression of ZFP91-P was found in the BXPC-3-H cell line. Subsequently, BXPC-3-H cells were transfected with ZFP91-P short hairpin RNA (shRNA) using a plasmid vector and termed shZFP91-P. Cells transfected with negative control plasmid vector were termed shCon. MTT and Transwell assays were performed to analyze the proliferation and migration of BXPC-3-H cells, respectively, and western blotting was used to detect epithelial-mesenchymal transition markers, including vimentin and β-catenin. The present study showed that depletion of ZFP91-P markedly decreased pancreatic cancer cell proliferation and inhibited cell migration capacity. In addition, the expression of β-catenin increased while vimentin expression decreased. The current findings suggest that high expression of ZFP91-P promotes the migration of BXPC-3-H cells and may be a novel marker for early diagnosis for pancreatic cancer.

In combination with gene expression profiles, the protein interaction network (PIN) constructs a dynamic network that includes multiple functional modules. Previous studies have demonstrated that rifampin can influence drug metabolism by regulating drug-metabolizing enzymes, transporters, and microRNAs (miRNAs). Rifampin induces gene expression, at least in part, by activating the pregnane X receptor (PXR), which induces gene expression; however, the impact of rifampin on global gene regulation has not been examined under the molecular network frameworks.

Bidirectional gene pairs tend to be highly coregulated and function in similar biological processes in eukaryotic genomes. Structural features and functional consequences of bidirectional promoters (BDPs) have received considerable attention among diverse species. However, the underlying mechanisms responsible for the bidirectional transcription and coexpression of BDPs remain poorly understood in plants. In this study, we integrated DNase-seq, RNA-seq, ChIP-seq and MNase-seq data and investigated the effect of physical DNase I hypersensitive site (DHS) positions on the transcription of rice BDPs. We found that the physical position of a DHS relative to the TSS of bidirectional gene pairs can affect the expression of the corresponding genes: the closer a DHS is to the TSS, the higher is the expression level of the genes. Most importantly, we observed that the distribution of DHSs plays a significant role in the regulation of transcription and the coexpression of gene pairs, which are possibly mediated by orchestrating the positioning of histone marks and canonical nucleosomes around BDPs. Our results demonstrate that the combined actions of chromatin structures with DHSs, which contain functional cis-elements for interaction with transcriptional machinery, may play an important role in the regulation of the bidirectional transcription or coexpression in rice BDPs. Our findings may help to enhance the understanding of DHSs in the regulation of bidirectional gene pairs.

Inflammation is extremely important in the development of cerebral ischemia/reperfusion injury. Pannexin 1 (Panx1) channel has been reported to activate inflammasome in astrocytes and be involved in ischemic injury, but this damage effect is reversed by a Panx1 inhibitor-probenecid. However, the mechanism of probenecid protects against cerebral ischemia/reperfusion injury remains unclear. In present study, we hypothesized that probenecid protected astrocytes from ischemia/reperfusion injury in vitro by modulating the inflammasome. Primary cultured neocortical astrocytes were exposed to oxygen-glucose deprivation/reoxygenation (OGD/RX) and probenecid was added in this model. Viability and nuclear morphology of astrocytes, production of reactive oxygen species (ROS), protein expressions of NLRP3 (NOD-like receptor protein 3), caspase-1, and AQP4 (Aquaporins 4), as well as release of cellular HMGB1 and IL-1β were observed to evaluate the effect and mechanisms of probenecid on OGD/reoxygenated astrocytes. Probenecid did not affect cell viability at concentrations of 1, 5, 10, and 100μM but induced significant astrocytes death at 500μM. Probenecid inhibited cell death and ROS generation in astrocytes subjected to 6h of OGD and 24h of reoxygenation. The expression levels of NLRP3, caspase-1, and AQP4 increased after 6h of OGD, but probenecid treatment attenuated this increase. Moreover, the extracellular release of IL-1β and HMGB1 from OGD/reoxygenated astrocytes increased significantly. However, treatment by probenecid resulted in substantial reduction of these proteins levels in extracellular space. In conclusion, The Panx1 inhibitor, probenecid, which was administered before OGD, provided protective effects on the OGD/reoxygenation model of cultured astrocytes by modulating inflammasome activity and downregulating AQP4 expression.

Mucosal associated invariant T (MAIT) cells are important for immune defense against infectious pathogens and regulate the pathogenesis of various inflammatory diseases. However, their roles in the development of colorectal cancer (CRC) are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of MAIT cells in CRC patients. We found that the percentages of circulating memory CD8(+) MAIT cells were significantly reduced while tumor infiltrating MAIT cells were increased, especially in patients with advanced CRC. The serum CEA levels were positively correlated with the percentages of tumor infiltrating MAIT cells in CRC patients, but negatively correlated with the percentages of circulating MAIT in advanced CRC patients. Activated circulating MAIT cells from CRC patients produced lower IFN-γ, but higher IL-17. Furthermore, higher levels of Vα7.2-Jα33, IFN-γ and IL-17A were expressed in the CRC tissues. Co-culture of activated MAIT cells with HCT116 cells enhanced IL-17 expression and induced HCT116 cell cycle arrest at G2/M phase in a contact- and dose-dependent manner, which was abrogated by treatment with anti-MR1. Therefore, MAIT cells preferably infiltrate into the solid tumor in CRC patients and may participate in the immune surveillance of CRC.

Conflicting evidence exists on the effect of vitamin D supplementation on glucose metabolism in subjects with type 2 diabetes (T2D). Therefore, this meta-analysis focuses on the relationship between vitamin D intervention and glycaemic control in subjects with T2D.

The present study aimed to elucidate the effects of dexmedetomidine on kidney injury of parturients with preeclampsia (PE) undergoing cesarean section. Total 134 cesarean delivery women with PE were randomly divided into intervention group (IG) and control group (CG). Both groups underwent combined spinal and epidural anesthesia (CSEA), the IG was treated with 0.4 μg/(kg·min) dexmedetomidine for 10 min before surgery. The CG was treated with equivalent saline. Heart rate (HR), blood pressure, oxygen saturation (SpO2) of the two groups were measured at different time point after administration. Level of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Visual analogue score (VAS), Ramsay sedation score (RSS), and kidney injury related indexes were evaluated at different time points. The plasma-drug concentration of patients was determined by High Performance Liquid Chromatography (HPLC) method. Compared with CG, HR, PE, and diastolic blood pressure (DBP) showed lower level while SpO2 showed higher level in IG. Furthermore, expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-10 in IG was decreased after drug administration, the contents of β2-MG, KIM-1 and urine protein were also decreased in contrast to the CG (all P<0.05). Besides, VAS score was decreased but Ramsay score was increased in the IG (both P<0.05). The results of HPLC showed that the half life of dexmedetomidine was about 20 min and it is speculated that the drug can be quickly metabolized within 24 h. Dexmedetomidine exerted protective effects on kidney injury of parturients with PE undergoing cesarean section.

Previously, we confirmed the anti-tumor effects of sodium butyrate (NaBu) in nasopharyngeal carcinoma (NPC). However, its molecular mechanisms have not be fully elucidated. In this study, we studied the effects of NaBu on autophagy and explored the relation between NaBu associated autophagy and apoptosis in NPC cells. EGFP-LC3 plasmids were introduced into NPC cells to observed the effects of NaBu on autophagy flux with or without chloroquine (CQ) addition. Autophagy markers were also detected by Western blot. Under NaBu treatment, autophagy and apoptosis markers were detected simultaneously at different time. Then, to explore the roles of autophagy in NaBu induced apoptosis, the effects of autophagy inhibition, via specific inhibitor treatment or key gene knockdown, were analyzed. At last, the upstream signaling and its roles in NaBu induced autophagy and apoptosis were also analyzed. Increased LC3 dots and LC3-II accumulation indicated that NaBu can promote autophagy flux in NPC cells. LC3-II accumulation was earlier than cleaved PARP increment suggesting autophagy activation is prior to apoptosis activation, which was validated by flow cytometry mediated apoptosis analysis. Moreover, autophagy inhibition, achieved by 3-MA treatment or BECN1 knockdown, can antagonize NaBu induced apoptosis reflecting by re-deregulated cPARP and apoptotic rates. Furthermore, NaBu treatment inhibited the AKT/mTOR axis indicated by deregulated p-AKT(S473) and p-mTOR(S2448) and ectopic AKT expression both suppressed NaBu induced autophagy and apoptosis. At last, Western blot showed that HDAC6 dependent EGFR deregulation may account for the NaBu associated AKT/mTOR inhibition. NaBu can induce autophagic apoptosis via suppressing AKT/mTOR axis in NPC cells. Our results suggest that combination of autophagy inhibitors and deacetylase inhibitors may not be recommended in NPC clinical treatment.

To explore the anti-atherosclerotic effects of recombinant high-density lipoproteins (rHDL) of apolipoprotein AI wild-type (apoA-Iwt), apolipoprotein AI Milano (apoA-IM), apolipoprotein AI (N74C) (apoA-I (N74C) )and apolipoprotein AV (apoA-V). We constructed rHDL liposomes (rHDLs), which included apoA-Iwt, apoA-IM, and apoA-I (N74C), followed by the synthesis of rHDLs, with the indicated ratios of apoA-Iwt, apoA-IM, apoA-I (N74C) and apoA-V. We investigated the anti-atherosclerotic effects by experiments including the DMPC clearance assay and experiments that assessed the in vitro antioxidation against low-density lipoprotein, the cellular uptake of oxidized low-density lipoprotein (oxLDL) and the in vitro intracellular lipid accumulation. Electron microscopy results revealed that as more apoA-V was present in rHDLs, the particle size of rHDLs was larger. The DMPC clearance assay subsequently showed that rHDL protein mixtures could promote DMPC turbidity clearance when more apoA-V was included in the reaction mixtures, with apoAV-rHDL showing the strongest turbidity clearance ability (P<0.05 vs AI-rHDL). In vitro antioxidation against low-density lipoprotein assays indicated that rHDLs containing apoA-V had increasing oxidation resistance against low-density lipoprotein (LDL) with higher apoA-V contents. Finally, cellular uptake of oxLDL and intracellular lipids suggested an apparent oxidation resistance to LDL oxidation in vitro and a reduced intracellular lipid accumulation in THP-1-derived macrophages, with AIM-rHDL demonstrating the greatest ability to decrease intracellular lipid accumulation. Different proportions of apolipoprotein A-I cysteine mutants and apolipoprotein A-V of rHDL changed the lipid binding capacity, particle size, and antioxidant capacity. These changes may show a beneficial effect of rHDL on atherosclerosis.

Objective: Exosomes (Exos) are membrane-encased vesicles derived by nearly all cell types for intercellular communication and regulation. They also received attention for their use as natural therapeutic platforms and drug delivery system. Classically activated M1 macrophages suppress tumor growth by releasing pro-inflammatory factors. This study investigated the suitability of M1-exosomes (M1-Exos) as drug carrier and their effect on the NF-κB signal pathway and further detected whether macrophages repolarization can potentiate the antitumor activities of chemotherapeutics. Methods: M1-Exos were isolated from M1-macrophages by ultracentrifugation and characterized by transmission electron, nanoparticle tracking analysis, dynamic light scattering and western blot. Then M1-Exos were used as Paclitaxel (PTX) carriers to prepare a nano-formulation (PTX- M1-Exos). A relatively simple slight sonication method was used to prepare the drug delivery system (PTX-M1-Exos). The cytotoxicity of PTX-M1-Exos on cancer cells was detected by MTT and flow cytometry in vitro. 4T1 tumor bearing mice were used to perform the therapeutic effect of PTX-M1-Exos in vivo. Results: The expression of caspase-3 in breast cancer cells was increased when co-incubated with macrophages in the presence of M1-Exos in vitro. The production of pro-inflammatory cytokines was increased after exposure of macrophages in M1-Exos. M1-Exos provided a pro-inflammatory environment which enhanced the anti-tumor activity via caspase-3 mediated pathway. The treatment of M1-Exos to the tumor bearing mice exhibit anti-tumor effects in vivo. Meanwhile, the treatment of PTX-M1-Exos demonstrated higher anti-tumor effects than the M1-Exos or PTX group. Conclusion: The results in our study indicate that the M1-Exos act as the carrier to deliver PTX into the tumor tissues, and also enhance the anti-tumor effects of chemotherapeutics in tumor bearing mice.

Side population (SP) cells are involved in the development of multidrug resistance (MDR) in human multiple myeloma (MM), due to their cancer stem cell (CSC)‑like phenotypes. ATP‑binding cassette (ABC) drug transporter proteins have been reported to be closely associated with MDR in leukemia; however, the correlation between ABC proteins and the progression of MM remains unclear. The present study used MM cell lines and clinical samples to determine the role of ABC subfamily G member 2 (ABCG2) in MM via flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blotting. SP cells sorted from MM cell lines, including NCI‑H929 cells, via fluorescence‑activated cell sorting, exhibited CSC‑like phenotypes and expressed high levels of ABCG2. Expression of ABCG2 and activation of the phosphatidylinositol 3‑kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway was positively associated with the proportion of SP cells in the NCI‑H929 cell line. In addition, suppression of the PI3K/AKT pathway using LY294002 or rapamycin counteracted the protective effects of ABCG2 against chemotherapeutic drug treatment. Mechanistically, PI3K/AKT signaling may regulate ABCG2 expression, and ABCG2 may regulate phosphatase and tensin homolog expression via a potential negative feedback loop. Furthermore, SP cell proportion, ABCG2 expression and PI3K/AKT pathway activation were associated with disease progression in patients with MM. These findings indicated the critical roles of ABCG2 and PI3K/AKT signaling in controlling stemness of MM cells, and suggested a novel strategy for targeting ABCG2 and PI3K/AKT signaling to treat MM with MDR.

Crustacea, the subphylum of Arthropoda which dominates the aquatic environment, is of major importance in ecology and fisheries. Here we report the genome sequence of the Pacific white shrimp Litopenaeus vannamei, covering ~1.66 Gb (scaffold N50 605.56 Kb) with 25,596 protein-coding genes and a high proportion of simple sequence repeats (>23.93%). The expansion of genes related to vision and locomotion is probably central to its benthic adaptation. Frequent molting of the shrimp may be explained by an intensified ecdysone signal pathway through gene expansion and positive selection. As an important aquaculture organism, L. vannamei has been subjected to high selection pressure during the past 30 years of breeding, and this has had a considerable impact on its genome. Decoding the L. vannamei genome not only provides an insight into the genetic underpinnings of specific biological processes, but also provides valuable information for enhancing crustacean aquaculture.

Average daily gain (ADG) is an important trait that contributes to the production efficiency and economic benefits in the beef cattle industry. The molecular mechanisms of ADG have not yet been fully explored because most recent association studies for ADG are based on SNPs or haplotypes. We reported a systematic CNV discovery and association analysis for ADG in Chinese Simmental beef cattle.

Chimeric antigen receptor T cell (CART) therapy is currently one of the most promising treatment approaches in cancer immunotherapy. However, the immunosuppressive nature of the tumor microenvironment, in particular increased reactive oxygen species (ROS) levels, provides considerable limitations. In this study, we aimed to exploit increased ROS levels in the tumor microenvironment with prodrugs of ROS accelerators, which are specifically activated in cancer cells. Upon activation, ROS accelerators induce further generation of ROS. This leads to an accumulation of ROS in tumor cells. We hypothesized that the latter cells will be more susceptible to CARTs. CD19-specific CARTs were generated with a CD19.CAR.CD28.CD137zeta third-generation retroviral vector. Cytotoxicity was determined by chromium-51 release assay. Influence of the ROS accelerators on viability and phenotype of CARTs was determined by flow cytometry. The combination of CARTs with the ROS accelerator PipFcB significantly increased their cytotoxicity in the Burkitt lymphoma cell lines Raji and Daudi, as well as primary chronic lymphocytic leukemia cells. Exposure of CARTs to PipFcB for 48 h did not influence T cell exhaustion, viability, or T cell subpopulations. In summary, the combination of CARTs with ROS accelerators may improve adoptive immunotherapy and help to overcome tumor microenvironment-mediated treatment resistance.

Early screening of pathogenic bacteria is key to preventing and controlling outbreaks of foodborne diseases. In this study, protein-inorganic hybrid nanoflowers were synthesized for signal amplification and used with a calcium ion selective electrode (Ca-ISE) to establish a new enzyme-free assay for rapid and sensitive detection of Salmonella. Calcium hydrophosphate crystals were first conjugated with polyclonal antibodies against Salmonella to synthesize immune calcium nanoflowers (CaNFs), and streptavidin modified magnetic nanobeads (MNBs) were conjugated with biotinylated monoclonal antibodies against Salmonella to form immune MNBs. After target bacteria were separated using immune MNBs to form magnetic bacteria, immune CaNFs were conjugated with magnetic bacteria to form nanoflower conjugated bacteria. Then, hydrogen chloride was used to release calcium ions from nanoflower conjugated bacteria. After magnetic separation, the supernatant was finally injected as a continuous-flow to fluidic chip with Ca-ISE for specific detection of calcium ions. The supernatant's potential had a good linear relationship with bacteria concentration, and this assay was able to detect the S. Typhimurium cells as low as 28 colony forming units/mL within two hours. The mean recovery of target bacteria in spiked chicken samples was 95.0%. This proposed assay shows the potential for rapid, sensitive, and on-line detection of foodborne pathogens.

Aberrant expression of zinc-finger proteins has been extensively reported to contribute to malignant progression in a variety of cancers. However, clinical significance and biological roles of ZNF280A in the field of cancer are poorly known. In this study, the expression of ZNF280A was detected in clinical colorectal cancer (CRC) tissues. Functional experiments in vitro and animal experiment in vivo were performed to measure the effect of ZNF280A on the proliferation and tumorigenesis in CRC cells. Western blot and luciferase assays were used to identify the underlying pathway mediating the biological roles of ZNF280A in CRC. Here we report that ZNF280A was upregulated in CRC tissues and cells and a high expression of ZNF280A correlated with tumor, lymph node, and metastasis (TNM) classifications, clinical stage, and predicted poor prognosis and disease progression in CRC patients. Moreover, silencing ZNF280A repressed proliferation and induced G0 and/or G1 arrest in vitro, and it inhibited tumorigenesis of CRC cells in vivo. Our results further demonstrate that silencing ZNF280A inhibited the proliferation of CRC cells by activating Hippo signaling. Therefore, our results uncover a novel mechanistic understanding of ZNF280A-mediated tumor progression in CRC, and meanwhile they provide a novel prognostic factor in CRC patients and a potential therapeutic target for the treatment of CRC.

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Here, we analyzed the impact of local and systemic environments on the tumor response to preoperative chemoradiotherapy in rectal cancer. We recruited 141 patients with rectal cancer treated with nCRT. We evaluated the local tumor environment, including tumor-infiltrating lymphocytes (TILs), intratumor budding (ITB), and the systemic inflammatory environment, including the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) level. Our finding revealed that tumor regression was significantly associated with the density of CD8+ TILs in the intraepithelial, the presence of ITB, the combination of NLR and CRP (NLR-CRP) value, and the combination of CD8+ intraepithelial TIL (iTIL) density and ITB presence. Moreover, multivariate analysis showed that only the combination of CD8+ iTILs and ITB was an independent predictive factor for the pathological response to nCRT in rectal cancer. Our finding demonstrate that the local tumor environment was a better predictor of the tumor response than the systemic environment and thus provided new insight into screening for patients who are more likely to benefit from cancer treatment.

Entosis is a homogeneous cell-in-cell phenomenon and a non-apoptotic cell death process. Tyrosine kinase inhibitors have been used in the treatment of prostate cancer and have already demonstrated efficacy in a clinical setting. The present study investigated the role of entosis in prostate cancer treated with the tyrosine kinase inhibitor nintedanib. Prostate cancer cells were treated with nintedanib in vitro and entosis was observed. Mice xenografts were created to evaluate whether nintedanib is able to induce entosis in vivo. The reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were performed to investigate whether the entosis pathway is induced by nintedanib. It was also investigated whether entosis can contribute to cell survival and progression under nintedanib stress, and nintedanib was revealed to enhance prostate cancer cell entosis. Nintedanib-induced entosis in prostate cancer cells occurred through phosphoinositide 3-kinase/cell division cycle 42 (CDC42) inhibition, followed by the upregulation of epithelial (E-)cadherin and components of the Rho kinase (ROCK) signaling pathway. In addition, nintedanib-resistant cells exhibiting entosis had a higher invasive ability. In addition, in vivo treatment of mice xenografts with nintedanib also increased the expression of E-cadherin and components of the ROCK signaling pathway. Nintedanib can promote entosis during prostate cancer treatment by modulating the CDC42 pathway. Furthermore, prostate cancer cells acquired nintedanib resistance and survived by activating entosis.

Adult hippocampal neurogenesis, a process considered important for hippocampal function, is regulated at multiple molecular levels. Mutations in the gene encoding the WD40 repeat-containing protein WDR81 are associated with neurological disorders, including cerebellar ataxia, mental retardation, quadrupedal locomotion syndrome (CAMRQ2), and microcephaly. In this study, we show that ablation of WDR81 in adult neural progenitor cells (aNPCs) markedly reduced adult hippocampal neurogenesis and impaired hippocampus-dependent learning. WDR81 suppresses endosomal PtdIns3P synthesis, likely by inhibiting the assembly of the PI3K-III complex. In the absence of WDR81, endosomal PtdIns3P levels are greatly elevated, leading to endosomal persistence of the PtdIns3P-binding protein SARA and consequently hyperactivation of SARA-dependent TGFβ signaling. Inhibition of PI3K-III activity or suppression of SARA-dependent TGFβ signaling markedly ameliorated the defective adult neurogenesis in WDR81-deficient mice. Taken together, these findings not only uncover the requirement for the WDR81-SARA-TGFβ axis in adult hippocampal neurogenesis, but also suggest that defective adult hippocampal neurogenesis contributes to the etiology of WDR81-related neurological diseases.