Interaction between intestinal microbiota and tumour immunity in the tumour microenvironment.

In recent years, an increasing number of studies have reported that intestinal microbiota have an important effect on tumour immunity by affecting the tumour microenvironment (TME). The intestinal microbiota are closely associated with various immune cells, such as T lymphocytes, natural killer cells (NK cells) and macrophages. Some bacteria, such as Akkermansia muciniphila (A. muciniphila) and Lactobacillus reuteri (L. reuteri), have been shown to improve the effect of tumour immunity. Furthermore, microbial imbalance, such as the increased abundance of Fusobacterium nucleatum (F. nucleatum) and Helicobacter hepaticus (H. hepaticus), generally causes tumour formation and progression. In addition, some microbiota also play important roles in tumour immunotherapy, especially PD-L1-related therapies. Therefore, what is the relationship between these processes and how do they affect each other? In this review, we summarize the interactions and corresponding mechanisms among the intestinal microbiota, immune system and TME to facilitate the research and development of new targeted drugs and provide new approaches to tumour therapy.

Anatomical study of the left colic artery in laparoscopic-assisted colorectal surgery.

BACKGROUND: It is important for lymph node dissection around the inferior mesenteric artery (IMA) with preservation of the left colic artery (LCA) to be aware of the track and the length of the LCA. We aimed to investigate the branching pattern and trajectory of LCA and measure the distances from the root of the IMA to the origin of the LCA (D mm) and from the origin of LCA to intersection of LCA and IMV (d mm) during laparoscopic left-sided colorectal operations. METHODS: We analyzed 106 patients who underwent laparoscope-assisted left-side colorectal surgery during laparoscopic surgery. The branching patterns among the IMA, LCA, and sigmoidal trunk were evaluated; the trajectory of LCA was examined; the D mm and d mm were measured using a length of silk in the surgical operation. RESULTS: In 59.5% patients, the LCA arose independently from the sigmoidal trunk (type A); in 8.5% patients, the LCA and sigmoidal trunk arose from the IMA at the same point (type B); in 29.2% patients, the LCA and sigmoidal trunk had a common trunk (type C); the LCA did not exist in 2.8% (type D).The D mm and d mm for all cases ranged from 15.0 to 65.3 mm (median, 43.1 mm) and from 20.3 to 46.2 mm (median, 34.8 mm), respectively. 74.8% of the LCA went straight upper left and upward to proximal part of descending colon (type I), 25.2% went to the lower left at first, then turned to travel straight upward to proximal part of descending colon (type II). CONCLUSION: This study showed the anatomic variations of LCA during laparoscopic left-sided colorectal operation, which would help surgeons safely perform laparoscopic surgery in the left-side colon and rectum.

Exosomal circRNAs: biogenesis, effect and application in human diseases.

Exosomes have emerged as critical mediators of intercellular communication, both locally and systemically, by regulating a diverse range of biological processes between cells. Circular RNA (circRNA) is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circular RNAs have been identified for their enrichment and stability in exosomes. In this review, we outline the origin, biogenesis and function of exosomal circRNAs as well as their roles in various diseases. Although their precise roles and mechanisms of gene regulation remain largely elusive, exosomal circRNAs have potential applications as disease biomarkers and novel therapeutic targets.

Effects of exosomes on pre-metastatic niche formation in tumors.

A pre-metastatic niche is a microenvironment prepared for the colonization of circulating tumor cells in specific organs. Exosomes are extracellular vesicles with a variety of biological functions. Exosomes play an irreplaceable role in the development of pre-metastatic niches, and mainly function as communication medium. In this review, we analyzed the effects of exosomes on pre-metastatic niches from various perspectives, including inflammation, immune response, angiogenesis, organotropism, matrix remodeling and biomarker expression. In particular, exosomes express programmed death ligand 1 (PD-L1) and cause the immune escape of tumor cells. The immunomodulatory effects of exosomes and their potential in liquid diagnosis have drawn our attention. The potential value of exosomes and pre-metastatic niches will be realized in the field of immunity therapy.

Effect of exosomal miRNA on cancer biology and clinical applications.

Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.

Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment.

Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively sorted into exosomes and can regulate cancer onset and progression in a variety of ways. In this review, we summarize the characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer. We provide an overview of current research on exosomal lncRNAs in tumor microenvironments, especially the functions of exosomal lncRNAs in regulating tumor biology. A deeper understanding of the role of exosomal lncRNAs in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.

The Biological Effect and Clinical Application of Long Noncoding RNAs in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in the world. Easier recurrence and metastasis is the main cause of mortality in CRC patients, and the markers applied for diagnosis and treatment of CRC is still urgently needed to early diagnose and evaluate therapeutic effect. Long noncoding RNA (lncRNA) is a class of noncoding RNA that the length is more than 200 nucleotides. With the development of sequencing technique about transcriptome, increasing lncRNAs are focused on their function and mechanism related to the nosogenesis and pathology of CRC. Recent studies report that lncRNAs acted as crucial role in CRC and could be as biomarker for CRC diagnosis and treatment. In this review, we display the regulation of lncRNA by interacting with DNA, RNA and protein and highlight the double role of lncRNAs as oncogene or anti-tumor gene involved in Wnt signaling pathway, p53 signaling pathway or others to be an regulator in CRC development. Lastly, we discuss some new finding of lncRNAs, especially lncRNA in exosome, which could be as potential markers for diagnosis and treatment of CRC in future.

Identification of liver metastasis-associated genes in human colon carcinoma by mRNA profiling.

OBJECTIVE: Liver metastasis, which contributes substantially to high mortality, is the most common recurrent mode of colon carcinoma. Thus, it is necessary to identify genes implicated in metastatic colonization of the liver in colon carcinoma. METHODS: We compared mRNA profiling in 18 normal colon mucosa (N), 20 primary tumors (T) and 19 liver metastases (M) samples from the dataset GSE49355 and GSE62321 of Gene Expression Omnibus (GEO) database. Gene ontology (GO) and pathways of the identified genes were analyzed. Co-expression network and protein-protein interaction (PPI) network were employed to identify the interaction relationship. Survival analyses based on The Cancer Genome Atlas (TCGA) database were used to further screening. Then, the candidate genes were validated by our data. RESULTS: We identified 22 specific genes related to liver metastasis and they were strongly associated with cell migration, adhesion, proliferation and immune response. Simultaneously, the results showed that C-X-C motif chemokine ligand 14 (CXCL14) might be a favorable prediction factor for survival of patients with colon carcinoma. Importantly, our validated data further suggested that lower CXCL14 represented poorer outcome and contributed to metastasis. Gene set enrichment analysis (GSEA) showed that CXCL14 was negatively related to the regulation of stem cell proliferation and epithelial to mesenchymal transition (EMT). CONCLUSIONS: CXCL14 was identified as a crucial anti-metastasis regulator of colon carcinoma for the first time, and might provide novel therapeutic strategies for colon carcinoma patients to improve prognosis and prevent metastasis.

Effects of mine wastewater irrigation on activities of soil enzymes and physiological properties, heavy metal uptake and grain yield in winter wheat.

In China, coal-mining industries are mainly located in the water shortage areas including arid or semiarid areas. Mine wastewater is used for irrigation of agricultural land in these areas. However, few studies have been conducted to address ecological and food safety risks caused by mine wastewater irrigation. In this research, a pot experiment was performed to examine the effects of mine wastewater irrigation on soil enzymes, physiological properties of wheat and potential risks of heavy metal contamination to wheat crop. Plants were subjected to three mine wastewater irrigation treatments: leacheate of coal gangue (T1), coal-washing wastewater (T2) and precipitated coal-washing wastewater (T3). Plants irrigated with well water were taken as the control (CK). The results showed that mine wastewater irrigation caused adverse effects on soil enzymes, physiological properties and grain yield of winter wheat. At anthesis, T1, T2 and T3 treatments significantly reduced the activities of soil enzymes (urease, sucrase and catalase), root activity and net photosynthetic rate of wheat compared to CK. At maturity, grain yield was decreased by 17.8%, 15.4% and 9.8% by T1, T2 and T3, respectively, as compared to that of CK. Importantly, mine wastewater irrigation resulted in accumulation of heavy metals (Cr, Pb, Cu and Zn) in wheat grain. Contents of these heavy metals in grains of winter wheat subjected to mine wastewater irrigation were significantly higher than those in CK. The comprehensive contamination indexes of wheat grain in T1, T2 and T3 all reached high pollution level. Our results showed that mine wastewater irrigation significantly increased the pollution risk of heavy metals, thus unsuitable for crop irrigation.

Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis.

BACKGROUND: Wear particle-induced periprosthetic osteolysis that results in aseptic loosening is the most common cause of long-term failure after total joint replacement. MATERIALS AND METHODS: Icariin (ICA), a flavonoid isolated from Epimedium pubescens, inhibits osteoclast formation, but its effects on wear particle-induced inflammatory osteoclastogenesis remains unclear. We investigated the role of ICA in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which is stimulated by titanium (Ti) particles and the receptor activator of NF-κB ligand. RESULTS: ICA effectively inhibited osteoclast formation and bone resorption in the differentiation medium. ICA (10(-7) mol/L) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells compared with the control, and significantly reduced the percentage of the surface covered by resorption lacunae. Quantitative real-time polymerase chain reaction analysis showed that ICA inhibited messenger RNA expression for the receptor activator of nuclear factor-κB, cathepsin K, tartrate-resistant acid phosphatase-positive, and matrix metalloproteinase-9 in RAW264.7 cells stimulated by Ti particles and receptor activator of NF-κB ligand. ICA also reduced pro-inflammatory cytokine expression of interleukin-1ß and tumor necrosis factor-α in RAW264.7 cells cultured with Ti particles. In addition, incubation with cholecystokinin-8 showed that ICA had no toxic effects on RAW264.7 cells. CONCLUSIONS: ICA possibly elicited inhibitory effects on inflammatory osteoclastogenesis induced by Ti particles, indicating that ICA may be useful for the prevention and treatment of wear particle-induced osteolysis.

Renal responses to acute volume expansion in spontaneously hypertensive rats is related to the baseline sodium excretion.

Essential hypertension is associated with an exaggerated natriuresis in response to intravenous infusion of isotonic saline. We examined proximal tubular fluid output and segmental tubular handling of sodium in conscious spontaneously hypertensive rats (SHR), their normotensive counterparts Wistar-Kyoto rats (WKY), and ordinary Wistar rats using servo-controlled sodium and fluid balance and Li clearance technique. Sodium (Na) excretion rose to 2.72 ± 0.75 (by a factor of 8) and 1.73 ± 0.68 µmol/min (by a factor of 6.3) (p < 0.05) in SHR and WKY, respectively, thus confirming the presence of exaggerated natriuresis in SHR. FE(Li) rose to 34 ± 4 and 29 ± 2 (p < 0.05) and C(Na)/C(Li) rose to 3.0 ± 0.8 and 2.0 ± 0.6 (p < 0.05) in SHR and WKY, respectively, demonstrating that Na reabsorption in both the proximal and the distal nephron was involved. Additional experiments showed that giving the rats saline instead of water to drink for four days prior to the clearance measurement led to a remarkable increase in the natriuretic response to volume expansion. There was a close correlation between the peak increase in FE(Na) and the logarithmic values of the baseline FE(Na) values. In conclusion, the study confirms the presence of an exaggerated natriuresis in response to volume expansion in conscious SHR rats compared to WKY rats, and that the renal response to acute volume expansion is related to the baseline sodium excretion.

Factors that contribute to trait mindfulness level among hospitalized patients with major depressive disorder.

Mindfulness training among patients with major depressive disorder (MDD) reduces symptoms, prevents relapse, improves prognosis, and is more efficient for those with a high level of trait mindfulness. Upon hospital admission, 126 MDD patients completed the Beck Depression Inventory (BDI), World Health Organization Quality of Life Brief, Five-Factor Mindfulness Questionnaire (FFMQ), and the Rumination Response Scale (RRS). The 65 patients that scored less than the median of all subjects on the FFMQ were placed into the low mindfulness level (LML) group. The other 61 patients were placed in the high mindfulness level (HML) group. All facet scores were statistically different between the mental health assessment scores of the HML and LML groups except for RRS brooding and FFMQ nonjudgement. Trait mindfulness level exhibited a negative and bidirectional association with MDD severity primarily through the facets of description and aware actions. Trait mindfulness was also related positively with age primarily through the facets of nonreactivity and nonjudgement. Being married is positively associated with trait mindfulness levels primarily through the facet of observation and by an associated increase in perceived quality of life. Mindfulness training prior to MDD diagnosis also associates positively with trait mindfulness level. Hospitalized MDD patients should have their trait mindfulness levels characterized to predict treatment efficiency, help establish a prognosis, and identify mindfulness-related therapeutic targets.

Age-related changes in expression in renal AQPs in response to congenital, partial, unilateral ureteral obstruction in rats.

Previously we demonstrated that neonatally induced partial unilateral ureteral obstruction (PUUO) in rats is associated with changes in the abundance of renal acid-base transporters that were paralleled by reduction in renal functions dependent on the severity and duration of obstruction. The aim of the present study was to identify whether changes in renal aquaporin abundance are age-dependent. Semiquantitative immunoblotting and immunohistochemistry were used to examine the changes in abundance of AQP1, AQP2, p-S256AQP2 (AQP2 phosphorylated at consensus site Ser(256)) and AQP3 in the kidneys of rats with neonatally induced PUUO within the first 48 h of life, and then monitored for 7 or 14 weeks. Protein abundance of AQP2 and AQP3 increased in both obstructed and non-obstructed kidneys 7 weeks after induction of neonatal PUUO (PUUO-7W). In contrast, AQP1 and AQP2 protein abundance in the obstructed kidney were reduced after 14 weeks of PUUO (PUUO-14W). Importantly, pS256-AQP2 protein abundance was reduced in obstructed kidneys of both PUUO-7W and PUUO-14W. Immunohistochemistry confirmed the persistent pS256-AQP2 downregulation in both PUUO-7W and PUUO-14W rats. The study shows that the protein abundance of AQP1, AQP2, and AQP3 in the obstructed kidney is increased in PUUO-7W, which may be a compensatory phenomenon and reduced in PUUO-14W rats suggesting a time-/age-dependent dysregulation in response to PUUO. pS256-AQP2 protein abundance is reduced consistent with obstruction-induced direct effects in the apical part of the collecting duct principal cells in response to PUUO.

Bis(2-amino-benzothia-zol-3-ium) bis-(7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl-ato-κ(3)O(2),O(3),O(7))nickelate(II) hexa-hydrate.

In the title compound, (C(7)H(7)N(2)S)(2)[Ni(C(8)H(8)O(5))(2)]·6H(2)O, the Ni(II) cation is located on an inversion center and is O,O',O''-chelated by two symmetry-related 7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl-ate anions in a distorted octa-hedral geometry. The 2-amino-benzothia-zol-3-ium cation links with the Ni complex anion via N-H⋯O hydrogen bonding. Extensive O-H⋯O and N-H⋯O hydrogen bonds involving the lattice water mol-ecules also occur in the crystal structure.

Exosome-derived noncoding RNAs: Function, mechanism, and application in tumor angiogenesis.

Exosomes are extracellular vesicles released by various cell types that perform various biological functions, mainly mediating communication between different cells, especially those active in cancer. Noncoding RNAs (ncRNAs), of which there are many types, were recently identified as enriched and stable in the exocrine region and play various roles in the occurrence and progression of cancer. Abnormal angiogenesis has been confirmed to be related to human cancer. An increasing number of studies have shown that exosome-derived ncRNAs play an important role in tumor angiogenesis. In this review, we briefly outline the characteristics of exosomes, ncRNAs, and tumor angiogenesis. Then, the mechanism of the impact of exosome-derived ncRNAs on tumor angiogenesis is analyzed from various angles. In addition, we focus on the regulatory role of exosome-derived ncRNAs in angiogenesis in different types of cancer. Furthermore, we emphasize the potential role of exosome-derived ncRNAs as biomarkers in cancer diagnosis and prognosis and therapeutic targets in the treatment of tumors.

Bilateral ureteral obstruction induces early downregulation and redistribution of AQP2 and phosphorylated AQP2.

Bilateral ureteral obstruction (BUO) is characterized by impairment of urine flow from the kidneys and altered expression of specific membrane proteins in the kidney involved in regulation of renal water and salt transport. Importantly, 24-h BUO reduces the abundance of the collecting duct water channel aquaporin-2 (AQP2) and AQP2 phosphorylated at serine 256 (AQP2pS256). To investigate the mechanism behind downregulation of AQP2 in BUO, rats were subjected to BUO and examined after 2, 6, 12, and 24 h. Q-PCR and immunoblotting showed significantly decreased AQP2 mRNA expression after 2-h BUO and decreased abundance of total AQP2 after 12 and 24 h. In parallel, immunohistochemistry showed weaker labeling of AQP2 at the apical surface of inner medullary collecting ducts (IMCD) compared with controls. The abundance of AQP2pS256 was significantly reduced from 6-h BUO and was confirmed by immunohistochemistry. Importantly, immunoblotting showed reduced abundance of AQP2pS261 after 12- and 24-h BUO mimicking total AQP2. Immunohistochemistry demonstrated early changed intracellular localization of AQP2pS261 in BUO, and colocalization studies showed redistribution from the apical membrane to early endosomes and lysosomes. In conclusion, BUO induces a very early regulation of AQP2 both at the level of abundance and on cellular localization. AQP2 and AQP2 phosphorylated at ser261 redistribute to more intracellular localizations and colocalize with the early endosomal marker EEA1 and the lysosomal marker cathepsin D, suggesting that early downregulation of AQP2 could in part be caused by degradation of AQP2 through a lysosomal degradation pathway.

Regulation of aquaporins and sodium transporter proteins in the solitary kidney in response to partial ureteral obstruction in neonatal rats.

Unilateral ureteral obstruction (UUO) impairs function of the obstructed kidney, and the contralateral nonobstructed kidney compensates depending on the degree and duration of UUO. This study aimed to determine the hemodynamic and molecular changes in the solitary kidney in response to partial ureteral obstruction (PUO) where any compensation from the contralateral kidney was eliminated so that all observed changes in the kidney tissue occurred in the kidney with PUO. Newborn rats were subjected to unilateral left nephrectomy (UNX) within the first 48 h of life and a subset of UNX rats was subjected to severe PUO of the right kidney at day 14. Renal blood flow and whole kidney volume were measured with MRI at week 10. The renal protein abundance of aquaporin 1 (AQP1), AQP2 and AQP3 as well as Na,K-ATPase, NaPi-2 (type 2 sodium-phosphate cotransporter) and NHE3 (type 3 sodium-proton exchanger) were examined by immunoblotting and immunocytochemistry. At 10 weeks of age, the protein abundance of AQP2, AQP3, Na,K-ATPase, NaPi-2 and NHE3 were increased in response to PUO. In contrast, AQP1 expression was markedly decreased compared to sham-operated rats. These findings were confirmed by immunohistochemistry. GFR, urine osmolality and urine sodium excretion were reduced and kidney weight increased in response to PUO. In conclusion, the present study demonstrated major changes in the protein abundance of renal AQP1, AQP2 and AQP3 and sodium transporters in the solitary PUO kidney. These changes were paralleled by decreased urinary sodium excretion and a significant reduction in urinary osmolality from the obstructed kidney, suggesting a functional association between the molecular changes and the ability of the obstructed kidney to handle sodium and water in this solitary kidney model.

Main-Chain Sulfonium-Containing Homopolymers with Negligible Hemolytic Toxicity for Eradication of Bacterial and Fungal Biofilms.

Antimicrobials against planktonic cells and established biofilms at low doses are in increasing demand to tackle antibiotic-resistant biofilm infections. As a promising alternative to antibiotics, cationic polymers can effectively kill planktonic microbes but usually require high concentrations to eradicate the established biofilms. Herein, we developed a series of sulfonium-based homopolymers with cationic sulfoniums and alkane spacers in the main chain. These polysulfoniums presented effective activity against planktonic fungi (Candida albicans) and bacteria (Escherichia coli and Staphylococcus aureus) with minimum inhibition concentrations (MICs) of 0.5-32 µg/mL, and the optimal composition can provide an 80-90% reduction in biofilm mass and >99% killing of Candida albicans and Escherichia coli cells in 3-day mature biofilms at 2 × MIC as well as steadily low hemolytic toxicity. The influence of amphiphilicity and charge density of polysulfonium homopolymers on their antimicrobial activity against planktonic microbes and mature biofilms was investigated to provide insights for effective antimicrobial polymer design.

RNA N 6-Methyladenosine in Cancer Metastasis: Roles, Mechanisms, and Applications.

Cancer metastasis is a symptom of adverse prognosis, a prime origin of therapy failure, and a lethal challenge for cancer patients. N 6-methyladenosine (m6A), the most prevailing modification in messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) of higher eukaryotes, has attracted increasing attention. Growing studies have verified the pivotal roles of m6A methylation in controlling mRNAs and ncRNAs in diverse physiological processes. Remarkably, recent findings have showed that aberrant methylation of m6A-related RNAs could influence cancer metastasis. In this review, we illuminate how m6A modifiers act on mRNAs and ncRNAs and modulate metastasis in several cancers, and put forward the clinical application prospects of m6A methylation.

Derivation and Clinical Validation of a Redox-Driven Prognostic Signature for Colorectal Cancer.

Colorectal cancer (CRC), a seriously threat that endangers public health, has a striking tendency to relapse and metastasize. Redox-related signaling pathways have recently been extensively studied in cancers. However, the study and potential role of redox in CRC remain unelucidated. We developed and validated a risk model for prognosis and recurrence prediction in CRC patients via identifying gene signatures driven by redox-related signaling pathways. The redox-driven prognostic signature (RDPS) was demonstrated to be an independent risk factor for patient survival (including OS and RFS) in four public cohorts and one clinical in-house cohort. Additionally, there was an intimate association between the risk score and tumor immune infiltration, with higher risk score accompanied with less immune cell infiltration. In this study, we used redox-related factors as an entry point, which may provide a broader perspective for prognosis prediction in CRC and have the potential to provide more promising evidence for immunotherapy.