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Previous studies have suggested that gut microbiota plays a critical role in colorectal cancer (CRC). Although preliminary comparisons of the oral and gut microbiota between CRC and healthy control (HC) patients have been made, the association between microbiome abundance and host clinical factors has not been fully illustrated, especially oral health conditions. Matching samples of unstimulated saliva, cancer tissues or biopsies and stools were collected from 30 CRC and 30 HC patients from Shanghai Jiao Tong University affiliated Renji Hospital for 16S rRNA sequencing analysis. The diversity in salivary and mucosal microbiome, but not stool microbiome of CRC group, was significantly different from that of HC, as demonstrated by the Principal Component Analysis. Logistic regression analysis revealed that older age and higher oral hygiene index (OHI) were independent risk factors for CRC, with odds ratios and 95% confidence intervals of 1.159 (1.045-1.284) and 4.398 (1.328-14.567), respectively. Salivary Firmicutes to Bacteroides ratio in CRC was significantly higher than that in the HC group (P < 0.001), while the mucosal ratio was slightly decreased in CRC (P < 0.05). Salivary Rothia and Streptococcus levels were positively correlated with OHI, while Alloprevotella, Fusobacterium, Peptostreptoccus and Prevotella genera levels were negatively associated with OHI. NetShift analysis revealed that salivary Peptococcus, Centipeda and mucosal Subdoligranulum genus might act as key drivers during the process of carcinogenesis. In conclusion, the current study provides insights into the potential influence of host clinical factors on oral and gut microbiome composition and can be a guide for future studies.

The molecular mechanisms that control the development of colorectal cancer (CRC) remain poorly defined. Here we show Synbindin promoted CRC oncogenesis by activating Wnt signaling and altering gut microbiome. Synbindin upregulation in human CRCs was associated with poor patient prognosis. Intestine-specific disruption of Synbindin balanced the disturbed gut microbiota and protected mice against tumor formation in the colitis-associated cancer (CAC) model. The protective role was compromised after gut microbiota depletion. In host, increased goblet cells and mucin2 expression, together with increased intestinal epithelial cells (IECs) apoptosis and decreased epithelial proliferation were observed. Further transcriptomic sequencing identified Wnt signaling a major regulatory node downstream of Synbindin. Combined molecular and cellular characterizations revealed that Synbindin confers Disheveled-3 (DVL3)-based signalosome assembly and acts as a modular scaffold for DVL3 and Axin2 complex, orchestrating the intensity of Wnt signaling. These findings identify a critical role of Synbindin in gut microbiome composition and Wnt signaling activation in colorectal carcinogenesis, and highlight Synbindin as an adaptor protein with multifaceted roles.

Platelet-rich plasma (PRP) has been reported to alleviate degenerative pathological damage to joint cartilage. This study aimed to investigate the effect of PRP on Wnt/β-catenin signaling in rabbit chondrocytes.Using 3-month-old New Zealand white rabbits, PRP was prepared from venous blood, and chondrocytes were cultured from knee joint cartilage and identified by staining for type II collagen and proteoglycan. The effects of PRP on chondrocyte viability were measured. The chondrocytes were divided into 5 groups: control, IL-1β, PRP (100-fold dilution), Dkk-1 (100ng/mL) and Dkk-1+PRP. The IL-1β, PRP, Dkk-1 and Dkk-1+PRP groups were treated with interleukin (IL)-1β (50μL, 10μg/mL) for24h. Chondrocyte morphology was observed by electron microscopy. Levels of carboxy terminal peptide (CTX-II) and cartilage oligomeric matrix protein (COMP) in culture media were measured by ELISA. Wnt-1, β-catenin and GSK-3β mRNA and protein expression were determined by RT-PCR and western blot respectively.PRP enhanced chondrocyte proliferation. Chondrocytes in the IL-1β group showed ultrastructural abnormalities that were less pronounced in the PRP, Dkk-1 and Dkk-1+PRP groups. CTX-II and COMP concentrations were higher in the IL-1β group than in the control, PRP, Dkk-1 and Dkk-1+PRP groups (P0.05). The IL-1β group had higher mRNA and protein Wnt1 and β-catenin levels and lower GSK-3β levels than the control, PRP, Dkk-1 and Dkk-1+PRP groups (P0.05).PRP may protect chondrocytes activated by IL-1β via inhibiting Wnt/β-catenin signaling.

The design and fabrication of new type viscosity sensor on molecular scale will enrich the detection means in both physical and life sciences. In this work, a rotor-containing fluorescent dye was prepared, which can reveal a typical viscosity-sensitive behavior due to the environment-induced non-radiative decay. The viscosity-sensitive behavior of this dye could be tunable (locked and activated) in aqueous environment, either with the reversible light-driven trans / cis -photoisomerization of the cyanostilbene moiety, or with the reversible assembly/disassembly process of β-cyclodextrin (β-CD) to the rotor part. Such dual-mode tunable viscosity sensitivity can be well distinguished by fluorescent spectra. A slope method, on double-logarithmic plots of the fluorescent signal to the corresponding environmental viscosity, makes a quantitative estimation to the tunable viscosity sensitivity, featuring the ‘Activated’ and the ‘Locked’ state in this molecular-scale viscometer.

A bistable porphyrin-containing [2]rotaxane is synthesized with a shuttling benzylic-amide macrocycle mechanically locked onto the thread subunit by formations of H-bonds with two potential stations. This macrocycle comprises two pyridine groups, which would be easily coordinated with zinc porphyrin. The Zn(II) coordination of porphyrin moiety on the thread subunit, immediately followed by the coordination with pyridine groups on the macrocycle, leads to an intermolecular axle-macrocycle-type nanostructure. Moreover, the self-assembly way shows great difference from the two states of the rotaxane monomer: The coordination-driven self-organization of the trans-state E2 leads to a network structure, whereas the cis-state Z2 gives birth to an irregular assembly.

A novel pH-responsive and photo-isomerizing β-cyclodextrin (β-CD) derivative DACD was synthesized and fully characterized by 1H-NMR, 13C-NMR, and HRMS. At room temperature, this compound would self-assemble to layer aggregations in an aqueous environment. The aggregated state can reversibly switch to a monomeric solution state attributed to the hydrophobic competition of an additional substance to the β-CD cavity. This self-aggregatable cyclodextrin derivative based nanosystem functioned by switching between the aggregated and monomeric state. An effective address-crossing digital information system, in response to pH and UV stimuli, was demonstrated based on such mechanism. This chemical system, capable of data memories and logic functions in nanoscale, can mimic the functions of pointer-based data processing.

The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK-MAPK) pathway is a critical intermediary for cell proliferation, differentiation, and survival. In the human colon cancer cell line SW1116, treatment with the DNA methyltransferase 1 (DNMT1) inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) or the ERK-MAPK inhibitors PD98059 or rottlerin, or transient transfection with the MAP/ERK kinase (MEK)1/2 small interfering RNA down-regulates DNMT1 and proliferating cell nuclear antigen levels. In this report, we found that drug treatment or small interfering RNA transfection of SW1116 cells induced promoter demethylation of the p16(INK4A) and p21(WAF1) genes, which up-regulated their mRNA and protein expression levels. Flow cytometry revealed that rottlerin treatment induced cell cycle arrest at phase G(1) (p0.05). Thus, the ERK-MAPK inhibitor treatment or siRNA-mediated knockdown of ERK-MAPK decreases DNA methylation via down-regulating DNMT1 expression and other unknown mediator(s) in SW1116 colon cancer cells.

Aims: To investigate the antitumor effects of probiotics Clostridium butyricum and Bacillus subtilis on colorectal cancer (CRC) progression. Materials & methods: The effects of C. butyricum and B. subtilis on CRC cells were studied. Male C57BL/6 mice with 1,2-dimethylhydrazine dihydrochloride (DMH)-induced CRC were intervened by these two probiotics and the antitumor effects were examined by comparing the tumor incidence and detecting the inflammatory and immune-related markers. Results & conclusions: C. butyricum and B. subtilis inhibited the proliferation of CRC cells, caused cell cycle arrest and promoted apoptosis. In vivo, these two probiotics inhibited the development of DMH-induced CRC. The molecular mechanism involved reduced inflammation and improved immune homeostasis. This work establishes a basis for the protective role of probiotics B. subtilis and C. butyricum in intestinal tumorigenesis.

Two novel bimetallic ruthenium complexes with an azobenzene-containing ligand were synthesized. Their photochromic properties were investigated.

The extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK-MAPK) is critical in human malignancies. It remained to be established whether DNA methyltransferases (Dnmt) and proliferating cell nuclear antigen (PCNA) involved in DNA methylation during RAF-transformed cell proliferation. The plasmid of constitutively active RAF was used to transfect gastric cell GES-1 and cancer cell AGS. RAF promoted cell proliferation, growth in soft agar and induced cell cycle progress faster than empty plasmid by accelerating G1/S transition in both cell lines, a massive induction of cyclin D1 and PCNA expression was observed, along with reduced expression of p16INK4A, p21WAF1 and p27KIP1. Methylation-specific polymerase chain reaction and bisulfite sequencing showed that the promoter of p16INK4A was methylated in RAF-transformed cells, treatment with 5-aza-dC or PD98059 restored the expression of p16INK4A, increased p21WAF1 and p27KIP1 partially, associated with upregulation of the activity of Dnmt in RAF-transformed cell GES-1, and also decreased the hypermethylation status of p16INK4A, but not all CpG islands of p21WAF1 and p27KIP1. These data suggest that RAF may induce cell proliferation through hypermethylation of tumor suppressor gene p16INK4A, while the epigenetic inactivation of p21WAF1 and p27KIP1 may be not a key factor in RAF-transformed cells.

To evaluate the effect of PKC-delta inhibitor Rottlerin on human colon cancer cells and its mechanism.Human colon cancer cell line SW1116 cells were treated with Rottlerin. The transcriptional level of DNA methyltransferase (Dnmt)1, Dnmt3a and Dnmt3b was detected by real-time RT-PCR. Cell cycle distribution was evaluated by flow cytometry (FCM). In addition, cellular morphological changes were examined by light microscopy.PKC-delta inhibitor decreased the expression of Dnmt1, Dnmt3a mRNA, up-regulated APC, p21(WAF1) and p16(INK4A) mRNA. Demonstarted by flow cytometry, Rottlerin increased the percentage of cell cycle G0/G1 phase cell numbers (P = 0.02) and decreased the percentage of cell cycle G2/M phase cell numbers (P = 0.01). Remarkable changes of cellular morphology were observed under light microscope: The volume and cytoplasm of cells treated with Rottlerin were increased. The cell contour was not very clear, and mitotic figures were less frequently seen.PKC-delta inhibitor Rottlerin inhibites cell division and proliferation of the colon cancer SW1116 cells through regulating DNA methylation and blocking the signaling pathway of mitogen-activated protein kinase (MAPK).