Ac34FGlcNAz is an effective metabolic chemical reporter for O-GlcNAcylated proteins with decreased S-glyco-modification.

O-GlcNAcylation is a ubiquitous post-translational modification governing vital biological processes in cancer, diabetes and neurodegeneration. Metabolic chemical reporters (MCRs) containing bio-orthogonal groups such as azido or alkyne, are widely used for labeling of interested proteins. However, most MCRs developed for O-GlcNAc modification are not specific and always lead to unexpected side reactions termed S-glyco-modification. Here, we attempt to develop a new MCR of Ac34FGlcNAz that replacing the 4-OH of Ac4GlcNAz with fluorine, which is supposed to abolish the epimerization of GALE and enhance the selectivity. The discoveries demonstrate that Ac34FGlcNAz is a powerful MCR for O-GlcNAcylation with high efficiency and the process of this labeling is conducted by the two enzymes of OGT and OGA. Most importantly, Ac34FGlcNAz is predominantly incorporated intracellular proteins in the form of O-linkage and leads to negligible S-glyco-modification, indicating it is a selective MCR for O-GlcNAcylation. Therefore, we reason that Ac34FGlcNAz developed here is a well characterized MCR of O-GlcNAcylation, which provides more choice for label and enrichment of O-GlcNAc associated proteins.

The role of the primary cilium in cancer.

As a common lethal disease, cancer is now responsible for the majority of deaths worldwide and has been the single most important barrier to increasing life expectancy in the world. The pathogenesis of cancer has been the key point of cancer therapeutics research. The primary cilium, a solitary microtubule-based organelle, is considered to be an important sensor for receiving mechanical and chemical stimulation from other cells and environments; it plays an important role in a variety of signal transduction and disease processes. More importantly, the primary cilium can also function as an elaborate structure to regulate cell proliferation because ciliogenesis regulates cell division by sequestering the centriole. Recently, many new findings have suggested that the length and incidence of the primary cilium are closely connected to carcinogenesis and responses to cancer therapy. Here, we review relevant evidences proving that the primary cilium plays a key role in the occurrence and treatment of cancer. We also summarize the primary cilium-associated signaling pathways in cancer, including Wnt signaling, Hedgehog signaling, PDGFR signaling, and Notch signaling, and anticipate that targeting proteins localized in the primary cilium may be a potential anti-cancer strategy.

Clinical characteristics and prognostic significance of galectins for patients with gastric cancer: A meta-analysis.

OBJECTIVE: To explore the relationships between the expression level of different galectins and its prognostic value for patients with gastric cancer. METHODS: The PubMed, EMbase, the Cochrane Library and Web of Science databases were systematically searched. All the eligible studies were included according to the inclusion and exclusion criteria. All the relevant data was extracted by two independent researchers. The quality assessment was conducted according to the evaluation of the quality of prognosis study which published by Harden in 2006. The STATA 12.0 software was used to perform a meta-analysis. RESULTS: All of 8 retrospective case-controlled studies involving 2093 patients with gastric cancer were included in this study. The results of meta-analysis presented that the elevated galectin-1 which is related to the poor overall survival (HR = 1.85, 95% CI: 1.33-2.58; P < 0.001) may predicted a larger tumor size (OR = 2.20, 95% CI: 1.35-3.35; P = 0.001) and was positively associated with the higher expression of VEGF (OR = 1.44, 95% CI: 1.14-1.82; P = 0.002). Moreover, the decreased galectin-3 (HR = 0.49, 95% CI: 0.36-0.67; P < 0.001), galectin-8 (HR = 0.49, 95% CI: 0.36-0.67; P < 0.001) and galectin-9 (HR = 0.78, 95% CI: 0.66-0.92; P = 0.003) were also significantly associated with poorer prognosis. Our meta-analysis also showed that lower expression of galectin-3 was also related to lymphatic vessel invasion (OR = 0.48, 95% CI: 0.26-0.89; P = 0.018), worse TNM stages (OR = 0.47, 95% CI: 0.32-0.40; P < 0.001), deeper invasive depth (OR = 0.33, 95% CI: 0.21-0.51; P < 0.001) and poorer differentiation grade (OR = 0.10, 95% CI: 0.04-0.25; P < 0.001). CONCLUSIONS: High expression of galectin-1 or low expression of galectin-3, -8 and -9 were significantly related to a poorer prognosis for patients with gastric cancer. The expression level of galectins was associated with clinical characteristics and were potential independent prognostic predictor for GC patients.

UBE2T knockdown inhibits gastric cancer progression.

Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for degradation via the proteasome. Here, we examined the effects of UBE2T on the progression of gastric cancer. UBE2T was highly expressed in gastric tumors and gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric cancer cell proliferation and colony formation by promoting cell cycle arrest at G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the invasive and metastatic abilities of gastric cancer cells by altering expression of epithelial-mesenchymal transition (EMT)-related factors. A xenograft model in which nude mice were injected with UBE2T knockdown human gastric cancer cells confirmed that suppression of UBE2T also decreased tumor formation and growth in vivo. Expression levels of CCND1, Phospho-GSK3B, WNT family members, and MYC were all affected by UBE2T knockdown. These results suggest that UBE2T plays a critical role in gastric cancer, and that it may serve as a useful prognostic biomarker and therapeutic target in gastric cancer patients.

Inferring human microbial dynamics from temporal metagenomics data: Pitfalls and lessons.

The human gut microbiota is a very complex and dynamic ecosystem that plays a crucial role in health and well-being. Inferring microbial community structure and dynamics directly from time-resolved metagenomics data is key to understanding the community ecology and predicting its temporal behavior. Many methods have been proposed to perform the inference. Yet, as we point out in this review, there are several pitfalls along the way. Indeed, the uninformative temporal measurements and the compositional nature of the relative abundance data raise serious challenges in inference. Moreover, the inference results can be largely distorted when only focusing on highly abundant species by ignoring or grouping low-abundance species. Finally, the implicit assumptions in various regularization methods may not reflect reality. Those issues have to be seriously considered in ecological modeling of human gut microbiota.

Possible Role of Cancer Stem Cells in Colorectal Cancer Metastasizing to the Liver.

Colorectal cancer (CRC) is one of the most common cancers in the world. In recent decades, drug therapy and surgery have not achieved satisfactory results in curing CRC. The identification of cancer stem cells (CSCs) has provided a possible mechanistic explanation of CRC growth and metastasis. Traditional chemotherapy targets rapidly dividing cells, and since the CSCs can escape these therapies and become circulating cells, CSCs may be responsible for cancer relapse and metastasis. A better understanding of the roles of CSCs in the pathogenesis of primary CRC and its metastasis, as well as how these CSCs are regulated at the molecular level, is of paramount importance. In this review, we summarize the current understanding of the role of colorectal CSCs in CRC liver metastasis, and provide some insights on the potential implication of colorectal CSCs to better design therapeutic regimens and prevent CRC metastasis.

On the Origins and Control of Community Types in the Human Microbiome.

Microbiome-based stratification of healthy individuals into compositional categories, referred to as "enterotypes" or "community types", holds promise for drastically improving personalized medicine. Despite this potential, the existence of community types and the degree of their distinctness have been highly debated. Here we adopted a dynamic systems approach and found that heterogeneity in the interspecific interactions or the presence of strongly interacting species is sufficient to explain community types, independent of the topology of the underlying ecological network. By controlling the presence or absence of these strongly interacting species we can steer the microbial ecosystem to any desired community type. This open-loop control strategy still holds even when the community types are not distinct but appear as dense regions within a continuous gradient. This finding can be used to develop viable therapeutic strategies for shifting the microbial composition to a healthy configuration.

Clinicopathological features of hepatitis B virus recurrence after liver transplantation: eleven-year experience.

OBJECTIVE: We sought to investigate new changes in the clinical pathology of hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) in era of new nucleoside or nucleotide analogues. METHODS: One hundred and eighty-four adult patients who underwent OLT for HBV-related end-stage liver disease between 1999 and 2010 were enrolled in this study. Of these patients, 156 received lamivudine (LAM) plus hepatitis B immune globulin (HBIG) and 28 were treated with LAM. The liver function, serologic parameters and HBV-DNA of the 184 recipients were followed up, and clinical pathological characteristics of grafts with HBV recurrence were examined in this study. RESULTS: One hundred and seventy-nine (97%) were alive at their last follow-up and eleven (6%) had developed HBV recurrence at a median of 22 (range 6 to 46) months post-OLT. Two of the 11 recipients were detected with HBV-S gene mutation, and 5 were tested with YMDD mutation. Four recipients who died of irreversible graft dysfunction secondary to HBV recurrence, developed fibrosing cholestatic hepatitis (FCH) because of no effective antiviral agents available in the early stages of HBV recurrence after OLT. Six recipients who received adefovir (ADV) (and Entecavir, ETV) in the early stages of HBV recurrence after OLT achieved improvement in hepatic histology. CONCLUSIONS: HBV recurrence post-OLT could be controlled at an acceptable level for a long time and the recipients could achieve long-term survival by using new antiviral agents, instead of advancing into FCH in the short term after HBV recurrence.

[Meta-analysis of total thyroidectomy for multinodular goiter].

OBJECTIVE: To systematically evaluate the efficiency and safety of total thyroidetomy (including near-total tyhroidectomy) versus subtotal thyroidectomy for multinodular goiter. METHODS: The literatures were searched from Cochrane Library, PubMed, Embase, Chinese Biological Medical Datebase, Chinese National Knowledge Infrastructure, and Chinese Science and Technology Journal Full-text Database as of November 2013. We included all randomizad controlled trials on total (including near-total) versus subtotal thyroidectomy in the treatment of multinodular goiter. The collecting of data and quality assessment were respectively completed by 2 researchers. RevMan5.1 software was used for Meta-analysis. RESULTS: We collected 7 literatures conforming to the standard, incuding 2 192 patients. The Metaanalysis outcomes showed that total thyroidectomy was associated with lower nodule recurrence rate (OR=0.13, 95% CI: 0.07-0.22, P<0.001) and higher in transient hypoparathyroidism rate (OR=2.33, 95% CI: 1.72-3.17, P<0.001). However, no statistical difference was seen comparing total and subtotal thyroidectomy in permanent recurrent laryngeal nerve paralysis rate (OR= 0.81, 95% CI: 0.24-2.74, P=0.74) and permanent hypoparathyroidism rate (OR=2.94, 95% CI: 0.48- 18.11, P=0.24). CONCLUSION: Nodule recurrence rate of total thyroidectomy for multinodular goiter is lower than subtotal thyroidectomy and does not increase permanent complications.