O-linked β-D-N-acetylglucosamine (O-GlcNAc) is an important post-translational modification of serine or threonine residues on thousands of proteins in the nucleus and cytoplasm of all animals and plants. In eukaryotes, only two conserved enzymes are involved in this process. O-GlcNAc transferase is responsible for adding O-GlcNAc to proteins, while O-GlcNAcase is responsible for removing it. Aberrant O-GlcNAcylation is associated with a variety of human diseases, such as diabetes, cancer, neurodegenerative diseases, and cardiovascular diseases. Numerous studies have confirmed that O-GlcNAcylation is involved in the occurrence and progression of cancers in multiple systems throughout the body. It is also involved in regulating multiple cancer hallmarks, such as metabolic reprogramming, proliferation, invasion, metastasis, and angiogenesis. In this review, we first describe the process of O-GlcNAcylation and the structure and function of O-GlcNAc cycling enzymes. In addition, we detail the occurrence of O-GlcNAc in various cancers and the role it plays. Finally, we discuss the potential of O-GlcNAc as a promising biomarker and novel therapeutic target for cancer diagnosis, treatment, and prognosis. 

/pdf/o-glcnacylation-an-important-post-translational-modification-3v2uo2ed.pdf

O-GlcNAcylation: an important post-translational modification and a potential therapeutic target for cancer therapy

Prenatal opioid exposure (POE) is commonly associated with neonatal opioid withdrawal syndrome (NOWS), which is characterized by a broad variability in symptoms and severity. Currently there are no diagnostic tools to reliably predict which infants will develop severe NOWS, while risk stratification would allow for proactive decisions about appropriate clinical monitoring and interventions. The aim of this prospective cohort study was to assess if extracellular microRNAs (miRNAs) in umbilical cord plasma of infants with POE could predict NOWS severity. Participants (n = 58) consisted of pregnant women receiving medications for opioid use disorder and their infants. NOWS severity was operationalized as the need for pharmacologic treatment and prolonged hospitalization (≥ 14 days). Cord blood miRNAs were assessed using semi-quantitative qRT-PCR arrays. Receiver operating characteristic curves and area under the curve (AUC) were estimated. The expression of three miRNAs (miR-128-3p, miR-30c-5p, miR-421) predicted need for pharmacologic treatment (AUC: 0.85) and prolonged hospitalization (AUC: 0.90). Predictive validity improved after two miRNAs (let-7d-5p, miR-584-5p) were added to the need for pharmacologic treatment model (AUC: 0.94) and another two miRNAs (let-7b-5p, miR-10-5p) to the prolonged hospitalization model (AUC: 0.99). Infant cord blood extracellular miRNAs can proactively identify opioid-exposed neonates at high-risk for developing severe NOWS. 

/pdf/prenatal-opioid-exposed-infant-extracellular-mirna-signature-1pbiduv7.pdf

Prenatal opioid-exposed infant extracellular miRNA signature obtained at birth predicts severity of neonatal opioid withdrawal syndrome

RATIONALE
Cervical cancer is one of the most common malignant tumors in women, and it is essential to explore the potential biomarkers such as glycopeptides closely related to cancer in physiological samples of the cervical cancer patient. Sample pretreatment is required before direct detection of mass spectrometry because there are certain limitations. Meanwhile, it is still highly desired to promote the functionalization and application of metal-organic frameworks (MOFs)-derived materials.


METHODS
By post-synthesis modification method, a novel type of boric acid-functionalized MOF probe (designated as UiO-66@PEI@Au@B (OH)2 ) is prepared for recognition of glycopeptides. The results are detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nano-LC-MS/MS.


RESULTS
The UiO-66@PEI@Au@B (OH)2 probe exhibits a low detection limit (0.6 fmol·μL-1 ), a relatively excellent recovery rate, comparatively good reusability and selectivity (HRP digests : BSA digests = 1:500). When UiO-66@PEI@Au@B (OH)2 is used to selectively capture glycopeptides from the serum of the healthy person and cervical cancer patient, 101 glycopeptides corresponding to 54 glycoproteins and 108 glycopeptides corresponding to 57 glycoproteins are detected, respectively.


CONCLUSIONS
The successful preparation of UiO-66@PEI@Au@B (OH)2 provides a path for the investigation of the functionalization of MOFs-derived materials. The excellent performance of UiO-66@PEI@Au@B (OH)2 not only demonstrates the huge potential of functionalized MOF in the glycoproteome, but also opens up new phases of the application of MOF-based materials.

Construction of boric acid functionalized metal organic frameworks for glycopeptides recognition in the serum of cervical cancer patient.

ALG2 inhibits the epithelial-to-mesenchymal transition and stemness of ovarian granulosa cells through the Wnt/β-catenin signaling pathway in polycystic ovary syndrome.

Hybrid cities and new working spaces – The case of Oslo

Inflammatory bowel disease (IBD), which affects about 7 million people globally, is a chronic inflammatory condition of the gastrointestinal tract caused by gut microbiota alterations, immune dysregulation, and genetic and environmental factors. The association of microbial and immune molecules with mucin-type O-glycans has been increasingly noticed by researchers. Mucin is the main component of mucus, which forms a protective barrier between the microbiota and immune cells in the colon. Mucin-type O-glycans alter the diversity of gastrointestinal microorganisms, which in turn increases the level of O-glycosylation of host intestinal proteins via the utilization of glycans. Additionally, alterations in mucin-type O-glycans not only increase the activity and stability of immune cells but are also involved in the maintenance of intestinal mucosal immune tolerance. Although there is accumulating evidence indicating that mucin-type O-glycans play an important role in IBD, there is limited literature that integrates available data to present a complete picture of exactly how O-glycans affect IBD. This review emphasizes the roles of the mucin-type O-glycans in IBD. This seeks to provide a better understanding and encourages future studies on IBD glycosylation and the design of novel glycan-inspired therapies for IBD.

/pdf/mucin-type-o-glycans-barrier-microbiota-and-immune-anchors-yeva5x91dv.pdf

Mucin-Type O-Glycans: Barrier, Microbiota, and Immune Anchors in Inflammatory Bowel Disease.

Cervical cancer has become the most frequent female malignancy and presents as a general health challenge in many countries undergoing economic development. Various human papillomaviruses (HPV) types have appeared as one of the most critically identifiable causes of widespread cervical cancers. Conventional cervical cytological inspection has limitations of variable sensitivity according to cervical cytology. Glycobiology has been fundamental in related exploration in various gynecologic and reproductive fields and has contributed to our understanding of cervical cancer. It is associated with altered expression of N-linked glycan as well as abnormal expression of terminal glycan structures. The analytical approaches available to determine serum and tissue glycosylation, as well as potential underlying molecular mechanisms involved in the cellular glycosylation alterations, are monitored. Moreover, cellular glycosylation influences various aspects of cervical cancer biology, ranging from cell surface expressions, cell-cell adhesion, cancer signaling, cancer diagnosis, and management. In general, discoveries in glycan profiling make it technically reproducible and affordable to perform serum glycoproteomic analyses and build on previous work exploring an expanded variety of glycosylation markers in the majority of cervical cancer patients.

/pdf/glycosylation-in-cervical-cancer-new-insights-and-clinical-598y262wv0.pdf

Yaqin Zhang

Papers

Mucin-Type O-Glycans: Barrier, Microbiota, and Immune Anchors in Inflammatory Bowel Disease.

Glycosylation in Cervical Cancer: New Insights and Clinical Implications.