Inflammatory bowel disease uncovered in fecal immunochemical test positive patients in a Canadian provincial colon cancer screening program.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition that usually affects younger adults but has a second incidence peak in the older population. Although diagnosis of IBD is driven by symptoms, some patients are asymptomatic and incidentally discovered while participating in colon screening program (CSP). We aimed to identify the incidence and outcome of IBD in fecal immunochemical test (FIT) positive patients in the British Columbia CSP.

Transient Receptor Potential Melastatin 7 (TRPM7) Ion Channel Inhibitors: Preliminary SAR and Conformational Studies of Xenicane Diterpenoids from the Hawaiian Soft Coral .

Waixenicin A, a xenicane diterpene from the octocoral , is a selective, potent inhibitor of the TRPM7 ion channel. To study the structure-activity relationship (SAR) of waixenicin A, we isolated and assayed related diterpenes from . In addition to known waixenicins A () and B (), we purified six xenicane diterpenes, 7,8-epoxywaixenicins A () and B (), 12-deacetylwaixenicin A (), waixenicin E (), waixenicin F (), and 20-acetoxyxeniafaraunol B ().

Integrating the analysis of human biopsies using post-translational modifications proteomics.

Proteome diversities and their biological functions are significantly amplified by post-translational modifications (PTMs) of proteins. Shotgun proteomics, which does not typically survey PTMs, provides an incomplete picture of the complexity of human biopsies in health and disease. Recent advances in mass spectrometry-based proteomic techniques that enrich and study PTMs are helping to uncover molecular detail from the cellular level to system-wide functions, including how the microbiome impacts human diseases.

Cannabigerolic Acid (CBGA) Inhibits the TRPM7 Ion Channel Through its Kinase Domain.

Cannabinoids are a major class of compounds produced by the plant Cannabis sativa. Previous work has demonstrated that the main cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) can have some beneficial effects on pain, inflammation, epilepsy, and chemotherapy-induced nausea and vomiting. While CBD and THC represent the two major plant cannabinoids, some hemp varieties with enzymatic deficiencies produce mainly cannabigerolic acid (CBGA).

N-Terminomics/TAILS of Human Tumor Biopsies and Cancer Cell Lines.

Proteases serve essential roles in numerous biological processes and signaling cascades by cleaving their substrates in a restricted manner or via degradation. It is important to determine which proteins are protease substrates and where their cleavage sites are located to characterize the impact of proteolysis on the molecular mechanisms of their substrates. N-terminomics is a branch of proteomics that enriches the N-terminal sequence of proteins.

A Platinum Nanowire Sensor for Ethylene in Air.

A single platinum nanowire (PtNW) chemiresistive sensor for ethylene gas is reported. In this application, the PtNW performs three functions: (1) Joule self-heating to a specified temperature, (2) resistance-based temperature measurement, and (3) detection of ethylene in air as a resistance change. Ethylene gas in air is detected as a reduction in nanowire resistance by up to 4.

C3/CD11b-Mediated Leishmania major Internalization by Neutrophils Induces Intraphagosomal NOX2-Mediated Respiratory Burst but Fails to Eliminate Parasites and Induces a State of Stalled Apoptosis.

Recruited neutrophils are among the first phagocytic cells to interact with the phagosomal pathogen Leishmania following inoculation into the mammalian dermis. Analysis of Leishmania-infected neutrophils has revealed alterations in neutrophil viability, suggesting that the parasite can both induce or inhibit apoptosis. In this study, we demonstrate that entry of Leishmania major into murine neutrophils is dependent on the neutrophil surface receptor CD11b (CR3/Mac-1) and is enhanced by parasite opsonization with C3.

CBGA ameliorates inflammation and fibrosis in nephropathy.

Cannabidiol (CBD) is thought to have multiple biological effects, including the ability to attenuate inflammatory processes. Cannabigerols (CBGA and its decarboxylated CBG molecule) have pharmacological profiles similar to CBD. The endocannabinoid system has recently emerged to contribute to kidney disease, however, the therapeutic properties of cannabinoids in kidney disease remain largely unknown.

A Nanojunction pH Sensor within a Nanowire.

pH sensors that are nanoscopic in all three dimensions are fabricated within a single gold nanowire. Fabrication involves the formation of a nanogap within the nanowire via electromigration, followed by electropolymerization of pH-responsive poly(aniline) (PANI) that fills the nanogap forming the nanojunction. All fabrication steps are performed using wet chemical methods that do not require a clean room.

Acidic Cannabinoids Suppress Proinflammatory Cytokine Release by Blocking Store-operated Calcium Entry.

has long been known to affect numerous biological activities. Although plant extracts, purified cannabinoids, or synthetic cannabinoid analogs have shown therapeutic potential in pain, inflammation, seizure disorders, appetite stimulation, muscle spasticity, and treatment of nausea/vomiting, the underlying mechanisms of action remain ill-defined. In this study we provide the first comprehensive overview of the effects of whole-plant extracts and various pure cannabinoids on store-operated calcium (Ca) entry (SOCE) in several different immune cell lines.

Sex-dependent effect of aging on calcium signaling and expression of TRPM2 and CRAC channels in human neutrophils.

The vulnerability of older adults to bacterial infections has been associated with age-related changes in neutrophils. We analyzed the consequences of aging on calcium (Ca) mobilization and TRPM2 and CRAC channels expression in human neutrophils. The percentages of granulocytes, mature neutrophils, and neutrophil precursors were equivalent between young and older adults.

Mutagenic Distinction between the Receptor-Binding and Fusion Subunits of the SARS-CoV-2 Spike Glycoprotein and Its Upshot.

We observe that a residue R of the spike glycoprotein of SARS-CoV-2 that has mutated in one or more of the current variants of concern or interest, or under monitoring, rarely participates in a backbone hydrogen bond if R lies in the S1 subunit and usually participates in one if R lies in the S2 subunit. A partial explanation for this based upon free energy is explored as a potentially general principle in the mutagenesis of viral glycoproteins. This observation could help target future vaccine cargos for the evolving coronavirus as well as more generally.

Enhancing the Sensitivity of the Virus BioResistor by Overoxidation: Detecting IgG Antibodies.

The Virus BioResistor (VBR) is a biosensor capable of rapid and sensitive detection of small protein disease markers using a simple dip-and-read modality. For example, the bladder cancer-associated protein DJ-1 (22 kDa) can be detected in human urine within 1.0 min with a limit of detection (LOD) of 10 pM.

Chemiresistive Hydrogen Sensors: Fundamentals, Recent Advances, and Challenges.

Hydrogen (H) is one of the next-generation energy sources because it is abundant in nature and has a high combustion efficiency that produces environmentally benign products (HO). However, H/air mixtures are explosive at H concentrations above 4%, thus any leakage of H must be rapidly and reliably detected at much lower concentrations to ensure safety. Among the various types of H sensors, chemiresistive sensors are one of the most promising sensing systems due to their simplicity and low cost.

Viruses Masquerading as Antibodies in Biosensors: The Development of the Virus BioResistor.

The 2018 Nobel Prize in Chemistry recognized in vitro evolution, including the development by George Smith and Gregory Winter of phage display, a technology for engineering the functional capabilities of antibodies into viruses. Such bacteriophages solve inherent problems with antibodies, including their high cost, thermal lability, and propensity to aggregate. While phage display accelerated the discovery of peptide and protein motifs for recognition and binding to proteins in a variety of applications, the development of biosensors using intact phage particles was largely unexplored in the early 2000s.

Moving Electrons Purposefully through Single Molecules and Nanostructures: A Tribute to the Science of Professor Nongjian Tao (1963-2020).

Electrochemistry intersected nanoscience 25 years ago when it became possible to control the flow of electrons through single molecules and nanostructures. Many surprises and a wealth of understanding were generated by these experiments. Professor Nongjian Tao was among the pioneering scientists who created the methods and technologies for advancing this new frontier.

Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones.

Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all known hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.

Virus Bioresistor (VBR) for Detection of Bladder Cancer Marker DJ-1 in Urine at 10 pM in One Minute.

DJ-1, a 20.7 kDa protein, is overexpressed in people who have bladder cancer (BC). Its elevated concentration in urine allows it to serve as a marker for BC.