Maackia amurensis Seed Lectin (MASL) Increases Movement Velocity of Mice with TNFα Induced Rheumatoid Arthritis

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN on chondrocytes to decrease inflammatory signaling cascades and reduce cartilage destruction in a lipopolysaccharide induced osteoarthritis mouse model. Here, we investigated the effects of MASL on rheumatoid arthritis progression in a TNFα transgenic (TNF-Tg) mouse model. Results from this study indicate that MASL can be administered orally to ameliorate joint malformation and increase velocity of movement exhibited by these TNF-Tg mice. These data support the consideration of MASL as a potential treatment for rheumatoid arthritis

A Case of Synchronous Colorectal Carcinoma Manifested as Three Separate Colon Masses

Colorectal cancer is the second leading cause of cancer-related deaths in the United States amongst cancers that affect both genders. Synchronous colorectal cancer is greater than one primary lesion detected on initial presentation and occurs about 5% of the time. This is a 78 year-old female with past medical history of left-sided breast cancer treated with neoadjuvant chemotherapy who presented with symptomatic anemia found to have a hemoglobin of five and positive fecal occult blood test. Patient was transfused and taken for EGD/colonoscopy, which showed three polypoid rectal lesions and three separate colon masses. Preliminary pathology showed high grade dysplasia in cecal mass and carcinoma in situ in rectal polyp. CT scan findings included 4.2 x 2.7 cm mass at cecum as well as areas of bowel wall thickening at proximal descending colon, proximal sigmoid colon, and distal rectosigmoid colon. Patient was taken to the operating room for rectal exam under anesthesia and laparoscopic subtotal colectomy. Post-operative pathology confirmed moderately-differentiated invasive adenocarcinoma arising from tubulovillous adenomas with lymph-vascular and perineural invasion. Five out of twelve lymph nodes sampled were involved. This patient never had a colonoscopy but was recommended to get one two years prior when some areas of her colon were found to be prominent on PET scan, however she did not follow up. The importance of screening for colorectal cancer has never been more apparent than it is today with its proven benefit to decrease mortality

Maackia Amurensis Seed Lectin (MASL) and soluble human podoplanin (shPDPN) Sequence Analysis and Effects on Human Oral Squamous Cell Carcinoma (OSCC) Cell Migration and Viability

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent

Impact of Madden-Julian Oscillation (MJO) on global distribution of total water vapor and column ozone

The Madden-Julian Oscillation (MJO) is the leading mode of intra-seasonal variability in the tropical troposphere, characterized by an eastward moving 'pulse' of cloud and rainfall near the equator. In this study, total precipitable water (TPW) and total column ozone (TCO) datasets from ECMWF ERA-Interim reanalysis were used to analyse the impact of the MJO on the distribution of water vapor and column ozone in the tropics from 1979 to 2013. The results show that seasonal variations of TPW modulated by the MJO are maximized in the tropics of about 10°S-10°N during boreal winter, while the variation in TCO is maximized in the mid-latitudes of about 30°S - 40°N in the same season. The composite analysis shows that MJO modulates TPW and TCO anomalies eastward across the globe. The underlying mechanism of the MJO's impact on TPW is mainly associated with variation of tropical convection modulated by the MJO, while the underlying mechanism of the MJO's impact on TCO is mainly associated with an intra-seasonal variability of tropopause height modulated by the MJO activity. This knowledge helps to improve the prediction skill of the intra-seasonal variation of water vapor and column ozone in the tropics during boreal winter

Incidence of submacular haemorrhage (SMH) in Scotland : a Scottish Ophthalmic Surveillance Unit (SOSU) study

PURPOSE: Submacular haemorrhage (SMH) is a cause of severe visual loss in neovascular age-related macular degeneration (nAMD). The incidence is uncertain and furthermore there is no widely used classification system nor agreed best practice. The aim of this national surveillance study was to identify the incidence, presenting features and clinical course of new fovea-involving submacular haemorrhage associated with nAMD. METHODS: A questionnaire was sent monthly to every ophthalmic specialist in Scotland over a 12-month period asking them to report all newly presenting patients with acute SMH secondary to nAMD of at least two disc diameters (DDs) in greatest linear diameter. A follow-up questionnaire was sent 6 months after initial presentation. Cases related to other causes were excluded. RESULTS: Twenty-nine cases were reported giving an incidence of 5.4 per million per annum (range 2-15). The mean age was 83 years (range 66-96) and females accounted for 17/29 (59%). Fifteen of the 29 cases (52%) had a past history of AMD, of which 7 had nAMD. Nineteen of the 29 cases (66%) presented within 7 days of onset and the majority had SMH of < 11 DD (20/29, 69%). Treatment options comprised the following: observation (n = 6, 21%), anti-VEGF alone (n = 6, 21%) or vitrectomy with co-application of tissue plasminogen activator (TPA), anti-VEGF and gas (n = 17, 58%). The vitrectomy group experienced the greatest change in vision from logMAR 1.89-1.50 (p = 0.374). Four of 20 (20%) cases with 6 months follow-up suffered a re-bleed at a mean time of 96 days. CONCLUSIONS: The incidence, clinical features and course of a consecutive national cohort of patients with SMH secondary to nAMD are presented