Objective: In Africa, the treatment outcomes of lupus nephritis (LN) are not well known. This is especially true in the current era where contemporary treatment options are more widely available. This retrospective study aimed to measure the outcomes of biopsy-proven LN treated at the Livingstone Tertiary Hospital (LTH) Renal Unit in Gqeberha (formerly Port Elizabeth), South Africa and to identify predictors of a poor outcome.
View Article and Find Full Text PDFβ-glucans found in cereal grains have been previously demonstrated to improve blood glucose control; however, current understanding points to their high viscosity as the primary mechanism of action. In this work, we present a novel, highly soluble, low-viscosity β-glucan fiber (HS-BG fiber) and a preclinical dataset that demonstrates its impact on two mechanisms related to the prevention of hyperglycemia. Our results show that HS-BG inhibits the activity of two key proteins involved in glucose metabolism, the α-glucosidase enzyme and the SGLT1 transporter, thereby having the potential to slow starch digestion and subsequent glucose uptake.
View Article and Find Full Text PDFBackground: The development of malocclusion is related to various factor, many of which are still not fully explained. The steroid hormone, 1,25-dihydroxyvitamin D3, has pleiotropic effects. It plays a key role in skeletal metabolism and the control of cell repair by attaching to the nuclear vitamin D steroid receptor (VDR).
View Article and Find Full Text PDFVirtual combinatorial libraries are prevalent in drug discovery due to improvements in the prediction of synthetic reactions that can be performed. This has gone hand in hand with the development of virtual screening capabilities to effectively screen the large chemical spaces spanned by exhaustive enumeration of reaction products. In this study, we generated a small-molecule dipeptide mimic library to target proteins binding small peptides.
View Article and Find Full Text PDFPresurgical preparation and postoperative care are cornerstones of all surgical procedures. Surgeons should be especially vigilant with malnourished cancer patients. Refeeding syn-drome (RFS) is a serious, potentially fatal complication of initiating appropriate nutrition in malnourished patients or after a period of starvation, although no standard precise definition has been proposed.
View Article and Find Full Text PDFBone tissue engineering using different scaffolds is a new therapeutic approach in regenerative medicine. This study explored the osteogenic potential of human dental pulp stem cells (hDPSCs) grown on a hydrolytically modified poly(L-lactide-co-caprolactone) (PLCL) electrospun scaffold and a non-woven hyaluronic acid (HYAFF-11™) mesh. The adhesion, immunophenotype, and osteogenic differentiation of hDPSCs seeded on PLCL and HYAFF-11™ scaffolds were analyzed.
View Article and Find Full Text PDFThe commentary by Colombo and Rich recently published in Cancer Cell provides a timely and comprehensive review of the clinical maximum tolerated doses (MTDs) of antibody-drug conjugates (ADCs) and their corresponding small molecules/chemotherapies. The authors identified similarities between their MTDs and therefore question the historic assumptions made for ADCs, namely, that they increase the MTDs of their corresponding cytotoxic molecules. However, the authors did not address the superior anti-tumor responses of ADCs compared to their corresponding chemotherapies, as reported in clinical trials.
View Article and Find Full Text PDFIndian J Otolaryngol Head Neck Surg
June 2023
In this article we present a case of a 35-year-old patient with a massive 43 × 35 × 34 mm cavernous venous malformation of the left orbit. The orbital lesion was initially observed in 2008 and remained untreated to 2021 due to the patient's refusal to consent to the surgical procedure; which caused the tumor to grow to monstrous dimensions.
View Article and Find Full Text PDFPerineurioma is a benign peripheral nerve sheath tumor. Several subtypes have been described, including plexiform, reticular, and sclerosing. The reticular variant has been previously described as having a net or lace-like growth pattern consisting of large anastomosing cords of spindle-shaped cells.
View Article and Find Full Text PDFpHLA complexes represent the largest class of cell surface markers on cancer cells, making them attractive for targeted cancer therapies. Adoptive cell therapies expressing TCRs that recognize tumor specific pHLAs take advantage of the unique selectivity and avidity of TCR: pHLA interactions. More recently, additional protein binding domains binding to pHLAs, known as TCR mimics (TCRm), were developed for tumor targeting of high potency therapeutic modalities, including bispecifics, ADCs, CAR T and -NK cells.
View Article and Find Full Text PDFPrevious studies demonstrated that polyclonal antibodies against foot-and-mouth disease virus (FMDV) generated by vaccination can mediate immune functions not only through virus neutralization but also through promoting virus uptake by macrophages and dendritic cells that are otherwise resistant to FMDV infection. This causes abortive infections resulting in activation, enhanced antigen presentation but also cell death. Here we report the use of RAW264.
View Article and Find Full Text PDFIn tRNA, tRNA, tRNA, and tRNA of most bacteria and eukaryotes, the anticodon wobble position may be occupied by the modified nucleoside queuosine, which affects the speed and the accuracy of translation. Since eukaryotes are not able to synthesize queuosine de novo, they have to salvage queuine (the queuosine base) as a micronutrient from food and/or the gut microbiome. The heterodimeric Zn containing enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into the above-named tRNAs in exchange for the genetically encoded guanine.
View Article and Find Full Text PDFExtra domain B splice variant of fibronectin (EDB+FN) is an extracellular matrix protein (ECM) deposited by tumor-associated fibroblasts, and is associated with tumor growth, angiogenesis, and invasion. We hypothesized that EDB+FN is a safe and abundant target for therapeutic intervention with an antibody-drug conjugate (ADC). We describe the generation, pharmacology, mechanism of action, and safety profile of an ADC specific for EDB+FN (EDB-ADC).
View Article and Find Full Text PDFPyrolysis converts nutrient-rich residues (e.g., sewage sludge and manures) into biochar with low levels of organic contaminants and high nutrient contents.
View Article and Find Full Text PDFBackground: The epidemic of cancer (including oral cancer) is a growing public health and economic problem in the European societies. A high percentage of patients who come for the appropriate treatment are in the late stages of advancement, often with nodal and/or distant metastases. The literature on the public oral cancer awareness in Poland and Germany is limited.
View Article and Find Full Text PDFObjective: Psychosocial factors, including combat-related distress (e.g., posttraumatic stress disorder [PTSD]), contribute to postconcussive symptoms (PCS) among veterans with mild traumatic brain injury (mTBI).
View Article and Find Full Text PDFActa Crystallogr D Struct Biol
September 2021
In recent years, crystallographic fragment screening has matured into an almost routine experiment at several modern synchrotron sites. The hits of the screening experiment, i.e.
View Article and Find Full Text PDFAberrant NOTCH3 signaling and overexpression is oncogenic, associated with cancer stem cells and drug resistance, yet therapeutic targeting remains elusive. Here, we develop NOTCH3-targeted antibody drug conjugates (NOTCH3-ADCs) by bioconjugation of an auristatin microtubule inhibitor through a protease cleavable linker to two antibodies with differential abilities to inhibit signaling. The signaling inhibitory antibody rapidly induces ligand-independent receptor clustering and internalization through both caveolin and clathrin-mediated pathways.
View Article and Find Full Text PDFThe aim of this study was to compare the reduced stresses according to Huber's hypothesis and the displacement pattern in the region of the facial skeleton using a tooth- or bone-borne appliance in surgically assisted rapid maxillary expansion (SARME). In the current literature, the lack of updated reports about biomechanical effects in bone-borne appliances used in SARME is noticeable. Finite element analysis (FEA) was used for this study.
View Article and Find Full Text PDFPurpose: Mortality due to acute myeloid leukemia (AML) remains high, and the management of relapsed or refractory AML continues to be therapeutically challenging. The reapproval of Mylotarg, an anti-CD33-calicheamicin antibody-drug conjugate (ADC), has provided a proof of concept for an ADC-based therapeutic for AML. Several other ADCs have since entered clinical development of AML, but have met with limited success.
View Article and Find Full Text PDFThe approval of ado-trastuzumab emtansine (T-DM1) in HER2 metastatic breast cancer validated HER2 as a target for HER2-specific antibody-drug conjugates (ADC). Despite its demonstrated clinical efficacy, certain inherent properties within T-DM1 hamper this compound from achieving the full potential of targeting HER2-expressing solid tumors with ADCs. Here, we detail the discovery of PF-06804103, an anti-HER2 ADC designed to have a widened therapeutic window compared with T-DM1.
View Article and Find Full Text PDFClinical evaluation of oral leukoplakia (OL), confirmed by the histological evaluation of the suspected area, provides the gold standard for diagnostics of this pathology. The aim of present study was to encrypt the significance of the histopathological results (oral intraepithelial neoplasia - OIN, WHO 2005, Ljubljana classification systems) of OL. The usefulness of osteonectin as a biomarker of changes in the oral cavity epithelium was evaluated.
View Article and Find Full Text PDFBackground: The first symptoms of oral cancer are nonspecific. They raise suspicions of other, less serious conditions. Treatment of oral cancer is challenging, and the time of its detection and the implementation of appropriate therapy affect the prognosis.
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