Last update 05 Sep 2024
RHBDF2
Last update 05 Sep 2024
Basic Info
Synonyms FLJ22341, Inactive rhomboid protein 2, iRhom2 + [12] |
Introduction Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own. |
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100 Clinical Results associated with RHBDF2
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100 Translational Medicine associated with RHBDF2
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21 Feb 2024Annals of vascular surgery
Delayed Closure of Guillotine Lower Extremity Amputation in Obese Patients is Associated with Increased Mortality.
Article
Author: Eyerusalem Workneh ; Allison Karwoski ; Natalie Chao ; Luke Pitsenbarger ; Nora Dunlap ; Suzanna Simmonds Fitzpatrick ; Khanjan H Nagarsheth
OBJECTIVE:
Staged surgery with open guillotine amputation (OGA) prior to a definitive major lower extremity amputation (LEA) has been shown to be effective for sepsis control and improving wound healing. Studies have evaluated postoperative complications including infection, return to the operating room for re-amputation, and amputation failure following OGA. However, the role of timing to close OGA for predictive outcomes remains poorly understood. We aim to assess outcomes of major LEA related to the time of OGA closure.
METHODS:
Data from patients who underwent major LEA from 2015 to 2021 was collected retrospectively. The study included all patients undergoing below-, through-, or above-knee amputations. Next, patients who had OGA prior to a definitive amputation were selected. Patients who died before amputation closure were excluded. Post-amputation outcomes such as surgical site infection (SSI), postoperative sepsis, postoperative ambulation, hospital length of stay (LOS), and 30-day, 1-year, and 5-year mortality were reviewed. The study cohort was stratified by demographics and comorbidities. Receiver operating characteristic (ROC) curve analysis was performed to determine the time of closure (TOC) cut-off value. Univariate and multivariate analysis was performed to assess outcomes. Statistical significance was set at p < 0.05.
RESULT:
Of 688 patients who underwent major LEA, 322 underwent staged amputation with OGA before the formalization procedure and were included. The TOC ranged from 1-47 days with a median of 4 days (interquartile range (IQR) from 3 to 7). The optimal TOC point of 8 days (ranging from 2 - 42 days) in obese patients (199/322) for predicting mortality showed the largest area under the curve (AUC) (0.709) with 64.71% sensitivity and 78.3% specificity. Patients who are obese and grouped in TOC less than 8 days had no 30-day mortality, significantly lower 1-year mortality, better survival, and a lower rate of deep venous thrombosis (DVT) complication. There was no significant difference in LOS, postoperative SSI, sepsis, and ambulation between the two subgroups of obese patients. Multivariable analysis showed that gender, CKD, and postoperative ambulation independently predict overall mortality in obese patients.
CONCLUSION:
TOC cutoff in obese patients showed statistically significant results in predicting mortality. Our findings indicated better survival in obese patients with a lower TOC (less than 8 days). This emphasizes the importance of earlier closure of OGA in obese patients.
05 Jan 2024The Journal of clinical endocrinology and metabolism
Enhancing Angioinvasion Assessment in Papillary Thyroid Cancer via a Biomarker Panel Involving TAC, 8-OHdG and Sortilin.
Article
Author: Angelika Buczyńska ; Maria Kościuszko ; Iwona Sidorkiewicz ; Aleksandra Anna Wiatr ; Agnieszka Adamska ; Katarzyna Siewko ; Janusz Dzięcioł ; Małgorzata Szelachowska ; Adam Jacek Krętowski ; Anna Popławska-Kita
CONTEXT:
Papillary thyroid cancer (PTC) aggressiveness and metastatic potential are closely associated with angioinvasion. Identifying angioinvasion accurately is imperative for treatment planning and prognosis.
OBJECTIVE:
This study explores serum biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and oxidative status markers (total oxidative capacity (TOC), total antioxidant capacity (TAC), and sortilin), as potential indicators of angioinvasion in PTC.
DESIGN:
A cross-sectional study involving 50 angioinvasive PTC patients (study group) and 30 PTC patients with low-risk features (reference group). Serum levels of biomarkers were analyzed to determine their association with angioinvasion.
SETTING:
Patients were recruited from Department of Endocrinology, Diabetology, and Internal Diseases, Medical University of Bialystok, Poland, ensuring representation from a diverse clinical context.
PATIENTS OR OTHER PARTICIPANTS:
Participants included PTC patients, with 50 in the study group and 30 in the reference group. Selection criteria, matching characteristics, and participant completion rates were duly recorded.
INTERVENTION(S):
Serum biomarkers were measured to evaluate their association with PTC angioinvasion.
MAIN OUTCOME MEASURE(S):
Primary outcome measures included serum levels of 8-OHdG, TOC, TAC, and sortilin.
RESULTS:
Serum levels of 8-OHdG and sortilin were significantly elevated in angioinvasive PTC, while TAC showed a notable decrease (all p < 0.01). A regression panel combining TAC, 8-OHdG, and sortilin demonstrated a high AUC value (0.963) for angioinvasion discernment.
CONCLUSIONS:
Measuring TAC, 8-OHdG, and sortilin levels may serve as potential biomarkers for identifying angioinvasion in PTC. The combined assessment of these biomarkers enhances angioinvasion discernment, aiding risk stratification and personalized treatment decisions. Further validation studies are required before integrating these biomarkers into routine clinical practice. The study adheres to the provided structure, providing concise and supported conclusions based on the results.
01 Jan 2024Molecular cell
Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.
Article
Author: Iqbal Dulloo ; Michael Tellier ; Clémence Levet ; Anissa Chikh ; Boyan Zhang ; Diana C Blaydon ; Catherine M Webb ; David P Kelsell ; Matthew Freeman
iRhoms are pseudoprotease members of the rhomboid-like superfamily and are cardinal regulators of inflammatory and growth factor signaling; they function primarily by recognizing transmembrane domains of their clients. Here, we report a mechanistically distinct nuclear function of iRhoms, showing that both human and mouse iRhom2 are non-canonical substrates of signal peptidase complex (SPC), the protease that removes signal peptides from secreted proteins. Cleavage of iRhom2 generates an N-terminal fragment that enters the nucleus and modifies the transcriptome, in part by binding C-terminal binding proteins (CtBPs). The biological significance of nuclear iRhom2 is indicated by elevated levels in skin biopsies of patients with psoriasis, tylosis with oesophageal cancer (TOC), and non-epidermolytic palmoplantar keratoderma (NEPPK); increased iRhom2 cleavage in a keratinocyte model of psoriasis; and nuclear iRhom2 promoting proliferation of keratinocytes. Overall, this work identifies an unexpected SPC-dependent ER-to-nucleus signaling pathway and demonstrates that iRhoms can mediate nuclear signaling.
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