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Engineering Strategies for Hyaluronan Synthesis: A Review of Enzyme Modifications, Strain Selection, and Molecular Weight Control
No full textHyaluronan is a biopolymer with significant biological and commercial importance, particularly due to its applications in medical, cosmetic, and tissue engineering fields. The molecular weight of HA is a key factor that influences its biological function, ranging from anti-inflammatory properties in high-molecular-weight HA to pro-inflammatory effects in low-molecular-weight HA. Recent advancements in protein and strain engineering have enabled precise control of the molecular weight of hyaluronan by manipulating both hyaluronan synthase enzyme variants and the host microbial strains used in hyaluronan production. Strain engineering, through genetic modification and metabolic pathway optimization, enhances the efficiency and yield of hyaluronan with defined molecular properties. Despite progress in industrial-scale hyaluronan production, achieving monodisperse hyaluronan with well-defined molecular weights remains a challenge. This review explores the current breakthroughs in enzyme and strain engineering strategies to optimize hyaluronan synthase enzyme activity and microbial host systems, aiming to produce size-controlled hyaluronan polymers with improved therapeutic efficacy. We discuss the role of specific hyaluronan synthase enzyme mutations and truncations, strain selection, and metabolic engineering, as well as the potential of in vitro cell-free systems for producing hyaluronan with tailored molecular properties for advanced biomedical applications
Integrated miRNA-mRNA Analyses of Triple-Negative Breast Cancer in Black and White Patients with or Without Obesity
No full textTriple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. miRNAs play an essential role in TNBC pathogenesis and prognosis. Obesity is linked with an increased risk for several cancers, including breast cancer. Obesity is also related to the dysregulation of miRNA expression in adipose tissues. However, there is limited knowledge about race- and obesity-specific differential miRNA expression in TNBC. We performed miRNA sequencing of 48 samples (24 tumor and 24 adjacent non-tumor tissues) and RNA sequencing of 24 tumors samples from Black (AA) and White (EA) TNBC patients with or without obesity. We identified 55 miRNAs exclusively associated with tumors in obese EA patients and 33 miRNAs in obese AA patients, each capable of distinguishing tumor tissues from obese from lean individuals within their respective racial groups. In EA, we detected 41 significant miRNA–mRNA correlations. Notably, miR-181b-5p and miR-877-5p acted as negative regulators of tumor-suppressor genes (e.g., HEY2, MCL2, HAND2), while miR-204-5p and miR-143-3p appeared to indirectly target oncogenes (e.g., RAB10, DR1, PTBP3, NCBP1). Among AA patients, we found 28 significant miRNA–mRNA interactions. miR-195-5p, miR-130a-3p, miR-130a-5p, miR-424-5p, miR-148a-3p, miR-374-5p, and miR-30a-5p each potentially downregulated two or more genes (e.g., CLCN4, PLCB1, CDC25B, AEBP2, ERBB4). Pathway enrichment analysis highlighted KRAS, ESR1, ESR2, RAB10, TNRC6C, and NCAN as the most commonly differentially expressed in EA, whereas ERBB4, PLCB1, and SERPINE1 were most frequently in AA. These findings highlight the importance of considering race-specific miRNA–mRNA signatures in understanding TNBC in the context of obesity, offering insights into biomarker-driven patient stratification for targeted therapeutic strategies
A Preliminary Analysis of Transaminitis Observed in Oxandrolone Versus Testosterone Therapy in Major Burn Injury
No full text57th Annual Meeting of the American Burn Association, ABA 2025, April 8 - 11, 2025, Phoenix, A
AhR Activation at the Air-Blood Barrier Alters Systemic microRNA Release After Inhalation of Particulate Matter Containing Environmentally Persistent Free Radicals
Full text linkParticulate matter containing environmentally persistent free radicals (EPFRs) is formed when organic pollutants are incompletely burned and adsorb to the surface of particles containing redox-active metals. Our prior studies showed that in mice, EPFR inhalation impaired vascular relaxation in a dose- and endothelium-dependent manner. We also observed that activation of the aryl hydrocarbon receptor (AhR) in the alveolar type-II (AT-II) cells that form the air-blood interface stimulates the release of systemic factors that promote endothelial dysfunction in vessels peripheral to the lung. AhR is a recognized regulator of microRNA (miRNA) biogenesis, and miRNA control diverse signaling pathways. We thus hypothesized that systemic EPFR-induced vascular endothelial dysfunction is initiated via AhR activation in AT-II cells, resulting in a systemic release of miRNA. Using a combustion reactor, we generated EPFR of two free radical concentrations—EPFRlo (1016–17 radicals/g particles) and EPFR (1018–19 radicals/g)—and exposed mice by inhalation. EFPR inhalation resulted in changes in a distinct array of miRNA in the plasma, and these miRNAs are linked to multiple systemic effects, including cardiovascular diseases and dysregulation of cellular and molecular pathways associated with cardiovascular dysfunction. We identified 17 miRNA in plasma that were altered dependent upon both AhR activation in AT-II cells and ~ 280 ug/m3 EPFR exposure. Using Ingenuity Pathway Analysis, we found that 5 of these miRNAs have roles in modulating endothelin-1 and endothelial nitric oxide signaling, known regulators of endothelial function. Furthermore, EPFR exposure reduced the expression of lung adherens and gap junction proteins in control mice but not AT-II-AhR deficient mice, and reductions in barrier function may facilitate miRNA release from the lungs. In summary, our findings support that miRNA may be systemic mediators promoting endothelial dysfunction mediated via EPFR-induced AhR activation at the air-blood interface
Serotonin, immune function, and psychedelics as potent anti-inflammatories
No full textPsychedelics are primarily recognized for their profound behavioral effects, leading most research on psychedelics and their primary target, the 5-HT2A receptor, to focus on brain activity. However, these receptors are not only found within the brain and are present in nearly every tissue and cell type throughout the body, playing a significant role alongside serotonin in modulating various processes, including immune function. Serotonin acting at 5-HT2A receptors generally promotes inflammation. Levels are elevated at sites of inflammation and through 5-HT2A receptor activation lead to events including increased cytokine production, eosinophil recruitment, T-cell activation, and mast cell degranulation. Some psychedelics, but not all, have been found to have powerful anti-inflammatory and immunomodulatory effects through activation of 5-HT2A receptors in preclinical experimental systems and models of human inflammatory diseases. Human studies examining anti-inflammatory effects of psychedelics are limited but suggestive that psychedelics may represent a new strategy to treat inflammatory diseases. In this review we will present an overview of serotonergic modulation of immune function, the role of 5-HT2A receptors in these processes, and a summary of key findings with psychedelics with regards to anti-inflammatory efficacy
Risk of fungal infection in psoriasis patients treated with IL-17 and IL-23 inhibitors: a multi-cohort study using real-world data
No full textHospital And Program Support Staff Affect Educational Experience And Wellbeing Of Trainees
No full textVascular & Endovascular Surgery Society 49th Annual Winter Meeting, February 6 - 9, 2025, Breckenridge, C
Percutaneous versus Transjugular Random Renal Biopsy in High-Risk Patients: Comparison of Outcomes
No full textSIR 2025 50th Annual Scientific Meeting Program, March 29 - April 2, 2025, Nashville, T
Lichen Sclerosus in Cancer Patients
No full textObjective To characterize the association between cancer therapies and the development of lichen sclerosus (LS) in a case series of patients. Methods A retrospective chart review was performed to screen for patients who were diagnosed with LS while undergoing cancer therapy at Memorial Sloan Kettering Cancer Center between 2003 and 2019. Patients were excluded if they had been diagnosed with LS prior to starting cancer therapy. Clinical and treatment characteristics were analyzed. Results The final study sample included 29 female patients who developed LS in the setting of systemic cancer therapy. Median time to LS onset after cancer therapy initiation was 420 days. Primary tumor types included breast (10, 34.5%), gynecologic (8, 27.6%), gastrointestinal (5, 17.2%), cutaneous (2, 6.9%), lung (2, 6.9%), and hematologic (2, 6.9%). Cancer therapy regimens included hormonal therapy (10, 34.5%), chemoradiation (7, 24.1%), cytotoxic chemotherapy (7, 24.1%), PD-1/PD-L1 inhibitors (3, 10.3%), local radiation (1, 3.4%), and allogeneic stem cell transplant (1, 3.4%). Across all patients, the mean number of treatments for LS was 2.8. Twenty-three (79.3%) patients received the first-line therapy of ultrapotent topical steroids, but 16 (69.6%) required additional topical and systemic treatment. Limitations include retrospective design and referral bias. Conclusions Breast cancer was the most common primary tumor among patients in this study. The most common cancer therapy regimen was hormonal therapy. Most patients required an escalation in therapy to manage their LS. For patients undergoing cancer treatment, concomitant LS management can present unique challenges due to the biological mechanism of some anticancer therapies and the pathophysiology of LS. There is limited data to guide treatment of LS for this population. Some of the patients included in this analysis had progression of LS and recurrence of cancer while undergoing management of both conditions, necessitating close follow-up