Factor VIII (Recombinate / rAHF, Baxter / rurioctocog alpha)

Spontaneous Retroperitoneal Hemorrhage in Anti-NXP2-Positive Dermatomyositis: a Rare but Severe Complication.

Zhang Hao H, Dai Bingbing B, Li Ningning N

Spontaneous hemorrhage is a rare but serious complication of dermatomyositis (DM). We report a 61-year-old man with anti-NXP2-positive DM who developed a retroperitoneal hematoma without anticoagulation, shortly after corticosteroid initiation. Laboratory investigations demonstrated rhabdomyolysis, hepatic injury and coagulopathy. The patient was managed with red blood cell transfusion, factor VIII, high-dose corticosteroids and intravenous immunoglobulin, resulting in complete recovery. Although hemorrhagic events in DM are most often linked to anti-MDA5 or anti-Ro52 antibodies, their association with anti-NXP2 antibodies remains uncertain. This case highlights the importance of early recognition and prompt intervention in managing spontaneous hemorrhage in DM.

Is Intact Anterior Pericardium a Factor in RV Function?

Baciewicz Frank A FA, Modukuri Shrikar S, Cardozo Shaun S

Insulin Resistance and Cutaneous Squamous Cell Carcinoma: A Narrative Review of Molecular Mechanisms.

Ardinata Dedi D, Alferraly Tengku Ibnu TI, Yosi Ariyati A, Pase Muhammad Aron MA

Although the association between diabetes and cutaneous squamous cell carcinoma (cSCC) is well recognized, the specific role of insulin resistance (IR) as an independent driver of cSCC pathogenesis remains underexplored. This review synthesized emerging evidence on the ultraviolet (UV)-independent molecular mechanisms by which IR promotes cSCC initiation and progression. Hyperinsulinemia activates the insulin-like growth factor-1 receptor (IGF-1R), which triggers both the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways, stimulating keratinocyte proliferation and suppressing apoptosis. In parallel, hyperglycemia-driven formation of advanced glycation end products (AGEs) and oxidative stress cause deoxyribonucleic acid (DNA) damage and impair tumor suppressor functions, notably that of tumor protein p53 (TP53). The resulting reactive oxygen species (ROS) activate nuclear factor-kappa B (NF-κB), establishing a chronic inflammatory milieu that remodels the tumor microenvironment through cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and by upregulating matrix metalloproteinases (MMPs). These processes collectively facilitate the malignant transformation of actinic keratosis (AK) to invasive cSCC. The analysis in the present study identified novel therapeutic targets and reaffirmed the importance of further studies on microbiome interactions and lifestyle interventions for IR-associated cSCC.

Protective effects of melatonin against hypoxia-induced TM3 cell damage via suppression of the TGF-β pathway.

Rashidi Sahar S, Saberivand Adel A, Gholami Mohammadreza M, Assadollahi Vahideh V et al.

This study aimed to explore whether melatonin protects TM3 Leydig cells from cobalt (II) chloride (CoCl2)-induced hypoxia through the transforming growth factor beta (TGF-β) signaling pathway. Cells were divided into four groups: a control group without treatment (Group 1), a melatonin group (10.00 ng mL-1; Group 2), a group treated with CoCl2 (100 µM) to induce hypoxia (Group 3), and a melatonin + CoCl2 group (Group 4). After 96 hr of incubation, cell viability was assessed using the MTT assay, and transforming growth factor beta 1, activin receptor-like kinase-5, and bone morphogenetic protein 4 gene and protein expressions were measured through RT‑PCR and western blotting. The CoCl2 and melatonin + CoCl2 groups exhibited significantly diminished cell viability compared to the control. However, melatonin treatment enhanced survival in the CoCl2-exposed cells. Notably, transforming growth factor beta 1 expression was elevated in all groups. Activin receptor-like kinase-5 (gene and protein expression increased in CoCl2-treated groups but was lower in the melatonin + CoCl2 group. Melatonin treatment reduced bone morphogenetic protein 4 expression compared to the control, while CoCl2 groups showed increased bone morphogenetic protein 4 levels. These findings suggest melatonin's potential as a therapeutic agent against oxidative stress and hypoxia in TM3 cells through its antioxidant properties.