Existing therapeutic strategies for breast cancer are limited by tumor recurrence and drug-resistance. Antioxidant plant-derived compounds such as flavonoids reduce adverse outcomes and have been identified as a potential source of antineoplastic agent with less undesirable side effects. Here, we describe the novel regulation of fatty-acid synthase (FASN), the key enzyme in de novo fatty-acid synthesis, whereby Vitis vinifera L. cv Vermentino leaf hydroalcoholic extract lowers its protein stability that is regulated by small ubiquitin-like modifier (SUMO)ylation. The phenolic compounds characterization was performed by liquid chromatography–mass spectrometry (LC–MS), whereas mass spectrometry (LC–MS/MS), Western blotting/co-immunoprecipitation (Co-IP) and RT-PCR, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenicity assays, and FACS analysis were used to measure the expression of targets and tumorigenicity. Vermentino extract exhibits antitumorigenic effects, and we went on to determine that FASN and ubiquitin-conjugating enzyme 9 (UBC9), the sole E2 enzyme required for SUMOylation, were significantly reduced. Moreover, FASN was found SUMOylated in human breast cancer tissues and cell lines, and lack of SUMOylation caused by SUMO2 silencing reduced FASN protein stability. These results suggest that SUMOylation protects FASN against proteasomal degradation and may exert oncogenic activity through alteration of lipid metabolism, whereas Vermentino extract inhibits these effects which supports the additional validation of the therapeutic value of this compound in breast cancer.

Alcohol-associated liver disease (ALD) remains a major public health challenge with limited treatment options. NF-κB–driven inflammation in Kupffer cells (KCs) plays a central role in ALD, but the upstream regulators remain poorly understood. Here, we identify the tyrosine kinase SRC as a key mediator of ALD. Chronic ethanol exposure activates SRC in KCs, which directly phosphorylates ubiquitin-conjugating enzyme 9 (UBC9), the only E2 SUMO enzyme, at tyrosine-68 (Y68). This modification enhances NF-κB signaling and increases proinflammatory cytokines (TNF-α, IL-6, and IL-1β). These cytokines then promote hepatic lipogenesis through SREBP1c- and CEBPβ-dependent induction of FASN and ACC. Inhibition of UBC9 phosphorylation by gene editing or SRC inhibitor reduces NF-κB–dependent inflammation and lessens ethanol-induced liver injury in mouse models. These findings uncover a previously unrecognized SRC–UBC9–NF-κB axis that drives inflammation in ALD and highlight it as a potential therapeutic target in liver disease.

Background: Upper extremity lymphedema occurs in 40% of patients following breast cancer treatments. In contrast, truncal lymphedema, a common complication of breast cancer treatment, is less understood and underreported. This study has 2 aims: (1) map lymphatic patterns of patients with truncal lymphedema and (2) describe our approach for the application of lymphovenous anastomosis (LVA) for truncal lymphedema and demonstrate the technical feasibility and potential clinical benefit. Methods: We retrospectively reviewed 95 patients (173 hemitrunks) following breast cancer treatment who underwent truncal ICG lymphography over 9 years. In 2 cases where conservative measures failed to provide relief, patients were treated with LVA placed inferior to the inframammary fold, directed by lymphographic findings. Results: Dermal backflow was significantly worse in the superior trunk, above the inframammary fold ( P < 0.001). Diffuse or absent superficial lymphatic channels were observed in 84% of mastectomy skin flaps. Lymphatic drainage was visualized to the ipsilateral axilla (40%), ipsilateral groin (66%), and contralateral trunk (26%). Conclusions: LVA can be used for surgical treatment of truncal lymphedema when conservative measures are insufficient. Patients treated in our practice had complete relief of symptoms by 12 months with reduced conservative management use, Lymphedema Life Impact Score, and number of infections per year. This work demonstrate that detailed lymphatic mapping enables targeted LVA planning and may offer an effective surgical option for managing breast cancer–related truncal lymphedema.

Background: Lipedema is a progressive adipofascial disorder marked by painful nodular fat deposition that is often mistaken for obesity. While tumescent liposuction reduces limb volume with relative lymphatic safety, persistent large, painful lobules frequently remain, and excisional strategies risk iatrogenic lymphatic injury. We evaluated the application of intraoperative indocyanine green (ICG) lymphography to identify and preserve lymphatic channels during debulking surgery for symptomatic lipedema. Methods: We conducted a single-center case series (University of Pittsburgh Medical Center, July 2023–December 2024) of adults with lipedema refractory to conservative therapy who underwent a selective dermato-lipectomy (lobule/skin excision) with or without tumescent liposuction. Patients with clinical lymphedema or dermal backflow in ICG were excluded. Near-infrared ICG (SPY-PHI) was used for pre-incision mapping and real-time intraoperative guidance; lymphatic trajectories were marked and spared during lobule excision. Primary measures included dermal backflow patterns and lymph node transit time; secondary outcomes were complications and symptom burden (Lymphedema Life Impact Scale, LLIS) through ≥24 months. Results: Eight patients (five female/three male; mean age 49.5 ± 14.4 years; median BMI 52.65 kg/m²) underwent ICG-guided surgery. Preoperatively, linear lymphatic patterns were visualized up to the knee in all patients, but dermal backflow patterns could not be visualized in 83% from the level of the knee to the groin. Still, 67% demonstrated inguinal nodal uptake (mean transit 24 min), suggesting preserved lymphatic transport. All cases achieved intraoperative confirmation of intact lymphatic flow after debulking. The mean liposuction aspirate was 925 ± 250 mL per lower extremity; the mean excision mass was 2209 ± 757 g per lower extremity. Complications included two superficial cellulitis events (25%) and one wound dehiscence (12.5%); no hematomas or skin necrosis occurred. No patient developed clinical or imaging evidence of iatrogenic lymphedema during follow-up. Conclusions: Intraoperative ICG lymphography is a practical adjunct for lymphatic-sparing debulking of symptomatic lipedema, enabling real-time identification and preservation of superficial collectors while addressing focal lobules. This hybrid approach—targeted tumescent liposuction followed by ICG-guided superficial dermato-lipectomy—was associated with meaningful symptom improvement and a low morbidity in this early series.

Introduction: Axillary reverse mapping (ARM) aims to reduce the risk of breast cancer-related lymphedema (BCRL) by preserving and limiting dissection of arm-draining lymphatics. The ideal type of dye and the location of injection, which maximize the sparing of lymphatics and improve outcomes of immediate lymphatic reconstruction (ILR), remain under-studied. The current literature reports inconsistent visualization of lymphatics using blue dye alone, whereas indocyanine green (ICG) near-infrared (NIR) lymphography has shown improved rates. However, optimized dual-dye workflows integrating breast–plastics co-surgery are lacking. Methods: A retrospective review of patients who underwent ILR following ALND for breast cancer between June 2021 and June 2023 was conducted. Patients who underwent ARM using our dual-dye technique were included, utilizing intradermal injections of indocyanine green (ICG) into the wrist and isosulfan blue (ISB) into the upper arm. Axillary reverse mapping channels were categorized by the type of dye used to visualize. Dye injection site, number of lymphatic channels visualized, channel diameter (mm), time-to-first channel, coordinates relative to fixed landmarks, ILR configuration, and pathologic findings were reviewed. Mann–Whitney U tests were used to compare channel visualization rates between types of dye. Results: Of 26 patients, 21 underwent dual-dye mapping and were included. A total of 115 ARM channels were identified: 99 (86%) via ICG and 29 (25%) via ISB. A total of 64 lymphaticovenous anastomoses were performed (mean: 2.46 per patient). Both dyes were identified in the axilla in only 11.7% of patients. At the end of the study, the lymphedema rate was 12%. Conclusions: We developed a reproducible dual-dye ARM technique for ALND with planned ILR, reducing lymphedema risk while maintaining oncologic safety. Dual-dye mapping reveals that proximal and distal lymphatics exhibit both overlapping and divergent drainage to axillary nodes. ICG’s higher axillary detection rate may reflect true anatomical differences or dye properties. These findings support the need for individualized lymphatic mapping during breast cancer surgery to guide preservation techniques and reduce the risk of BCRL.