The Antileukemic Effect of Xestoquinone, A Marine-Derived Polycyclic Quinone-Type Metabolite, Is Mediated through ROS-Induced Inhibition of HSP-90.

Xestoquinone is a polycyclic quinone-type metabolite with a reported antitumor effect. We tested the cytotoxic activity of xestoquinone on a series of hematological cancer cell lines. The antileukemic effect of xestoquinone was evaluated in vitro and in vivo. This marine metabolite suppressed the proliferation of Molt-4, K562, and Sup-T1 cells with IC50 values of 2.95 ± 0.21, 6.22 ± 0.21, and 8.58 ± 0.60 µM, respectively, as demonstrated by MTT assay. In the cell-free system, it inhibited the activity of topoisomerase I (Topo I) and II (Topo II) by 50% after treatment with 0.235 and 0.094 µM, respectively. The flow cytometric analysis indicated that the cytotoxic effect of xestoquinone was mediated through the induction of multiple apoptotic pathways in Molt-4 cells. The pretreatment of Molt-4 cells with N-acetyl cysteine (NAC) diminished the disruption of the mitochondrial membrane potential (MMP) and apoptosis, as well as retaining the expression of both Topo I and II. In the nude mice xenograft model, the administration of xestoquinone (1 µg/g) significantly attenuated tumor growth by 31.2% compared with the solvent control. Molecular docking, Western blotting, and thermal shift assay verified the catalytic inhibitory activity of xestoquinone by high binding affinity to HSP-90 and Topo I/II. Our findings indicated that xestoquinone targeted leukemia cancer cells through multiple pathways, suggesting its potential application as an antileukemic drug lead.

The Antioxidant from Ethanolic Extract of Rosa cymosa Fruits Activates Phosphatase and Tensin Homolog In Vitro and In Vivo: A New Insight on Its Antileukemic Effect.

Rosa cymosa Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of R. cymosa fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of R. cymosa fruits (RCE) along with its underlying mechanism of action. RCE showed a potent cytotoxic effect against Sup-T1 and Molt-4 lymphoblastic leukemia cells. In the xenograft animal model, the tumor size was significantly reduced to about 59.42% in the RCE-treated group in comparison with the control group. The use of RCE (37.5, 75, or 150 µg/mL) triggered apoptosis by 26.52-83.49%, disrupted mitochondrial membrane potential (MMP) by 10.44-58.60%, and promoted calcium release by 1.29-, 1.44-, and 1.71-fold compared with the control group. The extract induced redox oxygen species (ROS) generation through the elimination of Nrf2/Keap1/P62-mediated oxidative stress response. The loss of phosphatase and tensin homolog (PTEN) activation by RCE impaired PI3K/Akt/Foxo and Jak/Stat activation pathways, which contributed to tumorigenesis. These multiple targets of R. cymosa against hematologic cancer cells suggested its potential application as an antileukemic dietary supplement.

Comparison of flap outcomes between single- and multiple-perforator-based free anterolateral thigh flap in head and neck reconstruction.

INTRODUCTION: The number of perforators required for safe perfusion remains under debate. This study aimed to determine whether a single- or multiple-perforator-based anterolateral thigh flap yields better flap outcomes in head and neck reconstruction. PATIENTS AND METHODS: Between August 2012 and July 2016, 180 men and 4 women with a mean age of 52.8 ± 9.8 years underwent head and neck anterolateral thigh flap reconstruction for oncologic defect in 181 cases, plate exposure in two cases, and trismus release in one case. The flap was patched for inner or external lining, folded for through-through defect, or tubed for cervical esophageal reconstruction. Of 184 flaps, 136 (73.9%) were based on multiple perforators (range, 2-5 perforators), whereas 48 (26.1%) were based on a single perforator. The demographics, operative findings, and flap outcomes were compared. RESULTS: The prevalence of systemic diseases between groups was comparable. The mean flap size in the single-perforator group was smaller (92.8 ± 36.8 vs. 140.5 ± 99.9 cm2 , P < .0001). Twenty-one flaps (11.4%) required emergency take-back and 13 (61.9%) were successfully salvaged. Eight flaps failed, yielding a 95.7% flap survival rate. The single-perforator group had a significantly higher rate of emergency take-back for vascular compromise (8/48 (16.7%) vs. 8/136 (5.9%), P = .035), a decreased salvage success rate (2/8 (25.0%) vs. 11/13 (84.6%), P = .018), and a corresponding lower flap survival rate (42/48 (87.5%) vs. 134/136 (98.5%), P = .004). CONCLUSION: Whenever possible, we recommend including multiple cutaneous perforators in anterolateral thigh flaps to yield better flap outcomes in head and neck reconstruction.

Temporary Ectopic Implantation of an Amputated Leg Using the Distal Runoff Vessel of the Anterolateral Thigh Flap Followed by Subsequent Prefabricated Chimeric Replantation.

AIM: Infrapopliteal replantation is indicated in selected patients. When the patient is hemodynamically unstable or the amputation site is severely contaminated, temporary ectopic implantation of the amputated limb is an option. To the best of our knowledge, this is the first case report using the distal runoff vessel of the anterolateral thigh flap for temporary ectopic implantation of an amputated leg followed by replantation with the prefabricated anterolateral thigh flap. PATIENT AND METHODS: A 28-year-old male driver had left leg avulsion amputation after a car accident. Because of concerns about the high-energy trauma mechanism and extensive trauma zone, temporary ectopic implantation was planned to avoid a lengthy replantation procedure and to enable future replantation. The amputated leg was implanted to the thigh using the distal runoff vessel of the descending branch of the lateral circumflex femoral system in the preservation of proximal cutaneous perforator. When the patient became hemodynamically stable and the amputated stump was relatively clean and healthy, we replanted the amputated leg with the prefabricated anterolateral thigh flap on day 7. RESULTS: The replanted leg and anterolateral thigh flap survived well after the procedure. At the 15-month follow-up, the patient could walk independently. There was no need for custom-made shoes because there was no obvious leg length discrepancy and the flap was not bulky. CONCLUSIONS: We believe that the distal runoff vessel of the descending branch of the lateral circumflex femoral system can not only serve as a recipient site for temporary ectopic implantation but also enable the harvest of a prefabricated anterolateral thigh flap with the amputated part at the replantation stage. This prefabricated tissue containing the anterolateral thigh flap and the amputated part needs only 1 set of vascular anastomosis to accomplish replantation and simultaneous revascularization of the anterolateral thigh flap. Most importantly, this ectopically prefabricated chimeric tissue minimizes the need for extensive bone shortening after radial debridement by providing sufficient soft tissue coverage at the replantation stage.

An optoelectrokinetic technique for programmable particle manipulation and bead-based biosignal enhancement.

Technologies that can enable concentration of low-abundance biomarkers are essential for early diagnosis of diseases. In this study, an optoelectrokinetic technique, termed Rapid Electrokinetic Patterning (REP), was used to enable dynamic particle manipulation in bead-based bioassays. Various manipulation capabilities, such as micro/nanoparticle aggregation, translation, sorting and patterning, were developed. The technique allows for versatile multi-parameter (voltage, light intensity and frequency) based modulation and dynamically addressable manipulation with simple device fabrication. Signal enhancement of a bead-based bioassay was demonstrated using dilute biotin-fluorescein isothiocyanate (FITC) solutions mixed with streptavidin-conjugated particles and rapidly concentrated with the technique. As compared with a conventional ELISA reader, the REP-enabled detection achieved a minimal readout of 3.87 nM, which was a 100-fold improvement in sensitivity. The multi-functional platform provides an effective measure to enhance detection levels in more bead-based bioassays.