Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis.

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified. Here, we indicated that suppression of Golgi protein acyl-coenzyme A binding domain A containing 3 (ACBD3) increased the sensitivity of Henrieta Lacks and PANC1 cells to ferroptosis. ACBD3 knockdown increases labile iron levels by promoting ferritinophagy. This increase in free iron, coupled with reduced levels of glutathione peroxidase 4 due to ACBD3 knockdown, leads to the accumulation of reactive oxygen species and lipid peroxides. Moreover, ACBD3 knockdown also results in elevated levels of polyunsaturated fatty acid-containing glycerophospholipids through mechanisms that remain to be elucidated. Furthermore, inhibition of ferrtinophagy in ACBD3 downregulated cells by knocking down the nuclear receptor co-activator 4 or Bafilomycin A1 treatment impeded ferroptosis. Collectively, our findings highlight the pivotal role of ACBD3 in governing cellular resistance to ferroptosis and suggest that pharmacological manipulation of ACBD3 levels is a promising strategy for cancer therapy.

Severe mosquito bite allergy complicated by bacterial infection in a 7-year-old child: a case report and brief review of the literature.

INTRODUCTION: SMBA is a cutaneous form of CAEBV that predominantly affects adolescents and children from East Asian countries. It is characterized by local skin erythema, bullae, ulcers, necrosis, and scarring following a mosquito bite. Affected patients may experience IM-like systemic inflammatory reactions. SMBA mainly involves NK cells and has the potential to progress to NK/T-cell lymphoma or invasive NK-cell leukemia. CASE REPORT: A 7-year-old female was admitted to the hospital owing to recurring fever, skin allergies, and multifocal severe ulcerative necrotic skin lesions affecting both lower limbs. The authors primarily suspected bacterial infection, and debridement was insufficient to manage it. Pathological examination of residual skin tissues around the necrotic lesion revealed EBER-positive T cells. Eventually, the patient was diagnosed with SMBA complicated by bacterial infection based on diagnostic criteria and pathology findings. The patient responded well to timely antiviral and antibacterial treatment, with no deterioration during regular follow-up visits. CONCLUSIONS: SMBA is a subtype of CAEBV that is characterized by severe skin ulceration and is easily missed or misdiagnosed. Based on its mosquito bite history, pathological characteristics, and laboratory indicators, SMBA could expand new diagnostic and therapeutic approaches to the ulcerative skin diseases.

Application of 3 different types of pedicled adipofascial flaps in the repair of deep dead space wounds.

INTRODUCTION: Dead space is an important risk factor for poor wound healing; therefore, it is important to effectively fill deep dead space through individualized tissue flap design during the repair of complex wounds. Adipofascial flaps have yielded good results in the repair of deep dead space wounds. OBJECTIVE: The authors evaluated the efficacy of 3 kinds of adipofascial flaps to repair deep dead space wounds. METHODS: From January 2019 to January 2022, 15 patients with complicated wounds accompanied by deep dead space underwent repair via 1 of 3 kinds of adipofascial flaps, and the clinical efficacy was observed. RESULTS: All 15 transplanted adipofascial flaps exhibited complete survival, and within a mean follow-up of 14.7 months, both the donor and recipient sites had successfully healed. CONCLUSION: The traditional pedicled adipofascial flap was used to repair single deep dead space wounds, and pedicled perforator adipofascial extension flaps or layered fasciocutaneous flaps were used on compound tissue defect wounds, thus providing a relatively simple, safe, and effective method to repair a small area of tissue defect with deep dead space wounds.

Effect of the layered fasciocutaneous flap in the repair of complex wounds of the lower extremity.

INTRODUCTION: Repair of complex wounds of the lower extremity remains challenging for clinicians. When repairing complex wounds, it is necessary to customize the skin flap to simultaneously repair both the superficial soft tissue defect and the deep dead space wound. OBJECTIVE: This case series describes the use of a layered fasciocutaneous flap with pedicled perforator to repair complex wounds of the lower extremity. MATERIALS AND METHODS: Three cases with complex wounds of the lower extremity underwent repair using layered fasciocutaneous flap, and clinical efficacy was observed. RESULTS: In cases 1 and 3, complete survival of the layered flaps was achieved. In case 2, congestion measuring 1 cm × 1 cm occurred at the distal end of the skin paddle, followed by superficial skin ulceration, which healed 2 weeks after a dressing change. CONCLUSION: These findings indicate that a layered fasciocutaneous flap with pedicled perforator can be used to repair complex wounds of the lower extremity.

Exogenous L-carnitine ameliorates burn-induced cellular and mitochondrial injury of hepatocytes by restoring CPT1 activity.

BACKGROUND: Impaired hepatic fatty acid metabolism and persistent mitochondrial dysfunction are phenomena commonly associated with liver failure. Decreased serum levels of L-carnitine, a amino acid derivative involved in fatty-acid and energy metabolism, have been reported in severe burn patients. The current study aimed to evaluate the effects of L-carnitine supplementation on mitochondrial damage and other hepatocyte injuries following severe burns and the related mechanisms. METHODS: Serum carnitine and other indicators of hepatocytic injury, including AST, ALT, LDH, TG, and OCT, were analyzed in severe burn patients and healthy controls. A burn model was established on the back skin of rats; thereafter, carnitine was administered, and serum levels of the above indicators were evaluated along with Oil Red O and TUNEL staining, transmission electron microscopy, and assessment of mitochondrial membrane potential and carnitine palmitoyltransferase 1 (CPT1) activity and expression levels in the liver. HepG2 cells pretreated with the CPT1 inhibitor etomoxir were treated with or without carnitine for 24 h. Next, the above indicators were examined, and apoptotic cells were analyzed via flow cytometry. High-throughput sequencing of rat liver tissues identified several differentially expressed genes (Fabp4, Acacb, Acsm5, and Pnpla3) were confirmed using RT-qPCR. RESULTS: Substantially decreased serum levels of carnitine and increased levels of AST, ALT, LDH, and OCT were detected in severe burn patients and the burn model rats. Accumulation of TG, evident mitochondrial shrinkage, altered mitochondrial membrane potential, decreased ketogenesis, and reduced CPT1 activity were detected in the liver tissue of the burned rats. Carnitine administration recovered CPT1 activity and improved all indicators related to cellular and fatty acid metabolism and mitochondrial injury. Inhibition of CPT1 activity with etomoxir induced hepatocyte injuries similar to those in burn patients and burned rats; carnitine supplementation restored CPT1 activity and ameliorated these injuries. The expression levels of the differentially expressed genes Fabp4, Acacb, Acsm5, and Pnpla3 in the liver tissue from burned rats and etomoxir-treated hepatocytes were also restored by treatment with exogenous carnitine. CONCLUSION: Exogenous carnitine exerts protective effects against severe burn-induced cellular, fatty-acid metabolism, and mitochondrial dysfunction of hepatocytes by restoring CPT1 activity.

Efficacy of Treating Chronic Tibial Osteomyelitis With Bone Defect Using a Pedicled Perforator-Layered Flap and Fasciocutaneous Flap of the Posterior Tibial Artery: A Case Report.

INTRODUCTION: Tibial osteomyelitis is a common complication of bone tissue trauma. Obtaining good soft tissue coverage and effective infection management is key to the treatment of chronic osteomyelitis of the tibia accompanied with bone defect and bone exposure. The pedicled posterior tibial artery perforator layered fasciocutaneous flap can be used to repair soft tissue defects and can be used as a long-term, localized anti-infective. CASE REPORT: A 54-year-old male presented with an ulcer, purulent discharge at the left anterior tibia, and a fever 28 years after complete healing of the scar site. The patient received debridement and negative pressure wound therapy (NPWT) in a hospital setting. After presenting to the authors' department, there was difficulty in closing the exposed bone marrow cavity. On the basis of systemic use of intravenous antibiotics, multiple debridements and NPWT were used to effectively remove necrotic tissue and control infection. Afterward, the pedicled posterior tibial artery perforator layered fasciocutaneous flap was designed to fill the bone marrow cavity as well as cover and seal the wound of bone exposure and soft tissue defect simultaneously. The layered fasciocutaneous flap was well established after operation, and no recurrence of osteomyelitis was found. CONCLUSION: Debridement with negative pressure wound therapy can be an effective treatment for the wound bed preparation in advance of surgery, and the pedicled posterior tibial artery perforator layered fasciocutaneous flap can be used for the treatment of several soft tissue defects.

[Individualized therapy for burn wound].

Individualized therapy denotes that a suitable treatment project is chosen according to specific conditions of the patients with full benefit and minimal damage, and it is one of the contemporary surgical procedures that surgeons are looking for. But certain difficulties still exist in the treatment of burn patients, as well as repair of refractory or chronic wound as performed by burn surgeons. In this issue of the journal, application of individualized therapy in burn wound was discussed from various angles. For instance, through using Meek skin grafting technique, large sheets of skin graft could be saved for repair of wound on special body part of patients with severe burn, and combined flaps surgery could be applied to repair skin and soft tissue defects.

[Effects of docosahexaenoic acid on inflammation-associated cytokines in blood and pulmonary tissue of rats with severe scald injury].

OBJECTIVE: To observe the effects of docosahexaenoic acid (DHA) on the expressions of TNF-α, IL-6, and leukotriene B4 (LTB4) in serum and expression of NF-κB in pulmonary tissue of rats with severe scald injury. METHODS: One hundred and sixty SD rats were divided into sham injury (A), sham injury+DHA (B), scald (C), and scald+DHA (D) groups according to the random number table, with 40 rats in each group. Rats in groups A and B were sham injured, while rats in groups C and D were inflicted with 30% TBSA full-thickness scald on the back. Rats in groups B and D were injected with 0.5 mg/mL DHA solution with the dosage of 1 mL/kg via tail vein 5 minutes post injury, while rats in groups A and C with normal saline solution 1 mL/kg. At post injury hour (PIH) 3, 6, 12, 24, and 48, pulmonary tissue and abdominal aorta blood were collected from 8 rats in each group. The serum levels of TNF-α, IL-6, and LTB4 were determined with ELISA, and the protein expression of NF-κB p65 in pulmonary tissue was determined with Western blotting. Data were processed with analysis of variance of factorial design and LSD-t test. RESULTS: (1) The serum levels of TNF-α and IL-6 of rats in group A were similar to those of group B at each time point (with tTNF-α values from 0.223 to 0.947, tIL-6 values from 0.767 to 2.084, P values above 0.05). Compared with those of group A, the serum levels of TNF-α and IL-6 of rats in groups C and D were significantly higher at each time point (with tTNF-α values from 11.800 to 40.357, tIL-6 values from 10.334 to 39.321, P values below 0.01). The serum levels of TNF-α and IL-6 of rats in group D were significantly lower than those of group C at each time point (with tTNF-α values from -17.643 to -8.331, tIL-6 values from -21.596 to -6.332, P values below 0.01). The serum levels of TNF-α and IL-6 in groups C and D both showed a trend of increase earlier and decrease later, and they peaked at PIH 12, respectively (360.4 ± 13.2), (306.8 ± 7.2) pg/mL and (265.4 ± 12.3), (230.5 ± 2.2) pg/mL. (2) The serum level of LTB4 in group A was similar to that of group B at each time point (with t values from 0.787 to 1.096, P values above 0.05). The serum level of LTB4 was significantly higher in groups C and D than in group A at each time point (with t values from 7.501 to 38.962, P values below 0.01). The serum level of LTB4 in group D was obviously lower than that of group C at each time point (with t values from -19.244 to -2.532, P values below 0.01). The serum level of LTB4 in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, (4.59 ± 0.29) and (2.85 ± 0.32) ng/mL respectively. (3) The protein expression of NF-κB p65 in pulmonary tissue in group A was similar to that of group B at each time point (with t values from 0.847 to 1.256, P values above 0.05). The protein expression of NF-κB p65 was significantly higher in groups C and D than in group A at each time point (with t values from 15.167 to 98.074, P values below 0.01). The protein expression of NF-κB p65 in group D was obviously lower than that of group C at each time point (with t values from -37.190 to -14.415, P values below 0.01). The protein expression of NF-κB p65 in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, respectively 4.46 ± 0.12 and 2.94 ± 0.21. CONCLUSIONS: Parenteral supply of DHA to rats with severe scald injury can reduce the levels of TNF-α, IL-6, and LTB4 in serum and decrease the expression of NF-κB in pulmonary tissue, thus alleviating the inflammation response.

[Influence of omega-3 polyunsaturated fatty acids on inflammation-related parameters in lung tissue of rats with severe scald].

OBJECTIVE: To study the effect of omega-3 polyunsaturated fatty acids (omega-3 PUFA) on inflammation in lung tissue of rats with severe scald and its mechanism. METHODS: Seventy-two adult SD rats were divided into sham scald group (SS, n = 8), treatment group 1 (T1, n = 32), treatment group 2 (T2, n = 32) according to the random number table. Rats in T1 group and T2 group were inflicted with 30% TBSA full-thickness scald, and then they were respectively injected with 100 g/L omega-3 PUFA (1 mL/kg) and 200 g/L long-chain fatty acid (2 mL/kg) via tail vein within 5 minutes after burn. The above two fatty acids with equivalent calories were continuously injected for 10 days (once a day). On post burn day (PBD) 1, 4, 7, and 10, serum level of TNF-alpha and level of macrophage inflammatory protein 1alpha (MIP-lalpha) in lung homogenate of T1 and T2 groups were detected, the levels of NF-kappaBp65 and macrophage migration inhibitory factor (MIF) in lung tissue of T1 and T2 groups were observed with immunohistochemical staining (recorded as score). Above-mentioned parameters were also determined in SS group. Data were processed with t test. RESULTS: The levels of 4 parameters in T1 and T2 groups on PBD 1, 4, 7, 10 were higher than those in SS group (with t values from 3.411 to 8.782, P values all below 0.01), and those in T1 group on PBD 4, 7, 10 were lower than those in T2 group (with t values from 2. 321 to 2.785, P values all below 0.05). The serum level of TNF-alpha and levels of MIP-1alpha, NF-kappaBp65, and MIF in lung tissue in SS group was respectively (0.96 +/- 0.32) ng/mL, (76 +/- 16) pg/mL, 0.24 +/- 0.03, 1.31 +/- 0.03, and those in T1 and T2 groups all peaked on PBD 7 [(2.43 +/- 0.32) ng/mL, (210 +/- 56) pg/mL, 4.23 +/- 2.15, 4.69 +/- 1.83; (3.15 +/- 0.54) ng/mL, (274 +/- 64) pg/mL, 5.15 +/- 2.31, 5.37 +/- 2.16]. CONCLUSIONS: Omega-3 PUFA can effectively reduce serum level of TNF-alpha and levels of MIP-1alpha, NF-kappaBp65, and MIF in lung tissue of rats with severe scald, showing that it has a protective effect against injury of lung tissue.