Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap.

Avascular necrosis frequently occurs as a complication following surgery involving the distal perforator flap. Dihydrocapsaicin (DHC) can protect tissue from ischemia-reperfusion (I/R) injury, but its specific role in multizone perforator flaps remains unclear. In this study, the prospective target of DHC in the context of I/R injury was predicted using network pharmacology analysis. Flap viability was determined through survival area analysis, laser Doppler blood flow, angiograms, and histological examination. The expressions of angiogenesis, apoptosis, NLR family pyrin domain containing 3 (NLRP3) inflammasome, oxidative stress, and molecules related to cyclic guanosine monophosphate (GMP)-adenosine monophosphate synthase (cGAS)-interferon gene stimulant (STING) pathway were assessed using western blotting, immunofluorescence, TUNEL staining, and dihydroethidium (DHE) staining. Our finding revealed that DHC promoted the perforator flap survival, which involves the cGAS-STING pathway, oxidative stress, NLRP3 inflammasome, apoptosis, and angiogenesis. DHC induced oxidative stress resistance and suppressed the NLRP3 inflammasome, preventing apoptosis in vascular endothelial cells. Through regulation of STING pathway, DHC controlled oxidative stress in endothelial cells and NLRP3 levels in ischemic flaps. However, activation of the cGAS-STING pathway led to the accumulation of reactive oxygen species (ROS) and NLRP3 inflammasome, thereby diminishing the protective role of DHC. DHC enhanced the survival of multidomain perforator flaps by suppressing the cGAS-STING pathway, oxidative stress, and the formation of NLRP3 inflammasome. These findings unveil a potentially novel mechanism with clinical significance for promoting the survival of multidomain perforator flaps.

Physiological and Biochemical Mechanisms of Wood Vinegar-Induced Stress Response against Tomato Fusarium Wilt Disease.

Wood vinegar, a by-product of charcoal biomass pyrolysis, has been used as a biofungicide in plant disease management because of its antimicrobial properties. However, the physiological and biochemical mechanisms through which wood vinegar alleviates biotic stress are poorly understood. In this study, pot experiments were conducted to investigate the resistance and regulation mechanism of wood vinegar prepared from different raw materials (ZM) and from a single raw material (SM) in controlling tomato (Solanum lycopersicum "Bonny Best") Fusarium wilt at different concentrations (0.3%, 0.6%, 0.9%, 1.2%, and 1.5%). The results showed that ZM and SM had significant control effects on tomato fusarium wilt under different concentrations in the same growth cycle. Under biotic stress, the two kinds of wood vinegar significantly increased the plant height, stem diameter, leaf area and yield of tomato under the concentration of 0.3%, 0.6%, 0.9% and 1.2%, and significantly reduced the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in tomato leaves. The effect of 0.9% treatment was the most significant, ZM and SM significantly increased tomato yield by 122% and 74%, respectively, compared with CK under 0.9% treatment. However, the plant height, stem diameter and leaf area of tomato were significantly reduced under 1.5% treatment, but the content of soluble sugar, soluble protein and vitamin C in tomato fruit was the best. Compared with CK, ZM significantly increased by 14%, 193% and 67%, respectively, and SM significantly increased by 28%, 300% and 159%, respectively. Except for 0.3% treatment, both significantly increased the activities of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) in tomato leaves. The response intensity of two kinds of wood vinegar-physiological and biochemical-to tomato disease resistance, growth and development, showed ZM > SM. The disease index of tomato showed highly significant negative correlation with plant height, stem thickness, leaf area and antioxidant physiology CAT, and highly significant positive correlation with MDA and H2O2 content. In conclusion, ZM was more effective than SM in enhancing tomato disease resistance by promoting tomato growth and development, decreasing leaf MDA and H2O2 content, and inducing antioxidant enzyme activity in leaves at moderate concentrations.

Tetrahydropalmatine: Orchestrating survival - Regulating autophagy and apoptosis via the PI3K/AKT/mTOR pathway in perforator flaps.

BACKGROUND: Introduced in clinical practice in 1989, perforator flaps are vital for tissue defect repair, but they are challenged by distal necrosis. Tetrahydropalmatine (THP) from celandine is renowned for its anti-inflammatory and analgesic effects. This study investigates THP's use in perforator flaps. METHODS: Thirty rats were divided into a control group and four THP concentration groups, while seventy-eight rats were categorized as control, THP, THP combined with rapamycin (RAP), and RAP alone. We created 11 cm by 2.5 cm multi-regional perforator flaps on rat backs, assessing survival blood flow and extracting skin flap tissue for autophagy, oxidative stress, apoptosis, and angiogenesis markers. RESULTS: The THP group exhibited significantly reduced distal necrosis, increased blood flow density, and survival area on the seventh day compared to controls. Immunohistochemistry and Western blot results demonstrated improved anti-oxidative stress and angiogenesis markers, along with decreased autophagy and apoptosis indicators. Combining THP with RAP diminished flap survival compared to THP alone. This was supported by protein expression changes in the PI3K-AKT-mTOR pathway. CONCLUSION: THP enhances flap survival by modulating autophagy, reducing tissue edema, promoting angiogenesis, and mitigating apoptosis and oxidative stress. THP offers a potential strategy for enhancing multi-regional perforator flap survival through the PI3K/AKT/mTOR pathway. These findings highlight THP's promise in combatting perforator flap necrosis, uncovering a novel mechanism for its impact on flap survival.