Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia.

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in the treatment of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL); however, patients who receive CAR-T therapy are predisposed to infections, with considerable detrimental effects on long-term survival rates and the quality of life of patients. This study retrospectively analyzed infectious complications in 79 pediatric patients with R/R B-ALL treated with CAR-T cells at our institution. Overall, 53 patients developed 88 infections. Nine patients experienced nine infections during lymphodepletion chemotherapy, 35 experienced 41 infections during the early phase (days 0-+ 30 after infusion), and 29 experienced 38 infections during the late phase (day + 31-+ 90 after infusion). Pathogens were identified in 31 infections, including 23 bacteria, seven viruses, and one fungus. Four patients were admitted to the intensive care unit for infection and one died. In a univariate analysis, there were ten factors associated with infection, including tumor load, lymphodepleting chemotherapy, neutrophil deficiency and lymphocyte reduction, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), etc. In a multivariate analysis, CRS ≥ grade 3 was identified as a risk factor for infection (hazard ratio = 2.41, 95% confidence interval: 1.08-5.36, P = 0.031). Therefore, actively reducing the CRS grade may decrease the risk of infection and improve the long-term quality of life of these patients.

Antibacterial Micelles-Loaded Carboxymethyl Chitosan/Oxidized Konjac Glucomannan Composite Hydrogels for Enhanced Wound Repairing.

Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.

The development of local ambient air quality standards: A case study of Hainan Province, China.

The ambient air quality standard (AAQS) is a vital policy instrument for protecting the environment and human health. Hainan Province is at the forefront of China's efforts to protect its ecological environment, with an official goal to achieve world-leading air quality by 2035. However, neither the national AAQS nor the World Health Organization guideline offers sufficient guidance for improving air quality in Hainan because Hainan has well met the former while the latter is excessively stringent. Consequently, the establishment of Hainan's local AAQS becomes imperative. Nonetheless, research regarding the development of local AAQS is scarce, especially in comparatively more polluted countries such as China. The relatively high background values and significant interannual fluctuations in air pollutant concentrations in Hainan present challenges in the development of local AAQS. Our research proposes a world-class local AAQS of Hainan Province by reviewing the AAQS in major countries or regions worldwide, analyzing the influence of different statistical forms, and carefully evaluating the attainability of the standard. In the proposed AAQS, the annual mean concentration limit for PM2.5, the annual 95th percentile of daily maximum 8-h mean (MDA8) concentration limit for O3, and the peak season concentration limit for O3 are set at 10, 120, and 85 µg/m3, respectively. Our study indicates that, with effective control policies, Hainan is projected to achieve compliance with the new standard by 2035. The implementation of the local AAQS is estimated to avoid 1,526 (1,253-1,789) and 259 (132-501) premature deaths attributable to long-term exposure to PM2.5 and O3 in Hainan in 2035, respectively.

Adverse events and efficacy of second-round CAR-T cell therapy in relapsed pediatric B-ALL.

OBJECTIVE: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment approach for pediatric patients suffering from relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, there was a paucity of data on the challenges associated with second-round CAR-T therapy in this population. METHODS: Medical records of nine pediatric patients who received second-round CAR-T therapy in a single center from June 2019 to May 2023 were analyzed. Throughout the course of the clinical trial, we evaluated adverse events including CRS, CRES, infections, hematologic toxicity, and organ injury, as well as CAR-T responses. RESULTS: Except for one patient who chose CART therapy due to testicular relapse, the remaining patients had indications for CAR-T therapy due to relapse with bone marrow alone or combined with other site. There were no difference between the transfusion dose of CART1 and CART2. No differences of incidence and grade of CRS was found between the first-round CAR-T therapy (CART1) and second-round CAR-T therapy (CART2). Additionally, we found that the incidence of CRES was higher for CART1(3/9,33.3%) than CART2(1/9,11.1%). Our findings revealed that there were no differences of IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α between CART1 and CART2, but the peak level of IL-17A was significantly higher in patients receiving CART1 compared to those receiving CART2 (p = .011). Early and late infection rates after CART1 were higher than CART2. Based on the dynamic changes of ANC, hemoglobin and platelet, ANC, and platelet were reduced obviously post CART. It seems that the incidences of severe thrombocytopenia and severe anemia were higher in the CART1 group compared to CART2. The MRD-negative CR rates for CART1 and CART2 are 100% and 44.4%, respectively (p = .029). All patients experienced events (relapse, chemotherapy, transplantation, or death) after receiving CART2, including one died, three discharged automatically, and the remaining five patients survived. CONCLUSION: Although the remission rate of CART2 is not as high as the CART1 due to the severity of the disease, its safety regarding CRS, CRES, infections, and organ injury is still excellent. Therefore, CART2 remains a viable option for treating pediatric relapsed B-ALL.

Therapeutic Potential Evaluation of Silk Sericin Stabilized Fisetin to Ulcerative Colitis.

Ulcerative colitis is a chronic inflammatory bowel disease with a high recurrence rate. Natural phytochemical compounds are increasingly being considered as preventative and supportive treatments for this condition. However, the poor water solubility and stability of many of these compounds limit their effectiveness in vivo. To address this issue, fisetin (FT), a natural phytochemical with poor solubility, is stabilized using silk sericin (SS) to create a composite (SS/FT). The therapeutic potential of the SS/FT on ulcerative colitis is extensively investigated, and the results showed that it effectively alleviated the body weight loss and colon length shortening induced by dextran sulfate sodium. Notably, SS/FT downregulated the immune response, decreased colonic histopathological lesions, and reduced the cGAS/STING signal activation. This suggests that SS/FT may offer a promising therapy for treating ulcerative colitis.

Polyvinylpyrrolidone-Polydatin nanoparticles protect against oxaliplatin induced intestinal toxicity in vitro and in vivo.

Oxaliplatin (OXL) is a first-line drug for the treatment of colon cancer, with excellent efficacy. Intestinal toxicity is a common side effect of OXL, with unclear pathogenesis and a lack of effective treatment strategies. Polydatin (PD) has anti-inflammatory and antioxidant activities and is a potential drug for treating intestinal diseases, but its poor water solubility limits its application. In this study, polyvinylpyrrolidone (PVP) was used as a carrier to prepare nanoparticles loaded with PD (PVP-PD), with a particle size of 92.42 nm and exhibiting sustained release properties. In vitro results showed that PVP-PD protected NCM460 cells from OXL induced injury, mitochondrial membrane potential (MMP) disruption, and accumulation of reactive oxygen species (ROS). The in vivo results demonstrated the protective effect of PVP-PD on intestinal toxicity induced by OXL, such as alleviating weight loss and colon length reduction induced by OXL. Both in vivo and in vitro mechanisms indicated that OXL induced DNA damage and activated the cGAS-STING pathway, further inducing the expression of inflammatory factors such as IL-1ß and TNF-α. PVP-PD alleviated the aforementioned changes induced by OXL by inhibiting the DNA damage-cGAS-STING pathway. In summary, our study demonstrated that the DNA damage-cGAS-STING pathway was involved in OXL induced intestinal toxicity, and PVP-PD provided a potential strategy for treating OXL induced intestinal toxicity.

Encapsulation of Sericin-Decorated Efficient Agents in Silk Hydrogels for Wound Dressings.

Excessive oxidative stress, bacterial infections, and inflammation are the primary factors impeding the healing of skin wounds. Bioactive hydrogels are commonly employed in the treatment of skin injuries. However, the limited solubility of many drugs and active agents in water significantly hampers their effectiveness in hydrogel dressings. In this research, prior to incorporation into the silk fibroin (SF) hydrogel matrix, two active agents curcumin and silver nanoparticles (Ag NPs) were decorated by silk sericin to improve their dispersibility and stability in water. The resultant SF/Ag/C hydrogels combined the biological safety and nontoxicity of SF, the antioxidant and anti-inflammatory efficacy of curcumin, and the antibacterial effect of Ag NPs. These properties effectively enhanced wound repair by reducing bacterial infections, mitigating oxidative stress, suppressing the expression of pro-inflammatory factors, and promoting angiogenesis. This study presented a straightforward approach for constructing bioactive hydrogels for the promotion of the wound healing process.

Etamsylate loaded oxidized Konjac glucomannan-ε-polylysine injectable hydrogels for rapid hemostasis and wound healing.

Uncontrollable bleeding is a crucial factor that can lead to fatality. Therefore, the development of hemostatic dressings that enable rapid hemostasis is of utmost importance. Hydrogels with injectability, self-healing ability, and adhesiveness hold significant potential as effective hemostatic dressings. Herein, a composite hydrogel was fabricated by the oxidized Konjac glucomannan and ε-polylysine. After the encapsulation of a hemostatic drug, etamsylate, an oxidized Konjac glucomannan/ε-polylysine/etamsylate (OKGM/PL/E) composite hydrogel that possesses favorable properties including injectability, self-healing ability, tissue adhesiveness, hemocompatibility and cytocompatibility was fabricated. The OKGM/PL/E hydrogel demonstrated the ability to effectively adhere red blood cells and seal wounds, enabling rapid control of hemorrhaging. In vivo wound healing experiments confirmed the hemostatic and wound healing efficacy of the OKGM/PL/E hydrogel, highlighting its potential as a valuable hemostatic dressing.

Regulation of Eukaryotic Translation Initiation Factor 4E as a Potential Anticancer Strategy.

Eukaryotic translation initiation factors (eIFs) are highly expressed in cancer cells, especially eIF4E, the central regulatory node driving cancer cell growth and a potential target for anticancer drugs. eIF4E-targeting strategies primarily focus on inhibiting eIF4E synthesis, interfering with eIF4E/eIF4G interactions, and targeting eIF4E phosphorylation and peptide inhibitors. Although some small-molecule inhibitors are in clinical trials, no eIF4E inhibitors are available for clinical use. We provide an overview of the regulatory mechanisms of eIF4E and summarize the progress in developing and discovering eIF4E inhibitor strategies. We propose that interference with eIF4E/eIF4G interactions will provide a new perspective for the design of eIF4E inhibitors and may be a preferred strategy.

Drug-Loaded Konjac Glucomannan/Metal-Organic Framework Composite Hydrogels as Antibacterial and Anti-Inflammatory Cell Scaffolds.

Bacterial infections severely threaten human health; therefore, it is important to endow the matrix for tissue engineering with antibacterial efficiency. The loading of antibacterial drugs on nanomaterials provides an efficient strategy to realize synergistic antibacterial efficiency. By depositing various metal-organic frameworks, such as UIO-66, onto konjac glucomannan (KGM), composite hydrogels (KGM/UIO-66) were created. These hydrogels were used as drug carriers, enabling the development of antibacterial hydrogels with high drug loading capacities (e.g., the maximum loading amount of pterostilbene on KGM/UIO-66 reached 0.157 mg/mg) and sustained drug release. The resulting KGM/UIO-66/pterostilbene hydrogel exhibited a three-dimensional porous structure, excellent biocompatibility, antibacterial efficiency, and anti-inflammatory activity. It effectively protected cells from bacterial attacks while ensuring cell adhesion and proliferation, demonstrating great potential as a three-dimensional substrate for biomedical applications, including tissue engineering and regenerative medicine.

Silk fibroin peptide self-assembled nanofibers delivered naringenin to alleviate cisplatin-induced acute kidney injury by inhibiting mtDNA-cGAS-STING pathway.

Silk fibroin (SF) has excellent biocompatibility and biodegradability as a biomaterial. The purity and molecular weight distribution of silk fibroin peptide (SFP) make it more suitable for medical application. In this study, SFP nanofibers (molecular weight ∼30kD) were prepared through CaCl2/H2O/C2H5OH solution decomposition and dialysis, and adsorbed naringenin (NGN) to obtain SFP/NGN NFs. In vitro results showed that SFP/NGN NFs increased the antioxidant activity of NGN and protected HK-2 cells from cisplatin-induced damage. In vivo results also showed that SFP/NGN NFs protected mice from cisplatin-induced acute kidney injury (AKI). The mechanism results showed that cisplatin induced mitochondrial damage, as well as increased mitophagy and mtDNA release, which activated the cGAS-STING pathway and induced the expression of inflammatory factors such as IL-6 and TNF-α. Interestingly, SFP/NGN NFs further activated mitophagy and inhibited mtDNA release and cGAS-STING pathway. Demonstrated that mitophagy-mtDNA-cGAS-STING signal axis was involved in the kidney protection mechanism of SFP/NGN NFs. In conclusion, our study confirmed that SFP/NGN NFs are candidates for protection of cisplatin-induced AKI, which is worthy of further study.

Research on the Response Mechanism of Coal Rock Mass under Stress and Pressure.

In this paper, the strength and deformation failure characteristics of bearing coal rock mass are related to the confining pressure, and the SAS-2000 experimental system is used to carry out uniaxial and 3, 6, and 9 MPa triaxial tests on coal rock to assess the strength and deformation failure characteristics of coal rock under different confining pressure conditions. The results show that the stress-strain curve of coal rock undergoes four evolutionary stages after fracture: compaction, elasticity, plasticity, and rupture. With confining pressure, the peak strength of coal rock increases, and the elastic modulus increases nonlinearly. The coal sample changes more with confining pressure, and the elastic modulus is generally smaller than that of fine sandstone. The stage of evolution under confining pressure constitutes the failure process of coal rock, with the stress of different evolution stages causing various degrees of damage to coal rock. In the initial compaction stage, the unique pore structure of the coal sample makes the confining pressure effect more apparent; the confining pressure makes the bearing capacity of the coal rock plastic stage stronger, the residual strength of the coal sample has a linear relationship with the confining pressure, and the residual strength of the fine sandstone has a nonlinear relationship with the confining pressure. Changing the confining pressure state will cause the two kinds of coal rock samples to change from brittle failure to plastic failure. Different coal rocks under uniaxial compression experience more brittle failure, and the overall degree of crushing is higher. The coal sample in the triaxial state experiences predominantly ductile fracture. The whole is relatively complete after failure as a shear failure occurs. The fine sandstone specimen experiences brittle failure. The degree of failure is low, and the confining pressure's effect on the coal sample is obvious.

Enhanced biocompatibility of silk sericin/caffeic acid nanoparticles by red blood cell membranes cloaking.

Caffeic acid (CA) is an antioxidant phenolic compound that enriched in coffee beans, however, its administration often restrains by the instability and low solubility. Nanoparticle encapsulation is an effective approach to improve the therapeutic activity of CA. For example, silk sericin (SS), a natural biomaterial finds applications in food, cosmetics and biomedical fields, is proved here to be an appropriate encapsulation agent for CA, and a SS/CA composite nanoparticle has been fabricated. To further improve the biocompatibility of SS/CA, a red blood cell membranes (RM) cloaking strategy is adopted. The as-formed SS/CA/RM preserves the antioxidant activity of CA, and shows satisfactory biocompatibility especially under high concentration. Hope this can provide a potential appropriative strategy to adjust the chemical stability of insoluble drugs and to improve their biocompatibility.

Efficacy of Hemoperfusion Cartridge Procedure on Patients Undergoing Cardiac Valve Replacement Surgery with Cardiopulmonary Bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) induces inflammatory homeostasis dysregulation, closely related to many postoperative adverse effects. Minimizing the systemic inflammatory response to CPB is imperative to improving cardiac surgery safety. This study aimed to retrospectively evaluate the efficacy of the hemoperfusion cartridge, a device recently designed for extracorporeal blood purification to remove cytokines from the blood for patients undergoing cardiac valve replacement surgery using CPB. METHODS: The hemoperfusion (HP) group consisted of 138 patients, who underwent a hemoperfusion cartridge procedure during CPB. The control group included 149 patients, who received standard CPB management. The evaluated indices included inflammatory cytokines, blood biochemical indices, and postoperative outcome indices. RESULTS: Patients in the HP group had relatively lower interleukin (IL)-6 levels (days one and two post-CPB) and IL-8 (day one post-CPB) compared with the control group. Some relatively decreased biochemical blood indices also were observed in the HP group, including a significantly lower lactic acid level (days one, two, and three post-CPB), platelet counts (days one, two, and three post-CPB), and aspartate aminotransferase (days one and three post-CPB). Regarding the postoperative outcomes, no severe complications occurred in the patients; however, the HP group required less ventilation time than the control group. CONCLUSIONS: The hemoperfusion cartridge seems promising in limiting the inflammatory reactions during CPB, with noteworthy potential for application in cardiac surgery.

Modified cardiopulmonary bypass with low priming volume for blood conservation in cardiac valve replacement surgery.

BACKGROUND: The adverse effects of cardiopulmonary bypass during open cardiac surgery, including hemodilution, seem to be inevitable, especially for patients who generally have a relatively lower BMI with relatively small blood volumes. This study reports the modification and use of a cardiopulmonary bypass (CPB) system to reduce priming volume and hemodilution. METHODS: This is a retrospective study of 462 adult patients who underwent cardiac valve replacement surgery from January 2019 to September 2021 at the General Hospital of Western Theater Command. The modified group consisted of 212 patients undergoing modified CPB. The control group included 250 patients receiving conventional CPB. Evaluated indices included fluid intake and output volumes during CPB, intraoperative indices related to CPB operation, usage of blood products during the peri-CPB period, and postoperative outcomes. RESULTS: The modified group displayed a significant reduction in the crystalloid (200 mL vs. 600 mL, P < 0.05) and colloid priming volumes (450 mL vs. 1100 mL, P < 0.05), and ultrafiltration solution volume (750 mL vs. 1200 mL, P < 0.05). Furthermore, the modified group had a significantly lower rate of defibrillation (30.2% vs. 41.2%, P < 0.05). The intraoperative urine volume (650 mL vs. 500 mL, P < 0.05) and intraoperative hematocrit (Hct) (26% vs. 24%, P < 0.05) of the modified CPB group were also higher than in the control group. The modified group required a lower infusion volume of packed red blood cells (250 mL vs. 400 mL, P < 0.05) and lower infusion rates of packed red blood cells (17.9% vs. 25.2%, P < 0.05) and fresh frozen plasma (1.41% vs. 5.2%, P < 0.05). In addition, the modified group showed significantly improved indices related to postoperative recovery. CONCLUSIONS: The modified CPB system effectively conserves blood and shows noteworthy potential for application in cardiac valve replacement surgery.

Silicon Nanoparticles Embedded in Chemical-Expanded Graphite through Electrostatic Attraction for High-Performance Lithium-Ion Batteries.

Silicon (Si) is a promising next-generation anode for high-energy-density lithium-ion batteries. The application of silicon/carbon (Si/C) composites with high Si content is hindered by the huge volume change and insecure electrochemical interface of the Si anode. Herein, chemical-expanded graphite (CEG) is used as a carbon matrix to form Si@CEG/C composites with an embedded structure. CEG with an abundant pore structure and electropositivity can well disperse and accommodate a mass of Si nanoparticles (Si NPs). With the flexibility and porosity of CEG, the embedded structure of Si NPs fixed in an expanded graphite layer can adopt the volume change of Si NPs and offer the abundant path of diffusion of lithium-ion, which leads to a moderate cycle and rate performance. Si@CEG/C exhibits a high reversible capacity of 1232.4 mA h g-1 at a current density of 0.5 A g-1 and with a capacity retention rate of 87% after 200 cycles. This embedded structure of Si/C composites built by CEG is meaningful for the structure design of the Si-based anode with higher specific capacity, active material utilization, and satisfactory cycle stability.

Pterostilbene-Loaded Soluplus/Poloxamer 188 Mixed Micelles for Protection against Acetaminophen-Induced Acute Liver Injury.

Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected H2O2-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited H2O2-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.

Characterization, reactivity, source apportionment, and potential source areas of ambient volatile organic compounds in a typical tropical city.

Based on one-year observation, the concentration, sources, and potential source areas of volatile organic compounds (VOCs) were comprehensively analyzed to investigate the pollution characteristics of ambient VOCs in Haikou, China. The results showed that the annual average concentration of total VOCs (TVOCs) was 11.4 ppbV, and the composition was dominated by alkanes (8.2 ppbV, 71.4%) and alkenes (1.3 ppbV, 20.5%). The diurnal variation in the concentration of dominant VOC species showed a distinct bimodal distribution with peaks in the morning and evening. The greatest contribution to ozone formation potential (OFP) was made by alkenes (51.6%), followed by alkanes (27.2%). The concentrations of VOCs and nitrogen dioxide (NO2) in spring and summer were low, and it was difficult to generate high ozone (O3) concentrations through photochemical reactions. The significant increase in O3 concentrations in autumn and winter was mainly related to the transmission of pollutants from the northeast. Traffic sources (40.1%), industrial sources (19.4%), combustion sources (18.6%), solvent usage sources (15.5%) and plant sources (6.4%) were identified as major sources of VOCs through the positive matrix factorization (PMF) model. The southeastern coastal areas of China were identified as major potential source areas of VOCs through the potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models. Overall, the concentration of ambient VOCs in Haikou was strongly influenced by traffic sources and long-distance transport, and the control of VOCs emitted from vehicles should be strengthened to reduce the active species of ambient VOCs in Haikou, thereby reducing the generation of O3.

Myricetin-Loaded Nanomicelles Protect against Cisplatin-Induced Acute Kidney Injury by Inhibiting the DNA Damage-cGAS-STING Signaling Pathway.

Acute kidney injury (AKI) is the most common side effect of the anti-cancer drug cisplatin, and currently, no effective preventive measures are available in clinical practice. Oxidative stress and DNA damage mechanisms may be involved in cisplatin-induced AKI. In this study, we prepared Kolliphor HS15-based myricetin-loaded (HS15-Myr) nanomicelles and explored the mechanism of protection against cisplatin-induced AKI. In vitro results showed that the HS15-Myr nanomicelles enhanced the antioxidant activity of myricetin (Myr) and inhibited cisplatin-induced proliferation inhibition of HK-2 cells. Moreover, the HS15-Myr nanomicelles inhibited cisplatin-induced reactive oxygen species accumulation, mitochondrial membrane potential reduction, and DNA damage, which might be related to the inhibition of the cyclic GMP-AMP synthase (cGAS)─stimulating interferon gene (STING) signaling pathway. In vivo results in mice showed that the significant reductions in body weight and renal indices and the increased blood urea nitrogen and serum creatinine levels induced by cisplatin could be significantly reversed by pretreating with the HS15-Myr nanomicelles. Furthermore, nanomicelle pretreatment significantly altered the activities of antioxidant enzymes (e.g., GSH, MDA, and SOD) induced by cisplatin. In addition, cisplatin-induced inflammatory responses in mouse kidney tissue were found to be inhibited by pretreatment with HS15-Myr nanomicelles, such as IL-1ß and TNF-α expression. The nanomicelles also significantly inhibited cisplatin-induced activation of the DNA damage-cGAS-STING pathway in kidney tissues. Together, our findings suggest that Myr-loaded nanomicelles are potential nephroprotective drugs.

Fucoidan-ferulic acid nanoparticles alleviate cisplatin-induced acute kidney injury by inhibiting the cGAS-STING pathway.

Fucoidan (FU) is a natural sulfated polysaccharide with certain biological activity and has been shown to be an excellent nano-delivery material. In this study, ferulic acid (FA)-loaded FU nanoparticles (FA/FU NPs) were prepared and their nephroprotective mechanism was investigated. With a particle size of 158.6 ± 4.5 nm, FA/FU NPs increased the antioxidant activity of FA in vitro, possibly related to the increased dispersity of FA. In vitro results demonstrated that FA/FU NPs significantly protected human renal proximal tubule (HK-2) cells from cisplatin-induced damage, possibly by suppressing cisplatin-induced DNA damage and activating the cGAS-STING pathway. Furthermore, in vivo experiments confirmed that FA/FU NPs protected mice from cisplatin-induced acute kidney injury (AKI). Mechanistic studies confirmed that FA/FU NPs exerted nephroprotective effects by reducing MDA activity and increasing GSH and SOD activity. Our results demonstrated the potential of FU for delivering poorly soluble drug FA and protecting against cisplatin-induced AKI.