Renal Protective Effect of Umbelliferone on Acute Kidney Injury in Rats via Alteration of HO-1/Nrf2 and NF-κB Signaling Pathway.

Acute kidney injury (AKI), formerly known as acute renal failure, refers to a sudden and often reversible decline in kidney function. Inflammatory reaction and oxidative stress play a crucial role in the expansion of renal disease. In this experimental study, we scrutinized the renal protective effect of umbelliferone against gentamicin induced renal injury in the rats and explore the mechanism. Wistar rats were used in this study and Gentamicin was used for the induction the AKI in the rats and rats were received the oral administration of umbelliferone. The body weight, organ weight, renal, oxidative stress, cytokines, inflammatory parameters were estimated. The mRNA expression caspase-3, Bax, Bcl-2, TNF-α, IL-1ß, IL-6, IL-10, HO-1, and Nrf2 were estimated. Umbelliferone remarkably improved the body weight and altered the absolute and relative weight of hepatic and renal tissue. Umbelliferone significantly suppressed the level of BUN, Scr, magnesium, calcium, phosphorus, sodium, and potassium along with altered the level of oxidative stress parameters like CAT, SOD, GSH, LPO, and GPx. Umbelliferone altered the level of cytokines viz., TNF-α, Il-1ß, IL-6, IL-10; inflammatory parameters like PGE2, COX-2, TGF-ß, NF-κB, respectively. Umbelliferone significantly altered the mRNA expression of caspase-3, Bax, Bcl-2, TNF-α, IL-1ß, IL-6, IL-10, HO-1, and Nrf2. The result showed the renal protective effect of umbelliferone against gentamycin induced renal disease via alteration of HO-1/Nrf2 and NF-κB Signaling Pathway.

Realizing p-type NbCoSn half-Heusler compounds with enhanced thermoelectric performance via Sc substitution.

N-type half-Heusler NbCoSn is a promising thermoelectric material due to favourable electronic properties. It has attracted much attention for thermoelectric applications while the desired p-type NbCoSn counterpart shows poor thermoelectric performance. In this work, p-type NbCoSn has been obtained using Sc substitution at the Nb site, and their thermoelectric properties were investigated. Of all samples, Nb0.95Sc0.05CoSn compound shows a maximum power factor of 0.54 mW/mK2 which is the highest among the previously reported values of p-type NbCoSn. With the suppression of thermal conductivity, p-type Nb0.95Sc0.05CoSn compound shows the highest measured figure of merit ZT = 0.13 at 879 K.

Efficacy and safety of trastuzumab deruxtecan in treating human epidermal growth factor receptor 2-low/positive advanced breast cancer:A meta-analysis of randomized controlled trials.

BACKGROUND: A novel antibody-drug conjugate, trastuzumab deruxtecan is a combination of a human epidermal growth factor receptor 2 (HER2)-targeting antibody and DNA topoisomerase I inhibitor used to treat HER2-low/positive advanced breast cancer. To determine its safety and efficacy in treating HER2-low/positive advanced breast cancer, we performed a meta-analysis of several randomized clinical trials (RCTs) including DESTINY-Breast02 (NCT03523585), DESTINY-Breast03 (NCT03529110), and DESTINY-Breast04 (NCT03734029). METHODS: We searched PubMed, Embase, and the Cochrane Library for RCTs on the efficacy and safety of trastuzumab deruxtecan that were published before May 2023. The efficacy endpoints included median progressive-free survival (PFS), overall survival (OS), duration of response (DOR), overall response rate (ORR), and clinical benefit rate (CBR). The safety endpoints included treatment-related adverse events. Statistical analyses were performed using RevMan 5.4 software. To ensure transparency, this study was registered on the International Prospective Register of Systematic Reviews website (CRD42023414170). RESULTS: Three RCTs involving 1689 patients were included. Compared with physician-recommended and conventional treatments, trastuzumab deruxtecan exhibited statistically significant improvements in PFS, ORR, and CBR. The median OS and DOR failed to be combined; however, the analyzed studies showed that they were longer. The incidence of adverse events was generally higher with trastuzumab deruxtecan than with physician-recommended or conventional treatments. CONCLUSION: The results of this study suggest that trastuzumab deruxtecan is more effective in treating HER2-low/positive advanced breast cancer than physician-recommended or conventional treatments. However, trastuzumab deruxtecan-related adverse drug reactions should be closely monitored because of its higher incidence of adverse events.

Fruit and vegetable intake and the risk of non-alcoholic fatty liver disease: a meta-analysis of observational studies.

Purpose: This systematic review and meta-analysis of clinical observational studies aims to clarify the correlation between the intake levels of fruits and vegetables and non-alcoholic fatty liver disease (NAFLD). Materials and methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies on the association between vegetable or fruit intake with the risk of NAFLD from the foundation of each database up until September 2023. The relative risk (OR) and the 95% confidence interval (CI) were pooled for both the highest and lowest consumption levels of vegetables and fruits to explore their association with the incidence of NAFLD. Results: The meta-analysis encompassed 11 studies with a total of 493,682 patients. A higher consumption of vegetables (OR = 0.78, 95% CI = 0.67-0.91) and fruits (OR = 0.88, 95% CI = 0.83-0.93) was found to have a negative correlation with the risk of NAFLD, denoting an inverse association. This correlation, however, varied among different ethnic groups and gender. Conclusions: Our results indicate that increased consumption of vegetables and fruits is associated with a reduced likelihood of developing NAFLD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier: CRD42023460430.

Reyanning mixture inhibits M1 macrophage polarization through the glycogen synthesis pathway to improve lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Reyanning (RYN) mixture is a traditional Chinese medicine composed of Taraxacum, Polygonum cuspidatum, Scutellariae Barbatae and Patrinia villosa and is used for the treatment of acute respiratory system diseases with significant clinical efficacy. AIM OF THE STUDY: Acute lung injury (ALI) is a common clinical disease characterized by acute respiratory failure. This study was conducted to evaluate the therapeutic effects of RYN on ALI and to explore its mechanism of action. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical components of RYN. 7.5 mg/kg LPS was administered to induce ALI in rats. RYN was administered by gavage at doses of 2 ml/kg, 4 ml/kg or 8 ml/kg every 8 h for a total of 6 doses. Observations included lung histomorphology, lung wet/dry (W/D) weight ratio, lung permeability index (LPI), HE staining, Wright-Giemsa staining. ELISA was performed to detect the levels of TNF-α, IL-6, IL-10, Arg-1,UDPG. Immunohistochemical staining detected IL-6, F4/80 expression. ROS, MDA, SOD, GSH/GSSG were detected in liver tissues. Multiple omics techniques were used to predict the potential mechanism of action of RYN, which was verified by in vivo closure experiments. Immunofluorescence staining detected the co-expression of CD86 and CD206, CD86 and P2Y14, CD86 and UGP2 in liver tissues. qRT-PCR detected the mRNA levels of UGP2, P2Y14 and STAT1, and immunoblotting detected the protein expression of UGP2, P2Y14, STAT1, p-STAT1. RESULTS: RYN was detected to contain 1366 metabolites, some of the metabolites with high levels have anti-inflammatory, antibacterial, antiviral and antioxidant properties. RYN (2, 4, and 8 ml/kg) exerted dose-dependent therapeutic effects on the ALI rats, by reducing inflammatory cell infiltration and oxidative stress damage, inhibiting CD86 expression, decreasing TNF-α and IL-6 levels, and increasing IL-10 and Arg-1 levels. Transcriptomics and proteomics showed that glucose metabolism provided the pathway for the anti-ALI properties of RYN and that RYN inhibited lung glycogen production and distribution. Immunofluorescence co-staining showed that RYN inhibited CD86 and UGP2 expressions. In vivo blocking experiments revealed that blocking glycogen synthesis reduced UDPG content, inhibited P2Y14 and CD86 expressions, decreased P2Y14 and STAT1 mRNA and protein expressions, reduced STAT1 protein phosphorylation expression, and had the same therapeutic effect as RYN. CONCLUSION: RYN inhibits M1 macrophage polarization to alleviate ALI. Blocking glycogen synthesis and inhibiting the UDPG/P2Y14/STAT1 signaling pathway may be its molecular mechanism.

Effects of Doping Ni on the Microstructures and Thermoelectric Properties of Co-Excessive NbCoSn Half-Heusler Compounds.

The half-Heusler (HH) compound NbCoSn with 18 valence electrons is a promising thermoelectric (TE) material due to its appropriate electrical properties as well as its suitable thermal and chemical stability. Nowadays, doping/substitution and tailoring of microstructures are common experimental approaches to enhance the TE performance of HH compounds. However, detailed theoretical insights into the effects of doping on the microstructures and TE properties are still missing. In this work, the microstructure of NbCoSn was tailored through precipitating the full-Heusler phases in the matrix by changing the nominal ratio of Co and Ni on the Co sites, focusing on the resulting TE properties. Further, first-principles calculations were employed to understand the relationship between the microstructure and the TE properties from the thermodynamic point of view. Detailed analysis of the electronic structure reveals that the presence of excess Co/Ni contributes to the increasing carrier concentration. Through an increase in the electrical conductivity and a reduction in the thermal conductivity, the TE performance is improved. Therefore, the present work offers a new pathway and insights to enhance the TE properties by modifying the microstructure of HH compounds via tailoring the chemical compositions.

Catalytic patch with redox Cr/CeO2 nanozyme of noninvasive intervention for brain trauma.

Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. Methods: In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed in vitro and in vivo. The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Results: Herein, the prepared Cr-doped CeO2 (Cr/CeO2) nanozyme increases the reduced Ce3+ states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO2. Furthermore, Cr/CeO2 nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The in vivo experiments show the Cr/CeO2 nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. Conclusions: The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.

Synthesis and Characterization of 40 wt % Ce0.9Pr0.1O2-δ-60 wt % NdxSr1-xFe0.9Cu0.1O3-δ Dual-Phase Membranes for Efficient Oxygen Separation.

Dense, H2- and CO2-resistant, oxygen-permeable 40 wt % Ce0.9Pr0.1O2-δ-60 wt % NdxSr1-xFe0.9Cu0.1O3-δdual-phase membranes were prepared in a one-pot process. These Nd-containing dual-phase membranes have up to 60% lower material costs than many classically used dual-phase materials. The Ce0.9Pr0.1O2-δ-Nd0.5Sr0.5Fe0.9Cu0.1O3-δ sample demonstrates outstanding activity and a regenerative ability in the presence of different atmospheres, especially in a reducing atmosphere and pure CO2 atmosphere in comparison with all investigated samples. The oxygen permeation fluxes across a Ce0.9Pr0.1O2-δ-Nd0.5Sr0.5Fe0.9Cu0.1O3-δ membrane reached up to 1.02 mL min-1 cm-2 and 0.63 mL min-1 cm-2 under an air/He and air/CO2 gradient at T = 1223 K, respectively. In addition, a Ce0.9Pr0.1O2-δ-Nd0.5Sr0.5Fe0.9Cu0.1O3-δ membrane (0.65 mm thickness) shows excellent long-term self-healing stability for 125 h. The repeated membrane fabrication delivered oxygen permeation fluxes had a deviation of less than 5%. These results indicate that this highly renewable dual-phase membrane is a potential candidate for long lifetime, high temperature gas separation applications and coupled reaction-separation processes.

Inhibitor of growth 2 regulates the high glucose-induced cell cycle arrest and epithelial-to-mesenchymal transition in renal proximal tubular cells.

The epithelial-to-mesenchymal transition (EMT)-based tubulointerstitial fibrosis is the major pathological feature of diabetic kidney disease (DKD). While several studies have linked cell cycle dysregulation to various kidney injuries in recent years, its involvement in fibrosis of DKD is far from being clarified. ING2 (inhibitor of growth 2) is the second member of the inhibitor of growth family and participates in the regulation of many cellular processes. So far the role of ING2 in DKD remains largely unknown. In the present study, ING2 expression was detected by western blotting and immunofluorescent staining both in vitro high glucose-stimulated human proximal tubular epithelial cells (HK-2) and in vivo streptozotocin-induced diabetic mice. Cell proliferation was analyzed by CCK-8 and EdU assay, and cell cycle arrest was measured by flow cytometry. Quantitative polymerase chain reaction (qPCR) and western blotting were used to detect the EMT markers, and the p53 signaling activation was evaluated by chromatin immunoprecipitation (ChIP), qPCR, and western blotting. We found that the proliferation of the cells was reduced upon high glucose stimulation, which was accompanied by cell cycle arrest. The expression of ING2 was increased in hyperglycemia conditions both in vivo and in vitro. ING2 suppression ameliorated the reduced proliferation and cell cycle arrest induced by high glucose in HK-2 cells. Moreover, ING2 knockdown suppressed p21 expression by reducing p53 acetylation and finally alleviated the EMT progress in the high glucose-stimulated HK-2 cells. Our study demonstrated that cell cycle regulation is bound up with the kidney fibrosis in DKD, suggesting a novel function of ING2 as a potential therapeutic strategy targeting cell cycle arrest for DKD.

Correction to: Inhibitor of growth 2 regulates the high glucose-induced cell cycle arrest and epithelial-to-mesenchymal transition in renal proximal tubular cells.

The above article was published online first with the following errors which have now been corrected.

Carbon dot targeting to nitrogen signaling molecules for inhibiting neuronal death.

Free radical-induced oxidative damage and nitrosative stress have been identified as key factors in neuroinflammation responses after traumatic brain injury (TBI), with which reactive oxygen and nitrogen species (RONS), especially nitrogen signaling molecules, are strongly associated. Here, we prepared ultrasmall carbon dot (CD) by using a simple and facile method. In vitro assessment experiments show that the antioxidative CD exhibits an ultrahigh target-scavenging effect for nitrogen signaling molecules, especially the highly reactive ˙NO and ONOO-. However, CD can only partially eliminate conventional oxygen radials such as O2˙- and ˙OH, indicating CD has a preference for RNS modulation. Moreover, in vitro cell experiments and in vivo mice experiments reveal that CD can reduce the reactive oxygen species (ROS) level and lipid peroxidation, enhance superoxide dismutase (SOD) activity and GSSG level, and further improve the survival rate of neuron cells and TBI mice. These results declare that antioxidative CD could serve as an effective therapeutic for TBI.

Nanozyme-Based Bandage with Single-Atom Catalysis for Brain Trauma.

Neurotrauma is one of the most serious traumatic injuries, which can induce an excess amount of reactive oxygen and nitrogen species (RONS) around the wound, triggering a series of biochemical responses and neuroinflammation. Traditional antioxidant-based bandages can effectively decrease infection via preventing oxidative stress, but its effectiveness is limited to a short period of time due to the rapid loss of electron-donating ability. Herein, we developed a nanozyme-based bandage using single-atom Pt/CeO2 with a persistent catalytic activity for noninvasive treatment of neurotrauma. Single-atom Pt induced the lattice expansion and preferred distribution on (111) facets of CeO2, enormously increasing the endogenous catalytic activity. Pt/CeO2 showed a 2-10 times higher scavenging activity against RONS as well as 3-10 times higher multienzyme activities compared to CeO2 clusters. The single-atom Pt/CeO2 retained the long-lasting catalytic activity for up to a month without obvious decay due to enhanced electron donation through the Mars-van Krevelen reaction. In vivo studies disclosed that the nanozyme-based bandage at the single-atom level can significantly improve the wound healing of neurotrauma and reduce neuroinflammation.