Genomic landscape and distinct molecular subtypes of primary testicular lymphoma.

Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.

A new phenolic compound from Persicaria capitata.

Persicaria capitata was a frequently used Hmong medicinal flora in China. In this study, one new phenolic compound, capitaone A (1) together with 20 known ones, were isolated from the whole herb of P. capitata. Among them, 7 components (4, 9-11, 15-16, 20-21) were discovered from P. capitata for the first time. Their chemical structures were elucidated on the basis of extensive NMR and MS spectrum. Furthermore, three compounds (15, 20, 21) displayed remarkable cytotoxic activities against two human cancer cell lines (A549 and HepG2).

Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-κB signaling pathway.

Increasing evidence has demonstrated that the expression of coil domains containing 25 (CCDC25) in various malignancies is abnormally high. However, the potential regulatory role and mechanism of CCDC25 in the development of clear cell renal cell carcinoma (ccRCC) are still unclear. In this experiment, we combined in vitro experiments such as wound healing, CCK8, and transwell assay with in vivo experiments on tumor formation in nude mice to evaluate the effect of CCDC25 on the proliferation, migration, and invasion of renal cancer cells. In addition, we also used Western blotting and qPCR to evaluate the role of CCDC25 in activating the integrin-linked kinase (ILK)-NF-κB signaling pathway. Here, we demonstrate that compared to normal tissues and cell lines, CCDC25 is overexpressed in both human ccRCC tissues and cell lines. After CCDC25 knockdown, it has obvious inhibitory effect on the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In contrast, CCDC25 overexpression promotes these effects. Additionally, we also discovered that CCDC25 interacts with ILK and coordinates the activation of the NF-κB signaling pathway downstream. Generally, our study suggests that CCDC25 plays a vital role in the development of ccRCC, which also means that it may be a potential therapeutic target for ccRCC.

Association between periodontitis and inflammatory comorbidities: The common role of innate immune cells, underlying mechanisms and therapeutic targets.

Periodontitis, which is related to various systemic diseases, is a chronic inflammatory disease caused by periodontal dysbiosis of the microbiota. Multiple factors can influence the interaction of periodontitis and associated inflammatory disorders, among which host immunity is an important contributor to this interaction. Innate immunity can be activated aberrantly because of the systemic inflammation induced by periodontitis. This aberrant activation not only exacerbates periodontal tissue damage but also impairs systemic health, triggering or aggravating inflammatory comorbidities. Therefore, innate immunity is a potential therapeutic target for periodontitis and associated inflammatory comorbidities. This review delineates analogous aberrations of innate immune cells in periodontitis and comorbid conditions such as atherosclerosis, diabetes, obesity, and rheumatoid arthritis. The mechanisms behind these changes in innate immune cells are discussed, including trained immunity and clonal hematopoiesis of indeterminate potential (CHIP), which can mediate the abnormal activation and myeloid-biased differentiation of hematopoietic stem and progenitor cells. Besides, the expansion of myeloid-derived suppressor cells (MDSCs), which have immunosuppressive and osteolytic effects on peripheral tissues, also contributes to the interaction between periodontitis and its inflammatory comorbidities. The potential treatment targets for relieving the risk of both periodontitis and systemic conditions are also elucidated, such as the modulation of innate immunity cells and mediators, the regulation of trained immunity and CHIP, as well as the inhibition of MDSCs' expansion.

A novel hydrogen sulfide donor reduces neuroinflammation and seizures by activating ATP-sensitive potassium channels.

Epilepsy is a common neurological disorder worldwide. Hydrogen sulfide (H2S) has been found to have anti-seizure effects. However, its mechanism remains to be explored. In the present study, we showed that a novel H2S donor attenuated neuroinflammation by up-regulating ATP-sensitive potassium channel (KATP) expression to reduce seizures. The novel H2S donor significantly reduced the expression of TNF-α and increased the expression of IL-10 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. The modulatory effects of the H2S donor on inflammatory cytokines were prevented by glibenclamide, a common KATP channels blocker. The H2S donor promoted the expression of KATP channel subunits SUR2 and Kir6.1 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. In addition, the H2S donor reduced the electroencephalography amplitude of hippocampal epileptic waves and reduced seizures in pilocarpine-induced epileptic mice, which were also attenuated by glibenclamide. These results indicated that the novel H2S donor reduced seizures and regulated microglial inflammatory cytokines by activating KATP channels, which may provide a prospective therapeutic strategy for the anti-seizure effects of H2S donor.

Saccharomyces cerevisiae additions normalized hemocyte differential genes expression and regulated crayfish (Procambarus clarkii) oxidative damage under cadmium stress.

Because China produces the most crayfish in the world, safe solutions must be improved to mitigate the risks of ongoing heavy metal stressors accumulation. This study aimed to use Saccharomyces cerevisiae as a bioremediation agent to counteract the harmful effect of cadmium (Cd) on crayfish (Procambarus clarkia). Our study used three concentrations of S. cerevisiae on crayfish feed to assess their Cd toxicity remediation effect by measuring total antioxidant capacity (TAC) and the biomarkers related to oxidative stress like malondialdehyde (MDA), protein carbonyl derivates (PCO), and DNA-protein crosslink (DPC). A graphite furnace atomic absorption spectroscopy device was used to determine Cd contents in crayfish. Furthermore, the mRNA expression levels of lysozyme (LSZ), metallothionein (MT), and prophenoloxidase (proPO) were evaluated before and following the addition of S. cerevisiae. The results indicated that S. cerevisae at 5% supplemented in fundamental feed exhibited the best removal effect, and Cd removal rates at days 4th, 8th, 12th, and 21st were 12, 19, 29.7, and 66.45%, respectively, which were significantly higher than the basal diet of crayfish. The addition of S. cerevisiae increased TAC levels. On the other hand, it decreased MDA, PCO, and DPC, which had risen due to Cd exposure. Furthermore, it increased the expression of proPO, which was reduced by Cd exposure, and decreased the expression of LSZ and MT, acting in the opposite direction of Cd exposure alone. These findings demonstrated that feeding S. cerevisiae effectively reduces the Cd from crayfish and could be used to develop Cd-free crayfish-based foods.

Snow-cover loss attenuates the effects of N addition on desert nutrient cycling and microbial community.

Desert ecosystems are sensitive to nitrogen (N) deposition. Considering snow is an important source of soil water, which is vital for plant growth and the biogeochemical cycle in desert areas. The effects of N deposition on biological soil crusts (BSCs) could be impacted by the removal of snow-cover. Here, we established a split-plot experiment in the Gurbantunggut Desert to examine the effects of snow-cover treatments on soil nutrients, enzyme activities, and the bacterial community under various N addition. The removal of snow-cover reduced the soil nutrients with light and moderate N addition, it also reduced the activities of urease (URE) and alkaline phosphatase (PHOS). The structural equation model (SEM) result indicated that low soil moisture (SMO) under snow-uncover inhibited the bacterial community, particularly suppressed bacterial diversity. Additionally, N addition indirectly affected the bacterial community via modifications to soil nutrients, and soil organic matter (SOM) (P < 0.001) was the crucial factor. Snow-uncover weakened soil nutrient and enzyme responses to N addition, indicating that snow-cover removal reduced the sensitivity of the desert ecosystem to N deposition. The study highlights the critical role of snow-cover in the desert ecosystem, raising our awareness of the ecological risks of BSCs in future global change.

CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.

Cancer is a multi-step disease caused by the accumulation of genetic mutations and/or epigenetic changes, and is the biggest challenge around the world. Cytokines, including chemokines, exhibit expression changes and disorders in all human cancers. These cytokine abnormalities can disrupt homeostasis and immune function, and make outstanding contributions to various stages of cancer development such as invasion, metastasis, and angiogenesis. Chemokines are a superfamily of small molecule chemoattractive cytokines that mediate a variety of cellular functions. Importantly, the interactions of chemokine members CXCL12 and its receptors CXCR4 and CXCR7 have a broad impact on tumor cell proliferation, survival, angiogenesis, metastasis, and tumor microenvironment, and thus participate in the onset and development of many cancers including leukemia, breast cancer, lung cancer, prostate cancer and multiple myeloma. Therefore, this review aims to summarize the latest research progress and future challenges regarding the role of CXCL12-CXCR4/CXCR7 signaling axis in cancer, and highlights the potential of CXCL12-CXCR4/CXCR7 as a biomarker or therapeutic target for cancer, providing essential strategies for the development of novel targeted cancer therapies.

Reflection of Solar Light from Surface Snow Loaded with Light-Absorbing Impurities: A Case Study of Black Carbon, Mineral Dust, and Ash.

Using a hemispherical directional reflectance factor instrument, spectral data of dirty snow containing black carbon (BC), mineral dust (MD), and ash was collected from multiple locations to investigate the impact of these light-absorbing impurities (LAIs) on snow reflectance characteristics. The findings revealed that the perturbation of snow reflectance caused by LAIs is characterized by nonlinear deceleration, indicating that the reduction in snow reflectance per unit ppm of LAIs declines as snow contamination increases. The reduction in snow reflectance caused by BC may reach saturation at elevated particle concentrations (thousands of ppm) on snow. Snowpacks loaded with MD or ash initially exhibit a significant reduction in spectral slope around 600 and 700 nm. The deposition of numerous MD or ash particles can increase snow reflectance beyond the wavelength of 1400 nm, with an increase of 0.1 for MD and 0.2 for ash. BC can darken the entire measurement range (350-2500 nm), while MD and ash can only affect up to 1200 nm (350-1200 nm). This study enhances our understanding of the multi-angle reflection characteristics of various dirty snow, which can guide future snow albedo simulations and improve the accuracy of LAIs' remote sensing retrieval algorithms.

Engineered and Durable Antimicrobial Polymer via Controllable Immobilization of Ionic Liquids onto the Poly(lactic acid) Chains.

Nowadays, the development of effective modification methods for PLA has gained significant interest because of the wide application of antimicrobial PLA materials in the medical progress. Herein, the ionic liquid (IL) 1-vinyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide, has been grafted onto the PLA chains successfully in the PLA/IL blending films via electron beam (EB) radiation for the miscibility between PLA and IL. It was found that the existence of IL in the PLA matrix can significantly improve the chemical stability under EB radiation. The Mn of PLA-g-IL copolymer did not change obviously but was just decreased from 6.80 × 104 g/mol to 5.20 × 104 g/mol after radiation with 10 kGy. The obtained PLA-g-IL copolymers showed excellent filament forming property during electrospinning process. The spindle structure on the nanofibers can be completely eliminated after feeding only 0.5 wt % ILs for the improvement of ionic conductivity. Specially, the prepared PLA-g-IL nonwovens exhibited outstanding and durable antimicrobial activity for the enrichment of immobilized ILs on the nanofiber surface. This work provides a feasible strategy to realize the modification of functional ILs onto PLA chains with low EB radiation doses, which may have huge potential application in the medical and packaging industry.

Spatio-temporal heterogeneity of the coupling between digital economy and green total factor productivity and its influencing factors in China.

The synergy of the digital economy and green total factor productivity (TFP) is the foundation for achieving beneficial outcomes for both the economy and environment. This synergy is also the catalyst for high-quality development and sustainable economic growth in China. The study applied a modified Ellison-Glaeser (EG) index, super-efficiency slacks-based measure (SBM) with a Malmquist-Luenberger (ML) index, coupling coordination degree, and other models to explore the spatiotemporal heterogeneity of the coupling between the digital economy and green TFP from 2011 to 2020 and also analyzed the influencing factors of the coupling. The results show that the coupling between the digital economy and green TFP showed an overall upward trend from imbalance to synergy during the study period. The distribution of the synergistic coupling expanded from point-like to band-like, and there was a significant spreading pattern from the east to the center or west China. The number of cities in a transition state decreased significantly. Spatial jumps, a coupling linkage effect, and evolution in time were prominent. Additionally, the absolute difference among cities expanded. Although coupling in the west experienced the fastest growth rate, the coupling in the east and resource-based cities showed significant benefits. Coupling did not reach an ideal coordinated state, and a neutral interaction pattern remains to be formed. Industrial collaboration, industrial upgrading, government support, economic foundation, and spatial quality all positively impacted the coupling; technological innovation had a lagged effect; and environmental regulation has not reached its full potential. Further, the positive effects of government support and spatial quality performed better in the east and in non-resource-based cities. Due to the optimization of industrial structure, the coupling of the west and resource-based cities achieved better dividends; however, spatial quality needs further improvement. Therefore, the efficient coordination of China's digital economy and green TFP requires a scientific, reasonable, localized, and distinctive approach.

The regulatory role of PI3K in ageing-related diseases.

Ageing is a physiological/pathological process accompanied by the progressive damage of cell function, triggering various ageing-related disorders. Phosphatidylinositol 3-kinase (PI3K), which serves as one of the central regulators of ageing, is closely associated with cellular characteristics or molecular features, such as genome instability, telomere erosion, epigenetic alterations, and mitochondrial dysfunction. In this review, the PI3K signalling pathway was firstly thoroughly explained. The link between ageing pathogenesis and the PI3K signalling pathway was then summarized. Finally, the key regulatory roles of PI3K in ageing-related illnesses were investigated and stressed. In summary, we revealed that drug development and clinical application targeting PI3K is one of the focal points for delaying ageing and treating ageing-related diseases in the future.

Synthesis of KH550-Modified Hexagonal Boron Nitride Nanofillers for Improving Thermal Conductivity of Epoxy Nanocomposites.

In this work, KH550 (γ-aminopropyl triethoxy silane)-modified hexagonal boron nitride (BN) nanofillers were synthesized through a one-step ball-milling route. Results show that the KH550-modified BN nanofillers synthesized by one-step ball-milling (BM@KH550-BN) exhibit excellent dispersion stability and a high yield of BN nanosheets. Using BM@KH550-BN as fillers for epoxy resin, the thermal conductivity of epoxy nanocomposites increased by 195.7% at 10 wt%, compared to neat epoxy resin. Simultaneously, the storage modulus and glass transition temperature (Tg) of the BM@KH550-BN/epoxy nanocomposite at 10 wt% also increased by 35.6% and 12.4 °C, respectively. The data calculated from the dynamical mechanical analysis show that the BM@KH550-BN nanofillers have a better filler effectiveness and a higher volume fraction of constrained region. The morphology of the fracture surface of the epoxy nanocomposites indicate that the BM@KH550-BN presents a uniform distribution in the epoxy matrix even at 10 wt%. This work guides the convenient preparation of high thermally conductive BN nanofillers, presenting a great application potential in the field of thermally conductive epoxy nanocomposites, which will promote the development of electronic packaging materials.

A novel type lavandulyl flavonoid from Sophora flavescens as potential anti-hepatic injury agent that inhibit TLR2/NF-κB signaling pathway.

ETHNOPHARMACOLOGY RELEVANCE: Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens, which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. AIM OF THE STUDY: This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl4)-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. MATERIALS AND METHODS: The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1ß (IL-1ß), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1ß and cyclooxygenase-2 (COX2) in hepatic tissues were detected. RESULTS: The lavandulyl flavonoid (kurarinol A, 1) and the EtOAc extract from S. flavescens showed protective effects on CCl4-injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What's more, we found that treatment with kurarinol A (1) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1ß in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1ß, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. CONCLUSION: These findings demonstrated that the novel compound (kurarinol A, 1) possessed notable hepatoprotective activity against CCl4. It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl4, and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.

A transcription factor WRKY36 interacts with AFP2 to break primary seed dormancy by progressively silencing DOG1 in Arabidopsis.

The phytohormones abscisic acid (ABA) and gibberellic acid (GA) antagonistically control the shift between seed dormancy and its alleviation. DELAY OF GERMINATION1 (DOG1) is a critical regulator that determines the intensity of primary seed dormancy, but its underlying regulatory mechanism is unclear. In this study, we combined physiological, biochemical, and genetic approaches to reveal that a bHLH transcriptional factor WRKY36 progressively silenced DOG1 expression to break seed dormancy through ABI5-BINDING PROTEIN 2 (AFP2) as the negative regulator of ABA signal. AFP2 interacted with WRKY36, which recognizes the W-BOX in the DOG1 promoter to suppress its expression; Overexpressing WRKY36 broke primary seed dormancy, whereas wrky36 mutants showed strong primary seed dormancy. In addition, AFP2 recruited the transcriptional corepressor TOPLESS-RELATED PROTEIN2 (TPR2) to reduce histone acetylation at the DOG1 locus, ultimately mediating WRKY36-dependent inhibition of DOG1 expression to break primary seed dormancy. Our result proposes that the WRKY36-AFP2-TPR2 module progressively silences DOG1 expression epigenetically, thereby fine-tuning primary seed dormancy.

Identification of CCR2 as a hub in septic myocardial injury and cardioprotection of silibinin.

Myocardial injury is a serious complication of sepsis associated with high morbidity and mortality. Our previous work has confirmed that silibinin (SIL) alleviates septic myocardial injury, but the specific molecular mechanism has not been fully elucidated. This study aimed to identify its potential targets through network pharmacology combined with experimental verification. Firstly, a total of 29 overlapping genes between sepsis and SIL targets were obtained from RNA-seq analysis and the known databases. Subsequently, KEGG and GO analysis showed that these genes were enriched in immune response and cytokine-cytokine receptor interaction pathways. Notably, CCR2 was identified as an important candidate hub by protein-protein interaction analysis and molecular docking approach. In vivo experiments showed that SIL treatment significantly improved survival rate and cardiac function in septic mice, accompanied by decreased CCR2 expression. Moreover, in vitro experiments obtained the similar results. Especially, CCR2 siRNA attenuated inflammation response. In conclusion, this study systematically elucidated the key target of SIL in the treatment of septic myocardial injury. These findings provide valuable insights into the targets of sepsis and offer new avenues for exploring drug effect systematically.

The prognostic prediction of periodontal non-surgery therapy in periodontitis patients based on surface-enhanced Raman measurements of pre-treatment saliva.

Periodontitis is one of the most prevalent dental diseases, and the patients with periodontitis often suffer from refractory periodontitis or recurrence of disease due to improper or inadequate treatment. In clinical practice, the early and accurate assessment of post-treatment prognosis in periodontitis patients is always very important in order to implement timely interventions. In this study, a pre-treatment saliva SERS based prognostic protocol was explored to predict the prognosis of periodontal non-surgery therapy in periodontitis patients. According to the biomolecular analysis, significant differences in the levels of ascorbic acid, uric acid and glutathione are observed between good prognosis group and poor prognosis group, which are expected to serve as potential prognostic markers. Furthermore, high accuracy, sensitivity and specificity can also be achieved by using the proposed prognostic model. The excellent performance of the proposed method has demonstrated its potential for fast, accurate, and non-invasive prognostic prediction of periodontal non-surgery therapy in periodontitis patients, even at the time before implementing treatment, thus is expected to benefit timely and rational guidance on clinical interventions.

Nutritional qualities and antioxidant activity of Pleurotus floridanus grown on composted peach sawdust substrate with different composting time.

Recently, composting cultivation method is widely used in oyster mushroom production. In this study, we focused on the effects of composting processes on nutritional qualities and antioxidant activity of Pleurotus floridanus mushroom fruiting bodies. Three treatments of different composting time (2, 4, and 5 days) were performed with an atmospheric sterilization treatment as the control. The results showed that the pH value, total carbon content, and total nitrogen content of substrate were critical parameters which would significantly affect mushroom qualities and bioactivities. Fruiting bodies of the control demonstrated significantly higher crude protein content, total amino acid content, and essential amino acid content than that of composting treatments. Moreover, fruiting bodies of treatment D4 and D5 manifested significantly higher crude polysaccharide contents. Crude polysaccharide of treatment D4 represented the highest scavenging ability toward both radical 3-ethylbenzthiazoline-6-sulfonic acid (ABTS·+ ) and Hydroxyl radical (OH·). It suggests that composting processes is suitable for oyster mushroom cultivation based on nutritional and antioxidant qualities of fruiting bodies.

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis.

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.