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摘要： Castration-resistant prostate cancer (CRPC) nearly inevitably develops after long-term treatment with androgen deprivation therapy (ADT), leading to significant mortality. Investigating the mechanisms driving CRPC development is imperative. Here, we determined that the pioneer transcription factor GATA2, which is frequently amplified in CRPC patients, inhibits interferon (IFN)-beta-mediated antitumor immunity, thereby promoting CRPC progression. Employing a genetically engineered mouse model (GEMM), we demonstrated that GATA2 overexpression hindered castration-induced cell apoptosis and tumor shrinkage, facilitating tumor metastasis and CRPC development. Notably, GATA2 drives castration resistance predominantly via repressing castration-induced activation of IFN-beta signaling and CD8+ T-cell infiltration. This finding aligns with the negative correlation between GATA2 expression and IFNB1 expression, as well as CD8+ T-cell infiltration in CRPC patients. Mechanistically, GATA2 recruited PIAS1 as corepressor, and reprogramed the cistrome of IRF3, a key transcription factor of the IFN-beta axis, in an androgen-independent manner. Furthermore, we identified a novel silencer element that facilitated the function of GATA2 and PIAS1 through looping to the IFNB1 promoter. Importantly, depletion of GATA2 augmented antitumor immunity and attenuated CRPC development. Consequently, our findings elucidate a novel mechanism wherein GATA2 promotes CRPC progression by suppressing IFN-beta axis-mediated antitumor immunity, underscoring GATA2 as a promising therapeutic target for CRPC.

摘要： Between 2018 and 2023, the Department of Environmental, Land and Infrastructure Engineering (DIATI) at the Polytechnic University of Turin (PoliTo) implemented a project to advance research and education on climate change monitoring, adaptation and mitigation solutions. As part of their communication efforts, DIATI partnered with Faber Teater to create the play "Cambiare il clima"(in Italian, this means "Change the Climate"). This involved a collaboration between DIATI researchers, communication officers, and Faber Teater. The documentary theater that resulted was premiered at Biennale Tecnologia in 2020 and performed at various venues in Northern Italy, targeting both the general public and students.

关键词： BMMSCs   Aspirin   TNF-alpha   Stemness   YAP   SMAD7  

摘要： BackgroundBone marrow mesenchymal stem cells (BMMSCs) are commonly used for cell transplantation to treat refractory diseases. However, the presence of inflammatory factors, such as tumour necrosis factor-alpha (TNF-alpha), at the transplantation site severely compromises the stemness of BMMSCs, thereby reducing the therapeutic effect of cell transplantation. Aspirin (AS) is a drug that has been in use for over a century and has a wide range of effects, including the regulation of cell proliferation, multidirectional differentiation, and immunomodulatory properties of stem cells. However, it is still unclear whether AS can delay the damaging effects of TNF-alpha on BMMSC *** study investigated the effects of AS and TNF-alpha on BMMSC stemness and the molecular mechanisms using colony formation assay, western blot, qRT-PCR, and overexpression or knockdown of YAP and *** results demonstrated that TNF-alpha inhibited cell proliferation, the expression of stemness, osteogenic and chondrogenic differentiation markers of BMMSCs. Treatment with AS was shown to mitigate the TNF-alpha-induced damage to BMMSC stemness. Mechanistic studies revealed that AS may reverse the damage caused by TNF-alpha on BMMSC stemness by upregulating YAP and inhibiting the expression of *** can attenuate the damaging effects of TNF-alpha on BMMSC stemness by regulating the YAP-SMAD7 axis. These findings are expected to promote the application of AS to improve the efficacy of stem cell therapy.

关键词： HPV   IL-37   Inflammation   Growth   Oral epithelial cells  

摘要： This study investigated the impact of Human Papillomavirus (HPV) on inflammation and growth in oral epithelial cells, with a focus on the role of Interleukin-37 (IL37). Oral epithelial cells, including HOEC and HSC-3 cells, were employed in the research. The results revealed that HPV significantly induced inflammation in both types of oral epithelial cells, concurrently promoting cell growth and inhibiting apoptosis. IL37, a cytokine, was found to mitigate HPV-induced inflammation in oral epithelial cells. Moreover, IL37 counteracted HPV's effects on apoptosis and cell viability in oral epithelial cells. The study also identified a reduction in autophagy in HPV-infected oral epithelial cells, a phenomenon alleviated by IL37. Furthermore, chemical inhibition of autophagy was observed to attenuate HPV-induced inflammation and growth in oral epithelial cells. These findings contribute valuable insights into the pathogenesis of inflammation in oral epithelial cells associated with HPV and oral cancers, offering potential avenues for novel therapeutic strategies.

关键词： Anti-inflammatory   Arcangelisia flava   IL-1β   Nitric oxide   Osteoarthritis  

摘要： Introduction: One of the most frequent types of arthritis is osteoarthritis, also referred to as a degenerative joint disease. Interleukin-1β (IL-1β) and nitric oxide (NO) are essential factors in the pain response;IL-1β and NO are responsible for increasing the production of matrix metalloproteinases (MMP) and a disintegrin-like and metalloproteinases with thrombospondin motifs (ADAMS) in chondrocytes. Arcangelisia flava (L.) Merr. Has been traditionally used to treat jaundice, liver disease, diarrhea, fever, and inflammation. Methods: This study used in vitro and in vivo models to determine the effect of a 70 % ethanol extract of Arcangelisia flava (L.) Merr. stems on the inhibition of NO production in RAW 264.7 cells induced with lipopolysaccharide (LPS) and IL-1β in osteoarthritis rats induced with monosodium iodoacetate (MIA). The NO inhibition test was determined by the NO colorimetric assay using Griess reagent and measured by the ELISA plate reader. The measurement of joint diameter and hyperalgesia in osteoarthritis rats was carried out once a week for 7 weeks, and then the IL-1β levels were measured at weeks 3 and 7. Result: The viability of cell line this extract was greater than 80 %, and the extract at 25, 50, and 100 μg/mL significantly inhibited NO production (p < 0.0001) in RAW 264.7 cells induced with LPS. Meanwhile, this extract at 10, 30, and 90 mg/200g BW increased latency time, reduced joint swelling, and reduced IL-1β levels in the serum in the osteoarthritis rat model. Conclusion: 70 % ethanol extract of Arcangelisia flava (L.) Merr. Has the potential to be an anti-osteoarthritis drug. © 2024

关键词： Cyphos IL 101   萃取   Mo(VI)   离子液体   裂变   Mo  

摘要： 99Mo是重要的医用放射性核素，溶剂萃取法是反应堆辐照235U靶生产裂变99Mo的分离方法之一。为探讨离子液体Cyphos IL 101用于裂变99Mo分离的可能性，本研究评价了离子液体Cyphos IL 101在硝酸体系中对Mo（VI）的萃取行为，重点考察了稀释剂、水相初始pH、萃取时间、温度、离子液体浓度等对萃取Mo（VI）的影响。结果表明，选用甲苯作为稀释剂时，Cyphos IL 101对Mo（VI）的萃取效果最好，在pH=3条件下，萃取率高达98.87%；萃取为自发进行的过程，且可在5 min达到平衡；选用1 mol/L Na2CO3作为反萃剂，一次反萃可将负载有机相中96.56%的Mo反萃到水相中。构建的离子液体Cyphos IL 101萃取体系对Mo与主要杂质Sr、Cs、Te等有很好的分离效果，体现了其对Mo（VI）的高选择性萃取能力。以上结果可为将离子液体Cyphos IL 101引入裂变99Mo的分离工艺流程提供参考。

关键词： interleukin-22   bacterial disease   antioxidant   antiapoptotic   anti-inflammatory  

摘要： Mammalian interleukin-22 (IL-22) attenuates organismal injury by inhibiting reactive oxygen species (ROS) and impeding the NLRP3 inflammasome activation. However, the role of fish IL-22 in this process remains unclear. We characterized MaIL-22, an IL-22 homolog in blunt snout bream (Megalobrama amblycephala). Despite its low sequence identity, it shares conserved structures and close evolutionary relationships with other teleost IL-22s. Furthermore, Aeromonas hydrophila (A. hydrophila) infection leads to tissue injury in M. amblycephala immune organs and concomitantly altered Mail-22 mRNA expression, suggesting that MaIL-22 was involved in the antimicrobial immune response. To explore MaIL-22's biological functions, we produced recombinant MaIL-22 (rMaIL-22) protein and demonstrated it significantly enhanced the survival of M. amblycephala post-A. hydrophila infection. To unravel its protective mechanisms, we explored the ROS/NLRP3 inflammasome axis and its downstream signaling responses. The results showed that rMaIL-22 treatment significantly elevated antioxidant enzyme (T-SOD, CAT and GSH-PX) activities to inhibit MDA activity and scavenge ROS in visceral tissues. Meanwhile, rMaIL-22 impeded the activation of NLRP3 inflammasome by suppressing NLRP3 protein and mRNA expression. This indicated that rMaIL-22 contributed to inhibit A. hydrophila-induced activation of the ROS/NLRP3 inflammasome axis. Consistent with these findings, rMaIL-22 treatment attenuated the expression of proinflammatory cytokines (il-1 beta, tnf-alpha and il-6) and proapoptotic genes (caspase-3 and caspase-8) while promoting antiapoptotic genes (bcl-2b and mcl-1a) expression, ultimately mitigating tissue injury in visceral tissues. In conclusion, our research underscores MaIL-22's key role in microbial immune regulation, offering insights for developing IL-22-targeted therapies and breeding programs.

关键词： T1DM   STZ   Ranolazine   TXNIP   Beclin-1   NF-kappa B  

摘要： Approximately 90% of diabetic males have varying degrees of testicular dysfunction. The current study investigates the possible beneficial consequences of ranolazine against T1DM-induced testicular dysfunction in rats. Thirty-two male Sprague Dawley rats were assorted into 4 groups;normal, diabetic (single 50 mg/kg STZ, I. P.) and ranolazine (40 and 80 mg/kg, orally). The present investigation revealed that the hypoglycemic impact of ranolazine significantly improved the testicular weight and body weight of the final rats, as well as the concentration of blood testosterone, sperm count, and viability, all of which were associated with STZ-induced testicular dysfunction. Furthermore, as demonstrated by elevated reduced glutathione (GSH) activity and lowered malondialdehyde (MDA) levels, diabetic rats administered ranolazine showed a noteworthy improvement in the oxidant/antioxidant ratio. Furthermore, a substantial rise in beclin-1 concentration was seen in conjunction with a significant decrease in thioredoxin-interacting protein (TXNIP) and interleukin-18 (IL-18) concentrations when ranolazine was administered. Although ranolazine exhibited a reduction in inflammation as seen by lower expression of nuclear factor-kappa B (NF-kappa B) and cluster of differentiation (CD68) in the testicles, these biochemical findings were validated by improvements in the morphological and histopathological outcomes of both the pancreatic and testicular tissues. In conclusion, daily oral administration of ranolazine (40 and 80 mg/kg) for 8 weeks could be a promising therapy for T1DM-induced testicular dysfunction through its dose-dependent antioxidant and anti-inflammatory effects.

关键词： 牛呼肠孤病毒   多克隆抗体   蛋白   间接ELISA  

摘要： 为了制备牛呼肠孤病毒（MRV）结构蛋白σ1的多克隆抗体及建立血清学检测手段，本研究将σ1基因序列克隆至pET-32a(+)。获得重组质粒pET-32a-MRV3-σ1，并转化至BL21感受态细胞进行诱导表达与纯化，将纯化好的重组蛋白免疫于Balb/c小鼠制备多克隆抗体，同时以纯化后的σ1重组蛋白作为诊断抗原，建立检测MRV3的间接ELISA方法。结果显示，σ1蛋白的分子质量约为49.8 kDa，以包涵体形式表达，可应用于Western blot法及IFA检测，成功制备出MRV3-σ1多克隆抗体。建立的ELISA检测方法的批间及批内变异系数均小于10%；对MRV3阳性血清具有特异性，与牛冠状病毒、牛肠道病毒等阳性血清无交叉反应。表明该方法敏感性高、特异性强，为MRV3的临床检测和防控提供了技术支持。

关键词： Fraxinellone   Atopic dermatitis   IL-31   IL-31RA   TRPV1   TRPA1  

摘要： Chronic recurrent itch and skin inflammation are prominent features of atopic dermatitis (AD), which is closely related to the immune response driven by T-helper type 2 (Th2) cells. The expression of interleukin 31 (IL-31) is positively correlated with the severity of dermatitis. AntiIL-31 receptor alpha (IL-31RA) targeted drugs have been used to treat AD, however, they are expensive and have side effects. Fraxinellone (FRA) is one of the main limonoid components in the dried root bark of Dictamnus dasycarpus Turcz.;however, its anti-inflammatory and antipruritic effects on atopic dermatitis (AD) have not been previously reported. In this study, we investigated the anti-dermatitis effect of FRA and its potential mechanism of action using a 2,4dinitrofluorobenzene (DNFB)-induced AD-like mouse model and lipopolysaccharide (LPS)-stimulated HaCaT cells. FRA significantly inhibited chronic pruritus, epidermal thickening, and inflammatory infiltration in AD mice. FRA not only inhibited the levels of IL-31 in the serum and lesioned skin of AD mice but also significantly downregulated the mRNA expression and protein levels of IL-31, IL-31RA, transient receptor potential (TRP) V1, and TRPA1 in the lesioned skin and dorsal root ganglion (DRG) of AD mice. In LPS-stimulated HaCaT cells, FRA inhibited the production of iNOS and COX2, as well as the protein levels of IL-31, IL-31RA, TRPV1 and TRPA1, showing significant anti-inflammatory effects. In summary, our findings suggest that FRA exerts antipruritic and anti-inflammatory effects in AD by regulating the IL-31 pathway, and may hold promise for the clinical treatment of AD.