Explore the vast range of titles available.

Nitric oxide (NO) is a ubiquitous gas with free radical groups that is soluble in water, and which is involved in numerous physiological functions including inflammatory and immune responses. However, the role of NO in tumor biology is controversial and misunderstood. NO has been shown to have both anti-cancer and carcinogenic effects, which are dependent on the time, location, and concentration of NO. This duality presents a double challenge to determine the net impact of NO on cancer and to define the therapeutic role of NO-centered anti-cancer strategies. Nevertheless, it is believed that a comprehensive and dynamic understanding of the cascade of molecular and cellular events underlying tumor biology that are affected by NO will allow researchers to exploit the potential anti-tumor properties of drugs that interfere with NO metabolism.

Background Ischemia–reperfusion (I/R) injury is a major cause of surgical skin flap compromise and organ dysfunction. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, with tissue regenerative potential. PRP has shown promise in multiple I/R-induced tissue injuries, but its effects on skin flap injury remain unexplored. Methods We evaluated the effects of PRP on I/R-injured skin flaps, optimal timing of PRP administration, and the involved mechanisms. Results PRP protected against I/R-induced skin flap injury by improving flap survival, promoting blood perfusion and angiogenesis, suppressing oxidative stress and inflammatory response, and reducing apoptosis, at least partly via deactivating Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signalling pathway. PRP given before ischemia displayed overall advantages over that given before reperfusion or during reperfusion. In addition, PRP pretreatment had a stronger ability to reverse I/R-induced JAK/STAT activation and apoptosis than AG490, a specific inhibitor of JAK/STAT signalling. Conclusions This study firstly demonstrates the protective role of PRP against I/R-injured skin flaps through negative regulation of JAK/STAT activation, with PRP pretreatment showing optimal therapeutic effects.

Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet. In this study, we examined the role of hAECs-Exo on wound healing in a rat model. We found that hAECs, which exhibit characteristics of both embryonic and mesenchymal stem cells, have the potential to differentiate into all three germ layers. hAECs-Exo ranged from 50 to 150 nm in diameter, and positive for exosomal markers CD9, CD63, CD81, Alix, TSG101 and HLA-G. Internalization of hAECs-Exo promoted the migration and proliferation of fibroblasts. Moreover, the deposition of extracellular matrix (ECM) were partly abolished by the treatment of high concentration of hAECs-Exo (100 μg/mL), which may be through stimulating the expression of matrix metalloproteinase-1 (MMP-1). In vivo animal experiments showed that hAECs-Exo improved the skin wound healing with well-organized collagen fibers. Taken together, These findings represent that hAECs-Exo can be used as a novel hope in cell-free therapy for scarless wound healing.

Background Panax notoginseng (Burk) F. H. Chen is a valuable traditional Chinese medicinal plant, but its commercial production is seriously affected by root rot caused by some pathogenic fungi, including Fusarium solani . Nevertheless, the genetic breeding for disease resistance of P. notoginseng remains limited. The WRKY transcription factors have been revealed to play important roles in plant defense responses, which might provide an inspiration for resistance improvement in P. notoginseng . Results In this study, the regulatory mechanism of transcription factor PnWRKY15 on P. notoginseng resistance to F. solani infection was revealed. The suppressed expression of PnWRKY15 via RNA interference increased the sensitivity of P. notoginseng to F. solani and decreased the expression levels of some defense-related genes, including PnOLP1 , which encodes an osmotin-like protein that confers resistance to F. solani . Ectopic expression of PnWRKY15 in the model plant tobacco significantly enhanced the resistance to F. solani . Moreover, the transcriptome sequencing analysis discovered that some pathogenesis-related genes were expressed at higher levels in the PnWRKY15 -overexpressing tobacco than that in the wild-type tobacco. In addition, the jasmonic acid (JA) and salicylic acid (SA) signaling pathways were evidently induced by PnWRKY15 -overexpression, that was evidenced by that the JA and SA contents were significantly higher in the PnWRKY15 -overexpressing tobacco than that in the wild-type. Furthermore, PnWRKY15, which was localized in the nucleus, can trans-activate and up-regulate PnOLP1 expression according to the EMSA, yeast one-hybrid and co-expression assays. Conclusions PnWRKY15 contributes to P. notoginseng resistance to F. solani by up-regulating the expression of resistance-related gene PnOLP1 and activating JA/SA signaling pathways. These findings will help to further elucidate the transcriptional regulatory mechanism associated with the P. notoginseng defense response to F. solani .

Panax notoginseng (Burk) F.H. Chen is a rare and valuable Chinese herb, but root rot mainly caused by Fusarium solani severely affects the yield and quality of P. notoginseng herbal materials. In this study, we isolated 30 P. notoginseng WRKY transcription factors (TFs), which were divided into three groups (I, II, and III) on the basis of a phylogenetic analysis. The expression levels of 10 WRKY genes, including PnWRKY9 , in P. notoginseng roots increased in response to a methyl jasmonate (MeJA) treatment and the following F. solani infection. Additionally, PnWRKY9 was functionally characterized. The PnWRKY9 protein was localized to the nucleus. The overexpression of PnWRKY9 in tobacco ( Nicotiana tabacum ) considerably increased the resistance to F. solani , whereas an RNAi-mediated decrease in the PnWRKY9 expression level in P. notoginseng leaves increased the susceptibility to F. solani . The RNA sequencing and hormone content analyses of PnWRKY9 -overexpression tobacco revealed that PnWRKY9 and the jasmonic acid (JA) signaling pathway synergistically enhance disease resistance. The PnWRKY9 recombinant protein was observed to bind specifically to the W-box sequence in the promoter of a JA-responsive and F. solani resistance-related defensin gene ( PnDEFL1 ). A yeast one-hybrid assay indicated that PnWRKY9 can activate the transcription of PnDEFL1 . Furthermore, a co-expression assay in tobacco using β-glucuronidase (GUS) as a reporter further verified that PnWRKY9 positively regulates PnDEFL1 expression. Overall, in this study, we identified P. notoginseng WRKY TFs and demonstrated that PnWRKY9 positively affects plant defenses against the root rot pathogen. The data presented herein provide researchers with fundamental information regarding the regulatory mechanism mediating the coordinated activities of WRKY TFs and the JA signaling pathway in P. notoginseng responses to the root rot pathogen.

Background WRKY transcription factors (TFs) play vital roles in plant growth and development, secondary metabolite synthesis, and response to biotic and abiotic stresses. In a previous transcriptome sequencing analysis of Lilium regale Wilson, we identified multiple WRKY TFs that respond to exogenous methyl jasmonate treatment and lily Fusarium wilt ( Fusarium oxysporum ). Results In the present study, the WRKY TF LrWRKY3 was further analyzed to reveal its function in defense response to F. oxysporum . The LrWRKY3 protein was localized in the plant cell nucleus, and LrWRKY3 transgenic tobacco lines showed higher resistance to F. oxysporum compared with wild-type (WT) tobacco. In addition, some genes related to jasmonic acid (JA) biosynthesis, salicylic acid (SA) signal transduction, and disease resistance had higher transcriptional levels in the LrWRKY3 transgenic tobacco lines than in the WT. On the contrary, L. regale scales transiently expressing LrWRKY3 RNA interference fragments showed higher sensitivity to F. oxysporum infection. Moreover, a F. oxysporum -induced defensin gene, Def1 , was isolated from L. regale , and the recombinant protein LrDef1 isolated and purified from Escherichia coli possessed antifungal activity to several phytopathogens, including F. oxysporum . Furthermore, co-expression of LrWRKY3 and the LrDef1 promoter in tobacco enhanced the LrDef1 promoter-driven expression activity. Conclusions These results clearly indicate that LrWRKY3 is an important positive regulator in response to F. oxysporum infection, and one of its targets is the antimicrobial peptide gene LrDef1 .

Root rot, mainly caused by Fusarium oxysporum , is the most destructive disease affecting lily ( Lilium spp.) production. The WRKY transcription factors (TFs) have important roles during plant immune responses. To clarify the effects of WRKY TFs on plant defense responses to pathogens, a WRKY gene ( LrWRKY2 ) was isolated from Lilium regale Wilson, which is a wild lily species highly resistant to F. oxysporum . The expression of LrWRKY2 , which encodes a nuclear protein, is induced by various hormones (methyl jasmonate, ethephon, salicylic acid, and hydrogen peroxide) and by F. oxysporum infection. In this study, LrWRKY2 -overexpressing transgenic tobacco plants were more resistant to F. oxysporum than the wild-type plants. Moreover, the expression levels of jasmonic acid biosynthetic pathway-related genes ( NtAOC, NtAOS, NtKAT, NtPACX, NtJMT, NtOPR , and NtLOX ), pathogenesis-related genes ( NtCHI, NtGlu2 , and NtPR-1 ), and antioxidant stress-related superoxide dismutase genes ( NtSOD, NtCu-ZnSOD , and MnSOD ) were significantly up-regulated in LrWRKY2 transgenic tobacco lines. Additionally, the transient expression of a hairpin RNA targeting LrWRKY2 increased the susceptibility of L. regale scales to F. oxysporum . Furthermore, an F. oxysporum resistance gene ( LrCHI2 ) encoding a chitinase was isolated from L. regale . An electrophoretic mobility shift assay demonstrated that LrWRKY2 can bind to the LrCHI2 promoter containing the W-box element. Yeast one-hybrid assay results suggested that LrWRKY2 can activate LrCHI2 transcription. An examination of transgenic tobacco transformed with LrWRKY2 and the LrCHI2 promoter revealed that LrWRKY2 activates the LrCHI2 promoter. Therefore, in L. regale , LrWRKY2 is an important positive regulator that contributes to plant defense responses to F. oxysporum by modulating LrCHI2 expression.

To evaluate the agreement and repeatability of the S390L Firefly WDR slitlamp (S390L WDR+D130, MediWorks, Shanghai, China)   in tear film-related parameters measurement compared with Keratograph 5M(K5M) (Oculus Optikgeräte GmbH, Wetzlar, Germany). This prospective study assessed tear film parameters, including first non-invasive tear break-up time (NIBUTf), average non-invasive tear break-up time (NIBUTav), and tear meniscus height (TMH) using the S390L Firefly WDR slitlamp and K5M. Bland-Altman (BA) plots and the correlation coefficient r were used to assess the agreement of tear film parameters of two ocular surface analyzers. Intraclass correlation coefficient (ICC) was used to evaluate the repeatability of the S390L Firefly WDR slitlamp and K5M. Forty-four subjects from Shenyang He Eye Specialist Hospital were recruited in this study. There were no significant differences in the paired comparisons of NIBUTf, NIBUTav, and TMH ( p  > 0.05). The BA plots analysis showed a good agreement between the two devices for the NIBUTf (95% LoA, − 2.7 to 2.6), NIBUTav (95% LoA, − 4.5 to 3.6) and TMH (95% LoA, − 0.05 to 0.04). ICC of NIBUTf, NIBUTav, and TMH between the two measurements using S390L Firefly WDR slitlamp was 0.89, 0.84, and 0.98, respectively. The tear film-related parameters measurement of S390L Firefly WDR slitlamp had good repeatability and acceptable agreement with K5M. This study suggested a novel technique S390L Firefly WDR slitlampcan be considered an alternative to K5M in clinical settings, with an acceptable level of intrasession repeatability for clinical evaluation of tear film parameters.

ObjectiveTo systematically evaluate qualitative studies on the transition from paediatric to adult care during adolescence among patients with type 1 diabetes.DesignQualitative meta synthesis.MethodsThe search terms included four main categories: diabetes, transition, experience and qualitative studies. A total of 1214 studies were identified through the database search, and a total of 9 studies met all of the inclusion criteria for this review. Some studies included participants who were young or emerging adults at the time of interview; however, their accounts reflected retrospective experiences of transitioning from paediatric to adult care during adolescence.Data sourcesThe following nine electronic databases were searched: PubMed, Web of Science (Core Collection), The Cochrane Library, Embase, CINAHL, PsycINFO and CNKI, WanFang and Vip. The search period included material published up to July 2024.ResultsA total of nine studies revealed nine subthemes and three descriptive themes: difficulties and challenges, needs in transition, growing through adversity.ConclusionsAdolescents living with type 1 diabetes navigate complex experiences during the transition to adult healthcare. Healthcare professionals should be attentive to their feelings, encourage them to actively engage with challenges and provide adequate information and combined parental and peer support to facilitate a smooth transition.PROSPERO registration numberCRD42024560173.

Object. Hepatocellular carcinoma is one of the most common malignant tumors worldwide owing to its complicated molecular and cellular heterogeneity and its high incidence rate every year. It is an urgent need to search for new efficient molecular markers of HCC to reduce mortality and improve HCC prognosis. In this article, MCM4, a member of a family of proteins closely related to DNA replication and cell proliferation, was selected as a potential biomarker of HCC prognosis. Methods. MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort. Results. It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA (AUCMCM4=0.9461, AUCAFP=0.7056) and GEO (GSE19665: AUCMCM4=0.8800, AUCAFP=0.5100; GSE64041 AUCMCM4=0.8038, AUCAFP=0.6304). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC. Conclusion. MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.