Erectile dysfunction (ED) is widespread among individuals with high blood pressure and negatively affects quality of life. The effect of stromal vascular fraction (SVF) on hypertension-related ED remains unexplored. We used a hypertensive rat model to explore the relative efficacy of adipose tissue stromal vascular fraction (tSVF) and cellular SVF (cSVF). We then investigated the possible mechanisms of these treatments. Hypertensive rats were divided into three groups according to different treatments. Their intracavernous pressure (ICP) during erection and condition of cavernous tissue were compared to those of the controlled group. Endothelial-mesenchymal transformation (EndMT) markers as well as related inflammatory factors were also measured. cSVF and tSVF were labeled with CM-Dil before injection in order to determine whether cSVF and tSVF survived, proliferated, and transdifferentiated in vivo. The increased ICP during erection demonstrated that tSVF treatment significantly improved hypertension-related ED. tSVF increased the smooth muscle-to-collagen ratio and inhibiting the expression of fibrosis-related proteins in hypertensive rats while rescuing the expression of vWF and eNOS, which indicated the preserving of endothelial tissue of the penis. Immunofluorescence staining and western blotting of penile tissue clearly suggest the inhibitory effect of tSVF on the overoccurring EndMT. Immunofluorescence staining and Western blot analysis of endothelial cells in vitro corroborate the whole-tissue findings. The experiments in N-nitro-L-arginine methyl ester hydrochloride (L-NAME)–induced human umbilical vein endothelial cells (HUVECs) revealed tSVF suppresses EndMT via inhibiting the TGF- β 2–Smad2/Smad3 pathway. In vivo tSVF and cSVF tracing suggested that tSVF showed better longevity and transdifferentiation capacity than cSVF, thus exerting a more significant therapeutic effect. Treatment with tSVF significantly reserved erectile function in a hypertensive rat model. The mechanism appears to be inhibition of pathological EndMT through self-differentiation. We conclude that tSVF is a promising therapeutic candidate for treating hypertensive ED.

Interstitial cystitis/bladder pain syndrome (IC/BPS) and metabolic syndrome (MetS) are complex disorders with overlapping clinical features, and emerging evidence suggests oxidative stress and ferroptosis may underlie their pathogenesis. Here, using an integrative approach combining bioinformatics, immunohistochemistry, and functional studies in cellular and animal models, we identified NFE2 as a key regulator significantly upregulated in IC/BPS patients, particularly those with MetS comorbidity, where it promotes ferroptosis through competitive inhibition of Nrf2-mediated antioxidant responses, leading to reactive oxygen species accumulation and lipid peroxidation. We further demonstrated that the natural flavonoid naringenin (NAG) specifically binds to NFE2, downregulates its expression, and activates the Nrf2/NQO-1 pathway, resulting in improved bladder function, reduced inflammation, and attenuated fibrosis in animal models. These findings establish NFE2-mediated ferroptosis as a novel pathogenic link between IC/BPS and MetS and identify NAG as a promising therapeutic agent capable of simultaneously targeting metabolic and inflammatory components in refractory IC/BPS patients with metabolic dysfunction.

Renal ischemia–reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) in a variety of clinical settings. Current therapeutic interventions are significantly constrained by limitations include low drug specificity, requisite repeated administration, and a paucity of effective treatments. Although mesenchymal stem cells (MSCs) based therapies exhibit treatment prospects for mitigating renal IRI, low retention and translational efficacy still hinder clinical application. To address these pivotal limitations, this study employed an innovative combinatorial approach integrating genetic engineering with cell sheet technology. Specifically, we generated genetically engineered CX3CR1 overexpressing MSCs sheets to investigate their therapeutic effects and mechanism in attenuating renal IRI in a rat model. Results showed that CX3CR1-MSCs cell sheets were positive for CD31, CD34, α-SMA and Fibronectin. In vivo, these sheets amplified MSCs paracrine effects, promoted the recruitment and polarization of M2 macrophage phenotype, stimulated renal vascularization, and inhibited fibrosis and inflammation. In vivo imaging in animals revealed genetically engineered cell sheets markedly improved the retention of MSCs in the kidney, enhancing both cell engraftment and paracrine therapeutic action. Our results indicate that CX3CR1-engineered MSCs sheets offer superior prevention against renal IRI.

Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is a common challenge in various clinical practices, yet effective therapies remain elusive. Endothelial injury plays a crucial role in the pathogenesis of renal IRI. Endothelial progenitor cells (EPCs) derived extracellular vesicles (EVs) hold promise as cell-free therapies for treating renal IRI; however, their efficacy is limited by low delivery efficiency. In this study, we developed neutrophils (NEs) membrane-modified EVs (N-EVs) by exploiting the natural properties of NEs to target damaged endothelium. N-EVs inherited the characteristic membrane proteins of NEs along with the biological functions of EPCs-EVs. Results from in vitro and in vivo experiments demonstrated that N-EVs significantly enhanced the targeting efficiency of EVs towards IRI kidneys via P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, N-EVs effectively promoted the proliferation, migration, and tube-formation abilities of injured endothelial cells (ECs) and contributed to overall renal function improvement in IRI kidneys through targeted delivery of miR-21-5p. Additionally, N-EVs could restore damaged endothelial integrity, reduce cytokine release, and inhibit leukocyte infiltration, hence alleviating renal inflammation. In conclusion, our accessible engineering approach represents a promising strategy for treating renal IRI. Furthermore, this membrane hybrid modification can be tailored and optimized for broader applications in treating other diseases.

Repairing tissue, especially in chronic wounds, is a major clinical challenge. Traditional treatments often lead to slow recovery and poor biocompatibility. Adipose-derived stem cell exosomes (ADSC-exo) offer a promising solution for tissue regeneration due to their anti-inflammatory and immunomodulatory effects. However, directly injecting stem cells results in a low survival and function loss. This study introduces a Janus G-Avs patch that promotes tissue repair by releasing ADSC-exo and prevents postoperative tissue adhesion. The patch's top layer, created via coaxial electrospinning, acts as an ADSC-exo delivery system with a core-shell structure by incorporating ADSC-exo and hyaluronic acid (HA) into methacrylate gelatin (GelMA) to prolong exosome release. The bottom layer consists of a 4arm-PLGA(4aPLGA)-Glu/PCL electrospun membrane, offering a lubricated antifouling surface that prevents protein adsorption and provides mechanical support. In rat models, the G-Avs patch has demonstrated its ability to enhance cell proliferation, promote angiogenesis, and encourage macrophage polarization toward the M2 phenotype, thereby mitigating inflammatory responses and promoting tissue repair. Transcriptomic analysis indicates that the G-Avs patch augments cellular energy metabolism by upregulating metabolic pathways and downregulating immune-inflammatory pathways, collectively supporting tissue repair. In summary, the Janus G-Avs patch has a strong clinical potential.

Urethral stricture (US) is a common disease in urology, lacking effective treatment options. Although injecting a stem cells suspension into the affected area has shown therapeutic benefits, challenges such as low retention rate and limited efficacy hinder the clinical application of stem cells. This study evaluates the therapeutic impact and the mechanism of adipose-derived vascular fraction (SVF) combined with cell sheet engineering technique on urethral fibrosis in a rat model of US. The results showed that SVF-cell sheets exhibit positive expression of α-SMA, CD31, CD34, Stro-1, and eNOS. In vivo study showed less collagen deposition, low urethral fibrosis, and minimal tissue alteration in the group receiving cell sheet transplantation. Furthermore, the formation of a three-dimensional (3D) tissue-like structure by the cell sheets enhances the paracrine effect of SVF, facilitates the infiltration of M2 macrophages, and suppresses the TGF-β/Smad2 pathway through HGF secretion, thereby exerting antifibrotic effects. Small animal in vivo imaging demonstrates improved retention of SVF cells at the damaged urethra site with cell sheet application. Our results suggest that SVF combined with cell sheet technology more efficiently inhibits the early stages of urethral fibrosis.

Prostate cancer (PCa) ranks as the sixth most serious male malignant disease globally. While docetaxel (DTX) chemotherapy is the standard treatment for advanced PCa patients with distant metastasis, some individuals exhibit insensitivity or resistance to DTX. Cancer-associated fibroblasts (CAFs) play a pivotal role as stromal cells within the tumor microenvironment, influencing tumor development, progression, and drug resistance through exosomes. Ferroptosis, a novel form of programmed cell death, is characterized by intracellular iron accumulation that triggers lipid peroxidation, ultimately leading to cell demise. To delve into the potential mechanisms of chemotherapy resistance in prostate cancer, our research delved into the impact of CAF-derived exosomes on ferroptosis. Our findings revealed that CAF exosomes hindered the buildup of lipid reactive oxygen species (ROS) in prostate cancer cells induced by erastin, as well as mitigated erastin-induced mitochondrial damage, thereby impeding iron-induced cell death in prostate cancer cells. Furthermore, miR-432-5p was identified to diminish glutathione (GSH) consumption by targeting CHAC1, consequently inhibiting ferroptosis in prostate cancer cells. Our study found that miR-432-5p, originating from cancer-associated fibroblast (CAF) exosomes, suppresses ferroptosis by targeting CHAC1, thereby increasing resistance to docetaxel (DTX) in PCa. This research introduces a novel approach to address resistance to DTX.

Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders; however, the lack of retention leads to limited distribution of AMEs in the scaffold areas and low bioavailability of AMEs after bladder reconstruction. To improve retention of AMEs, we developed a novel strategy that modifies the surface charge of the bladder acellular matrix (BAM) via oxidative self-polymerization of dopamine-reducing graphene oxide (GO) and AMEs using ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD). We evaluated two BAM surface modification methods and evaluated the biocompatibility of materials and PPD and electrostatic adherence effects between PPD-modified AMEs and rGO-PDA/BAM in vivo and in vitro. Surface modification increased retention of AMEs, enhanced regeneration of bladder structures, and increased electrical conductivity of rGO-PDA/BAM, thereby improving bladder function recovery. RNA-sequencing revealed 543 miRNAs in human AMEs and 514 miRNAs in rat AMEs. A Venn diagram was used to show target genes of miRNA with the highest proportion predicted by the four databases; related biological processes and pathways were predicted by KEGG and GO analyses. We report a strategy for improving bioavailability of AMEs for bladder reconstruction and reveal that enriched miR-21-5p targets PIK3R1 and activates the PI3K/Akt pathway to promote cell proliferation and migration.

The extracellular matrix (ECM) regulates many biological functions involved in tumorigenesis and tumor development; however, the underlying mechanism remains unknown. Sigma 1 receptor (Sig1R), a stress-activated chaperone, regulates the crosstalk between the ECM and tumor cells and is related to the malignant characteristics of several tumors. However, the link between Sig1R overexpression and ECM during malignancy has not been established in bladder cancer (BC). Here, we analyzed the interaction of Sig1R and β-integrin in BC cells and its role in ECM-mediated cell proliferation and angiogenesis. We found that Sig1R forms a complex with β-integrin to promote ECM-mediated BC cell proliferation and angiogenesis, which enhances the aggressiveness of the tumor cells. This leads to poor survival. Our research revealed that Sig1R mediates the cross-talk between BC cells and their ECM microenvironment, thereby driving the progression of BC. Promisingly, targeting an ion channel function through Sig1R inhibition may serve as a potential approach for BC treatment.

BACKGROUND AIMS:Cell failure and angiogenesis are the key to bladder wall regeneration. Three-dimensional (3D) culture using porous gelatin microspheres (GMs) as a vehicle promotes stem cell proliferation and improves the paracrine capacity of cells. This study aimed to evaluate the therapeutic potential of GMs constructed from adipose-derived mesenchymal stromal cells (ADSCs) (ADSC-GMs) combined with bladder acellular matrix (BAM) in tissue-engineered bladders. METHODS:Isolation of ADSCs, flow cytometry, scanning electron microscopy and cell counting kit-8, β-galactosidase and enzyme-linked immunosorbent assays were performed in vitro to compare two-dimensional (2D) and 3D cultures. In the in vivo study, male Sprague-Dawley rats were randomly divided into three groups: the BAM replacement alone (BAM) group, ADSCs grown on BAM in replacement (ADSC) group and ADSC-GMs combined with BAM followed by replacement (ADSC-GM) group. Bladder function assessed by urodynamics after 12 weeks of bladder replacement, and the rats were sacrificed at 4 and 12 weeks for further experiments. RESULTS:The in vitro results showed that GM culture promoted ADSC proliferation, inhibited apoptosis and delayed senescence compared with those in the 2D culture. In addition, ADSC-GMs increased the secretion of the angiogenic factors vascular endothelial growth factor, platelet-derived growth factor-BB, and basal fibroblast growth factor. In vivo experiments revealed that ADSC-GMs adhered to the BAM for longer than ADSCs. Moreover, ADSC-GMs significantly promoted the regeneration of bladder vessels and smooth muscle, thereby facilitating the recovery of bladder function. The expression of phosphorylated protein kinase B (AKT) and phosphorylated endothelial nitric oxide synthase (eNOS) was significantly greater in the ADSC-GMs group compared with the BAM and ADSCs groups. CONCLUSIONS:ADSC-GMs increased retention of ADSCs on the BAM, thereby promoting the regeneration and functional recovery of the bladder tissue. ADSC-GMs promoted angiogenesis by activating the AKT/eNOS pathway.

Tissue engineering approaches offer promising alternative strategies for reconstructing bladder tissue; however, the low retention of transplanted cells and the possible risk of rejection limit their therapeu-tic efficacy. Clinical applicability is further limited by the lack of suitable scaffold materials to support the needs of various cell types. In the present study, we developed an artificial nanoscaffold system con-sisting of stromal vascular fraction (SVF) secretome (Sec) loaded onto zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, which were then incorporated into bladder acellular matrix. This artificial acellu-lar nanocomposite scaffold (ANS) can achieve gradient degradation and slowly release SVF-Sec to promote tissue regeneration. Furthermore, even after long-term cryopreservation, this completely acellular bladder nanoscaffold material still maintains its efficacy. In a rat bladder replacement model, ANS transplantation demonstrated potent proangiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function. Our study demonstrates the safety and efficacy of the ANS, which can play a stem cell-like role while avoiding the disadvantages of cell therapy. Furthermore, the ANS can replace the bladder regeneration model based on cell-binding scaffold materials and has the potential for clinical application.Statement of significance This study aimed to develop a gradient-degradable artificial acellular nanocomposite scaffold (ANS) loaded with stromal vascular fraction (SVF) secretome for rehabilitating bladders. Using various in vitro methods as well as rat-and zebrafish-based in vivo models, the developed ANS was assessed for effi-cacy and safety. Results indicated that the ANS achieved gradient degradation and slowly released the SVF secretome to promote tissue regeneration, even after long-term cryopreservation. Furthermore, ANS transplantation demonstrated a potent pro-angiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function in a bladder replacement model. Our study demonstrates that ANS may replace bladder regeneration models based on cell-binding scaffold materials and have potential clinical application & COPY; 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Protein posttranslational modification regulates several biological mechanisms, including tumor progression. In this study, we show that the mitochondrial Sirtuin 4 (SIRT4), which has ADP-ribosylation activity, plays a role in prostate cancer (PCa) progression. Firstly, SIRT4 expression was verified in PCa tissues and cell lines by quantitative real-time PCR (qRT-PCR) and western blotting. Subsequently, we established stable PC-3 and 22rv1 cells that overexpressed SIRT4 and knocked down SIRT4, respectively. The functions of SIRT4 in PCa were explored through various phenotype experiments. The mechanism underlying the functions of SIRT4 was investigated through western blotting, immunoprecipitation, immunofluorescence, and nuclear and cytoplasmic extraction assays. We revealed that SIRT4 inhibited cell progression both in vivo and in vitro. Mechanistically, on the one hand, SIRT4 promoted the ADP-ribosylation of glutamate dehydrogenase 1 to inhibit the glutamine metabolism pathways. On the other hand, SIRT4 inhibited the phosphorylation of AKT, thereby affecting p21 phosphorylation and its cellular localization for cell cycle arrest. In conclusion, our study indicates that SIRT4 is directly associated with PCa progression and could be a novel target for PCa therapy.

Emerging evidence suggests that KIF11 could play a pivotal role in cancer cell proliferation; however, its biological functions and molecular mechanisms in Wilms tumor (WT) cells are largely unknown. The aim of this study was to evaluate the clinical significance and therapeutic potential of KIF11 proteins in WT. KIF11 expression in WT tissues and adjacent nontumor tissues was determined using qRT-PCR, Western blotting, immunohistochemistry (IHC) and bioinformatics. The function of KIF11 protein was determined by its correlation with tumor cell growth, angiogenesis, and apoptosis using IHC and lentiviral vector-mediated KIF11 depletion. KIF11 expression was upregulated in WT tissues and was associated with WT clinical outcomes. Tumor KIF11 expression was significantly associated with the Ki67 proliferation index. CCK-8, flow-cytometric analysis, and Western blotting revealed that KIF11 knockdown significantly inhibited WT cell growth. Functional studies have indicated that increased KIF11 expression is significantly correlated with vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density. We further confirmed that downregulated expression of KIF11 promoted cell apoptosis and significantly increased Bcl-2 and Bax expression. Our findings demonstrate that KIF11 plays a role in promoting the development of human WT and can serve as a potential molecular marker for the treatment of WT.

OBJECTIVE:To explore the research progress of hair follicle and related stem cells in scar-free skin healing in recent years.METHODS:The literature related to hair follicle and related stem cells, wound healing, and scar formation in recent years was extensively reviewed and summarized from the aspects of cell function and molecular mechanism.RESULTS:Scar tissue after wound healing treated with hair follicle transplantation and related stem cell therapy is more mild or even without scar formation. The cell types and molecular mechanisms of the above phenomena are complex, and the bone morphogenetic protein signal transduction pathway and Wnt signal transduction pathway are strongly correlated.CONCLUSION:The research of hair follicle and related stem cells in scar-free skin healing is at the initial stage at present. Strengthening the mechanism research may provide new ideas for the treatment of wound and scar.

BACKGROUND:We aim at investigating the correlation between skip N2 metastases (SN2) and SUVmax, long diameter of tumor mass after 18F-FDG PET/CT, and pathological Ki67 expression in patients with non-small-cell lung cancer (NSCLC).METHODS AND RESULTS:We retrospectively analyzed the factors that might affect the pathogenesis of SN2 in these patients. The clinical SN2 symptoms in patients with squamous carcinoma or adenocarcinoma were investigated. The work curve was utilized to analyze the optimal cutoff value for the SUVmax and long diameter of tumor. Multivariate analysis revealed that high expression of Ki67 was a risk factor for mediastinal SN2 (OR = 1.042, 95% CI: 1.009-1.076). Subgroup analysis indicated that the SUVmax of the non-SN2 group was significantly higher than that of the SN2 group in patients with squamous carcinoma (16.3 ± 6.0 vs. 10.7 ± 5.6, P = 0.026). In the patients with adenocarcinoma, the long diameter of tumor in the SN2 group was significantly longer than that of the non-SN2 group (43.8 ± 16.3 mm vs. 30.1 ± 13.8 mm, P = 0.032). The Ki67 expression in the SN2 group was significantly higher than that of the non-SN2 group (51.7 ± 24.0 vs. 30.0 ± 19.2, P = 0.028).CONCLUSIONS:The differences of clinical features of the patients in the SN2 group and non-SN2 group in the NSCLC patients were associated with the pathological subtypes, which were featured by lower SUVmax in the SN2 of the squamous carcinoma, and longer diameter of SN2 in the adenocarcinoma patients.

目的 制备纯化钙调蛋白突变体CaMD130G和CaMD96V的蛋白,为后续体外实验研究提供高浓度高纯度的突变体蛋白奠定基础.方法 采用基因重组将重组质粒pGEX-6P-3/GST-CaMD130G和pGEX-6P-3/GST-CaMD96V转化入大肠杆菌,在大肠杆菌中诱导表达相应的蛋白,再采用超声破碎法制备融合蛋白,并且采用Precission protease进行酶切,SDS-PAGE确认制备蛋白的浓度与纯度,Pull-down assay的方法检测蛋白的活性.结果 本研究制备了较高浓度与纯度的钙调蛋白突变体CaMD130G和CaMD96V蛋白,CaMD130G蛋白能浓度依赖性地与心肌钙通道蛋白片段CT1结合,而CaMD96V蛋白能浓度依赖性地与心肌钙通道蛋白片段pre-IQ结合,制备的CaMD130G和CaMD96V蛋白具有很好的活性.结论 基因重组、超声破碎的方法能制备高浓度、高纯度以及高活性的突变体CaMm0G和CaMD96V蛋白,为进一步研究奠定坚实的基础.

Although interaction between BMP and Notch signaling has been demonstrated to be crucial for osteogenic differentiation of mesenchymal stem cells (MSCs), the precise molecular mechanism remains unknown. Here, we show that Notch intracellular domain (NICD) overexpression inhibits BMP9-induced C3H10T1/2 cell osteogenesis in vivo and in vitro. Our results show that activated Notch signaling results in down-regulation of Runx2 and early osteogenesis differentiation factors, without affecting p-Smad1/5/8 expression, and that blocking Notch signaling with DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) significantly increases p-Smad1/5/8 expression. Interestingly, Notch signaling also regulates the cell cycle by increasing PCNA (proliferation cell nuclear antigen) and CyclinD1 expression. Furthermore, similar results were obtained by ectopic bone formation and histological analyses, indicating that Notch signaling activation significantly inhibits BMP9-induced MSC osteogenic, cartilage and adipogenic differentiation. Moreover, we are the first to show that Notch regulates by suppressing JunB synthesis and that the negative effect of Notch is partially reversed by treatment with the JunB activator TPA (12-O-tetradeca-noylphorbol-13-acetate). Our findings demonstrate that Notch signaling significantly enhances cell proliferation but inhibits MSC osteogenic differentiation induced by BMP9 via JunB protein suppression rather than by BMP/Smad signaling regulation.

Objective To investigate a method for the purification of the N?terminal peptide fragment(NT)of the myocardial calcium channel Cav1.2,and characterize its interaction with calmodulin(CaM). Methods EscherichiacoliBL?21 cells were transformed with plasmid pGEX?6p?3/NT harboring the NT?GST fusion gene. The cells harboring pGEX?6p?3/NT were cultured and protein expression was induced with isopropyl?β?D?thiogalactoside(IPTG). Then,the GST?NT fusion protein was purified by using glutathione Sepharose 4B(GS?4B)beads. GST was cleaved off with the PreScission protease,and SDS?PAGE was performed to detect the purity and relative molecular weight of the purified peptide. Further, GST pull?down assay was performed to characterize the interaction of the NT peptide with CaM. Results SDS?PAGE analysis showed that the NT peptide was successfully purified,with high purity. Results of the GST pull?down assay showed that the NT peptide could interact with CaM. Conclusion This study establishes a method for the purification of the NT peptide and lays the foundation for further research on the interaction partners and biological functions of NT.

OBJECTIVE:To explore the expressive characteristics of SKP2 and p16 proteins in lung carcinoma tissues and their affection to patients'prognosis. METHODS:The expressions of SKP2 and p16 proteins were detected in 89 NSCLC,13 SCLC,10 lung benign lesion tissues by tissue chip and immuno-histochemistry technology. RESULTS:The positive rates of SKP2 and p16 protein stain were (23.52±13.57)% and (44.72±15.97)%,(53.85±12.26)% and (28.25±5.68)%,(2.91±1.27)% and (91.13±6.57)% in NSCLC,SCLC and lung benign lesion tissues,respectiveely. There were significantly differences among them(P=0.000). The expressive level of SKP2 protein in lung carcinoma tissues was closely related to the cell differentiation,pathological type,TNM stage and lymph node metastasis (P=0.000). The expressive level of p16 protein in lung carcinoma tissues was closely related to the cell differentiation,pathological type,TNM stage,lymph node metastasis (P=0.000). The expression of SKP2 protein was negative correlation with p16 protein in NSCLC(r=-0.660,P=0.000). The expression rate of SKP2 protein in lung carcinoma was negative correlation with tumorous malignant degree(r=-0.286,P=0.000). The expression rate of p16 protein in NSCLC was positive correlated with tumorous malignant degree(r=0.132,P=0.000). CONCLUSION:The high expression of SKP2 protein and low expression of p16 protein concurrently play a facilitative role in the occurrence and development of lung carcinoma. Moreover,there i s a certain opposite role to lung tumorous malignant degree. Yet,the interactive mechanism between them needs further research.

To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase (Smac) proteins in non-small cell lung cancer (NSCLC), and analyze their effect on patients’ prognosis.