Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.

Identifying the core competencies of backup nurses in the acute care hospital through a modified Delphi process

Background:The backup nurses are created to meet emergencies in the case of inadequate nursing staff and emergency circumstances,and there are no clear definitions of the core competencies for training and evaluation of backup nurses in the acute care hospitals in China.Methods:This study used a modified Delphi process where an initial list of potential competencies is established following a framework of training need analysis(TNA),literature review,and focus groups.This process generated as a list of 47 core competencies,which is presented to an expert panel(n=20)for consideration in two rounds.Results:As determined by the survey,a combination of 26 core competencies in three specified categories is identified:professional practice ability,critical thinking ability,and interpersonal skills.A total of 154.99 h is required to complete all 26 core competencies,and each item has a corresponding evaluation method.Conclusions:The core competencies provide a scientific basis for the hospital nursing managers to train and evaluate backup nurses,and it may ensure consistency in standards across the country.

Vibration-reduced anxiety-like behavior relies on ameliorating abnormalities of the somatosensory cortex and medial prefrontal cortex

Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.

Lycium barbarum glycopeptide(wolfberry extract)slows N-methyl-N-nitrosourea-induced degradation of photoreceptors

Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

BACKGROUND Colorectal cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.Syndecan-2 methylation(mSDC2)testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.Cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.AIM To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China.METHODS A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing.Sensitivity and specificity for CRC,advanced adenoma(AA)and advanced colorectal neoplasia(ACN)were determined.High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test.RESULTS A total of 1035 high-risk individuals were included in this study according to established criteria.Among them,16 suffered from CRC(1.55%),65 from AA(6.28%)and 189 from non-AAs(18.26%);150 patients were diagnosed with polyps(14.49%).Diagnoses were established based upon colonoscopic and pathological examinations.Sensitivities of the mSDC2 test for CRC and AA were 87.50%and 40.00%,respectively;specificities were 95.61%for other groups.Positive predictive values of the mSDC2 test for CRC,AA and ACN were 16.09%,29.89%and 45.98%,respectively;the negative predictive value for CRC was 99.79%.After adjusting for other high-risk covariates,mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN(P<0.001).CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Novel Role of Calcium-Sensitive Receptors in Chronic Hypoxia-Induced Proliferation of Pulmonary Vein Smooth Muscle Cells

Objective:Vascular remodeling due to chronic hypoxia(CH)occurs not only in the pulmonary arteries but also in the pulmonary veins.Pulmonary vascular remodeling arises from the proliferation of pulmonary vascular myocytes.However,the mechanism by which CH induces the proliferation of pulmonary vein smooth muscle cells(PVSMCs)is unknown.This study aimed to investigate the mechanism by which CH affects the proliferation of PVSMCs.Methods:PVSMCs were isolated from rat distal pulmonary veins and exposed to CH(4%O2,60h),and the expression of the calcium-sensitive receptor(CaSR)was detected by Western blotting and immunofluorescence.MTT assay was used to detect the proliferation viability of the cells,and the changes in the intracellular calcium concentration were detected by laser confocal scanning technique.Results:CaSR expression was present in rat distal PVSMCs,and CaSR protein expression was upregulated under hypoxia.The positive regulator spermine not only enhanced CH-induced CaSR upregulation but also enhanced CH-induced increase in cell viability and calcium ion concentration.The negative CaSR regulator NPS2143 not only attenuated CH-induced CaSR upregulation but also inhibited CH-induced cell viability and calcium ion concentration.Conclusion:CaSR-mediated hyperproliferation is a novel pathogenic mechanism for the development of proliferation in distal PVSMCs under CH conditions.

Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status:5-year follow-up of a prospective cohort study

Objective:We investigated the relation between man papillomavirus(HPV)integration status and the immediate risk of cervical intraepithelial neoplasia(CIN),as well as the triage strategy based on HPV integration test.Methods:4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective,population-based,clinical observational study to evaluate the triage performance of HPV integration.Cervical exfoliated cells were collected for HPV testing and cytologic test.If high-risk HPV was positive,HPV integration test was performed at baseline,2-year and 5-year follow-up.Results:At baseline,HPV integration was positively correlated with the severity of cervical pathology,ranging from 5.0%(15/301)in normal diagnosis,6.9%(4/58)in CIN1,31.0%(9/29)in CIN2,70%(14/20)in CIN3,and 100%(2/2)in cervical cancer(P<0.001).Compared with cytology,HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+,higher specificity(92.8%[90.2%-95.4%]vs.75.5%[71.2%-79.8%],P<0.001)and higher positive predictive value(36.4%[22.1%-50.6%]vs.15.2%[8.5%-21.8%],P<0.001).HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy(10.7%[44/410]vs.27.3%[112/410],P<0.001).The HPV integration-negative group exhibited the lowest immediate risk for CIN3+(1.6%)and accounted for the largest proportion of the total population(89.3%),when compared with the normal cytology group(risk,1.7%;proportion,72.7%).Conclusion:As a key molecular basis for the development of cervical cancer,HPV integration might be a promising triage strategy for HPV-positive patients.

Characteristics of PVT1 and Its Roles in Diseases

With the development of genome-wide sequencing technology, 195 types of functional, long non-coding RNAs(lnc RNAs) have been identified so far, and their cellular roles are gradually being revealed. Lnc RNAs have now become a hotspot in the field of life sciences. These small molecules exist in almost all higher eukaryotes and play very important regulatory roles in these organisms. This review briefly summarizes the recent progress in research on plasmacytoma variant translocation 1 gene(PVT1), an lnc RNA.

Lutein delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration.There is currently no effective treatment for retinitis pigmentosa.Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration,the role of lutein alone remains unclear.In this study,we administered intragastric lutein to Pde6brd10 model mice,which display degeneration of retinal photoreceptors,on postnatal days 17(P17)to P25,when rod apoptosis reaches peak.Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control.Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells,in line with an increased survival rate of photoreceptors.Functionally,lutein improved visual behavior,visual acuity,and retinal electroretinogram responses in Pde6brd10 mice.Mechanistically,lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells.The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects.This study was approved by the Laboratory Animal Ethics Committee of Jinan University(approval No.LACUC-20181217-02)on December 17,2018.

Characterization of inflammatory factor-induced changes in mesenchymal stem cell exosomes and sequencing analysis of exosomal microRNAs

BACKGROUND Treatments utilizing stems cells often require stem cells to be exposed to inflammatory environments,but the effects of such environments are unknown.AIM To examine the effects of inflammatory cytokines on the morphology and quantity of mesenchymal stem cell exosomes(MSCs-exo)as well as the differential expression of microRNAs(miRNAs)in the exosomes.METHODS MSCs were isolated from human umbilical tissue by enzymatic digestion.Exosomes were then collected after a 48-h incubation period in a serum-free medium with one of the following the inflammatory cytokines:None(control),vascular cell adhesion molecule-1(VCAM-1),tumor necrosis factor(TNF)α,and interleukin(IL)6.The morphology and quantity of each group of MSC exosomes were observed and measured.The miRNAs in MSCs-exo were sequenced.We compared the sequenced data with the miRBase and other non-coding databases in order to detect differentially expressed miRNAs and explore their target genes and regulatory mechanisms.In vitro tube formation assays and Western blot were performed in endothelial cells which were used to assess the angiogenic potential of MSCs-exo after inflammatory cytokine stimulation.RESULTS MSCs-exo were numerous,small,and regularly shaped in the VCAM-1 group.TNFαstimulated MSCs to secrete larger and irregular exosomes.IL6 led to a reduced quantity of MSCs-exo.Compared to the control group,the TNFαand IL6 groups had more downregulated differentially expressed miRNAs,particularly angiogenesis-related miRNAs.The angiogenic potential of MSCs-exo declined after IL6 stimulation.CONCLUSION TNFαand IL6 may influence the expression of miRNAs that down-regulate the PI3K-AKT,MAPK,and VEGF signaling pathways;particularly,IL6 significantly down-regulates the PI3K-AKT signaling pathway.Overall,inflammatory cytokines may lead to changes in exosomal miRNAs that abnormally impact cellular components,molecular function,and biological processes.

Progress in research on tumor microenvironment-based spatial omics technologies

Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information.It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results.Spatial omics technologies include spatial transcriptomics,spatial proteomics,spatial metabolomics,and other technologies,the most widely used of which are spatial transcriptomics and spatial proteomics.The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist,including the surrounding blood vessels,immune cells,fibroblasts,bone marrow-derived inflammatory cells,various signaling molecules,and extracellular matrix.A key issue in modern tumor biology is the application of spatial omics to the study of the tumor microenvironment,which can reveal problems that conventional research techniques cannot,potentially leading to the development of novel therapeutic agents for cancer.This paper summarizes the progress of research on spatial transcriptomics and spatial proteomics technologies for characterizing the tumor immune microenvironment.

Diagnostic Value of the Post-Processing Technique of Multi-Slice Spiral CT in Orbital Cyst Diseases

Purpose:To analyze the features of CT imaging of orbital cystic disease. Methods:.A total of 30 patients were pathologically confirmed with orbital cystic disease between January 2007 and March 2012. Prior to operation, the participants underwent CT scans with image processing by maximum intensity projection (MIP) and volume rendering (VR). Preoperative CT diagnostic outcomes were compared with postoperative pathological findings. Results:.The patients presented with round,.oval and dumbbell shaped masses. Fourteen cases of dermoid cyst and 8 cases of epidermoid cyst showed heterogeneous density. Among the dermoid cyst patients, 6 cases had demixing phenomenon, 3 cases had lipid drift and 5 cases showed mild or moderate intensity enhancement in the cyst wall. No intensity enhancement was observed in the epidermoid cyst patients. Five cases had high intensity due to hemorrhage and 3 patients presented with adjacent sclerotin arc compression;.5 cases of myxoid cyst had homogenous density and no intensity enhancement was found when iohexol was injected..Three patients with atheromatous cyst had heterogeneous density,.with CT value ranging from -36Hu to 191Hu. Floss was noted centrally in 1 case and mild to moderate intensity enhancement was observed in the cyst wall with iohexol injection. Conclusion:.Multi-slice CT is useful in the diagnosis of orbital cystic disease. Multi-slice CT combined with image processing can be helpful in displaying the location and size of masses, and revealing the relationship between masses and surrounding boney tissue, providing an objective basis for surgical planning when combined with 3D-CT imaging.

Combination therapy of hydrogel and stem cells for diabetic wound healing

Diabetic wounds(DWs)are a common complication of diabetes mellitus;DWs have a low cure rate and likely recurrence,thus affecting the quality of patients’lives.As traditional therapy cannot effectively improve DW closure,DW has become a severe clinical medical problem worldwide.Unlike routine wound healing,DW is difficult to heal because of its chronically arrested inflammatory phase.Although mesenchymal stem cells and their secreted cytokines can alleviate oxidative stress and stimulate angiogenesis in wounds,thereby promoting wound healing,the biological activity of mesenchymal stem cells is compromised by direct injection,which hinders their therapeutic effect.Hydrogels form a three-dimensional network that mimics the extracellular matrix,which can provide shelter for stem cells in the inflammatory microenvironment with reactive oxygen species in DW,and maintains the survival and viability of stem cells.This review summarizes the mechanisms and applications of stem cells and hydrogels in treating DW;additionally,it focuses on the different applications of therapy combining hydrogel and stem cells for DW treatment.

Characteristics of Antisense Non-coding RNA in the INK4 Locus and Its Roles in Disease

Abstract With the development of genome-wide sequencing technology, 195 types of functional long non-coding RNAs （lncRNAs） have so far been found, and their cellular roles are gradually being revealed. Now lncRNAs have become a hotspot in the life science. These small molecules exist in almost all higher eukaryotes, and have very important regulatory roles in these organisms. This review briefly summarizes recent progress in researches on antisense non-coding RNA in the INK4 locus.

The Impact of Chemotherapy on EGFR Mutation Status in Non-Small-Cell Lung Cancer: A Meta-Analysis

Background: Emerging evidence indicates that chemotherapy for lung cancer may alter EGFR mutation status. However, whether chemotherapy as a firstline treatment may increase or reduce the frequency of EGFR mutations in NSCLC remains uncertain. Therefore, we conducted a meta-analysis to evaluate whether chemotherapy leads to altered EGFR mutation status. Methods: A systematic literature search was performed using the PubMed, OVID, Science Direct, Cochrane Library, and CNKI databases for studies on pre- and post-chemotherapy EGFR mutation status. Relevant studies documenting perichemotherapy EGFR mutation ratios were included. Analyses of pooled odds ratios (OR) were performed. Results: Six studies involving 656 patients were included in this meta-analysis. It was found that chemotherapy may alter EGFR status (OR = 1.93, 95% CI 1.05 - 3.56;p < 0.0001). No significant differences in EGFR mutation alterations were observed in terms of gender, smoking history, EGFR loci, or chemotherapy response in NSCLC patients. Conclusions: Chemotherapy may contribute to altered EGFR status. NSCLC patients with EGFR mutations might need to be considered for EGFR status redeterminations prior to second-line EGFR-TKI treatment or upon tumor recurrence after chemotherapy. Further randomized clinical trials should investigate the impact of neoadjuvant or first-line chemotherapy on EGFR mutation status in NSCLC patients.

Investigation of pelvic symmetry:A systematic analysis using computer aided design software

Objectives:This study aimed to investigate the symmetry of the Chinese pelvis.Methods:Computed tomography scan images of each of 50 Chinese pelvises were converted to 3D models and the left sides of the pelvises were reflected on Mimics software.Then,the reflected left side model was aligned with the right side using the closest point algorithm function of Geomagic software to perform symmetry analysis.The volume and surface area of either side of the pelvises were also calculated.The mean standard deviation(SD),the mean percentage of permissible deviations within the±2mm range,the percentage differences in volume and surface area were measured to compare pelvic symmetry.In addition,the distribution of pelvic bilateral symmetry associated with both age and sex were compared.Results:The mean SD was 1.15±0.16mm and the mean percentage of permissible deviations was 90.82%±4.67%.The deviation color maps showed that the specific areas of asymmetry were primarily localized to major muscle or ligament attachment sites and the sacroiliac joint surfaces.There was no significant difference between the bilateral sides of the pelvis in either volume or surface area.Additionally,no difference in any indexes was exhibited in relation to sex and age distribution.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study

Background:Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer(CLAP study;NCT03816553).We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival.The outcomes of patients who underwent immune checkpoint inhibitor(ICI)retreatment were also reported.Methods:In this phase II trial,eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years.Treatment was continued until disease progression,unacceptable toxicity,or withdrawal of consent.Results:Between January 21 and August 1,2019,a total of 45 patients were enrolled.Data were analyzed as of July 31,2023,representing>48 months since treatment initiation for all patients.Nine(20.0%)patients completed the 2-year study.The median duration of response(DOR)was 16.6 months,and 45.0%of patients achieved a DOR of≥24 months.The 12-month progression-free survival(PFS)rate was 40.7%(95%confidence interval[CI],25.2-55.6),with an 18-month PFS rate of 37.8%(95%CI,22.7-52.8).The median overall survival(OS)was 20.3 months(95%CI,9.3-36.9),and the 24-month OS rate was 47.8%(95%CI,31.7-62.3).Age>50 years,programmed death-ligand 1(PD-L1)combined positive score(CPS)≥1(versus[vs.]<1),CPS≥10(vs.<1),high tumor mutational burden,and PIK3CA mutations were associated with improved PFS(hazard ratio[HR]<1)and longer OS(HR<1).Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs.Among them,2(25.0%)achieved a partial response,while 5(62.5%)had stable disease.Notably,four patients who received retreatment with ICIs survived for more than 45months.No new safety signals were identified in the present study.Conclusion:Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust,sustained,and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy.No new safety signals were noted with long-term treatment.

Harnessing cytokine-induced killer cells to accelerate diabetic wound healing:an approach to regulating post-traumatic inflammation

Impaired immunohomeostasis in diabetic wounds prolongs infiammation and cytokine dysfunction,thus,delaying or pre-venting wound-surface healing.Extensive clinical studies have been conducted on cytokine-induced killer(CIK)cells recently,as they can be easily proliferated using a straightforward,inex-pensive protocol.Therefore,the function of CIK cells in regulat-ing inflammatory environments has been drawing attention for clinical management.Throughout the current investigation,we discovered the regenerative capacity of these cells in the chal-lenging environment of wounds that heal poorly due to diabe-tes.We demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory microenviron-ment.promote larizationand.ultimatel accelerateskin healing in diabetic mice.The results indicated that CIK cell treatment affects macrophage polarization and restores the function regenerative cells under hyperglycemic conditions.This novel cellular therapy offers a promising intervention for clinical applic tions through specific inflammatory regulation functions.

Narciclasine induces colon carcinoma cell apoptosis by inhibiting the IL-17A/Act1/TRAF6/NF-kB signaling pathway

IL-17 A is a promoter of colorectal cancer initiation and progression.Narciclasine is a polyhydroxy alkaloid compound isolated from Narcissus plants,which has potent anti-inflammatory and antitumor actions.The effects of narciclasine on colorectal tumors were evaluated,with a focus on IL-17 A.Narciclasine reduced the growth of HCT-116 and SW-480 colon cancer cells in vitro and in vivo in murine xenografts.The results of flow cytometry on JC-1 and Annexin V/PI revealed that narciclasine significantly reduced the mitochondrial membrane potential and induced apoptosis,findings confirmed by western blotting results of reduced Bcl2 and enhanced Bax expression,as well as accumulation of cleaved Caspase-3,Caspase-8,Caspase-9,and cytoplasmic Cytochrome-c.After narciclasine incubation,IL-17 A,Act1,and TRAF6 were down-regulated,while p-P65(Ser536)accumulated in the cytoplasm,a finding confirmed by laser scanning confocal microscopy.IL17A substitution could partly reverse these narciclasine effects while they were elevated by IL17A silencing.Moreover,IL-17 A,Act1,and TRAF6 were significantly expressed to greater extents in human colorectal cancer compared to normal adjacent tissue specimens and were closely linked with a poor prognosis.This study provided evidence that narciclasine may be a useful therapeutic drug for colorectal cancer treatment through its actions in down-regulating the L-17A/Act1/TRAF6/NF-kB anti-apoptotic signaling pathway.