Bursaphelenchus xylophilus: An Important Pathogenic Factor of Pine Wilt Disease and Its Relationship with Bursaphelenchus mucronatus.

Pine wilt disease is the most devastating pine disease caused by Bursaphelenchus xylophilus. Bursaphelenchus mucronatus is morphologically similar to B. xylophilus and geographically overlaps in its distribution. Although interspecific hybridization of the two nematodes has been performed in vitro, the dynamic regularity of hybrid formation and its risk in forests has not been well evaluated. In this study, a hybrid of B. xylophilus and Bursaphelenchus mucronatus mucronatus was identified in the laboratory and fields by molecular markers. The heterozygosity of ITS-5.8S loci for identification was unstable in the hybrid population, and the allele inherited from B. m. mucronatus was lost over several generations. We also provided evidence that hybrids existed in some new epidemic areas, while old epidemic areas were usually dominated by B. xylophilus. Hybrids could be generated when B. m. mucronatus was invaded by B. xylophilus, and the pathogenicity of the hybrids was similar to that of B. xylophilus. These findings may improve the understanding of the natural hybridization between B. xylophilus and B. m. mucronatus and pathogenic variation in pine wilt disease, providing new insights for future studies on disease detection, transmission, and quarantine.

An autoantibody against a 48-Kd fragment of human DNA-topoiomerase I in breast cancer: Implication for diagnosis and prognosis, and antibody-dependent cellular cytotoxicity in vitro.

Previously, we reported a novel tumor-associated antigen (TAA) derived from human DNA-topoiomerase I (TOP 1). In the present study, we demonstrated that the autoantibody against the TAA could be a potential biomarker in the early diagnosis and favorable prognosis of patients with breast cancer (BC). To understand the survival benefits in BC patients, we investigated whether the autoantibody could induce antibody-dependent cellular cytotoxicity activities (ADCC) against breast cancer cells in vitro. We found that the autoantibody exhibited significant ADCC activities that destroyed breast cancer MCF-7 and MDA-MB-231cells with peripheral blood mononuclear cells (PBMCs). The ADCC activities of the autoantibody were significantly correlated with the number of natural killer (NK) cells, NKT cells, and CD4+/CD8+ T cells. Accordingly, our findings showed that the autoantibody not only represented an early index of immune response to the TAA, but also was involved in host immune defense mechanisms that initiated the destruction of cancer cells.

A specific autoantibody against a novel tumour-association antigen derived from human DNA-topoiomerase I is a potential biomarker for early diagnosis and favourable prognosis in patients with colorectal carcinoma.

Context: We previously reported a novel tumour associated antigen (TTA) with molecular weight around 48 kDa and identified the novel TTA as a fragment derived from human DNA-topoiomerase I (TOP1). We termed the novel TAA as TOPO48 and termed autoantibody against the TAA as anti-TOPO48 autoantibody.Objective: To explore the clinical significance of anti-TOPO48 autoantibody in patients with colorectal carcinoma (CRC).Materials and methods: Serum levels of the autoantibody in patients with CRC or benign tumours and healthy volunteers were measured with a specific ELISA.Results: CRC patients at early stage had higher frequency of positive levels of the autoantibody and CRC patients with positive autoantibody levels had higher overall survival rate than those with negative autoantibody levels.Conclusion: The autoantibody is a potential biomarker for early diagnosis and favourable prognosis of CRC.

Clinical significance of plasma anti-TOPO48 autoantibody and blood survivin-expressing circulating cancer cells in patients with early stage endometrial carcinoma.

PURPOSE: To examine the clinical significance of an autoantibody (AAb) against a novel tumor-associated antigen (TAA) derived from human DNA-topoisomerase I, termed as TOPO48 AAb, and peripheral blood survivin-expressing circulating cells (CCC) in patients with early stage endometrial cancer (EC). METHODS: Blood samples were collected from 80 patients with early stage EC and 80 age-matched healthy subjects. Plasma levels of the TOPO48 AAb were measured with a specific antibody capture enzyme-linked immunosorbent assay (ELISA) and blood survivin-expressing CCC assessed with a reverse transcription-polymerase chain reaction products based on a hybridization-enzyme-linked immunosorbent assay (RT-PCR-ELISA). Sixty patients were followed up for 36 months after the initial assay test. RESULTS: There were 75% and 60% samples with positive levels of the TOPO48 AAb and survivin-expressing CCC in the cancer patients, respectively. However, the cumulative positive rate of combination of the two markers was increased to 93.3% with 0.927 (95% CI 0.871-0.984) of area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. During the follow-up period, patients with positive TOPO48 AAb but negative surviving-expressing CCC had a higher survival rate and a longer survival time than those with negative AAb but positive CCC (P = 0.01). CONCLUSIONS: The combination of TOPO48 AAb and survivin-expressing CCC may be used as a novel recipe to improve the efficiency of early diagnosis and provide more accurate prognostic prediction in patients with early stage EC.

[Protective effects of artesunate combination on experimental cerebral malaria and nerve injury].

Cerebral malaria (CM) is the leading cause of death in children under 5 years in Africa, severe neurological sequelae may occur in surviving children. Although artesunate has made breakthrough progress in the clinical treatment of CM, the clinical problems of high mortality and high morbidity have not yet been completely resolved. In this study, an experimental cerebral malaria (ECM) model was established by infecting C57BL/6 mice with Pb ANKA (Plasmodium berghei ANKA) to compare parasitemia level, survival rates, and rapid murine coma behavior scale scores, cerebral microvascular obstruction, haemozoin deposition in the liver, body temperature and weight to investigate the anti-cerebral malaria effect of the artesunate compound combination. The results showed that the artesunate compound combination could improve the survival rate of Pb ANKA-infected mice, reduce the level of parasitemia, effectively improve the symptoms of ECM neurological injury, reduce cerebrovascular obstruction and haemozoin deposition in the liver, and also significantly improve body temperature, weight and other basic indicators. The results showed that the artesunate compound combination improved the pathological changes and neurological damage caused by CM. It is expected to provide a theoretical basis for human cerebral malaria patients in clinical adjuvant therapy.

[Effect of dihydroartemisinin at low concentration on intervention of Plasmodium falciparum 3D7 strain].

Malaria is still the most severe strain of the human malaria parasites, and malaria disease is life-threatening which can result in severe anemia and cerebral malaria, especially in children in tropical Africa. Previous studies have shown that artemisinin and its derivatives could selectively kill erythrocytic stage of malaria and have a greater impact on the ring period. In recent years, there have been new findings of its mechanism continually. However, the concentration of artemisinin and its derivatives used in these studies can reach 50 to 80 times the half-inhibitory concentration in vitro. In this study, the international standard strain 3D7 of Plasmodium falciparum was used to culture in vitro. After half-inhibitory concentration of dihydroartemisinin was treated, the morphological changes of P. falciparum intraerythrocytic stage were observed, and then the 3D7 life cycle and effects of different developmental stages after dosing was explored. The 3D7 strain of P. falciparum was continuously synchronised more than 3 times. And dihydroartemisinin (DHA) at half maximal inhibitory concentration (10 nmol·L⁻¹) was administered for 6 hours after the last synchronization, and 3 life cycles were continuously observed (132 h). The results showed that compared with the parasites untreated by DHA, there was a noticeable delay in the life cycle of at least 36 h, indicating that the growth of 3D7 was significantly inhibited by DHA (P<0.001), and the rate of ring formation was significantly reduced (P<0.05). The trophozoites were abnormal in shape, such as shrink in size, and the number of merozoites in schizonts was significantly decreased (P<0.05). These results suggested that non-killing concentrations of DHA (meaning parasites can be inhibited but not killed) can significantly inhibit the growth of P. falciparum, which may not only affect the ring stage, but also have an impact on other stages of the P. falciparum.

[Current advance in cerebral malaria].

Cerebral malaria (CM), a severe neurological syndrome caused by Plasmodium falciparum infection, is a serious life-threatening disease with a high mortality. Survivors' persistent brain injury is manifested as long-term neurocognitive disorders. The main neuropathological feature of CM is the sequestration of parasited red blood cells (pRBCs) in cerebral microvessels. Other neuropathological features of CM include petechial hemorrhage in the brain parenchyma, annular hemorrhage, extensive brain endothelial cell activation, and focal endothelial cell injury and necrosis. However, its pathogenesis is still not clear. Currently, some studies have suggested that the pathogenesis of cerebral malaria mainly include pRBC adhesion, inflammatory reaction cascade, vascular leakage damage and brain hypoxia. Studies have shown that the biomarkers currently used as diagnostic and prognostic markers for CM include C-X-C motif chemokine ligand 10 (CXCL10), CXC chemokine ligand 4 (CXCL4), angiopoietin (Ang). In this paper, we systematically summarize the basic and clinical research for cerebral malaria in recent years and the latest literatures for drug studies, and focused on the advance of studies on cerebral malaria and its immunologic mechanism in the recent three years in the aspects of cytokines, immune cells, regulatory factors and biomarkers, so as to provide references for relevant studies.

[Establishment of vulnerable plaque model by mast cell activation in adventitia and evaluation of effectiveness of intervention of Shenlian tablet].

This study was designed to investigate the activity of Shenlian tablet in stabilization of the atherosclerosis (As) plaque in apoE(-/-) mice and explore the mechanisms. Rat peritoneal mast cells were randomly allocated and treated with Shenlian tablet (100, 50, 25, 12.5 mg·L(-1)) or cromoglicate sodium (200 µg·L(-1)) for 2 h before exposure to substance P. Histamine, tryptase, IL-1ß and NF-κB were measured in the cell culture supernatant by ELISA assay. The plaque formation was induced by common carotid artery cannula method combined with high-fat diet in apoE(-/-) mice, and the plaque instability was induced by substance P through local mast cell degranulation. Mice were divided into eight groups that included the model 1 (M1, sham-operated group), M2 (carotid artery cannula combined with high-fat diet）, M3 (M2 combined with substance P 0.5 µg/mouse, Shenlian extract (95, 190 and 380 mg·kg(-1)·d(-1)), atorvastatin (2.6 mg·kg-1·d(-1)) and normal control group. Total cholesterol (TC), high-density lipoprotein (HDL-C), high-sensitivity C-reactive protein (hs CRP), matrix metalloproteinases 9 (MMP-9) and histamine were measured by ELISA. Thickness, plaque area, mast cell degranulation were observed by hematoxylin and eosin staining, toluidine blue staining. CD117 antigen expression were observed by confocal microscopy. Intracellular phosphorylation was detected using the Bio-Plex 6-plex phosphoprotein assay kit. The results show that the mast cell membrane was stabilized by Shenlian tablet. Histamine, tryptase, interleukin l-ß and NF-κB exhibited a significantly reduction in the Shenlian tablet-treated group (P < 0.05 or P < 0.01). Substance P significantly enhanced activation and degranulation of adventitial mast cells. In addition, it increased adventitia inflammatory cells infiltration and promoted intraplaque hemorrhages in apoE(-/-) mice model group. The proliferation, degranulation and inflammation of mast cell were significantly inhibited by Shenlian tablet. On the other hand, the same treatment decreased hs-CRP, MMP-9 and histamine in serum. IκB, p38 MAPK phosphorylation, intraplaque hemorrhage and collagen degradation were reduced in the presence of Shenlian tablet, which increased the stability of the As plaque. The results show that the vulnerable plaque model induced by mast cell activation in adventitia was established. Shenlian tablet exhibited a protective effect in this model. Shenlian tablet may increase the plaque stability via inhibition of mast cell-mediated inflammatory response.

Rectification inversion in oxygen substituted graphyne-graphene-based heterojunctions.

Current rectification is found in oxygen-substituted zigzag graphyne nanoribbon/hydrogen-terminated zigzag graphene nanoribbon heterostructure junctions, from the application of nonequilibrium Green's function formalism combined with density functional theory. This behavior could be tuned by varying the number and location of oxygen atoms in the zigzag graphyne nanoribbon parts, and the rectification direction could be reversed due to the parity limitation tunneling effect. Moreover, an obvious negative differential resistance behavior is found and may be explained by two different mechanisms.

Amplification and overexpression of TP63 and MYC as biomarkers for transition of cervical intraepithelial neoplasia to cervical cancer.

OBJECTIVE: Biopsy confirmed that cervical intraepithelial neoplasia (CIN) may naturally regress or progress. Currently, the risk assessment for CIN progression to cervical cancer is still not satisfactory in clinical practice. We investigated copy number and protein expression of TP63 and MYC and explored the possibility to use them as progression biomarkers. METHODS: Copy numbers of TP63 and MYC, as well as human papilloma virus (HPV) integration status, were determined by fluorescence in situ hybridization in 39 patients with CIN and 66 patients with cervical cancer. Corresponding protein expressions were analyzed by immunohistochemistry. Receiver operating characteristic curves were used to measure the diagnostic test performance for the detection of cervical cancer from CIN. Sensitivity and specificity values of biomarkers were calculated. RESULTS: The average copy number and expression of TP63 and MYC, as well as the HPV integration rate, increased in the progression of CIN to cervical cancer. Receiver operating characteristic analysis for detection of cervical cancer resulted in area under the curve (AUC) values of TP63 copy number (AUC, 0.96; 95% confidence interval [CI], 0.91-1.00), MYC copy number (AUC, 0.92; 95% CI, 0.85-0.96), TP63 expression (AUC, 0.73; 95% CI, 0.61-0.85), and HPV-16 integration (AUC, 0.73; 95% CI, 0.60-0.85). MYC expression was not able to statistically distinguish cancer from CIN (P = 0.393). The combinations increased the specificity slightly but not sensitivity. Among them, TP63 amplification showed the best diagnostic performance. CONCLUSIONS: Amplification and overexpression of TP63 and MYC, and HPV integration rate, are associated with the transition of CIN to cervical cancer. Future studies on these biomarkers will help to assess the risk of CIN progression.

A Prediction Model of Sperm Retrieval in Males with Idiopathic Non-obstructive Azoospermia for Microdissection Testicular Sperm Extraction.

Patients with Idiopathic non-obstructive azoospermia (iNOA) can achieve fertility by extracting testicular sperm through microdissection testicular sperm extraction (mTESE). But more than half of iNOA patients still cannot benefit from mTESE. In recent years, some studies had reported that serum hormones may be related to the outcome of sperm retrieval, but few had been verified. We hope to obtain a predictive method that is convenient for clinical application and can help judge the outcome of sperm extraction before implementing mTESE. We performed a retrospective analysis of NOA patients who underwent mTESE in the same andrology center from June 2020 to November 2022. A total of 261 patients with complete data were collected, logistic regression analysis was performed and a predictive model was constructed. Then, from December 2022 to May 2023, one prospective cohort of 48 NOA patients who met the inclusion criteria from the same center was recruited to validate the risk prediction model. We successfully constructed a logistic regression model to predict the outcome of iNOA patients undergoing mTESE and found that higher serum anti-Müllerian hormone (AMH) levels were associated with failure sperm retrieval, resulting in an AMH cut-off of 2.60 ng/ml. The area under the receiver operating curve was 0.811, the sensitivity was 0.870, and the specificity was 0.705. Decision curve analysis demonstrated that the threshold probability was above 4%, and unnecessary mTESE could be reduced using this model. In a prospective cohort at the same center, 85.42% (41/48) of iNOA patients correctly identified the mTESE outcome using this model. A logistic regression model with AMH as an independent predictor can predict mTESE outcomes in iNOA patients. Preoperative selection of mTESE in patients with iNOA using this model had clinical benefit in reducing unnecessary surgery. The model demonstrated good accuracy in a small prospective cohort validation.

Case report: remedial microdissection testicular sperm extraction after onco-microdissection testicular sperm extraction failure.

BACKGROUND: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE. METHODS: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE. RESULTS: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy. CONCLUSIONS: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients.

Identification of Hub Genes for Colorectal Cancer with Liver Metastasis Using miRNA-mRNA Network.

Background: Liver metastasis is an important cause of death in patients with colorectal cancer (CRC). Increasing evidence indicates that microRNAs (miRNAs) are involved in the pathogenesis of colorectal cancer liver metastasis (CRLM). This study is aimed at exploring the potential miRNA-mRNA regulatory network. Methods: From the GEO database, we downloaded the microarray datasets GSE56350 and GSE73178. GEO2R was used to conduct differentially expressed miRNAs (DEMs) between CRC and CRLM using the GEO2R tool. Then, GO and KEGG pathway analysis for differentially expressed genes (DEGs) performed via DAVID. A protein-protein interaction (PPI) network was constructed by the STRING and identified by Cytoscape. Hub genes were identified by miRNA-mRNA network. Finally, the expression of the hub gene expression was assessed in the GSE81558. Results: The four DEMs (hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p) were identified as common DEMs in GSE56350 and GSE73178 datasets. The SP1 was likely to adjust the upregulated DEMs; however, the YY1 could regulate both the upregulated and downregulated DEMs. A total of 3925 genes (3447 upregulated DEM genes and 478 downregulated DEM genes) were screened. These predicted genes were mainly linked to Platinum drug resistance, Cellular senescence, and ErbB signaling pathway. Through the gene network construction, most of the hub genes were found to be modulated by hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p. Among the top 20 hub genes, the expression of CREB1, RHOA, and EGFR was significantly different in the GSE81558 dataset. Conclusion: In this study, miRNA-mRNA networks in CRLM were screened between CRC patients and CRLM patients to provide a new method to predict for the pathogenesis and development of CRC.

Loss-of-function CFTR p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis.

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.

[The effects of activin A and inhibin A on the IVM of mice immature oocytes].

OBJECTIVE: To study the effects of activin A (ACTA) and inhibin A (INHA) on the in vitro maturation (IVM) of mice immature eggs and early embryonic development. METHODS: 1. The mice oocytes were cultured in the culture medium contained different concentration of ACTA and INHA (50 ng/mL, 100 ng/mL, 200 ng/mL) to find the optimum concentration; 2. The effects of different concentration of ACTA, INHA, ACTA+ INHA on the mature rates of mice oocytes were compared; 3. The effects of different concentration of ACTA, INHA, ACTA+INHA on the fertility rates and blastocysts formation rates of IVM mice eggs were also compared. RESULTS: The mature rates of mice oocytes in culture medium contained (100 ng/mL and 200 ng/mL) ACTA and INHA were significantly higher than that contained 50 ng/mL ACTA and INHA (P < 0.05); There was no difference between 100 ng/mL and 200 ng/mL groups. The mature rates, fertility rates and blastocyst rates of mice oocytes were significantly higher than those of control (P < 0.05). CONCLUSION: The mature rates, fertility rates and embryonic development potential after fertilization of mice oocytes were significantly promoted by ACTA, INHA. The optimum concentration of ACTA and INHA in culture medium was 100 ng/mL.

[Influence of compound Chinese medicine for reinforcing kidney on mouse sperm fertilizing ability].

OBJECTIVE: To study the influence of Compound Chinese medicine for reinforcing kidney on sperm fertilizing ability of mice. METHODS: Twenty male mice were randomly divided into two groups. The mice in treatment groups were given Compound Chinese medicine for reinforcing kidney every day for 14 d, and the mice in control group were given saline. Seven days after the treatments, the male mice mated with superovulated female mice. After the successful mating, the female mice were executed, then 1 cell embryos and fertilized eggs were harvested from oviduct. The embryos cleavage rate and the percentage rate of blastocysts were observed in vivo. In vitro fertilization (IVF%), the percentage of blastocysts, the percentage of acrosome-intact spermatozoa (AIS%) and the acrosin activity were studied in vitro. RESULTS: Compared with the controls, the mice receiving Compound Chinese medicine had higher embryos cleavage rate and IVF%. The percentage of blastocysts between the two groups was no difference. The acrosin activity of treated mice was significant higher than that of control mcie, and AIS% between the two groups was no significant different. CONCLUSION: Compound Chinese medicine for reinforcing kidney can improve the mouse sperm fertilizing ability, which may be relevant to acrosin activity.

A ratiometric fluorescent sensing of proanthocyanidins by MnO2 nanosheets simultaneously tuning the photoluminescence of Au/AgNCs and thiamine.

By simultaneously regulating the photoluminescence of alloy Au/Ag nanoclusters (NCs) and thiamine (VB1) through MnO2 nanosheets (MnO2 NS), a novel ratiometric fluorescent probe (RF-probe) was established for sensitively and selectively monitoring proanthocyanidins (PAs). The introduction of Ag (I) ions could enhance significantly the quantum yields (QYs, 11.1%) of AuNCs based on the synthetic method of UVI (UV irradiation) combined with MWH (microwave heating). MnO2 NS could quench the fluorescence (FL) of Au/AgNCs mainly coming from Förster resonance energy transfer (FRET), while it could act as a nanozyme catalyst for directly catalyzing the oxidation of VB1 to produce highly fluorescent oxVB1. In the presence of PAs, MnO2 was reduced to Mn2+, which caused that its quenching capacity and oxidase-like activity were vanished, thus the FL of oxVB1 and Au/AgNCs was reduced and recovered. The concentration of PAs could be monitored by the RF-probe with a linear range of 0.27-22.4 µmol L-1 and corresponding limit of detection (LOD) and limit of quantification (LOQ) were calculated to be 75.9 and 250.5 nmol L-1. Furthermore, the RF-probe was successfully used for the determination of PAs in mineral water, PAs additive and PAs capsule with satisfactory results compared to the standard HPLC method.

MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients.

BACKGROUND: MicroRNAs (miRNAs) have been demonstrated to exhibit important regulatory roles in multiple malignancies, including hepatocellular carcinoma (HCC). hsa-miR-497-5p was reported to involve in cancer progression and poor prognosis in many kinds of tumors. However, the expression and its clinical significance of hsa-miR-497-5p in HCC remain unclear. METHODS: In the present study, we investigated the expression of hsa-miR-497-5p in HCC and analyzed the correction of clinical features with prognosis. The expression levels of hsa-miR-497-5p and potential target genes were analyzed in HCC and adjacent noncancerous tissues using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze hsa-miR-497-5p levels in 328 HCC tissues and 30 paired adjacent noncancer tissues. Overall survival (OS) and progression-free survival (PFS) of patients with HCC were assessed using the Kaplan-Meier method and the log-rank test. RESULTS: The hsa-miR-497-5p expression levels were decreased, and its target genes ACTG1, CSNK1D, PPP1CC, and BIRC5 were upregulated in HCC tissues compared with normal tissues. Lower levels of hsa-miR-497-5p expression and higher levels of the four target genes were significantly associated with higher tumor diameter. Moreover, patients with lower hsa-miR-497-5p expression and higher target genes levels had shorter OS. CONCLUSION: The expression levels of hsa-miR-497-5p may play an important regulatory role in HCC and are closely correlated with HCC progression and poor prognosis in patients. The hsa-miR-497-5p may be a specific therapeutic target for the treatment of HCC.

microRNA-873 inhibits self-renewal and proliferation of pancreatic cancer stem cells through pleckstrin-2-dependent PI3K/AKT pathway.

Recent studies have emphasized microRNAs (miRs) as crucial regulators in the occurrence and development of pancreatic cancer that continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-873 and its associated mechanism to unravel the biological characteristics of pancreatic cancer stem cells in tumor growth. The expression patterns of pleckstrin-2 (PLEK2) and miR-873 were detected in the pancreatic cancer tissues. Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis. Finally, the tumor formation in nude mice was measured to verify the preceding results in vivo. Pancreatic cancer tissues exhibited a decline of miR-873 expression and an enhancement of PLEK2 expression. miR-873 targeted PLEK2 and downregulated its expression, leading to inhibition of PI3K/AKT pathway. Overexpressed miR-873 or silenced PLEK2 inhibited the self-renewal and proliferation while promoting the apoptosis of pancreatic cancer stem cells. Tumor formation was inhibited by overexpressed miR-873 or silenced PLEK2 in nude mice. Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.

Exosomal microRNA-15a from mesenchymal stem cells impedes hepatocellular carcinoma progression via downregulation of SALL4.

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.