Metformin, a widely used antidiabetic drug, has previously been demonstrated to exert anti-cancer effects in certain hematological malignancies, but its effects on the transformation of ...myelodysplastic syndromes to acute myeloid leukemia (AML-MDS) remain unclear. The present study aimed to investigate the effects of metformin on SKM-1 cells (an AML-MDS cell line) and its underlying mechanisms. SKM-1 cells were treated with different concentrations of metformin. Cell proliferation was assayed by CCK-8. Apoptosis and cell cycle phases were detected by flow cytometry, while cell cycle related proteins and AMPK were tested by Western blot. SKM-1 cells were transfected with LV-AMPKα1-RNAi to reduce the expression of AMPK. Metformin inhibited cell proliferation in a dose and time dependent manner by inducing G0/G1 phase arrest rather than apoptosis induction. Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1. AMPK knockdown attenuated the effects of metformin on SKM-1 cells. These findings suggested that metformin inhibited proliferation of SKM-1 cells, potentially through an AMPK-mediated cell cycle arrest.
The spread of coronavirus disease 2019 (COVID-19) around the world has put a heavy burden on human society and is also a great challenge facing medical staff. This study aimed to assess the ...difficulties faced by health care personnel (HCP) in using personal protective equipment (PPE) in clinical practice during the COVID-19 outbreak in Wuhan, China. One hundred twenty medical staff from the First Affiliated Hospital of Chongqing Medical University presented to the Wuhan First Hospital to provide medical assistance, from whom 20 HCP volunteered to participate in a focus group discussion attended by infection control nurse leaders. Participants' responses and discussions were recorded, and the content was analyzed for themes. Observed difficulties included inappropriate PPE sizes, the design of the PPE and its complexity of use, doubts related to the quality and effectiveness of PPE, potential risks during doffing, space layout between clean and contaminated area, and poor comfort with PPE use. Other factors, such as the support environment, management, processes, preparedness, HCP, and equipment can also have a positive or negative impact on the use of PPE. Future efforts to optimize PPE use should focus on strengthening training for HCP using real items for increasing compliance with standardized protocols, improving PPE design, and performing further research on the risks, benefits, and best practices of PPE use.
Heparan sulfate proteoglycan 2 (HSPG2), also known as perlecan, is a large multi-domain extracellular matrix proteoglycan, which contributes to the invasion, metastasis and angiogenesis of solid ...tumor. However, very little is known about the effect of HSPG2 on acute myeloid leukemia (AML). This study aims to investigate the prognostic value of the HSPG2 gene in terms of overall survival and leukemia-free survival in patients with AML. Bone marrow mononuclear cells (BMMCs) from 4 AML patients and 3 healthy controls were processed for RNA-Sequencing (RNA-seq). The mRNA expression level of HSPG2 in BMMCs and CD34
hematopoietic stem/progenitor cells (HSPC) obtained from enrolled participants and human leukemic cell lines was detected by RT-qPCR. Then the correlations between the expression of HSPG2 and a variety of important clinical parameters, such as median white blood cell (WBC) count and bone marrow (BM) blasts, were further analyzed. The expression level of HSPG2 was significantly upregulated in AML patients at the time of diagnosis, downregulated after complete remission and then elevated again at relapse. Moreover, HSPG2 expression was associated with median WBC count (P < 0.001), median hemoglobin (P = 0.02), median platelet count (P = 0.001), and BM blasts (P < 0.001) in AML patients. Patients with high HSPG2 expression had both worse overall survival (OS) (P = 0.001) and poorer leukemia-free survival (LFS) (P = 0.047). In the multivariate analysis model, HSPG2 was identified as an independent prognostic biomarker of AML. Taken together, these results indicate that HSPG2 overexpression was associated with poor prognosis in AML patients, and may be a prognostic biomarker and therapeutic target of AML.
Acupuncture may be an effective complementary treatment for Alzheimer's disease (AD). The aim of this study was to summarize the evidence provided by systematic reviews (SRs)/meta-analyses (MAs) on ...the effect of acupuncture on AD.
Eight electronic databases were searched from their inception until October 19, 2020. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Moreover, the evidence quality of the outcome measures was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).
Eleven SRs/MAs met all inclusion criteria. According to the results of the AMSTAR-2, all included reviews were rated critically as being of low quality. With PRISMA, the reporting checklist was relatively complete, but some reporting weaknesses remained in the topics of the protocol and registration, search strategy, risk of bias, additional analyses, and funding. Based on the ROBIS tool, only two SRs/MAs had a low risk of bias. With the GRADE system, no high-quality evidence was found, and only seven outcomes provided moderate-quality evidence. Among the downgraded factors, the risk of bias within the original trials was ranked first, followed by inconsistency, imprecision, and publication bias.
Acupuncture is a promising complementary treatment for AD. However, due to the low quality of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.
Background
Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, of which the clear cell renal cell carcinoma (ccRCC) accounts for the most subtypes. The ...increasing discoveries of abundant autophagy-related long non-coding RNAs (ARLNRs) lead to a resurgent interest in evaluating their potential on prognosis prediction. Based on a large number of ccRCC gene samples from TCGA and clinics, ARLNRs analysis will provide a novel perspective into this field.
Methods
We calculated the autophagy scores of each sample according to the expression levels of autophagy-related genes (ARGs) and screened the survival-related ARLNRs (sARLNRs) of ccRCC patients by Cox regression analysis. The high-risk group and the low-risk group were distinguished by the median score of the autophagy-related risk score (ARRS) model. The functional annotations were detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA). The expression levels of two kinds of sARLNRs in the renal tumor and adjacent normal tissues and cell lines were verified.
Results
There were 146 ARLNRs selected by Pearson analysis. A total of 30 sARLNRs were remarkably correlated with the clinical outcomes of ccRCC patients. Eleven sARLNRs (AC002553.1, AC092611.2, AL360181.2, AP002807.1, AC098484.1, AL513218.1, AC008735.2, MHENCR, AC020907.4, AC011462.4, and AC008870.2) with the highest prognosis value were recruited to establish the ARRS in which the overall survival (OS) in the high-risk group was shorter than that in the low-risk group. ARRS could be treated as an independent prognostic factor and has significant correlations with OS. The distributions of autophagy genes were different between the high-risk group and the low-risk group. In addition, we also found that the expression levels of AC098484.1 in ccRCC cell lines and tumor tissues were lower than those in HK-2 and adjacent normal tissues, but AL513218.1 showed the inverse level. Furthermore, the AC098484.1 expressed decreasingly with the more advanced T-stages, but AL513218.1 gradually increased.
Conclusion
Our study identified and verified some sARLNRs with clinical significances and revealed their potential values on predicting prognoses of ccRCC patients, which may provide a novel perspective for autophagy-related research and clinical decisions.
Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape ...immune response by impairing DC migration. Prostaglandin E2 (PGE2) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE2 could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE2 rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE2 also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE2 treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.
Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape ...immune response by impairing DC migration. Prostaglandin E
(PGE
) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE
could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXR
activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE
rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXR
. Further, it was observed that PGE
also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE
treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.
Natural killer (NK) cells play a potent role in antitumor immunity via spontaneously eliminating tumor directly. However, some tumors such as prostate cancer constantly escape this immune response by ...down-regulating cell surface molecule recognition and/or secreting immune impressive cytokines. Here, we found pterostilbene, a natural agent with potent anticancer activity, could enhance expression of major histocompatibility complex class I chain-related proteins A and B (MICA/B) on prostate cancer cells surface, which are ligands of the natural killer group 2 member D (NKG2D) expressed by NK cells, and inhibit TGF-β1 secretion by prostate cancer cells. Further, we discovered that these effects were caused by inhibition of miR-20a in prostate cancer cells by pterostilbene. MiR-20a could target the 3’ untranslated region (UTR) of MICA/B, resulting in their expression down-regulation. Inhibition of TGF-β1 function by its specific antibody attenuated its impairment to NKG2D on NK cells. Finally, we observed that pterostilbene-treated prostate cancer cells were more easily to be killed by NK cells. Taken together, our findings demonstrated inhibition of miR-20a by pterostilbene in prostate cancer cells could increase MICA/B expression and decrease TGF-β1 secretion, which enhanced NK cell-mediated cytotoxicity againt prostate cancer cells, suggesting a potential approach for increasing anti-prostate cancer immune.
Glioma is one of the most common primary brain tumors. Gambogic acid (GA) is widely used in tumor chemotherapy. However, GA has poor water solubility, low bioavailability, and difficult permeability ...across the blood–brain barrier (BBB), leading to poor efficacy against brain tumors. In our study, we developed negatively charged GA-loaded PLGA nanobubbles GA/poly(lactic-co-glycolic acid) (PLGA) and conjugated them onto the surface of cationic lipid microbubbles (CMBs) through electrostatic interactions. The resulting GA/PLGA–CMB complex was characterized for its particle size, distribution, drug encapsulation efficiency, and ultrasound imaging property, revealing a high drug encapsulation efficiency and excellent contrast imaging capability. Importantly, significantly enhanced GA delivery into the brain could be observed after the intravenous administration of GA/PLGA–CMBs combined with low-intensity focused ultrasound (FUS) due to the cavitation from CMBs, which mediated blood–brain barrier (BBB) opening. Taking advantage of the opened BBB, GA/PLGA nanobubbles could be delivered into the tumor. Then, the second FUS irradiation at higher energy was used to induce the cavitation of GA/PLGA nanobubbles, producing the second cavitation on tumor cells, significantly enhancing the ability of GA to enter tumor cells and inhibit tumor growth inhibition efficacy.
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Genomic imprinting plays an important role in the growth and development of mammals. When the original imprint status of these genes is lost, known as loss of imprinting (LOI), it may affect growth, ...neurocognitive development, metabolism, and even tumor susceptibility. The LOI of imprint genes has gradually been found not only as an early event in tumorigenesis, but also to be involved in progression. More than 120 imprinted genes had been identified in humans. In this review, we summarized the most studied LOI of two gene clusters and 13 single genes in cancers. We focused on the roles they played, that is, as growth suppressors and anti-apoptosis agents, sustaining proliferative signaling or inducing angiogenesis; the molecular pathways they regulated; and especially their clinical significance. It is notable that 12 combined forms of multi-genes' LOI, 3 of which have already been used as diagnostic models, achieved good sensitivity, specificity, and accuracy. In addition, the methods used for LOI detection in existing research are classified into detection of biallelic expression (BAE), differentially methylated regions (DMRs), methylation, and single-nucleotide polymorphisms (SNPs). These all indicated that the detection of imprinting genes' LOI has potential clinical significance in cancer diagnosis, treatment, and prognosis.
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