The water-extractable (QWP) and the alkali-extractable (QAP) polysaccharides from quinoa (named QWP and QAP, respectively) and their four polysaccharide sub-fractions (QWP-1, QWP-2, QAP-1 and QAP-2), were isolated and purified by anion-exchange and gel filtration chromatography. QWP-1 and QWP-2 were composed of Rha, Ara, Gal and GalA. QAP-1 and QAP-2 were composed of Rha, Ara, Man, Gal and GalA. Antioxidant and immunoregulatory activities of the polysaccharides were evaluated. The results showed that QWP-1, QWP-2, QAP-1 and QAP-2 had significant antioxidant and immunoregulatory activities. The results suggest that QWP-1, QWP-2, QAP-1 and QAP-2 could be used as potential antioxidants and immunomodulators.

This study is aimed at investigating the effect of amifostine (AMI) on rat bone marrow stromal stem cells (BMSCs) exposed to 2 Gy radiation. The BMSCs were divided into four groups, namely, group A that received 0 Gy radiation, group B that received 0 Gy radiation and AMI, group C that received 2 Gy radiation, and group D that received 2 Gy radiation and AMI. The proliferation, apoptosis, and distribution of BMSCs in the cell cycle, along with their osteogenesis ability, adipogenesis ability, and ROS production, were subsequently examined. The levels of ALP, PPARγ, P53, and TNFα were determined by Western blotting. The results demonstrated that the proliferation of BMSCs and the levels of ALP in group C were much lower than those in group A. The production of ROS and levels of PPARγ, P53, and TNFα in the group that received 2 Gy radiation were much higher than those in group A. Furthermore, the production of ROS and the levels of PPARγ, P53, and TNFα were much lower in group D than in group C. Additionally, the levels of ALP and extent of cell proliferation were much higher in group D than in group C. The results demonstrated the potential of AMI in reducing the side effects of radiation in BMSCs and in treatment of bone diseases caused by radiation.

The development of the female gametophyte (FG) is one of the key processes of life cycle alteration between the haploid gametophyte and the diploid sporophytes in plants and it is required for successful seed development after fertilization. It is well demonstrated that free nuclear mitosis (FNM) of FG is crucial for the development of the ovule. However, studies of the molecular mechanism of ovule and FG development focused mainly on angiosperms, such as Arabidopsis thaliana and further investigation of gymnosperms remains to be completed. Here, Illumina sequencing of six transcriptomic libraries obtained from developing and abortive ovules at different stages during free nuclear mitosis of magagametophyte (FNMM) was used to acquire transcriptome data and gene expression profiles of Pinus tabulaeformis. Six cDNA libraries generated a total of 71.0 million high-quality clean reads that aligned with 63,449 unigenes and the comparison between developing and abortive ovules identified 7174 differentially expressed genes (DEGs). From the functional annotation results, DEGs involved in the cell cycle and phytohormone regulation were highlighted to reveal their biological importance in ovule development. Furthermore, validation of DEGs from the phytohormone signal transduction pathway was performed using quantitative real-time PCR analysis, revealing the dynamics of transcriptional networks and potential key components in the regulation of FG development in P. tabulaeformis were identified. These findings provide new insights into the regulatory mechanisms of ovule development in woody gymnosperms.

Identifying prognostic factors for osteosarcoma (OS) aids in the selection of patients who require more aggressive management. CD133 has been found to be a prognostic factor of certain tumor types. However, the association between CD133 expression and the prognosis of OS remains unknown. In this study, we analyzed the association of CD133 expression in OS with clinical factors and overall survival, and further investigated its potential role in metastasis in vitro. We found CD133 expression in 65.7% (46/70) of OS samples using immunohistochemistry, and it was positively correlated with lung metastasis analyzed by Chi-square test (P=0.002) and shorter overall survival time using the Kaplan-Meier method compared by log-rank test (P=0.000). Multivariate analysis showed that CD133 expression was an independent prognostic factor of patients with OS. To test for direct participation of CD133, we separated CD133(+) and CD133(-) cells in the MG63 cell line using magnetic-activated cell sorting and found that CD133(+) cells were more active in migration by scratch wound-healing assay and invasion by Matrigel invasion assay compared with CD133(-) cells. Elevated mRNA expression of the stemness gene octamer-binding transcription factor 4 (Oct-4) and NANOG, and the metastasis-related receptor C-X-C chemokine receptor type 4 (CXCR4) were also found in CD133(+) cells by reverse transcription-polymerase chain reaction. Thus, expression of CD133 was correlated with lung metastasis and poor prognosis in OS patients. CD133(+) cells may be a type of cancer stem cell with high expression of self-renewal capacity and metastasis-related genes.

Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.

The coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is overexpressed in several types of cancer. This study aimed to investigate the role of CHCHD2 in hepatocellular carcinoma (HCC). The expression of CHCHD2 in HCC and non-tumorous tissues was detected by immunohistochemistry and Western blot analysis, and the correlation between CHCHD2 expression and clinicopathological features of HCC was analyzed. Furthermore, the proliferation, apoptosis and migration of HepG2 cells with CHCHD2 knockdown were examined. We found that CHCHD2 was upregulated in HCC tissues, and high CHCHD2 expression was associated with poor differentiation, lymph node metastasis, local tissue invasion, high TNM grade of HCC and poor patient survival. Depletion of CHCHD2 led to significantly reduced cell proliferation, increased apoptosis and diminished migratory capacity in HepG2 cells. In addition, HCC tissues had high expression of CD105, a microvessel marker, and HepG2 cells depleted of CHCHD2 had low CD105 expression. In conclusion, CHCHD2 may play an oncogenic role in HCC via promoting tumor cell growth and migration while preventing apoptosis. CHCHD2 is a potential biomarker for poor outcome of HCC patients.

Ginsenosides, which have strong biological activities, can be divided into polar or less-polar ginsenosides.

Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4+ macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3+ T cells with high proportion of TIGIT+ cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.

Two water-extractable polysaccharide fractions designated as CWP (7. 37 × 105 Da) and CWP-0.2 (1.58 × 104 Da) were isolated and purified from chickpea (Cicer arietinum L.) seeds. The chemical structure of the two polysaccharides was characterized by various methods. Monosaccharide composition and methylation analysis showed that CWP was composed of Man and Glc in a molar ratio of 44.6:55.4, and CWP-0.2 was composed of Rha, Ara, Man, Glc, and Gal in a molar ratio of 10.6:23.3:5.2:4.9:56. Further structural characterization indicated that the main chain connection of CWP was → (2-β-d-Fruf-1) n →, and the main chain connection of CWP-0.2 was explored as → 2,4)-α-l-Rhap-(1 → 3)-α-d-Galp-(1 → with the branched chain of → 2,4)-α-l-Rhap-(1 → o-4. Besides, both CWP and CWP-0.2 had antioxidant and immunoregulatory activity in vitro, through scavenging DPPH· and ABTS·+ as well as stimulating production of NO, IL-6, TNF-α and MCP-1 in RAW 264.7 macrophages. CWP-0.2 revealed significantly higher bioactivity than CWP.

Finding cancer-driver genes has been a central theme of cancer research. We took a different perspective; instead of considering normal cells, we focused on cancerous cells and genes that maintained abnormal cell growth, which we named cancer-keeper genes (CKGs). Intervening CKGs may rectify aberrant cell growth, making them potential cancer therapeutic targets. We introduced control-hub genes and developed an efficient algorithm by extending network controllability theory. Control hub are essential for maintaining cancerous states and thus can be taken as CKGs. We applied our CKG-based approach to bladder cancer (BLCA). All genes on the cell-cycle and p53 pathways in BLCA were identified as CKGs, showing their importance in cancer. We discovered that sensitive CKGs - genes easily altered by structural perturbation - were particularly suitable therapeutic targets. Experiments on cell lines and a mouse model confirmed that six sensitive CKGs effectively suppressed cancer cell growth, demonstrating the immense therapeutic potential of CKGs.

Rationale: Ischemic stroke poses a significant health burden with limited treatment options. Lymphocyte Cytosolic Protein 1 (LCP1) facilitates cell migration and immune responses by aiding in actin polymerization, cytoskeletal rearrangements, and phagocytosis. We have demonstrated that the long non-coding RNA (lncRNA) Maclpil silencing in monocyte-derived macrophages (MoDMs) led to LCP1 inhibition, reducing ischemic brain damage. However, the role of LCP1 of MoDMs in ischemic stroke remains unknown. Methods and Results: We investigated the impact of LCP1 on ischemic brain injury and immune cell signaling and metabolism. We found that knockdown of LCP1 in MoDMs demonstrated robust protection against ischemic infarction and improved neurological behaviors in mice. Utilizing the high-dimensional CyTOF technique, we demonstrated that knocking down LCP1 in MoDMs led to a reduction in neuroinflammation and attenuation of lymphopenia, which is linked to immunodepression. It also showed altered immune cell signaling by modulating the phosphorylation levels of key kinases and transcription factors, including p-PLCg2, p-ERK1/2, p-EGFR, p-AKT, and p4E-BP1 as well as transcription factors like p-STAT1, p-STAT3, and p-STAT4. Further bioinformatic analysis indicated that Akt and EGFR are particularly involved in fatty acid metabolism and glycolysis. Indeed, single-cell sequencing analysis confirmed that enrichment of fatty acid and glycolysis metabolism in Lcp1high monocytes/macrophages. Furthermore, Lcp1high cells exhibited enhanced oxidative phosphorylation, chemotaxis, migration, and ATP biosynthesis pathways. In vitro experiments confirmed the role of LCP1 in regulating mitochondrial function and fatty acid uptake. Conclusions: These findings contribute to a deeper understanding of LCP1 in the context of ischemic stroke and provide valuable insights into potential therapeutic strategies targeting LCP1 and metabolic pathways, aiming to attenuating neuroinflammation and lymphopenia.

Despite the overall success of using R-CHOP for the care for non-Hodgkin's lymphoma patients, it is clear that the disease is quite complex and new insight is needed to further stratify the patient for a better personized treatment. In current study, based on previous studies from animal model, new panels combining well-established cytokine (BAFF) and autoantibodies (anti-SSA/Ro) with newly identified cytokine (IL14) and autoantibodies (TSA) were used to evaluate the association between B cell growth factor and Sjögren's related autoantibodies in NHL patients. The result clearly indicates that there was a unique difference between BAFF and IL14 in association with autoantibodies. While serum BAFF was negatively associated with the presence of both traditional anti-SSA/Ro and novel TSA antibodies in GI lymphoma patient, IL14 was positively associated with the presence of both traditional anti-SSA/Ro and novel TSA antibodies in non-GI lymphoma patient. Long-term follow-ups on these patients and evaluation of their response to the R-CHOP treatment and recurrence rate will be very interesting. Our result provides a solid evidence to support using novel diagnostic panel to better stratify the NHL patients.

Breast cancer is the most frequently diagnosed cancer in women worldwide. The antiproliferative activities of biochanin A (BA) and ginsenoside Rh₂ were determined by evaluating their inhibitory effect on MDA-MB-231 human breast cancer cell proliferation. The combination of BA with Rh₂ was also assessed. In MDA cells, combination treatment led to a decrease in the EC50 values of BA and Rh₂ to 25.20 μM and 22.75 μM, respectively. In MCF-7 cells, the EC50 values of combined BA and Rh₂ decreased to 27.68 μM and 25.41 μM, respectively. BA combined with Rh₂ also improved the inhibition of MDA-MB-231 and MCF-7 cell migration and invasion compared to the individual compounds. Western blot analysis demonstrated upregulation in p-p53, p-p38, and p-ASK1 proteins while levels of TRAF2 were downregulated. These results suggest that BA combined with Rh₂ exhibits synergistic effects against MDA-MB-231 and MCF-7 cell proliferation.

Krüppel-like factor 8 (KLF8) is a transcription factor that is important in the regulation of the cell cycle and has a critical role in oncogenic transformation and epithelial to mesenchymal transition (EMT). EMT is a key process in tumor metastasis. Although overexpression of KLF8 has been observed in a variety of human tumor types, the role of KLF8 in human osteosarcoma is yet to be elucidated. The present study aimed to investigate the biological impact of KLF8 on Saos-2 osteosarcoma cells. KLF8 gene expression was knocked down in vitro using a lentivirus-mediated small interfering (si)RNA method. Cell proliferation and cell cycle distribution were evaluated using 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide and colony formation assays, and flow cytometry, respectively. Cell invasion was analyzed using a Transwell® invasion assay. Knockdown of KLF8 was found to significantly inhibit proliferation and invasion in osteosarcoma cells. These data suggest that KLF8 may exhibit an important role in osteosarcoma tumorigenesis and that KLF8 may be a potential therapeutic target for the treatment of osteosarcoma.

The purpose of this study was to comprehensively evaluate the effect of short-term exercise intervention on the cardiovascular functions and quality of life (QoL) of patients with chronic heart failure (CHF).

Circular RNAs (circRNAs), a type of non-coding RNA with circular structure, were generated by back splicing and widely expressed in animals and plants. Recent studies have shown that circRNAs extensively participate in cell proliferation, cell differentiation, cell autophagy and other biological processes. However, the role and expression of circRNAs in the development and growth of muscle have not been studied in sheep. In our study, we first used RNA-seq to study the circRNAs in prenatal and postnatal longissimus dorsi muscle of sheep. A total of 6113 circRNAs were detected from the RNA-seq data. Several circRNAs were identified using reverse transcription PCR, DNA sequencing and RNase R digestion experiments. The expression levels of several circRNAs in prenatal and postnatal muscle were confirmed by Real-Time RT-PCR. The gene ontology (GO) and KEGG enrichment analysis of the host gene of the circRNAs showed that these circRNAs were mainly involved in the growth and development of muscle related signaling pathways. These circRNAs might sponge microRNAs (miRNAs) in predicted circRNA-miRNA-mRNA networks. The circRNAs expression profiles in muscle provided an important reference for the study of circRNAs in sheep.

Circular RNAs (circRNAs) are a newfound class of non-coding RNA in animals and plants. Recent studies have revealed that circRNAs play important roles in cell proliferation, differentiation, autophagy and apoptosis during development. However, there are few reports about muscle development-related circRNAs in livestock.

Adipose-derived stromal cells (ASCs) have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial. In this study, we established a three-dimensional (3D) angiogenesis model by co-culturing ASCs and endothelial cells (ECs) in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel-based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC-mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear co-factor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1). The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.

The aim of this study was to analyze the psychological status of and its influencing factors in health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) outbreak so as to provide sufficient theory and scientific basis for the formulation and implementation of relevant policies and measures in improving the psychological status of HCWs.

Research on the biological role of exosomes is rapidly developing, and recent evidence suggests that exosomal effects involve ferroptosis. Exosomes derived from different tissues inhibit ferroptosis, which increases tumour cell chemoresistance. Therefore, exosome-mediated regulation of ferroptosis may be leveraged to design anticancer drugs. This review discusses three pathways of exosome-mediated inhibition of ferroptosis: (1) the Fenton reaction; (2) the ferroptosis defence system, including the Xc-GSH-GPX4 axis and the FSP1/CoQ10/NAD(P)H axis; and (3) lipid peroxidation. We also summarize three recent approaches for combining exosomes and ferroptosis in oncology therapy: (1) promoting exosome-inhibited ferroptosis to enhance chemotherapy; (2) encapsulating exosomes with ferroptosis inducers to inhibit cancers; and (3) developing therapies that combine exosomal inhibitors and ferroptosis inducers. This review will contribute toward establishing effective cancer therapies.